Primary Amenorrhea Accompanied by Adrenal Adenoma: Start of Menarche Soon After Tumor Resection

Internal Medicine (Tokyo, Japan). Nov, 2002  |  Pubmed ID: 12487170

We report a patient with primary amenorrhea accompanied by adrenal adenoma. A 21-year-old woman was admitted to our hospital because of primary amenorrhea and hyperprogesteronemia without virilization. Venous sampling showed progesterone overproduction at the left adrenal gland. Computed tomography revealed a 7 cm mass in left adrenal gland. Serum pregnenorone, 17-hydroxypregnenorone, dehydroepiandrosterone, 17-hydroxyprogesterone, deoxycorticosterone, and 11-deoxycortisol were elevated. The diagnosis of steroid hormone producing tumor was made. Following tumor resection, serum progesterone normalized 4 days later, and menarche occurred 51 days after operation. The present case indicated that adrenal functioning tumor should not be overlooked in patients with primary amenorrhea.

The Relationship Between Smoking Habits and Serum Levels of 8-OHdG, Oxidized LDL Antibodies, Mn-SOD and Carotenoids in Rural Japanese Residents

Journal of Epidemiology / Japan Epidemiological Association. Jan, 2003  |  Pubmed ID: 12587611

This study investigated the relationship between smoking habits and serum levels of 8-OHdG, oxidized LDL antibodies (oLAB), Mn-SOD, and carotenoids. Subjects were 79 males (mean age +/- standard deviation; 62.1 +/- 10.0 years) and 79 females (60.3 +/- 10.3 y) who attended a health examination screening in the town of Hokkaido, Japan. Serum 8-OHdG, Mn-SOD, and oLAB levels were measured by ELISA and serum carotenoids levels were measured by HPLC. Smoking habits were assessed by public health nurses using a questionnaire. Serum 8-OHdG levels were significantly higher in males than in females. On the other hand, serum levels of beta-carotene, alpha-carotene, beta-cryptoxanthin, and zeaxanthin and lutein were significantly lower in males than in females. Serum beta-carotene, beta-cryptoxanthin, and zeaxanthin and lutein were significantly lower in males who were current smokers, compared to non-smokers. Serum 8-OHdG levels were also significantly higher in current smokers. Furthermore, in males, serum oLAB and beta-carotene levels were significantly and negatively correlated with the number of cigarettes smoked per day. Serum Mn-SOD levels were unrelated to smoking habits in males. In conclusion, this preliminary study suggests that cigarette smoking increases serum 8-OHdG levels and reduces serum levels of oLAB and carotenoids, such as beta-carotene, beta-cryptoxanthin, and zeaxanthin and lutein in healthy male subjects. Serum levels of 8-OHdG, oLAB, and carotenoids may be useful biomarkers of oxidative conditions affected by smoking.

Soy Product Intake is Inversely Associated with Serum Homocysteine Level in Premenopausal Japanese Women

The Journal of Nutrition. Mar, 2003  |  Pubmed ID: 12612155

Soybeans, which are an excellent source of folate, vitamin B-6 and minerals, may reduce serum homocysteine level. However, there is a possibility that dietary soy raises the serum homocysteine level because isoflavones, which are weak estrogens contained in soybeans, may exert antiestrogenic effects in a high estrogen environment, such as in premenopausal women. The present study examined a cross-sectional relationship between soy product intake and serum homocysteine level in 201 premenopausal Japanese women. Intakes of soy products, folate, methionine and vitamins B-6 and B-12 were estimated by a semiquantitative food frequency questionnaire. Folate status was also assessed by measuring serum folate. Soy product intake in terms of soy protein as well as soy isoflavone intake was modestly but significantly inversely associated with serum homocysteine level (r = -0.15, P = 0.04) after controlling for covariates. Soy product intake was also significantly positively correlated with serum folate (r = 0.15, P = 0.04). Although it is unclear the extent to which each component of soy, such as folate and isoflavones, is associated with the serum homocysteine concentration, this biochemical complex appears to have a favorable effect on homocysteine metabolism in premenopausal women.

Sleep Spindles in Human Prefrontal Cortex: an Electrocorticographic Study

Neuroscience Research. Apr, 2003  |  Pubmed ID: 12657455

To investigate the sleep spindle activity of the human prefrontal cortex (PFC), we simultaneously recorded whole nights of polysomnographic and electrocorticographic (ECoG) activities during the natural sleep of epileptic patients. Subjects were nine patients with intractable epilepsy who had subdural electrodes surgically attached to the orbital (seven cases), medial (three cases), or dorsolateral (two cases) PFC, and in one case to the frontal pole. To examine spindle frequencies, fast Fourier transformation (FFT) and auto-correlation analyses were performed on the PFC ECoG and Cz EEG data, primarily on epochs of stage 2 sleep. Lower sigma band ECoG oscillations of about 12 Hz were widely distributed across all prefrontal cortical areas including the frontal limbic regions, but none of the PFC sigma frequency peaks coincided with the faster (about 14 Hz) Cz EEG sleep spindles. Combining our results with anatomical and electrophysiological facts, it is suggested that the thalamofrontal circuit involving the rostral reticular and the mediodorsal nucleus of the thalamus is responsible for the generation of 12 Hz frontal spindles in humans.

The Impact of Changes in Marital Status on the Mortality of Elderly Japanese

Annals of Epidemiology. Apr, 2003  |  Pubmed ID: 12684186

To assess the impact of changes in marital status on the mortality of elderly Japanese men and women.

[Chemotherapy of Osteoporosis: Discussion]

Nihon Rinsho. Japanese Journal of Clinical Medicine. Feb, 2003  |  Pubmed ID: 12703540

[Hypothalamo-hypophyseal Diseases--progress in Diagnosis and Treatment]

Nihon Naika Gakkai Zasshi. The Journal of the Japanese Society of Internal Medicine. Mar, 2003  |  Pubmed ID: 12710049

Association of Blood Pressure with Intake of Soy Products and Other Food Groups in Japanese Men and Women

Preventive Medicine. Jun, 2003  |  Pubmed ID: 12744912

Soy diet has been suggested to have antihypertensive effect in animal studies. The present study examined the cross-sectional relationship between blood pressure and intake of soy products and other food groups in Japanese men and women.

Theta Oscillation in the Anterior Cingulate and Beta-1 Oscillation in the Medial Temporal Cortices: a Human Case Report

Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. May, 2003  |  Pubmed ID: 12763350

In previous studies we observed gamma (30-150 Hz) and beta-1 (10-20 Hz) oscillations in the medial temporal lobe (MTL) using subdural electrodes. The beta-1 was present during wake and REM sleep while gamma was present in all states. Recently we studied a patient (35 years M) with electrodes attached to the anterior cingulate cortex (ACC). This structure showed regular theta (5-6 Hz) oscillations. In the first recording, electrodes were attached to the MTL, that demonstrated the beta-1 and gamma oscillations. Two months later, electrodes were placed on orbitofrontal and ACC and an all night sleep recording was carried out. The ACC exhibited a highly regular and continuous theta oscillation during wakefulness and REM sleep, but not during NREM sleep. Since this same subject showed beta-1 oscillations in the MTL, it is probable that the theta in the ACC is independent of beta-1 in the MTL. This single case suggests the existence of two different frequency oscillators in the human limbic system. Elucidating their functional roles will be an interesting challenge for future studies.

Troglitazone Inhibits Isolated Cell Proliferation, and Induces Apoptosis in Isolated Rat Mesangial Cells

American Journal of Nephrology. Jul-Aug, 2003  |  Pubmed ID: 12840598

Troglitazone is one of thiazolidinedione derivatives as a high affinity ligand for peroxisome proliferator-activated receptor-gamma (PPAR-gamma). The in vivo studies demonstrated that troglitazone ameliorated microalbuminuria. There have been few reports about direct effect of thiazolidinedione derivatives on mesangial cell function. We determined the effect of troglitazone on isolated rat mesangial cell proliferation.

Suppression of Leaf Feeding and Oviposition of Phytophagous Ladybird Beetles (Coleoptera: Coccinellidae) by Chitinase Gene-transformed Phylloplane Bacteria and Their Specific Bacteriophages Entrapped in Alginate Gel Beads

Journal of Economic Entomology. Jun, 2003  |  Pubmed ID: 12852588

The chitinase gene-transformed strain KPM-007E/chi of Enterobacter cloacae was vitally entrapped in sodium alginate gel beads with its specific virulent bacteriophage EcP-01 to provide a new method for microbially digesting chitinous peritrophic membranes of phytophagous ladybird beetles Epilachna vigintioctopunctata. First, chitinase SH1 from a gram-positive bacterium Kurthia zopfii was overproduced by Escherichia coli cells and purified by affinity column chromatography. The purified enzyme effectively digested peritrophic membranes dissected from the ladybird beetles to expose epithelial tissues beneath the peritrophic membrane, and the beetles that had ingested chitinase after submergence in chitinase solution had considerably reduced their feeding on tomato leaves. KPM-007E/chi, entrapped in the alginate beads, released the chitinase. More chitinase was released when KPM-007E/chi was present with their specific virulent bacteriophage EcP-01 in the beads because of lysis of bacterial cells infected with the bacteriophages. This chitinase release from the microbial beads (containing KPM-007E/chi and EcP-01) was sufficient to digest the peritrophic membrane as well as to suppress feeding of bead-sprayed tomato leaves by the ladybird beetles. A daily supply of tomato leaves treated with the microbial beads considerably suppressed leaf feeding and oviposition by the ladybird beetles, suggesting a possible application of chitinase-secreting bacteria for suppressing herbivorous insect pests.

Syntaxin 4 and Synip (syntaxin 4 Interacting Protein) Regulate Insulin Secretion in the Pancreatic Beta HC-9 Cell

The Journal of Biological Chemistry. Sep, 2003  |  Pubmed ID: 12855681

Although syntaxin 1 is generally thought to function as the primary target-N-ethylmaleimide-sensitive factor attachment protein receptor required for pancreatic beta cell insulin secretion, we have observed that overexpression of a dominant-interfering syntaxin 4 mutant (syntaxin 4/DeltaTM) attenuated glucose-stimulated insulin secretion in betaHC-9 cells. Furthermore, these cells express the selective syntaxin 4-binding protein Synip (syntaxin 4 interacting protein), and Synip was specifically co-immunoprecipitated with syntaxin 4 but not syntaxin 1. Overexpression of the full-length Synip protein (Synip/wild type) inhibited VAMP2 association with syntaxin 4 and decreased glucose-stimulated insulin secretion. This did not occur with a Synip mutant (Synip/ DeltaEF) that was incapable of binding syntaxin 4. Consistent with a functional role of syntaxin 4 in this process, expression of syntaxin 4/DeltaTM also inhibited glucose-stimulated insulin secretion. Furthermore, analysis of first and second phase insulin secretion demonstrated that syntaxin 4/DeltaTM mainly suppressed the second phase of insulin secretion. In contrast, overexpression of Synip resulted in an inhibition of both the first and second phase of glucose-stimulated insulin secretion. These data demonstrate that syntaxin 4 plays a functional role on insulin release and granule fusion in beta cells and that this process is regulated by the syntaxin 4-specific binding protein Synip.

Circulation of Endemic Type 2 Vaccine-derived Poliovirus in Egypt from 1983 to 1993

Journal of Virology. Aug, 2003  |  Pubmed ID: 12857906

From 1988 to 1993, 30 cases of poliomyelitis associated with poliovirus type 2 were found in seven governorates of Egypt. Because many of the cases were geographically and temporally clustered and because the case isolates differed antigenically from the vaccine strain, it was initially assumed that the cases signaled the continued circulation of wild type 2 poliovirus. However, comparison of sequences encoding the major capsid protein, VP1 (903 nucleotides), revealed that the isolates were related (93 to 97% nucleotide sequence identity) to the Sabin type 2 oral poliovirus vaccine (OPV) strain and unrelated (<82% nucleotide sequence identity) to the wild type 2 polioviruses previously indigenous to Egypt (last known isolate: 1979) or to any contemporary wild type 2 polioviruses found elsewhere. The rate and pattern of VP1 divergence among the circulating vaccine-derived poliovirus (cVDPV) isolates suggested that all lineages were derived from a single OPV infection that occurred around 1983 and that progeny from the initiating infection circulated for approximately a decade within Egypt along several independent chains of transmission. Complete genomic sequences of an early (1988) and a late (1993) cVDPV isolate revealed that their 5' untranslated region (5' UTR) and noncapsid- 3' UTR sequences were derived from other species C enteroviruses. Circulation of type 2 cVDPVs occurred at a time of low OPV coverage in the affected communities and ceased when OPV coverage rates increased. The potential for cVDPVs to circulate in populations with low immunity to poliovirus has important implications for current and future strategies to eradicate polio worldwide.

Characterization of Molecular Forms of Probrain Natriuretic Peptide in Human Plasma

Clinica Chimica Acta; International Journal of Clinical Chemistry. Aug, 2003  |  Pubmed ID: 12867297

Measurement of brain natriuretic peptide (BNP) in plasma is useful for the diagnosis and prognosis of heart failure. However, the molecular forms of BNP, especially proBNP in the blood, have been poorly characterized.

Dietary Soy and Fats in Relation to Serum Insulin-like Growth Factor-1 and Insulin-like Growth Factor-binding Protein-3 Levels in Premenopausal Japanese Women

Nutrition and Cancer. 2003  |  Pubmed ID: 12881012

Circulating levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have each been associated with premenopausal breast cancer risks. We analyzed data from a cross-sectional study of 261 premenopausal Japanese women aged 20-54 yr with adequate nutritional status to evaluate the relationships between concentrations of IGF-1 and IGFBP-3 in serum and dietary intakes of soy, fats and other nutrients. Diet was assessed by a semiquantitative food frequency questionnaire. There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level. Total fat intake was significantly inversely correlated with serum IGFBP-3 level (r = -0.13, P = 0.04). The correlations of saturated and monounsaturated fats with serum IGFBP-3 were of borderline significance (r = -0.12, P = 0.06 and r = -0.11, P = 0.07, respectively).

Effect of Extracorporeal Shock Waves on Callus Formation During Bone Lengthening

Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2003  |  Pubmed ID: 12898297

The effects of extracorporeal shock waves (ESWs) on callus formation during bone lengthening were studied in 25 female Japanese white rabbits. Bone lengthening of 9.8 mm was obtained over 2 weeks using the Orthofix M-100 bone fixator. ESWs were applied 3 weeks after surgery. Pins were removed 7 weeks after surgery, and specimens were prepared after the animals were killed at 9 and 24 weeks. The shock wave setting used was 0.42 mJ/mm(2) with a pulse interval of 2 Hz; 3000 shots each were applied to the central and peripheral areas. The specimens were evaluated using radiography, bone mineral density (BMD) measured by dual energy absorptiometry (DXA), and a three-point bending test to evaluate mechanical strength. Histological examination was performed on the lengthened portion. Radiographs and histological observations revealed no apparent fractures in nonlengthening tibias at the shock wave energy densities used. Radiographic observations revealed no apparent differences between the control group and the ESW group. BMD measurements by DXA revealed significantly increased bone mass in the ESW group 9 weeks after surgery. At 24 weeks after surgery the mean BMD had decreased to 25% and 15% of the values at 9 weeks in the control and ESW groups, respectively. The three-point bending test revealed no significant differences between the groups. Histological observations revealed significant capillary formation and osteoblasts and chondrocytes in the bone marrow as well as bridging of newly formed trabeculae 2 weeks after the bone was lengthened. At 4 weeks after treatment, observations included parts of the lengthened portion with no cortex or immature bone. At 9 weeks after surgery, cortex formation and a normal medullary cavity were clearly observed in the control group, whereas observations in the treated group included areas of the lengthened portion with no cortex and formation of immature trabecular structures and increased cancellous bone in the center of the lengthened portion. At 24 weeks after surgery, more prominent cortex formation and fatty marrow were observed in the ESW group than in the control group.

Relationship Between Hyperinsulinemia and Pulse Wave Velocity in Moderately Hyperglycemic Patients

Diabetes Research and Clinical Practice. Oct, 2003  |  Pubmed ID: 14581153

Arterial stiffness assessed by pulse wave velocity (PWV) reflects early stage arteriosclerosis. The influence of hyperinsulinemia on peripheral vascular disease (PVD) is still unknown. We determined the influences of hyperinsulinemia on PVD assessed by PWV in moderately hyperglycemic patients.

Molecular Epidemiology of Type 2 Vaccine-associated Paralytic Poliomyelitis in China

Japanese Journal of Infectious Diseases. Aug, 2003  |  Pubmed ID: 14583649

Cholesterol Crystal Embolization (CCE) After Cardiac Catheterization: a Case Report and a Review of 36 Cases in the Japanese Literature

Japanese Heart Journal. Sep, 2003  |  Pubmed ID: 14587658

Cholesterol crystal embolization (CCE) is a complication of atherosclerosis. A 67-year-old Japanese man underwent coronary artery bypass grafting. After the surgery, he underwent coronary angiography via the right femoral artery. Twelve days later, he suddenly developed acalculous cholecystitis and was treated with antibiotics. Gradual deterioration in renal function, purplish discoloration of the distal portion of his toes, and eosinophilia were noted. We performed a skin biopsy and made a diagnosis of CCE. Cilostazol and intravenous heparin improved the symptoms and decreased the creatinine level. We retrospectively studied the clinical features of 36 cases registered with a diagnosis of CCE in the Japanese literature.

Surveillance of Poliovirus-isolates in Japan, 2002

Japanese Journal of Infectious Diseases. Oct-Dec, 2003  |  Pubmed ID: 14695435

[Hypothalamic Hypogonadism Associated with GRH and CRH Deficiencies]

Nihon Naika Gakkai Zasshi. The Journal of the Japanese Society of Internal Medicine. Dec, 2003  |  Pubmed ID: 14743764

The Relationships of a Rationality/antiemotionality Personality Scale to Mortalities of Cancer and Cardiovascular Disease in a Community Population in Japan

Journal of Psychosomatic Research. Jan, 2004  |  Pubmed ID: 14987971

Grossarth-Maticek et al. reported that an individual's level on a rationality/antiemotionality (R/A) personality was strongly predictive of cancer, ischemic heart disease and stroke mortality. To investigate the relationships of an individual's level on the R/A personality to cancer and cardiovascular disease mortality in Japan, we conducted a population-based cohort study.

A Comparison of Dietary Habits Among Women in Japan and Hawaii

Public Health Nutrition. Apr, 2004  |  Pubmed ID: 15003140

To compare the dietary habits of Japanese women in Japan with those of Japanese and Caucasian women living in Hawaii.

Health Attitudes and Behaviors: Comparison of Japanese and Americans of Japanese and European Ancestry

Health & Place. Jun, 2004  |  Pubmed ID: 15019909

Adults living in Japan (N = 357) and the US (N = 223) completed semi-structured interviews assessing health-related attitudes and practices. The US respondents were of Japanese (N = 106) and European (N = 117) ancestry. Results indicated considerable similarity between the two US groups and significant differences between the Japanese and American respondents. The Japanese respondents placed less priority on health, had less belief in the efficacy of health screening tests, lower levels of internal health locus of control (HLOC), and higher levels of chance and powerful-others HLOC. While Japanese and Americans had similar overall levels of healthy behaviors, the Japanese were less likely to have obtained health screening tests (especially gynecologic exams). The findings have implications for adapting health promotion programs in the context of Japanese and American cultures.

Molecular Epidemiology of Enterovirus 71 Infection in the Western Pacific Region

Pediatrics International : Official Journal of the Japan Pediatric Society. Apr, 2004  |  Pubmed ID: 15056257

Recently, there have been large outbreaks of hand, foot and mouth disease (HFMD) mainly caused by enterovirus 71 (EV71) associated with severe neurological diseases in the Western Pacific Region (WPR). To monitor the realtime trend of EV71 transmission throughout the WPR, the authors conducted a molecular epidemiological analysis of EV71 infection.

Association Between Birth Weight and Serum Lipid Concentration in Premenopausal Japanese Women

Journal of Epidemiology / Japan Epidemiological Association. Jan, 2004  |  Pubmed ID: 15065686

The relationships between birth weight and serum lipid concentrations in pre-menopausal Japanese women were not well identified and also diet and serum hormone status in these women would be considered.

Circulating Vaccine-derived Polioviruses: Current State of Knowledge

Bulletin of the World Health Organization. Jan, 2004  |  Pubmed ID: 15106296

Within the past 4 years, poliomyelitis outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) have occurred in Hispaniola (2000-01), the Philippines (2001), and Madagascar (2001-02). Retrospective studies have also detected the circulation of endemic cVDPV in Egypt (1988-93) and the likely localized spread of oral poliovirus vaccine (OPV)-derived virus in Belarus (1965-66). Gaps in OPV coverage and the previous eradication of the corresponding serotype of indigenous wild poliovirus were the critical risk factors for all cVDPV outbreaks. The cVDPV outbreaks were stopped by mass immunization campaigns using OPV. To increase sensitivity for detecting vaccine-derived polioviruses (VDPVs), in 2001 the Global Polio Laboratory Network implemented additional testing requirements for all poliovirus isolates under investigation. This approach quickly led to the recognition of the Philippines and Madagascar cVDPV outbreaks, but of no other current outbreaks. The potential risk of cVDPV emergence has increased dramatically in recent years as wild poliovirus circulation has ceased in most of the world. The risk appears highest for the type 2 OPV strain because of its greater tendency to spread to contacts. The emergence of cVDPVs underscores the critical importance of eliminating the last pockets of wild poliovirus circulation, maintaining universally high levels of polio vaccine coverage, stopping OPV use as soon as it is safely possible to do so, and continuing sensitive poliovirus surveillance into the foreseeable future. Particular attention must be given to areas where the risks for wild poliovirus circulation have been highest, and where the highest rates of polio vaccine coverage must be maintained to suppress cVDPV emergence.

Sodium Intake and Risk of Death from Stroke in Japanese Men and Women

Stroke; a Journal of Cerebral Circulation. Jul, 2004  |  Pubmed ID: 15143292

Despite the evidence for a positive association of dietary salt and blood pressure, the few prospective studies that have assessed the association between dietary salt and stroke have reported inconsistent results. The purpose of this study was to examine the relation between sodium intake and death from stroke in a population-based cohort of Japanese men and women.

Spontaneous Regression of a Primary Cerebral Tumor Following Vasospasm Caused by Subarachnoid Hemorrhage Due to Rupture of an Intracranial Aneurysm--case Report

Neurologia Medico-chirurgica. Apr, 2004  |  Pubmed ID: 15185757

A 40-year-old man demonstrated spontaneous regression of a malignant glioma following vasospasm caused by subarachnoid hemorrhage due to rupture of an intracranial aneurysm. The patient had been treated under a diagnosis of malignant glioma for 5 years. He presented with a ruptured aneurysm manifesting as subarachnoid hemorrhage. Single photon emission computed tomography with N-isopropyl-p-123I-iodoamphetamine and diffusion-weighted magnetic resonance (MR) imaging revealed severe flow reduction due to vasospasm in the bilateral temporoparietal cortical regions, including the tumor. MR imaging performed 5 months later showed marked tumor regression. The present case suggests that treatment targeting angiogenesis of malignant gliomas may be effective as a part of multimodality treatment.

Differential Activation of Epidermal Growth Factor (EGF) Receptor Downstream Signaling Pathways by Betacellulin and EGF

Endocrinology. Sep, 2004  |  Pubmed ID: 15192046

To determine the downstream signaling pathways regulated by betacellulin (BTC) in comparison with epidermal growth factor (EGF), we used Chinese hamster ovary cells overexpressing the human EGF receptor (ErbB1/EGFR). The overall time-dependent activation of EGFR autophosphorylation was identical in cells treated with 1 nm BTC or 1.5 nm EGF. Analysis of site-specific EGFR phosphorylation demonstrated that the BTC and EGF tyrosine phosphorylation of Y1086 was not significantly different. In contrast, the autophosphorylation of Y1173 was markedly reduced in BTC-stimulated cells, compared with EGF stimulation that directly correlated with a reduced BTC stimulation of Shc tyrosine phosphorylation, Ras, and Raf-1 activation. On the other hand, Y1068 phosphorylation was significantly increased after BTC stimulation, compared with EGF in parallel with a greater extent of Erk phosphorylation. Expression of a dominant interfering MEK kinase 1 (MEKK1) and Y1068F EGFR more efficiently blocked the enhanced Erk activation by BTC, compared with EGF. Interestingly BTC had a greater inhibitory effect on apoptosis, compared with EGF, and expression of Y1068F EGFR abolished this enhanced inhibitory effect. Together, these data indicated that although BTC and EGF share overlapping signaling properties, the ability of BTC to enhance Erk activation occurs independent of Ras. The increased BTC activation results from a greater extent of Y1068 EGFR tyrosine phosphorylation and subsequent increased recruitment of the Grb2-MEKK1 complex to the plasma membrane, compared with EGF stimulation. The increased Erk activation by BTC associated with antiapoptotic function.

Soy, Fat and Other Dietary Factors in Relation to Premenstrual Symptoms in Japanese Women

BJOG : an International Journal of Obstetrics and Gynaecology. Jun, 2004  |  Pubmed ID: 15198788

To evaluate the relations of intakes of soy, fat and other dietary components to premenstrual symptoms.

Fenofibrate, Troglitazone, and 15-deoxy-Delta12,14-prostaglandin J2 Close KATP Channels and Induce Insulin Secretion

The Journal of Pharmacology and Experimental Therapeutics. Sep, 2004  |  Pubmed ID: 15201343

It is known that peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands stimulate acute-phase insulin secretion with a rapid Ca2+ influx into pancreatic beta-cells, but the precise mechanisms are not clear. The effects of PPAR-alpha ligands on pancreatic beta-cells also remain unclear. We investigated the effects of PPAR-alpha ligands (fenofibrate and fenofibric acid), a PPAR-gamma ligand (troglitazone), and an endogenous ligand of PPAR-gamma [15-deoxy-Delta12,14-prostaglandin J2 (15-deoxy-Delta12,14-PGJ2)] on KATP channel activity in clonal hamster insulinoma cell line, HIT-T15 cells. As assessed by whole-cell patch clamp, fenofibrate, fenofibric acid, troglitazone, and 15-deoxy-Delta12,14-PGJ2 reduced the KATP channel currents, and inhibition continued after washout of these agents. The concentration-response curves of fenofibrate, fenofibric acid, troglitazone, and 15-deoxy-Delta12,14-PGJ2 showed half-maximal inhibition of KATP channel currents (IC50) at 3.26, 94, 2.1, and 7.3 micromol/l, respectively. Fenofibrate (> or = 10(-6) mol/l), 15-deoxy-Delta12,14-PGJ2 (> or = 5 x 10(-5) mol/l), and troglitazone (> or = 10(-6) mol/l) inhibited [3H]glibenclamide binding, but fenofibric acid did not. In addition, fenofibrate (> or = 10(-6) mol/l), fenofibric acid (10(-4) mol/l), troglitazone (10(-4) mol/l), and 15-deoxy-Delta12,14-PGJ2 (> or = 10(-5) mol/l) increased insulin secretion from HIT-T15 when applied for 10 min. Our data suggest that PPAR-alpha and -gamma ligands interact directly with the beta-cell membrane and stimulate insulin secretion.

Characterization of in Vitro and in Vivo Phenotypes of Poliovirus Type 1 Mutants with Reduced Viral Protein Synthesis Activity

The Journal of General Virology. Jul, 2004  |  Pubmed ID: 15218178

Sabin vaccine strains of poliovirus (PV) contain major attenuation determinants in the internal ribosomal entry site (IRES), an area that directs viral protein synthesis. To examine the effect of reduced viral protein synthesis on PV neurovirulence, spacer sequences, consisting of short open reading frames of different lengths, were introduced between the IRES and the initiation codon of viral polyprotein, resulting in PV mutants with reduced viral protein synthesis. These PV mutants had a viral protein synthesis activity 8.8-55 % of that of the parental Mahoney strain as measured in HeLa S3 cells. Only viruses with more than 28 % of the wild-type activity had intact spacer sequences following plaque purification. Mutants with 17 % or 21 % of the wild-type activity were unstable and a mutant with 8.8 % was lethal. The neurovirulence of PV mutants was evaluated in transgenic mice carrying the human PV receptor gene. In this test, mutants with more than 28 % of the wild-type activity remained neurovirulent, while a mutant with 17 % of wild-type activity exhibited a partially attenuated phenotype. This mutant stably replicated in the spinal cord; however, the stability was severely affected during the course of virus infection from the cerebrum to the spinal cord. These results suggest that reduced viral protein synthesis activity as measured in cultured cells (17-55 % of the wild-type activity) is not the main determinant of PV attenuation.

Effect of Adjuvant Transarterial Infusion of Anticancer Agents After Transurethral Resection in Patients with PT2a Muscle Invasive Transitional Cell Carcinoma of the Bladder: Five and Ten-year Outcome

Journal of Nihon Medical School = Nihon Ika Daigaku Zasshi. Aug, 2004  |  Pubmed ID: 15329486

Five- and ten-year survival rates in patients who had transurethral resection for pT2aN0M0 muscle invasive transitional cell carcinoma of the bladder was studied with emphasis on the effect of adjuvant transarterial infusions of anticancer agents (TAI). A total of 17 patients out of 290 patients with bladder cancer who had initial treatment in our department between January 1991 and May 2001 were found to be pT2aN0M0 and were included in the present study. Fifteen patients received intravesical instillations of BCG after transurethral resection of the bladder tumor and 8 patients received TAI which was given two weeks after bacillus Calmette-Guerin therapy, with the exception of 1 patient. Five- and ten-year overall survival rates were 76.0% and 52.1%, respectively, and both five- and ten-year cancer-specific survival rates were 76.0% with an average follow up of 71 months. Significant prognostic factor associated with survival rates was only the infiltration pattern of the tumor cells between the alpha and beta group and gamma group (P = 0.0420) in cancer-specific survival rates. The data support conservative management of transurethral resection followed by intravesical instillation of BCG and TAI in patients with pT2a bladder cancer.

Cancer-related Attitudes: A Comparative Study in Japan and the US

Psycho-oncology. Sep, 2004  |  Pubmed ID: 15334534

The cancer-related attitudes and beliefs of adults living in central Japan (N = 357) were compared to those of respondents in a US state (Hawaii) (N = 223) consisting of both Japanese (n = 106) and Caucasian (n = 117) individuals. Almost all US subjects endorsed doctors disclosing cancer diagnoses to their patients, while a minority of the Japan sample supported cancer disclosure as a general practice. However, the majority of Japan respondents expressed a personal preference to be told if they themselves were diagnosed with cancer, as did virtually all US respondents. US subjects were more optimistic than Japanese subjects about cancer's curability, both at the present time and in the future; Japanese Americans scored intermediate between Japanese and Caucasian Americans. Word-association data indicated that cancer was most likely to be associated with death by Japanese respondents. The data support the continued international differences in views about cancer and suggest that some of these differences persist over many generations of US residence.

Intracranial Metastatic Prostate Carcinoma Presenting As Intermittent Double Vision

Urology. Sep, 2004  |  Pubmed ID: 15351603

We describe a prostate cancer patient whose initial symptom was intermittent double vision. Intracranial magnetic resonance imaging demonstrated a pituitary mass extending to the cavernous sinus, which caused the double vision. After hormonal therapy for prostate cancer, the pituitary mass disappeared, and double vision was completely resolved without local therapy for the brain. In the 19 months of follow-up after hormone treatment, the prostate cancer remained stable, and the patient remained neurologically intact.

Differential Localization of Neurons Susceptible to Enterovirus 71 and Poliovirus Type 1 in the Central Nervous System of Cynomolgus Monkeys After Intravenous Inoculation

The Journal of General Virology. Oct, 2004  |  Pubmed ID: 15448361

Poliovirus and enterovirus 71 (EV71) are both neurotropic enteroviruses that cause serious neurological diseases, such as poliomyelitis and encephalitis. The neurovirulence of EV71 in cynomolgus monkeys was demonstrated previously by intraspinal inoculation. In this study, an improved simian model of EV71 infection was established by using intravenous inoculation, which revealed clinical and neuropathological similarities between this model and human cases of encephalitis. Experimental EV71 infection induced direct neurological manifestations, such as tremor, ataxia and brain oedema, but not non-neurological complications, such as pulmonary oedema and cardiac failure. Using this model of EV71 infection, the neurotropic characteristics of the prototype strains of EV71 and poliovirus type 1 (PV1) were compared. Three monkeys were inoculated intravenously with 10(5.5) TCID50 EV71 and all developed neurological disease signs within 4-6 days of inoculation. However, after inoculation with 10(5.5) TCID50 PV1 strain OM1 (PV1-OM1), the major manifestation was flaccid paralysis, starting from the lower limbs 6-9 days post-inoculation. Histopathological and virological analyses of moribund monkeys revealed that disseminated EV71 infection was characterized by severe panencephalitis involving both the pyramidal and extrapyramidal systems. In contrast, the lesions induced by PV1-OM1 were mainly restricted to the pyramidal tract, particularly the spinal motor neurons, thalamus and motor cortex. In conclusion, neuropathological involvement in this model correlated well with the apparent differences in neurological disease induced by EV71 and PV1-OM1. Thus, intravenous inoculation with EV71 is an excellent model to study the neuropathology of EV71 and to evaluate candidate vaccines and potential antiviral agents.

Impulse Response Function Based on Multivariate AR Model Can Differentiate Focal Hemisphere in Temporal Lobe Epilepsy

Epilepsy Research. Sep-Oct, 2004  |  Pubmed ID: 15451010

The purpose of this study is to propose and investigate a new approach for discriminating between focal and non-focal hemispheres in intractable temporal lobe epilepsy, based on applying multivariate time series analysis to the discharge-free background brain activity observed in nocturnal electrocorticogram (ECoG) time series. Five unilateral focal patients and one bilateral focal patient were studied. In order to detect the location of epileptic foci, linear multivariate autoregressive (MAR) models were fitted to the ECoG data; as a new approach for the purpose of summarizing these models in a single relevant parameter, the behavior of the corresponding impulse response functions was studied and described by an attenuation coefficient. In the majority of unilateral focal patients, the averaged attenuation coefficient was found to be almost always significantly larger in the focal hemisphere, as compared to the non-focal hemisphere. Also the amplitude of the fluctuations of the attenuation coefficient was significantly larger in the focal hemisphere. Moreover, in one patient showing a typical regular sleep cycle, the attenuation coefficient in the focal hemisphere tended to be larger during REM sleep and smaller during Non-REM sleep. In the bilateral focal patient, no statistically significant distinction between the hemispheres was found. This study provides encouraging results for new investigations of brain dynamics by multivariate parametric modeling. It opens up the possibility of relating diseases like epilepsy to the properties of inconspicuous background brain dynamics, without the need to record and analyze epileptic seizures or other evidently pathological waveforms.

Theta Oscillation in the Human Anterior Cingulate Cortex During All-night Sleep: an Electrocorticographic Study

Neuroscience Research. Nov, 2004  |  Pubmed ID: 15488296

Ten epileptic patients each with subdural electrodes surgically attached to the anterior cingulate cortex (ACC; two cases), the orbitofrontal cortex (OFC; seven cases), or both (one case) were included in this study. We recorded each patient's ACC or OFC electrocorticogram (ECoG) during the time period that the patient was awake and naturally asleep. We performed a Fast Fourier Transformation (FFT) power spectral analysis on each ECoG to examine its frequency component. We found that the ACC showed regular and continuous theta oscillation (5-7Hz) during wakefulness and rapid eye movement (REM) sleep, but not during slow wave sleep. Theta waves observed in REM sleep were not as distinct as those found in wakefulness. We also discovered that the orbitofrontal signals represented spectral peaks in the theta band only during wakefulness. This suggests the coexistence of theta oscillation in the ACC. Considering our previous observations of gamma and beta oscillations in the human hippocampus, we hypothesize that the human limbic system manifests two oscillatory activities. The results obtained in this study suggest that electrophysiological activity in the ACC could be related to particular psychological functions in wakefulness and in REM sleep. These results are useful in elucidating the human brain mechanism.

9HODE Stimulates Cell Proliferation and Extracellular Matrix Synthesis in Human Mesangial Cells Via PPARgamma

Experimental Biology and Medicine (Maywood, N.J.). Nov, 2004  |  Pubmed ID: 15522842

Plasma oxidized low-density lipoprotein (OX-LDL) levels are elevated in patients with renal diseases, including diabetic nephropathy. We examined effects of OX-LDL on cell proliferation and extracellular matrix (ECM) production by using normal human mesangial cells. Furthermore, we examined possible involvement of peroxisome proliferator-activated receptor gamma (PPARgamma). Mesangial cell proliferation with OX-LDL, 9-hydroxy-10,12-octadecadienoic acid (9HODE), and 13-hydroxy-9,11-octadecadienoic acid (13HODE), the major components of OX-LDL, were determined by 5-bromo-2'-deoxyuridine (BrdU) or 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) incorporation. The effect of OX-LDL on mesangial cell proliferation with PD98059 pretreatment was determined by BrdU incorporation. Type IV collagen, fibronectin, and PPARgamma expression with OX-LDL or 9HODE or 13HODE was determined by Western blotting. Type IV collagen expression with antisense oligonucleotide against PPARgamma pretreatment was also determined by Western blotting. The effect of PD98059 pretreatment on PPARgamma expression was determined by Western blotting. In mesangial cells exposed to isolated OX-LDL from human plasma, BrdU incorporation was increased, and this increase was deleted by PD98059. Type IV collagen expression was significantly increased by OX-LDL. 9HODE and 13HODE increased BrdU and MTT incorporation into mesangial cells and also increased expressions of Type IV collagen and fibronection, the major components of ECM. PPARgamma expression in mesangial cells was stimulated by 9HODE. The reduction of PPARgamma synthesis by pretreatment of antisense oligonucleotide against PPARgamma remarkably attenuated Type IV collagen synthesis induced by 9HODE. PPARgamma expression induced by 9HODE was also reduced by PD98059 pretreatment. These findings demonstrate that 9HODE, the major component of OX-LDL, stimulates cell proliferation and ECM production of human mesangial cells. In addition, the stimulatory effects are, at least in part, mediated by PPARgamma, which may exist in downstream of ERK1/2 pathway.

[Surgical Treatment for Temporal Lobe Epilepsy with Preservation of Postoperative Memory Function]

Rinshō Shinkeigaku = Clinical Neurology. Nov, 2004  |  Pubmed ID: 15651317

Temporal lobe epilepsy is frequently drug-resistant in adult epilepsy. However, its surgical treatment is very effective and about 70% of operated patients become seizure-free. As preoperative evaluation, analysis of seizure characteristics, scalp EEG with sphenoidal lead, and neuroimaging are most important. When these noninvasive examinations are concordant in focus localization, surgical treatment without prolonged recording by intracranial electrodes become feasible. In spite of good seizure outcome after temporal lobectomy, postoperative impairment of verbal memory has remained to be a long-standing problem. To cope with this ominous complication, we developed a new surgical method of hippocampal transection, based on the principle of multiple subpial transection (MST). Placing a small corticotomy on the anterior part of superior temporal gyrus, the inferior ventricle is opened through suctioning the temporal stem. Intraoperative electrocorticography (ECoG) is recorded over the hippocampus. After the extent of the epileptic area is determined, the alveus is cut with microscissors and the pyramidal layer is transected in parallel with neuronal fibers by a specially designed ring transector. With this procedure, epileptic discharges from the hippocampus can be completely abolished. In all 7 cases undergoing left hippocampal transection, postoperative verbal memory was preserved with excellent seizure outcome.

Lifetime and 6-month Prevalence of DSM-III-R Psychiatric Disorders in an Urban Community in Japan

Psychiatry Research. Jan, 2004  |  Pubmed ID: 14675748

We conducted a community-based interview survey of a random sample of residents aged 20 years or older in an urban community in Japan using the University of Michigan Version of the WHO Composite International Diagnostic Interview for selected mood and anxiety disorders and alcohol abuse/dependence according to DSM-III-R. The final sample consisted of 1029 respondents (response rate, 57%). The lifetime and 6-month prevalences of selected mood, anxiety and alcohol use disorders were low in general. Alcohol abuse/dependence was more prevalent in men than in women. Younger respondents had a greater risk of generalized anxiety disorder and alcohol dependence. A greater risk of mood, anxiety and alcohol use disorders was observed among a recent birth cohort. We confirmed a lower prevalence of mood and anxiety disorders and alcohol use disorders in a community population in Japan than in Western countries, observations that were similar to previous ones in East-Asian countries. The patterns of demographic correlates and comorbidity are similar to those of most other countries.

Usefulness of [11C]methionine PET in the Diagnosis of Dysembryoplastic Neuroepithelial Tumor with Temporal Lobe Epilepsy

Epilepsia. Jan, 2004  |  Pubmed ID: 14692906

We assessed the diagnostic value of [11C]methionine (MET) positron emission tomography (PET) in the differential diagnosis of dysembryoplastic neuroepithelial tumors (DNETs) among benign tumors associated with temporal lobe epilepsy (TLE).

Sleep Disturbance and Onset of Type 2 Diabetes

Diabetes Care. Jan, 2004  |  Pubmed ID: 14694011

The Prevalence of Primary Open-angle Glaucoma in Japanese: the Tajimi Study

Ophthalmology. Sep, 2004  |  Pubmed ID: 15350316

To assess the prevalence of primary open-angle glaucoma (POAG) and its association with intraocular pressure (IOP) in Tajimi City in central Japan.

Clinical Outcomes After Corpus Callosotomy in Patients with Bihemispheric Malformations of Cortical Development

Journal of Neurosurgery. Aug, 2004  |  Pubmed ID: 16206965

Epilepsy in patients with bihemispheric malformations of cortical development (MCD) is typically medically intractable. Focal resection has been reported to be ineffective. Corpus callosotomy has been advocated as a treatment option, but the results have been reported only in several case reports. The authors describe a series of 10 patients with bihemispheric MCDs who underwent total corpus callosotomy.

Circulation of Type 1 Vaccine-derived Poliovirus in the Philippines in 2001

Journal of Virology. Dec, 2004  |  Pubmed ID: 15564462

In 2001, highly evolved type 1 circulating vaccine-derived poliovirus (cVDPV) was isolated from three acute flaccid paralysis patients and one contact from three separate communities in the Philippines. Complete genomic sequencing of these four cVDPV isolates revealed that the capsid region was derived from the Sabin 1 vaccine strain but most of the noncapsid region was derived from an unidentified enterovirus unrelated to the oral poliovirus vaccine (OPV) strains. The sequences of the cVDPV isolates were closely related to each other, and the isolates had a common recombination site. Most of the genetic and biological properties of the cVDPV isolates were indistinguishable from those of wild polioviruses. However, the most recently identified cVDPV isolate from a healthy contact retained the temperature sensitivity and partial attenuation phenotypes. The sequence relationships among the isolates and Sabin 1 suggested that cVDPV originated from an OPV dose given in 1998 to 1999 and that cVDPV circulated along a narrow chain of transmission. Type 1 cVDPV was last detected in the Philippines in September 2001, and population immunity to polio was raised by extensive OPV campaigns in late 2001 and early 2002.

Identification of the Layers of the Bladder Wall on High-frequency Endoluminal Ultrasonography by a Needle Puncture Experiment

Ultrasound in Medicine & Biology. Mar, 2005  |  Pubmed ID: 15749551

The purpose of this study was to identify the layers of the bladder wall on high-frequency endoluminal ultrasonography (ELUS). We performed a needle puncture experiment using five normal pig bladders. The histologic layer structure was compared with the ELUS images obtained using a 30-MHz miniature transducer. The bladder wall was depicted as five layers by ELUS and these corresponded to the histologic layers. The first layer (hyperechoic) was a margin echo that included the epithelium and the upper part of the lamina propria. The second layer (hypoechoic) corresponded to the lamina propria and the third layer (hyperechoic) was a margin echo that included the upper part of the muscle layer. The fourth layer (hypoechoic) corresponded to the muscle layer, and the fifth layer (hyperechoic) was a margin echo that included the upper part of the adventitia.

The Brain-adipose Axis: a Review of Involvement of Molecules

Nutritional Neuroscience. Feb, 2005  |  Pubmed ID: 15909763

Many molecules are involved in the regulation of feeding behavior, and they and their receptors are located in the brain hypothalamus and adipocytes. On the basis of evidence suggesting an association between the brain and adipose tissue, we propose the concept of the brain-adipose axis. This model consists of (l) the expression of endogenous molecules and/or their receptors in the hypothalamus and peripheral adipose tissue, (2) the function of these molecules as appetite regulators in the brain, (3) their existence in the general circulation as secreted proteins and (4) the physiological affects of these molecules on fat cell size and number. These molecules can be divided into two anorexigenic and orexigenic classes. In adipose tissue, all orexigenic molecules possess adipogenic activity, and almost all anorexigenic molecules suppress fat cell proliferation. Although the manner, in which they present in the circulating blood connect the brain and peripheral adipocytes, remains to be well-organized, these observations suggest the positive feedback axis affecting molecules in the hypothalamus and adipose tissue. Analysis of the disturbance and dysregulation of this axis might promote the development of new anti-obesity drugs useful in treating the metabolic syndrome.

Molecular Mechanisms Associated with Leptin Resistance: N-3 Polyunsaturated Fatty Acids Induce Alterations in the Tight Junction of the Brain

Cell Metabolism. May, 2005  |  Pubmed ID: 16054080

High-fat diets cause peripheral leptin resistance, and dietary lipid composition affects sensitivity to leptin. We examined the role of n-3 polyunsaturated fatty acid (PUFA) in peripheral leptin resistance. Dietary PUFAs (0.4% wt/wt) caused insensitivity to peripherally but not intracerebroventricularly administered leptin. n-3 PUFA increased body weight, associated with a significant reduction of leptin concentration in the cerebrospinal fluid. Dietary n-3 PUFA reduced transport of endogenous or exogenously administered leptin into the brain, associated with increased expression of hypothalamic occludin, but caused no change in expression of leptin receptors, proteins associated with leptin signaling or other tight junction proteins. Continuous intracerebroventricular infusion of an antisense morpholino oligonucleotide targeted to occludin mRNA reversed n-3 PUFA-induced insensitivity to peripherally administered leptin. We conclude that n-3 PUFA induces peripheral leptin resistance via an increase in the expression of hypothalamic occludin, reducing paracellular transport of leptin into the brain.

Persistence of Oral Polio Vaccine Virus After Its Removal from the Immunisation Schedule in New Zealand

Lancet. Jul 30-Aug 5, 2005  |  Pubmed ID: 16054940

On Feb 1, 2002, inactivated poliomyelitis vaccines replaced live-attenuated oral poliovirus vaccine (OPV) in New Zealand's immunisation schedule, allowing systematic monitoring of OPV virus circulation. Findings of paediatric-inpatient surveillance indicate that 7% of children excreted polioviruses before this switch, but none did so 1 month afterwards. Acute flaccid paralysis surveillance detected no poliovirus during and after the switch, whereas enterovirus surveillance detected poliovirus only once during the switch. Environmental surveillance identified polioviruses in sewage samples until May, 2002, after which they were detected infrequently. Intratypic differentiation and sequencing showed that all polioviruses were Sabin-like. Multiple surveillance methods hence showed that OPV strains did not persist for extended periods after a vaccine switch in a developed country with a temperate climate. Sequence homology with Sabin vaccine parent strains indicated that polioviruses detected more than 4 months after the switch were of recent origin, consistent with importation from OPV-using countries.

[Laboratory Diagnosis for Non-polio Enteroviruses]

Nihon Rinsho. Japanese Journal of Clinical Medicine. Jul, 2005  |  Pubmed ID: 16111280

[Laboratory Diagnosis for Acute Hemorrhagic Conjunctivitis]

Nihon Rinsho. Japanese Journal of Clinical Medicine. Jul, 2005  |  Pubmed ID: 16111281

[Laboratory Diagnosis for Enterovirus 71 Infection]

Nihon Rinsho. Japanese Journal of Clinical Medicine. Jul, 2005  |  Pubmed ID: 16111282

The Tajimi Study Report 2: Prevalence of Primary Angle Closure and Secondary Glaucoma in a Japanese Population

Ophthalmology. Oct, 2005  |  Pubmed ID: 16111758

To determine the prevalence of primary angle-closure glaucoma (PACG), secondary glaucoma (SG), and all glaucoma in a Japanese population as a part of the Tajimi Study.

Kremezin (AST-120) Delays the Progression of Diabetic Nephropathy in Japanese Type 2 Diabetic Patients

Diabetes Care. Oct, 2005  |  Pubmed ID: 16186309

Intratypic Recombination Among Lineages of Type 1 Vaccine-derived Poliovirus Emerging During Chronic Infection of an Immunodeficient Patient

Journal of Virology. Oct, 2005  |  Pubmed ID: 16188964

We determined the complete genomic sequences of nine type 1 immunodeficient vaccine-derived poliovirus (iVDPV) isolates obtained over a 337-day period from a poliomyelitis patient from Taiwan with common variable immunodeficiency. The iVDPV isolates differed from the Sabin type 1 oral poliovirus vaccine (OPV) strain at 1.84% to 3.15% of total open reading frame positions and had diverged into at least five distinct lineages. Phylogenetic analysis suggested that the chronic infection was initiated by the fifth and last OPV dose, given 567 days before onset of paralysis, and that divergence of major lineages began very early in the chronic infection. Key determinants of attenuation in Sabin 1 had reverted in the iVDPV isolates, and representative isolates of each lineage showed increased neurovirulence for PVR-Tg21 transgenic mice. None of the isolates had retained the temperature-sensitive phenotype of Sabin 1. All isolates were antigenic variants of Sabin 1, having multiple amino acid substitutions within or near neutralizing antigenic sites 1, 2, and 3a. Antigenic divergence of the iVDPV variants from Sabin 1 followed two major independent evolutionary pathways. The emergence of distinct coreplicating lineages suggests that iVDPVs can replicate for many months at separate sites in the gastrointestinal tract. Some isolates had mosaic genome structures indicative of recombination across and within lineages. iVDPV excretion apparently ceased after 30 to 35 months of chronic infection. The appearance of a chronic VDPV excretor in a tropical, developing country has important implications for the strategy to stop OPV immunization after eradication of wild polioviruses.

A Sabin 3-derived Poliovirus Recombinant Contained a Sequence Homologous with Indigenous Human Enterovirus Species C in the Viral Polymerase Coding Region

Journal of Virology. Oct, 2005  |  Pubmed ID: 16188967

Outbreaks of poliomyelitis caused by circulating vaccine-derived polioviruses (cVDPVs) have been reported in areas where indigenous wild polioviruses (PVs) were eliminated by vaccination. Most of these cVDPVs contained unidentified sequences in the nonstructural protein coding region which were considered to be derived from human enterovirus species C (HEV-C) by recombination. In this study, we report isolation of a Sabin 3-derived PV recombinant (Cambodia-02) from an acute flaccid paralysis (AFP) case in Cambodia in 2002. We attempted to identify the putative recombination counterpart of Cambodia-02 by sequence analysis of nonpolio enterovirus isolates from AFP cases in Cambodia from 1999 to 2003. Based on the previously estimated evolution rates of PVs, the recombination event resulting in Cambodia-02 was estimated to have occurred within 6 months after the administration of oral PV vaccine (99.3% nucleotide identity in VP1 region). The 2BC and the 3D(pol) coding regions of Cambodia-02 were grouped into the genetic cluster of indigenous coxsackie A virus type 17 (CAV17) (the highest [87.1%] nucleotide identity) and the cluster of indigenous CAV13-CAV18 (the highest [94.9%] nucleotide identity) by the phylogenic analysis of the HEV-C isolates in 2002, respectively. CAV13-CAV18 and CAV17 were the dominant HEV-C serotypes in 2002 but not in 2001 and in 2003. We found a putative recombination between CAV13-CAV18 and CAV17 in the 3CD(pro) coding region of a CAV17 isolate. These results suggested that a part of the 3D(pol) coding region of PV3(Cambodia-02) was derived from a HEV-C strain genetically related to indigenous CAV13-CAV18 strains in 2002 in Cambodia.

Fat Intake is Associated with Serum Estrogen and Androgen Concentrations in Postmenopausal Japanese Women

The Journal of Nutrition. Dec, 2005  |  Pubmed ID: 16317133

A reduction in fat intake has been associated with decreased estrogen levels in dietary intervention studies. However, previous cross-sectional studies conducted mainly among Western populations did not find a positive association between fat intake and postmenopausal estrogen levels. This study examined the cross-sectional association of fat intake with serum levels of estrone, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEAS) in women. Study subjects were 324 healthy postmenopausal Japanese women. Diet including fat intake was assessed by a validated semiquantitative FFQ. After controlling for age and other potential breast cancer risk factors, serum estrone was positively associated with the percentage of energy from total fat (P = 0.04). The associations of serum estrone with monounsaturated fat and polyunsaturated fat were of borderline significance (P = 0.05). Serum DHEAS was positively associated with the percentage of energy from total fat (P = 0.007), saturated fat (P = 0.009), monounsaturated fat (P = 0.006), and polyunsaturated fat (P = 0.04). Serum estrone and DHEAS concentrations increased 11.8 and 9.3%, respectively, with a 5% increase in the percentage of energy from total fat. These data suggest that a high intake of fat is associated with higher serum levels of estrone and DHEAS in postmenopausal women.

Associations of Mammographic Density with Dietary Factors in Japanese Women

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Dec, 2005  |  Pubmed ID: 16365004

A high percentage of mammographic dense area has been strongly associated with a risk of beast cancer. The present cross-sectional study evaluated the relations of percent density with dietary factors, such as fats, protein, dietary fiber, and soy isoflavones.

Insulin Resistance Determines Efficacy of Glimepiride in Type 2 Diabetic Patients Not Well Controlled by Diet Alone

Diabetic Medicine : a Journal of the British Diabetic Association. Feb, 2005  |  Pubmed ID: 15660744

Akt2 Phosphorylates Synip to Regulate Docking and Fusion of GLUT4-containing Vesicles

The Journal of Cell Biology. Mar, 2005  |  Pubmed ID: 15753124

We have identified an unusual potential dual Akt/protein kinase B consensus phosphorylation motif in the protein Synip (RxKxRS(97)xS(99)). Surprisingly, serine 97 is not appreciably phosphorylated, whereas serine 99 is only a specific substrate for Akt2 but not Akt1 or Akt3. Although wild-type Synip (WT-Synip) undergoes an insulin-stimulated dissociation from Syntaxin4, the Synip serine 99 to phenylalanine mutant (S99F-Synip) is resistant to Akt2 phosphorylation and fails to display insulin-stimulated Syntaxin4 dissociation. Furthermore, overexpression of WT-Synip in 3T3L1 adipocytes had no effect on insulin-stimulated recruitment of glucose transporter 4 (GLUT4) to the plasma membrane, whereas overexpression of S99F-Synip functioned in a dominant-interfering manner by preventing insulin-stimulated GLUT4 recruitment and plasma membrane fusion. These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4-containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip-Syntaxin4 interaction.

Urinary Cadmium and Serum Levels of Estrogens and Androgens in Postmenopausal Japanese Women

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Mar, 2005  |  Pubmed ID: 15767353

Recent laboratory studies have suggested that cadmium is an estrogenic compound and may be a potential risk factor for breast cancer.

New Ultrasonic Cystofiberscope for Staging Bladder Tumors

Journal of Endourology / Endourological Society. Mar, 2005  |  Pubmed ID: 15798403

We report on a new ultrasonic cystofiberscope for staging bladder tumors. The endoscope makes it possible to view endoscopic and ultrasound images of bladder tumors at any location, either alternately in full screen or simultaneously on the same monitor, with higher resolution. The cystofiberscope is useful for assessing the depth of bladder tumor invasion accurately.

Our Experience with Pediatric Epilepsy Surgery Focusing on Corpus Callosotomy and Hemispherotomy

Epilepsia. 2005  |  Pubmed ID: 15816976

In pediatric patients with intractable epilepsy, surgical intervention should be considered in terms of seizure control and prevention of neuronal deterioration. We present our experience with pediatric epilepsy surgery, focusing on corpus callosotomy and hemispherotomy.

High Frequency Activities in the Human Orbitofrontal Cortex in Sleep-wake Cycle

Neuroscience Letters. May, 2005  |  Pubmed ID: 15823426

We recorded human orbitofrontal electrocorticogram during wakefulness and sleep in epileptic patients using subdural electrodes. During wakefulness and rapid eye movement (REM) sleep, we observed beta activity in the raw orbitofrontal signals. Power spectral analysis demonstrated beta enhancement during wakefulness and REM sleep when compared to slow wave sleep (SWS). During the phasic REM periods, the beta power was significantly lower than during the tonic REM periods. Gamma enhancement manifested itself in four out of six subjects during the phasic periods. This study is the first that has focused on electrical activity in the human orbitofrontal cortex. Although the role of the orbitofrontal cortex during sleep still remains unclear, high frequency activities give us important suggestions in elucidating the human sleep mechanism.

Temperature-sensitive Mutants of Enterovirus 71 Show Attenuation in Cynomolgus Monkeys

The Journal of General Virology. May, 2005  |  Pubmed ID: 15831951

Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease and is sometimes associated with serious neurological disorders. In this study, an attempt was made to identify molecular determinants of EV71 attenuation of neurovirulence in a monkey infection model. An infectious cDNA clone of the virulent strain of EV71 prototype BrCr was constructed; temperature-sensitive (ts) mutations of an attenuated strain of EV71 or of poliovirus (PV) Sabin vaccine strains were then introduced into the infectious clone. In vitro and in vivo phenotypes of the parental and mutant viruses were analysed in cultured cells and in cynomolgus monkeys, respectively. Mutations in 3D polymerase (3D(pol)) and in the 3' non-translated region (NTR), corresponding to ts determinants of Sabin 1, conferred distinct temperature sensitivity to EV71. An EV71 mutant [EV71(S1-3')] carrying mutations in the 5' NTR, 3D(pol) and in the 3' NTR showed attenuated neurovirulence, resulting in limited spread of virus in the central nervous system of monkeys. These results indicate that EV71 and PV1 share common genetic determinants of neurovirulence in monkeys, despite the distinct properties in their original pathogenesis.

A 30-year-old Male Treated by Neurosurgery Against Temporal Lobe Epilepsy

Neuropathology : Official Journal of the Japanese Society of Neuropathology. Jun, 2005  |  Pubmed ID: 15875912

Association of Vegetable Intake with Urinary 6-sulfatoxymelatonin Level

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. May, 2005  |  Pubmed ID: 15894698

Melatonin is present in plants consumed as vegetables; however, only a limited number of vegetables have been tested for melatonin. The antiproliferative, antioxidative, and immunostimulatory effects of melatonin have been reported from laboratory studies. The potential protective effects of vegetable against cancer and cardiovascular disease may be partially attributable to an increased melatonin intake from vegetables. As a first step to test this hypothesis, we evaluated whether vegetable intake is associated with an increased urinary melatonin in 289 community-dwelling Japanese women. Diet, including vegetable consumption, was assessed with a validated 169-item semiquantitative food-frequency questionnaire. Urinary 6-sulfatoxymelatonin (aMT6-s) was measured in the first-void morning urines. There was a significant positive association between vegetable intake and urinary aMT6-s levels. The mean urinary aMT6-s was 16% higher in women with the highest quartile of vegetable intake than it was in those with the lowest quartile of intake. This association may be explained by the melatonin contained in vegetables. However, data should be regarded as preliminary because it is impossible to estimate dietary melatonin intake from vegetables and or from the entire diet because of incomplete data for melatonin in plants.

[Surgical Treatment for Epilepsy, Focusing on Temporal Lobe Epilepsy]

Nō to Shinkei = Brain and Nerve. Mar, 2005  |  Pubmed ID: 15912756

Brachial-ankle Pulse Wave Velocity

Internal Medicine (Tokyo, Japan). Jul, 2005  |  Pubmed ID: 16093585

[Laboratory Diagnosis for Poliovirus]

Nihon Rinsho. Japanese Journal of Clinical Medicine. Jul, 2005  |  Pubmed ID: 16111279

Intrafamilial Transmission of a Sabin 1-related Poliovirus in Shizuoka Prefecture, Japan

Japanese Journal of Infectious Diseases. Aug, 2006  |  Pubmed ID: 16936354

One Percent Ability and Ninety-nine Percent Perspiration: a Study of a Japanese Memorist

Journal of Experimental Psychology. Learning, Memory, and Cognition. Sep, 2006  |  Pubmed ID: 16938056

In 1987, Hideaki Tomoyori, a Japanese memorist, set a world record for reciting the first 40,000 digits of pi. The authors report results from a series of tests that give a view of Tomoyori's memory performance compared with that of a control group, matched for age and educational level. He showed very good scores on tasks with digits, such as digit memory span tasks and 5 x 5 number matrix learning, although some of the control participants were nearly as good. In contrast, his performance was not particularly good for learning word lists and story recall. Overall, his performance on the tasks does not suggest that he has superior cognitive abilities. We believe that his extraordinary memory performance in reciting the digits of pi results from his effective use of a combination of digit-syllable transformations and imagery mnemonics developed from extensive practice. These results are consistent with the skilled memory framework.

Effects of E. Coli Chaperones on the Solubility of Human Receptors in an in Vitro Expression System

Molecular Biotechnology. Jul, 2006  |  Pubmed ID: 16946450

The implementation of efficient technologies for the production of recombinant mammalian membrane receptors is an outstanding challenge in understanding receptor-ligand actions and the development of therapeutic antibodies. In order to improve the solubility of recombinant extracellular domains of human membrane receptors expressed in Escherichia coli, proteins were synthesized by an E. coli in vitro translation system supplemented with bacterial molecular chaperones, such as GroEL-GroES (GroEL/ES), Trigger factor (TF), a DnaK-DnaJ-GrpE chaperone system (DnaKJE), and/or a heat shock protein Hsp100, ClpB. The following three proteins that are prone to aggregation were examined: the extracellular domain (ECD) or the second immunoglobulin-like domain (IgII) of the human neurotrophin receptor TrkC (TrkC-ECD and TrkC-IgII), and the C-type lectin carbohydrate recognition domain of the human asialoglycoprotein receptor (ASGPR HI CRD). The cooperative chaperone system including GroEL/ES, DnaKJE and ClpB had a marked effect on the solubility of TrkC-ECD and TrkC-IgII, and the GroEL/ES-DnaKJE-TF chaperone system was more effective for TrkC-IgII. The GroEL/ES-DnaKJE-TF chaperone network increased the yield of soluble ASGPR HI CRD. The present findings demonstrate that E. coli molecular chaperones are useful in improving the yield of soluble recombinant extracellular domains of human membrane receptors in an E. coli expression system.

Molecular Epidemiology of Echoviruses 11 and 13, Based on an Environmental Surveillance Conducted in Toyama Prefecture, 2002-2003

Applied and Environmental Microbiology. Sep, 2006  |  Pubmed ID: 16957267

Nineteen echovirus 11 (E11) and 12 E13 isolates were isolated from three rivers in Toyama Prefecture, Japan, during an environmental surveillance conducted from April 2002 to March 2003. The nucleotide sequences of E13 isolates were closely related to those from patients with aseptic meningitis, with less than 1.3% divergence in the VP1 region of the viral capsid gene, and belonged to the same clade responsible for a worldwide outbreak that started in 2000. In contrast, E11 isolates were clustered into three genomic groups and were not closely related to echovirus strains isolated from patients. These results suggest that the combination of both virus isolation from environmental sources and phylogenetic analysis could be complementary assessment approaches to trace prevalent and minor circulating enteroviruses in the human population.

[Bone and Joint Infection]

Nihon Rinsho. Japanese Journal of Clinical Medicine. Sep, 2006  |  Pubmed ID: 16972689

Older adults are at risk for the immune dysfunction associated with advanced age, which contribute to their increased risk of infection. Hematogenous osteomyelitis occurs not only in children, but also in older adults. Iatrogenic septic arthritis can be occured after the intraarticular injection for the osteoarthritis in aging society. Tuberculous spondylitis occurs in older adults and the differential diagnosis with pyogenic spondylitis and vertebral metastasis is important.

Associations Among Maternal Soy Intake, Isoflavone Levels in Urine and Blood Samples, and Maternal and Umbilical Hormone Concentrations (Japan)

Cancer Causes & Control : CCC. Nov, 2006  |  Pubmed ID: 17006716

In utero exposure to high levels of endogenous estrogens has been hypothesized to increase breast cancer risk in later life. A high intake of soy has been suggested to protect against breast cancer. We examined the hypothesis that maternal soy intake may be inversely associated with pregnancy hormone levels.

Quantitative Analysis of Poliomyelitis-like Paralysis in Mice Induced by a Poliovirus Replicon

The Journal of General Virology. Nov, 2006  |  Pubmed ID: 17030866

Poliovirus (PV) infection causes severe paralysis, typically of the legs, by destruction of the motor neurons in the spinal cord. In this study, the relationship between PV replication in the spinal cord, damage in the motor neurons and poliomyelitis-like paralysis was analysed in transgenic mice expressing the human PV receptor (TgPVR21). First, a PV replicon encoding firefly luciferase in place of the capsid genes (PV-Fluc mc) was trans-encapsidated in 293T cells and the trans-encapsidated PV-Fluc mc (TE-PV-Fluc mc) was then inoculated into the spinal cords of TgPVR21 mice. TE-PV-Fluc mc was recovered with a titre of 6.3 x 10(7) infectious units ml(-1), which was comparable to those of PV1 strains. TgPVR21 mice inoculated with TE-PV-Fluc mc showed non-lethal paralysis of the hindlimbs, with severity ranging from a decline in grip strength to complete flaccid paralysis. The replication of TE-PV-Fluc mc in the spinal cord reached peak levels at 10 h post-inoculation (p.i.), followed by the appearance of paralysis at as early as 12 h p.i., reaching a plateau at 16 h p.i. Histological analysis showed a correlation between the lesion and the severity of the clinical symptoms in most mice. However, severe paralysis could also be observed with an apparently low lesion score, where as few as 5.3 x 10(2) motor neurons (1.4 % of the susceptible cells in the lumbar cord) were infected by TE-PV-Fluc mc. These results indicate that PV replication in a small population of the motor neurons was critical for severe residual poliomyelitis-like paralysis in TgPVR21 mice.

Identification of Nesfatin-1 As a Satiety Molecule in the Hypothalamus

Nature. Oct, 2006  |  Pubmed ID: 17036007

The brain hypothalamus contains certain secreted molecules that are important in regulating feeding behaviour. Here we show that nesfatin, corresponding to NEFA/nucleobindin2 (NUCB2), a secreted protein of unknown function, is expressed in the appetite-control hypothalamic nuclei in rats. Intracerebroventricular (i.c.v.) injection of NUCB2 reduces feeding. Rat cerebrospinal fluid contains nesfatin-1, an amino-terminal fragment derived from NUCB2, and its expression is decreased in the hypothalamic paraventricular nucleus under starved conditions. I.c.v. injection of nesfatin-1 decreases food intake in a dose-dependent manner, whereas injection of an antibody neutralizing nesfatin-1 stimulates appetite. In contrast, i.c.v. injection of other possible fragments processed from NUCB2 does not promote satiety, and conversion of NUCB2 to nesfatin-1 is necessary to induce feeding suppression. Chronic i.c.v. injection of nesfatin-1 reduces body weight, whereas rats gain body weight after chronic i.c.v. injection of antisense morpholino oligonucleotide against the gene encoding NUCB2. Nesfatin-1-induced anorexia occurs in Zucker rats with a leptin receptor mutation, and an anti-nesfatin-1 antibody does not block leptin-induced anorexia. In contrast, central injection of alpha-melanocyte-stimulating hormone elevates NUCB2 gene expression in the paraventricular nucleus, and satiety by nesfatin-1 is abolished by an antagonist of the melanocortin-3/4 receptor. We identify nesfatin-1 as a satiety molecule that is associated with melanocortin signalling in the hypothalamus.

Hippocampal Transection for Treatment of Left Temporal Lobe Epilepsy with Preservation of Verbal Memory

Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. Apr, 2006  |  Pubmed ID: 16517167

Despite good seizure outcome with temporal lobectomy, postoperative impairment of verbal memory remains unsolved. To address this problem we developed a new method, applying the rationale of multiple subpial transection (MST) to the hippocampus. The inferior ventricle is accessed without disrupting the neuronal pathways related to verbal memory. Intraoperative electrocorticography is recorded over the hippocampus and amygdala. After the extent of the epileptic area is determined, multiple transections of the pyramidal layer under the alveus is performed using specially designed ring transectors. After this procedure, epileptic discharges from the hippocampus can be completely abolished. Of 21 cases undergoing this operation, 12 left-sided and nine right-sided, 17 were followed up for more than one year. Fourteen (82%) are seizure free, two (12%) have rare seizures, and one (6%) has significantly improved. Of eight patients who underwent a battery of neuropsychometric tests both before and after left hippocampal transection, postoperative verbal memory was completely preserved in seven cases, and one transiently worsened patient recovered within 6 months. However, these results are still preliminary as the number of patients is small and the follow-up time short. The accumulation of cases and follow-up of greater duration will be necessary to precisely confirm the efficacy of this new technique.

The Relationship Between the Consumption of Meat, Fat, and Coffee and the Risk of Colon Cancer: a Prospective Study in Japan

Cancer Letters. Dec, 2006  |  Pubmed ID: 16519996

The risk of the development of colon cancer in relation to a western diet was studied in a community-based cohort in Japan. From 1992 to 2000, 13,894 men and 16,327 women were followed. In men, high consumption of processed meat increased the risk in comparison with low consumption (adjusted RR=1.98, 95% CI: 1.24-3.16). In women, daily coffee drinkers had a reduced risk in comparison with individuals who never or rarely drank coffee (adjusted RR=0.43, 95% CI: 0.22-0.85). The findings suggest the possible linkage between a western diet and risk of colon cancer.

Effectiveness of Cerebral Hemispherotomy for Improving Behavioral Disorders Associated with Intractable Post-traumatic Seizures

Neurologia Medico-chirurgica. Apr, 2006  |  Pubmed ID: 16636508

A 25-year-old man presented with intractable post-traumatic seizures after suffering cerebral contusion in a traffic accident at age 5 years. Cerebral hemispherotomy was performed to transect the neuronal fibers to interrupt connections between seizure foci in wide areas of the brain, and to minimize the resected brain parenchyma. His seizures resolved and behavioral disorders improved, which had been impaired since age 8 years. Increased glucose metabolism in the normal frontal lobe detected by interictal fluorodeoxyglucose-positron emission tomography was correlated with the improvements in behavioral disorders. These findings suggest that the effects of seizures may be reversible in brain areas connected with, but remote from, the epileptogenic cortex.

Temporal Lobe Epilepsy Caused by Dermoid Cyst

Neurologia Medico-chirurgica. Apr, 2006  |  Pubmed ID: 16636514

A 15-year-old boy presented with a dermoid cyst in the left temporal lobe manifesting as complex partial seizures. Magnetic resonance imaging demonstrated a tumor with mixed signal intensity in the left anterior temporal subdural area, but no evidence of rupture. Intraoperatively, the tumor was located mainly in the deep sylvian fissure, adjacent to the amygdala, and had compressed the hippocampus. Intraoperative electrocorticography (ECoG) showed sporadic interictal spikes in both the adjacent areas of the tumor and over the anterior segment of the hippocampus. Total removal of the tumor and gliotic area of the surrounding tissue including the amygdala was performed. The hippocampal epileptic region was treated by transection of the pyramidal layer to preserve verbal memory function. Histological examination showed the dermoid tumor was closely attached to the brain parenchyma. The complex partial seizures ceased completely after surgery. Intraoperative recording of ECoG from the hippocampus and other limbic structures was very important to determine the epileptogenic area even if the tumor did not directly invade the hippocampus.

Risk Factors for Open-angle Glaucoma in a Japanese Population: the Tajimi Study

Ophthalmology. Sep, 2006  |  Pubmed ID: 16828504

To identify the risk factors associated with primary open-angle glaucoma (POAG) in the Tajimi Study.

Effectiveness of Cervical Cancer Screening over Cervical Cancer Mortality Among Japanese Women

Japanese Journal of Clinical Oncology. Aug, 2006  |  Pubmed ID: 16844732

Various studies have revealed that cervical cancer (CC) screening significantly reduces both CC incidence and mortality in developed countries. Although Japan introduced a nationwide government funded annual CC screening for the women aged 30+ in 1982, the effectiveness of CC screening on CC mortality has not yet been evaluated by any prospective cohort study. Therefore, the present study evaluated the association of CC mortality with self-reported CC screening and some other factors by a nationwide cohort study.

Prevalence and Causes of Low Vision and Blindness in a Japanese Adult Population: the Tajimi Study

Ophthalmology. Aug, 2006  |  Pubmed ID: 16877074

To determine the prevalence and causes of low vision and blindness in a Japanese adult population.

Estrogen and Alpha-fetoprotein Levels in Maternal and Umbilical Cord Blood Samples in Relation to Birth Weight

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Aug, 2006  |  Pubmed ID: 16896034

Birth weight has been associated with a subsequent risk of breast cancer. The present study examined associations between birth weight and pregnancy estrogens and alpha-fetoprotein (AFP). The concentrations of estradiol, estriol, and AFP were measured in maternal and umbilical cord blood samples from 194 women during pregnancy and at birth. Birth weight was significantly positively correlated with maternal serum estradiol and estriol levels in the 29th week (estradiol: r = 0.16, P = 0.03; estriol: r = 0.29, P = 0.001) and at delivery (estradiol: r = 0.20, P = 0.01; estriol: r = 0.41, P < 0.0001) after controlling for covariates. The umbilical cord estriol level was moderately but significantly correlated with birth weight (r = 0.15, P = 0.049). There was no significant association between umbilical cord serum estradiol and birth weight. There was no significant association between birth weight and maternal serum AFP in any gestational week. Umbilical cord AFP was significantly inversely correlated with birth weight (r = -0.16, P = 0.04). Umbilical cord AFP was unrelated to cord levels of estradiol and estriol. The data suggested a greater exposure to estriol and a lower exposure to AFP among high birth weight babies.

Associations of Menstrual Cycle Length with Intake of Soy, Fat, and Dietary Fiber in Japanese Women

Nutrition and Cancer. 2006  |  Pubmed ID: 16898860

A decreased risk of breast cancer has been reported among women who have longer menstrual cycles or anovulatory cycles. The present study examined the relationships between intake of fat, soy, and dietary fiber and length of menstrual cycle among 341 Japanese women aged 18 to 29 yr old at two colleges and three nursing schools. Intake of nutrients and foods including fats, dietary fiber, and soy products was estimated through the use of a validated semi-quantitative food frequency questionnaire. The mean cycle length was determined for each women based on a prospective record of menstruation. Polyunsaturated fat intake was significantly inversely associated with cycle length; the means of cycle length were 33.2 and 31.0 days for the lowest and the highest quintiles of intake, respectively, after controlling for covariates (trend = 0.03). The odds ratio of a long cycle (> 35 days) for the highest vs. lowest quintile of dietary fiber intake was 2.12 (95% confidence interval 1.00-4.47), although the trend was not statistically significant. The data suggest that polyunsaturated fat and dietary fiber intake are associated with the parameters of menstrual cycle length, but further studies are required to better characterize these associations.

[A Case of Sturge-Weber Syndrome with Severe Temper Tantrum]

No Shinkei Geka. Neurological Surgery. Aug, 2006  |  Pubmed ID: 16910495

We report a case of Sturge-Weber syndrome with intractable epilepsy presenting complex partial seizures(CPSs) and severe temper tantrum successfully treated with anterior temporal lobectomy. A 23-month-old girl without facial angioma presented with seizures from 8 months after birth. Neuroradiological examination demonstrated angioma in the left temporooccipital lobes and calcification in the left occipital lobe. Thus she was diagnosed as having Sturge-Weber syndrome. Her parents sought medical advice because of intractable and more frequent CPSs and a change in temperament manifesting as severe temper tantrums. Interictal electroencephalogram (EEG) showed relatively mild abnormal slow wave discharges in the left temporal region. The patient underwent left anterior temporal lobectomy based on intraoperative electrocorticography (ECoG) findings. Histopathological examination demonstrated gliotic change in the amygdala. After the surgery, she has remained seizure-free for 14 months while taking anticonvulsants and temper tantrums ultimately showed remission 10 months following surgery. This case may indicate that severe temper tantrum was associated with a change in amygdala structures.

[Brain-adipose Axis and Leptin Resistance]

Nihon Rinsho. Japanese Journal of Clinical Medicine. Dec, 2006  |  Pubmed ID: 17458203

[Analysis of Self-assessment of Everyday Memory Using Metamemory Questionnaires]

Shinrigaku Kenkyu : The Japanese Journal of Psychology. Oct, 2006  |  Pubmed ID: 17447447

Several metamemory questionnaires have been widely used in psychological research with various populations including young or elderly, and clinical or non-clinical participants. This study investigates the factor structures in three typical metamemory questionnaires. The Everyday Memory Questionnaire (EMQ: 28 items), the Cognitive Failures Questionnaire (CFQ: 25 items), and the Memory Ability Questionnaire (MAQ: 31 items) were administered to 860 undergraduate students. Factor analyses for the data from each questionnaire indicated that the EMQ. the CFQ, and the MAQ mainly consisted of five, five, and four factors, respectively. A factor analysis was performed on the combined data relating to these 14 factors to examine the relatedness among the factors. Three factors were obtained: retrospective memory, prospective memory, and memory for person's names. The results were discussed in terms of the differences of content and formats of the questionnaire.

[Testicular Metastasis and Local Recurrence of Renal Cell Carcinoma After Nephron-sparing Surgery in Von Hippel-Lindau Disease]

Hinyokika Kiyo. Acta Urologica Japonica. Mar, 2007  |  Pubmed ID: 17447484

Bilateral nephron-sparing surgery was performed on a 56-year-old man with von Hippel-Lindau disease as initial therapy for renal cell carcinoma (RCC). Two years after the surgery, an abdominal computerized tomography (CT) scan revealed local recurrence of RCC. The patient was admitted to our hospital after another CT scan three years later that indicated aggravation of the cancer. On physical examination, he complained of swelling of the scrotum. The patient was diagnosed with an intra-scrotal malignant tumor and local recurrence of RCC. We performed high orchiectomy and nephrectomy. The testicular tumor was diagnosed as testicular metastasis of RCC on pathological examination.

Sex Differences in Preferences for Coffee Sweetness Among Japanese Students

Perceptual and Motor Skills. Oct, 2007  |  Pubmed ID: 18065062

The purpose of the present study was to examine sex differences in preferences for coffee sweetness. The participants were 59 Japanese undergraduate students. Men preferred sweeter coffee than women, while both men and women showed almost the same preference for acidic beverage sweetness. The sex difference in preferences for coffee sweetness may be related to coffee-drinking habits.

Rapid Genome Sequencing of RNA Viruses

Emerging Infectious Diseases. Feb, 2007  |  Pubmed ID: 17479903

We developed a system for rapid determination of viral RNA sequences whereby genomic sequence is obtained from cultured virus isolates without subcloning into plasmid vectors. This method affords new opportunities to address the challenges of unknown or untypeable emerging viruses.

[Hand, Foot and Mouth Disease]

Nihon Rinsho. Japanese Journal of Clinical Medicine. Mar, 2007  |  Pubmed ID: 17491403

Factors Shaping Vividness of Memory Episodes: Visitors' Long-term Memories of the 1970 Japan World Exposition

Memory (Hove, England). Feb, 2007  |  Pubmed ID: 17534111

This study investigated how visitors' psychological and behavioural factors, identified in the literature, shaped their vivid long-term memories of their experiences of the Japan World Exposition, Osaka, 1970 (Expo '70) as a context. In this study, 112 memory episodes were identified from the long-term memories of 48 participants; they were rated in terms of their memory vividness and on a set of factors including affect, agenda fulfilment, intentionality, and rehearsal. The influence of these factors on the vividness of episodic and/or autobiographic memories of experiences that occurred 34 years ago was examined in two stages. First, the relationship between memory vividness and individual factors was investigated separately. Second, the relationship between memory vividness and all factors was examined through a multiple regression analysis, and the relative importance of these factors on memory vividness identified. Stage one analysis showed that all factors except intentionality were related to memory vividness in individual analyses, and curvilinear relationships between memory vividness and the factors found. Stage two analysis, in which all factors were included in a multiple regression analysis, found that rehearsal was positively related to memory vividness and all other factors not significant in the presence of rehearsal.

An Attenuated Strain of Enterovirus 71 Belonging to Genotype a Showed a Broad Spectrum of Antigenicity with Attenuated Neurovirulence in Cynomolgus Monkeys

Journal of Virology. Sep, 2007  |  Pubmed ID: 17567701

Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also sometimes associated with serious neurological disorders. In this study, we characterized the antigenicity and tissue specificity of an attenuated strain of EV71 [EV71(S1-3')], which belongs to genotype A, in a monkey infection model. Three cynomolgus monkeys were inoculated with EV71(S1-3'), followed by lethal challenge with the parental virulent strain EV71(BrCr-TR) via an intravenous route on day 45 postinoculation of EV71(S1-3'). Monkeys inoculated with EV71(S1-3') showed a mild neurological symptom (tremor) but survived lethal challenge by virulent EV71(BrCr-TR) without exacerbation of the symptom. The immunized monkey sera showed a broad spectrum of neutralizing activity against different genotypes of EV71, including genotypes A, B1, B4, C2, and C4. For the strains examined, the sera showed the highest neutralization activity against the homotype (genotype A) and the lowest neutralization activity against genotype C2. The order of decreasing neutralization activity of sera was as follows: A > B1 > C4 > B4 > C2. To examine the tissue specificity of EV71(S1-3'), two monkeys were intravenously inoculated with EV71(S1-3'), followed by examination of virus distribution in the central nervous system (CNS) and extraneural tissues. In the CNS, EV71(S1-3') was isolated only from the spinal cord. These results indicate that EV71(S1-3') acts as an effective antigen, although this attenuated strain was still neurotropic when inoculated via the intravenous route.

Soy Product Consumption and the Risk of Colon Cancer: a Prospective Study in Takayama, Japan

Nutrition and Cancer. 2007  |  Pubmed ID: 17571948

The relationship of the intake of soy products and the incidence of colon cancer was prospectively evaluated in a population-based cohort study in Japan. The total intake of soy products and isoflavones in a daily diet was estimated from a validated questionnaire administered at the baseline. The participation rate of the questionnaire was 92.0%. The participants were followed from 1992 to 2000, and colon cancer diagnoses were identified at the main hospitals in the study area. In the analysis, 13,894 men and 16,327 women were included. The medians for energy-adjusted soy product intake were 85.52 g/day for men and 79.60 g/day for women. During follow-up, 111 men and 102 women were diagnosed with colon cancer. A Cox-proportional hazard model was applied to assess the risk of colon cancer incidence. Among women, the risk was reduced with an increased soy product consumption; the hazard ratio in the highest tertile was 0.56 (95% CI 0.34-0.92) compared as the lowest tertile (trend: P=0.04), after adjusting for multiple potential confounders. Among men, no significant association was observed. Our results exhibited the weak benefit of soy foods only among women. Further research to confirm our results may be beneficial.

Clinical Anatomical Study of Pedicled Vascularised Scapular Bone Graft Using the Angular Branch

Hand Surgery : an International Journal Devoted to Hand and Upper Limb Surgery and Related Research : Journal of the Asia-Pacific Federation of Societies for Surgery of the Hand. 2007  |  Pubmed ID: 17613180

This study is an anatomical investigation of the angular branch of thoracodorsal artery, and examines the possible range of clinical targets for pedicled vascularised scapular bone graft. Forty-six cadavers were studied. The blood vessel length was calculated, and the distance required to reach the distal humerus from the lower end of the articular surface of the humeral head as reference point was compared with bone length. The length from reference point was an average of 121.7 mm. It was thought that the maximum distance to arrive in reference point to the distal humerus was a total of blood vessel length and transplantation bone length, which was an average of 246.3 mm. This was longer than the average of 240.8 mm of bone length from reference point to humeral medial condyle. This study had confirmed that a pedicled vascularised scapular bone graft using the angular branch could be transplanted to the distal humerus.

Chop-deficient Mice Showed Increased Adiposity but No Glucose Intolerance

Obesity (Silver Spring, Md.). Jul, 2007  |  Pubmed ID: 17636082

CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP)-10/growth arrest and DNA damage 153 is a dominant-negative member of the C/EBP transcription family and inhibits adipogenesis in vitro. The study was undertaken to determine the role of CHOP in obesity in vivo.

A Quantitative Trait Locus for Cold Tolerance at the Booting Stage on Rice Chromosome 8

TAG. Theoretical and Applied Genetics. Theoretische Und Angewandte Genetik. Sep, 2007  |  Pubmed ID: 17657471

A quantitative trait locus (QTL) for cold tolerance at the booting stage of a cold-tolerant rice breeding line, Hokkai-PL9, was analyzed. A total of 487 simple sequence repeat (SSR) markers distributed throughout the genome were used to survey for polymorphism between Hokkai-PL9 and a cold-sensitive breeding line, Hokkai287, and 54 markers were polymorphic. Single marker analysis revealed that markers on chromosome 8 are associated with cold tolerance. By interval mapping using an F(2) population between Hokkai-PL9 and Hokkai287, a QTL for cold tolerance was detected on the short arm of chromosome 8. The QTL explains 26.6% of the phenotypic variance, and its additive effect is 11.4%. Substitution mapping suggested that the QTL is located in a 193-kb interval between SSR markers RM5647 and PLA61. We tentatively designated the QTL as qCTB8 (quantitative trait locus for cold tolerance at the booting stage on chromosome 8).

Prospective Cohort Study of Body Mass Index in Adolescence and Death from Stomach Cancer in Japan

Cancer Science. Nov, 2007  |  Pubmed ID: 17725807

We investigated the association between body mass index (BMI) values and the risk of death from stomach cancer later in life. From 1992 to 2000, 28 443 participants (13 211 men and 15 232 women) were followed, and 129 deaths from stomach cancer (86 men and 43 women) occurred. BMI (BMI at the baseline) and BMI(20y) (BMI at age 20 years) were obtained by questionnaire at the beginning of the study. Men in the middle and highest tertiles of BMI(20y) had a higher risk of death from stomach cancer than those in the lowest tertile (after controlling for covariates, hazard ratio [HR] = 2.73 with 95% confidence interval [CI] 1.26-5.89 for the middle tertile; HR = 2.15 with 95% CI 0.97-4.73 for the highest tertile), although there was no significant trend (P = 0.30). Likewise, women in the middle and highest tertiles of BMI(20y) had an increased risk of death from stomach cancer (HR = 5.17 with 95% CI 1.50-17.87 for the middle tertile; HR = 4.22 with 95% CI 1.18-15.05 for the highest tertile; P for trend = 0.05). The analysis of BMI at the baseline did not show a significant relationship with the risk of death from stomach cancer. These results suggest that a high BMI(20y) is associated with an increased risk of death from stomach cancer.

Antigenic Characterization of a Formalin-inactivated Poliovirus Vaccine Derived from Live-attenuated Sabin Strains

Vaccine. Oct, 2007  |  Pubmed ID: 17825459

A candidate inactivated poliovirus vaccine derived from live-attenuated Sabin strains (sIPV), which are used in the oral poliovirus vaccine (OPV), was prepared in a large-production scale. The modification of viral antigenic epitopes during the formalin inactivation process was investigated by capture ELISA assays using type-specific and antigenic site-specific monoclonal antibodies (MoAbs). The major antigenic site 1 was modified during the formalin inactivation of Sabin 1. Antigenic sites 1-3 were slightly modified during the formalin inactivation of Sabin 2 strain. Sites 1 and 3 were altered on inactivated Sabin 3 virus. These alterations were different to those shown by wild-type Saukett strain, used in conventional IPV (cIPV). It has been previously reported that type 1 sIPV showed higher immunogenicity to type 1 cIPV whereas types 2 and 3 sIPV induced lower level of immunogenicity than their cIPV counterparts. Our results suggest that the differences in epitope structure after formalin inactivation may account, at least in part, for the observed differences in immunogenicity between Sabin and wild-type inactivated poliovaccines.

Urinary 6-sulfatoxymelatonin and Mammographic Density in Japanese Women

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Nov, 2007  |  Pubmed ID: 18006946

A protective role of melatonin in the etiology of breast cancer has been suggested. The down-regulation of estrogen secretion by melatonin is thought to be a main cause of the link between melatonin and breast cancer risk. The present cross-sectional study examined whether the urinary 6-sulfatoxymelatonin (aMT6-s) level is inversely associated with mammographic density, which is regarded as a marker of breast cancer risk. The study subjects were 289 Japanese women (175 premenopausal and 123 postmenopausal women) who were recruited from participants in a mammographic breast cancer screening. The size of the total breast area and that of the dense area were measured quantitatively using an automated mammographic mass detection method. The concentration of aMT6-s was measured using first-void morning urine. In premenopausal women, the urinary aMT6-s level was significantly positively associated with percent density after controlling for covariates (P for trend=0.02). There was no significant association between urinary aMT6-s level and the percent density in postmenopausal women. We found no evidence that the melatonin level is inversely associated with mammographic density.

Diagnostic Surgical Neuropathology of Intractable Epilepsy

Neuropathology : Official Journal of the Japanese Society of Neuropathology. Dec, 2007  |  Pubmed ID: 18021382

As neurosurgical treatments have been increasingly applied to patients who have intractable epilepsy, much knowledge on pathological changes in surgically removed brain tissues have become clearer in recent years, as well as on the neuroimaging findings which are analyzed with a variety of techniques, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT) in combination with digital imaging and communication in medicine (DICOM), statistical parametric mapping (SPM), subtraction ictal SPECT coregistered to MRI (SISCOM) and/or PET-guided intraoperative navigation system, as mentioned in detain in another article in this issue by Maehara et al. Representative and relatively common diseases, treated by epilepsy-surgery, are as follows; hippocampal sclerosis, amygdaloid sclerosis, coarse and macroscopic brain malformation (focal cortical dysplasia, hemimegalencephaly, tuberous sclerosis), tumors (dysembryoplastic neuroepithelial tumor, ganglioglioma, etc.), destructive lesions and the others. It is a fact, however, that there remains many problems in the diagnostic criteria or histological grading systems, especially in various cortical dysplasias described above. On the other hand, histologically minor but clinically serious lesions have become to be known through careful observations on surgically removed tissues which showed no neuroradiological findings. A good well-known example is microdysgenesis of the cerebrum which is characterized by the presence of both the white mater ectopic neurons and the vascular meandering abnormalities with glial satellitosis. There must be another important histological phenotypes of microdysgenesis, except the above-mentioned ones, that are not yet established at present. Therefore, it is believed that there remains various problems on the diagnostic neuropathology of epileptic lesions with or without neuroimaging findings in which we have to give answers in a few days to come.

Leptin Resistance and Obesity

Endocrine Journal. Feb, 2007  |  Pubmed ID: 17053294

Performance of Frequency-doubling Technology Perimetry in a Population-based Prevalence Survey of Glaucoma: the Tajimi Study

Ophthalmology. Jan, 2007  |  Pubmed ID: 17070580

To evaluate the performance of frequency-doubling technology (FDT) perimetry in a population-based glaucoma prevalence survey.

Transventricular Hemispherotomy for Surgical Treatment of Intractable Epilepsy

Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. Feb, 2007  |  Pubmed ID: 17118663

Surgical procedures for cerebral hemispherotomy may be broadly divided into those using a lateral and those using a vertical approach. However, careful study of surgical procedures using the lateral approach described in the literature shows differences in the approach to the ventricles. We discuss the application of transventricular hemispherotomy as a technique which provides relatively easy ventricular access for cerebral hemispherotomy. Transventricular hemispherotomy was successfully performed in a 36-year-old woman who was diagnosed with intractable epilepsy due to Sturge-Weber disease, and in a 25-year-old man who had developed intractable post-traumatic seizures after suffering cerebral contusion in a traffic accident as a child. These patients had no seizures or complications after surgery, and both patients have been weaned from antiepileptic drugs. The transventricular approach, as compared with other lateral approaches described in the literature, provides easy access to the ventricular cavity. Transventricular hemispherotomy proved to be a useful approach that allowed the following four common steps in cerebral hemispherotomy to be performed safely: (i) interruption of the internal capsule and corona radiata; (ii) resection of the medial temporal structures; (iii) transventricular corpus callosotomy; and (iv) disruption of the frontal horizontal fibers.

Efficacy of Intraoperative Electrocorticography for Assessing Seizure Outcomes in Intractable Epilepsy Patients with Temporal-lobe-mass Lesions

Seizure : the Journal of the British Epilepsy Association. Mar, 2007  |  Pubmed ID: 17158074

The findings of previous studies have been controversial regarding the optimal surgical procedures required for effective seizure control. In particular, there are varying views as to whether or not lesionectomy of a temporal-lobe-mass lesion is a satisfactory process or whether removal of additional seizure foci is necessary. In this study, we evaluated the efficacy of additional removal of electrically positive foci using intraoperative electrocorticography on mass lesions related to temporal lobe epilepsy.

Neutralization Assays for Echovirus 18 Isolates in 2006

Japanese Journal of Infectious Diseases. Feb, 2007  |  Pubmed ID: 17314433

Synip Phosphorylation is Required for Insulin-stimulated Glut4 Translocation

Biochemical and Biophysical Research Communications. Apr, 2007  |  Pubmed ID: 17336927

Previously we identified an unusual potential dual Akt/protein kinase B consensus phosphorylation motif in the protein Synip (RxKxRS(97)xS(99)) with serine 99 as a unique Akt2, but not Akt1 or for Akt3, substrate phosphorylation site. Although we have previously reported that serine 99 to phenylalanine (S99F-Synip) resulted in a constitutive inhibition of insulin-stimulated Glut4 translocation, a recent report indicated that Synip serine 99 to alanine mutant (S99A-Synip) failed to inhibit insulin-stimulated Glut4 translocation [H. Sano, S. Kane, E. Sano, G.E. Lienhard, Synip phosphorylation does not regulate insulin-stimulated GLUT4 translocation, Biochem. Biophys. Res. Commun. 332 (2005) 880-884]. To address this apparent discrepancy, we have now examined the S99A-Synip mutant and find that this mutant behaves essentially identical to S99F-Synip in that overexpression inhibits insulin-stimulated Glut4 translocation and is incapable of undergoing insulin-stimulated Syntaxin4 dissociation. These data are consistent with Synip serine 99 phosphorylation required for insulin-stimulated Glut4 translocation.

The Leptin-dependent and -independent Melanocortin Signaling System: Regulation of Feeding and Energy Expenditure

The Journal of Endocrinology. Apr, 2007  |  Pubmed ID: 17400797

The brain hypothalamus coordinates extra-hypothalamic regions to maintain energy homeostasis through the regulation of food intake and energy expenditure. A number of anorexigenic and orexigenic molecules in the hypothalamic nuclei participate in the control of energy homeostasis. Leptin and pro-opiomelanocortin (POMC)-derived alpha-melanocyte-stimulating hormone are key anorectic molecules, and the leptin receptor and POMC gene are both expressed in the hypothalamic arcuate nucleus. Although it has been considered that melanocortin signaling is localized downstream to leptin signaling, data have accumulated to support the concept of a leptin-independent melanocortin signaling system. We focus on and review the melanocortin signaling system that functions dependently or independently of leptin signaling in the regulation of energy homeostasis.

Association of Maternal Fat and Alcohol Intake with Maternal and Umbilical Hormone Levels and Birth Weight

Cancer Science. Jun, 2007  |  Pubmed ID: 17428259

High levels of estrogen during pregnancy have been hypothesized to increase the risk of breast cancer in offspring. Some studies have reported a positive association of estrogen level during pregnancy with fetal size, which has been linked to the subsequent risk of breast cancer in offspring. We examined whether maternal diet, including fat and alcohol intake, was associated with hormone levels during pregnancy, as well as with birth weight. The concentrations of estradiol, estriol, and testosterone were measured in the maternal serum and umbilical cord blood of 189 women during pregnancy and at delivery. Intakes of fat, alcohol, and other nutrients were assessed by 5-day diet records at approximately the 29th week of pregnancy before blood sampling. Intake of polyunsaturated fatty acids was moderately but significantly positively correlated with the umbilical cord estriol level (r = 0.17, P = 0.03) after controlling for covariates. The positive association between intake of polyunsaturated fatty acids and birth weight was of borderline significance (r = 0.14, P = 0.06). Intake of long-chain n-3 fatty acids was significantly inversely correlated with the umbilical cord estradiol and testosterone levels (r = -0.18, P = 0.02 and r = -0.24, P = 0.002, respectively). Alcohol intake was significantly positively correlated with the maternal estradiol level in the 29th week of pregnancy (r = 0.19, P = 0.01), but was unrelated to birth weight. Estrogen level during pregnancy may be regulated by dietary polyunsaturated fatty acids and mediate their effects on fetal growth.

Nesfatin-1 Neurons in Paraventricular and Supraoptic Nuclei of the Rat Hypothalamus Coexpress Oxytocin and Vasopressin and Are Activated by Refeeding

Endocrinology. Mar, 2008  |  Pubmed ID: 18048495

Nesfatin-1, a newly discovered satiety molecule, is located in the hypothalamic nuclei, including the paraventricular nucleus (PVN) and supraoptic nucleus (SON). In this study, fine localization and regulation of nesfatin-1 neurons in the PVN and SON were investigated by immunohistochemistry of neuropeptides and c-Fos. In the PVN, 24% of nesfatin-1 neurons overlapped with oxytocin, 18% with vasopressin, 13% with CRH, and 12% with TRH neurons. In the SON, 35% of nesfatin-1 neurons overlapped with oxytocin and 28% with vasopressin. After a 48-h fast, refeeding for 2 h dramatically increased the number of nesfatin-1 neurons expressing c-Fos immunoreactivity by approximately 10 times in the PVN and 30 times in the SON, compared with the fasting controls. In the SON, refeeding also significantly increased the number of nesfatin-1-immunoreactive neurons and NUCB2 mRNA expression, compared with fasting. These results indicate that nesfatin-1 neurons in the PVN and SON highly overlap with oxytocin and vasopressin neurons and that they are activated markedly by refeeding. Feeding-activated nesfatin-1 neurons in the PVN and SON could play a role in the postprandial regulation of feeding behavior and energy homeostasis.

Cooperative Effect of the Attenuation Determinants Derived from Poliovirus Sabin 1 Strain is Essential for Attenuation of Enterovirus 71 in the NOD/SCID Mouse Infection Model

Journal of Virology. Feb, 2008  |  Pubmed ID: 18057246

Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also associated with serious neurological disorders. An attenuated EV71 strain [EV71(S1-3')] has been established in the cynomolgus monkey infection model; this strain contains the attenuation determinants derived from the type 1 poliovirus vaccine strain, Sabin 1 [PV1(Sabin)], in the 5' nontranslated region (NTR), 3D polymerase, and 3' NTR. In this study, we analyzed the effect of the attenuation determinants of PV1(Sabin) on EV71 infection in a NOD/SCID mouse infection model. We isolated a mouse-adapted EV71 strain [EV71(NOD/SCID)] that causes paralysis of the hind limbs in 3- to 4-week-old NOD/SCID mice by adaptation of the virulent EV71(Nagoya) strain in the brains of NOD/SCID mice. A single mutation at nucleotide 2876 that caused an amino acid change in capsid protein VP1 (change of the glycine at position 145 to glutamic acid) was essential for the mouse-adapted phenotype in NOD/SCID mice. Next, we introduced attenuation determinants derived from PV1(Sabin) along with the mouse adaptation mutation into the EV71(Nagoya) genome. In 4-week-old mice, the determinants in the 3D polymerase and 3' NTR, which are the major temperature-sensitive determinants, had a strong effect on attenuation. In contrast, the effect of individual determinants was weak in 3-week-old NOD/SCID mice, and all the determinants were required for substantial attenuation. These results suggest that a cooperative effect of the attenuation determinants of PV1(Sabin) is essential for attenuated neurovirulence of EV71.

Tyrosine Phosphorylation of Munc18c Regulates Platelet-derived Growth Factor-stimulated Glucose Transporter 4 Translocation in 3T3L1 Adipocytes

Endocrinology. Jan, 2008  |  Pubmed ID: 17916632

Platelet-derived growth factor (PDGF) stimulation of skeletal muscle, cultured myotubes, and 3T3L1 adipocytes results in glucose transporter 4 (Glut4) translocation, albeit to a reduced level compared with insulin. To address the mechanism of PDGF action, we have determined that the Syntaxin 4 negative regulatory protein, Munc18c, undergoes PDGF-stimulated phosphorylation on tyrosine residue 521. The tyrosine phosphorylation of Munc18c on Y521 occurred concomitant with the dissociation of the Munc18c protein from Syntaxin 4 in a time frame consistent with Glut4 translocation. Moreover, expression of the wild-type Munc18c protein did not inhibit PDGF-induced Glut4 translocation, whereas expression of Y521A-Munc18c mutant was inhibitory and failed to dissociate from Syntaxin 4. In contrast, expression of either wild-type Munc18c or the Y521A-Munc18c mutant both resulted in a marked inhibition of insulin-stimulated Glut4 translocation. Together, these data demonstrate that one mechanism accounting for the PDGF induction of Glut4 translocation is the suppression of the Munc18c negative regulation of Syntaxin 4 function.

Molecular Typing and Epidemiology of Non-polio Enteroviruses Isolated from Yunnan Province, the People's Republic of China

Journal of Medical Virology. Apr, 2008  |  Pubmed ID: 18297723

This report presents an overview of human enteroviruses in Yunnan Province, the People's Republic of China. A total of 210 non-polioviruses isolated under acute flaccid paralysis (AFP) surveillance during a total study period of 5 years--1997 to 2000 and 2004--were examined. Of the 210 non-poliovirus isolates, 12 adenoviruses were serologically identified, and the remaining 198 isolates were used for molecular typing. The viral genomes of 195 non-polio enteroviruses (NPEVs) on VP1 partial region of virus capsid were translated to the corresponding amino acid sequences; these were compared with those of prototype strains. Based on molecular typing, 5 isolates were classified into 5 serotypes of the human enterovirus A species, 158 isolates, into 35 serotypes of the human enterovirus B species; and 32 isolates, into 6 serotypes of the human enterovirus C species. Viruses belonging to the human enterovirus D species were not isolated. Thus, under AFP surveillance, the human enterovirus B species accounted for 75.2% of the 210 isolates, and it was considered the predominant species. This was followed by human enterovirus C (12.2%), adenovirus (5.7%), and human enterovirus A (2.4%). Further, molecular analysis suggested that several serotypes of human enteroviruses B and C that exhibited genetic polymorphism were indigenous. Molecular typing methods may aid in understanding the epidemiology of NPEVs in Yunnan Province.

[Successful Treatment of Azole-refractory Candida Guilliermondii Fungemia with a Combination Therapy of Micafungin and Liposomal Amphotericin B]

[Rinshō Ketsueki] The Japanese Journal of Clinical Hematology. Feb, 2008  |  Pubmed ID: 18341039

Candida guilliermondii (C. guilliermondii) are uncommon, representing approximately 1% of all Candida infections, but have been reported to show a higher rate of drug-resistance and mortality rate than C. albicans. Current guidelines for treatment of non-albicans candidemia in neutropenic patients now recommend the use of amphotericin B or voriconazole (VRCZ). We describe here the successful treatment for a 58-year-old male with azole-refractory C. guilliermondii fungemia by combination with liposomal (L-AmB) and micafungin (MCFG) therapy. He was diagnosed as having mantle cell lymphoma, and treatment with HyperCVAD (Rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) was started. Despite prophylactic treatment with fluconazole, he developed fungemia due to C. guilliermondii 41 days after the start of chemotherapy. Positive blood culture and high levels of (1-->3)-beta-D-glucan persisted despite changing the treatment from fluconazole to voriconazole. Although L-AmB was also added to VRCZ, the clinical symptoms worsened. When MCFG was combined with L-AmB, the symptoms and data dramatically improved. Thus, combination therapy consisting of MCFG and L-AmB might be more effective against candidemia that is refractory to azole than combination therapy with VRCZ and L-AmB.

Correlation of Bone Status in Mothers and Daughters and the Improvement of Bone Status

Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. Sep, 2008  |  Pubmed ID: 18843453

Acquiring a higher peak bone mass during puberty reduces the risk of osteoporosis later in life. Peak bone mass is influenced by a variety of genetic and environmental factors. Age-appropriate nutrition and physical education for school-age children is indispensable. In the present study, bone examinations were performed on 1611 female students in junior and senior high school along with their 1376 mothers, and a 5-year follow-up survey was conducted.

[Universal Use of Inactivated Poliovirus Vaccine--the Needs and Challenges]

Nihon Rinsho. Japanese Journal of Clinical Medicine. Oct, 2008  |  Pubmed ID: 18939495

During the final stage of global polio eradication, universal use of inactivated poliovirus vaccine (IPV) might be one of the feasible options to minimize the inherent risk of oral polio vaccine (OPV), such as vaccine-associated paralytic poliomyelitis and polio outbreaks due to vaccine-derived polioviruses. A unique IPV, derived from attenuated polioviruses (Sabin IPV), has been developing in Japan, as a promising polio vaccine candidate, particularly in developing countries in the future. Thus, further polio immunization strategies, including the introduction of Sabin IPV, instead of OPV, to Japan and to developing countries, should be carefully considered.

The Role of CHOP Messenger RNA Expression in the Link Between Oxidative Stress and Apoptosis

Metabolism: Clinical and Experimental. Dec, 2008  |  Pubmed ID: 19013284

Low expression of antioxidant enzymes makes pancreatic beta-cells susceptible to cell damage by oxidative stress. Pancreatic beta-cell loss caused by endoplasmic reticulum stress is associated with the onset of diabetes mellitus. The present studies were undertaken to investigate a possible involvement of proapoptotic gene CHOP in pancreatic beta-cells damage by oxidative stress. The induction of CHOP messenger RNA and apoptosis were investigated in betaHC-9 cells after the oxidative stress by hydrogen peroxide and ribose. Latter was examined after the suppression of CHOP by small interfering RNA. For in vivo study, the pancreatic beta-cells were examined in CHOP-knockout (KO) mice after multiple low-dose streptozotocin (MLDS) administration. In betaHC-9 cells, both hydrogen peroxide and ribose obviously increased apoptotic cells, accompanied with enhanced CHOP messenger RNA expression. However, the number of apoptotic cells by those stimulations was significantly reduced by the addition of small interfering RNA against CHOP. In vivo study also showed that CHOP-KO mice were less susceptible to diabetes after MLDS administration. Although the oxidative stress marker level was similar to that of MLDS-treated wild type, the pancreatic beta-cell area was maintained in CHOP-KO mice. The present studies showed that CHOP should be important in pancreatic beta-cell injury by oxidative stress and indicate that CHOP may play a role in the development of pancreatic beta-cell damage on the onset of diabetes mellitus.

Acute Encephalitis Caused by Intrafamilial Transmission of Enterovirus 71 in Adult

Emerging Infectious Diseases. May, 2008  |  Pubmed ID: 18439374

Enterovirus 71 (EV71) is a common cause of hand, foot, and mouth disease and sometimes causes severe neurologic complications, mainly in children. We report a case of adult-onset encephalitis caused by intrafamilial transmission of a subgenogroup C4 strain of EV71. This case elucidates the risk for EV71 encephalitis even in adults.

Dietary and Lifestyle Correlates of Urinary Excretion Status of Equol in Japanese Women

Nutrition and Cancer. 2008  |  Pubmed ID: 18444135

The isoflavone metabolite equol has been identified in urine or blood samples in some but not all humans. In this cross-sectional study, we examined the association between lifestyle, including diet, and the urinary excretion of equol. Study subjects were 419 Japanese women who were recruited from a breast cancer screening center. Each woman responded to a self-administered questionnaire seeking information about health and lifestyle factors. Diet was assessed by a validated semiquantitative food frequency questionnaire. Urinary isoflavones were measured using spot urine samples. Equol was detected in the urine of 84 (20.0%) women. After controlling for covariates, it was found that dairy product intake was significantly lower in those who excreted detectable equol levels in urine than in those who did not. Because equol is derived from daidzein, individuals with low intake of daidzein may produce undetectable levels of equol. To account for this, the study subjects were restricted to 163 women with urinary daidzein levels of 10 nmol/mg creatinine or higher. The association of equol excretion with dairy product intake remained significant. Demographic factors, smoking status, and menstrual and reproductive factors were unrelated to equol excretion. These data suggest that dairy product intake may be associated with the production of equol.

Fruit and Vegetable Intake and Mortality from Cardiovascular Disease Are Inversely Associated in Japanese Women but Not in Men

The Journal of Nutrition. Jun, 2008  |  Pubmed ID: 18492845

Some epidemiological studies undertaken in Western countries have demonstrated that high intake of fruit and vegetables results in decreased risk of cardiovascular disease (CVD). The objective of this study was to examine the hypothesis that high intake of fruit and vegetables lowers CVD mortality in a population-based cohort of Japanese subjects. In 1992, fruit and vegetable intake was assessed in 13,355 men and 15,724 women in Takayama, Gifu, Japan using a validated FFQ. During the follow-up (1992-99), 200 men and 184 women died from CVD. For women, the highest quartile of vegetable intake compared with the lowest was marginally significant and inversely associated with CVD mortality after adjusting for total energy, age, and nondietary and dietary covariates [hazard ratio (HR) = 0.62; 95% CI, 0.36-1.08; P-trend = 0.007]. An inverse trend with borderline significance was also observed in fruit intake, excluding CVD deaths in the first 2 y of this study, after adjusting for the above-mentioned covariates (HR = 0.83; 95% CI, 0.51-1.34; P-trend = 0.10). In men, CVD death was not associated with fruit (HR = 1.16; 95% Cl, 0.77-1.74; P-trend = 0.61) and vegetable (HR = 0.81, 95% CI: 0.49-1.34; P-trend = 0.47) intake. These data suggest that higher intake of vegetables is associated with reduced risk of death from CVD for women.

Contribution of Fasting and Postprandial Hyperglycemia to Hemoglobin A1c in Insulin-treated Japanese Diabetic Patients

Endocrine Journal. Aug, 2008  |  Pubmed ID: 18497454

The contribution of fasting and postprandial glucose to hemoglobin A(1c) (HbA(1c)) levels was evaluated in insulin-treated patients. In 57 insulin-treated, diabetic out-patients, fasting glucose (before breakfast (B-FG), lunch (L-FG) and dinner (D-FG)) and postprandial glucose (B-PPG, L-PPG and D-PPG) levels were determined by the patients themselves at home using glucose self-monitoring apparatus over the course of one week. The correlation between HbA(1c) levels and self monitored blood glucose levels were calculated. In the conventionally treated group, there was a significant correlation between HbA(1c) and fasting glucose (FG) levels only before lunch, but at 2 hr after (PPG) all meals. In the intensively treated group, a significant correlation between HbA(1c) levels and FG levels was found before lunch and at 2 hr after breakfast and dinner. In all subjects, only FG levels before lunch correlated significantly with HbA(1c) levels, although PPG levels were significantly correlated with HbA(1c) at all points. The correlation was highest with PPG after breakfast and dinner. The sum of all FG, PPG and FG + PPG levels was significantly correlated with HbA(1c) levels. Postprandial hyperglycemia after breakfast and dinner should be regarded as most important for improving HbA(1c) levels in insulin treated diabetic patients.

Smoking and Risk of Cedar Pollinosis in Japanese Men and Women

International Archives of Allergy and Immunology. 2008  |  Pubmed ID: 18520156

Pollinosis induced by the cedar pollen antigen is the most common seasonal allergic reaction in Japan. We aimed to examine the relationship between smoking and risk of cedar pollinosis in a population-based cohort of the Japanese.

[Clinical Study on Temporal Lobe Epilepsy in Childhood Caused by Temporal Lobe Space-occupying Lesions]

No to Hattatsu. Brain and Development. May, 2008  |  Pubmed ID: 18524262

We studied the clinicoelectrical and neuroimaging features of 11 patients with symptomatic temporal lobe epilepsy (TLE) caused by temporal lobe space occupying lesions (SOLs), and compared its characteristics with those of 19 mesial TLE (MTLE) patients. Brain MRI demonstrated SOLs in the mesiotemporal lobe in 9, and laterotemporal lobe in the remaining 2 patients. Ten of the 11 patients successfully underwent surgery, which revealed tumors in 7 and focal cortical dysplasia in 3 patients. Comparisons of the clinical features between those with SOTLE and MTLE showed that both conditions shared the same clinical seizure manifestations such as gastric uprising sensation or ictal fear and a favorable response to surgery. However, the patients with SOTLE had fewer febrile convulsion, and more frequent seizure recurrences as well as TLE EEG discharges and associations of the monophasic clinical course than those with MTLE. In addition, the MRI findings were characterized by unilateral hippocampal atrophy in MTLE and expanding or SOLs in the SOTLE group. Children with complex partial seizures of suspected temporal lobe origin should undergo extensive neuroimaging evaluation.

Light Exposure at Night, Urinary 6-sulfatoxymelatonin, and Serum Estrogens and Androgens in Postmenopausal Japanese Women

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Jun, 2008  |  Pubmed ID: 18559557

It has been hypothesized that exposure to light at night increases the risk of breast cancer by suppressing the normal nocturnal increase in melatonin production and release, thereby resulting in increased levels of circulating estrogen. We assessed associations among concentrations of serum estrogen and androgen and the principal metabolite of melatonin in urine, 6-sulfatoxymelatonin, and exposure to light at night based on information regarding the sleeping habits and history of graveyard-shift work of 206 postmenopausal Japanese women. Serum estradiol level was significantly higher in women who were not asleep at or after 1:00 a.m. (the approximate time of the melatonin peak) than those who were asleep after controlling for covariates. Significantly increased estrone levels were observed in women who had worked graveyard shift. Serum testosterone and DHEA sulfate were unrelated to sleeping habits and history of graveyard-shift work. Urinary 6-sulfatoxymelatonin was lower in women who were not asleep at or after 1:00 a.m. on weekends than those who were asleep at this time, but the difference was of borderline significance (P = 0.08). There was no significant association between urinary 6-sulfatoxymelatonin and any serum hormone levels. These data suggest that exposure to light at night has implications for the risk of breast cancer in postmenopausal women. However, the potential role of melatonin as an intervening factor between light exposure at night and the serum concentrations of estrogen was equivocal.

Soy Isoflavone Intake is Not Associated with the Development of Cedar Pollinosis in Adults

The Journal of Nutrition. Jul, 2008  |  Pubmed ID: 18567763

Although soy isoflavone has been suggested to have both immune-enhancing and immune-suppressive effects, the effects of soy isoflavone intake on allergic disorders are unclear. A cross-sectional study indicated that a high intake of soy isoflavone is associated with a decreased risk of allergic rhinitis. We aimed to prospectively examine the relationship between soy isoflavone intake and risk of cedar pollinosis, the most common seasonal allergic rhinitis in Japan. The study was conducted in a population-based cohort of Japanese men and women. Each subject's usual diet, including soy isoflavone intake, was determined with the use of a validated FFQ in 1992. In 2002, a total of 11,229 persons who were 35-69 y old and had no history of cancer or allergic diseases at the baseline responded to a follow-up questionnaire asking about 4 symptoms related to cedar pollinosis. Cox hazard regression model was used to determine the association between soy isoflavone intake and the risk of cedar pollinosis. During the 10-y follow-up, 931 of these subjects reported that they had cedar pollinosis. There was no significant association between soy isoflavone intake and risk of cedar pollinosis in men and women after controlling for covariates. For the highest compared with the lowest quartile of soy isoflavone intake, hazard ratios were 1.07 (95% CI: 0.81-1.42) in men and 0.89 (95% CI: 0.68-1.15) in women. These data did not support an association between soy isoflavone intake and risk of cedar pollinosis.

Rationality/anti-emotionality Personality and Dietary Habits in a Community Population in Japan

Journal of Epidemiology / Japan Epidemiological Association. 2008  |  Pubmed ID: 18603826

There are no strong and consistent predictors of dietary habits although some associations have been shown with psychological factors. The purpose of the present study was to examine the relationships between the rationality and anti-emotionality (R/A) personality and dietary consumption in a Japanese community.

Diphyllobothriasis Nihonkaiense: Possibly Acquired in Switzerland from Imported Pacific Salmon

Internal Medicine (Tokyo, Japan). 2008  |  Pubmed ID: 18628587

A 5-year-old Japanese boy passed tapeworm strobila while he was living in Switzerland. During a short visit to Japan, he was successfully treated with a single dose of praziquantel. DNA sequences of ITS1, cox1 and nd3 genes from the tapeworm were compatible with those of Diphyllobothrium nihonkaiense rather than Diphyllobothrium latum, which is prevalent in Europe. The patient consumed imported salmon in Switzerland. This case highlights the globalization of D. nihonkaiense, which was once restricted to the Far East, and reflects the worldwide demand for seafood.

Self-reported Diabetes Mellitus and Risk of Mortality from All Causes, Cardiovascular Disease, and Cancer in Takayama: a Population-based Prospective Cohort Study in Japan

Journal of Epidemiology / Japan Epidemiological Association. 2008  |  Pubmed ID: 18753735

Diabetes mellitus has been reported to be a major risk factor for cardiovascular disease (CVD), and higher risk of CVD among women than that among men has been observed in many studies. Further, the association of diabetes with increasing risk of cancer has also been reported. Well-designed studies conducted among men and women in the general Japanese population remain scarce.

Characterization of Pharmacologically Active Compounds That Inhibit Poliovirus and Enterovirus 71 Infectivity

The Journal of General Virology. Oct, 2008  |  Pubmed ID: 18796721

Poliovirus (PV) and enterovirus 71 (EV71) cause severe neurological symptoms in their infections of the central nervous system. To identify compounds with anti-PV and anti-EV71 activities that would not allow the emergence of resistant mutants, we performed drug screening by utilizing a pharmacologically active compound library targeting cellular factors with PV and EV71 pseudoviruses that encapsidated luciferase-encoding replicons. We have found that metrifudil (N-[2-methylphenyl]methyl)-adenosine) (an A2 adenosine receptor agonist), N(6)-benzyladenosine (an A1 adenosine receptor agonist) and NF449 (4,4',4'',4'''-[carbonylbis[imino-5,1,3-benzenetriyl bis(carbonyl-imino)]] tetrakis (benzene-1,3-disulfonic acid) octasodium salt) (a Gs-alpha inhibitor) have anti-EV71 activity, and that GW5074 (3-(3, 5-dibromo-4-hydroxybenzylidine-5-iodo-1,3-dihydro-indol-2-one)) (a Raf-1 inhibitor) has both anti-PV and anti-EV71 activities. EV71 mutants resistant to metrifudil, N(6)-benzyladenosine and NF449 were isolated after passages in the presence of these compounds, but mutants resistant to GW5074 were not isolated for both PV and EV71. The inhibitory effect of GW5074 was not observed in Sendai virus infection and the treatment did not induce the expression of OAS1 and STAT1 mRNA. Small interfering RNA treatment against putative cellular targets of GW5074, including Raf-1, B-Raf, Pim-1, -2, and -3, HIPK2, GAK, MST2 and ATF-3, did not consistently suppress PV replication. Moreover, downregulation of Raf-1 and B-Raf did not affect the sensitivity of RD cells to the inhibitory effect of GW5074. These results suggest that GW5074 has strong and selective inhibitory effect against the replication of PV and EV71 by inhibiting conserved targets in the infection independently of the interferon response.

CDK5-dependent Phosphorylation of the Rho Family GTPase TC10(alpha) Regulates Insulin-stimulated GLUT4 Translocation

The Journal of Biological Chemistry. Dec, 2008  |  Pubmed ID: 18948252

Insulin stimulation results in the activation of cyclin-dependent kinase-5 (CDK5) in lipid raft domains via a Fyn-dependent phosphorylation on tyrosine residue 15. In turn, activated CDK5 phosphorylates the Rho family GTP-binding protein TC10alpha on threonine 197 that is sensitive to the CDK5 inhibitor olomoucine and blocked by small interfering RNA-mediated knockdown of CDK5. The phosphorylation deficient mutant T197A-TC10alpha was not phosphorylated and excluded from the lipid raft domain, whereas the phosphorylation mimetic mutant (T197D-TC10alpha) was lipid raft localized. Insulin resulted in the GTP loading of T197D-TC10alpha but not T197A-TC10alpha and in parallel, T197D-TC10alpha but not T197A-TC10alpha depolymerized cortical actin and inhibited insulin-stimulated GLUT4 translocation. These data demonstrate that CDK5-dependent phosphorylation maintains TC10alpha in lipid raft compartments thereby disrupting cortical actin, whereas subsequent dephosphorylation of TC10alpha through inactivation of CDK5 allows for the re-assembly of F-actin. Because cortical actin reorganization is required for insulin-stimulated GLUT4 translocation, these data are consistent with a CDK5-dependent TC10alpha cycling between lipid raft and non-lipid raft compartments.

[Tajimi Study Review]

Nihon Ganka Gakkai Zasshi. Dec, 2008  |  Pubmed ID: 19157025

The results of The Tajimi Study (a population-based prevalence survey of glaucoma in Tajimi City performed by the Japan Glaucoma Society) are summarized. The Tajimi Study was carried out from September, 2000 to October, 2001 to investigate the prevalence of glaucoma among residents aged 40 years old or over in Tajimi. Seventy-eight point one % of 3,870 eligible people from 4,000 subjects who had been randomly selected from the 54,165 over 40 years old residents in Tajimi participated in the study. Estimated prevalence of all glaucoma and glaucoma/suspected glaucoma were 5.0 (95% confidence interval [CI], 4.2-5.8)% and 7.5 (95% CI, 6.5-8.4)%. The prevalence of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG), and secondary glaucoma (SG) were 3.9 (95% CI, 3.2-4.6)%, 0.6 (95% CI, 0.4-0.9)%, and 0.5 (95% CI, 0.2-0.7)%, respectively. Including suspected cases, the prevalence of POAG, PACG, and SG was 6.0 (5.1-6.8)%, 0.8 (0.5-1.2)%, 0.7 (0.4-1.0)%. High intraocular pressure, myopia, and older age were shown to be statistically significant risk factors for POAG. It was suggested that the Frequency Doubling Technology is a good candidate as a screening test for glaucoma. The leading cause of low vision was cataracts. Investigation of refractive status showed that the prevalence of myopia(spherical equivalence [SE] < 0.5 diopters) and high myopia (SE < -5.0 diopters) was 41.8 (40.0-43.6)% and 8.2 (7.2-9.2)%, respectively.

[Historical Background and Current Status of Hemispherotomy]

No Shinkei Geka. Neurological Surgery. Jan, 2009  |  Pubmed ID: 19175028

Oral Poliovirus Vaccine Type 3 from a Patient with Transverse Myelitis is Neurovirulent in a Transgenic Mouse Model

Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. Apr, 2009  |  Pubmed ID: 19269246

It is accepted that oral poliovirus vaccine (OPV) can cause vaccine-associated paralytic poliomyelitis (VAPP) and that wild poliovirus infection can rarely present as transverse myelitis. It is therefore possible that OPV could cause transverse myelitis. We previously reported a case of transverse myelitis that developed in a 6-month-old boy, 7 days after receiving his second dose of OPV.

GAK, a Regulator of Clathrin-mediated Membrane Trafficking, Localizes Not Only in the Cytoplasm but Also in the Nucleus

Genes to Cells : Devoted to Molecular & Cellular Mechanisms. May, 2009  |  Pubmed ID: 19371378

The ubiquitously expressed Cyclin G-associated kinase (GAK) regulates clathrin-mediated membrane trafficking in the cytoplasm. However, the association of GAK with a nuclear protein Cyclin G1 that is unrelated to membrane trafficking suggests an unidentified role of GAK in the nucleus. Indeed, we report here that GAK localizes in both cytoplasm and nucleus by immunostaining, ectopic expression of GFP-GAK and pull-down assays using dissected GAK fragments. GAK forms complexes not only with cyclin G1 but also with other nuclear proteins such as p53, clathrin heavy chain (CHC) and protein phosphatase 2A (PP2A) B'alpha1. Moreover, CHC associates with GAK via a different domain depending on whether it is in the cytoplasm or nucleus. Immunostaining revealed that about 20-30% of B'alpha1, cyclin G1 and p53 complex with nuclear GAK. CHC also displayed dots in the nucleus and almost all nuclear CHC signals colocalized with GAK. These observations together suggest an important function of GAK in the nucleus.

Administration Time Difference of Candesartin Effect on Albuminuria in Type 2 Diabetic Patients

Hypertension Research : Official Journal of the Japanese Society of Hypertension. Jun, 2009  |  Pubmed ID: 19373237

Cellular Kinase Inhibitors That Suppress Enterovirus Replication Have a Conserved Target in Viral Protein 3A Similar to That of Enviroxime

The Journal of General Virology. Aug, 2009  |  Pubmed ID: 19439558

Previously, we identified a cellular kinase inhibitor, GW5074, that inhibits poliovirus (PV) and enterovirus 71 replication strongly, although its target has remained unknown. To identify the target of GW5074, we searched for cellular kinase inhibitors that have anti-enterovirus activity similar or related to that of GW5074. With this aim, we performed screenings to identify cellular kinase inhibitors that could inhibit PV replication cooperatively with GW5074 or synthetically in the absence of GW5074. We identified MEK1/2 inhibitors (SL327 and U0126), an EGFR inhibitor (AG1478) and a phosphatidylinositol 3-kinase inhibitor (wortmannin) as compounds with a cooperative inhibitory effect with GW5074, and an Akt1/2 inhibitor (Akt inhibitor VIII) as a compound with a synthetic inhibitory effect with MEK1/2 inhibitors and AG1478. Individual treatment with the identified kinase inhibitors did not affect PV replication significantly, but combined treatment with MEK1/2 inhibitor, AG1478 and Akt1/2 inhibitor suppressed the replication synthetically. The effect of AG1478 in this synthetic inhibition was compensated by other receptor tyrosine kinase inhibitors (IGF-1R inhibitor II and Flt3 inhibitor II). We isolated mutants resistant to Flt3 inhibitor II and GW5074 and found that these mutants had cross-resistance to each treatment. These mutants had a common mutation in viral protein 3A that results in an amino acid change at position 70 (Ala to Thr), a mutation that was previously identified in mutants resistant to a potent anti-enterovirus compound, enviroxime. These results suggest that cellular kinase inhibitors and enviroxime have a conserved target in viral protein 3A to suppress enterovirus replication.

Cigarette Smoking and the Adult Onset of Bronchial Asthma in Japanese Men and Women

Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. Apr, 2009  |  Pubmed ID: 19441599

Although smoking is a well-known risk factor for the onset of airway diseases, the associations between smoking and asthma are inconsistent.

A New Anorexigenic Protein, Nesfatin-1

Peptides. May, 2009  |  Pubmed ID: 19452636

An anorexigenic peptide, nesfatin-1 was found in rat hypothalamus, and its expression in the paraventricular nucleus of the hypothalamus was reduced by starvation. Intracerebroventricular administration dose-dependently inhibited food intake for 6 h in male Wistar and leptin resistant, Zucker fatty rats. There may be a crosstalk between nesfatin-1 pathway and melanocortin pathway in the brain. Nesfatin-1 neurons co-express with oxytocin, vasopressin and melanin concentrating hormone in the hypothalamus. Intraperitoneal administration of nesfatin-1 and its mid-segment dose-dependently inhibited food intake for 3 h. Mid-segment of nesfatin-1 decreased food intake under leptin-resistant animal models of obesity. Intraperitoneal administration of the mid-segment of nesfatin-1 increased proopiomelanocortin and cocain- and amphetamine-related peptide mRNA expression in the nucleus of the solitary tract, but not in arcuate nucleus of the hypothalamus. In this review, we summarized recent progress in the research about the possible mechanism of nesfatin-1-induced anorexia.

Nesfatin-1: an Overview and Future Clinical Application

Endocrine Journal. 2009  |  Pubmed ID: 19461159

Nesfatin/nucleobindin 2 (NUCB2) is expressed in the appetite-control hypothalamic nuclei and brainstem nuclei. Nesfatin/NUCB2 expression in the paraventricular nucleus of the hypothalamus was modulated by starvation and refeeding. Intracerebroventricular administration of nesfatin-1 dose-dependently inhibited food intake for 6 hours in male Wistar and leptin resistant, Zucker fatty rats. Intraperitoneal administration of nesfatin-1 and its mid-segment (M30) dosedependentlyinhibited food intake for 3 hours in male ICR mice. Intraperitoneal administration of M30 also decreased foodintake in leptin-resistant, genetically obese (ob/ob), diabetic (db/db) mice and mice fed a 45% high fat diet for 28 days. Intraperitoneal administration of M30 increased proopiomelanocortin and cocaine- and amphetamine- related peptide mRNA expression in the nucleus of the solitary tract of mice. In addition, intranasal administration of nesfatin-1 significantly inhibited food intake for 6 hours in male Wistar rats. We summarize recent observations about nesfatin-1, and attempt to present future direction of nesfatin-1 research for developing a new anti-obesity treatment.

[A Case of Recurrent Endocrine Cell Carcinoma of the Common Bile Duct Successfully Treated by Hepatic Artery Infusion with CPT-11 and CDDP]

Gan to Kagaku Ryoho. Cancer & Chemotherapy. May, 2009  |  Pubmed ID: 19461186

A 77-year-old woman underwent pancreatoduodenectomy with the diagnosis of biliary tract cancer. Postoperative immunohistochemical study showed endocrine cell carcinoma originating in the common bile duct. Systemic infusion of gemcitabine was started as adjuvant chemotherapy, however, 6 months after the operation, multiple liver and lymph node metastases were revealed by computed tomography. Then hepatic artery infusion with CPT-11 (40 mg/body) and CDDP (20 mg/body) were repeated every two weeks. Tumor markers normalized, and the size of both lymph nodes and liver tumors was remarkably decreased after 5 months. Endocrine cell carcinoma of the bile duct generally has a poor prognosis. This method could be a therapeutic option for recurrent endocrine cell carcinoma of the bile duct.

Human P-selectin Glycoprotein Ligand-1 is a Functional Receptor for Enterovirus 71

Nature Medicine. Jul, 2009  |  Pubmed ID: 19543284

Enterovirus 71 (EV71) is a major causative agent of hand, foot and mouth disease (HFMD), a common febrile disease occurring mainly in young children. Although clinical manifestations of HFMD are usually mild and self limiting, a severe EV71 outbreak can lead to a diverse array of neurological diseases. Identification of the specific cellular receptors is crucial for elucidating the mechanism of early virus-host interactions and the pathogenesis of enteroviruses. Here we identify human P-selectin glycoprotein ligand-1 (PSGL-1; CD162), a sialomucin membrane protein expressed on leukocytes that has a major role in early stages of inflammation, as a functional receptor for EV71 using an expression cloning method by panning. The N-terminal region of PSGL-1 binds specifically to EV71. Stable PSGL-1 expression allowed EV71 entry and replication, and development of cytopathic effects in nonsusceptible mouse L929 cells. Five out of eight EV71 strains bound soluble PSGL-1 and used intact PSGL-1 as the primary receptor for infection of Jurkat T cells. Three other EV71 strains did not use PSGL-1, suggesting the presence of strain-specific replication of EV71 in leukocytes. EV71 replicated in nonleukocyte cell lines in a PSGL-1-independent manner, indicating the presence of alternative receptor(s) for EV71. The identification of PSGL-1 as a receptor for EV71 sheds new light on a role for PSGL-1-positive leukocytes in cell tropism and pathogenesis during the course of HFMD and other EV71-mediated diseases.

Hypothalamic Neuronal Histamine Signaling in the Estrogen Deficiency-induced Obesity

Journal of Neurochemistry. Sep, 2009  |  Pubmed ID: 19619143

Menopause is one of the triggers that induce obesity. Estradiol (E2), corticotropin-releasing hormone (CRH), and hypothalamic neuronal histamine are anorexigenic substances within the hypothalamus. This study examined the interactions among E2, CRH, and histamine during the regulation of feeding behavior and obesity in rodents. Food intake was measured in rats after the treatment of E2, alpha-fluoromethyl histidine, a specific suicide inhibitor of histidine decarboxylase that depletes hypothalamic neuronal histamine, or CRH antagonist. We measured food intake and body weight in wild-type mice or mice with targeted disruption of the histamine receptors (H1-R) knockout (H1KO mice). Furthermore, we investigated CRH content and histamine turnover in the hypothalamus after the E2 treatment or ovariectomy (OVX). We used immunohistochemical staining for estrogen receptors (ERs) in the histamine neurons. The E2-induced suppression of feeding was partially attenuated in rats pre-treated with alpha-fluoromethyl histidine or CRH antagonist and in H1KO mice. E2 treatment increased CRH content and histamine turnover in the hypothalamus. OVX increased food intake and body weight, and decreased CRH content and histamine turnover in the hypothalamus. In addition, E2 replacement reversed the OVX-induced changes in food intake and body weight in wild-type mice but not in H1KO mice. Immunohistochemical analysis revealed ERs were expressed on histamine neurons and western blotting analysis and pre-absorption study confirmed the specificity of ER antiserum we used. These results indicate that CRH and hypothalamic neuronal histamine mediate the suppressive effects of E2 on feeding behavior and body weight.

GAK, a Regulator of Clathrin-mediated Membrane Traffic, Also Controls Centrosome Integrity and Chromosome Congression

Journal of Cell Science. Sep, 2009  |  Pubmed ID: 19654208

Cyclin G-associated kinase (GAK) is an association partner of clathrin heavy chain (CHC) and is essential for clathrin-mediated membrane trafficking. Here, we report two novel functions of GAK: maintenance of proper centrosome maturation and of mitotic chromosome congression. Indeed, GAK knockdown by siRNA caused cell-cycle arrest at metaphase, which indicates that GAK is required for proper mitotic progression. We found that this impaired mitotic progression was due to activation of the spindle-assembly checkpoint, which senses protruded, misaligned or abnormally condensed chromosomes in GAK-siRNA-treated cells. GAK knockdown also caused multi-aster formation, which was due to abnormal fragmentation of pericentriolar material, but not of the centrioles. Moreover, GAK and CHC cooperated in the same pathway and interacted in mitosis to regulate the formation of a functional spindle. Taken together, we conclude that GAK and clathrin function cooperatively not only in endocytosis, but also in mitotic progression.

Diet Based on the Japanese Food Guide Spinning Top and Subsequent Mortality Among Men and Women in a General Japanese Population

Journal of the American Dietetic Association. Sep, 2009  |  Pubmed ID: 19699833

The Japanese Food Guide Spinning Top was developed by the Japanese Ministry of Health, Labor, and Welfare and the Ministry of Agriculture, Forestry, and Fishery to promote healthful diets.

Nesfatin-1 Evokes Ca2+ Signaling in Isolated Vagal Afferent Neurons Via Ca2+ Influx Through N-type Channels

Biochemical and Biophysical Research Communications. Dec, 2009  |  Pubmed ID: 19852938

Nesfatin-1, processed from nucleobindin 2, is an anorexigenic peptide expressed in the brain and several peripheral tissues including the stomach and pancreas. Peripheral, as well as intracerebroventricular, administration of nesfatin-1 suppresses feeding behavior, though underlying mechanisms are unknown. In this study, we examined effects of nesfatin-1 on cytosolic Ca(2+) concentration ([Ca(2+)](i)) in the neurons isolated from the vagal afferent nodose ganglion of mice. Nesfatin-1 at 10(-10)-10(-8)M increased [Ca(2+)](i) in the isolated neurons in a concentration-dependent manner, and at 10(-8)M it increased [Ca(2+)](i) in 33 out of 263 (12.5%) neurons. These responses were inhibited under Ca(2+)-free conditions and by N-type Ca(2+) channel blocker, omega-conotoxin GVIA. All the nesfatin-1-responsive neurons also exhibited [Ca(2+)](i) responses to capsaicin and cholecystokinin-8. These results provide direct evidence that nesfatin-1 activates vagal afferent neurons by stimulating Ca(2+) influx through N-type channels, demonstrating the machinery through which peripheral nesfatin-1 can convey signals to the brain.

Rhombencephalitis and Coxsackievirus A16

Emerging Infectious Diseases. Oct, 2009  |  Pubmed ID: 19861078

Nesfatin-1-regulated Oxytocinergic Signaling in the Paraventricular Nucleus Causes Anorexia Through a Leptin-independent Melanocortin Pathway

Cell Metabolism. Nov, 2009  |  Pubmed ID: 19883614

The hypothalamic paraventricular nucleus (PVN) functions as a center to integrate various neuronal activities for regulating feeding behavior. Nesfatin-1, a recently discovered anorectic molecule, is localized in the PVN. However, the anorectic neural pathway of nesfatin-1 remains unknown. Here we show that central injection of nesfatin-1 activates the PVN and brain stem nucleus tractus solitarius (NTS). In the PVN, nesfatin-1 targets both magnocellular and parvocellular oxytocin neurons and nesfatin-1 neurons themselves and stimulates oxytocin release. Immunoelectron micrographs reveal nesfatin-1 specifically in the secretory vesicles of PVN neurons, and immunoneutralization against endogenous nesfatin-1 suppresses oxytocin release in the PVN, suggesting paracrine/autocrine actions of nesfatin-1. Nesfatin-1-induced anorexia is abolished by an oxytocin receptor antagonist. Moreover, oxytocin terminals are closely associated with and oxytocin activates pro-opiomelanocortin neurons in the NTS. Oxytocin induces melanocortin-dependent anorexia in leptin-resistant Zucker-fatty rats. The present results reveal the nesfatin-1-operative oxytocinergic signaling in the PVN that triggers leptin-independent melanocortin-mediated anorexia.

[Roles and Functions of WHO Enterovirus Collaborating Center]

Uirusu. Jun, 2009  |  Pubmed ID: 19927988

The Laboratory of Enteroviruses of the Department of Virology II, National Institute of Infectious Diseases, is functioning as a WHO-designated Collaborating Center for Virus Reference and Research (Enterovirus) in virus isolation and identification, development, evaluation, and quality control of new laboratory diagnosis methods, training technical staffs and experts, preparing, maintaining and supplying of standard reagents and reference materials for the laboratory diagnosis of enterovirus infections including poliomyelitis. The infectious agents surveillance of polioviruses is one of the critical components for the Global Polio Eradication Initiative, and the laboratory diagnosis of non-polio enteroviruses is also important in current outbreaks of hand, foot and mouth disease, mainly due to enterovirus 71. Thus, human resources and consistent international cooperation among technical staffs, based on the global and regional polio laboratory networks, are playing critical roles also in the surveillance activities for non-polio enterovirus infections in the Western Pacific Region.

Development of a Reverse Transcription-loop-mediated Isothermal Amplification (RT-LAMP) System for a Highly Sensitive Detection of Enterovirus in the Stool Samples of Acute Flaccid Paralysis Cases

BMC Infectious Diseases. 2009  |  Pubmed ID: 20015403

In the global eradication program for poliomyelitis, the laboratory diagnosis plays a critical role by isolating poliovirus (PV) from the stool samples of acute flaccid paralysis (AFP) cases. In this study, we developed a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) system for a rapid and highly sensitive detection of enterovirus including PV to identify stool samples positive for enterovirus including PV.

Long-term Follow-up of Seizure Outcomes After Corpus Callosotomy

Seizure : the Journal of the British Epilepsy Association. Mar, 2009  |  Pubmed ID: 18799327

Corpus callosotomy can be an effective surgical treatment for medically intractable generalized seizures, particularly for drop attacks. We studied long-term seizure outcomes after callosotomy, mainly focusing on drop attacks as the seizure type.

Causal Attributions to Epidemiological Risk Factors and Their Associations to Later Psychological Adjustment Among Japanese Breast Cancer Patients

Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. Jan, 2009  |  Pubmed ID: 18386072

The objective of this study was to evaluate the causal attributions for breast cancer and their association with the subsequent psychological adjustment.

[Identification of P-selectin Glycoprotein Ligand-1 As One of the Cellular Receptors for Enterovirus 71]

Uirusu. Dec, 2009  |  Pubmed ID: 20218328

Enterovirus 71 (EV71) is a major causative agent of hand, foot and mouth disease (HFMD), a common febrile disease in young children. Although clinical manifestations of HFMD are usually mild and self-limiting, EV71 can cause large outbreaks of HFMD including severe neurological complications. We identified human P-selectin glycoprotein ligand-1 (PSGL-1; CD162) as a functional receptor for EV71 using an expression cloning method with a human T cell cDNA library by panning. PSGL-1 is a sialomucin membrane protein, expressed on leukocytes, that has a major role in early stages of inflammation by interacting with selections and chemokines. EV71 specifically binds to the N terminal region of PSGL-1 and the expression of human PSGL-1 allowed EV71 replication in nonsusceptible mouse cells, suggesting that PSGL-1 is a functional EV71 receptor. We found the presence of strain-specific EV71 replication in leukocytes. In addition, EV71 replicates in nonleukocyte cell lines in a PSGL-1-independent manner. Thus, further elucidation of the PSGL-1-dependent EV71 replication may provide valuable insights into the molecular basis of EV71 infection including HFMD and various neurological diseases.

Genetic Control of Phenotypic Plasticity in Asian Cultivated and Wild Rice in Response to Nutrient and Density Changes

Genome / National Research Council Canada = Génome / Conseil National De Recherches Canada. Mar, 2010  |  Pubmed ID: 20237598

Phenotypic plasticity is an adaptive mechanism adopted by plants in response to environmental heterogeneity. Cultivated and wild species adapt in contrasting environments; however, it is not well understood how genetic changes responsible for phenotypic plasticity were involved in crop evolution. We investigated the genetic control of phenotypic plasticity in Asian cultivated (Oryza sativa) and wild rice (O. rufipogon) under 5 environmental conditions (2 nutrient and 3 density levels). Quantitative trait locus (QTL) analysis was conducted for traits affecting plant architecture and biomass production. By analysing the phenotypic means, QTLs of large effects were detected as a cluster on chromosome 7 under all the environmental conditions investigated; this might have contributed to transitions of plant architecture during domestication, as reported previously. Multiple QTLs of plasticity were also found within this QTL cluster, demonstrating that allele-specific environmental sensitivity might control plasticity. Furthermore, QTLs controlling plasticity without affecting phenotypic means were also identified. The mode of action and direction of allele effects of plasticity QTLs varied depending on the traits and environmental signals. These findings confirmed that cultivated and wild rice show distinctive genetic differentiation for phenotypic plasticity, which might have contributed to adaptation under contrasting environmental heterogeneity during the domestication of rice.

Dietary Glycemic Index, Glycemic Load, and Intake of Carbohydrate and Rice in Relation to Risk of Mortality from Stroke and Its Subtypes in Japanese Men and Women

Metabolism: Clinical and Experimental. Nov, 2010  |  Pubmed ID: 20303126

We assessed the relationship of the dietary glycemic index (GI), glycemic load (GL), and intake of carbohydrate and rice, and risk of mortality from stroke and its subtypes. The cohort consisted of 12,561 men and 15,301 women residing in Takayama, Japan, in 1992. At the baseline, a food frequency questionnaire was administered; and the dietary GI, GL, and intake of carbohydrates and rice were estimated. Deaths from stroke occurring in the cohort were prospectively noted until 1999 with data from the office of the National Vital Statistics. The risk of mortality from stroke was assessed with a Cox proportional hazard model after adjusting for age; body mass index; smoking status; physical activity; history of hypertension; education; and intake of total energy, alcohol, dietary fiber, salt, and total fat. The risk of stroke subtypes was assessed in the age-adjusted model. The hazard ratios of total stroke comparing the highest vs the lowest quartiles of the dietary GI were 0.78 (95% confidence interval [CI], 0.41-1.47) with P(trend) = .50 in men and 2.09 (95% CI, 1.01-4.31) with P(trend) = .10 in women. Among women, the association was also significant with the risk of ischemic stroke (hazard ratio = 2.45; 95% CI, 1.01-5.92; P(trend) = .03); and a significant positive trend was also observed between dietary GL and mortality from hemorrhagic stroke (P(trend) = .05). The current study implies that diets with a high dietary GI increase the risk of mortality from stroke among Japanese women.

Troglitazone, a Ligand of Peroxisome Proliferator-activated Receptor-{gamma}, Stabilizes NUCB2 (Nesfatin) MRNA by Activating the ERK1/2 Pathway: Isolation and Characterization of the Human NUCB2 Gene

Endocrinology. Jun, 2010  |  Pubmed ID: 20427483

We recently identified a novel satiety peptide, nesfatin-1, containing 82 amino acids derived from the precursor peptide, nucleobindin 2 (NUCB2), from a troglitazone (TZ)-induced cDNA library. We examined the molecular mechanism underlying TZ-induced NUCB2 mRNA expression. Although TZ induced the mRNA expression in HTB185 cells, a nuclear run-on assay revealed no significant change in the transcription of the gene. Surprisingly, HTB185 cells possessed no functional peroxisome proliferator-activated receptor-gamma. We therefore examined the effect of TZ on the mRNA's stability. The half-life of NUCB2 mRNA was approximately 6 h, and incubation with TZ increased this to 27 h. Furthermore, this increase was completely inhibited by an ERK inhibitor, PD98059, and phosphorylated ERK1/2 was significantly increased after 30 min incubation with TZ. In addition, we cloned the entire NUCB2 gene and identified four adenylate/uridylate-rich elements (AREs) in the 3' untranslated region (UTR), to which several proteins of HTB185 extracts treated with TZ bound. The reporter assay fused with 3'UTR showed that the second and third AREs were crucial. Furthermore, the human NUCB2 gene spanned 55 kb and contained 14 exons and 13 introns. The transcriptional start site formed clusters around 246 bp upstream from the translational start site. We confirmed that a construct containing 5889 bp of the promoter region was very active in neuron-derived cell lines but not stimulated by TZ. These findings demonstrated a novel action of derivatives of thiazolidinediones, oral insulin-sensitizing antidiabetic agents, to stabilize the mRNA of NUCB2 through AREs in the 3'UTR by activating the ERK1/2 pathway independently of peroxisome proliferator-activated receptor-gamma.

Eukaryotic Translation Initiation Factor 1 (eIF1), the Inspector of Good AUG Context for Translation Initiation, Has an Extremely Bad AUG Context

Journal of Bioscience and Bioengineering. Jun, 2010  |  Pubmed ID: 20471606

The nucleotide sequence surrounding the translation initiation AUG codon (AUG context) is important for the effective translation initiation. A compilation analysis revealed that all the genes of the eukaryotic translation initiation factor 1, which plays a crucial role in the recognition of the optimal AUG context, ironically have extremely bad AUG contexts.

A Case of Paralytic Poliomyelitis Associated with Poliovirus Vaccine Strains in Hokkaido, Japan

Japanese Journal of Infectious Diseases. May, 2010  |  Pubmed ID: 20495280

Development of a Particle Agglutination Method with Soluble Virus Receptor for Identification of Poliovirus

Journal of Clinical Microbiology. Aug, 2010  |  Pubmed ID: 20519462

In the Global Polio Eradication Initiative, laboratory diagnosis plays a critical role by isolating and identifying poliovirus (PV) from the stool samples of patients with acute flaccid paralysis (AFP). In this study, we developed a particle agglutination (PA) method with a soluble human PV receptor (hPVR) in the form of an immunoadhesin (PVR-IgG2a) for the simple and rapid identification of PV. Sensitized gelatin particles with PVR-IgG2a showed specific agglutination with the culture fluid of PV-infected cells within 2 h of reaction in a one-step procedure. Detection limits for type 1, 2, and 3 PV(Sabin) strains were 1.5 x 10(6) 50% cell culture infectious doses (CCID(50)), 5.3 x 10(5) CCID(50), and 9.1 x 10(5) CCID(50), respectively. Wild-type PVs and PV isolates from acute flaccid paralysis cases examined were identified correctly with this PA method, except for some samples with a mixture of different serotypes of PVs, where a minor population of PV failed to be detected. These results suggest that this PA method is useful for the simple and rapid identification of PV, although the sensitivity was not high enough to detect a minor population of PV (<1/10 of the major population) among mixed PVs.

Fasting Concentrations of Nesfatin-1 Are Negatively Correlated with Body Mass Index in Non-obese Males

Clinical Endocrinology. Oct, 2010  |  Pubmed ID: 20550530

We recently identified a novel anorexigenic protein, nesfatin-1, which is processed from nesfatin/nucleobindin-2 (NUCB2). However, the clinical importance of this protein has not been determined.

A Bifunctional Anti-enterovirus Compound That Inhibits Replication and the Early Stage of Enterovirus 71 Infection

The Journal of General Virology. Nov, 2010  |  Pubmed ID: 20660150

Enviroxime is an anti-enterovirus compound that targets viral protein 3A and/or 3AB and suppresses a replication step of enterovirus by an unknown mechanism. To date, a number of anti-enterovirus compounds that have little structural similarity to enviroxime but induce common resistance mutations in the 3A-encoding region have been identified. The present study identified a novel type of functionally enviroxime-like compound, AN-12-H5. This compound had no structural similarity to enviroxime or to known enviroxime-like compounds, including TTP-8307, GW5074 and Flt3 Inhibitor II. A resistance phenotype of poliovirus (PV) to these compounds was conferred by a major enviroxime-resistance mutation of PV (G5318A, 3A-Ala70Thr), but not by resistance mutations to guanidine hydrochloride and brefeldin A. AN-12-H5 had a common structure with the anti-enterovirus 71 (EV71) compound AN-23-F6. AN-12-H5 and AN-23-F6 inhibited an early stage of EV71 infection after virus binding to the cells. Mutations in capsid proteins (G3112A, VP1-Ala224Thr, and G2396A, VP3-Arg227Lys mutations) were determined as resistant mutations to AN-12-H5 and AN-23-F6 in the early stage of EV71 infection. These results suggest that AN-12-H5 is a bifunctional anti-enterovirus compound that belongs to a novel class of enviroxime-like compounds and targets both a replication step and an early stage of EV71 infection.

[The Lost Decade of Global Polio Eradication and Moving Forward]

Uirusu. Jun, 2010  |  Pubmed ID: 20848864

The Global Polio Eradication Initiative was aimed to eradicate poliomyelitis by the year 2000, however, polio eradication is still not in sight even in 2010, over 10 years after the initial target date. In 2010, indigenous transmission of wild polioviruses has been interrupted throughout the world except four countries, Afghanistan, Pakistan, India, and Nigeria. Despite the intense use of monovalent oral polio vaccines, type 1 and type 3 wild polioviruses still circulate in the four remaining polio-endemic countries, and multiple importations of wild polioviruses have also occurred extensively from Nigeria and India to a number of previously polio-free countries in Africa, Asia, and Europe. Furthermore, the emergence of type 2 vaccine-derived polioviruses has raised concerns about low level of immunity against type 2 poliovirus in some polio-endemic areas like Nigeria and India. On the other hand, operational improvements in 2009 were reported in high-risk states in northern Nigeria and transmission of type 1 and type 3 polioviruses in Nigeria is markedly declining from 2009 to 2010. Moreover, bivalent oral polio vaccine containing Sabin 1 and Sabin 3 strains has been introduced in 2010 as a promising tool to improve and simplify the supplemental immunization activities in high-risk areas. Although there was no apparent decline in the annual number of polio cases in 2000-2009 globally, it would be critical to review our experience during "the lost decade of global polio eradication" to move forward into the final stage of global polio eradication.

Association of Farming with the Development of Cedar Pollinosis in Japanese Adults

Annals of Epidemiology. Nov, 2010  |  Pubmed ID: 20933187

Although cross-sectional studies have reported that the prevalence of allergy is reduced on a farm, few prospective studies were carried out on adults. We examined the association of experience of farming with occurrence of cedar pollinosis in a prospective cohort in Japan.

Tyrosine Sulfation of the Amino Terminus of PSGL-1 is Critical for Enterovirus 71 Infection

PLoS Pathogens. 2010  |  Pubmed ID: 21079683

Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease, a common febrile disease in children; however, EV71 has been also associated with various neurological diseases including fatal cases in large EV71 outbreaks particularly in the Asia Pacific region. Recently we identified human P-selectin glycoprotein ligand-1 (PSGL-1) as a cellular receptor for entry and replication of EV71 in leukocytes. PSGL-1 is a sialomucin expressed on the surface of leukocytes, serves as a high affinity counterreceptor for selectins, and mediates leukocyte rolling on the endothelium. The PSGL-1-P-selectin interaction requires sulfation of at least one of three clustered tyrosines and an adjacent O-glycan expressing sialyl Lewis x in an N-terminal region of PSGL-1. To elucidate the molecular basis of the PSGL-1-EV71 interaction, we generated a series of PSGL-1 mutants and identified the post-translational modifications that are critical for binding of PSGL-1 to EV71. We expressed the PSGL-1 mutants in 293T cells and the transfected cells were assayed for their abilities to bind to EV71 by flow cytometry. We found that O-glycosylation on T57, which is critical for PSGL-1-selectin interaction, is not necessary for PSGL-1 binding to EV71. On the other hand, site-directed mutagenesis at one or more potential tyrosine sulfation sites in the N-terminal region of PSGL-1 significantly impaired PSGL-1 binding to EV71. Furthermore, an inhibitor of sulfation, sodium chlorate, blocked the PSGL-1-EV71 interaction and inhibited PSGL-1-mediated viral replication of EV71 in Jurkat T cells in a dose-dependent manner. Thus, the results presented in this study reveal that tyrosine sulfation, but not O-glycosylation, in the N-terminal region of PSGL-1 may facilitate virus entry and replication of EV71 in leukocytes.

Advanced Carcinoma of the Prostatic Urethra in a Patient with Marked Response to Chemotherapy, Leading to Preservation of the Bladder

International Journal of Clinical Oncology / Japan Society of Clinical Oncology. Feb, 2010  |  Pubmed ID: 20087614

We performed transurethral resection of the prostate (TUR-P) for a 66-year-old man with benign prostatic hyperplasia. Pathological examination diagnosed poorly differentiated urothelial carcinoma of the urethra with broad prostatic permeation. Random bladder biopsies showed no malignancy, but a second TUR-P revealed urothelial carcinoma in the prostate and bladder neck. Computed tomography (CT) showed lymph node metastases from para-aortic to right/left external iliac and left obturator nodes, so clinical stage T3N2M0 carcinoma of the prostatic urethra was diagnosed. Given the presence of lymph node metastases, neoadjuvant chemotherapy using cisplatin 70 mg/m(2), ifosfamide 1.2 g/m(2) and docetaxel 70 mg/m(2) (PIT) was considered. After chemotherapy, CT showed complete response (CR) of all lymph nodes. Local control in the bladder was considered to be good, so total prostatectomy and retroperitoneal lymph node dissection was selected instead of total cystoprostatectomy. Pathological findings of surgical specimens showed no residual carcinoma in the prostatic urethra or lymph nodes, although prostatic adenocarcinoma was recognized. No recurrences or metastases have been encountered as of 3 years and 5 months since surgery.

A Comparison of the VP1, VP2, and VP4 Regions for Molecular Typing of Human Enteroviruses

Journal of Medical Virology. Apr, 2010  |  Pubmed ID: 20166171

The VP4, VP2, and VP1 gene regions were evaluated for their usefulness in typing human enteroviruses. Three published RT-PCR primers sets targeting separately these three gene regions were used. Initially, from a total of 86 field isolates (36 HEV-A, 40 HEV-B, and 10 HEV-C) tested, 100% concordance in HEV-A was identified from all three gene regions (VP4, VP2, and VP1). However, for HEV-B and HEV-C viruses, only the VP2 and VP1 regions, and not VP4, showed 100% concordance in typing these viruses. To evaluate further the usefulness of VP4 in typing HEV-A enteroviruses, 55 Japanese and 203 published paired VP4 and VP1 nucleotide sequences were also examined. In each case, typing by VP4 was 100% in concordance with typing using VP1. Given these results, it is proposed that for HEV-A enteroviruses, all three gene regions (VP4, VP2, and VP1), would be useful for typing these viruses. These options would enhance the capability of laboratories in identifying these viruses and would greatly help in outbreaks of hand, foot, and mouth disease.

[Insulin Allergy Whose Local/systemic Reactions Were Reduced by Desensitization with Long-acting Insulin Analog, Glargine]

Nihon Naika Gakkai Zasshi. The Journal of the Japanese Society of Internal Medicine. Jan, 2010  |  Pubmed ID: 20196485

Prostaglandin E2 Regulates the Expression of Connective Tissue Growth Factor (CTGF/CCN2) in Human Osteoarthritic Chondrocytes Via the EP4 Receptor

BMC Research Notes. 2010  |  Pubmed ID: 20205862

ABSTRACT:

Consumption of Coffee, Green Tea, Oolong Tea, Black Tea, Chocolate Snacks and the Caffeine Content in Relation to Risk of Diabetes in Japanese Men and Women

The British Journal of Nutrition. Feb, 2010  |  Pubmed ID: 19818197

Although the inverse association between coffee consumption and risk of diabetes has been reported numerous times, the role of caffeine intake in this association has remained unclear. We evaluated the consumption of coffee and other beverages and food containing caffeine in relation to the incidence of diabetes. The study participants were 5897 men and 7643 women in a community-based cohort in Takayama, Japan. Consumption of coffee, green tea, oolong tea, black tea and chocolate snacks were measured with a semi-quantitative FFQ in 1992. At the follow-up survey in 2002, the development of diabetes and the time of diagnosis were reported. To assess the association, age, smoking status, BMI, physical activity, education in years, alcohol consumption, total energy intake, fat intake and women's menopausal status were adjusted. Among men who consumed one cup per month to six cups per week and among those who consumed one cup per d or more, the associated hazard ratios were 0.69 (95 % CI 0.50, 0.97) and 0.69 (95 % CI 0.49, 0.98) compared with those who drank little to no coffee, with a P value for trend of 0.32. The hazard ratios for women with the same coffee consumption patterns were 1.08 (95 % CI 0.74, 1.60) and 0.70 (95 % CI 0.44, 1.12), with a P value for trend of 0.03. The association between estimated total caffeine intake and risk of diabetes was insignificant both among men and among women. The results imply that coffee consumption decreased the risk of developing diabetes. The protective effect may exist aside from the influence of caffeine intake.

Characterization of a Rare Natural Intertypic Type 2/type 3 Penta-recombinant Vaccine-derived Poliovirus Isolated from a Child with Acute Flaccid Paralysis

The Journal of General Virology. Feb, 2010  |  Pubmed ID: 19846676

A type 2 vaccine-derived poliovirus (VDPV) (strain CHN1025), with a 1.1 % (10/903) difference from Sabin strain in the VP1 coding region, was isolated from a child with poliomyelitis caused by a poliovirus variant infection. The patient was from Shandong Province of China and developed acute flaccid paralysis in 1997. The child was infected with a rare and complicated penta-recombinant poliovirus with the uncommon genomic recombinant organization S2/S3/S1/S3/S1/S3. At least five successive rounds of recombination occurred in the VP1 capsid coding region and in the 2C, 3C (twice) and 3D(pol) non-capsid coding regions, respectively, during virus evolution. Strain CHN1025 had most of the characteristics of the type 2 vaccine strain; it had Sabin-specific epitopes, suggesting that the virus was antigenically indistinguishable from the Sabin 2 reference strain. Typical mutations in the 5'-untranslated region and VP1 associated with reversion to neurovirulence for Sabin 2 poliovirus were found, and the virus showed moderate neurovirulence in transgenic mice. A few nucleotide substitutions were located in the donor sequences, and two donor sequences contained no nucleotide substitutions, suggesting that these sequences were relatively new. The appearance of these mutations within approximately 192 days of at least five successive rounds of recombination events derived from a single ancestral infection illustrates the rapid emergence of new recombinants among VDPVs. This is the first report on the isolation of a type 2/type 3 poliovirus capsid recombinant with one of the five crossover sites located in the VP1 coding region.

[Laboratory Diagnosis of Poliovirus]

Nihon Rinsho. Japanese Journal of Clinical Medicine. Jun, 2010  |  Pubmed ID: 20942094

[Iaboratory Diagnosis of Human Enteroviruses]

Nihon Rinsho. Japanese Journal of Clinical Medicine. Jun, 2010  |  Pubmed ID: 20942095

Cigarette Smoking and Other Lifestyle Factors in Relation to the Risk of Pancreatic Cancer Death: a Prospective Cohort Study in Japan

Japanese Journal of Clinical Oncology. Feb, 2011  |  Pubmed ID: 21075833

To examine the association of smoking and lifestyle factors with pancreatic cancer death in the prospective design.

Cumulative Effects of Genetic Risk Variants on the Development of Common Atherosclerosis

Expert Review of Cardiovascular Therapy. Mar, 2011  |  Pubmed ID: 21438807

Endemic Transmission of Echovirus 30 in Toyama, Japan in 2010 is Verified by Environmental Surveillance

Japanese Journal of Infectious Diseases. 2011  |  Pubmed ID: 21519136

Fourteen Years' Surveillance of Coxsackievirus Group A in Kyoto 1996‒2009 Using Mouse, RD-18S, and Vero Cells

Japanese Journal of Infectious Diseases. 2011  |  Pubmed ID: 21519137

Prevalence of Tinnitus in Community-dwelling Japanese Adults

Journal of Epidemiology / Japan Epidemiological Association. Jul, 2011  |  Pubmed ID: 21646745

Several studies have reported the prevalence of tinnitus among general populations; however, most of these studies were conducted in Europe or the United States. We estimated the prevalence of tinnitus among the general adult population in Japan.

[Inhibitory Factors of Feeding Behavior and Its Physiological Roles]

Nihon Rinsho. Japanese Journal of Clinical Medicine. Jan, 2011  |  Pubmed ID: 21766581

[Inactivated Poliovirus Vaccine]

Nihon Rinsho. Japanese Journal of Clinical Medicine. Sep, 2011  |  Pubmed ID: 21922761

During the final stage of global polio eradication program, universal use of inactivated poliovirus vaccine (IPV) is the most feasible option to minimize the inherent risk of oral poliovirus vaccine (OPV), such as vaccine-associated paralytic poliomyelitis (VAPP) and polio outbreaks due to vaccine-derived polioviruses. Introduction of diphtheria, pertussis, tetanus, IPV (DPT-IPV) products, instead of OPV, to routine polio immunization should be seriously and urgently considered to minimize ongoing risk of VAPP in Japan. Accordingly, a further polio immunization strategy, including the immunization schedule using DPT-IPV, interchangeability of different DPT-IPV products, intensified polio surveillance activities, and appropriate polio vaccine stockpile, should be developed to maintain polio-free status in Japan prior to the introduction of DPT-IPV.

Neonatal Lethality in Knockout Mice Expressing the Kinase-dead Form of the Gefitinib Target GAK is Caused by Pulmonary Dysfunction

PloS One. 2011  |  Pubmed ID: 22022498

Gefitinib (Iressa) is an inhibitor of the epidermal growth factor receptor (EGFR) that has shown promising activity in the treatment of patients with non-small cell lung cancer (NSCLC). However, adverse side effects of gefitinib treatment, such as respiratory dysfunction, have limited the therapeutic benefit of this targeting strategy. The present results show that this adverse effect can be attributed to the inhibition of the novel gefitinib target GAK (Cyclin G-associated kinase), which is as potently inhibited by the drug as the tyrosine kinase activity of EGFR. Knockout mice expressing the kinase-dead form of GAK (GAK-kd) died within 30 min after birth primarily due to respiratory dysfunction. Immunohistochemical analysis revealed that surfactant protein A (SP-A) was abundant within alveolar spaces in GAK-kd(+/+) mice but not in GAK-kd(-/-) pups. E-cadherin and phosphorylated EGFR signals were also abnormal, suggesting the presence of flat alveolar cells with thin junctions. These results suggest that inhibition of GAK by gefitinib may cause pulmonary alveolar dysfunction, and the present study may help prevent side effects associated with gefitinib therapy in NSCLC patients.

Detection and Molecular Characterization of Cosavirus in Adults with Diarrhea, Thailand

Virus Genes. Dec, 2011  |  Pubmed ID: 22173983

Human cosavirus (HCoSV) is a newly discovered virus in Picornaviridae family. At present it is not clear whether HCoSV is associated with diseases, including gastroenteritis in humans, as epidemiological data is limited. Epidemiological surveillance of HCoSV was conducted on 150 fecal specimens collected from children and 150 samples from adults with diarrhea in Thailand by RT-PCR screening. HCoSV was found in a single adult specimen and not in any of the fecal specimens from children. This represents the first report of HCoSV infection in patients with diarrhea in Thailand. Extensive epidemiological surveillance of novel viruses associated with diarrhea in other populations may provide a better understanding of the distribution, genetic diversity, and association of the viral agents associated with acute gastroenteritis in humans.

Phosphatidylinositol 4-kinase III Beta is a Target of Enviroxime-like Compounds for Antipoliovirus Activity

Journal of Virology. Mar, 2011  |  Pubmed ID: 21177810

Enviroxime is an antienterovirus compound that targets viral protein 3A and/or 3AB and suppresses a step in enterovirus replication by unknown mechanism. To date, four antienterovirus compounds, i.e., GW5074, Flt3 inhibitor II, TTP-8307, and AN-12-H5, are known to have similar mutations in the 3A protein-encoding region causing resistance to enviroxime (a G5318A [3A-Ala70Thr] mutation in poliovirus [PV]) and are considered enviroxime-like compounds. Recently, antienterovirus activity of a phosphatidylinositol 4-kinase III beta (PI4KB) inhibitor, PIK93, was reported, suggesting that PI4KB is an important host factor targetable by antienterovirus compounds (N. Y. Hsu et al., Cell 141:799-811, 2010). In this study, we analyzed the inhibitory effects of previously identified enviroxime-like compounds (GW5074 and AN-12-H5) and a newly identified antienterovirus compound, T-00127-HEV1, on phosphoinositide (PI) kinases. We found that T-00127-HEV1 inhibited PI4KB activity with a higher specificity for than other PI kinases, in contrast to GW5074, which had a broad specificity for PI kinases. In contrast, AN-12-H5 showed no inhibitory effect on PI4KB activity and only moderate inhibitory effects on PI 3-kinase activity. Small interfering RNA (siRNA) screening targeting PI kinases identified PI4KB is a target of GW5074 and T-00127-HEV1, but not of AN-12-H5, for anti-PV activity. Interestingly, T-00127-HEV1 and GW5074 did not inhibit hepatitis C virus (HCV) replication, in contrast to a strong inhibitory effect of AN-12-H5. These results suggested that PI4KB is an enterovirus-specific host factor required for the replication process and targeted by some enviroxime-like compounds (T-00127-HEV1 and GW5074) and that enviroxime-like compounds may have targets other than PI kinases for their antiviral effect.

Attainment of Glycaemic Goals by Step-up Therapy with Biphasic Insulin Aspart-70/30 in Japanese Type 2 Diabetic Patients

Endocrine Journal. 2011  |  Pubmed ID: 21186332

We have made step-up titration protocol with biphasic insulin aspart-70/30 (BIAsp 30), and tried to achieve glycemic goals in poorly controlled Japanese type 2 diabetic patients. We summarized all results obtained to analyze the effectiveness of our protocol. The target of glycaemic control was defined as HbA1c over 7.0 %. In our insulin initiation protocol, all patients started a once-daily injection of BIAsp 30 before the breakfast in addition to their oral hypoglycaemic agents. The patients who could not achieve the target from 12 to 16 weeks after the start of insulin treatment proceeded to twice daily insulin injection before breakfast and dinner. Next, the patients who could not achieve the target from 12 to 16 weeks after the addition of another BIAsp injection proceeded to thrice daily insulin injection before each meal a day. The results of 39 patients were analyzed, and 10.3 % of all patients achieved the target after the start of once daily injection of BIAsp 30, 41.7 % achieved in twice daily injection of BIAsp, and 51.4 % achieved in thrice daily injection of BIAsp. Daily insulin dose at the end of each treatment was 9.3±4.1 U in once daily, 17.4±6.3 U in twice daily, and 28.4±10.4 U in thrice daily. Total body weight increase by 2.0±2.6 kg. The initiation and titration protocol with BIAsp 30 improved glycaemic control, and increased the number of patients with the achievement of glycaemic goals.

Cell Proliferation in Visceral Organs Induced by Ventromedial Hypothalamic (VMH) Lesions: Development of Electrical VMH Lesions in Mice and Resulting Pathophysiological Profiles

Endocrine Journal. 2011  |  Pubmed ID: 21325743

We have found that ventromedial hypothalamic (VMH) lesions produced by electrocoagulation induce cell proliferation in visceral organs through vagal hyperactivity, and also stimulate regeneration of partially resected liver in rats. To facilitate identification of proliferative and/or regenerative factors at the gene level, we developed electrical production of VMH lesions in mice, for which more genetic information is available compared to rats, and examined the pathophysiological profiles in these mice. Using ddy mice, we produced VMH lesions with reference to the previously reported method in rats. We then examined the pathophysiological profiles of the VMH-lesioned mice. Electrical VMH lesions in mice were produced using the following coordinates: 1.6 mm posterior to the bregma, anteriorly; 0.5 mm lateral to the midsagittal line, transversely; and 0.2 mm above the base of the skull, vertically, with 1 mA of current intensity and 10 s duration. The VMH-lesioned mice showed similar metabolic characteristics to those of VMH-lesioned rats, including body weight gain, increased food intake, increased percentage body fat, and elevated serum insulin and leptin. However, there were some differences in short period of hyperphagia, and in normal serum lipids compared to those of VMH-lesioned rats. The mice showed a similar cell proliferation in visceral organs, including stomach, small intestine, liver, and, exocrine and endocrine pancreas. In conclusion, procedures for development of VMH lesions in mice by electrocoagulation were developed and the VMH-lesioned mice showed pathophysiological profiles similar to those of VMH-lesioned rats, particularly in cell proliferation in visceral organs. These findings have not been observed previously in gold thioglucose-induced VMH-lesioned mice. This model may be a new tool for identifying factors involved in cell proliferation or regeneration in visceral organs.

The Preparation of an Infectious Full-length CDNA Clone of Saffold Virus

Virology Journal. 2011  |  Pubmed ID: 21385468

The pathogenicity of Saffold virus (SAFV) among humans still remains unclear, although it was identified as a novel human cardiovirus in 2007. In order to encourage the molecular pathogenetic studies of SAFV, we generated an infectious cDNA clone of SAFV type 3 (SAFV-3). The present study demonstrated that the synthesis of the full-length infectious RNA by T7 RNA polymerase was terminated by a homologous sequence motif with the human preproparathyroid hormone (PTH) signal in the SAFV-3 genome. To obtain the infectious RNA using T7 promoter, a variant of T7 RNA polymerase, which fails to recognize the PTH signal, was useful. This study will provide a valuable technical insight into the reverse genetics of SAFV.

Efficacy of Hippocampal Transection for Left Temporal Lobe Epilepsy Without Hippocampal Atrophy

Epilepsy & Behavior : E&B. May, 2011  |  Pubmed ID: 21497556

We describe a case of left temporal lobe epilepsy without hippocampal atrophy. A 31-year-old woman presented with typical symptoms of complex partial seizures. Magnetic resonance imaging demonstrated slightly obscure internal structures in the left hippocampus. Scalp electroencephalography revealed interictal epileptiform discharges in the left temporal lobe. A Wada test with propofol determined the language-dominant hemisphere to be the left. Intraoperative electrocorticography revealed active epileptic discharges in the hippocampus and the anterior temporal basal area. The hippocampal epileptic area was treated with multiple transection, which led to the complete cessation of epileptic discharges. After surgery, the Rey Auditory Verbal Learning Test score decreased from 12 to 9. However, it returned to the preoperative level 6months after surgery. We describe this case as a typical example demonstrating the efficacy of hippocampal transection for seizure control and the preservation of verbal memory.

Glucagon Plays an Important Role in the Modification of Insulin Secretion by Leptin

Islets. Jul-Aug, 2011  |  Pubmed ID: 21623172

Obese people show marked hyerinsulinemia, but the exact mechanism has not been clarified. Hyperleptinemia is one of possible candidates, although there is an obvious difference in the effect of leptin on insulin secretion between isolated pancreatic islets and β-cell line. Since glucagon may modulate the effect of leptin on insulin secretion, we determined the influences of glucagon in the leptin effect on insulin secretion. The influences of glucagon in the leptin effect on insulin secretion for 10 minutes were determined by using isolated mouse islets and HIT-T 15 cells. The influences of 3-isobutyl-1- methylxanthine (IBMX), forskolin, and dibutyryl cyclic AMP were investigated in the leptin effect on insulin secretion. Leptin-inhibited insulin and glucagon secretion in isolated mouse pancreatic islets. In contrast, leptin stimulated insulin secretion in isolated mouse islets previously incubated with monoclonal anti-glucagon antibodies for 18 hours. In HIT-T 15 cells, leptin dose-dependently increased insulin secretion, but this effect was attenuated by the addition of glucagon. The stimulatory effect of leptin on insulin secretion was attenuated by 48 hour pre-incubation with glucagon. In the presence of 100 mM IBMX, leptin decreased insulin secretion from HIT-T 15 cells. Leptin also reduced insulin secretion in the presence of 1mM forskolin or 1mM dibutyryl cyclic AMP. The leptin effects on insulin secretion were affected by the existence of glucagon. Intracellular cyclic AMP concentrations may determine the leptin effects on insulin secretion in pancreatic β-cells.

Development of a Poliovirus Neutralization Test with Poliovirus Pseudovirus for Measurement of Neutralizing Antibody Titer in Human Serum

Clinical and Vaccine Immunology : CVI. Nov, 2011  |  Pubmed ID: 21880850

In the Global Polio Eradication Initiative, laboratory diagnosis plays a critical role by isolating and identifying poliovirus (PV) from the stool samples from acute flaccid paralysis (AFP) cases. In recent years, reestablishment of PV circulation in countries where PV was previously eliminated has occurred because of decreased herd immunity, possibly due to poor vaccination coverage. To monitor the vulnerability of countries to PV circulation, surveillance of neutralizing-antibody titers against PV in susceptible populations is essential in the end game of the polio eradication program. In this study, we have developed a PV neutralization test with type 1, 2, and 3 PV pseudoviruses to determine the neutralizing-antibody titer against PV in human serum samples. With this test, the neutralizing-antibody titer against PV could be determined within 2 days by automated interpretation of luciferase signals without using infectious PV strains. We validated the pseudovirus PV neutralization test with 131 human serum samples collected from a wide range of age groups (ages 1 to >60 years) by comparison with a conventional neutralization test. We found good correlation in the neutralizing-antibody titers determined by these tests. These results suggest that a pseudovirus PV neutralization test would serve as a safe and simple procedure for the measurement of the neutralizing-antibody titer against PV.

Beneficial Effects of Ventromedial Hypothalamus (VMH) Lesioning on Function and Morphology of the Liver After Hepatectomy in Rats

Brain Research. Nov, 2011  |  Pubmed ID: 21962532

Liver has a high regenerative capacity and restores its mass and function shortly after partial hepatectomy through increased proliferation and metabolic modification of hepatocytes. The proliferation of hepatocytes can be triggered by its mass reduction after hepatectomy or by the neural factors including lesioning of the ventromedial hypothalamus (VMH). In the present study, we examined the effect of VMH lesioning on liver regeneration in hepatectomized rats by evaluating liver function and morphology. We found that functional deficits caused by partial hepatectomy [prolonged prothrombin time (PT), increased indocyanine green (ICG) retention, and decrease in PAS (periodic Acid-Schiff staining)-positive hepatocytes] were restored by VMH lesioning at 1 week after the surgery, whereas these alterations disappeared at 4 weeks. Morphologically, lipid microdroplets, which are considered to be important for maintaining contiguous liver function via supplying fuel for cell proliferation, were found to accumulate in hepatocytes of the hepatectomized rats at early period (1 day) after partial hepatectomy. Interestingly, such lipid microdroplets were also detected in the VMH lesioned rats and the more abundantly in the VMH lesioned, hepatectomized rats up to 1 week after the surgery. In conclusion, our results suggest that VMH lesioning in rats promotes recovery of liver anatomically and functionally after partial hepatectomy by promoting cell proliferation process.

Adaptive Mutations in the Genomes of Enterovirus 71 Strains Following Infection of Mouse Cells Expressing Human P-selectin Glycoprotein Ligand-1

The Journal of General Virology. Feb, 2011  |  Pubmed ID: 20943886

We recently identified human P-selectin glycoprotein ligand-1 (PSGL-1) as a functional enterovirus 71 (EV71) receptor and demonstrated PSGL-1-dependent replication for some EV71 strains in human leukocytes. Here, we report that four out of five PSGL-1-binding strains of EV71 replicated poorly in mouse L929 cells stably expressing human PSGL-1 (L-PSGL-1 cells). Therefore, we compared the replication kinetics and entire genomic sequence of five original EV71 strains and the corresponding EV71 variants (EV71-LPS), which were propagated once in L-PSGL-1 cells. Direct sequence comparison of the entire genome of the original EV71 strains and EV71-LPS variants identified several possible adaptive mutations during the course of replication in L-PSGL-1 cells, including a putative determinant of the adaptive phenotype in L-PSGL-1 cells at VP2-149. The results suggest that an adaptive mutation, along with a PSGL-1-binding phenotype, may facilitate efficient PSGL-1-dependent replication of the EV71 strains in L-PSGL-1 cells.

Human Parechovirus Infection in Children Hospitalized with Acute Gastroenteritis in Sri Lanka

Journal of Clinical Microbiology. Jan, 2011  |  Pubmed ID: 21048003

Of 362 fecal specimens collected from infants and children hospitalized with acute gastroenteritis in Sri Lanka from September 2005 to August 2006, 30 (8.3%) were positive for human parechovirus (HPeV). Six different HPeV genotypes, including HPeV1, -3, -4, -5, -10, and -11, were identified, of these, HPeV11 was reported for the first time.

Cyclin G-associated Kinase Regulates Protein Phosphatase 2A by Phosphorylation of Its B'γ Subunit

Cell Cycle (Georgetown, Tex.). Feb, 2012  |  Pubmed ID: 22262175

Protein phosphatase 2A (PP2A) bearing the B'γ (= B'α/B56γ1/PR61γ) subunit is recruited to dephosphorylation targets by cyclin G. We demonstrate here that cyclin G-associated kinase (GAK), a component of the GAK/B'γ/cyclin G complex, directly phosphorylates the B'γ-Thr104 residue and regulates PP2A activity. Indeed, an anti-B'γ-pT104 antibody detected immunofluorescence signals at the chromosome and centrosome during mitosis; these signals were reduced by siRNA-mediated GAK knockdown. After DNA damage by γ-irradiation, the chromosome signals formed foci that colocalized with a DNA double-strand break (DSB) marker H2AX-pS139 (γH2AX) and CHK2-pT68. Moreover, B'γ-pT104 enhanced PP2A holoenzyme assembly and PP2A activity, as shown by the results of an in vitro phosphatase assay. These results suggest a novel role for GAK as a regulator of dephosphorylation events under the control of the PP2A B'γ subunit.

Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6, Japan, 2011

Emerging Infectious Diseases. Feb, 2012  |  Pubmed ID: 22304983

TO THE EDITOR: Coxsackievirus A6 (CVA6) belongs to human enterovirus species A of the genus Enterovirus. According to a Japanese Infectious Agents Surveillance Report, this virus is one of the major causes of herpangina, an acute febrile disease characterized by vesicles, ulcers, and redness around the uvula, which occurs mainly in young children and infants (1).

Light Exposure at Night, Sleep Duration and Sex Hormone Levels in Pregnant Japanese Women

Endocrine Journal. Feb, 2012  |  Pubmed ID: 22333297

The association between light exposure at night and sex hormone levels in utero has scarcely reported. We assessed the associations between sleep duration or being awake in the late evening hours, which can be as indicator of light exposure at night, and the maternal and umbilical blood hormone levels during pregnancy and at delivery among Japanese women. The data for 236 women and their newborns who visited a maternal clinic in Gifu, Japan, between May 2000 and October 2001 were analyzed. Maternal blood samples were obtained at approximately the 10th weeks, 29th weeks of gestation, and at delivery. Umbilical cord artery blood was immediately drawn after birth. Information for sleep during pregnancy was obtained by a self-administered questionnaire. The levels of estradiol and testosterone were measured using radioimmunoassay. Maternal serum testosterone level in the 10th week was higher among those who were awake at or after 1:00 a.m. than among those who were asleep at that time (P = 0.032). Maternal estradiol level in the 29th week was inversely associated with sleep duration on weekends (P = 0.043). Umbilical testosterone level at delivery inversely correlated with sleep duration on weekdays (P = 0.030). These associations were somewhat stronger among mothers with female offspring than those with male offspring. These results suggested that exposure to light at night might increase sex hormone levels during pregnancy.

Associations of Physical Activity and Diet with the Onset of Menopause in Japanese Women

Menopause (New York, N.Y.). Jan, 2012  |  Pubmed ID: 21926924

Prospective studies on physical activity and diet and the onset of natural menopause are scarce. The aim of this study was to examine the association of physical activity and dietary factors potentially related to endogenous estrogen levels such as fats, dietary fiber, soy isoflavones, and alcohol with the onset of menopause in a cohort of premenopausal women.