The present study was performed to evaluate pregnancy outcomes in women with type 1 and type 2 diabetes mellitus (DM) in Japan. This multi-institutional retrospective study was conducted in 40 general hospitals in Japan during 2003-2009. We evaluated 369 and 579 pregnant women with type 1 and type 2 DM, respectively, and compared pregnancy outcomes between the two groups. Glycosylated hemoglobin levels in the first trimester did not differ significantly between the studied groups. Gestational weight gain was lower in type 2 DM than in type 1 DM. Although there were no significant differences in perinatal outcomes between the groups, the primary cesarean section rate was higher in type 2 DM than in type 1 DM. Multiple logistic regression analysis revealed that primigravida status, pre-gestational body mass index (BMI), gestational weight gain, chronic hypertension, and microvascular disease including diabetic retinopathy or nephropathy were associated with onset of pregnancy-induced hypertension. Further, pre-gestational BMI was associated with the need for primary cesarean section. This study demonstrated that no differences were observed in the rates of perinatal mortality and congenital malformation between pregnant women with type 1 DM and type 2 DM; however, women with type 2 DM displayed a higher risk of primary cesarean section.
Molecular imaging is a powerful tool for investigating intracellular signalling, but it is difficult to acquire conventional fluorescence imaging from photoreceptive cells. Here we demonstrated that human opsin5 (OPN5) photoreceptor mediates light-induced Ca(2+) response in human embryonic kidney (HEK293) and mouse neuroblastoma (Neuro2a) cell lines using a luminescence imaging system with a fluorescent indicator and a newly synthesized bioluminescent indicator. Weak light fluorescence and bioluminescence imaging revealed rapid and transient light-stimulated Ca(2+) release from thapsigargin-sensitive Ca(2+) stores, whereas long-lasting Ca(2+) elevation was observed using a conventional fluorescence imaging system. Bioluminescence imaging also demonstrated that OPN5 activation in HEK293 cells induced a decrease in pertussis toxin-sensitive cAMP, confirming previous reports. In addition, ultraviolet radiation induced the phosphorylation of mitogen-activated protein kinases when OPN5 was stimulated in Neuro2a cells. These findings suggest that the combination of these imaging approaches may provide a new means to investigate the physiological characteristics of photoreceptors.
This study explores the correlation between the impact of the Great East Japan Earthquake and the incidence of postpartum depression in Miyagi prefecture, Japan. The design used was a cross-sectional study with self-administered questionnaires, 6-9 months after the disaster. The results showed the prevalence of postnatal women with Edinburgh Postnatal Depression Scale (EPDS) score of ?9 to be 21.3 %. Multivariate analysis showed that exposure to tsunami (odds ratio, 1.80; 95 % confidence interval, 1.16-2.78) was significantly and independently associated with an EPDS score of ?9. Postnatal women and their children should be treated as a vulnerable population, and a protective framework must be established to prepare for future devastating disasters.
Diabetic ketoacidosis (DKA) during pregnancy is a serious complication in both mother and fetus. Most incidences occur during late pregnancy in women with type 1 diabetes mellitus. We report the rare case of a woman with type 1 diabetes mellitus who had normal glucose tolerance during the first trimester but developed DKA during late pregnancy. Although she had initially tested positive for screening of gestational diabetes mellitus during the first trimester, subsequent diagnostic 75-g oral glucose tolerance tests showed normal glucose tolerance. She developed DKA with severe general fatigue in late pregnancy. The patient's general condition improved after treatment for ketoacidosis, and she vaginally delivered a healthy infant at term. The presence of DKA caused by the onset of diabetes should be considered, even if the patient shows normal glucose tolerance during the first trimester.
The aim of this study was to determine the effects of pre-gestational body mass index on pregnancy outcomes of women with gestational diabetes in Japan. A multi-institutional retrospective study was performed. We examined pregnant women who met the former criteria for gestational diabetes in Japan, receiving dietary intervention with self-monitoring of blood glucose with or without insulin therapy. Women with gestational diabetes were divided into three groups according to pre-gestational body mass index: body mass index <25 (control group), 25 ? body mass index <30 (overweight group), body mass index ?30 (obese group). Data from a total of 1,758 eligible women were collected from 40 institutions. Participants included 960 controls, 426 overweight women, and 372 obese women with gestational diabetes. Gestational weight gain was highest in the control and lowest in the obese group. The prevalences of chronic hypertension and pregnancy induced hypertension were higher in the overweight and obese groups than in the control group. Multiple logistic regression analysis revealed pre-gestational body mass index, gestational weight gain, chronic hypertension, and nulliparity to be associated with the onset of pregnancy induced hypertension, while the 75-g OGTT results were unrelated to pregnancy induced hypertension. The prevalence of large-for-gestational age was lower in infants born to obese women than in those born to overweight or control women. The present results suggest that medical interventions for obese women with gestational diabetes may contribute to reducing the prevalence of large-for-gestational age but would not achieve marked reductions in maternal complications.
A 32-year-old-immunologically healthy woman suffered from mumps. A few days later, she was brought to our hospital because of generalized convulsions. On arrival, she developed a decorticate posture. Anti-mumps virus antibodies were detected in her serum. Elevated protein levels without pleocytosis were observed in her cerebrospinal fluid. On the basis of a diagnosis of mumps-associated encephalitis/encephalopathy, steroid pulse therapy was administered, which improve her disturbance of consciousness. She exhibited akinetic mutism, which was followed by deterioration of the frontal lobe. Single-photon emission computed tomography demonstrated decreased regional cerebral blood flow in the bilateral frontal regions. Therefore, she was suspected with frontal lobe dysfunction associated with the lesion, including the thalamus and/or brain stem. We consider that the encephalitis/encephalopathy present in this case was caused by a reversible autoimmune process triggered by mumps virus infection.
Uterine papillary serous carcinoma (UPSC) morphologically resembles ovarian serous carcinoma and is categorized as a type II endometrial cancer. UPSC comprises about 10% of all types of endometrial cancer and has an aggressive clinical course and a poor prognosis. The 14-3-3? gene was originally discovered as a p53-inducible gene; its expression is induced by DNA damage in a p53-dependent manner, which leads to G2 arrest and repair of damaged DNA. Moreover, it has been reported that expression of 14-3-3? is frequently lost in various types of human cancer, including ovarian cancer. We therefore examined the association between 14-3-3? expression determined by immunohistochemistry and clinical outcomes of 51 patients with UPSC. UPSC was considered positive for 14-3-3? when > 30% of tumor cells were stained with a specific antibody. Of these patients, 29 (58.7%) showed positive immunoreactivity for 14-3-3? and 22 (41.3%) had decreased 14-3-3? staining. Decreased immunoreactivity for 14-3-3? was associated with stage (P = 0.001) and lymphovascular space involvement (P = 0.005). Moreover, decreased 14-3-3? expression was an independent risk factor for reduced overall survival (P = 0.0416) in multivariate analysis. Direct bisulfite sequencing was performed to evaluate the methylation status of the 27 CpG islands in the promoter region and first exon of the 14-3-3? gene. These CpG islands were hypermethylated in 30% of 14-3-3?-positive UPSC and 80% of 14-3-3?-negative UPSC, although the difference was not statistically significant. These findings suggest that decreased expression of immunoreactive 14-3-3? may be a predictor of poor prognosis in patients with UPSC.
This clinical study evaluated the effectiveness of guided tissue regeneration using a resorbable collagen membrane and bone swaging in noncontained infrabony defects by assessing changes in probing pocket depth, probing attachment level, and radiographic bone level after 6 months, 1 year, and 2 years. Postsurgical clinical and radiographic measurements were statistically significantly different from presurgical measurements. The rate of bone fill was positively associated with the baseline depth of the bone defect but not associated with the width. The noncontained infrabony defects treated with this combined regenerative method improved clinically and radiographically.
Cytokines released from microglia mediate defensive responses in the brain, but the underlying mechanisms are obscure. One proposed process is that nucleotide leakage or release from surrounding cells is sensed by metabotropic (P2Y) and ionotropic (P2X) purinergic receptors, which may trigger long-term intracellular Ca(2+) flux and tumor necrosis factor ? (TNF-?) release. Indeed, 3h of exposure to ATP was required to evoke TNF-? release from a murine microglial cell line (MG5). A Ca(2+) chelator, ethylene glycol tetraacetic acid (EGTA), reduced ATP-induced TNF-? release, suggesting that intracellular Ca(2+) is important in this response. Therefore, Ca(2+) sensor genes (YC3.6) were transfected into MG5 cells to investigate the Ca(2+) dynamics underlying ATP-induced TNF-? release. The results demonstrated ATP-induced biphasic Ca(2+) mobilization mediated by P2Y (~5min) and P2X7 receptors (5-30min). Moreover, Ca(2+) spiking activity in cell processes progressively increased with a reduction in P2X7 receptor-mediated Ca(2+) elevation during 3-h ATP stimulation. Increased Ca(2+) spiking activity paralleled the reduction in thapsigargin-sensitive internal Ca(2+) stores, dendrite extension, and expression of macrophage scavenger receptors with collagenous structure. The Ca(2+) spiking activity was enhanced by a P2X7 receptor antagonist (A438079), but inhibited by a store-operated channel antagonist (SKF96365) or by co-transfection of small interference ribonucleic acid (siRNA) targeted on the channel component (Orai1). Furthermore, ATP-induced TNF-? release was enhanced by A438079 but was inhibited by SKF96365. Because store-operated channels (Stim1/Orai1) were expressed both in MG5 and primary microglial cultures, we suggest that P2X7 receptor signaling inhibits store-operated channels during ATP stimulation, and disinhibition of this process gates TNF-? release from microglial cells.
Pain and itch are closely related sensations, yet qualitatively quite distinct. Despite recent advances in brain imaging techniques, identifying the differences between pain and itch signals in the brain cortex is difficult due to continuous temporal and spatial changes in the signals. The high spatial resolution of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) has substantially advanced research of pain and itch, but these are uncomfortable because of expensiveness, importability and the limited operation in the shielded room. Here, we used near infrared spectroscopy (NIRS), which has more conventional usability. NIRS can be used to visualize dynamic changes in oxygenated hemoglobin and deoxyhemoglobin concentrations in the capillary networks near activated neural circuits in real-time as well as fMRI. We observed distinct activation patterns in the frontal cortex for acute pain and histamine-induced itch. The prefrontal cortex exhibited a pain-related and itch-related activation pattern of blood flow in each subject. Although it looked as though that activation pattern for pain and itching was different in each subject, further cross correlation analysis of NIRS signals between each channels showed an overall agreement with regard to prefrontal area involvement. As a result, pain-related and itch-related blood flow responses (delayed responses in prefrontal area) were found to be clearly different between pain (??=?+18.7 sec) and itch (??=?+0.63 sec) stimulation. This is the first pilot study to demonstrate the temporal and spatial separation of a pain-induced blood flow and an itch-induced blood flow in human cortex during information processing.
It was previously reported that the brachial-ankle pulse wave velocity (baPWV) is elevated in preeclamptic women. However, baPWV is strongly affected by blood pressure. Recently, a new index of vascular stiffness, the cardioankle vascular index (CAVI), was developed. CAVI is thought to be an index independent of blood pressure. We assessed CAVI in normotensive and hypertensive pregnant women. We studied a total of 109 Japanese women consisting of 23 nonpregnant healthy women (group A), 45 normotensive pregnant women (group B), 28 pregnant women complicated with established preeclampsia (group C), and 13 pregnant women with chronic hypertension (group D). The subject remained supine while the blood pressure, baPWV, and CAVI were recorded. No significant difference in baPWV was present between groups C and D, but the difference in CAVI was significantly high in group D. We believe that we can distinguish the vessel structural change between chronic hypertension and preeclampsia through simultaneous baPWV and CAVI measurements.
Greater antenatal weight or body mass index (BMI) gains may lead to larger fetuses and thus increase the risk for operative deliveries, such as cesarean deliveries. In order to examine the effect of weekly maternal weight and BMI changes on large-for-gestational-age (LGA) infants and cesarean delivery, delivery records from overall healthy women were analyzed.
The infiltration of classically activated macrophages (M1) and alternatively activated macrophages (M2) in subcutaneous adipose tissue (SAT) and parametrial adipose tissue (PAT) was analyzed to investigate whether local inflammatory change in adipose tissue occurs in late pregnancy. C57BL/6N female mice at 6 weeks of age were fed a normal chow diet for 4 weeks prior to mating at 10 weeks of age and were sampled on day 17 of pregnancy. The serum levels of adipokines and biochemical markers were measured using ELISA and enzymatic methods. The identification of M1 and M2 was analyzed by double immunofluorescence with anti-F4/80 and anti-CD11c antibodies. The gene expression of adipokines in adipose tissues was analyzed by quantitative RT-PCR. The pregnant group showed adipocyte hypertrophy, higher macrophage infiltration, and higher M1/M2 in both SAT and PAT compared with the non-pregnant (NP) group. Serum levels of free fatty acids, tumor necrosis factor ? (TNF?), interleukin 6 (IL6), and IL10 were higher, and serum levels of adiponectin were lower in the pregnant group than those in the NP group. The gene expressions of CD68, Itgax, CCR2, TNF?, and PAI1 in SAT during pregnancy were significantly higher than those in the NP group, as were the gene expressions of CD68, Emrl, Itgax, MCP1, TNF?, IL6, PAI1, adiponectin, and IL10 in PAT. These results suggest that the low-grade inflammation of adipose tissue indicated by increased macrophage infiltration occurs in late normal pregnancy.
Human breast cancer resistance protein (BCRP)/MXR/ABCG2 is a well-recognized ABC half-transporter that is highly expressed at the apical membrane of many normal tissues and cancer cells. BCRP facilitates disposition of endogenous and exogenous harmful xenobiotics to protect cells/tissues from xenobiotic-induced toxicity. Despite the enormous impact of BCRP in the physiological and pathophysiological regulation of the transport of a wide variety of substrates, little is known about the factors that regulate posttranslational expression of BCRP. Here, we identified Derlin-1, a member of a family of proteins that bears homology to yeast Der1p, as a posttranslational regulator of BCRP expression. Overexpression of Derlin-1 suppressed ER to Golgi transport of wild-type (WT) BCRP that is known to be efficiently trafficked to the plasma membrane. On the other hand, protein expression of N596Q variant of BCRP, N-linked glycosylation-deficient mutant that preferentially undergoes ubiquitin-mediated ER-associated degradation (ERAD), was strongly suppressed by the overexpression of Derlin-1, whereas knockdown of Derlin-1 stabilized N596Q protein, suggesting a negative regulatory role of Derlin-1 for N596Q protein expression. Notably, knockdown of Derlin-1 also stabilized the expression of tunicamycin-induced deglycosylated WT BCRP protein, implying the importance of glycosylation state for the recognition of BCRP by Derlin-1. Thus, our data demonstrate that Derlin-1 is a negative regulator for both glycosylated and non-glycosylated BCRP expression and provide a novel posttranslational regulatory mechanism of BCRP by Derlin-1.
Pruritus, also known as itch, is a sensation that causes a desire to scratch. Prolonged scratching exacerbates skin lesions in several skin diseases such as atopic dermatitis. Here, we identify the cystic fibrosis transmembrane conductance regulator (CFTR/Cftr), an integral membrane protein that mediates transepithelial chloride transport, as a determinant factor in mice for the susceptibility to several cutaneous symptoms during mite infestation. Mice that endogenously express dysfunctional Cftr (Cftr(?F508/?F508)) show significant increase of scratching behavior and skin fibrosis after mite exposure. These phenotypes were due to the increased expression of nerve growth factor (NGF) that augments the sensitization of peripheral nerve fibers. Moreover, protein gene product 9.5 (PGP9.5)-positive neurites were abundant in the epidermis of mite-infested Cftr(?F508/?F508) mice. Furthermore, mite-infested Cftr(+/+) mice orally administered with a chloride channel inhibitor glibenclamide had higher scratching count and increased level of NGF than vehicle-treated mice. Consistently, mite extract-exposed primary and transformed human keratinocytes, treated with CFTR inhibitor, had significantly higher level of NGF mRNA compared with vehicle-treated, mite extract-exposed cells. These results reveal that CFTR in keratinocytes plays a critical role for the regulation of peripheral nerve function and pruritus sensation, and suggest that Cftr(?F508/?F508) mice may serve as a novel mouse model that represents NGF-dependent generation of pruritus.
Group-A-streptococcus-(GAS)-induced toxic shock syndrome (TSS) is uncommon, but carries a high risk of maternal mortality during pregnancy. The onset of gravidic GAS-TSS has been reported mostly during the puerperium. A 16-year-old woman, who was at 37 weeks of gestation, and without obstetrical care during the last 30 weeks, was referred to our hospital. She complained of fever for one day with headache and abdominal pain after the fever developed. On admission, her consciousness was drowsy, intrauterine fetal death was recognized, and she rapidly developed shock status with coma and hypotension, hemolysis, disseminated intravascular coagulation (DIC), and multi-organ failure. Although we had not obtained the results of a bacterial culture, we suspected sepsis with DIC with homolysis and multi-organ failure resulting from an infection. The patient was treated with antibiotics and intubation because of respiratory insufficiency. Twelve hours after admission to the intensive care unit in our hospital, she died. Cultures from blood, subcutaneous tissue, vaginal discharge, and pharynx all revealed GAS bacteria, and therefore she was diagnosed as having GAS-TSS. GAS-TSS in pregnancy is rare. However, once the infection occurs in a pregnant woman, it rapidly develops into sepsis with multi-organ failure. Therefore, early recognition and intensive treatment for GAS during pregnancy is recommended in women with high fever, muscular pain, hemolysis and DIC during pregnancy.
The mechanisms underlying the inhibitory effects of deuterium oxide (D?O; heavy water) are likely to provide insight into the fundamental significance of hydrogen bonds in biological functions. Previously, to begin elucidating the effect of D?O on physiological functions in living cells, we studied the effects of D?O on voltage-sensitive Ca²(+) channels in AtT 20 cells and showed that actin distribution, Ca²(+) currents, and ?-endorphin release were affected. However, the molecular mechanisms underlying the inhibitory effects of D?O in whole animals and living cells remain obscure, especially in the effects of D?O on the cell signaling.
There are three different diagnostic score systems for disseminated intravascular coagulation (DIC) established by the Japanese Ministry Health and Welfare (JMHW), the International Society on Thrombosis and Haemostasis (ISTH) and the Japanese Association for Acute Medicine (JAAM). The JMHW criteria are still used in Japan. In the present study, all three diagnostic criteria were used to prospectively evaluate 413 patients with different underlying diseases of DIC who were treated at the Mie University Hospital (JMHW, n= 166; ISTH, n=143; JAAM, n=291). The odds ratio (95% confidence interval) for death was 1.88 (1.22 - 2.90) in JMHW, 2.55 (1.65 - 3.95) in ISHT and 1.99 (1.19 - 3.32) in JAAM. The platelet count, prothrombin time, fibrin and fibrinogen degradation products and fibrinogen were significantly important for diagnosis of DIC by all three diagnostic criteria. Haemostatic molecular markers were significantly high in all patients and were useful for the diagnosis of DIC. The JAAM diagnostic criteria displayed a high sensitivity for DIC and the ISTH overt-DIC diagnostic criteria displayed a high specificity for DIC. All three diagnostic criteria for DIC were related to a poor patient outcome.
THE SLEEP SEQUENCE: i) non-REM sleep, ii) REM sleep, and iii) wakefulness, is stable and widely preserved in mammals, but the underlying mechanisms are unknown. It has been shown that this sequence is disrupted by sudden REM sleep onset during active wakefulness (i.e., narcolepsy) in orexin-deficient mutant animals. Phospholipase C (PLC) mediates the signaling of numerous metabotropic receptors, including orexin receptors. Among the several PLC subtypes, the beta4 subtype is uniquely localized in the geniculate nucleus of thalamus which is hypothesized to have a critical role in the transition and maintenance of sleep stages. In fact, we have reported irregular theta wave frequency during REM sleep in PLC-beta4-deficient mutant (PLC-beta4-/-) mice. Daily behavioral phenotypes and metabotropic receptors involved have not been analyzed in detail in PLC-beta4-/- mice, however.
Fulminant type 1 diabetes associated with pregnancy is very rare. However if it occurs, the rapid onset is associated with an extremely high risk of fetal death. Therefore, it is important for physicians to make an appropriate diagnosis as early as possible and to begin immediate treatment of both the mother and the fetus. We report a case of fulminant type 1 diabetes associated with pregnancy in which a good outcome was achieved for both the mother and the fetus.
Most patients with malignant diseases are frequently complicated with some type of thrombosis, such as disseminated intravascular coagulation (DIC) or deep vein thrombosis (DVT)/pulmonary embolism (PE).
Congenital diaphragmatic hernia (CDH) occurs in multiple malformation syndromes and associations, and has been associated with cytogenetic aberrations on almost every chromosome arm. However, CDH with a duplication of chromosome 1q is very rare in the literature, and all previously reported cases with detailed clinical courses died soon after birth. We present the first surviving case of CDH with a duplication of 1q12-q23, who had arthrogryposis multiplex congenita and hypertrophic cardiomyopathy. CDH patients with a proximal duplication of chromosome 1q may have a chance for survival, and CDH with a duplication of chromosome 1q is not necessarily a lethal association.
Related JoVE Video
Journal of Visualized Experiments
What is Visualize?
JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
How does it work?
We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.
Video X seems to be unrelated to Abstract Y...
In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.