The aim of this study was to evaluate the correlation between the mental health status of caseworkers at welfare offices and factors affecting mental health (i.e., working conditions, participation in training courses and workshops, lifestyle habits, presence of illness, social support, and self-efficacy).
"Spatial statistics" is an academic field that deals with the statistical analysis of spatial data, and has been applied to econometrics and various other policy fields. These methods are easily applied by hematologists and oncologists using better and much less expensive software. To encourage physicians to use these methods, this review introduces the methods and demonstrates the analyses using R and FleXScan, which can be freely downloaded from the website, with sample data. It is demonstrated that spatial analysis can be used by physicians to analyze hematological diseases. In addition, applying the technique presented to the investigation of patient prognoses may enable generation of data that are also useful for solving health policy-related problems, such as the optimal distribution of medical resources.
Lymphomatosis cerebri (LC) is a rare form of primary central nervous system lymphoma (PCNSL). Little is known about cases of LC with spinal cord involvement. Among the 11 PCNSL patients treated in our hospital during a four-year period, we identified two cases of LC with spinal cord lesions. One showed a spinal cord lesion followed by leukoencephalopathy. The other showed a spinal cord lesion after LC. In both cases, the histopathology was diffuse large B-cell lymphoma. It is possible that LC may affect the entire central nerve system, and tumor infiltration to the brain and spinal cord in LC may occur more frequently than has been previously considered.
The serotonin (5-HT) system in the brain plays an important role in mood regulation. The postpartum period is considered a high-risk time for mood and anxiety disorders. We assessed changes in 5-HT levels in whole blood (as an indicator of brain 5-HT concentrations) and mood states before and after delivery in 28 healthy, lactating postpartum women. Mood states were evaluated using Profile of Mood States questionnaires (POMS). Measurements were done on the same day in early (first week) and late (third-fourth and sixth-seventh weeks) postpartum, and compared with those in the third trimester and in age-matched, healthy, non-pregnant women. Mean 5-HT concentrations were significantly higher and mean tension/anxiety scores of POMS were significantly lower in late (but not early) postpartum than in the third trimester or non-pregnant controls. 5-HT concentrations correlated with tension/anxiety in the third trimester and late postpartum, indicating an important role for the 5-HT system in the regulation of tension/anxiety in healthy postpartum women. The mechanism underlying the changes in the 5-HT system may be rapid inhibition induced by the marked decrease in estradiol after delivery and gradual excitation caused by lactation-induced brain oxytocin release during the postpartum period.
We report a first case of HIV-associated lymphoma (HAL) presenting with acute kidney injury (AKI) and inflammatory immune reconstitution syndrome (IRIS). A 39-year-old male, treated with nonsteroidal anti-inflammatory drugs (NSAIDs) for one month prior to admission, developed AKI, left testicular tumor, and recurrent swelling of the right parotid gland. A resected testicular tumor exhibited features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Renal biopsy showed hydro-degeneration of renal tubules, interstitial inflammatory cells, and a small number of lymphoma cells in the sub-capsule, compatible with acute interstitial nephritis. His renal dysfunction rapidly recovered following chemotherapy and combination antiretroviral therapy (cART). He developed pneumonia concomitantly with a decrease in HIV-RNA level and an increase in CD4+ cells after the first cycle of chemotherapy, which spontaneously resolved after the second cycle of chemotherapy without additional anti-infection drugs; thus, his pneumonia fulfilled the diagnostic criteria for IRIS. We suggest that IRIS may frequently develop during chemotherapy for HAL, but may be overlooked. He was coinfected with hepatitis B virus (HBV), which genotypes known as is associated with liver-related mortality and response to antiviral therapy; recently, an intimate interplay between HIV and HBV in the onset of lymphoma has been reported. Therefore, we addressed the HBV genotype in the patient. The analysis revealed that he exhibited a mixed genotype (A/E) not native to Japan and primarily found in Europe and North America or West Africa. These findings suggest that universal vaccination for juveniles against HBV is warranted in Japan.
To evaluate the involvement of the mitogen-activated protein kinase (MAPK) cascade in orofacial neuropathic pain mechanisms, this study assessed nocifensive behavior evoked by mechanical or thermal stimulation of the whisker pad skin, phosphorylation of extracellular signal-regulated kinase (ERK) in trigeminal spinal subnucleus caudalis (Vc) neurons, and Vc neuronal responses to mechanical or thermal stimulation of the whisker pad skin in rats with the chronic constriction nerve injury of the infraorbital nerve (ION-CCI). The mechanical and thermal nocifensive behavior was significantly enhanced on the side ipsilateral to the ION-CCI compared to the contralateral whisker pad or sham rats. ION-CCI rats had an increased number of phosphorylated ERK immunoreactive (pERK-IR) cells which also manifested NeuN-IR but not GFAP-IR and Iba1-IR, and were significantly more in ION-CCI rats compared with sham rats following noxious but not non-noxious mechanical stimulation. After intrathecal administration of the MEK1 inhibitor PD98059 in ION-CCI rats, the number of pERK-IR cells after noxious stimulation and the enhanced thermal nocifensive behavior but not the mechanical nocifensive behavior were significantly reduced in ION-CCI rats. The enhanced background activities, afterdischarges and responses of wide dynamic range neurons to noxious mechanical and thermal stimulation in ION-CCI rats were significantly depressed following i.t. administration of PD98059, whereas responses to non-noxious mechanical and thermal stimulation were not altered. The present findings suggest that pERK-IR neurons in the Vc play a pivotal role in the development of thermal hypersensitivity in the face following trigeminal nerve injury.
A 31-year-old pregnant woman was diagnosed with chronic-phase chronic myeloid leukemia at gestational week 16. To avoid exposure of the fetus to teratogenic agents, the patient opted for a course of careful observation only for the duration of her pregnancy. We detected 9.1% of BCR-ABL-positive cells in the patients colostrum with fluorescence in situ hybridization.
To gain insight into the neurophysiological mechanisms involved in Zen meditation, we evaluated the effects of focused attention (FA) on breathing movements in the lower abdomen (Tanden) in novices. We investigated hemodynamic changes in the prefrontal cortex (PFC), an attention-related brain region, using 24-channel near-infrared spectroscopy during a 20-minute session of FA on Tanden breathing in 15 healthy volunteers. We found that the level of oxygenated hemoglobin in the anterior PFC was significantly increased during FA on Tanden breathing, accompanied by a reduction in feelings of negative mood compared to before the meditation session. Electroencephalography (EEG) revealed increased alpha band activity and decreased theta band activity during and after FA on Tanden breathing. EEG changes were correlated with a significant increase in whole blood serotonin (5-HT) levels. These results suggest that activation of the anterior PFC and 5-HT system may be responsible for the improvement of negative mood and EEG signal changes observed during FA on Tanden breathing.
The paper entitled "Effects of Exercise on the Prevention of Conditions Leading to the Need for Long-term Care" by M. Ohtake et al, which was published online on 2 November 2010, has been withdrawn at the authors request.
To evaluate whether P2X receptors are involved in responses to noxious pulp stimulation, the P2X3 and P2X2/3 receptor agonist ?,?-methyleneATP (?,?-meATP) was applied to the molar tooth pulp and nocifensive behavior and extracellular-signal regulated kinase (ERK) phosphorylation in trigeminal spinal subnucleus caudalis (Vc), trigeminal spinal subnucleus interpolaris (Vi), upper cervical spinal cord (C1/C2) and paratrigeminal nucleus (Pa5) neurons were analyzed in rats.
The purpose of this study was to evaluate mechanisms underlying the action of selective serotonin reuptake inhibitors on the improvement of negative mood symptoms in premenstrual syndrome. We assessed relationships between serotonin (5-HT) levels in the brain (estimated from 5-HT concentrations in whole blood) and negative mood states during the premenstrual phase in 13 healthy women. Mood states were evaluated using the Profile of Mood States questionnaire. We also evaluated relationships between 5-HT and ovarian hormones (oestradiol and progesterone). A significant negative correlation was seen between 5-HT concentrations in whole blood and negative mood scores (tension-anxiety and fatigue) observed in the premenstrual phase. A significant positive correlation was observed between 5-HT and oestradiol in the premenstrual phase, but not in the follicular phase. These results suggest that healthy women with lower whole blood 5-HT concentrations in the premenstrual phase exhibit enhanced negative mood due to lower 5-HT concentrations at brain synapses, which may be caused in part by lower oestrogen concentration.
This study evaluates a possible involvement of the prefrontal cortex (PFC) and serotonergic (5-HT) system in psychiatric and electroencephalography (EEG) changes during and after pedaling exercise (PE). The subjects performed PE for 15 min using a cycle ergometer. PE rate was kept at 60 rpm, and the work load (93+/-5.4 W) was decided for each subject before the experiment based on a Rating of Perceived Exertion of 12-13 for self-selected exercise intensity. Cerebral oxygenation in the PFC was assessed by concentration changes in oxygenated hemoglobin (oxyHb) using 24-channel near-infrared spectroscopy. We found that PE evoked a significant increase in oxyHb levels in the ventral PFC during PE as compared with that in the dorsal PFC. Subjects had a feeling of reduced negative mood accompanied by a tendency of increased vigor-activity after PE, as assessed by the Profile of Mood States (POMS) questionnaire. Because the ventral PFC is associated with mood state, we hypothesized that the observed mood changes may have been induced by the activation of the ventral PFC. As for EEG changes during and after PE, we found a significant increase in the relative powers of high-frequency alpha bands (10-13 Hz) during and after PE. A significant increase in whole blood 5-HT level was obtained after PE. Because cortical attenuation would be caused by the 5-HT-induced inhibition of the basal forebrain, we hypothesized that the observed EEG changes are linked with the increased blood 5-HT level or an augmentation of the 5-HT system in the brainstem.
Immunosuppression is one of the common side effects of many anti-tumor agents targeting proliferating cells. We previously reported the development of a new class of pan-cyclin-dependent kinase (Cdk) inhibitor compounds that induce immunosuppression in rodents. Here, we demonstrated that a pan-Cdk inhibitor, Compound 1 very rapidly reduced white blood cells in mice, only 8 h after administration. Compound 1 induced death of peripheral blood cells or purified resting (non-stimulated) lymphocytes ex vivo. Cell death was induced very rapidly, after 4 h of incubation, suggesting that acute immunosuppression observed in rodents might be, at least in part, due to direct cytotoxic effects of Compound 1 on resting lymphocytes. While cell cycle-related Cdks were not activated, the carboxyl terminal domain (CTD) of the largest subunit of RNA polymerase II was phosphorylated, indicating activation of Cdk7 or Cdk9, which phosphorylates this domain, in resting lymphocytes. Indeed, the pan-Cdk inhibitor suppressed CTD phosphorylation in resting cells at the dose required for cell death induction. Inhibition of Cdk7 or Cdk9 by Compound 1 was also confirmed by suppression of nuclear factor-kappa B (NF-?B)-dependent transcription activity in the human cancer cell line U2OS. Interestingly, a Cdk4/6 inhibitor with selectivity against Cdk7 and Cdk9 did not induce cell death in resting lymphocytes. These results suggest that CTD phosphorylation possibly by Cdk7 or Cdk9 might be important for survival of resting lymphocytes and that Cdk inhibitors without inhibitory activity on these kinases might be an attractive agent for cancer chemotherapy.
Wee1 is a tyrosine kinase that phosphorylates and inactivates CDC2 and is involved in G(2) checkpoint signaling. Because p53 is a key regulator in the G(1) checkpoint, p53-deficient tumors rely only on the G(2) checkpoint after DNA damage. Hence, such tumors are selectively sensitized to DNA-damaging agents by Wee1 inhibition. Here, we report the discovery of a potent and selective small-molecule inhibitor of Wee1 kinase, MK-1775. This compound inhibits phosphorylation of CDC2 at Tyr15 (CDC2Y15), a direct substrate of Wee1 kinase in cells. MK-1775 abrogates G(2) DNA damage checkpoint, leading to apoptosis in combination with DNA-damaging chemotherapeutic agents such as gemcitabine, carboplatin, and cisplatin selectively in p53-deficient cells. In vivo, MK-1775 potentiates tumor growth inhibition by these agents, and cotreatment does not significantly increase toxicity. The enhancement of antitumor effect by MK-1775 was well correlated with inhibition of CDC2Y15 phosphorylation in tumor tissue and skin hair follicles. Our data indicate that Wee1 inhibition provides a new approach for treatment of multiple human malignancies.
The aim of this study was to investigate whether astroglia in the medullary dorsal horn (trigeminal spinal subnucleus caudalis; Vc) may be involved in orofacial neuropathic pain following trigeminal nerve injury. The effects of intrathecal administration of the astroglial aconitase inhibitor sodium fluoroacetate (FA) were tested on Vc astroglial hyperactivity [as revealed by glial fibrillary acid protein (GFAP) labeling], nocifensive behavior, Vc extracellular signal-regulated kinase phosphorylation (pERK), and Vc neuronal activity in inferior alveolar nerve-transected (IANX) rats. Compared with sham-control rats, a significant increase occurred in GFAP-positive cells in ipsilateral Vc at postoperative day 7 in IANX rats, which was prevented following FA administration. FA significantly increased the reduced head withdrawal latency to high-intensity heat stimulation of the maxillary whisker pad skin in IANX rats, although it did not significantly affect the reduced escape threshold to low-intensity mechanical stimulation of the whisker skin in IANX rats. FA also significantly reduced the increased number of pERK-like immunoreactive cells in Vc and the enhanced Vc nociceptive neuronal responses following high-intensity skin stimulation that were documented in IANX rats, and glutamine administration restored the enhanced responses. These various findings provide the first documentation that astroglia is involved in the enhanced nociceptive responses of functionally identified Vc nociceptive neurons and in the associated orofacial hyperalgesia following trigeminal nerve injury.
Although propofol (PRO) is widely used in clinic as a hypnotic agent, the underlying mechanisms of its action on pain pathways is still unknown. Sprague-Dawley rats were assigned to receive PRO or pentobarbital (PEN) and were divided into 2 groups as LIGHT and DEEP hypnotic levels based on the EEG analysis. Rats in each hypnotic level received capsaicin injection into the face and phosphorylated extracellular signal-regulated kinase (pERK) immunohistochemistry was performed in subnucleus caudalis (Vc) and upper cervical spinal cord. In the rats with PEN or PRO administration, a large number of pERK-like immunoreactive (LI) cells was observed in the trigeminal spinal subnuclei interpolaris and caudalis transition zone (Vi/Vc), middle Vc, and transition zone between Vc and upper cervical spinal cord (Vc/C2) following capsaicin injection into the whisker-pad region. The number of pERK-LI cells in Vi/Vc, middle Vc, and Vc/C2 was significantly larger in rats with PRO infusion than those with PEN infusion. The number of pERK-LI cells was increased following an increase in the dose of PRO but not in PEN. The pERK-LI cells were mainly distributed in the Vi/Vc, middle Vc, and Vc/C2 after the bolus infusion of PRO. The expression of pERK-LI cells was depressed after the intravenous lidocaine application before bolus PRO infusion. The present findings suggest that PRO induced an enhancement of the activity of trigeminal nociceptive pathways through nociceptors innervating the venous structure, as indicated by a lidocaine-sensitive increase in pERK. This may explain deep pain around the injection regions during intravenous bolus infusion of PRO.
In the orofacial region, limited information is available concerning pathological tongue pain, such as inflammatory pain or neuropathic pain occurring in the tongue. Here, we tried for the first time to establish a novel animal model of inflammatory tongue pain in rats and to investigate the roles of metabotropic glutamate receptor 5 (mGluR5)-extracellular signal-regulated kinase (ERK) signaling in this process.
Cardiac tamponade caused by perforation is a rare but potentially lethal complication of central venous catheter (CVC) insertion. We herein report a case of cardiac perforation associated with the use of a soft J-tipped guide wire. Twenty minutes after the insertion of a CVC, the patient developed unexpected cardiac arrest. An autopsy revealed 400 mL of pericardial blood. The right ventricular wall was 1 mm thick with about 10 myocyte layers, which is one-third that of the normal heart. A histological analysis revealed widespread fatty infiltration of the right ventricular wall (right ventricular lipomatosis).
Increased expression of the transient receptor potential vanilloid 1 (TRPV1) channels, following nerve injury, may facilitate the entry of QX-314 into nociceptive neurons in order to achieve effective and selective pain relief. In this study we hypothesized that the level of QX-314/capsaicin (QX-CAP)--induced blockade of nocifensive behavior could be used as an indirect in-vivo measurement of functional expression of TRPV1 channels. We used the QX-CAP combination to monitor the functional expression of TRPV1 in regenerated neurons after inferior alveolar nerve (IAN) transection in rats. We evaluated the effect of this combination on pain threshold at different time points after IAN transection by analyzing the escape thresholds to mechanical stimulation of lateral mental skin. At 2 weeks after IAN transection, there was no QX-CAP mediated block of mechanical hyperalgesia, implying that there was no functional expression of TRPV1 channels. These results were confirmed immunohistochemically by staining of regenerated trigeminal ganglion (TG) neurons. This suggests that TRPV1 channel expression is an essential necessity for the QX-CAP mediated blockade. Furthermore, we show that 3 and 4 weeks after IAN transection, application of QX-CAP produced a gradual increase in escape threshold, which paralleled the increased levels of TRPV1 channels that were detected in regenerated TG neurons. Immunohistochemical analysis also revealed that non-myelinated neurons regenerated slowly compared to myelinated neurons following IAN transection. We also show that TRPV1 expression shifted towards myelinated neurons. Our findings suggest that nerve injury modulates the TRPV1 expression pattern in regenerated neurons and that the effectiveness of QX-CAP induced blockade depends on the availability of functional TRPV1 receptors in regenerated neurons. The results of this study also suggest that the QX-CAP based approach can be used as a new behavioral tool to detect dynamic changes in TRPV1 expression, in various pathological conditions.
To evaluate the involvement of trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluR2 and GluR3 subunits in an acute inflammatory orofacial pain, we analyzed nocifensive behavior, phosphorylated extracellular signal-regulated kinase (pERK) and Fos expression in Vi/Vc, Vc and C1/C2 in GluR2 delta7 knock-in (KI), GluR3 delta7 KI mice and wild-type mice. We also studied Vc neuronal activity to address the hypothesis that trafficking of GluR2 and GluR3 subunits plays an important role in Vi/Vc, Vc and C1/C2 neuronal activity associated with orofacial inflammation in these mice. Late nocifensive behavior was significantly depressed in GluR2 delta7 KI and GluR3 delta7 KI mice. In addition, the number of pERK-immunoreactive (IR) cells was significantly decreased bilaterally in the Vi/Vc, Vc and C1/C2 in GluR2 delta7 KI and GluR3 delta7 KI mice compared to wild-type mice at 40 min after formalin injection, and was also significantly smaller in GluR3 delta7 KI compared to GluR2 delta7 KI mice. The number of Fos protein-IR cells in the ipsilateral Vi/Vc, Vc and C1/C2 was also significantly smaller in GluR2 delta7 KI and GluR3 delta7 KI mice compared to wild-type mice 40 min after formalin injection. Nociceptive neurons functionally identified as wide dynamic range neurons in the Vc, where pERK- and Fos protein-IR cell expression was prominent, showed significantly lower spontaneous activity in GluR2 delta7 KI and GluR3 delta7 KI mice than wild-type mice following formalin injection. These findings suggest that GluR2 and GluR3 trafficking is involved in the enhancement of Vi/Vc, Vc and C1/C2 nociceptive neuronal excitabilities at 16-60 min following formalin injection, resulting in orofacial inflammatory pain.
The aim of this study was to evaluate spatial organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1), and to clarify the involvement in mechanisms underlying orofacial secondary hyperalgesia following infraorbital nerve injury. We found that the head-withdrawal threshold to non-noxious mechanical stimulation of the maxillary whisker pad skin was significantly reduced in chronic constriction injury of the infraorbital nerve (ION-CCI) rats from day 1 to day 14 after ION-CCI. On day 3 after ION-CCI, mechanical allodynia was obvious in the orofacial skin areas innervated by the 1st and 3rd branches of the trigeminal nerve as well as the 2nd branch area. Hyperactive microglial cells in Vc and C1 were observed on days 3 and 7 after ION-CCI. On day 3 after ION-CCI, a large number of phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) cells were observed in Vc and C1. Many hyperactive microglial cells were also distributed over a wide area of Vc and C1 innervated by the trigeminal nerve. The intraperitoneal administration of minocycline significantly reduced the activation of microglial cells and the number of pERK-IR cells in Vc and C1, and also significantly attenuated the development of mechanical allodynia. Furthermore, enhanced background activity and mechanical evoked responses of Vc wide dynamic range neurons in ION-CCI rats were significantly reversed following minocycline administration. These findings suggest that activation of microglial cells over a wide area of Vc and C1 is involved in the enhancement of Vc and C1 neuronal excitability in the early period after ION-CCI, resulting in the neuropathic pain in orofacial areas innervated by the injured as well as uninjured nerves.
Chronic pain often develops in the orofacial region after inferior alveolar nerve (IAN) injury. In animal models IAN injury often causes severe neuropathic pain-like behavior in the IAN-innervated region as well as the adjacent region that includes the whisker pad skin. However, the basis for the spreading of pain to adjacent facial areas after IAN injury is still unknown. In this study we determined if the transient receptor potential vanilloid 1 (TRPV1) was associated with altered nocifensive behavior evoked by stimulation of the whisker pad skin following IAN transection. Grooming behavior after capsaicin injection into the whisker pad region was significantly increased after IAN transection and the increase in the behavior was reversed by systemic administration of a TRPV1 antagonist. The number of phosphorylated extracellular signal-regulated kinase immunoreactive (IR) neurons in trigeminal spinal subnucleus caudalis and upper cervical spinal cord following capsaicin injection into the whisker pad region was significantly greater in IAN-transected rats than sham-operated rats. The number of TRPV1-IR trigeminal ganglion (TG) neurons innervating the whisker pad skin was also increased significantly after IAN transection. The present findings suggest that an increase in TRPV1 expression in TG neurons innervating the whisker pad skin after IAN transection may underlie the spreading of pain to the adjacent whisker pad skin.
Although erythroid abnormalities (anemia and polycythemia) are commonly observed pathological conditions, not much information about borderline abnormalities is available. In the present study, a cross-sectional study to analyze the relationships between erythropoiesis and nutrition, physical features, and laboratory test findings was conducted in middle-aged and older men and women. The study included 3519 Japanese people (1579 men and 1940 women), age 40 years and over. Analysis of variance showed that the group with a tendency to anemia was older, had a lower body mass index and diastolic blood pressure, and higher serum adiponectin and creatinine. Multiple regression analysis showed that adiponectin, triglycerides, and total protein were common factors that affected erythropoiesis in both men and women. Hepatic, renal, and cardiac functions were also factors involved in erythropoiesis in men and in postmenopausal women. In addition, nutrient factors such as alcohol, vitamins, and carbohydrates were also significantly involved in erythropoiesis in men, but there were no significant nutrient factors involved in erythropoiesis in either premenopausal or postmenopausal women. This study showed that factors that influence erythropoiesis differ among men, premenopausal women, and postmenopausal women, and it suggested that appropriately modifying erythropoiesis management for each group of people is essential. This article is protected by copyright. All rights reserved.
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