ヒトT細胞白血病ウイルスI型(HTLV-I)Taxタンパクの構造と転写活性化機構の解析

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1009号,学位授与年月日：平成3年9月30日,学位授与年：199

Voxel-based structural magnetic resonance imaging (MRI) study of patients with early onset schizophrenia

<p>Abstract</p> <p>Background</p> <p>Investigation into the whole brain morphology of early onset schizophrenia (EOS) to date has been sparse. We studied the regional brain volumes in EOS patients, and the correlations between regional volume measures and symptom severity.</p> <p>Methods</p> <p>A total of 18 EOS patients (onset under 16 years) and 18 controls matched for age, gender, parental socioeconomic status, and height were examined. Voxel-based morphometric analysis using the Brain Analysis Morphological Mapping (BAMM) software package was employed to explore alterations of the regional grey (GM) and white matter (WM) volumes in EOS patients. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS).</p> <p>Results</p> <p>EOS patients had significantly reduced GM volume in the left parahippocampal, inferior frontal, and superior temporal gyri, compared with the controls. They also had less WM volume in the left posterior limb of the internal capsule and the left inferior longitudinal fasciculus. The positive symptom score of PANSS (higher values corresponding to more severe symptoms) was negatively related to GM volume in the bilateral posterior cingulate gyrus. The negative symptom score was positively correlated with GM volume in the right thalamus. As for the association with WM volume, the positive symptom score of PANSS was positively related to cerebellar WM (vermis region), and negatively correlated with WM in the brain stem (pons) and in the bilateral cerebellum (hemisphere region).</p> <p>Conclusion</p> <p>Our findings of regional volume alterations of GM and WM in EOS patients coincide with those of previous studies of adult onset schizophrenia patients. However, in brain regions that had no overall structural differences between EOS patients and controls (that is, the bilateral posterior cingulate gyrus, the right thalamus, the cerebellum, and the pons), within-subject analysis of EOS patients alone revealed that there were significant associations of the volume in these areas and the symptom severity. These findings suggest that at an early stage of the illness, especially for those with onset before brain maturation, a wide range of disturbed neural circuits, including these brain regions that show no apparent morphological changes, may contribute to the formation of the symptomatology.</p

Deconstructing the traditional Japanese medicine “Kampo”: compounds, metabolites and pharmacological profile of maoto, a remedy for flu-like symptoms

Pharmacological activities of the traditional Japanese herbal medicine (Kampo) are putatively mediated by complex interactions between multiple herbal compounds and host factors, which are difficult to characterize via the reductive approach of purifying major bioactive compounds and elucidating their mechanisms by conventional pharmacology. Here, we performed comprehensive compound, pharmacological and metabolomic analyses of maoto, a pharmaceutical-grade Kampo prescribed for flu-like symptoms, in normal and polyI:C-injected rats, the latter suffering from acute inflammation via Toll-like receptor 3 activation. In total, 352 chemical composition-determined compounds (CCDs) were detected in maoto extract by mass spectrometric analysis. After maoto treatment, 113 CCDs were newly detected in rat plasma. Of these CCDs, 19 were present in maoto extract, while 94 were presumed to be metabolites generated from maoto compounds or endogenous substances such as phospholipids. At the phenotypic level, maoto ameliorated the polyI:C-induced decrease in locomotor activity and body weight; however, body weight was not affected by individual maoto components in isolation. In accordance with symptom relief, maoto suppressed TNF-α and IL-1β, increased IL-10, and altered endogenous metabolites related to sympathetic activation and energy expenditure. Furthermore, maoto decreased inflammatory prostaglandins and leukotrienes, and increased anti-inflammatory eicosapentaenoic acid and hydroxyl-eicosapentaenoic acids, suggesting that it has differential effects on eicosanoid metabolic pathways involving cyclooxygenases, lipoxygenases and cytochrome P450s. Collectively, these data indicate that extensive profiling of compounds, metabolites and pharmacological phenotypes is essential for elucidating the mechanisms of herbal medicines, whose vast array of constituents induce a wide range of changes in xenobiotic and endogenous metabolism

Literature survey on epidemiology and pathology of gangliocytic paraganglioma

<p>Abstract</p> <p>Background</p> <p>Although gangliocytic paraganglioma (GP) has generally been regarded as a neuroendocrine tumor, its origin remains unclear. We therefore aimed to investigate the details of this disease by carefully analyzing and extracting common features of the disease as presented in selected publications.</p> <p>Methods</p> <p>We searched for English and Japanese cases of GP using the PubMed and IgakuChuoZasshi databases on August 2010. We then extracted and sampled raw data from the selected publications and performed appropriate statistical analyses. Additionally, we evaluated the expression of hormone receptors based on our previously reported case.</p> <p>Results</p> <p>192 patients with GP were retrieved from the databases. Patient ages ranged from 15 y to 84 y (mean: 52.3 y). The gender ratio was 114:76 (male to female, 2 not reported). Maximum diameter of the tumors ranged from 5.5 mm to 100 mm (mean: 25.0 mm). The duodenum (90.1%, 173/192) was found to be the most common site of the disease. In 173 patients with duodenal GP, gastrointestinal bleeding (45.1%, 78/173) was found to be the most common symptom of the disease, followed by abdominal pain (42.8%, 74/173), and anemia (14.5%, 25/173). Rate of lymph node metastasis was 6.9% (12/173). Our statistical analysis indicated that significant differences were found for gender between GP within the submucosal layer and exceeding the submucosal layer. Furthermore, our immunohistochemical evaluation showed that both epithelioid and pancreatic islet cells showed positive reactivity for progesterone receptors.</p> <p>Conclusions</p> <p>Our literature survey revealed that there were many more cases of GP exceeding the submucosal layer than were expected. Meanwhile, our statistical analyses and immunohistochemical evaluation supported the following two hypotheses. First, vertical growth of GP might be affected by progesterone exposure. Second, the origin of GP might be pancreatic islet cells. However, it is strongly suspected that our data have been affected by publication bias and to confirm these hypotheses, further investigation is required.</p