Role of putative phosphorylation sites in down-regulation of histamine H1 receptors.
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Biomedical subjects
Publications and source records attributed to T Katoh.
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Our study was designed to assess the contributions of the physical and constitutional factors to osteophyte formation, disc degeneration, and bone mineral density (BMD) in lumbar vertebrae of elderly postmenopausal women. A total of 126 Japanese women with back pain, aged over 60 years, were invited to participate in the study. Then 80 subjects with a full set of data for physical examinations, radiographs, MRI, and DXA were examined. TaqI polymorphism of vitamin D receptor (VDR) gene was examined in 60 subjects. Prevalence rates of osteophytes (on radiographs) and disc degeneration (on MRI) were 61 and 68%, respectively. Body weight and BMI correlated significantly with anteroposterior (AP) and lateral (LAT) BMD (r = 0.354 for weight, r = 0.347 for BMI) and mean osteophyte area (r = 0.557 for weight, r = 0.486 for BMI), and body weight also correlated with number of discs with osteophytes. However, these did not correlate with the disc area or the number of degenerated discs. Stepwise regression analysis revealed that body weight and LAT-BMD values independently related to the osteophyte area. Disc area (r = 0.386 for AP view) and osteophyte area (r = 0.384 for AP view) significantly correlated with BMD. However, disc area and osteophyte area did not correlate with each other (r = 0.056). The proportion of degenerated discs was higher in the lower lumbar discs, but not the proportion of discs with osteophytes. Frequencies of T and t alleles of VDR did not correlate with disc degeneration, osteophyte formation, or osteoporosis. Our data showed that increases in osteophyte formation and BMD in the lumbar vertebrae are influenced by body weight and BMI, but did not correlate with disc area, which correlated inversely with BMD. Disc degeneration and osteophyte formation seem to represent two different factors that affect lumbar spine in elderly women.
BACKGROUND AND OBJECTIVE: The aim was to determine the effect of acute and chronic administration of 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, on the righting reflex ED50 and the minimum alveolar concentration during sevoflurane anaesthesia in rats. METHODS: 7-Nitroindazole was acutely (0, 50 and 100 mg kg(-1)) and chronically (0 and 150 mg kg(-1) day(-1), 4 days) administered to rats. After the preparation, the minimum alveolar concentration and the righting reflex ED50 were measured. The concentration of cGMP in the brain, cerebellum and spinal cord was also measured. RESULTS: Acute administration reduced the minimum alveolar concentration (50 mg kg(-1), 58.8% (95% CI: 50.3-67.3%) of the baseline value, P < 0.01; 100 mg kg(-1), 55.8 (46.9-64.7), P < 0.01) and the righting reflex ED50 (50 mg kg(-1), 27.2 (17.2-37.2), P < 0.01; 100 mg kg(-1), 14.3 (6.6-22.0), P < 0.01). Chronic administration did not reduce the minimum alveolar concentration; however, it reduced the righting reflex ED50 (65.3 (52.9-77.7), P < 0.01). Overall, the reduction in minimum alveolar concentration in the acute and chronic protocol did not correlate with that of the righting reflex ED50. 7-Nitroindazole (100 mg kg(-1), acute) reduced the cGMP concentration within the cerebellum by 55.4%; however, it did not decrease concentrations in the brain or spinal cord. CONCLUSIONS: Different mechanisms are responsible for the observed alterations to the minimum alveolar concentration and the righting reflex ED50 following treatment with 7-nitroindazole. The nitric oxide-cGMP pathway might play a less important role in the determination of minimum alveolar concentration than the righting reflex ED50.
A rare case of metastatic hepatocellular carcinoma (HCC) of the maxillary sinus in a 67-year-old man is reported along with the findings at autopsy. A fine needle aspiration biopsy specimen revealed a characteristic tumour structure resembling primary HCC. At autopsy, metastatic lesions were recognized in the bilateral adrenals, spleen, sternum, vertebrae and lymph node at the lesser curvature of the stomach, but not in the lung, suggesting that the HCC had metastasized to the maxillary sinus via the plexus venous vertebralis and/or the azygos vein, or lymph duct. In our reviewed 29 cases of metastatic HCC in the oro-maxillofacial region, most patients were men in the 50- to 70-year age range. At least 11 cases did not have lung metastasis, and in 18, metastasis to the oro-maxillofacial region was the first sign of HCC. One should be aware of the possibility to encounter the oral lesion as first sign of metastatic HCC.
A method for measuring entrance surface dose in intraoral radiography for nationwide survey for the determination of guidance levels was developed using a commercially available radiophotoluminescent dosemeter (RPLD) system. From the ratio of the readings of the RPLD detectors. with and without a 1 mm thick aluminium filter, half value layer (HVL) and the energy dependency correction factor were derived. HVL and exposure for intraoral radiography were obtained with uncertainties of +/- 0.11 mmAl (SD) and +/- 2.1% (CV), respectively. This has been achieved by calibration at various beam qualities used in intraoral radiography. The HVLs and outputs of intraoral radiography units were measured by means of the mailed RPLD holders and also by ionisation chambers in 19 dental schools in Japan. Results obtained from the two methods of measurement agreed well for both HVLs and outputs.
BACKGROUND: Insulin resistance has been reported to induce hypertension. Previous studies described that there was no relationship between insulin resistance and hypertension in patients with chronic renal diseases with mild to moderate renal dysfunction. The aim of the present study is to clarify the relationship between insulin resistance and blood pressure, renal function, histopathological changes and other characteristics in IgA nephropathy (IgAN). METHODS: Eighty-eight IgAN patients were included in this cross-sectional study. Hypertension was diagnosed according to the WHO/ISH criteria. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR). RESULTS: Male gender, age, body mass index, serum creatinine, urinary protein excretion, triglycerides and HOMA-IR were positively correlated with hypertension. C(Cr), serum albumin and HDL cholesterol were negatively correlated with blood pressure by Spearman's simple correlation test. By logistic multivariate analysis, C(Cr), insulin resistance, age and male gender were significantly correlated with hypertension, independently of all other variables. CONCLUSIONS: Insulin resistance is not directly related to renal dysfunction, but is also independently associated with hypertension in IgAN. Since hypertension is considered as a risk factor for renal disease progression, insulin resistance may be an indirect deteriorating factor for IgAN. To identify and improve insulin resistance may be another therapeutic target in the clinical management of IgAN.
The background linkage disequilibrium (LD) in genetic isolates is of great interest in human genetics. Although many empirical studies have evaluated the background LD in European isolates, such as the Finnish and Sardinians, few data from other regions, such as Asia, have been reported. To evaluate the extent of background LD in East Asian genetic isolates, we analyzed the X chromosome in the Japanese population and in four Mongolian populations (Khalkh, Khoton, Uriankhai, and Zakhchin), the demographic histories of which are quite different from one another. Fisher's exact test revealed that the Japanese and Khalkh, which are the expanded populations, had the same or a relatively higher level of LD than did the Finnish, European American, and Sardinian populations. In contrast, the Khoton, Uriankhai, and Zakhchin populations, which have kept their population size constant, had a higher background LD. These results were consistent with previous genetic anthropological studies in European isolates and indicate that the Japanese and Khalkh populations could be utilized in the fine mapping of both complex and monogenic diseases, whereas the Khoton, Uriankhai, and Zakhchin populations could play an important role in the initial mapping of complex disease genes.
BACKGROUND: In an anomalous arrangement of the pancreaticobiliary duct (AAPBD), two-way regurgitation, including pancreaticobiliary reflux and biliopancreatic reflux (BPR), might occur. Although pancreaticobiliary reflux has been shown by high levels of pancreatic enzymes in bile, there have been few reports of clinical evidence of BPR in AAPBD. Recently, spiral computed tomography combined with intravenous infusion cholangiography (IVC-SCT) has been reported to be useful for visualizing the biliary anatomy, which may allow a new insight into bile flow dynamics in AAPBD. METHODS: Fifteen paediatric patients with AAPBD were examined before operation using both IVC-SCT and endoscopic retrograde cholangiopancreatography. Visualization of the main pancreatic duct on IVC-SCT defined the presence of BPR. Blood samples were also analysed when the initial symptom was strongly present. RESULTS: BPR was observed in six of 15 patients. Pancreatic enlargement and hyperamylasaemia were significantly more frequent in patients without BPR than in those with BPR. Levels of enzyme markers of cholestasis were also higher in the former group. CONCLUSION: The present study, using IVC-SCT, has identified clinical evidence of BPR in AAPBD. Further studies are necessary to determine the correlation between BPR and clinical manifestations.
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OBJECTIVE: Recent studies have demonstrated an association between vitamin D receptor (VDR) genotype and prostate cancer. Currently, there is a scarcity of data regarding the association of VDR genotype with benign prostatic hyperplasia (BPH). The purpose of this study was to investigate the TaqI VDR polymorphism in Japanese prostate cancer patients, Japanese BPH patients and Japanese controls in order to determine if an association exists between VDR genotype and the risk of developing prostate cancer and BPH as well as disease severity. METHODS: 110 prostate cancer patients, 83 BPH patients and 90 male age-matched controls were genotyped for a previously described TaqI restriction fragment length polymorphism at codon 352 in exon 9 of the VDR gene. Products were digested into T allele or t allele according to the absence or presence of a TaqI restriction site with individuals being classified as TT, Tt or tt. RESULTS: The frequency of the genotype tt was higher in the control group (6.7%) compared to patients with prostate cancer (1.8%) and BPH (3.6%) but this was not statistically significant. However, the frequency of the genotype TT was significantly higher among prostate cancer patients with locally advanced or metastatic disease (T3/ T4/N1/M1) compared to controls (p = 0.001). In addition, the genotype TT was significantly higher among prostate cancer patients with a high Gleason grade of tumor (grade 5) compared to controls (p = 0.0001). In addition, the genotype TT was statistically higher in BPH patients with high prostate volume (volume >50 cm(3)) compared to controls (p = 0.001). CONCLUSION: These data demonstrate that VDR genotype plays an important role in determining the risk of more advanced and aggressive prostate cancer as well as prostatic enlargement in Japanese men.
A 71-year-old man was admitted because of an abnormal shadow on the chest X-ray film. Chest computed tomography (CT) revealed a tumor in the right upper lobe. The diagnosis of lung cancer was made by transbronchial lung biopsy. He had suffered an infarction of the inferior myocardial wall at the age of 55 years. Preoperative coronary angiography revealed total occlusion of segment 1, 75% stenosis of segments 5 and 6, and 90% stenosis of segment 13. Since these coronary lesions could cause perioperative and postoperative myocardial infarction, the patient was scheduled to undergo surgery of both the heart and lung in a one-stage operation. Under intraaortic balloon pumping (IABP), we performed a right upper lobectomy of the lung, and coronary artery bypass grafting with cardiopulmonary bypass through median sternotomy. During the lobectomy and first postoperative day, a stable circulation was achieved with IABP. The postoperative course was uneventful. At present, that is 33 months after the operation, the patient presents no sighs of recurrence of lung cancer and has not suffered any anginal attack during follow-up. Lung cancer and coronary artery disease can be treated simultaneously by this procedure.
A case of contralateral pneumothorax after pneumonectomy was reported. Intrathoracic drainage was performed and pneumothorax was healed. Recurrent pneumothorax was occurred in this patient and intrathoracic drainage was performed again and pneumothorax was healed. We suspected that bulla was the cause of pneumothorax and thought that contralateral pneumothorax after pneumonectomy must be carefully follow-up.
The effects of intracerebroventricular injection of endomorphin-1 and 2, endogenous mu-opioid receptor agonists, on the scopolamine-induced impairment of spontaneous alternation performance associated with short-term memory were investigated in mice. Endomorphin-1 (0.03 microg) inhibited scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without affecting total arm entries, while endomorphin-2 (0.01-10 microg) failed to significantly influence the scopolamine (1 mg/kg)-induced impairment. Endomorphin-1 (0.03 microg) itself had no marked effects on spontaneous alternation performance in intact mice. Although beta-funaltrexamine (5 microg), a mu-opioid receptor antagonist, did not significantly affect the inhibitory effects of endomorphin-1 (0.03 microg) on the scopolamine (1 mg/kg)-induced impairment, naloxonazine (35 mg/kg), a mu1-opioid receptor antagonist, significantly reversed the inhibitory effects of endomorphin-1 (0.03 microg) on the impairment. Naloxonazine (35 mg/kg) unlike beta-funaltrexamine (5 microg) did not significantly influence the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. These results suggest that endomorphin-1 improves the disturbance of short-term memory resulting from cholinergic dysfunction through the mediation of mu1-opioid receptors.
Cross-sectional and longitudinal studies were done to investigate the influence that a change in smoking habit can have on the pulmonary function. Seventeen hundred and thirty nine people (698 men, 1,041 women), 39 years of age or older, from the population of a farming village located in the central part of Miyazaki Prefecture were examined. A population-based cohort study with a 4-time observation was done over an interval of 12 years. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1.0) were used as the index of respiratory function, and adjusted annual change of FVC and adjusted annual change of FEV1.0 were used as a pulmonary function inspection index. There was a statistical significance in both %FVC and %FEV1.0 to the predicted values between smokers and non-smokers at the beginning of observation. The adjusted annual change of FVC both of male- and female-smokers and the adjusted annual change of FEV1.0 of male-smokers was higher than those of non-smokers in the longitudinal study. Percent FVC, %FEV1.0 and the adjusted FEV1.0 change of former male-smokers were lower than those of continuing smokers. In addition to %FVC and %FEV1.0, annual change of FVC and annual change of FEV1.0 were important predictors of pulmonary function related to cigarette smoking.
TipAL is a Streptomyces transcriptional activator assigned to the MerR/SoxR family based both on homology within its putative DNA recognition domain and the fact that its operator binding sites lie within a region of its promoter normally occupied by RNA polymerase. The tipA gene is also independently translated as the C-terminal ligand-binding domain of TipAL (TipAS; residues 111-254). Both TipAS and TipAL share broad recognition specificity for cyclic thiopeptide antibiotics. The molecular mechanism by which TipAL catalyzes prokaryotic transcriptional activation at the tipA promoter (ptipA) in response to thiostrepton was studied using a combination of analytical ultracentrifugation (AU), circular dichroism (CD), optical waveguide lightmode spectroscopy (OWLS; a sensitive in situ binding assay), and mutational analyses. AU showed that TipAL, but not TipAS, was a dimer in solution in the presence or absence of thiostrepton. This indicated that activation of TipAL by thiostrepton was not mediated by changes in multimerization and mapped the dimerization domain to its N-terminal 110 amino acids, presumably within amino acids predicted to form a coil-coil domain (residues 77-109). CD spectra showed that TipAL had more alpha-helical content than TipAS, probably because of the presence of the additional N-terminal region. The helicity of TipAL and TipAS both increased slightly after binding thiostrepton demonstrating conformation changes upon thiostrepton binding. OWLS experiments determined the overall binding constants via measurements of association and dissociation rates for both TipA proteins and RNA polymerase with ptipA. Thiostrepton slightly enhanced the rate of specific association of TipAL with ptipA, but drastically lowered the rate of dissociation from the binding site. TipAL-thiostrepton increased the affinity of RNA polymerase for ptipA more than 10-fold. In conjunction with genetic experiments, we propose that, while there are some similarities, the mechanism by which TipAL activates transcription is distinctly different from the established MerR/SoxR paradigm.
[structure: see text]. 8-O-methylpopolohuanone E (2) was synthesized in a highly convergent manner starting from the cis-fused decalin derivative accessible from the (-)-Wieland-Miescher ketone analogue. The synthetic method features a biogenetic-type annulation of the phenolic and quinone segments to regioselectively construct the central tricyclic ring system as the key step.
Steroid hormones, especially testosterone, play important roles in the carcinogenesis of prostate cancer, and several studies have reported changes in risk with polymorphisms of genes involved in steroid metabolism. One example is the CYP17 gene, which has a polymorphic T-to-C substitution in the 5'-untranslated region giving rise to A1 (T) and A2 (C) alleles. Steroid 5alpha-reductase type II (SRD5A2), which converts testosterone to the metabolically more active dihydrotestosterone, exhibits 2 polymorphisms: V89L, which substitutes leucine for valine at codon 89, and A49T, which substitutes threonine for alanine at codon 49. We therefore designed a case-control study of 105 prostate-cancer patients and 210 controls with benign prostatic hyperplasia for the purpose of investigating the association between prostate-cancer risk and polymorphisms in the SRD5A2 and CYP17 genes among the Japanese. The frequency of the CYP17 A2/A2 genotype in cases (18.8%) was higher than in controls (14.5%). Compared with the A1/A1 genotype, the odds ratio for the A2/A2 genotype was 2.39 (95% confidence interval 1.04-5.46, p = 0.04). The frequency of the SRD5A2 LL genotype in cases (29.3%) was also slightly higher than in controls (24.6%), but this was not significant. Regarding the A49T polymorphism of SRD5A2, we could not detect the T allele in any of the examined samples. These data suggest a significant association between the CYP17 polymorphism and prostate-cancer risk among the Japanese.
The cyclohexenone segment 2 of scyphostatin (1), a potent inhibitor of neutral sphingomyelinase, was synthesized in an enantioselective manner starting from the bromo ether 5 and D-serinal derivative 3. The synthetic method features a coupling reaction of 5 with 3 to construct the asymmetric quaternary carbon center and a stereospecific epoxide ring formation as the key steps.