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Biomedical subjects

H Shimizu

Publications and source records attributed to H Shimizu.

At least 235 records · Page 13Linked to original sources

[Diffusion-weighted magnetic resonance imaging (MRI) in acute brain stem infarction].

Diffusion-weighted magnetic resonance imaging (DWI) provides one of the earliest demonstrations of ischemic lesions. However, some lesions may be missed in the acute stage due to technical limitation of DWI. We therefore conducted the study to clarify the sensitivity of DWI to acute brain stem infarctions. Twenty-eight patients with the final diagnosis of brain stem infarction(midbrain 2, pons 9, medulla oblongata 17) who had been examined by DWI within 24 hours of onset were retrospectively analyzed for how sensitively the initial DWI demonstrated the final ischemic lesion. Only obvious(distinguishable with DWI alone without referring clinical symptoms and other informations) hyperintensity on DWI was regarded to show an ischemic lesion. Sixteen(57.1%) out of 28 patients had brain stem infarctions demonstrated by initial DWI. In the remaining 12 cases, no obvious ischemic lesion was evident on initial DWI. Subsequent MRI studies obtained 127 hours, on average after the onset showed infarction in the medulla oblongata in 11 cases and in the pons in one case. Negative findings of DWI in the acute stage does not exclude possibility of the brain stem infarction, in particulary medulla oblongata infarction.

Adult↗

Neurovirulence of Sabin 1-derived polioviruses isolated from an immunodeficient patient with prolonged viral excretion.

We have analysed the neurovirulence of Sabin 1-derived isolates which persisted more than nine years in an immunodeficient patient in the U.S.A. Samples were collected from stool specimens at days 11 (St1), 23 (St2), 48 (St3), 126 (St5), and 200 (St7) after the onset of paralysis. Critical nucleotides associated with the reversion of virulence were examined. All the isolates had the substitutions at nucleotide positions 480 (G to A) in the 5'-non-coding region (NCR), 2438 (A to U) in VP3, 2795 (A to G) in VP1, and 6203 (C to U) in 3D. Serially diluted samples were injected intracerebrally to transgenic mice harbouring the human poliovirus receptor gene. Samples St2, 3, 5 and 7 showed typical virulent characters in transgenic mice, whereas the sample ST1 showed intermediate neurovirulence. It seemed that there were two variant viruses providing for a major (M) and a minor (m) populations. After disappearance of the m-variant, samples obtained at the later stages showed neurovirulence almost equivalent to that of the Mahoney strain. Thus, the Sabin 1 strain evolved towards full neuropathogenicity after long-term replication in humans by accumulating mutations. Therefore, OPV-vaccination of immunodeficient persons should be avoided.

Animals↗

[A case with left mesial temporal lobe epilepsy characterized by abnormal massive salivation].

A 26-year-old woman was admitted because of a 12-year history of intractable epileptic seizures. Every seizure began with an upper abdominal discomfort, and often followed by massive salivation. Whenever the epileptic salivation happened, the patient lost consciousness, and sometimes she developed generalized convulsions. In terictal sphenoidal EEG recordings revealed abnormal discharges in the left mesial temporal region. MRI demonstrated left hippocampal atrophy. Since her seizures were medically intractable, left temporal lobectomy was performed. Neuropathologic examination revealed hippocampal sclerosis. After the operation, she became completely seizure-free with no episode of massive salivation. From the literature, epileptic salivation can originates from the rolandic area; fronto-orbital cortex & cingulate gyrus; insula & operculum; and mesial temporal structures. The abnormal massive salivation in our patient might be attributable to the activation of frontal limbic system triggered by hippocampal abnormal firing during the ictal period of TLE.

Adult↗

[Surgical treatment for intractable epilepsy].

Epilepsy surgery can be divided into two categories, resective and disconnective procedures. The former includes lesionectomy, corticectomy, and lobectomy. The latter comprises MST (multiple subpial transection), corpus callosotomy, and hemispherotomy. In this presentation, the preoperative diagnosis and surgical outcomes of temporal lobectomy and MST will be illustrated. Temporal lobe epilepsy is one of the most common seizures in adult intractable epilepsy. Noninvasive preoperative evaluation, including analysis of seizure semiology, repetitive scalp EEG, and MR imaging, can definitely localize the seizure focus, without depending on invasive monitoring, in 70% of the cases. Seizure outcome after temporal lobectomy is generally satisfactory, with 70% seizure-free and > 90% significantly improved. However, verbal amnesia is an unavoidable sequela when the focus is on the speech-dominant side and preoperative MRI reveals little or no hippocampal atrophy. MST is an epoch-making surgical technique by which surgical treatment of eloquent cortex has become possible. In cases with neocortical epilepsy treated by MST alone or combined with corticectomy, 80% showed significant improvement, that is compatible with reported outcomes of corticectomy. MST can be also applied to treatments of extensive epileptic foci, Rasmussen's encephalitis, or Landau-Kleffner syndrome.

Epilepsy↗

Job stress, social support at work, and insomnia in Japanese shift workers.

A cross-sectional study was conducted to clarify the contribution of psychological job stress to insomnia in shift workers. A self-administered questionnaire concerning job stress, sleep, depressive symptoms and lifestyle factors was submitted to a sample of 530 rotating shift workers of age 18-59 years (mean age 27) in an electric equipment manufacturing company. Perceived job stress, i.e., job demands, job control and social support at work, was assessed using the Japanese version of the Job Content Questionnaire. Insomnia was regarded as prevalent if the workers had at least one of the following symptoms in the last year; less than 30 minutes to fall asleep, difficulty in maintaining sleep, or early morning awakening almost everyday. Overall prevalence was 37.8%. Logistic regression analyses while adjusting relevant factors showed that lower social support at work was significantly associated with a greater risk of insomnia than the higher social support (adjusted OR 2.5). Higher job strain with lower social support at work increased the risk, compared to lower strain with higher support at work (crude OR 1.8; adjusted OR 1.5). Our findings suggest the low social support at work independently associated with insomnia in shift workers.

Adolescent↗

Association of diet with the onset of menopause in Japanese women.

A prospective study was conducted in Takayama, Gifu, Japan, to evaluate the association between diet and the onset of menopause. A total of 1,130 female residents aged 35-54 years who were premenopausal and completed a validated semiquantitative food frequency questionnaire in 1992 were contacted by mail with a follow-up questionnaire in 1998 to update information on menopause. Onset of menopause was defined as a woman's age at the last menstrual period prior to stopping menstruation for 12 months. During the 6-year study period, 296 women experienced natural menopause. The Cox proportional hazards model was used to estimate hazard ratios of the onset of menopause after controlling for age, total energy, body mass index, years of smoking, and age at which regular menstrual cycle began. The authors found that green and yellow vegetable intake was significantly inversely associated with the 6-year incidence of menopause (hazard ratio = 0.71, 95% confidence interval: 0.54, 0.95 for the highest vs. lowest tertile of intake, p for trend = 0.02). Association of carotene intake with the incidence of menopause was of borderline significance (hazard ratio = 0.78, 95% confidence interval: 0.59, 1.04, p for trend = 0.07).

Adult↗

Localization of the binding site for the oligosaccharide moiety of Gb3 on verotoxin 1 using NMR residual dipolar coupling measurements.

By use of NMR residual dipolar coupling measurements in a dilute liquid-crystalline solvent, the solution structure has been determined of the complex between the oligosaccharide moiety of globotriaosylceramide (Gb(3)-OS) and the B-subunit homopentamer of verotoxin 1 (VTB). The dipolar coupling data indicate that Gb(3)-OS binds in a single binding site per monomer, which is identical to one of three sites inferred from the X-ray structure of the same complex. We find no evidence within experimental error for occupancy at either of the two additional binding sites observed per monomer in the crystal structure.

Binding Sites↗

Allelic loss in human intrahepatic cholangiocarcinoma: correlation between chromosome 8p22 and tumor progression.

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant primary tumor of the liver in Japan. Despite progress in operative techniques and adjuvant therapy, the prognosis of ICC remains very poor. Therefore, it is important to investigate the mechanism of carcinogenesis and progression of ICC. We screened allelic losses at 6 loci, including that of novel tumor-suppressor gene FEZ1 on chromosome 8p, and at 5 microsatellite loci to define the association with tumor-suppressor genes (HNPCC, APC, RB1, p53, DCC) in tumors from 18 unrelated ICC patients by PCR-loss of heterozygosity (LOH) assay and correlated the alterations with clinicopathological parameters. As a result, 61.1% (11 of 18) of patients showed LOH at 1 of the loci at least, and microsatellite instability was observed in 16.7% (3 of 18). At locus D8S258, relatively frequent LOH was detected (17.6%) compared with other loci on chromosome 8p. Among the other 5 chromosomal arms tested, the highest frequency of LOH (23.5%) was observed at D17S153. Fifty percent of cases with the mass-forming + periductal infiltrating type were frequently detected by LOH at D8S258 compared to cases of the mass-forming or intraductal growth type. In conclusion, we show that 1 putative tumor-suppressor gene on 8p22 may relate to progression of ICC and suggest that the p53 tumor-suppressor gene may be associated with carcinogenesis of ICC.

Aged↗

Enhanced motor cortical excitability in the unaffected hemisphere after hemispherectomy.

We evaluated motor cortical excitability of the unaffected hemisphere in three patients with intractable epilepsy who underwent hemispherectomy, using transcranial magnetic stimulation (TMS) and PET. TMS of the unaffected hemisphere evoked motor responses not only in the contralateral muscles but also in the ipsilateral ones in all the patients. A PET study in one patient showed activation of the unaffected motor cortex by movement of either arm. All of these responses were enhanced after the hemispherectomy, probably due to motor cortical disinhibition by transection of the corpus callosum. The PET study also showed postoperative activation of the premotor area of the unaffected hemisphere. These phenomena indicate posthemispherectomy neuroplastic reorganization leading to preservation of the motor function after the operation.

Adult↗

Effects of hypoxia on cholesterol metabolism in human monocyte-derived macrophages.

We assessed the metabolism of low density lipoprotein (LDL) of human monocyte-derived macrophages under hypoxia. The specific binding and association of 125I-labeled LDL (125I-LDL) were not changed under hypoxia compared to normoxia. However, the degradation of 125I-LDL under hypoxia decreased to 60%. The rate of cholesterol esterification under hypoxia was 2-fold greater on incubation with LDL or 25-hydroxycholesterol. The cellular cholesteryl ester content was also greater under hypoxia on incubation with LDL. Secretion of apolipoprotein E into the medium was not altered under hypoxia, suggesting that apolipoprotein E independent cholesterol efflux may be reduced under hypoxia. Thus, hypoxia affects the intracellular metabolism of LDL, stimulates cholesterol esterification, and enhances cholesteryl ester accumulation in macrophages. Hypoxia is one of the important factors modifying the cellular lipid metabolism in arterial wall.

Apolipoproteins E↗

Involvement of tyrosine hydroxylase up regulation in dexamethasone-induced hypertension of rats.

We investigated the effect of dexamethasone (DEX) on tyrosine hydroxylase (TH) mRNA level, and TH activity and catecholamine levels in the adrenal medulla of the rat. DEX (1 mg/kg/day, s.c.) was administered for 2 days, and a control group was given corn oil. DEX significantly increased systolic blood pressure. TH mRNA level, TH activity, epinephrine level, and norepinephrine level in the adrenal medulla of DEX-treated rats were significantly higher than those of control rats. Also, epinephrine and norepinephrine levels in plasma were significantly higher in DEX-treated rats than in controls. alpha-Methyl-p-tyrosine prevented the DEX-induced blood pressure increase. These results suggest that the catecholamine synthetic pathway may be involved in DEX-induced hypertension.

Actins↗

High-frequency endoluminal ultrasonography for staging transitional cell carcinoma of the bladder.

OBJECTIVES: To assess the feasibility and limitations of endoluminal ultrasound (ELUS) for clinical staging of bladder tumors. METHODS: From 1998 to 1999, 32 patients with transitional cell carcinoma of the bladder were evaluated by high-frequency ELUS using miniature ultrasound transducers (20 MHz, 5.1F or 7.2F) before transurethral resection. Clinical staging using ELUS was compared with the results of pathologic staging. RESULTS: Seventeen (94%) of the 18 patients with superficial tumors on ELUS were confirmed by pathologic examination to have Stage pTa (n = 12) or Stage pT1 (n = 5) disease, and 11 (63%) of the 14 patients with muscle-invasive tumors on ELUS were confirmed by pathologic evaluation to have Stage pT2a (n = 2) or Stage pT2b (n = 9) disease. In all of the misdiagnosed patients, the tumor lacked a well-defined base and was larger than 2 cm in size. It was difficult to distinguish between Stage Ta and Stage T1 tumors because of the limited resolution of ELUS and between Stage T2a and Stage T2b tumors because of its low penetration. CONCLUSIONS: ELUS using a high-frequency (20 MHz), miniature ultrasound transducer is able to distinguish superficial tumors from those with muscle invasion. However, the lack of penetration of the sonographic beam places major limitations on the evaluation of the depth of the invasion in large (greater than 2 cm) tumors with a broad base.

Adult↗

Crystal structures of cytochrome P450nor and its mutants (Ser286-->Val, Thr) in the ferric resting state at cryogenic temperature: a comparative analysis with monooxygenase cytochrome P450s.

Cytochrome P450nor (P450nor) is a heme enzyme isolated from the denitrifying fungus Fusarium oxysporum and catalyzes the NO reduction to N2O. Crystal structures of the wild type and two Ser286 mutants (Ser286-->Val, Ser286-->Thr) of P450nor have been determined for the ferric resting forms at a 1.7 A resolution at cryogenic temperature (100 K). We carried out three comparative analyses: (1) between the structures of P450nor at room temperature and cryogenic temperature, (2) between the structures of P450nor and four monooxygenase P450s, and (3) between the structures of the WT and the Ser286 mutant enzymes of P450nor. Comparison of the charge distribution on the protein surface suggests that proton and electron flow to the heme site is quite different in P450nor than in monooxygenase P450s. On the basis of the mutant structures, it was found that a special hydrogen-bonding network, Wat99-Ser286-Wat39-Asp393-solvent, acts as a proton delivery pathway in NO reduction by P450nor. In addition, the positively charged cluster located beneath the B'-helix is suggested as possible NADH binding site in P450nor, from which the direct two-electron transfer to the heme site allows to generate the characteristic intermediate in the NO reduction. These structural characteristics were not observed in structures of monooxygenase P450s, implying that these are factors determining the unique NO reduction activity of P450nor.

Binding Sites↗

Role of the DExH motif of the Japanese encephalitis virus and hepatitis C virus NS3 proteins in the ATPase and RNA helicase activities.

The role of the conserved DExH motif of the Japanese encephalitis virus (JEV) NS3 protein in the ATPase and RNA helicase activities was compared with that of the hepatitis C virus (HCV) NS3 protein. In the DExH motif of JEV NS3, Asp-285 and Glu-286 were essential for both ATPase and RNA helicase activities. Cys-287 was critical for the RNA helicase activity of JEV NS3 but not for ATPase activity. A His-288-to-Ala substitution in the DExH motif of HCV NS3 resulted in an increase in ATPase activity which was suppressed by poly(U). In contrast, alanine substitution at the same site in JEV NS3 did not increase basal ATPase activity which remained to be stimulated by poly(U). Thus, the mutational effect at His in motif II was different in the HCV and JEV NS3 proteins. Mutagenesis at His-288 of JEV NS3 revealed that His was the most preferable amino acid for ATPase activity and Ala, Gly, Asn, Gln, Ser, or Arg could partly substitute for it. However, any other mutation at His-288 completely disrupted the RNA helicase activity of JEV NS3. The results suggest that Cys-287 and His-288 are essential residues especially for the RNA helicase activity of JEV NS3 and the ATPase and helicase activities are separable enzymatic functions.

Adenosine Triphosphatases↗

Impact of Helicobacter pylori infection on gastric cancer incidence in a general Japanese population: the Hisayama study.

BACKGROUND: Several nested case-control studies have reported the potentially causal relationship between Helicobacter pylori infection and the development of gastric cancer. However, there has been no prospective study evaluating this issue. The purpose of this study is to examine the impact of H pylori infection on gastric cancer occurrence in a general Japanese population (Hisayama, Japan) stratified according to sex, using a prospective study design. METHODS: A total of 2602 subjects aged 40 years or older (1070 men; mean age, 57 years; 1532 women; mean age, 59 years) without a history of gastrectomy or gastric cancer were classified according to the status of the serum IgG antibodies to H pylori and observed prospectively for 9 years from 1988. RESULTS: Infection of H pylori was more common in men (71.5%) than in women (62.5%; P<.001). The age-adjusted incidence of gastric cancer for men (5.3 per 1000 person-years) was 4-fold higher than that for women (1.3; P<.001). In men, the age-adjusted incidence of gastric cancer was significantly higher in the subjects with H pylori infection than in those without it (6.2 vs 2.5; relative risk, 2.59 [95% confidence interval, 1.03-6.50]), whereas no significant difference was observed in women (1.2 vs 1.1; relative risk, 0.99 [95% confidence interval, 0.36-2.68]). These results were similar even after controlling for other risk factors in multivariate analysis. It was estimated that 40.1% of gastric cancers for men in this cohort were attributable to H pylori infection. CONCLUSION: A significant relationship exists between infection with H pylori and subsequent occurrence of gastric cancer for men but not for women in this Japanese population.

Adult↗

Effect of interferon-alpha on tyrosine hydroxylase and catecholamine levels in the brain of rats.

We investigated the effect of interferon on tyrosine hydroxylase (TH) and catecholamine levels in the brains of 12-week-old male Wistar rats. Interferon-alpha (300,000 IU/kg/day, s.c.) was administered to rats for 7 days. Locomotor activity of interferon-alpha-treated rats was significantly lower than that of control rats. Norepinephrine and dopamine levels and TH activities in the cerebral cortex, hypothalamus and medulla oblongata of interferon-alpha-treated rats were significantly higher than those of control rats. Norepinephrine and dopamine levels and TH activities in the thalamus and hippocampus were not different between interferon-alpha treated and control rats. These results suggest that interferon-alpha-induced depression may be related to change in the catecholamine synthetic pathway in the central nervous system.

Animals↗

Identification of an optimal Ncx binding sequence required for transcriptional activation.

The Ncx gene encodes a homeobox containing transcription factor that belongs to the Hox11 gene family. We determined specific Ncx protein binding consensus DNA sequences. Optimal Ncx binding sequences were 5'-CGGTAATTGG-3' (TAAT core) and 5'-CGGTAAGTGG-3' (TAAG core), which coincided with the Hox11 binding sequence. Both Ncx and Hox11 could bind to the TAAT and the TAAG core oligonucleotide in vitro. However, they could efficiently transactivate the reporter plasmid linked to the TAAT core sequence but not to the TAAG core sequence. Thus, Ncx and Hox11 act as transcriptional activators via their target sequence, 5'-CGGTAATTGG-3'.

Binding Sites↗