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Biomedical subjects

Hiroyuki Shimizu

Publications and source records attributed to Hiroyuki Shimizu.

At least 109 records · Page 6Linked to original sources

Comparison of mammographic densities and their determinants in women from Japan and Hawaii.

Breast cancer incidence increases considerably in women who migrate from Japan to the United States. Based on the hypothesis that mammographic density in healthy mammograms reflects differences in breast cancer risk, we compared mammographic density in 3 groups of women at different levels of risk: Caucasian and Japanese women in Hawaii and Japanese women in Japan. In a cross-sectional design, pre- and postmenopausal women without a history of breast cancer and with a mammogram free of suspicious lesions were recruited in mammography clinics and completed a self-administered questionnaire. Cranio-caudal mammograms were scanned into a computer and the densities measured using a computer-assisted method. Statistical analyses included ANOVA and multiple linear regression. Breast size among women of Japanese ancestry was similar in Hawaii and Japan but 50% smaller than that among Caucasian women. Dense areas were smallest among women in Japan, intermediate among Japanese women in Hawaii and largest among Caucasian women. Percent densities were greater in Japanese women than Caucasian women because of the larger breast sizes in Caucasians. However, percent densities were significantly higher among Japanese women in Hawaii than in Japan. These results indicate that the size of the total breast differs primarily by ethnicity and the size of the dense areas differs mainly by place of residence. Therefore, when comparing ethnic groups with distinct physical proportions, the absolute size of the dense areas appears to be a better measure of breast cancer risk than the relative density.

Adult↗

Soy and fish oil intake and mortality in a Japanese community.

The relation between intake of fish and soy products and subsequent all-cause and cause-specific mortality was examined in a cohort of 13,355 male and 15,724 female residents of Takayama, Gifu, Japan. A diet that included soy and fish intake was assessed in 1992 by using a validated semiquantitative food frequency questionnaire. Over 7 years of follow-up, 2,062 participants (1,163 men and 899 women) died. For men, the highest compared with the lowest quintile of total soy product intake was marginally significantly inversely associated with total mortality after adjustment for total energy and nondietary covariates (hazard ratio = 0.83, 95% confidence interval: 0.69, 1.01; p for trend = 0.07). After adjustment for nondietary covariates, a decreased hazard ratio for the highest compared with the lowest quintile of total soy product intake was also observed for women (hazard ratio = 0.83, 95% confidence interval: 0.68, 1.02; p for trend = 0.04). Additional adjustment for dietary factors significantly associated with total mortality did not attenuate these associations. For women but not for men, n-3 fatty acids from fish were significantly inversely associated with total mortality. Results showed that soy intake may have moderate but beneficial effects on total mortality.

Adult↗

Cortical perivascular satellitosis in intractable epilepsy; a form of cortical dysplasia?

This report describes two cases of cortical dysplasia in patients with intractable epilepsy: the first case presents a 12-year-old male with a simple partial seizure of his left arm (case 1), while the second case presents an 8-year-old female with a complex partial seizure (case 2). Magnetic resonance images showed high signal intensity on T2-weighted and fluid attenuated inversion-recovery images in the cerebral cortex of right frontal convexity in case 1 and in the medial temporal lobe and anterior amygdala in case 2. The latter lesion showed focal contrast enhancement. Light microscopy revealed perivascular clustering of small round cells accompanied by dysplastic neurons in the second to sixth layers of the cerebral cortex. The perivascular small cells had uniformly round nuclei and plump, ground-glass-like cytoplasm. These cells closely apposed each other and were adhered to the capillaries. In case 2, a ganglioglioma was also found in the amygdala. Immunohistochemistry revealed that the perivascular small cells were vimentin and focally S-100 protein positive, but were negative for glial fibrillary acid protein, synaptophysin, neurofilament protein, microtubule-associated protein 2, neuronal nuclei antigen, nestin, carbonic anhydrase II, myelin basic protein, CD68, factor VIII, cytokeratin, epithelial membrane antigen, alpha-smooth muscle actin, CD20, CD45 and CD45RO. These data suggest that this is a previously undescribed form of cortical dysplasia comprising dysplastic neurons and immature perivascular cells of possible oligodendroglial or meningothelial lineage. We suggest the term cortical perivascular satellitosis be used to describe this lesion.

Amygdala↗

Activation of peroxisome proliferator-activated receptor-gamma stimulates the growth arrest and DNA-damage inducible 153 gene in non-small cell lung carcinoma cells.

Activation of peroxisome proliferator-activated receptor (PPAR)-gamma by the thiazolidinedione (TZD) class of antidiabetic drugs elicits growth inhibition in a variety of malignant tumors. We clarified the effects of TZDs on growth of human non-small cell lung carcinoma (NSCLC) cells that express endogenous PPAR-gamma. Troglitazone and pioglitazone caused inhibition of cellular growth and induced apoptosis of NSCLC cells in a time- and dose-dependent manner. Subtraction cloning analysis identified that troglitazone stimulated expression of the growth arrest and DNA-damage inducible (GADD)153 gene, and the increased expression of GADD153 mRNA was also confirmed by an array analysis of the 160 apoptosis-related genes. Western blot analysis revealed that troglitazone also increased GADD153 protein levels in a time-dependent manner. Troglitazone did not stimulate GADD153 mRNA levels in undifferentiated 3T3-L1 cells lacking PPAR-gamma expression, whereas its induction was clearly observed in differentiated adipocytes expressing PPAR-gamma. Activity of the GADD153 promoter occurred in a NSCLC cell line in transient transcription assays and was significantly stimulated by troglitazone, although binding of PPAR/retinoid X receptor heterodimer was not detected in the promoter region in gel retardation assays. Inhibition of GADD153 gene expression by an antisense phosphorothionate oligonucleotide attenuated the troglitazone-induced growth inhibition. These findings collectively indicated that activation of PPAR-gamma by TZDs could cause growth inhibition and apoptosis of NSCLC cells and that GADD153 might be a candidate factor implicated in these processes.

Apoptosis↗

Outbreak of poliomyelitis in Hispaniola associated with circulating type 1 vaccine-derived poliovirus.

An outbreak of paralytic poliomyelitis occurred in the Dominican Republic (13 confirmed cases) and Haiti (8 confirmed cases, including 2 fatal cases) during 2000-2001. All but one of the patients were either unvaccinated or incompletely vaccinated children, and cases occurred in communities with very low (7 to 40%) rates of coverage with oral poliovirus vaccine (OPV). The outbreak was associated with the circulation of a derivative of the type 1 OPV strain, probably originating from a single OPV dose given in 1998-1999. The vaccine-derived poliovirus associated with the outbreak had biological properties indistinguishable from those of wild poliovirus.

5' Untranslated Regions↗

Pyramidal and extrapyramidal involvement in experimental infection of cynomolgus monkeys with enterovirus 71.

Among the enteroviruses, polioviruses and enterovirus 71 (EV71) are two major neurotropic viruses causing serious neurological manifestations. While polioviruses are being eradicated globally by vaccination, EV71 still has the potential to cause a large outbreak such as that in Taiwan in 1998, in which there were many fatalities. In this study, we determined the neurovirulence of EV71 by neuropathological analysis of cynomolgus monkeys after experimental infection with five EV71 strains, which were isolated from individual patients with fatal encephalitis; meningitis; and hand, foot, and mouth disease. After intraspinal inoculation, the monkeys developed neurological manifestations within 1-6 days post-inoculation, irrespective of the inoculated strains. These manifestations included not only pyramidal tract signs such as flaccid paralysis, but also extrapyramidal tract signs such as tremor and ataxia. Histological and viral examinations confirmed virus replication in the spinal cord, brainstem, cerebellar cortex, and dentate nuclei, and cerebrum. The strains isolated during the 1970s and 1990s showed no particular differences with respect to neurotropism. Thus, it is clear that EV71 has a wider neurotropism than that of polioviruses.

5' Untranslated Regions↗

Functional analysis of recombinant pancreatic secretory trypsin inhibitor protein with amino-acid substitution.

BACKGROUND: We hypothesized that mutation of the pancreatic secretory trypsin inhibitor ( PSTI) gene may promote a predisposition to pancreatitis, possibly by reducing the inhibition of trypsin activity. Based on this hypothesis, we performed a biochemical analysis of recombinant PSTI protein. METHODS: The trypsin inhibitory activity of the recombinant protein was analyzed. The activity of PSTI protein with a point mutation of the most common type: (34)Asn (AAT)-to-Ser (AGT)(101A>G N34S: N34S) in exon 3, was compared with that of the wild type. RESULTS: The function of N34S PSTI remained unchanged under both the usual alkaline and acidic conditions compared with the wild-type PSTI. The calcium concentration did not affect the activity of recombinant PSTI. The trypsin susceptibility of the N34S protein was not increased either. CONCLUSIONS: Mechanisms other than the conformational change of PSTI associated with amino-acid substitution, such as abnormal splicing, may underlie the predisposition to pancreatitis in patients with the N34S mutation.

Amino Acid Substitution↗

Molecular forms of human brain natriuretic peptide in plasma.

BACKGROUND: Brain natriuretic peptide (BNP) is a vasoreactive peptide hormone, which is synthesized and secreted mainly from the heart ventricles. METHODS: Molecular forms of immunoreactive human brain natriuretic peptide (BNP) were examined. Chemically synthesized human BNP was added to whole blood samples from a healthy volunteer. The immunoreactive peptide was recovered by immunoaffinity chromatography followed by reversed-phase HPLC (RP-HPLC). Molecular form of immunoreactive BNP in plasma from heart failure patients was also examined. RESULTS: Sequential analysis and amino acid analysis of the peptide revealed that two amino acid residues were deleted from the amino terminus of BNP. When roughly classified according to molecular weight (MW), two forms of BNP (high-MW BNP and low-MW BNP) were observed. The estimated MW of high-MW BNP (36 kDa) was three times that of pro-BNP (12 kDa). CONCLUSIONS: Analysis of low-MW BNP by RP-HPLC revealed that a small amount of BNP 1-32 or des-SerPro-BNP (BNP 3-32) was contained in plasma from heart failure patients.

Amino Acid Sequence↗

Postoperative development of children after hemispherotomy.

We studied the postoperative development of 14 children with cortical dysgenesis who underwent modified functional hemispherectomy (hemispherotomy) at the age of 6 years or younger. At follow-up of 24-72 months (median of 47 months), six (43%) were seizure-free, six achieved>90% reduction, one achieved 50-90% reduction, and one achieved 0-50% reduction in seizure frequency. At the preoperative and final postoperative examinations, mean scores of developmental quotient (DQ) were as follows: 25.5 and 31.9 in total DQ, 26.0 and 33.7 in intellectual DQ, and 27.4 and 22.9 in motor DQ. Children scoring >50 points in preoperative intellectual DQ score obtained near-normal intellectual DQ postoperatively, while, those scoring <10 DQ preoperatively remained at a low developmental level. Among children with DQ scores in the range from 10 to 50, two children who obtained seizure-free outcome and were operated upon in the first 3 years of life achieved marked developmental progress. The present study indicated that high preoperative intellectual DQ and cessation of seizures seem to be associated with better postoperative intellectual development. However, long-term observation of postoperative development and an accumulation of more cases will be needed before we can reach a firm conclusion.

Cerebral Cortex↗

Circulating concentrations of soluble leptin receptor: influence of menstrual cycle and diet therapy.

Concentrations of the soluble leptin receptor (sOB-R) may be related to leptin resistance in obesity. We measured sOB-R concentrations in serum in 103 non-diabetic Japanese men and women. All subjects were grouped according to body mass index (BMI; in kg/m(2)). Serum sOB-R concentrations did not differ significantly between normal-weight (18.5 < or = BMI < 25.0) men and women, but were significantly higher in underweight subjects (BMI < 18.5) than in normal-weight subjects. In contrast, overweight (25 < or = BMI < 30) and obese (30 < or = BMI < 35.0, 35.0 < or = BMI < 40, and BMI > or = 40) subjects had significantly lower sOB-R concentrations than did normal-weight subjects. Serum sOB-R concentrations were inversely correlated with BMI and serum immunoreactive leptin concentrations. Very low-energy diet therapy for 4 wk significantly lowered serum immunoreactive leptin concentrations but did not significantly affect serum sOB-R concentrations. Serum sOB-R concentrations did not change significantly during the menstrual cycle. Our results showed that serum sOB-R concentrations decrease with increasing BMI and that sex hormones likely do not affect serum sOB-R concentrations in non-pregnant women. The reduction in serum sOB-R concentrations in overweight and obese persons may reflect downregulation of hypothalamic leptin receptor production as a result of an increase in circulating leptin and might be an important factor in leptin resistance.

Adult↗

Weight change in relation to natural menopause and other reproductive and behavioral factors in Japanese women.

PURPOSE: To evaluate the effect of menopause on weight change in Japanese women. METHODS: Community-based sample of 828 Japanese women who were premenopausal and aged 40 to 54 years completed a self-administered questionnaire asking information on demographic factors, body size, reproductive history and dietary and behavioral factors in 1992. They responded to a follow-up questionnaire asking weight and menopausal status in 1998. RESULTS: Women gained weight modestly, on average, 0.17 kg during the 6-year study period. Weight gain was significantly higher in women who remained premenopausal at follow-up than those who had natural menopause during the study period. Weight gain was significantly associated with early menarche in women who had natural menopause and with high parity in women remained premenopausal. CONCLUSION: Reproductive factors rather than sociodemographic and behavioral factors appeared to be associated with weight change during the perimenopausal period. Onset of menopause may diminish weight gain. In contrast, early menarche and high parity showed relationships with weight gain.

Adult↗

Pathological effect of seizures on the hippocampus in cases with temporal lobe epilepsy caused by brain tumors.

The cause of Ammon's horn sclerosis in temporal lobe epilepsy has not yet been clarified. In the present study, the pathological effect of epileptic seizures on the hippocampus was investigated in surgically treated patients with brain tumor-induced temporal lobe epilepsy. Tumors involving the hippocampus were identified as the foci of epilepsy in 13 patients (seven male and six female) and resected after epileptic discharges were found at the hippocampus on intraoperative electrocorticogram. The mean age at operation was 29.8 +/- 11.5 years and the mean age of seizure onset was 19.9 +/- 10.8 years. Because only three of the 13 patients who underwent temporal lobectomy for brain tumors involving the hippocampus had Ammon's horn sclerosis pathologically, it was concluded that it was very unlikely that the Ammon's horn sclerosis was produced by the epileptic seizures. Two of the three patients with pathological signs of Ammon's horn sclerosis had episodes of coma, covulsion, high fever and cyanosis in their past histories that might have portended the appearance of Ammon's horn sclerosis later in their lives.

Adolescent↗

Is leptin a key factor which develops obesity by ovariectomy?

Withdrawal of estrogen by ovariectomy increases adiposity, but decreases the circulating levels of the ob gene product, leptin, which inhibits food intake. The reduction of circulating leptin levels may thus play an important role in the induction of obesity by ovariectomy. To examine this hypothesis, body weight change by ovariectomy was investigated in leptin-deficient genetically obese (ob/ob) mice with leptin supplement. Prior to the operation, obese (ob/ob) female mice were treated with intraperitoneal administration of recombinant mouse leptin (1.0 microg/g body weight/day) for 8 days. Then, half of the leptin-treated mice and their lean littermates were bilaterally ovariectomized and their body weight changes were observed for 56 days. From 16 days after the operation, a significant increase in body weight by ovariectomy was observed only in lean mice without leptin treatment. From 44 days, a significant body weight gain by ovariectomy was observed in leptin-treated obese mice. Ovariectomy significantly increased retroperitoneal white adipose tissue weight in their lean littermates, but not in leptin-treated obese mice. It was suggested that the reduction of circulating leptin levels may play an important role in the increases of acute phase body weight gain by ovariectomy, but during static phase, the direct effects of estrogen withdrawal may appear independent of leptin-mediated effects.

Adipose Tissue↗

Primary amenorrhea accompanied by adrenal adenoma: start of menarche soon after tumor resection.

We report a patient with primary amenorrhea accompanied by adrenal adenoma. A 21-year-old woman was admitted to our hospital because of primary amenorrhea and hyperprogesteronemia without virilization. Venous sampling showed progesterone overproduction at the left adrenal gland. Computed tomography revealed a 7 cm mass in left adrenal gland. Serum pregnenorone, 17-hydroxypregnenorone, dehydroepiandrosterone, 17-hydroxyprogesterone, deoxycorticosterone, and 11-deoxycortisol were elevated. The diagnosis of steroid hormone producing tumor was made. Following tumor resection, serum progesterone normalized 4 days later, and menarche occurred 51 days after operation. The present case indicated that adrenal functioning tumor should not be overlooked in patients with primary amenorrhea.

Adenoma↗

Outcome of long-term vagus nerve stimulation for intractable epilepsy.

The outcome of long-term vagus nerve stimulation (VNS) was evaluated in 13 Japanese patients with intractable epilepsy, all followed up for more than 4 years (48-91 months, median 56 months). VNS achieved a long-lasting and cumulative seizure-control effect in nine of 13 patients. The mean reduction of seizure frequency in the 1st to 4th year was 28%, 47%, 54%, and 63%, respectively. The percentage of patients with >60% seizure reduction in the 1st to 4th year was 15%, 46%, 54%, and 69%, respectively. One patient did not respond to the treatment at all. No patient became completely free from seizure or free from medication, but the number and/or dosage of antiepileptic drugs was reduced in five patients. Ten patients underwent exchange of the generator and continued treatment, and two patients underwent removal of the generator because of the unsatisfactory result. VNS controlled more disabling seizures earlier and more efficiently than less disabling seizures in seven patients. The cumulative reduction of seizures was partly associated with changes in the device setting toward increased stimulation. These effects were similar in patients with or without previous resective surgery. Long-term VNS therapy achieved a favorable outcome in a significant proportion of patients with intractable epilepsy.

Adult↗