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Biomedical subjects

Hiroyuki Shimizu

Publications and source records attributed to Hiroyuki Shimizu.

At least 19 recordsLinked to original sources

Multivariate Effects of SNPs on Environmental Streptococcal Mastitis Evaluated With an NGS-Based Association Study Using Targeted Resequencing in the Bovine MHC Region.

Mastitis is an inflammatory reaction caused by bacterial infection of the teat, and a relationship between its onset and cattle major histocompatibility complex (BoLA) region has been reported. However, no comprehensive genetic analysis of mastitis caused by environmental streptococci has been reported. Here, we resequenced the BoLA region using a hybridisation capture target next-generation sequencing (NGS) method to identify disease susceptibility markers mapped to the BoLA region in environmental streptococcal mastitis. This study examined 75 cows with mastitis caused by environmental streptococci selected from 1641 cows with mastitis and 222 healthy cows without mastitis in Japan. Targeted sequences obtained from MiSeq NGS were aligned to the bovine reference genome (ARS-UCD1.2/bosTau9), and 2,920,355 variants were detected within the BoLA region of the 297 Holstein cattle. In an association study using 2264 variants after quality control, the top 20 variants with the lowest P values were selected and assigned to the 18 surrounding candidate genes, and a gene network analysis of these genes resulted in the narrowing down of five candidate genes POU5F1, IER3, GNL1, ABCF1, and PRR3. Multivariate effect analysis of all 6 SNPs associated with these 5 genes revealed that they were significantly correlated with mastitis, indicating that they were useful for classification of mastitis-resistant and mastitis-susceptible cattle. This is the first report to identify SNPs associated with environmental streptococcal mastitis with an NGS-based association study using targeted resequencing in the BoLA region, and understanding host factors may provide important clues for mastitis control.

Animals↗

Efficacy of intraoperative electrocorticography for assessing seizure outcomes in intractable epilepsy patients with temporal-lobe-mass lesions.

PURPOSE: The findings of previous studies have been controversial regarding the optimal surgical procedures required for effective seizure control. In particular, there are varying views as to whether or not lesionectomy of a temporal-lobe-mass lesion is a satisfactory process or whether removal of additional seizure foci is necessary. In this study, we evaluated the efficacy of additional removal of electrically positive foci using intraoperative electrocorticography on mass lesions related to temporal lobe epilepsy. METHODS: Thirty-five medically intractable epilepsy patients with temporal-lobe benign mass lesions, who had been surgically treated, were assessed. The relationship between resection of the epilepsy focus using intraoperative electrocorticography and seizure outcome was analyzed. In addition, the sites of residual spikes after lesion removal were evaluated. RESULTS: In this study, the benign mass lesions consisted of 21 gangliogliomas, 8 cavernous angiomas and 6 dysembryoplastic neuroepithelial tumors. The number of 3-year postoperative seizure-free incidences for the group that underwent lesionectomy plus additional spike-positive site resection equated to 90.9%. In contrast, in the group that underwent a lesionectomy only, 76.9% were seizure-free for 3-years postoperatively. After complete removal of mass lesions, 86.4% of the residual spikes were detected over the hippocampus. CONCLUSION: Even after the complete removal of temporal-lobe-mass lesions, a high frequency of residual spikes was obtained from the hippocampus. Effective surgical seizure control was achieved by carrying out additional procedures on the affected hippocampus. To detect seizure foci surrounding the lesion, especially over the hippocampus, intraoperative electrocorticogram monitoring was shown to be an effective technique.

Adult↗

Transventricular hemispherotomy for surgical treatment of intractable epilepsy.

Surgical procedures for cerebral hemispherotomy may be broadly divided into those using a lateral and those using a vertical approach. However, careful study of surgical procedures using the lateral approach described in the literature shows differences in the approach to the ventricles. We discuss the application of transventricular hemispherotomy as a technique which provides relatively easy ventricular access for cerebral hemispherotomy. Transventricular hemispherotomy was successfully performed in a 36-year-old woman who was diagnosed with intractable epilepsy due to Sturge-Weber disease, and in a 25-year-old man who had developed intractable post-traumatic seizures after suffering cerebral contusion in a traffic accident as a child. These patients had no seizures or complications after surgery, and both patients have been weaned from antiepileptic drugs. The transventricular approach, as compared with other lateral approaches described in the literature, provides easy access to the ventricular cavity. Transventricular hemispherotomy proved to be a useful approach that allowed the following four common steps in cerebral hemispherotomy to be performed safely: (i) interruption of the internal capsule and corona radiata; (ii) resection of the medial temporal structures; (iii) transventricular corpus callosotomy; and (iv) disruption of the frontal horizontal fibers.

Adult↗

Performance of frequency-doubling technology perimetry in a population-based prevalence survey of glaucoma: the Tajimi study.

OBJECTIVE: To evaluate the performance of frequency-doubling technology (FDT) perimetry in a population-based glaucoma prevalence survey. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Participants older than 40 years randomly selected from the population of Tajimi City. METHODS: Each participant underwent screening ophthalmic examinations including a visual field test using FDT with the C-20-1 screening protocol. A diagnosis of glaucoma was determined by glaucoma specialists with another detailed visual field test using Humphrey Field Analyzer (HFA; Humphrey Instruments, San Leandro, CA) with the 30-2 Swedish interactive threshold algorithm standard protocol and stereoscopic disc photographs. MAIN OUTCOME MEASURES: The ratios of reliable FDT results and the sensitivity and specificity for detecting glaucoma in a general population. RESULTS: Of 5784 eyes of 2892 participants (age range, 40-92 years; refractive error, -23 to 11 diopters) in whom FDT was performed in both eyes, reliable results (< or =33% fixation loss and < or =33% false-positive errors) were obtained in 5707 eyes (98.7%), including 2871 right eyes (99.3%) and 2836 left eyes (98.1%) with a significant bilateral difference (P<0.001, chi-square test). The rate of reliable FDT results did not differ between men and women (P = 0.81) but decreased with age. In 5582 eyes with reliable FDT results, FDT showed 1 or more abnormal points in the visual field in 502 eyes (9.0%), including 388 (7.3%) of 5295 normal eyes, 19 (16.4%) of 116 eyes of glaucoma suspects, and 95 (55.6%) of 171 eyes with definite glaucoma. The sensitivity and specificity values for detecting definite glaucoma were 55.6% and 92.7%, respectively. The positive and negative predictive values were 18.9% and 98.5%, respectively. In further analyses stratified with the mean deviation (MD) of the HFA, the sensitivities were 32.1%, 48.4%, 73.7%, and 96.6% for detecting definite glaucoma with an MD of more than -2 dB, an MD of -2 dB or less and more than -5 dB, an MD of -5 dB or less and more than -8 dB, and an MD of -8 dB or less, respectively. CONCLUSIONS: In a population-based glaucoma screening study, FDT perimetry with the C-20-1 screening protocol was reliably performed in more than 98% of participants. The sensitivity for detecting glaucomatous visual field damages, especially early damage, was not sufficiently high, whereas the specificity was high.

Adult↗

Identification of nesfatin-1 as a satiety molecule in the hypothalamus.

The brain hypothalamus contains certain secreted molecules that are important in regulating feeding behaviour. Here we show that nesfatin, corresponding to NEFA/nucleobindin2 (NUCB2), a secreted protein of unknown function, is expressed in the appetite-control hypothalamic nuclei in rats. Intracerebroventricular (i.c.v.) injection of NUCB2 reduces feeding. Rat cerebrospinal fluid contains nesfatin-1, an amino-terminal fragment derived from NUCB2, and its expression is decreased in the hypothalamic paraventricular nucleus under starved conditions. I.c.v. injection of nesfatin-1 decreases food intake in a dose-dependent manner, whereas injection of an antibody neutralizing nesfatin-1 stimulates appetite. In contrast, i.c.v. injection of other possible fragments processed from NUCB2 does not promote satiety, and conversion of NUCB2 to nesfatin-1 is necessary to induce feeding suppression. Chronic i.c.v. injection of nesfatin-1 reduces body weight, whereas rats gain body weight after chronic i.c.v. injection of antisense morpholino oligonucleotide against the gene encoding NUCB2. Nesfatin-1-induced anorexia occurs in Zucker rats with a leptin receptor mutation, and an anti-nesfatin-1 antibody does not block leptin-induced anorexia. In contrast, central injection of alpha-melanocyte-stimulating hormone elevates NUCB2 gene expression in the paraventricular nucleus, and satiety by nesfatin-1 is abolished by an antagonist of the melanocortin-3/4 receptor. We identify nesfatin-1 as a satiety molecule that is associated with melanocortin signalling in the hypothalamus.

Animals↗

Effectiveness of cervical cancer screening over cervical cancer mortality among Japanese women.

BACKGROUND: Various studies have revealed that cervical cancer (CC) screening significantly reduces both CC incidence and mortality in developed countries. Although Japan introduced a nationwide government funded annual CC screening for the women aged 30+ in 1982, the effectiveness of CC screening on CC mortality has not yet been evaluated by any prospective cohort study. Therefore, the present study evaluated the association of CC mortality with self-reported CC screening and some other factors by a nationwide cohort study. METHODS: Baseline survey of the Japan Collaborative Cohort Study for the enrollment of subjects was completed during 1988-90 and followed until 2003. This study only analyzed 63,541 women, aged 30-79 years, who were free from any cancer history at enrollment. RESULTS: During the follow-up period, 38 CC deaths were identified. The mean age at mortality was 67.0 years, with a mortality rate of 4.2 per 100,000 person-years. Participation rate in CC screening was 46.9%. Age-adjusted Cox model indicated significantly lower CC mortality [hazard ratio (HR) = 0.30, 95% confidence interval (CI) = 0.12-0.74] due to CC screening. Protectiveness remained almost the same (HR = 0.30, 95% CI = 0.12-0.76) when adjusted for age, body mass index and number of deliveries. The results also revealed that CC screening could reduce at least 50% of CC deaths even after excluding the effect of possible self-selection bias. CONCLUSIONS: CC screening in Japan may reduce CC mortality significantly for women aged 30-79 years. However, further studies with more CC deaths and increased statistical power are needed to validate the findings.

Adult↗

Risk factors for open-angle glaucoma in a Japanese population: the Tajimi Study.

PURPOSE: To identify the risk factors associated with primary open-angle glaucoma (POAG) in the Tajimi Study. DESIGN: Population-based cross-sectional epidemiologic study. PARTICIPANTS: One hundred nineteen POAG patients and 2755 controls. METHODS: Univariate and multivariate comparison of ocular factors and systemic factors between POAG patients and controls. MAIN OUTCOME MEASURES: Difference in factors between POAG patients and controls, factors associated with POAG patients, and their odds ratio (OR). RESULTS: Intraocular pressure (IOP), age, myopia, and history of hypertension differed between POAG patients and controls in univariate analyses. Multivariate analysis with logistic regression with stepwise selection of variables demonstrated that higher IOP (OR, 1.12 [95% confidence interval (CI), 1.04-1.21]), myopia (ORs, 1.85 [95% CI, 1.03-3.31] for low myopia and 2.60 [95% CI, 1.56-4.35] for moderate to high myopia), and older age (OR, 1.06 [95% CI, 1.04-1.08]) were associated with an increased risk of having POAG. CONCLUSIONS: Although the majority (92%) of POAG patients diagnosed in the Tajimi Study had IOP within the normal range, IOP was still identified as a significant risk factor for POAG. Together with IOP, myopia and age were significant risk factors for having POAG.

Age Factors↗

The relationship between the consumption of meat, fat, and coffee and the risk of colon cancer: a prospective study in Japan.

The risk of the development of colon cancer in relation to a western diet was studied in a community-based cohort in Japan. From 1992 to 2000, 13,894 men and 16,327 women were followed. In men, high consumption of processed meat increased the risk in comparison with low consumption (adjusted RR=1.98, 95% CI: 1.24-3.16). In women, daily coffee drinkers had a reduced risk in comparison with individuals who never or rarely drank coffee (adjusted RR=0.43, 95% CI: 0.22-0.85). The findings suggest the possible linkage between a western diet and risk of colon cancer.

Adult↗

Hippocampal transection for treatment of left temporal lobe epilepsy with preservation of verbal memory.

Despite good seizure outcome with temporal lobectomy, postoperative impairment of verbal memory remains unsolved. To address this problem we developed a new method, applying the rationale of multiple subpial transection (MST) to the hippocampus. The inferior ventricle is accessed without disrupting the neuronal pathways related to verbal memory. Intraoperative electrocorticography is recorded over the hippocampus and amygdala. After the extent of the epileptic area is determined, multiple transections of the pyramidal layer under the alveus is performed using specially designed ring transectors. After this procedure, epileptic discharges from the hippocampus can be completely abolished. Of 21 cases undergoing this operation, 12 left-sided and nine right-sided, 17 were followed up for more than one year. Fourteen (82%) are seizure free, two (12%) have rare seizures, and one (6%) has significantly improved. Of eight patients who underwent a battery of neuropsychometric tests both before and after left hippocampal transection, postoperative verbal memory was completely preserved in seven cases, and one transiently worsened patient recovered within 6 months. However, these results are still preliminary as the number of patients is small and the follow-up time short. The accumulation of cases and follow-up of greater duration will be necessary to precisely confirm the efficacy of this new technique.

Electroencephalography↗

Associations among maternal soy intake, isoflavone levels in urine and blood samples, and maternal and umbilical hormone concentrations (Japan).

OBJECTIVES: In utero exposure to high levels of endogenous estrogens has been hypothesized to increase breast cancer risk in later life. A high intake of soy has been suggested to protect against breast cancer. We examined the hypothesis that maternal soy intake may be inversely associated with pregnancy hormone levels. METHODS: The concentrations of hormones (estradiol, estriol, and testosterone) and isoflavones (genistein, deidzein, and equol) were measured in the maternal urine and serum, and umbilical cord blood of 194 women during pregnancy and at delivery. Soy intake during pregnancy was assessed by 5-day diet records at approximately the 29th week of pregnancy. RESULTS: High correlations were observed for isoflavone levels between maternal samples and umbilical cord blood, indicating that isoflavone can be transferred from the maternal to the fetal compartment. None of the hormones measured in umbilical cord blood was significantly associated with any of the isoflavones measured. There were a few significant associations between maternal hormone levels and isoflavone measures during pregnancy, but their patterns of associations varied by gestational week and differed depending on whether isoflavone exposure was measured by diet records, urine or serum. CONCLUSION: Our data contain no strong evidence showing that soy intake affects hormone levels during pregnancy.

Adult↗

Prevalence and causes of low vision and blindness in a Japanese adult population: the Tajimi Study.

OBJECTIVE: To determine the prevalence and causes of low vision and blindness in a Japanese adult population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Randomly selected residents (n = 3870) of Tajimi City, Japan, who were 40 years of age or older. METHODS: Of the 3021 study participants (78.1% of 3870 eligible persons), 2977 (76.9%) underwent a complete ophthalmologic examination including measurement of the best-corrected visual acuity (BCVA) with full subjective refraction using a Landolt ring chart at 5 m. Age- and gender-specific prevalence rates of low vision and blindness were estimated and causes were identified. MAIN OUTCOME MEASURES: Low vision and blindness were defined as BCVA in the better eye worse than 20/60 to a lower limit of 20/400 and worse than 20/400, respectively (World Health Organization [WHO] criteria) and worse than 20/40 but better than 20/200 and 20/200 or worse, respectively (United States criteria). RESULTS: The overall prevalence of blindness according to the WHO or U.S. criteria was 0.14% (n = 4; 95% confidence interval [CI], 0.06-0.32). The primary causes were optic atrophy, myopic macular degeneration, retinitis pigmentosa, and uveitis. The overall prevalence of low vision according to the WHO criteria was 0.39% (95% CI, 0.18%-0.60%) and according to the U.S. criteria was 0.98% (95% CI, 0.66%-1.30%), which was significantly greater in women and in the older half of the participants than in the younger half (P = 0.0079 and <0.0001, respectively). The leading causes of low vision in descending order were cataract followed by glaucoma, and those of monocular blindness were myopic macular degeneration, glaucoma, and trauma. CONCLUSIONS: The prevalence of low vision and blindness in Japanese adults was one of the lowest among those reported. The major causes of low vision were cataract and glaucoma, and the leading cause of monocular blindness was myopic macular degeneration.

Aged↗

One percent ability and ninety-nine percent perspiration: a study of a Japanese memorist.

In 1987, Hideaki Tomoyori, a Japanese memorist, set a world record for reciting the first 40,000 digits of pi. The authors report results from a series of tests that give a view of Tomoyori's memory performance compared with that of a control group, matched for age and educational level. He showed very good scores on tasks with digits, such as digit memory span tasks and 5 x 5 number matrix learning, although some of the control participants were nearly as good. In contrast, his performance was not particularly good for learning word lists and story recall. Overall, his performance on the tasks does not suggest that he has superior cognitive abilities. We believe that his extraordinary memory performance in reciting the digits of pi results from his effective use of a combination of digit-syllable transformations and imagery mnemonics developed from extensive practice. These results are consistent with the skilled memory framework.

Aged↗

Quantitative analysis of poliomyelitis-like paralysis in mice induced by a poliovirus replicon.

Poliovirus (PV) infection causes severe paralysis, typically of the legs, by destruction of the motor neurons in the spinal cord. In this study, the relationship between PV replication in the spinal cord, damage in the motor neurons and poliomyelitis-like paralysis was analysed in transgenic mice expressing the human PV receptor (TgPVR21). First, a PV replicon encoding firefly luciferase in place of the capsid genes (PV-Fluc mc) was trans-encapsidated in 293T cells and the trans-encapsidated PV-Fluc mc (TE-PV-Fluc mc) was then inoculated into the spinal cords of TgPVR21 mice. TE-PV-Fluc mc was recovered with a titre of 6.3 x 10(7) infectious units ml(-1), which was comparable to those of PV1 strains. TgPVR21 mice inoculated with TE-PV-Fluc mc showed non-lethal paralysis of the hindlimbs, with severity ranging from a decline in grip strength to complete flaccid paralysis. The replication of TE-PV-Fluc mc in the spinal cord reached peak levels at 10 h post-inoculation (p.i.), followed by the appearance of paralysis at as early as 12 h p.i., reaching a plateau at 16 h p.i. Histological analysis showed a correlation between the lesion and the severity of the clinical symptoms in most mice. However, severe paralysis could also be observed with an apparently low lesion score, where as few as 5.3 x 10(2) motor neurons (1.4 % of the susceptible cells in the lumbar cord) were infected by TE-PV-Fluc mc. These results indicate that PV replication in a small population of the motor neurons was critical for severe residual poliomyelitis-like paralysis in TgPVR21 mice.

Animals↗

Molecular epidemiology of echoviruses 11 and 13, based on an environmental surveillance conducted in Toyama Prefecture, 2002-2003.

Nineteen echovirus 11 (E11) and 12 E13 isolates were isolated from three rivers in Toyama Prefecture, Japan, during an environmental surveillance conducted from April 2002 to March 2003. The nucleotide sequences of E13 isolates were closely related to those from patients with aseptic meningitis, with less than 1.3% divergence in the VP1 region of the viral capsid gene, and belonged to the same clade responsible for a worldwide outbreak that started in 2000. In contrast, E11 isolates were clustered into three genomic groups and were not closely related to echovirus strains isolated from patients. These results suggest that the combination of both virus isolation from environmental sources and phylogenetic analysis could be complementary assessment approaches to trace prevalent and minor circulating enteroviruses in the human population.

Capsid Proteins↗

Estrogen and alpha-fetoprotein levels in maternal and umbilical cord blood samples in relation to birth weight.

Birth weight has been associated with a subsequent risk of breast cancer. The present study examined associations between birth weight and pregnancy estrogens and alpha-fetoprotein (AFP). The concentrations of estradiol, estriol, and AFP were measured in maternal and umbilical cord blood samples from 194 women during pregnancy and at birth. Birth weight was significantly positively correlated with maternal serum estradiol and estriol levels in the 29th week (estradiol: r = 0.16, P = 0.03; estriol: r = 0.29, P = 0.001) and at delivery (estradiol: r = 0.20, P = 0.01; estriol: r = 0.41, P < 0.0001) after controlling for covariates. The umbilical cord estriol level was moderately but significantly correlated with birth weight (r = 0.15, P = 0.049). There was no significant association between umbilical cord serum estradiol and birth weight. There was no significant association between birth weight and maternal serum AFP in any gestational week. Umbilical cord AFP was significantly inversely correlated with birth weight (r = -0.16, P = 0.04). Umbilical cord AFP was unrelated to cord levels of estradiol and estriol. The data suggested a greater exposure to estriol and a lower exposure to AFP among high birth weight babies.

Adolescent↗

Associations of menstrual cycle length with intake of soy, fat, and dietary fiber in Japanese women.

A decreased risk of breast cancer has been reported among women who have longer menstrual cycles or anovulatory cycles. The present study examined the relationships between intake of fat, soy, and dietary fiber and length of menstrual cycle among 341 Japanese women aged 18 to 29 yr old at two colleges and three nursing schools. Intake of nutrients and foods including fats, dietary fiber, and soy products was estimated through the use of a validated semi-quantitative food frequency questionnaire. The mean cycle length was determined for each women based on a prospective record of menstruation. Polyunsaturated fat intake was significantly inversely associated with cycle length; the means of cycle length were 33.2 and 31.0 days for the lowest and the highest quintiles of intake, respectively, after controlling for covariates (trend = 0.03). The odds ratio of a long cycle (> 35 days) for the highest vs. lowest quintile of dietary fiber intake was 2.12 (95% confidence interval 1.00-4.47), although the trend was not statistically significant. The data suggest that polyunsaturated fat and dietary fiber intake are associated with the parameters of menstrual cycle length, but further studies are required to better characterize these associations.

Adolescent↗

Effects of E. coli chaperones on the solubility of human receptors in an in vitro expression system.

The implementation of efficient technologies for the production of recombinant mammalian membrane receptors is an outstanding challenge in understanding receptor-ligand actions and the development of therapeutic antibodies. In order to improve the solubility of recombinant extracellular domains of human membrane receptors expressed in Escherichia coli, proteins were synthesized by an E. coli in vitro translation system supplemented with bacterial molecular chaperones, such as GroEL-GroES (GroEL/ES), Trigger factor (TF), a DnaK-DnaJ-GrpE chaperone system (DnaKJE), and/or a heat shock protein Hsp100, ClpB. The following three proteins that are prone to aggregation were examined: the extracellular domain (ECD) or the second immunoglobulin-like domain (IgII) of the human neurotrophin receptor TrkC (TrkC-ECD and TrkC-IgII), and the C-type lectin carbohydrate recognition domain of the human asialoglycoprotein receptor (ASGPR HI CRD). The cooperative chaperone system including GroEL/ES, DnaKJE and ClpB had a marked effect on the solubility of TrkC-ECD and TrkC-IgII, and the GroEL/ES-DnaKJE-TF chaperone system was more effective for TrkC-IgII. The GroEL/ES-DnaKJE-TF chaperone network increased the yield of soluble ASGPR HI CRD. The present findings demonstrate that E. coli molecular chaperones are useful in improving the yield of soluble recombinant extracellular domains of human membrane receptors in an E. coli expression system.

Cell-Free System↗