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Biomedical subjects

M Itoh

Publications and source records attributed to M Itoh.

At least 235 records · Page 13Linked to original sources
PubMed2000

Apoptosis of acinar cells is involved in chronic pancreatitis in Wbn/Kob rats: role of glucocorticoids.

The involvement of pancreatic acinar cell apoptosis and its relation to glucocorticoid exposure were investigated in spontaneously occurring chronic pancreatitis in male Wistar Bonn/Kobori (WBN/Kob) rats. Although most lobules were not inflamed in 10-week-old WBN/Kob, increased apoptosis of pancreatic acinar cells, confirmed by TUNEL staining was focally observed (0.10 +/- 0.10 vs. 0.05 +/- 0.10/field in 10-week Wistar rats). Localized hemorrhagic lesions and brown foci in the splenic lobes were apparent, with significant decrease in pancreas weight in 20-week WBN/Kob rats along with marked apoptosis (1.95 +/- 0.31 vs. 0.07 +/- 0.04/field in 20-week Wistar rats). Electron microscopy revealed apoptotic bodies to be present in acinar cells. Pancreatic myeloperoxidase activities, indirect indices of granulocyte infiltration, as well as histologic scores were significantly increased at 15 and 20 weeks, and endogenous corticosterone levels were significantly decreased at 10, 15, and 20 weeks as compared with values for age-matched Wistar rats. Prednisolone in the drinking water (0.01 mg/mL; calculated dose, 1.03 0.03 mg/kg/d) for 10 weeks significantly attenuated increases in numbers of apoptotic acinar cells and pancreatic myeloperoxidase activities and tended to reduce the histologic scores in 20-week WBN/Kob rats as compared with the vehicle group. In summary, (a) apoptosis of pancreatic acinar cells is involved in chronic pancreatitis, (b) endogenous corticosterone is decreased, and (c) prednisolone treatment attenuates both apoptosis of pancreatic acinar cells and chronic pancreatitis in male WBN/Kob rats. We conclude that apoptosis of acinar cells related to decreased corticosterone may be a trigger of chronic pancreatitis in this model.

Adrenocorticotropic Hormone↗
PubMed2000

Normalization and subtraction of cap-trapper-selected cDNAs to prepare full-length cDNA libraries for rapid discovery of new genes.

In the effort to prepare the mouse full-length cDNA encyclopedia, we previously developed several techniques to prepare and select full-length cDNAs. To increase the number of different cDNAs, we introduce here a strategy to prepare normalized and subtracted cDNA libraries in a single step. The method is based on hybridization of the first-strand, full-length cDNA with several RNA drivers, including starting mRNA as the normalizing driver and run-off transcripts from minilibraries containing highly expressed genes, rearrayed clones, and previously sequenced cDNAs as subtracting drivers. Our method keeps the proportion of full-length cDNAs in the subtracted/normalized library high. Moreover, our method dramatically enhances the discovery of new genes as compared to results obtained by using standard, full-length cDNA libraries. This procedure can be extended to the preparation of full-length cDNA encyclopedias from other organisms.

Animals↗
PubMed2000

RIKEN integrated sequence analysis (RISA) system--384-format sequencing pipeline with 384 multicapillary sequencer.

The RIKEN high-throughput 384-format sequencing pipeline (RISA system) including a 384-multicapillary sequencer (the so-called RISA sequencer) was developed for the RIKEN mouse encyclopedia project. The RISA system consists of colony picking, template preparation, sequencing reaction, and the sequencing process. A novel high-throughput 384-format capillary sequencer system (RISA sequencer system) was developed for the sequencing process. This system consists of a 384-multicapillary auto sequencer (RISA sequencer), a 384-multicapillary array assembler (CAS), and a 384-multicapillary casting device. The RISA sequencer can simultaneously analyze 384 independent sequencing products. The optical system is a scanning system chosen after careful comparison with an image detection system for the simultaneous detection of the 384-capillary array. This scanning system can be used with any fluorescent-labeled sequencing reaction (chain termination reaction), including transcriptional sequencing based on RNA polymerase, which was originally developed by us, and cycle sequencing based on thermostable DNA polymerase. For long-read sequencing, 380 out of 384 sequences (99.2%) were successfully analyzed and the average read length, with more than 99% accuracy, was 654.4 bp. A single RISA sequencer can analyze 216 kb with >99% accuracy in 2.7 h (90 kb/h). For short-read sequencing to cluster the 3' end and 5' end sequencing by reading 350 bp, 384 samples can be analyzed in 1.5 h. We have also developed a RISA inoculator, RISA filtrator and densitometer, RISA plasmid preparator which can handle throughput of 40,000 samples in 17.5 h, and a high-throughput RISA thermal cycler which has four 384-well sites. The combination of these technologies allowed us to construct the RISA system consisting of 16 RISA sequencers, which can process 50,000 DNA samples per day. One haploid genome shotgun sequence of a higher organism, such as human, mouse, rat, domestic animals, and plants, can be revealed by seven RISA systems within one month.

Animals↗
PubMed2000

Role of Gab1 in heart, placenta, and skin development and growth factor- and cytokine-induced extracellular signal-regulated kinase mitogen-activated protein kinase activation.

Gab1 is a member of the Gab/DOS (Daughter of Sevenless) family of adapter molecules, which contain a pleckstrin homology (PH) domain and potential binding sites for SH2 and SH3 domains. Gab1 is tyrosine phosphorylated upon stimulation of various cytokines, growth factors, and antigen receptors in cell lines and interacts with signaling molecules, such as SHP-2 and phosphatidylinositol 3-kinase, although its biological roles have not yet been established. To reveal the functions of Gab1 in vivo, we generated mice lacking Gab1 by gene targeting. Gab1-deficient embryos died in utero and displayed developmental defects in the heart, placenta, and skin, which were similar to phenotypes observed in mice lacking signals of the hepatocyte growth factor/scatter factor, platelet-derived growth factor, and epidermal growth factor pathways. Consistent with these observations, extracellular signal-regulated kinase mitogen-activated protein (ERK MAP) kinases were activated at much lower levels in cells from Gab1-deficient embryos in response to these growth factors or to stimulation of the cytokine receptor gp130. These results indicate that Gab1 is a common player in a broad range of growth factor and cytokine signaling pathways linking ERK MAP kinase activation.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Inhibin is an important factor in the regulation of FSH secretion in the adult male hamster.

We investigated the importance of inhibin and testosterone in the regulation of gonadotropin secretion in adult male golden hamsters (Mesocricetus auratus). After castration, plasma concentrations of inhibin and testosterone were reduced to undetectable, whereas plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were increased. After hemicastration, plasma FSH and LH increased moderately and plasma inhibin decreased to one-half its initial level. Plasma testosterone levels in hemicastrated animals decreased 3 h after hemicastration but returned to those in sham-operated animals at 6 h. Plasma LH in the castrated hamster declined comparably to intact animals with testosterone treatment; plasma FSH also decreased but still remained at levels higher than those in intact animals. After treatment with inhibin in long-term-castrated animals, plasma FSH decreased, whereas plasma LH was not altered. Intact males treated with flutamide, an anti-androgen, showed a significant increase in plasma LH but not in FSH. On the other hand, treatment with anti-inhibin serum induced a significant elevation in plasma FSH, but not in LH. Using immunohistochemistry, we showed that the inhibin alpha-subunit was localized to both Sertoli and Leydig cells. The present study in adult male hamsters indicates that FSH secretion is regulated mainly by inhibin, presumably from Sertoli and Leydig cells, and that LH secretion is controlled primarily by androgens produced from the Leydig cells. This situation is more similar to that of primates than of rats.

3-Hydroxysteroid Dehydrogenases↗
PubMed2000

Functional mapping of human brain in olfactory processing: a PET study.

This study describes the functional anatomy of olfactory and visual naming and matching in humans, using positron emission tomography (PET). One baseline control task without olfactory or visual stimulation, one control task with simple olfactory and visual stimulation without cognition, one set of olfactory and visual naming tasks, and one set of olfactory and visual matching tasks were administered to eight normal volunteers. In the olfactory naming task (ON), odors from familiar items, associated with some verbal label, were to be named. Hence, it required long-term olfactory memory retrieval for stimulus recognition. The olfactory matching task (OM) involved differentiating a recently encoded unfamiliar odor from a sequentially presented group of unfamiliar odors. This required short-term olfactory memory retrieval for stimulus differentiation. The simple olfactory and visual stimulation resulted in activation of the left orbitofrontal region, the right piriform cortex, and the bilateral occipital cortex. During olfactory naming, activation was detected in the left cuneus, the right anterior cingulate gyrus, the left insula, and the cerebellum bilaterally. It appears that the effort to identify the origin of an odor involved semantic analysis and some degree of mental imagery. During olfactory matching, activation was observed in the left cuneus and the cerebellum bilaterally. This identified the brain areas activated during differentiation of one unlabeled odor from the others. In cross-task analysis, the region found to be specific for olfactory naming was the left cuneus. Our results show definite recruitment of the visual cortex in ON and OM tasks, most likely related to imagery component of these tasks. The cerebellar role in cognitive tasks has been recognized, but this is the first PET study that suggests that the human cerebellum may have a role in cognitive olfactory processing as well.

Adolescent↗
PubMed2000

Nocturnal enuresis and the pontine reticular formation.

OBJECTIVES: To assess the previously proposed hypothesis that enuretic patients have a dysfunction in the pontine reticular formation. METHODS: In 18 patients with intractable nocturnal enuresis, rapid eye movement (REM)-related phasic chin muscle activity loss in REM sleep was examined by means of a single-night polysomnography. RESULTS: In 5 of 18 patients, this physiologically seen phenomenon was found to be disturbed. CONCLUSIONS: Since REM-related phasic chin muscle activity loss is disturbed by the functional impairment in the pontine reticular formation, some enuretic patients could be considered as presenting a dysfunction in this structure.

Adolescent↗
PubMed2000

The human serotonin receptor gene (HTR2) MspI polymorphism in Japanese schizophrenic and alcoholic patients.

Epidemiological and genetic studies of alcoholism and schizophrenia have been performed, and in this study, the human serotonin receptor (HTR2) polymorphism was examined in 75 alcoholics and 31 schizophrenic patients. We found that there might not be a significant difference between these psychiatric disease patients and controls in the frequency of the C1/C2 HTR2 gene (MspI polymorphism). The results suggest that the human HTR2 MspI polymorphism might not be associated with a risk factor for developing alcohol dependence or susceptibility to schizophrenia. It is possible that there may be a racial difference in the frequency of the C1/C2 gene between Japanese and Caucasians. Further studies are required to determine whether or not the novel serotonin receptor polymorphism reflects the pathogenesis of alcoholism or schizophrenia.

Alcoholism↗
PubMed2000

Roles of glutamate transporter and receptors, poly (ADPribose) polymerase, and transforming growth factor-beta1 in pontosubicular neuron necrosis.

The expression of neuron-type glutamate transporters (EAAC-1), AMPA glutamate receptor subunits (GluR1 and GluR2/3), polyadenosine (5'diphosphate-ribose) polymerase (PARP), and transforming growth factor-beta1 was investigated in 20 cases of neonatal pontosubicular neuron necrosis and 12 gestational-age matched controls. Developmental immunoreactivities of EAAC-1, GluR1, and GluR2/3 appeared in the neurons of the pontine nuclei at 29 to 30 weeks' gestation in controls, and then gradually increased with age. However, these activities were decreased in the pontine nucleus of patients with pontosubicular neuron necrosis. Decreases in these immunoreactivities might indicate early degeneration of neurons. Although PARP and transforming growth factor-beta1 immunoreactivity was insignificant or very weak in the pontine nuclei at any age in controls, PARP was markedly expressed in karyorrhectic neurons of the pontine nucleus in patients with pontosubicular neuron necrosis. Transforming growth factor-beta1 immunoreactivity was observed in nonkaryorrhectic neurons of the pontine nuclei. PARP could contribute to the pathogenesis of pontosubicular neuron necrosis more than EAAC-1 or GluR1 or GluR2/3. Transforming growth factor-beta1 could play a role in the protection and repair of damaged neurons.

ATP-Binding Cassette Transporters↗
PubMed2000

Hypocapnia under hypotension induces apoptotic neuronal cell death in the hippocampus of newborn rabbits.

We investigated the adverse effect of hypocapnia on the neonatal rabbit brain. Two-week-old Japanese white rabbits were assigned to three groups, hyperventilation (H group), ischemia (I group), or hypocapnia with ischemia (HI group) and then subjected for 1.5 h with simultaneous measurement of the mean arterial blood pressure (MABP) and intracranial Hb concentration changes. Marked reductions of PaCO2 and MABP were induced in the hyperventilation-loaded groups and the ischemia-loaded groups, respectively. The intracranial oxyhemoglobin and total Hb concentrations decreased slightly in the H group and markedly in the I and HI groups after the start of experimental protocols, although there were no statistical differences between the I and HI groups. Animals were killed at 24 h after experiments and then subjected to pathologic examination. Damaged neurons with shrunken cell bodies and nuclear changes were found on light microscopic examination, mainly in the pyramidal cell layer of the subiculum and cornu ammonis 1. The numerical density of damaged neurons was significantly higher in the HI group than those in the H or I groups (p < 0.05). These damaged neurons were positive on DNA nick end labeling. A DNA ladder was detected on electrophoresis with a DNA sample extracted from hippocampal tissue in the HI group, but not in the other two groups. On electron microscopic examination, not only condensation of the nucleus but also disruption of mitochondria and the cell membrane were detected. These results suggested that hypocapnia under hypotension might cause neuronal cell death in the hippocampus of neonatal rabbit. Not only ischemia but also a metabolic change induced by hypocapnia might contribute to this apoptotic neuronal cell damage.

Animals↗
PubMed2000

Adriamycin causes dual inotropic effects through complex modulation of myocardial Ca2+ handling.

Effects of adriamycin (ADR) on the twitch contraction of isolated guinea pig cardiac muscles were examined to elucidate its actions on intracellular Ca2+ mobilization. In right ventricular papillary muscles, ADR (100-300 micromol/L) caused positive inotropy when the muscles were constantly stimulated at low frequencies (0.1-0.5 Hz), whereas it caused negative inotropy when the muscles were stimulated at higher frequencies (2.0-3.0 Hz). Action potential duration was prolonged significantly by ADR, especially at the lower frequencies. The potentiation of twitch contraction of the first beat (B 1) following a short rest period (2-10 s) in ventricular muscles was inhibited by ADR. In untreated papillary muscles, B1 contraction showed time-dependent decay in response to a prolongation of the preceding rest period up to 120 s. ADR (300 micromol/L) caused ryanodin-like acceleration for the early B1 decay with rest period less than 20 s, but a substantial deceleration for the later B1 decay (> or =30 s). In left atrial muscles stimulated constantly, ADR had significant negative inotropy throughout the entire range of stimulation frequencies tested (0.1-4.0 Hz). The post-rest potentiation of B 1 contraction of atrial muscle in the presence of nifedipine was also inhibited by ADR. These findings suggest that ADR has dual inotropic effects through a complex modulation of myocardial Ca2+ handling, which may involve (1) an increase of Ca2+ influx through a prolongation of action potential duration, (2) ryanodine-like inhibition of Ca2+ release from the sarcoplasmic reticulum, and (3) inhibition of sarcolemmal Ca2+ extrusion probably through the Na+/Ca2+ exchange.

Animals↗
PubMed2000

Beneficial application of quantitative coronary angiography (edge detection algorithm) in analysis of dissected coronary arteries to predict long-term patency.

The present study evaluated the application of quantitative coronary angiography (edge detection algorithm) for the analysis of coronary dissection lesions after balloon angioplasty. Acute and late results were obtained by the edge detection algorithm in 60 patients with 66 dissected lesions (NHLBI types B-C). The edge detection algorithm delineated the border of the true lumen in 32 lesions (group with automated analysis alone, 48.5%) and included the dissection cap in the analysis in 34 lesions in which manual editing was adjuncted (group with manual editing, 51.5%). In both groups, the minimal lumen diameter after balloon angioplasty obtained by initial automated analysis was correlated to that obtained at the 5.3-month follow-up similarly (r=0.554, p=0.0010 for the group with automated analysis alone and r=0.613, p=0.0001 after automated analysis for the group with manual editing). However, additional manual editing reduced the correlation coefficient (r=0.240, p=0.1707) in the latter group. Thus, in terms of predicting long-term patency, it is reasonable to let the edge detection algorithm decide the measurements in types B and C dissected lesions.

Algorithms↗
PubMed2000

Relationship between effects of alcohol on psychomotor performances and blood alcohol concentrations.

Ethanol is a social drug and has been generally known to be a CNS depressant. A large fluctuation of blood alcohol concentration (BAC) is well-known to occur due to main factors such as the genetic polymorphism of the main alcohol metabolizing enzymes and the effect of blood. Few studies have substantially discussed the relationship between impaired CNS activities and BAC. In this study, focusing on the correlation of BAC, we investigated the acute effects of alcohol intake on cognitive performance in humans by objective evaluation methods consisting of the attention-demanding cognitive tasks. Tasks were administered to ten healthy male volunteers before and after ingesting established amounts of alcohol. With increased BAC, we observed prolongation of reaction time performances and lowering of a coordination performance. From the results, we concluded that cognitive performance deteriorates with an increase of BAC. Additionally, the BAC threshold that causes significant impairment of cognitive performance was estimated to be approximately 50 mg/dl (ca. 10 mM).

Adult↗
PubMed2000

Sympathetic activity and body mass index contribute to blood pressure levels.

The purpose of this study was to clarify the relationships between obesity (BMI) and BP levels, leptin levels, sympathetic activity, and insulin sensitivity in a Japanese male population. In 912 young, non-diabetic, Japanese men with a wide range of BMI (16.5-33.6 kg/m2), blood pressure (BP), fasting plasma norepinephrine (NE), insulin and leptin levels were measured after an overnight fast. The cohort consisted of 603 normotensive and 309 hypertensive subjects. The study was carried out using a cross-sectional design. When the subjects were subdivided by tertile in relation to BMI, the 101 subjects in the heaviest group (BMI > 27.9 kg/m2) had a significantly higher systolic BP (p< 0.05) and pulse rate (p< 0.05) as well as higher NE (p< 0.01), insulin (p< 0.01), and leptin (p< 0.01) levels than 86 subjects in the leanest group (BMI < 22.2 kg/m2). In the whole cohort, BMI correlated with mean BP (p< 0.01), plasma NE (p< 0.05), insulin (p< 0.001) and leptin (p< 0.001). The mean BP correlated with BMI (p< 0.001), plasma NE (p< 0.01), insulin (p< 0.01) and leptin (p< 0.05). Plasma leptin levels correlated with fasting plasma insulin levels (p < 0.05), but not with plasma NE levels (NS). As analyzed by multiple regression analysis, only plasma NE (p< 0.05) and BMI (p< 0.001), but not plasma insulin levels, were significant, independent predictors of BP levels (r2=0.125, F= 10.51, p=0.0001). These results suggest that obesity (BMI) and heightened sympathetic nervous system activity contribute to BP elevation (hypertension).

Adult↗
PubMed2000

Changes in plasma concentrations of inhibin A and inhibin B throughout sexual maturation in the male chimpanzee.

Profiles of circulating plasma inhibin A and inhibin B during sexual maturation in male chimpanzees were investigated by using two-site enzyme-linked immunoassay (ELISA). Plasma concentrations of testosterone and pituitary gonadotropins were also measured. Concentrations of inhibin B, testosterone, luteinizing hormone (LH) and prolactin increased with age throughout prepuberty to adulthood, whereas inhibin A level was low and there were no age-related changes in concentrations of either inhibin A and follicle-stimulating hormone (FSH). Inhibin B showed an inverse correlation with FSH in adult (7 years or order) but not in immature (6 years or younger) male chimpanzees. There was no correlation between plasma levels of FSH and testosterone throughout the period of sexual maturation. However, testosterone levels were positively correlated with inhibin B levels. These results suggest that circulating inhibin B is involved in the regulation of FSH secretion after puberty in adult male chimpanzees, and also that circulating inhibin B is an important form of inhibin as a marker of Sertoli cell function in adult male chimpanzees.

Aging↗
PubMed2000

Development of non-bacterial thrombotic endocarditis after percutaneous transvenous mitral commissurotomy for severely calcified mitral stenosis.

We encountered a case of mitral stenosis, complicated with non-bacterial thrombotic endocarditis, that developed after percutaneous transvenous mitral commissurotomy (PTMC). A 71-year-old female Japanese patient had severe congestive heart failure and underwent PTMC for critical and severely calcified mitral stenosis. Four weeks later, the echocardiogram demonstrated a highly echoic protrusion in the postero-medial commissure of the mitral valve. There was little evidence of inflammation at that time. She had been anticoagulated adequately since she was admitted. The patient underwent replacement of the mitral valve. She did not show any evidence of systemic embolization. Microscopic evaluation showed only organized thrombus but no evidence of inflammation in the mitral valve. Silent development of non-bacterial thrombotic endocarditis after PTMC should be recognized as a rare but potentially lethal complication of PTMC.

Aged↗