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M Nishino

Publications and source records attributed to M Nishino.

At least 19 recordsLinked to original sources
PubMed2006

Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.

von Willebrand disease (VWD) is a bleeding disorder caused by inherited defects in the concentration, structure, or function of von Willebrand factor (VWF). VWD is classified into three primary categories. Type 1 includes partial quantitative deficiency, type 2 includes qualitative defects, and type 3 includes virtually complete deficiency of VWF. VWD type 2 is divided into four secondary categories. Type 2A includes variants with decreased platelet adhesion caused by selective deficiency of high-molecular-weight VWF multimers. Type 2B includes variants with increased affinity for platelet glycoprotein Ib. Type 2M includes variants with markedly defective platelet adhesion despite a relatively normal size distribution of VWF multimers. Type 2N includes variants with markedly decreased affinity for factor VIII. These six categories of VWD correlate with important clinical features and therapeutic requirements. Some VWF gene mutations, alone or in combination, have complex effects and give rise to mixed VWD phenotypes. Certain VWD types, especially type 1 and type 2A, encompass several pathophysiologic mechanisms that sometimes can be distinguished by appropriate laboratory studies. The clinical significance of this heterogeneity is under investigation, which may support further subdivision of VWD type 1 or type 2A in the future.

ADAM Proteins↗
PubMed2006

Tuberin activates the proapoptotic molecule BAD.

TSC1, encoding hamartin, and TSC2, encoding tuberin, are tumor suppressor genes responsible for the autosomal dominantly inherited disease tuberous sclerosis (TSC). TSC affects approximately 1 in 6000 individuals and is characterized by the development of tumors, named hamartomas, in different organs. Hamartin and tuberin form a complex, of which tuberin is assumed to be the functional component. The TSC proteins have been implicated in the control of cell cycle and cell size. In addition to enhanced growth, reduced death rates can lead to tumor development. Therefore, defects in the apoptosis-inducing pathways contribute to neoplastic cell expansion. Here, we show that tuberin triggers apoptosis, accompanied by downregulation of p70S6K activity and of phosphorylation of BAD on residue Ser136, and by upregulation of the interaction of BAD/BCL-2 and BAD/BCL-XL. AKT phosphorylation negatively regulates tuberin's potential to trigger apoptosis. Experiments with BAD-/- cells demonstrate BAD to be a mediator of tuberin's effects on the regulation of apoptosis. Tuberin interferes with insulin-like growth factor-1-induced BAD Ser136 phosphorylation and cell survival. Our work proposes a model in which tuberin-mediated inhibition of p70S6K activates BAD to heterodimerize with BCL-2 and BCL-XL to promote apoptosis. A mutation of TSC2--as it occurs in TSC patients--attenuates this proapoptotic potential, underscoring the relevance of our findings for human pathophysiology.

Animals↗
PubMed2006

Hemorrhagic symptoms and bleeding risk in obligatory carriers of type 3 von Willebrand disease: an international, multicenter study.

OBJECTIVES: We undertook an international, multicenter study to describe the clinical picture and to estimate the bleeding risk in a group of obligatory carriers of type 3 von Willebrand disease (VWD). PATIENTS AND METHODS: Obligatory carriers (OC) of type 3 VWD were identified by the presence of offspring with type 3 VWD or by being an offspring of a type 3 patient. Normal controls were age- and sex-matched with the obligatory carriers. A physician-administered standardized questionnaire was used to evaluate hemorrhagic symptoms at presentation. A score system ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion) was used to quantitate bleeding manifestations. Odds ratios were computed for each symptom. RESULTS: Ten centers participated to the study, enrolling a total of 35 type 3 VWD families, with 70 OC. A total of 215 normal controls and 42 OC for type 1 VWD were also included. About 40% of type 3 OC had at least one bleeding symptom compared to 23% of normal controls and 81.8% of type 1 OC (P < 0.0001 by chi-squared test), showing that type 3 OC clearly represent a distinct population from type 1 OC. The clinical situations associated with an increase of bleeding risk in type 3 OC were epistaxis [odds ratio 3.6; 90% confidence intervals (CI) 1.84-21.5], cutaneous bleeding (odds ratio 5.5; 90% CI 2.5-14.1) and postsurgical bleeding (odds ratio 16.3; 90% CI 4.5-59). The severity of bleeding score correlated with the degree of factor (F) VIII reduction in plasma. CONCLUSIONS: OC for type 3 VWD represent a distinctive population from type 1 OC. These patients, however, present with more frequent bleeding symptoms in comparison to normal controls, especially in case of significantly low FVIII. Desmopressin and/or tranexamic acid might be useful to prevent or treat bleeding in these cases.

Adolescent↗
PubMed2006

Decrease in herbicide concentrations and affected factors in lagoons located around Lake Biwa.

The contamination levels and changes in the concentrations in four lagoons around Lake Biwa of paddy-use herbicide were studied. Four lagoons, Sone-numa (52 days of HRT (hydraulic residence time) estimated from the lagoon volume and the average discharge at the outlet, 21 ha area), Yanagihira-ko (40 days, 5.0 ha), Noda-numa (11 days, 6.0 ha), and Iba-naiko (2 days, 55.5 ha), were selected as monitoring sites. Intensive water sampling was carried out once a week from May to June at the outlet of each lagoon. Although twelve of the monitored herbicides were detected, the maximum concentrations did not exceed the guidelines for water-supply law in Japan. The relation between half-lives in herbicide concentrations and characteristics of a lagoon such as HRT and chlorophyll-a concentrations were examined. The shorter half-lives of herbicide concentrations in lagoons with shorter HRT means that replacement by influent water effectively decreased the pesticide concentrations. Shorter half-lives in lagoons with high chlorophyll-a concentrations between the lagoons with similar HRT suggest that biological degradation during the residence time worked more efficiently in the lagoon with high chlorophyll-a concentrations.

Chlorophyll↗
PubMed2005

A 90-day oral toxicity study of beta-carotene derived from Blakeslea trispora, a natural food colorant, in F344 rats.

A subchronic oral toxicity study of beta-carotene derived from Blakeslea trispora, a natural food colorant, was performed with groups of 10 male and 10 female F344 rats fed the agent at dietary levels of 0%, 0.2%, 1.0% and 5.0% for 90 days. There were no treatment-related adverse effects with regard to body weight, food and water consumption, urinalysis, ophthalmology, hematology, serum biochemistry, and organ weight data. On clinical observation, red coloring of fur was noted in both sexes of the 1.0% and 5.0% group rats, with red feces observed in all treated group animals, and necropsy revealed all rats of the treated groups to have reddish coloration of the contents of the gastro-intestinal tract, due to the pigmentation and thus lacking toxicological significance. On histopathological examination, sporadic spontaneous lesions known to occur in this strain of rats were the only findings, with no specific relation to the test substance. Thus, the no-observed-adverse-effect-level (NOAEL) was judged to be a dietary level of at least 5.0% (3127 mg/kg body weight/day for males, 3362 mg/kg body weight/day for females) for beta-carotene derived from B. trispora under the present experimental conditions.

Animals↗
PubMed2005

Acute myocardial infarction caused by a septic coronary embolism diagnosed and treated with a thrombectomy catheter.

Acute myocardial infarctions are common in bacteraemia but are seldom diagnosed during life. A 64 year old man with severe chest pain who had fever for several days due to possible bacteraemia was shown by ECG and echocardiography to have possible lateral infarction. Immediate coronary angiography showed possible thrombus in the left circumflex artery, which was treated by thrombectomy catheter. Bacterial thrombus was removed and was verified by histological examination. A stent was implanted without complications. Acute myocardial infarction caused by septic embolism is usually fatal; however, thrombectomy may be useful in these cases.

Cardiac Catheterization↗
PubMed2002

Effects of steroids on femoral diaphyseal intramedullary circulation in rabbits.

We examined the effect of steroid treatment on the intraosseous femoral vasculature in rabbits, with particular emphasis on the morphologic changes in bone marrow sinusoids and central veins. Adult rabbits were divided into three treatment groups: group A, untreated control; group B, animals were treated with intramuscular injections of methylprednisolone acetate (4 mg/kg/week) for 4 weeks; and group C, rabbits which received injections for 8 weeks. Examination of the intraosseous femoral vasculature was performed using microangiography, scanning electron micrography using a corrosion cast method, and retrograde venography. Bone marrow sinusoids of group C were dilated and the network of anastomosed vessels was irregular compared with those of group A. Changes in group B were intermediate between the control rabbits and group C. Retrograde venography of the central vein showed an irregular course and frequent narrowing of the signal. There were no arterial changes in the steroid-treated groups. These findings indicate that steroid therapy does not induce arterial ischemia but rather intraosseous venous stasis extending from bone marrow sinusoids to the central veins. These changes are attributable to bulging or dilatation of sinusoids, a rise in intraosseous pressure, and reduced blood flow.

Animals↗
PubMed2001

Relationship between evaluation by quantitative fatty acid myocardial scintigraphy and response to beta-blockade therapy in patients with dilated cardiomyopathy.

Predicting the effect of beta-blockade therapy on the clinical outcome of patients with dilated cardiomyopathy (DCM) is difficult prior to the initiation of therapy. Myocardial fatty acid metabolism has been shown to be impaired in patients with DCM. We examined whether the extent of myocardial injury, as assessed by iodine-123 15-( p-iodophenyl)-3- R, S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy, is related to the response of patients with DCM to beta-blockade therapy. Thirty-seven patients with DCM were examined using BMIPP myocardial scintigraphy before and after 6 months of treatment with metoprolol. Myocardial BMIPP uptake (%BM uptake) was estimated quantitatively as a percentage of the total injected count ratio. The left ventricular end-diastolic and end-systolic dimensions (LVDd, LVDs) and ejection fraction (LVEF) were also evaluated. The patients were divided into two groups according to their functional improvement (>10% elevation of LVEF) after 6 months of metoprolol therapy. Twenty-eight patients responded to the therapy, while nine did not. Prior to the therapy, no significant differences in LVDd, LVDs or LVEF were observed between the responders and non-responders. However, the %BM uptake was significantly lower in the non-responders than in the responders (1.0%+/-0.2% vs 2.1%+/-0.5%, P<0.001). The %BM uptake could be used to distinguish the responders from the non-responders with a sensitivity of 0.93 and a specificity of 1.00 at a threshold value of 1.4. After the metoprolol therapy, the %BM uptake improved significantly in the responders (2.5%+/-0.5%, P<0.01) but did not change in the non-responders. These results indicate that myocardial BMIPP uptake could predict the response of DCM patients to beta-blockade therapy.

Adrenergic beta-Antagonists↗
PubMed2001

Increased angiotensin-converting enzyme activity in coronary artery specimens from patients with acute coronary syndrome.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are effective in the secondary prevention of ischemic heart disease, but they do not reduce the rate of restenosis. Vascular ACE activity in the culprit coronary lesions of these patients, however, has never been quantified. METHODS AND RESULTS: We measured the ACE activity of vascular tissue obtained by directional coronary atherectomy in patients with acute coronary syndrome (n=17) and in patients with stable ischemic heart disease (n=36), with and without restenosis. The ACE activity of the culprit coronary lesions was significantly increased in patients with acute coronary syndrome (0.87+/-0.12 nmol. min(-1). mg protein(-1); P:<0.01) but not in patients with ischemic heart disease with restenosis (n=11, 0.19+/-0.05 nmol. min(-1). mg protein(-1)) when compared with those patients with ischemic heart disease without restenosis (n=25, 0.20+/-0.05 nmol. min(-1). mg protein(-1)). There was no difference between the ACE activity of the coronary tissue of the in-stent (n=5) and stent-unrelated (n=6) restenosis patients (0.24+/-0.10 versus 0.15+/-0.04 nmol. min(-1). mg protein(-1)). Serum ACE activity did not differ significantly among the patients. CONCLUSIONS: The present study demonstrates increased ACE activity in culprit lesions in acute coronary syndrome, indicating that enhanced ACE activity is related to the causative mechanism of active coronary lesions.

Acute Disease↗
PubMed2001

Power motion imaging can improve image quality in stress conditions with tachycardia.

BACKGROUND: Stress echocardiographic studies are useful, but the evaluation of wall motion is sometimes suboptimal. The recently developed technique of power motion imaging can enhance mobile tissue definition. HYPOTHESIS: The study was undertaken to determine whether power motion imaging improves endocardial definition during tachycardia compared with conventional two-dimensional (2-D) imaging. METHODS: Twenty pigs were studied during pacing rates of 100, 120, and 150 beats/min. We compared power motion imaging with standard 2-D imaging using systolic thickening visualization (STV) scores (3 = excellent definition of systolic thickening approximately 0 = total lack of visualization of systolic thickening) at each heart rate. We calculated the sum of the scores of 22 left ventricular segments as the overall STV score, and also calculated the sum of the scores in 10 parasternal segments and 12 apical segments separately. RESULTS: The overall STV scores in both imaging methods were similar at 100 beats/min, but scores for power motion imaging were significantly higher than those of usual 2-D imaging at 120 and 150 beats/min. Using power motion imaging, the overall STV scores were similar as heart rate was increased; however, while using standard 2-D imaging, STV scores were significantly decreased as heart rate was increased. Findings were analyzed separately by parasternal and apical images. Especially in the parasternal images, the scores were significantly increased as heart rate was increased using power motion imaging. CONCLUSIONS: We conclude that power motion imaging improves the detection of endocardial border in stress condition with tachycardia, and thus this modality is useful for stress echocardiography.

Animals↗
PubMed2001

High- and moderately high-methionine uptake demonstrated by PET in a patient with a subacute cerebral infarction.

In patients with cerebral tumors, high accumulations of L-methyl-11C-methionine (11C-Met) have been reported in some cases of cerebral ischemic disease, but no high accumulations of 11C-Met in areas where only transient arterial occlusions are most likely to occur have been reported. Herein we present a case of a high accumulation of 11C-Met in an area of frontal interhemispheric cerebral infarction and a moderately high accumulation with an unclear margin in a distant frontal convexity area. A craniotomy revealed a subacute stage of cerebral infarction in the interhemispheric lesion, and an ischemic change in the distant convexity area. Sixteen months after onset, CT scans demonstrated an infarction area in the interhemispheric lesion only, and no atrophic changes were observed in the distant convexity area indicating that no serious tissue damage had occurred.

Adult↗
PubMed2001

Polymorphism in gene for islet autoantigen, IA-2, and type 1 diabetes in Japanese subjects.

Autoantibodies against IA-2 have been detected in up to 86% of newly diagnosed patients with type 1 diabetes and appear to identify a subgroup of prediabetic subjects who rapidly progress to type 1 diabetes. We examined the association of IA-2 gene polymorphism with type 1 diabetes in Japanese subjects. A total of 276 Japanese subjects were studied for disease association and, in addition, another 53 patients were studied for association with the autoantibody status to IA-2. A microsatellite marker D2S1753E, located in the intron of the IA-2 gene, was used as a genetic marker in this study. In Japanese, two alleles (161mu and 165mu) were more frequent, and the 163mu allele was less frequent than in Caucasians (p = 0.0001). There was no significant difference in frequencies of alleles between diabetic patients and control subjects. The frequency of IA-2 gene polymorphism was not significantly different between patients stratified by age-at-onset, or between patients with and without susceptible HLA, DRB1*0405, DRB1*0802 and DRB1*0901. There was no significant difference in allele frequency of the IA-2 gene polymorphism between patients with and without autoantibody to IA-2. In conclusion, IA-2 gene polymorphism is not associated with either susceptibility to, or heterogeneity in type 1 diabetes in Japanese subjects.

Alleles↗
PubMed2001

Enhanced expression of heat shock proteins in activated polymorphonuclear leukocytes in patients with sepsis.

BACKGROUND: Heat shock proteins (HSPs) in cells, as molecular chaperons, have been reported to regulate cell functions. The objective of this study was to investigate the HSP expression in polymorphonuclear leukocytes (PMNLs) from severe septic patients and the relation between the expression of HSPs and PMNL function. METHODS: In blood samples from 21 patients with sepsis and serum C-reactive protein levels more than 10 mg/dL, we used flow cytometry to measure expressions of HSP27, HSP60, HSP70, and HSP90; oxidative activity; and levels of apoptosis in PMNLs during sepsis. In in vitro studies, we used cells from 14 healthy volunteers to examine the relation between the expression of HSP70 and PMNL function. Quercetin (30 microM), a suppressor of HSP, and sodium arsenite (100 microM), an inducer of HSP, were used to regulate the expression of HSP70 in PMNLs, and oxidative activity and apoptosis in these cells were measured. RESULTS: In patients with sepsis, the expressions of HSP27, HSP60, HSP70, and HSP90 and oxidative activity in PMNLs were significantly increased. Apoptosis of these PMNLs was markedly inhibited. In the in vitro studies, administration of sodium arsenite enhanced the expression of HSP70, significantly increased oxidative activity, and inhibited apoptosis. Administration of quercetin before sodium arsenite prevented the expression of HSP70, the increase in oxidative activity, and the inhibition of apoptosis. CONCLUSION: Sepsis causes the enhanced expression of HSPs in activated PMNLs. In PMNLs with enhanced expression of HSP70, oxidative activity is increased and apoptosis is inhibited. The enhanced expression of HSPs may play a role in regulating PMNL function in patients with sepsis.

Adult↗
PubMed2001

Granulocyte colony-stimulating factor (G-CSF) stiffens leukocytes but attenuates inflammatory response without lung injury in septic patients.

OBJECTIVE: To determine whether granulocyte colony-stimulating factor (G-CSF) administration changes leukocyte deformability resulting in lung injury in patients with sepsis. METHODS: Twenty-five consecutive septic patients were divided randomly into two groups. Twelve patients were given recombinant human G-CSF subcutaneously at 2 microg/kg once a day for 5 days (group G). The remaining 13 patients were given sterilized saline as placebo (group N). Leukocyte count; concentrations of C-reactive protein (CRP) and thrombomodulin (TM); respiratory index (RI) and lung injury score (LIS); and APACHE II score and Goris MOF index were determined before and after G-CSF or placebo administration. Leukocyte deformability was observed in a microchannel array etched on a single-crystal silicon tip, which simulates the microvasculature. The number of microchannels obstructed (NOM) by stiffened leukocytes was counted. Transit time (TT), that is, the time taken for 100 microL of whole blood to pass through the microchannel, was determined. RESULTS: G-CSF administration significantly increased leukocyte count and decreased CRP concentration. In group G, both NOM and TT increased significantly 5 days after G-CSF administration; they did not change in group N. However, RI, LIS, and TM did not change, suggesting that no patient developed lung injury. CONCLUSION: G-CSF causes leukocyte stiffness but attenuates inflammatory response without inducing lung injury in septic patients.

APACHE↗
PubMed2001

Detection of antipituitary antibodies in patients with autoimmune thyroid disease.

The aim of the present study was to investigate the prevalence of antipituitary antibodies (APA) in patients with autoimmune thyroid disease as determined by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Results by Western blot analysis showed positivity for APA in serum of 22.4% of patients with Graves' disease (n=143, p<0.05) and 18.5% of patients with Hashimoto's thyroiditis (n=54, p<0.05), which were significantly higher than 6.2% in healthy controls (n=97). Similar results were obtained with ELISA. The titers of APA measured by ELISA (APA/ELISA) remained unchanged before and after therapy with antithyroid drug for Graves' disease, while thyrotropin-binding inhibitor immunoglobulins (TBII) decreased significantly. Similarly, no changes in APA by Western blot analysis were observed after therapy. In patients with Graves' disease, APA were not associated with thyroid status. There was no difference in APA between patients with positive and negative thyroid autoantibodies. A significant but weak positive correlation between APA/ELISA and anti-human GH measured by ELISA (anti-hGH/ELISA) was observed in patients with Graves' disease (r=0.601 p<0.001) and Hashimoto's thyroiditis (r=0.428 p<0.005). These findings have demonstrated the existence of APA detected by Western blot analysis and ELISA in some cases of autoimmune thyroid disease. The present results suggest that hGH and other antigens may be involved in APA in patients with Graves' disease and Hashimoto's thyroiditis.

Adolescent↗
PubMed2001

Sequence analysis of candidate genes for common susceptibility to type 1 and type 2 diabetes in mice.

Although type 1 and type 2 diabetes are regarded as clinically distinct diseases, several lines of evidence have suggested common genetic factors between the two types of diabetes. The non-obese diabetic (NOD) mouse, an animal model of type 1 diabetes, and the Nagoya-Shibata-Yasuda (NSY) mouse, a model of type 2 diabetes, are derived from the same outbred colony, Jcl:HCR, suggesting a shared susceptibility between the two types of diabetes in mice. Genetic as well as functional studies have supported the possibility that Tcf2, which encodes the transcription factor, hepatocyte nuclear factor 1beta (HNF-1beta), is a candidate gene for the common susceptibility between NSY and NOD mice. Txn, encoding thioredoxin which is a redox (reduction/oxidation)-active protein, is also a positional and functional candidate for a common susceptibility gene. To investigate whether either of these two genes is a common susceptibility gene, the coding nucleotide sequences of these two genes were compared among the NSY, NOD and control C3H strains. The coding sequence of Tcf2 of the NOD mouse was identical to that of the C3H mouse, but was different from that of the NSY mouse. The coding sequence of Txn was identical in the three strains. These data suggest that neither of the two genes is a common susceptiblity gene between type 1 and type 2 diabetes in mice.

Animals↗
PubMed2001

Lack of association between hepatocyte nuclear factor-1beta gene and common forms of type 2 diabetes in the Japanese population.

Mutations in the hepatocyte nuclear factor-1beta (HNF-1beta) gene have been shown to be a cause of maturity-onset diabetes of the young (MODY). We studied the contribution of the HNF-1beta gene to susceptibility to common forms of Type 2 diabetes in the genetically homogeneous Japanese population, by investigating the allelic association of Type 2 diabetes with two markers in the HNF-1beta region. The frequency of a nonsense mutation, R177X, which was previously reported in a Japanese family, was also studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using a mismatch primer. A total of 200 subjects were studied. There was no significant difference in allele frequencies of either of the two polymorphisms studied between patients with Type 2 diabetes and control subjects, or between subgroups of patients subdivided by the presence of mild or severe diabetic nephropathy. None of the subjects studied had R177X mutation, giving a frequency of less than 1.1% in common forms of Type 2 diabetes in Japan. These results suggest that mutations in the HNF-1beta gene derived from a limited number of founders are not a major cause of common forms of Type 2 diabetes, even in the genetically homogeneous Japanese population.

Adult↗