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Biomedical subjects

M Sata

Publications and source records attributed to M Sata.

At least 199 records · Page 11Linked to original sources
PubMed1997

Abnormalities in the protein C anticoagulant pathway detected by a novel assay using human thrombomodulin.

We developed a novel assay using human thrombomodulin (TM), which detected overall abnormalities in the protein C anticoagulant pathway (PC pathway). This assay indicates the degree of inhibition of prothrombinase by TM, which is represented as the percentage of prothrombinase inhibition by 25 ng/ml of TM, termed PIP25 (Prothrombinase Inhibition Percentage). We examined PIP25 in plasma samples from patients with systemic lupus erythematosus (SLE) with or without lupus anticoagulant (LA), patients with Behcet's disease (BD), and patients with miscellaneous thrombotic vasculitis and compared these with the PIP25 of plasma samples from healthy volunteers in Japan. The PIP25S were significantly lower in SLE alone (35.5 +/- 12.8%, P = 0.036) and SLE with LA (33.0 +/- 13.3%, P = 0.030) and BD (33.3 +/- 13.4%, P = 0.010) than those in healthy volunteers (43.5 +/- 10.7%). There was no significance between healthy PIP25 and those with miscellaneous thrombotic vasculitis (44.2 +/- 8.4%, P = 0.823). These results suggest that the abnormalities of the protein C anticoagulant pathway were present in patients with SLE(LA) and BD.

Behcet Syndrome↗
PubMed1997

Systemic sclerosis associated with diabetes insipidus.

A rare case of systemic sclerosis that preceded the development of diabetes insipidus is reported. This 25-year-old man presented with Raynaud's phenomenon and ulceration of the tip of the right thumb. The diagnosis of systemic sclerosis was based on findings of proximal scleroderma, sclerodactyly, serological abnormalities, and skin abnormalities verified histologically. Partial central diabetes insipidus was later diagnosed after the sudden appearance of polyuria and polydipsia. Coexistence of systemic sclerosis with diabetes insipidus suggests that diabetes insipidus in this patient might have occurred via an autoimmune mechanism.

Adult↗
PubMed1997

Effects of interferon alpha 2a on incidence of hepatocellular carcinoma in chronic active hepatitis without cirrhosis. Hepatitis Treatment Study Group.

To determine the incidence of hepatocellular carcinoma among patients with chronic hepatitis C who received interferon (IFN) therapy, 63 patients with chronic hepatitis C who underwent IFN therapy (IFN alpha 2a 9 x 10(6) IU daily for 2 weeks and followed 9 x 10(6) IU three times weekly for 14 weeks) from January to December 1992, were studied. Selection criteria were as follows: within six months before IFN therapy patients were diagnosed with chronic active hepatitis without cirrhosis by hepatic histological examination, and were hepatitis C virus antibody positive. Furthermore, patients had records of follow-up liver function tests (once a month) for more than six months after IFN therapy completion, and of ultrasound scanning (once in three to four months) before and for at least more than six months after the therapy completion. An average period of observation was 2.7 years (0.6 to 3.8 years). Twenty five of 63 patients (39.7%) returned to normal values of serum ALT, whereas 38 of 63 (60.3%) still showed abnormal values at six months after IFN therapy completion. Nine of 63 (14.2%) and 6/63 (9.5%) developed cirrhosis and hepatocellular carcinoma, respectively. All patients who developed cirrhosis and hepatocellular carcinoma were from those (n = 38) that showed abnormal ALT values after therapy completion. The five of six patients that progressed to hepatocellular carcinoma were associated with cirrhosis. No patients who returned to normal ALT values developed hepatocellular carcinoma during the period of observation. These results suggest that IFN therapy is effective to prevent the development of hepatocellular carcinoma.

Adult↗
PubMed1997

A case of malignant lymphoma with hemophagocytic syndrome presenting as hepatic failure.

We report the case of a 50-year-old female with malignant lymphoma presenting hemophagocytic syndrome and liver failure. She developed high fever, marked jaundice, and progressive liver failure, followed by evidence of disseminated intravascular coagulation (DIC). The course was complicated by severe hepatitis and the patient died six days after admission. Pathological diagnosis on autopsy specimens of the lung hilar lymph nodes was non-Hodgkin's T cell lymphoma, of the diffuse small cell type. Histopathologic examination of the liver demonstrated diffuse liver cell destruction with prominent T lymphocyte infiltration in the portal and periportal area. In addition to marked lymphoma cell infiltration, hemophagocytosis by prominent infiltrative macrophages was observed in various organs, such as the liver and bone marrow, indicating the hemophagocytic syndrome. The hemophagocytic syndrome characterized in the present case may have been responsible for the extremely rapid and fulminant course.

Fatal Outcome↗
PubMed1997

The significance of colocalization of plasminogen activator inhibitor-1 and vitronectin in hepatic fibrosis.

BACKGROUND: We examined the relationships among vitronectin (VN), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor beta 1 (TGF-beta 1) in liver diseases to evaluate the presence of plasmin cascade in human hepatic fibrosis. METHODS: Blood and liver tissues were obtained from 57 patients with liver disease. Plasma VN, PAI-1 antigen, and PAI-1 activity levels were evaluated. Biopsied liver specimens were observed by light and electron microscopy after immunohistochemical staining. Morphometric analysis was performed on these specimens. RESULTS: Plasma VN and PAI-1 activity levels decreased significantly with the progression of hepatic fibrosis and were particularly marked in the liver cirrhosis group. Plasma PAI-1 antigen level increased significantly. The immunolocalization of the active form of TGF-beta became more intense with the progression of hepatic fibrosis, whereas that of the dual-stained positive areas of PAI-1 and VN (PAI-1.VN) decreased. There was a positive correlation between TGF-beta and PAI-1, whereas there was a negative correlation between TGF-beta and PAI-1.VN. Immunoelectron microscopy showed the localization of PAI-1-VN in the extracellular space around the sinusoidal cells or surface of aggregating platelets, TGF-beta mainly in Ito cells, and VN in hepatocytes near the focal necrotic area or fibrous septa. CONCLUSIONS: These findings suggest that VN and PAI-1 are related to the active form of TGF-beta and that it is possible that the plasmin cascade is present in the human liver.

Adult↗
PubMed1997

Routes of transmission of hepatitis C virus in an endemic rural area of Japan. Molecular epidemiologic study of hepatitis C virus infection.

We conducted an epidemiological study to investigate the routes of transmission of hepatitis C virus (HCV) infection in an area endemic for HCV. Subjects were the 857 adult inhabitants of K area, Japan. The prevalence of antibody to HCV (anti-HCV) was 26.3%. The HCV genotype 1b was the most prevalent (89.3%) among the anti-HCV positive subjects. Molecular evolutionary analysis, based on the nucleotide sequences of the HCV core region from 23 participants with type 1b, showed that the isolates were distributed into more than 1 group. Multivariate regression analysis demonstrated that an age over 40 years, a history of blood transfusion, the presence of antibody to hepatitis B core antigen (anti-HBc), or a history of surgery were each independently associated with the presence of anti-HCV. No significant differences in the presence of anti-HCV prevalence were observed between the wives of men positive for anti-HCV (33.3%) and age-matched women (36.4%), or between the husbands of women positive for anti-HCV (36.4%) and age-matched men (38.3%), from the same area. Findings suggest that the various strains of HCV type 1b were transmitted via medical procedures, not by the intrafamilial route.

Adult↗
PubMed1997

Hepatitis C virus seroconversion rate in a hyperendemic area of HCV in Japan: a prospective study.

We have studied the prevalence, seroconversion rate of anti-hepatitis C virus (HCV), and the transmission of HCV in a cohort of individuals living in a hyperendemic area of HCV in Japan. We investigated 509 subjects, of which 375 could be studied again after 5 years. A remarkable high prevalence of anti-HCV (23.4-24.0%) was observed. Of 287 subjects negative at the first examination in 1990, 4 became positive until the second in 1995 (seroconversion rate: 0.28% per year). Furthermore, we investigated the route of transmission in HCV seroconverted subjects through a detailed interview. All of the HCV seroconverted subjects had past histories of medical treatment. Seroconversion rates of HCV in a hyperendemic area of HCV, were extremely high. Medical treatment was considered to be a causative route of HCV transmission.

Adult↗
PubMed1997

Hepatic iron stainings in chronic hepatitis C patients with low HCV RNA levels: a predictive marker for IFN therapy.

OBJECTIVES: Interferon (IFN) therapy is ineffective in about 20-30% of chronic hepatitis C (CH-C) patients who have low HCV RNA levels. Besides the serum HCV RNA level or HCV genotype, hepatic iron concentrations are thought to be correlated with the subsequent response to IFN therapy. Our objective in the present study was to evaluate serum iron, ferritin, and hepatic iron staining in patients with low HCV RNA levels, as predictive markers for IFN therapy. METHODS: We evaluated 75 CH-C patients whose serum HCV RNA levels were below 1 million genome equivalent (mEq)/ml as shown by a bDNA assay. RESULTS: There were no significant differences in age, sex, serum aminotransferase levels, or serum iron concentrations between responders and nonresponders. The total iron scores (TIS) were significantly higher in responders (p < 0.01). The TIS was an independent factor relating to the response to IFN therapy by multivariate analysis (p = 0.0062). The TIS significantly correlated with serum ferritin levels (r = 0.637, p < 0.001), but not with any other parameter. bi] CONCLUSIONS: Among CH-C patients within the limits of low HCV RNA levels, TIS of the liver may be used as a predictive marker for IFN therapy.

Adult↗
PubMed1996

Functional analysis of the mutations in the human cardiac beta-myosin that are responsible for familial hypertrophic cardiomyopathy. Implication for the clinical outcome.

More than 30 missense mutations in the beta-cardiac myosin heavy chain gene have been shown to be responsible for familial hypertrophic cardiomyopathy. To clarify the effects of these point mutations on myosin motor function, we expressed wild-type and mutant human beta-cardiac myosin heavy chains in insect cells with human cardiac light chains. The wild-type myosin was well purified with similar enzymatic and motor activities to those of the naturally isolated V3 cardiac myosin. Arg249-->Gln and Arg453-->Cys mutations resulted in decreased actin translocating activity (61 and 23% of the wild-type, respectively) with decreased intrinsic ATPase activity. Arg403-->Gln mutation greatly decreased actin translocating activity (27% of wild type) with a 3.3-fold increased dissociation constant for actin, while intrinsic ATPase activity was unchanged. Val606-->Met mutation only mildly affected the actin translocating activity as well as ATPase activity of myosin. The degree of deterioration by each mutation was closely correlated with the prognosis of the affected kindreds, indicating that myosin dysfunction caused by the point mutations is responsible for the pathogenesis of the disease. Structure/function relationship of myosin is discussed.

Actins↗
PubMed1996

Characterization of the motor and enzymatic properties of smooth muscle long S1 and short HMM: role of the two-headed structure on the activity and regulation of the myosin motor.

Truncated mutants of smooth muscle myosin containing various lengths of the S2 portion were expressed in Sf9 cells and purified. Truncated myosin having a heavy chain molecular mass of 128 kDa and larger formed a stable dimer, while 108 kDa myosin remained a monomer. On the other hand, 114 and 110 kDa myosins existed as both monomer and dimer. The enzymatic activity and also the in vitro actin sliding activity of these mutant myosins were measured, and the following findings were obtained. (1) Both the actin sliding activity and the actin-activated ATPase activity showed phosphorylation dependence when myosin forms a dimer while the monomeric form was phosphorylation-independent. This indicates that the interaction between the two heads is operating and critical for the regulation. (2) The actin sliding velocity of the dimer form was twice as large as that of the monomer form, while the actin-activated ATPase activity of the two forms was identical, suggesting that the mechano-chemical efficiency is affected by the interaction between the two heads. (3) The depression of the Mg(2+)-ATPase activity of myosin at low ionic strength, characteristic of the 6S-10S transition of smooth muscle myosin, is abolished with the monomer form, suggesting that the association of the two heads is critical for the 6S-10S transition.

Actins↗
PubMed1996

Functional expression of mammalian myosin I beta: analysis of its motor activity.

The motor function of vertebrate unconventional myosins is not well understood. In this study, we initiated the baculovirus expression system to characterize a novel myosin I from bovine adrenal gland that we had previously cloned [Zhu, T., & Ikebe, M. (1994) FEBS Lett. 339, 31-36], which is classified as myosin I beta. The expressed myosin I beta was well extracted when calmodulin was coexpressed in Sf9 cells. The recombinant myosin I beta cosedimented with actin in an ATP dependent manner. The purified myosin I beta was composed of one heavy chain and three calmodulins. The electron microscopic image of myosin I beta confirmed its single-headed structure with a short tail, which is similar to that of brush border myosin I (BBMI). Myosin I beta showed high K+,EDTA--ATPase activity (approximately 0.14 mumol/min/mg) and Ca(2+)-ATPase activity (approximately 0.32 mumol/min/mg), and the KCl/pH dependence of these activities was different from that of conventional myosin. Mg(2+)-ATPase activity of myosin I beta alone was increased above pCa 6, while the actin dependent activity was not affected by Ca2+. Actin sliding velocity of myosin I beta in the absence of Ca2+ was 0.3-0.5 microns/s at 25 degrees C, which is much greater than that of BBMI (< 0.05 microns/s). The actin sliding activity was abolished above pCa 6, and the sliding activity was restored when exogenous calmodulin was added in the absence of Ca2+. Within similar Ca2+ concentrations, one of the three calmodulins was dissociated from myosin I beta. The results suggest that Ca2+ dependent association of calmodulin may function as a regulatory mechanism of myosin I beta motor activity and that the motor activity of mammalian myosin I is largely different among distinct myosin I isoforms.

Actins↗
PubMed1996

Coupling between myosin ATPase cycle and creatinine kinase cycle facilitates cardiac actomyosin sliding in vitro. A clue to mechanical dysfunction during myocardial ischemia.

BACKGROUND: There is much evidence to support the favorable effects of the phosphocreatine shuttle on myocardial contraction and relaxation. However, experiments in which cardiac muscle fiber or myofibril was used have not elucidated its precise mechanism. METHODS AND RESULTS: Active movements of fluorescently labeled actin filaments on a cardiac myosin layer coimmobilized with creatinine kinase (CK) onto a nitrocellulose-coated glass coverslip were studied under various concentrations of adenine nucleotides. At a constant phosphocreatine concentration (5 mmol/L, pH 7.1), the relation of sliding velocity to MgATP concentration followed Michaelis-Menten kinetics. The apparent Km was significantly smaller in the presence of CK (0.041 +/- 0.001 mmol/L) than in the absence of CK (0.080 +/- 0.001 mmol/L), indicating that coattached CK facilitated the propelling of actin filaments by the myosin ATPase. This phenomenon was also seen under acidic conditions (pH 6.7) as well as in the presence of inorganic phosphate (10 mmol/L. At a constant MgATP concentration (1 mmol/L), the inhibitory effect of MgADP on the actin-myosin interaction was weaker in the presence of CK than in the absence of CK. Another ATP-regenerating system, pyruvate kinase and phospho(enol)pyruvate, while maintaining a low ratio of [MgADP] to [MgATP], did not reduce the Km value (0.156 +/- 0.001 mmol/L), suggesting that the effect of coattached CK was not achieved only by prevention of MgADP accumulation. CONCLUSIONS: Coupling between the ATPase cycle and the CK cycle may serve not only to maintain the ATP concentration within the myofibril but also to provide optimal conditions for cardiac actomyosin interaction. Consideration of this coupling will offer a clue to elucidating the systolic or diastolic dysfunction during myocardial ischemia or reperfusion.

Actomyosin↗
PubMed1996

Effectiveness of glycyrrhizin for oral lichen planus in patients with chronic HCV infection.

Oral lichen planus (OLP), an intractable inflammatory disease characterized by a band-like lymphocytic invasion under the oral mucosa, is frequently associated with hepatitis C virus (HCV) infection. We investigated the effects of glycyrrhizin, which is used to treat chronic liver dysfunction, in nine patients with OLP who were positive for HCV antibody and HCV RNA. A control group, eight patients with OLP who were also positive for HCV antibody and HCV RNA, was given only dental cleaning. Glycyrrhizin (GL) was given intravenously, at a dose of 40 ml (0.2% solution) daily, for 4 consecutive weeks. Six (66.7%) of the nine patients given GL improved clinically (P = 0.0141 vs non-GL group), suggesting that GL is useful in treating OLP.

Adult↗
PubMed1996

Analysis of serum hepatitis A virus antibody response in different courses of hepatitis A virus infection.

Changes in the serum hepatitis A virus antibody (anti-HAV) response in patients with different clinical courses of HAV infection were examined using immune adherence hemagglutination (IAHA). Anti-HAV was detected 2-6 weeks after the onset of clinical symptoms in patients with the typical course of acute hepatitis A and 1-4 weeks after the onset in those with fulminant hepatitis A. Maximal anti-HAV titers were observed 8-20 weeks after the onset of clinical symptoms, and changes in anti-HAV were similar in the typical and the prolonged course of acute hepatitis A, but maximal antibody titers were higher in the prolonged course. Maximal anti-HAV titers in patients with subclinical HAV infection were significantly lower than titers in patients with the typical and prolonged courses of acute hepatitis A, and in those with fulminant hepatitis A. High titers of anti-HAV remained positive for at least 6 years after infection in patients with clinical infection and for at least 4 years in patients with subclinical infection on follow-up. These findings suggest that the maximum anti-HAV titer correlates with the clinical severity of HAV infection; knowledge of the antibody response should be useful for analyzing the pathogenesis of HAV infection.

Acute Disease↗
PubMed1996

Protein C activation in NIDDM patients.

Enhanced activation of the clotting system has been recently implicated in the pathogenesis of vascular complications in patients with diabetes mellitus. Abnormalities of the anticoagulant system may constitute a potential trigger factor for the haemostatic activation observed in diabetic subjects. The current study aimed to evaluate anticoagulant activity in diabetic patients by assessing the plasma levels of activated protein C-protein C inhibitor complex; and by measuring the anticoagulant response to exogenous thrombomodulin. This study comprised 61 patients (34 men, 27 women) with non-insulin-dependent diabetes mellitus (NIDDM) of whom 22 showed microalbuminuria and 39 normoalbuminuria. Data obtained in 31 non-obese and non-diabetic subjects were available for comparison. The plasma levels of fibrinogen (p < 0.02), prothrombin fragment 1 + 2 (p < 0.05), fibrin monomer (p < 0.0001), protein C antigen (p < 0.005), total protein S antigen (p < 0.02), soluble thrombomodulin (p < 0.005) and soluble E-selectin (p < 0.005) were significantly higher in diabetic patients than in healthy subjects. The plasma level of activated protein C-protein C inhibitor complex (7.4 +/- 3.8 vs 3.0 +/- 0.4 pmol/l) was significantly higher (p < 0.0001) and the anticoagulant response to exogenous thrombomodulin (23.4 +/- 2.6 vs 35.3 +/- 3.0 ng/ml) was markedly lower (p = 0.005) in all diabetic patients than in healthy subjects. Cases with microalbuminuria presented low plasma levels of activated protein C-protein C inhibitor complex (5.5 +/- 0.6 vs 8.6 +/- 0.7 pmol/l, p < 0.05) and significantly decreased values of the anticoagulant response to exogenous thrombomodulin (16.5 +/- 2.9 vs 23.4 +/- 2.6%, p = 0.03) as compared to those with normoalbuminuria. The present study suggests that the hyper-coagulable state in NIDDM is associated with an increased activation of protein C but with a poor plasma reactivity to the anticoagulant effect of thrombomodulin.

Adult↗
PubMed1996

Evaluation of hyaluronic acid binding ability of hepatic sinusoidal endothelial cells in rats with liver cirrhosis.

BACKGROUND & AIMS: In liver cirrhosis, the binding and degradation of hyaluronic acid in the hepatic sinusoidal endothelial cells are considered to be reduced by development of hepatic sinusoidal capillarization, resulting in high serum hyaluronic acid concentration. The aim of this study is to clarify the cause of high blood hyaluronic acid concentration in liver cirrhosis. METHODS: Liver cirrhosis was induced in rats by thioacetamide administration. In vivo observation of sinusoidal capillarization, in vitro immunolocalization of factor VIII-related antigen and CD44, and [14C]hyaluronic acid binding in cultured sinusoidal endothelial cells were determined. RESULTS: Basement membranes were observed on the basal side of sinusoidal endothelial cells. The fenestrae and fluorescent intensity of anti-CD44 bound to the cells decreased with progression of hepatic fibrosis. Immunofluorescent reactive products of factor VIII-related antigen were more abundant in the cirrhotic rats compared with the controls. Amount of [14C]hyaluronic acid binding was significantly decreased in the cirrhotic group compared with the controls. CONCLUSIONS: One reason that the blood hyaluronic acid concentration increases markedly in liver cirrhosis is considered to be the reduction in hyaluronic acid receptors of hepatic sinusoidal endothelial cells and in the amount of hyaluronic acid binding to the cells.

Animals↗