Biomedical subjects

M Sata

Publications and source records attributed to M Sata.

At least 163 records · Page 9Linked to original sources

PubMed1998

A case of chronic hepatitis C with sinus bradycardia during IFN therapy.

The patient was a 55-year-old male with no history of heart diseases. He was administered recombinant IFN alpha-2b under the diagnosis of chronic hepatitis C. Since sinus bradycardia (heart rate 40 bpm) appeared in the fourth week of administration (cumulative dose; 240 M.U), IFN was discontinued. Bradycardia was resolved 1 week after discontinuation of IFN, and the treatment was resumed with a change of the regimen to IFN-beta. Since no bradycardia was noted thereafter, IFN therapy could be completed (total dose; 108 M.U). These observations suggest that the type of IFN or total dose contributed to the appearance of cardiotoxicity.

Arrhythmia, Sinus↗

PubMed1998

Mutations of glucocorticoid responsive element of HBV DNA.

The mutation of glucocorticoid responsive element (GRE) of HBV DNA obtained from a patient with chronic hepatitis B was evaluated. This patient showed fatal course by glucocorticoid administration. The HBV DNA from this patient (GRE-M) and two patients with HBeAg positive chronic hepatitis B (GRE-W1,2) whose HBV DNA have few mutations, were examined. The 212 bp region from nt.274 to nt.485 (GRE region) was amplified by PCR and the nucleotide sequence was determined. A base mismatched sequence of the latter half of the GRE consensus sequence was confirmed at nt.296-301 (G1), nt.347-352 (G2), nt.359-364 (G3), and nt.473-478 (G4). Also one base mismatched sequence of the AP-1 response element was detected at nt.331-337 (A1). The nucleotide substitutions in GRE-M generate three putative loop formation sites, four bases in length, from nt.22 to nt.31 (L1), nt.35 to nt.42 (L2), and nt.74 to nt.83 (L3). The L1 was located just upstream of the G1. The L2 was located between the A1 and the G2. These mutations followed by three-dimensional form change may affect the responses to glucocorticoid.

Base Sequence↗

PubMed1998

Negative-strand HCV RNA was not detected in bone marrow cells of patients with HCV infection.

To determine whether hepatitis C virus (HCV) replicates in bone marrow, we investigated positive- and negative-strand HCV RNA in bone marrow cells and fluids, and sera from patients with HCV infection. The study population consisted of 15 patients positive for antibodies to HCV (anti-HCV). Positive- and negative-strands HCV RNA were detected using highly strand-specific rTth reverse transcription-polymerase chain reaction (rTth RT-PCR) followed by Southern blotting analysis. Positive-strand HCV RNA was detected in 12 (80%) serum samples, in 13 (86.7%) bone marrow fluid specimens, and in 6 (40.0%) bone marrow cell samples. Negative-strand HCV RNA was detected in 9 (60.0%) serum samples, 11 (91.7%) fluid specimens, while it was not detected in bone marrow cells. The absence of negative-strand HCV RNA in bone marrow cells suggested that HCV does not replicate in these cells. Negative-strand HCV RNA detected in serum and bone marrow fluid samples may have been due to contamination with circulating HCV RNA from hepatocytes.

Adult↗

PubMed1998

Evaluation of third generation anti-HCV test kit (SYNPEP HCV-EIA II) using sera of inhabitants from HCV hyperendemic area.

We examined the characteristics and usefulness of a third generation anti-HCV test kit, SYNPEP HCV-EIA II (Kyokuto Pharmaceutical Inc., Tokyo, Japan). The sera of inhabitants from a hepatitis C virus (HCV) hyperendemic area were used. The kit had even or more anti-HCV detection sensitivity and reproducibility than ORTHO HCV III ELISA Test System (Ortho-Clinical Diagnostic K.K., Tokyo, Japan) or HCV PHA 2nd Generation (Dinabot Co., Ltd., Tokyo, Japan). SYNPEP HCV-EIA II needed less total reaction time than other EIA kits, resulting in a simple procedure. Also, HCV RNA was detected in 90% of subjects who had a 7.5 or greater cut-off index (COI) of SYNPEP HCV-EIA II kit. In conclusion, SYNPEP HCV-EIA II require cheap cost and simple procedure and it could be applied to mass screening to find out HCV RNA positive persons who may need clinical care.

Antibodies, Viral↗

PubMed1998

Serum carboxy-terminal cross-linked telopeptide of type I collagen reflects bone metastasis in hepatocellular carcinoma.

Carboxy-terminal telopeptide of type I collagen (ICTP) is a degradation product of type I collagen. In this study, we investigated the usefulness of measuring the serum ICTP concentration for diagnosing and monitoring bone metastasis from hepatocellular carcinoma (HCC). The serum concentrations of ICTP, type I procollagen carboxy-terminal propeptide (PICP), type III procollagen aminoterminal propeptide (PIIIP), type IV collagen (Ty IV), type IV collagen 7S-domain (7S), and hyaluronic acid (HA) were measured in patients with liver cirrhosis, HCC with or HCC without bone metastasis, and in healthy controls. The diagnostic efficiency of the serum ICTP and fibrosis marker levels in the HCC patients with and without bone metastasis was evaluated using receiver operating characteristic curves. We also retrospectively examined the changes in the serum ICTP levels before and after bone metastasis in the HCC patients. The serum ICTP level was significantly higher in the HCC patients with bone metastasis than in the patients with other diseases and the healthy controls. The serum PICP, PIIIP, Ty IV, 7S and HA levels of the HCC patients with bone metastasis did not differ significantly from those of the patients without bone metastasis. The diagnostic efficiency for HCC with bone metastasis was 87% for ICTP, 51% for PICP, 65% for Ty IV, 55% for PIIIP and 51% for HA. During the follow-up, the changes in the serum ICTP values paralleled the behavior of bone metastasis. These results indicate that the measurement of serum ICTP concentration is useful for detecting and monitoring HCC patients with bone metastasis.

Adult↗

PubMed1998

Usefulness of the high-frequency ultrasound probe in pretherapeutic staging of superficial-type colorectal tumors.

We evaluated the usefulness of the high-frequency ultrasound probe (HFUP, 20 MHz) to determine the depth of tumor invasion in 45 patients with superficial colorectal tumors. The correct diagnostic rate was 66% (30/45) when the depth of tumor invasion was classified into the following 6 layers: mucosa (m), upper 1/3 (sm1), middle 1/3 (sm2), and lower 1/3 (sm3) areas of the submucosa, muscularis propria (mp), and the subserosa or deeper areas (s). However, when the depth of tumor invasion was evaluated in 3 layers (m-sm1, sm2-sm3, and mp-deeper layer), which is the classification used to select cases for endoscopic mucosal resection, the correct diagnostic rate was 88.9% (40/45). These results suggest that the HFUP is useful to determine the depth of invasion to select treatment for superficial colorectal tumors.

Aged↗

PubMed1998

[The diagnosis of the early stage of hepatocellular carcinoma by US-angiography with intraarterial Albunex (sonicated serum albumin) infusion].

Contrast-enhanced ultrasonography (arterial infusion) has been clinically established as a qualitative diagnosis imaging tool for hepatocellular carcinoma (HCC). Contrast-enhanced ultrasonography (CEUS) was performed after of Albunex (sonicated serum albumin) or Carbon Dioxide (CO2) microbubble by hand, into the hepatic artery as a diagnostic modality for the early HCC. Here, we discussed the diagnosis of the early HCC by CEUS using Albunex as a contrast medium. Briefly, a diagnosis of the early HCC was made CEUS examination of the hemodynamics of the arteries showed a hypovascular pattern. And tumor size was under 20 mm in diameter, the histopathologic examination was essential to reach a final diagnosis, well-differentiated HCC.

Albumins↗

PubMed1998

Effects of recombinant human soluble thrombomodulin (rhs-TM) on clot-induced coagulation in human plasma.

Recent studies have suggested that clot-bound thrombin plays an important role in thrombus growth. In this study, we examined the effects of recombinant human soluble thrombomodulin (rhsTM) on clot-induced coagulation. rhsTM enhanced the activation of protein C by clots, and attenuated clot-induced thrombin generation and fibrinopeptide A (FPA) production in a dose-dependent manner. The inhibitory effect of rhsTM was abolished by anti-protein C antibody. The inhibitory effect of rhsTM on clot-induced thrombin generation continued for over 60 min after the addition of the clot, while an active site-directed thrombin inhibitor, argatroban, produced a more transient inhibition. rhsTM also inhibited the regrowth of the clot in (125)I-fibrinogen-supplemented plasma. We also examined the effect of rhsTM by thromboelastography, rhsTM reduced the growth of the clot but had little effect on the time to begin clotting, while heparin and Fragmin (low molecular weight heparin) had effects opposite to those of rhsTM. These findings suggest that rhs-TM attenuates the growth of the clot by activating protein C and inhibiting further thrombin generation in the clot.

Antithrombins↗

PubMed1997

Selection of prognostic factors of acute hepatitis type non-A, non-B for patient listing for liver transplantation.

The aim of this study was to select prognostic factors from information available on admission in order to list patients for liver transplantation before the onset of hepatic encephalopathy in patients with fatal hepatitis type non-A, non-B. Information regarding patient profile and biochemical data obtained on admission was analyzed by multiple stepwise logistic regression, and independent prognostic factors related to death were selected. Four parameters were selected as independent prognostic factors. Patient age (over 50 years), serum total bilirubin level (over 10 mg/dl), peripheral leukocyte count, and prothrombin time were independently related to death. Positive predictive value, negative predictive value, and predictive accuracy were 0.86, 0.79, and 0.84, respectively. Our model is able to predict a patient's fatal outcome much earlier than other currently used models. It will be helpful for early referral to a transplant center.

Adult↗

PubMed1997

CD4+ hepatic cancer-specific cytotoxic T lymphocytes in patients with hepatocellular carcinoma.

We investigated T cell immunity against hepatocellular carcinoma (HCC), and showed that both peripheral blood mononuclear cells and tumor-infiltrating lymphocytes incubated with interleukin-2 alone displayed HLA-nonrestricted but hepatic cancer-specific cytotoxicity in a majority of patients with HCC. Namely, they lysed both HCC and cholangiocellular carcinomas in an HLA-nonrestricted manner, but they did not lyse any tumors with the other histological types tested, normal hepatocytes, or the cells transfected with hepatitis C virus or MUC1 gene. These CTL lines and clones were phenotypically CD3+CD4+CD8-. These unique CTL could play important roles in T cell immunity against HCC.

CD4-Positive T-Lymphocytes↗

PubMed1997

The motor domain and the regulatory domain of myosin solely dictate enzymatic activity and phosphorylation-dependent regulation, respectively.

While the structures of skeletal and smooth muscle myosins are homologous, they differ functionally from each other in several respects, i.e., motor activities and regulation. To investigate the molecular basis for these differences, we have produced a skeletal/smooth chimeric myosin molecule and analyzed the motor activities and regulation of this myosin. The produced chimeric myosin is composed of the globular motor domain of skeletal muscle myosin (Met1-Gly773) and the C-terminal long alpha-helix domain of myosin subfragment 1 as well as myosin subfragment 2 (Gly773-Ser1104) and light chains of smooth muscle myosin. Both the actin-activated ATPase activity and the actin-translocating activity of the chimeric myosin were completely regulated by light chain phosphorylation. On the other hand, the maximum actin-activated ATPase activity of the chimeric myosin was the same as skeletal myosin and thus much higher than smooth myosin. These results show that the C-terminal light chain-associated domain of myosin head solely confers regulation by light chain phosphorylation, whereas the motor domain determines the rate of ATP hydrolysis. This is the first report, to our knowledge, that directly determines the function of the two structurally separated domains in myosin head.

Actins↗

PubMed1997

Nuclear DNA fragmentation and expression of Bcl-2 in primary biliary cirrhosis.

It is uncertain whether or not apoptosis is involved in the pathogenesis of primary biliary cirrhosis (PBC). The aims of this study were to assess the nuclear DNA fragmentation and expression of Bcl-2 in the biliary epithelial cells (BECs) and in the hepatocytes of PBC. Additionally, the effects of ursodeoxycholic acid (UDCA) on DNA fragmentation and Bcl-2 expression in PBC were evaluated. Liver tissue specimens from 35 PBC patients were examined by in situ nick-end labeling to detect any nuclear DNA fragments, and by immunohistochemistry for Bcl-2. Ten of these patients underwent a second liver biopsy after the treatment with UDCA. Sixteen histologically normal liver tissues and 17 chronic viral hepatitis C (CVHC) samples were chosen as controls. DNA fragmentation in BECs was more frequently found in PBC than in CVHC and more frequently than in the normal controls (both P < .05), and fragmentation in the hepatocytes of PBC more frequently than in normal controls (P < .01). Bcl-2 expression was more frequently found in both the BECs and hepatocytes of PBC than in the controls. UDCA significantly decreased the DNA fragmentation in BECs (P < .05) and the positivity for Bcl-2 in BECs (P < .01), although no significant decrease was found in hepatocytes. In conclusion, de novo Bcl-2 expression in hepatocytes of PBC was shown, and the increased nuclear DNA fragmentation and the Bcl-2 expression both in BECs and in hepatocytes may reflect apoptotic stress, although nuclear DNA fragmentation in BECs did not necessarily represent apoptosis. UDCA showed a potential effect of reducing nuclear DNA fragmentation in BECs.

Apoptosis↗

PubMed1997

Relaxing effect of interleukin-1 on rat cultured Ito cells.

Interleukin-1beta (IL-1beta) is closely involved in liver disorders. IL-1beta produces nitric oxide (NO) in vascular smooth muscle cells and relaxes vascular smooth muscle via cyclic guanosine 3',5'-monophosphate (cGMP). In this study, we evaluated the relaxing effect of IL-1beta on cultured Ito cells. Ito cells were isolated from the livers of male Wistar rats and cultured for 24 hours. Immunolocalization of inducible nitric oxide synthase (iNOS) and cGMP and intensity of fluorescence of cGMP were examined using a confocal laser microscope. Ito cells were treated with 0, 200, and 1,000 pmol/L IL-1beta, and the intracellular cGMP concentration was measured after 12 hours. Moreover, Ito cells treated with 200 and 1,000 pmol/L IL-1beta and not treated with IL-1beta were observed over 12 hours, and the area of the same Ito cell was compared before and after the addition of IL-1beta. Next, effects of N(G)-monomethyl-L-arginine (L-NMMA) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) on Ito cell relaxation by IL-1beta treatment were examined. In Ito cells, immunofluorescence of iNOS was observed, and fluorescent intensity of cGMP increased after addition of IL-1beta. Intracellular cGMP concentration increased dose-dependently after addition of IL-1beta. Cell area significantly increased in the IL-1beta-treated group compared with the untreated group. Relaxation of Ito cells by IL-1beta treatment was inhibited by L-NMMA in a dose-dependent manner, but was enhanced by SNAP. These results indicate that IL-1beta produces NO in cultured Ito cells and relaxes the cells via cGMP.

Animals↗

PubMed1997

Pathology of chronic hepatitis C in children. Child Liver Study Group of Japan.

Limited information is available regarding the histology of hepatitis C virus infection in children. The aim of this study was to determine the histological pattern of chronic hepatitis C (CHC) in children, and liver biopsy specimens from 109 pediatric patients with CHC were examined. Each biopsy specimen was evaluated based on a numerical scoring system for the stage of fibrosis (1-4), the grade of portal/periportal necroinflammation (0-4), the grade of lobular necroinflammation (0-4), and their sum (final grade). The histological lesions considered to be characteristic of chronic hepatitis were also evaluated. None of the children had liver cirrhosis, and 105 cases (97%) were stage 1 or 2. Only 4 children were stage 3. Two of these 4 cases showed hemosiderosis. A significant correlation was observed between the staging score and the final grade in the pediatric patients (r = .59; P < .0001). The histological characteristics of adult CHC, such as lymphoid aggregate, bile duct injury, and fatty changes, were also observed in the children. In conclusion, the majority of children with CHC presented with mild fibrosis, but a few showed CHC with lobular distortion and hemosiderosis. Frequent blood transfusion may aggravate hepatic lesions in pediatric CHC.

Adolescent↗

PubMed1997

Immunological evaluation in oral lichen planus with chronic hepatitis C.

Oral lichen planus (OLP) is frequently associated with hepatitis C virus (HCV) infection. We have previously reported that the pathogenesis of OLP arises from host rather than viral factors. In this study, we investigated the role of these factors in 41 patients with chronic hepatitis C: 22 with OLP (group 1) and 19 without OLP (group 2). All patients had antibodies to HCV (anti-HCV) and were serum HCV RNA-positive; none were HBsAg-positive. Immune abnormalities in serum were evaluated by testing for antinuclear antibody (ANA), rheumatoid factor (RF) activity, immunoglobulins (IgG, IgM, and IgA), and cryoglobulin. The rate for ANA positivity and IgM levels were significantly higher in group 1 than in group 2 (P < 0.05). Mean age in group 1 was significantly higher in group 2 (P = 0.0001). Of the factors tested, ANA, IgM, and age, logistic regression showed that age correlated independently with OLP (P = 0.003). In 5 patients in group 1, the infiltrating lymphocytic subsets of the OLP lesion were examined histopathologically. Predominant T cell infiltration was shown in all 5 patients. In addition to host factors, wer also examined viral factors in both groups of patients, measuring serum HCV RNA level and determining HCV genotype. There were no significant differences between the groups in these viral factors. This study suggested that host factors induced by the HCV infection are more important than viral factors in the pathogenesis of OLP associated with hepatitis C.

Chronic Disease↗

PubMed1997

Mechanisms of thrombocytopenia induced by interferon therapy for chronic hepatitis B.

To clarify the mechanisms of thrombocytopenia observed in patients with chronic hepatitis B treated with interferon. We studied six patients with chronic active hepatitis B who received intramuscular injections of natural interferon-alpha (3 or 5 million IU/ day) for 4 weeks. Peripheral blood platelet counts, bone marrow findings, and platelet kinetics, determined using 111In-labeled platelets, were analyzed. Platelets decreased significantly 1 week after the beginning of treatment and remained decreased until the completion of treatment. The number of nucleated cells and megakaryocytes in bone marrow decreased in three of five patients studied during treatment. The kinetic study showed platelet survival time to be 8.1 +/- 1.3 days (range, 5.8-10.0). One day after platelet injection, platelets accumulated predominantly in the splenic area in all patients, whereas hepatic accumulation was predominant 7 days after injection in three of the six patients. Thrombocytopenia during interferon treatment arises from the inhibition of stem cell proliferation and differentiation in the bone marrow and from the capture of platelets by the liver.

Adult↗

PubMed1997

Hepatic stellate cells and intralobular innervation in human liver cirrhosis.

In normal and cirrhotic human liver tissues, we examined immunolocalization of alpha-smooth muscle actin (alpha-SMA), endothelin-1 receptor (ET-1R), and S-100 protein, with special emphasis on the intralobular spaces, using immunohistochemical methods. The ratio of the number of hepatic stellate cells (HSCs) with closely apposing nerve endings to the total number of HSCs in normal livers was compared with that in cirrhotic livers by electron microscopy. Immunolocalization of alpha-SMA and ET-1R was obviously recognized along the sinusoidal walls in cirrhotic liver and was significantly increased in cirrhotic liver compared with that in normal liver. Immunoreactive products for these substances were mainly localized in HSCs. However, immunolocalization of S-100 protein in intralobular spaces was markedly decreased in cirrhotic liver compared with that in normal liver. Nerve fibers were ultrastructurally hardly visible in intralobular spaces of cirrhotic livers. The ratio of the number of HSCs with closely apposing nerve endings to the total number of HSCs was significantly reduced in cirrhotic liver compared with that in normal liver. These results indicate that in liver cirrhosis, alpha-SMA-positive HSCs may play an important role in hepatic sinusoidal microcirculation through vasoactive agents such as ET-1 rather than through intralobular innervation.

Actins↗

PubMed1997

Coordinated expression of integrin alpha6beta1 and laminin in hepatocellular carcinoma.

The interaction between tumor cells and laminin mediated by laminin-binding integrins is critical for tumor invasion and metastasis. The aim of this study was to clarify the altered expression of laminin-binding integrins with the change of laminin deposition in hepatocellular carcinoma (HCC) in comparison with cirrhotic or normal liver by immunohistochemistry. In HCC, hepatoma cells and sinusoidal endothelial cells expressed integrins alpha1beta1, alpha2beta1, alpha3beta1, and alpha6beta1. Integrins alpha1beta1 and alpha6beta1 were detected in a continuous pattern along the sinusoids in accordance with laminin assembly. Integrins alpha2beta1 and alpha3beta1 were detected in a discontinuous pattern at these sites. Integrin alpha6beta4 was not detected. In cirrhotic liver, although integrins alpha1beta1 and alpha6beta1 as well as laminin were detected in a continuous pattern along the sinusoids, integrins alpha2beta1, alpha3beta1, and alpha6beta4 were not detected. In normal liver, although integrin alpha1beta1 was detected in a continuous pattern along the sinusoids, neither integrins alpha2beta1, alpha3beta1, alpha6beta1, alpha6beta4, nor laminin were detected. We have clarified that, of laminin-binding integrins, the localization of integrin alpha6beta1 shows the best correspondence with the localization of laminin. These results suggest that of laminin-binding integrins, integrin alpha6beta1 is very important for cell-laminin interactions in HCC.

Adult↗