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Biomedical subjects

M Masuzawa

Publications and source records attributed to M Masuzawa.

At least 37 records · Page 2Linked to original sources

Reappraisal of biochemical hepatitis C activity in hemodialysis patients.

We reappraised biochemical hepatitis C activity in hemodialysis patients in comparison with normal controls. A total of 111 hemodialysis patients and 66 healthy volunteer blood donors with hepatitis C virus (HCV) infection were consecutively enrolled. Serum alanine aminotransferase (ALT) levels were normal (< or =45 U/L) in 103 (93%) hemodialysis patients and 34 (52%) donors (p < 0.001). HCV viremic levels were lower in the hemodialysis group (p = 0.044), with no difference in the HCV genotype prevalence. During two-year follow-up, 60 (67%) of 90 hemodialysis patients and 13 (26%) of 50 donors showed persistently normal ALT levels (p < 0.001). For hemodialysis patients, however, the upper normal limit of ALT activity was reset at 25 U/L corresponding to the mean + 2 x SD for the normalized ALT distribution in 400 control patients. The adjusted ALT levels were initially normal in 73 (66%) hemodialysis patients and persistently normal in 19 (21%). Thus, ALT levels were the same for the two groups. GB virus C (GBV-C)/hepatitis G virus (HGV) coinfection found only in the hemodialysis group (10/111) had no influence on the disease. A relationship was noted between low disease activity and female gender in both groups. These findings indicate that biochemical hepatitis C activity in hemodialysis patients is similar to that in normal controls and should be monitored based on adjusted ALT levels.

Alanine Transaminase↗

Retreatment with interferon for chronic hepatitis C after transient response.

Approximately half of all patients with chronic hepatitis C show an initial biochemical response to interferon, but only 15% to 20% of patients achieve a sustained response. We studied the efficacy of retreatment with interferon for patients with chronic hepatitis C who showed transient biochemical responses to initial treatment. Thirty patients who relapsed were retreated 1 to 52 months (median 14) after the end of initial treatment, according to the previously used regimens. The responses were correlated with the pre-retreatment patient data. The liver histologic grades, compared with those found before the initial treatment, were better in eight (27%) patients but worse in six (20%), whereas the fibrosis stage was improved in five (17%) but worsened in eight (27%). All patients displayed end-of-retreatment biochemical responses. Of the 30 patients, 10 (33%) achieved sustained aminotransferase normalization and serum hepatitis C virus (HCV) RNA clearance, but the remaining 20 patients showed relapse within 1 year after cessation of retreatment. Univariate analysis associated the sustained response with low pre-retreatment viral loads (0.8 +/- 0.7 MEq/mL vs. 9.1 +/- 6.5 MEq/mL; p = 0.006), short treatment intervals (13 +/- 13 months vs. 22 +/- 14 months; p = 0.031), and low histologic grades (1.3 +/- 0.7 vs. 1.9 +/- 0.7; p = 0.039). However, multivariate analysis indicated that only the pre-retreatment viral load was predictive of the sustained response (p = 0.049). These findings suggest that transient responders to interferon are likely to respond to retreatment but the achievement of a sustained response depends on the HCV viral load before retreatment.

Adult↗

Establishment of a human hemangiosarcoma cell line (ISO-HAS).

A cell line (ISO-HAS) has been established from tumor tissue of a human hemangiosarcoma arising on the scalp by the use of conditioned medium from a murine-phenotypic angiosarcoma cell line (ISOS-1). Cells have been cultured for more than 2 years with up to 100 passages. The cells retained endothelial-cell properties, such as a characteristic cobblestone appearance at confluency, contact-inhibited growth, active uptake of acetylated low-density lipoprotein labeled with 1,1-dioctadecyl 1,3,3,3,3-tetramethyl-indocarbocyanine perchlorate (DiI-Ac-LDL) and CD31 expression. However, they were weakly positive for von-Willebrand-factor (vWf) antigen and for binding of Ulex europaeus agglutinin-I (UEA-I) lectin, and lacked tube-formation activity. These findings indicate that ISO-HAS is a poorly differentiated endothelial cell line. ISO-HAS cells showed accumulation of p53 protein in the nuclei, and a new-typed p53-gene point mutation was found in exon 7 at codon 240. When inoculated s.c. into severe-combined-immunodeficiency (SCID) mice, the cells showed solid-tumor growth that caused death. These properties suggest that ISO-HAS is a malignant endothelial cell line with high tumorigenicity.

Animals↗

Clinical implications of coinfection with a novel DNA virus (TTV) in hepatitis C virus carriers on maintenance hemodialysis.

A novel hepatitis-associated DNA virus, designated as transfusion-transmitted virus (TTV), was identified recently. We investigated the frequency of TTV viremia in hepatitis C virus (HCV) carriers on maintenance hemodialysis to determine whether TTV coinfection has any clinical relevance. The subjects were 50 hemodialysis patients who had been followed over 4 years after diagnosis of HCV infection. Stored serum samples derived from each patient every 12th month after enrollment were subjected to polymerase chain reaction to amplify TTV DNA and HCV RNA. At enrollment, TTV viremia was detected in 24 (48%) HCV-positive patients irrespective of the number of previous blood transfusions and the duration of hemodialysis. The presence of TTV viremia had no relation to serum alanine aminotransferase (ALT) levels, HCV viremic levels or HCV genotypes. After enrollment, HCV infection persisted in all patients over the 4-year follow-up period, whereas spontaneous resolution of TTV infection was observed in 7 (29%) of the 24 TTV viremic cases (annual rate 7.3%, 95% confidence interval [CI] 0.8-25.5%). Evidence for TTV infection was found in 4 (15%) of the 26 TTV nonviremic patients (annual incidence 3.9%, 95% CI 0.1-19. 6%). The relationship between the ALT profile and TTV infection during follow up was not evident. Active TTV coinfection occurs frequently in HCV carriers undergoing hemodialysis but exerts no biochemical or virological influence on the underlying hepatitis C. Lack of disease association and the frequent spontaneous resolution of infection suggest that the clinical significance of TTV infection remains unclear.

Adult↗

Urocortin in human placenta and maternal plasma.

Plasma immunoreactive (IR-) urocortin (Ucn) and corticotropin-releasing factor (CRF) levels in pregnant women were measured by their specific radioimmunoassays after extraction. Although plasma IR-CRF levels were increased in pregnant women as compared to men and non-pregnant women, there was no difference of plasma IR-Ucn levels among groups. Ucn mRNA was detected in cytotrophoblasts and syncytiotrophoblasts by in situ hybridization. A reverse-phase high-performance liquid chromatography (HPLC) showed the major peak of IR-Ucn in placenta and plasma that had similar chromatographic mobility to synthetic Ucn1-40. These data suggest that Ucn is produced and processed into the same form of synthetic Ucn in placenta, but not secreted into maternal blood.

Adult↗

Corticotropin-releasing factor but not urocortin is involved in adrenalectomy-induced adrenocorticotropin release.

Urocortin, a new corticotropin-releasing factor (CRF)-related peptide, has been reported to have the ability to bind to CRF receptors and to stimulate adrenocorticotropin (ACTH) secretion from the rat anterior pituitary in vivo and in vitro. In this study, we examined the effect of intravenous administration of urocortin-antiserum to investigate the role of endogenous urocortin on ACTH secretion from rat anterior pituitary after adrenalectomy. Male Sprague-Dawley rats, which were maintained in a conscious and undisturbed condition, were administered non-immunized rabbit serum (NRS), CRF-antiserum or urocortin-antiserum at a volume of 1 ml/kg b.w. 15 min before the injection of secretagogues. Synthetic rat urocortin (2 microg/kg B.W.) increased plasma ACTH concentrations by about sixfold the basal concentration. The pretreatment with urocortin-antiserum but not CRF-antiserum abolished the urocortin-induced increase in plasma ACTH concentrations. In adrenalectomized rats, plasma ACTH concentrations were markedly increased at basal conditions, and rapidly reduced after the administration of CRF-antiserum. By contrast, administration of urocortin-antiserum did not alter ACTH secretion induced by adrenalectomy. Our results suggest that endogenous urocortin is unlikely to be involved in ACTH release in adrenalectomized rats.

Adrenalectomy↗

Thrombotic thrombocytopenic purpura developed suddenly during interferon treatment for chronic hepatitis C.

A 57-year-old man had abnormal hepatic function identified in April 1994. In October 1994, chronic hepatitis C was diagnosed. Based on the findings of a liver biopsy, administration of recombinant interferon (rIFN)-alpha2b was begun. In the 16th week of treatment, the patient experienced headache and fever and developed a markedly decreased, platelet count and hemolytic anemia. He was admitted on May 19, 1995 and thrombotic thrombocytopenic purpura (TTP) was diagnosed. He died on the 3rd hospital day. The causes of TTP have yet to be elucidated, but in this patient the occurrence of TTP appeared to be related to the IFN treatment for chronic hepatitis C.

Antiviral Agents↗

Distribution and concentration of urocortin, and effect of adrenalectomy on its content in rat hypothalamus.

We developed a specific and sensitive radioimmunoassay (RIA) for rat urocortin (rUcn) and investigated the tissue distribution and concentration of immunoreactive (IR-)Ucn in rats. Antiserum was obtained by immunizing rabbits with synthetic rUcn21-35 coupled with bovine thyroglobulin. 125I-[Tyr]18-rUcn19-37 was used as the tracer. The RIA detected synthetic rUcn1-40 as low as 0.4 fmol/tube, and did not cross-react with other corticotropin-releasing factor-related peptides. IR-Ucn was widely distributed in central nervous system, endocrine organs, and digestive system. Its concentration was highest in pituitary (11.0 +/- 1.36 pmol/g.w.w., mean +/- SEM, n=4). Reverse-phase HPLC revealed that hypothalamic IR-Ucn had similar chromatographic mobility to synthetic rUcn1-40. However, bilateral adrenalectomy did not influence the hypothalamic IR-Ucn content. Our results suggest that Ucn may play important roles in various tissues in normal rats, but not behave as a hypothalamic hypophysiotropic factor in mediating adrenocorticotropin secretion in adrenalectomized rats.

Adrenal Glands↗

Multiple, unique, and common p53 mutations in a thorotrast recipient with four primary cancers.

Four primary cancers found at autopsy of a patient who received the thorium-based contrast agent Thorotrast 50 years ago and who was healthy up until a few months before his death from liver failure were analyzed for p53 mutations. The data suggest that the chronic alpha-irradiation may be a large causative factor. Multiple mutations were found in all the cancer tissues: two foci of a cholangiocellular carcinoma, a tubular adenocarcinoma of the stomach, a squamous cell carcinoma of the lung, and an adenocarcinoma of Vater's ampulla. The total number of point mutations detected were 13. Moreover, homozygous aberrations were detected in a large area of normal small intestine and noncancer liver tissues suggesting that nontumor cells which harbored p53 abnormalities gained a survival advantage and clonally expanded.

Adenocarcinoma↗

Effect of urocortin and its interaction with adrenocorticotropin (ACTH) secretagogues on ACTH release.

We examined the effect of urocortin (Ucn) on the adrenocorticotropin (ACTH) release from cultured rat anterior pituitary cells and AtT 20 cells. Synthetic rat (r)Ucn was not soluble in 0.1 N HCl but soluble in alkaline solvents with diminished corticotropin-releasing activity. rUcn dissolved in 0.1 M sodium phosphate buffer as a stock solution maintained its bioactivity and had the equal corticotropin-releasing activity with rat/human corticotropin-releasing factor (r/hCRF). rUcn stimulated the adrenocorticotropin release via CRF-receptors accompanied by the additive effect with r/hCRF, the synergistic effect with arginine vasopressin and the dose-dependent inhibition of a potent CRF-receptor antagonist.

Adrenocorticotropic Hormone↗

Establishment of a new murine-phenotypic angiosarcoma cell line (ISOS-1).

A cell line, designated ISOS-1, was established from a tumor formed by transplantation of a human angiosarcoma into mice with severe combined immunodeficiency (SCID). The cells showed endothelial properties, based on the uptake of Dil-Ac-LDL and binding of UEA-I/GSA-I lectins, but were negative for CD11b and Pan Cytokeratin. However, the cells lost differentiated characteristics such as expression of von Willebrand factor, contact inhibition growth and tube formation activity. These findings indicate that ISOS-1 is a poorly-differentiated endothelial cell line. At the 81st passage, all of the cells were positive for H-2Dd in various intensity, but not HLA-ABC. The metaphase chromosomes consistently showed a characteristic mouse, but not human, telocentric form. Furthermore, this cell line produced fatal tumor growth in SCID mice and also in BALB/c mice. These results suggest that ISOS-1 is a murine-phenotypic angiosarcoma cell line.

Animals↗

Direct ethanol injection for skull metastasis from hepatocellular carcinoma. The techniques and consequences of a therapeutic trial.

The frequency of skull metastasis from hepatocellular carcinoma (HCC) is increasing together with the recent progress in the management of the primary lesion. Cases are often complicated with poor general conditions or metastasis to the other organs, and not readily indicated for surgery. A direct injection of ethanol to the lesion could be one of the therapeutic options to cope with this complicated situation. To evaluate the feasibility of this technique, we planned a therapeutic trial in a patient with HCC associated with lumbar and skull metastasis, the latter metastasis repeated twice during the past one year. A total of 10 ml of ethanol was injected into the skull metastasis percutaneously under ultrasound (US) guidance. US guidance was very useful in determining the sites of injections and the distribution of ethanol as well as monitoring the blood flow within the tumor vessels. The patient transiently complained of local pain at the injection sites, but there were no other adverse effects. Four days after the injection, the lesion was resected by surgery, which confirmed the pathologic diagnosis as well as the nearly-total necrosis of the tumor. This technique is simple, safe and repeatable with low cost. The technical details and the histologic effects are described.

Aged↗

The analysis of mRNA expression of cytokines from skin lesions in Churg-Strauss syndrome.

We report our recent clinical experience with a patient suffering from Churg-Strauss syndrome and the results of our investigation into the mRNA expression of cytokines in the patient's lesions as well as in the frozen sections from a previous patient. In both cases, blood IgG was at a high level. Cytokine mRNA expression differed according to the degree of cellular infiltration. In the presence of marked infiltration, counteracting Th1 and Th2 cytokines were simultaneously detected; the former included IL-12 and IFN-gamma, and the latter, IL-6 and IL-10. The concurrence of both types of cytokine could be attributed to several factors. For example, IL-6 is involved through some mechanism in the formation of immune complexes by IgG, and IL-12 and IFN-gamma appeared to participate in the development of granuloma. These suppositions support the suggested immunological etiology of the disease. It is also inferred that the dominance of one of the two types of cytokines depends on the clinical phase of the disease.

Biomarkers↗

GBV-C/HGV infection in chronic hepatitis C patients: its effect on clinical features and interferon therapy.

A novel virus (GBV-C/HGV) may be associated with some liver diseases including fulminant hepatitis and acute and chronic hepatitis. On the other hand, many investigations showed that this infection does not contribute to liver disease. GBV-C/HGV has been found to occur in association with infection with other hepatitis viruses. We investigated the effect of GBV-C/HGV infection on the clinical features and interferon treatment in patients with chronic hepatitis C. A total of 262 hepatitis C virus (HCV) RNA positive patients with chronic hepatitis were examined in this study. The detection of serum GBV-C/HGV RNA was done by RT-PCR using specific primers from the NS5 regions. Interferon-alpha was given at a dose of 6 MU/day for 16 or 24 weeks. A responder was defined as a patient with ALT normalization and HCV RNA disappearance after treatment. GBV-C/HGV RNA was detected in 28 (11%) patients. No significant difference was detected in clinical features (age, sex, liver-related biochemical tests, and histological examination) between the 28 GBV-C/HGV-positive patients and the GBV-C/HGV-negative patients. Using interferon therapy for hepatitis C, the responder rates of GBV-C/HGV-positive and -negative patients were 14% and 20%, respectively. Of the 28 patients with GBV-C/HGV RNA, GBV-C/HGV RNA was tested after interferon therapy in 16 and of these GBV-C/HGV RNA was not detected in nine patients after therapy. These findings suggest that GBV-C/HGV infection dose not affect the clinical features in patients with HCV and the efficacy of interferon therapy for chronic hepatitis C.

Adolescent↗

[Results of clinical study with epirubicin hydrochloride injectable solution in hepatoma].

A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with hepatocellular carcinoma. Epirubicin-RTU 60 mg/m2 was injected into the hepatic artery and a three-week drug-free interval followed. Of 15 patients with hepatocellular carcinoma registered in this study, 14 patients were eligible, and they all completed the entire course. The objective was to investigate the safety of treatment with Epirubicin-RTU in 14 eligible patients. The adverse drug reactions frequently observed in these 14 eligible cases were leukopenia, neutropenia, thrombocytopenia, alopecia, and fever. They were all reversible and tolerable. With these results. Epirubicin-RTU was considered to be a safe pharmaceutical product to inject into the hepatic artery.

Adult↗

Endoscopic follow-up study of development of gastric antral vascular ectasia associated with liver cirrhosis.

Gastric antral vascular ectasia is an important cause of chronic gastrointestinal blood loss. However, its development and progression have not yet been clarified. We investigated its early lesions and progression by reviewing endoscopic films of five patients with gastric antral vascular ectasia followed for liver cirrhosis. In all patients, early findings were prepyloric red spots. In two patients, anemia due to gastrointestinal bleeding was already observed when vascular lesions were confined to the distal antrum. In the other three patients, anemia was observed 1-2 years after they showed a diagnostic pattern of gastric antral vascular ectasia. The vascular lesions gradually thickened and extended throughout the antrum, with the complete picture shown in 1.5-5 years. The pattern of distribution was classified into three types: diffuse spotty, diffuse confluent, and striped. These types could be predicted before the complete formation. Gastric antral vascular ectasia associated with liver cirrhosis started as prepyloric red spots and extended to the proximal antrum in various ways and varying time courses of less than 5 years; this entity may cause hemorrhage even in the early stage.

Aged↗

Disease stage of chronic hepatitis C assessed by both peritoneoscopic and histologic findings and its relationship with response to interferon therapy.

BACKGROUND: Disease stage in patients with chronic hepatitis C was assessed by both peritoneoscopy and histology and correlated with responses to interferon therapy. METHODS: The subjects were 105 patients with chronic hepatitis C treated with interferon who were classified into 28 sustained responders, 34 transient responders, and 43 nonresponders according to alanine aminotransferase normalization. The influence of various patient's characteristics on responses to interferon therapy was investigated by multivariate analysis. RESULTS: Patients were categorized into 21 patients who exhibited a "smooth liver" on peritoneoscopy and did not demonstrate histologic bridging fibrosis (group I) and 84 patients who exhibited a "granular" or "nodular liver" on peritoneoscopy and/or had histologic bridging fibrosis (group II). Multivariate analysis showed that genotype 2a/2b (p = .0002), low viremia (p = .0048), and early disease stage (group I) (p = .0290) were significant independent factors contributing to sustained response, and that early disease stage (group I) (p = .0010) and genotype 2a/2b (p = .0085) were those contributing to sustained or transient response. Neither peritoneoscopic nor histologic findings alone were a significant factor influencing responses to interferon therapy. CONCLUSION: Disease stage assessed by both peritoneoscopic and histologic findings may serve as a reliable marker for predicting responses to interferon therapy in chronic hepatitis C.

Adult↗