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Biomedical subjects

M Masuzawa

Publications and source records attributed to M Masuzawa.

At least 55 records · Page 3Linked to original sources

Conversion of the CD4+ T cell profile from T(H2)-dominant type to T(H1)-dominant type after varicella-zoster virus infection in atopic dermatitis.

Skin lesions of atopic dermatitis were examined for cytokine expression by reverse transcription-polymerase chain reaction. The profile of mRNA for various cytokines revealed that both T(H1) and T(H2) types of CD4+ T cells, probably including T(H0) type, infiltrate into the skin lesion. We observed that atopic skin lesions improved after varicella infection. In such lesions, expression of T(H1) type cytokines predominated. The peripheral blood T cells from atopic patients exhibited a differentiation into T(H2) type cells upon in vitro stimulation with mite antigen. In contrast they differentiated into T(H1) type cells upon stimulation by varicella antigen. Since IL-12 has been reported to switch the in vitro recall response of allergen-specific T cells of atopic donors from a T(H2)- to a T(H1)-like phenotype, we examined its local production in varicella lesions. IL-12 p35 and p40 mRNA were expressed in fresh lesions. Peripheral blood mononuclear cells from atopic patients expressed p40 mRNA upon in vitro stimulation with live varicella zoster virus, but they did not show p40 mRNA without stimulation. This finding suggested that in atopic skin lesions containing the virus, IL-12 was produced and the cell type was changed to T(H1) type-predominance. These results suggested that patients with atopic dermatitis always have highly reactive CD4+ T cells infiltrating into their skin, and that the switch to T(H1) or T(H2) dominance is related to whether the lesion is improved or exacerbated.

Antigens, Viral↗

Circulating matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 as serum markers of fibrosis in patients with chronic hepatitis C. Relationship to interferon response.

BACKGROUND/AIMS/METHODS: The imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is considered to be an important determinant of extracellular matrix deposition and breakdown. We measured serum MMP-1, MMP-2, TIMP-1 and TIMP-2 levels using the respective one-step sandwich enzyme immunoassays in 98 patients with chronic hepatitis C treated with interferon beta to examine their clinical significance for assessment of liver histology and to determine whether they can be useful as predictors of the interferon response. RESULTS: Serum TIMP-1 levels showed a positive correlation with the degree of fibrosis (r(s)=0.30, p= 0.004). Serum MMP-2 levels revealed positive relationships with the degree of periportal necrosis (r(s)= 0.32, p=0.002), the degree of fibrosis (r(s)=0.26, p= 0.01) and total score of histological activity index (r(s)=0.24, p=0.02). Serum MMP-2 levels were significantly higher in patients with no response than in those with sustained and transient response (p<0.01 and p<0.05, respectively), while serum MMP-1 levels did not differ among the three groups. Compared with the levels in sustained responders, the total amounts of serum TIMP-1 were significantly lower in transient responders and non-responders (p<0.01 and p<0.001, respectively). As for serum TIMP-2 levels, a significant decrease was found in transient responders and non-responders (p<0.01). The ratios of serum MMP-2 to TIMP-1 levels were significantly higher in transient responders and non-responders than in sustained responders (p<0.001, respectively) even when HCV RNA levels were low in patients with HCV genome subtype 1b or when the HCV genome subtype was 2a or 2b. Sustained response was never found in type 1b patients with ratios of serum MMP-2 to TIMP-1 levels of over 6.0. In logistic multivariate regression analysis, the ratios of serum MMP-2 to TIMP-1 level (p=0.0001), HCV genome subtype (p=0.005) and serum TIMP-2 level (p=0.03) were the independent predictors for sustained response, while serum MMP-2 level (p=0.0006) was the only predictor for no response. CONCLUSIONS: Serum MMP-2 and TIMP-1 levels might be useful for estimating the degree of liver fibrosis. The ratio of serum MMP-2 to TIMP-1 levels may serve as a new predictor of interferon response in patients with chronic hepatitis C.

Alanine Transaminase↗

Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized, controlled clinical trial was conducted to compare the use of epirubicin (EPI) and doxorubicin (DOX) in Lipiodol (Laboratoire Guerbet, Roissy-Charles-de-Gaulle Cedex, France)-transcatheter arterial chemoembolization as a treatment of hepatocellular carcinoma. One hundred ninety-two hospitals participated, and 415 patients were enrolled in the study during the period between October 1989 and December 1990. The patients were randomly allocated to group A (EPI) or group B (DOX) by a centralized telephone registration. The actual doses of EPI and DOX were 72 mg/body and 48 mg/body, respectively. The 1-, 2-, and 3-year survival rates were, respectively, 69%, 44%, and 33% for group A and 73%, 54%, and 37% for group B. There were no statistically significant differences (P = .2296, log-rank test). When each group of patients was classified retrospectively into high-risk and low-risk subgroups based on the severity index calculated by the Cox regression model from the significant prognostic factors (the pretreatment tumor size, the pretreatment serum alpha-fetoprotein level, tumor encroachment, and Child's classification), the survival curve of the low-risk DOX subgroup was significantly superior to that of the low-risk EPI subgroup (P = .0182). However, there was no significant difference between the high-risk subgroups (P = .4606). The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction after the treatment did not show any significant differences between the groups. The white blood cell count in group B showed a tendency to decrease slightly more than in group A at 3 weeks after Lipiodol-transcatheter arterial chemoembolization. In conclusion, there was no statistically significant difference between the survival curves of the EPI and DOX groups in Lipiodol-transcatheter arterial embolization treatment of hepatocellular carcinoma.

Adult↗

Evaluation of combined therapy with chemoembolization and ethanol injection for advanced hepatocellular carcinoma.

To evaluate the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol injection therapy (PEIT) for advanced hepatocellular carcinoma, we studied the effectiveness of TACE therapy combined with PEIT (50 cases) and TACE alone (50 cases). In both groups, patients had multiple lesions, or a single lesion with a diameter exceeding 2 cm or with vascular invasion (stages II, III, and IV in the tumor staging classification of the Liver Cancer Study Group of Japan). The clinical features in the two groups were comparable. The cumulative survival rates with TACE-PEIT were 95.0% for 1 year, 72.5% for 2 years, and 50.0% for 3 years, whereas the rates with TACE alone were 92.5% for 1 year, 57.5% for 2 years, and 20.0% for 3 years. The survival rate in the TACE-PEIT group was significantly higher than that in the TACE alone group. Moreover, the survival rate of patients with stage II or III disease in the TACE-PEIT group was significantly better than that in the TACE alone group, and the survival rate of patients with Child's classification B or C in the TACE-PEIT group was significantly higher than that in the TACE alone group. Multivariate analysis using Cox's proportional hazard regression model showed that the most significant prognostic factors in the TACE-PEIT group were tumor embolus in the portal vein and the number of tumors. These results suggest the effectiveness of combining TACE and PEIT for the treatment of advanced hepatocellular carcinoma.

Antibiotics, Antineoplastic↗

Long-term biochemical and virological response to natural interferon-alpha in patients with chronic hepatitis C.

To determine the long-term response to interferon-alpha, 134 patients with chronic hepatitis C were followed for more than a year after therapy. Follow-up was stopped for 14 patients and 43 patients received retreatment. The remaining 77 patients were followed for 26-46 months, and 39 of them achieved long-term sustained alanine aminotransferase (ALT) normality. This normality was achieved in 35/38 short-term sustained responders, which was significantly higher (P < 0.001) than in the short-term relapsers (2/38) and the short-term nonresponders (2/44). Hepatitis C virus (HCV) RNA remained negative in 27 (73%) of 37 patients in the long-term sustained ALT normality group. However, only one (1.6%) of 63 long-term responders was negative for HCV RNA. The results of HCV RNA testing for the long-term period agreed with those at three to six months after therapy. Serum ALT levels during the first six months after therapy and HCV RNA testing at three to six months after therapy are important for predicting long-term sustained ALT normality and HCV RNA negativity.

Adult↗

Local expression of IFN-gamma mRNA in skin lesions of patients with dermatophytosis.

Delayed type hypersensitivity (DTH) response to dermatophyte antigens is one of the host defense mechanisms in dermatophytosis. Skin lesions of dermatophytosis were examined for the cytokine mRNAs expression using the reverse transcriptase/polymerase chain reaction (RT-PCR) method. Interferon-gamma (IFN-gamma) mRNA was expressed in all of the dermatophytosis lesions. IFN-gamma plays an important role in the effector phase of the DTH reaction. Therefore, these findings indicate that DTH response is elicited in the skin lesions with dermatophytosis.

Adult↗

An endoscopic follow-up study of the development of diffuse antral vascular ectasia.

No endoscopic follow-up studies are available on the development of diffuse antral vascular ectasia (DAVE). We present here a ten-year follow-up study from discrete initial lesions to the full picture of DAVE. In a 72-year-old female patient with liver cirrhosis, the earliest findings of DAVE were several red spots, with or without a white halo, in the distal antrum. During follow-up, the spots increased in number, coalesced, and extended to the proximal antrum. Three years after the initial findings, latent hemorrhage occurred at a time when confluent lesions were formed. One year later, diffuse distribution of the antral lesions was observed, which led to the diagnosis of DAVE and developed to the full picture within three more years. Two years later, the patient presented with hematemesis, which confirmed the diagnosis of DAVE clinically. Treatment consisted of monopolar electrocoagulation, leading to a stable hemoglobin value for one year. This case study provides some substantial clues to the early detection and treatment of DAVE.

Aged↗

Treatment with recombinant interferon-alpha 2a for patients with chronic hepatitis C: predictive factors for biochemical and virologic response. Osaka Liver Disease Study Group.

BACKGROUND: The heterogeneity of the hepatitis C virus (HCV) genome has been reported to be associated with the effectiveness of interferon therapy. We investigated the correlation of the viral and host factors, including the degree of sequence complexity of the HCV genome for responses to interferon-alpha in patients with chronic hepatitis C. METHODS: Ninety-seven patients received a 26-week course of recombinant interferon-alpha 2a therapy. The sequence complexity of the envelope 1-2 region was evaluated by polymerase chain reaction-mediated single-strand conformation polymorphism (PCR-SSCP) analysis. RESULTS: Of the 85 patients who completed the treatment, 31 (36%) achieved a sustained response, and 28 (33%) showed a sustained loss of HCV RNA. A low HCV RNA level, determined by the branched DNA probe assay, and serotype group 2 HCV correlated with a sustained response. In patients with serotype group 1 HCV of more than the threshold of the branched DNA probe assay, a band number on PCR-SSCP analysis of more than 2 could be associated with inefficacy of interferon therapy. Multivariate analysis in the 50 patients whose sera were available for all the virologic tests showed that only the HCV RNA level is independently predictive of a sustained response. CONCLUSIONS: Determination of the HCV RNA level is most important for predicting the response before interferon therapy. PCR-SSCP analysis may be useful as an additional test for patients with a high HCV RNA level of serotype group 1 HCV.

Adult↗

Long-term follow-up of hepatitis B virus and hepatitis C virus replicative levels in chronic hepatitis patients coinfected with both viruses.

Dual infection with hepatitis B and C viruses is often encountered in endemic areas of both viruses. However, understanding of the clinical and virological implications is limited. The aim of this study was to investigate the role of each virus in liver injury and the interaction between the two viruses in dual infection with hepatitis B and C viruses. Three patients who had chronic infection with both hepatitis B and C viruses were examined, and a longitudinal study of both serum hepatitis B virus DNA and hepatitis C virus RNA levels over 4 years was undertaken. The results were correlated with serum alanine aminotransferase levels. Serum alanine aminotransferase values showed a relationship with hepatitis B virus replicative levels, but not with hepatitis C virus replicative levels in all 3 patients. Serial changes of replicative levels of both viruses were studied, and it was found that hepatitis C virus replicative levels were enhanced after the decline of hepatitis B virus replication in 1 of the 3 patients. In the remaining 2 patients, a transient rise of hepatitis C virus replicative levels in association with a decrease of hepatitis B virus replication was also observed during part of the follow-up period. These findings indicate that hepatitis B virus may play a dominant etiological role in liver injury, and that a suppressive action between hepatitis B and C viruses may occur in dual infection with both viruses.

Adult↗

Electron microscopic observations of epithelioid cell granulomas experimentally induced by prototheca in the skin of mice.

Electron microscopic analysis was conducted on epithelioid cell granulomas experimentally induced by prototheca in the skin of mice. In BALB/c mice, epithelioid cell granulomas were easily induced. Each cell had a round nucleus with euchromatin on the margin, abundant cytoplasmic organelles, and particularly abundant rough endoplasmic reticulum (rER). Cells with a plasmacytoid appearance were the most common. Fibroblast-like epithelioid cells were sometimes observed. The whole body and cell membrane of an organism was usually within the cytoplasm of epithelioid cell. In ICR mice, epithelioid cell granulomas were not easily induced. Cells which had ingested whole organisms had spindle shaped and/or oval nuclei with marginated heterochromatin and with abundant dilated rER. Near completion of organism digestion, the cells had irregular and/or indented nuclei with marginated heterochromatin and often one or two distinct nucleoli. The cytoplasm was often replaced with numerous phagocytic vacuoles. At higher magnification, secondary lysosomes and Golgi complexes forming Golgi lamellae could be seen in the cells in which cytoplasmic organelles such as endoplasmic organelles and mitochondria were abundantly present. In contrast to the BALB/c mice, the remnants of digested organisms, split up into many small pieces, could be seen in the cytoplasm. The cells with a fibroblast-like appearance were most frequent, but plasmacytoid cells were sometimes observed. In the present study, the ultrastructural features of epithelioid cells in BALB/c and ICR mice clearly differed. Plasmacytoid cells were the most abundant in BALB/c mice, while fibroblast-like cells were in ICR mice.

Animals↗

Epithelioid cell granulomas experimentally induced by prototheca in the skin of mice: a light microscopic study.

Prototheca wickerhamii, an achlorophyllous algae, was previously found to induce massive epithelioid cell granulomas in the skin of mice. By means of light microscopy, examination was made of the histological reactions involved in epithelioid cell granulomas induced by intradermal and/or subcutaneous inoculation of Prototheca wickerhamii in BALB/c and ICR mice. Six BALB/c mice showed granuloma nodules while only three of six ICR mice did so. Based on the results of the present and previous studies, BALB/c mice may be considered a strain particularly vulnerable to contracting epithelioid cell granuloma and ICR mice, a resistant strain. In very early lesions at one week following initial prototheca inoculation, cellular infiltration with varying numbers of polymorphonuclear leukocytes, lymphocytes and some macrophages was observed throughout the dermis and subcutaneous fat tissue. In early lesions at one to two months after inoculation, focal granulomas composed of histiocytic cells and/or macrophages were observed. Mast cells were occasionally present among the histiocytic cell infiltrates. In the granulomatous lesions at two to three months, scattered eosinophils and some lymphocytes were seen. Central necrosis, with numerous neutrophils and many endospores surrounded by the granuloma, was often observed. In late stage lesions at six months, massive lymphocyte and plasma cell infiltration surrounding and/or intervening between vacuolated epithelioid cell clusters was evident. Histological reactions in epithelioid cell granuloma and the ultimate course of this disease can be staged from the histological point of view as follows: 1) diffuse inflammation, 2) cell proliferation leading to epithelioid cell formation, 3) hypertrophy of epithelioid cells with consequent formation of cell aggregates and/or organized granuloma and 4) degeneration of granuloma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ability of prolonged interferon treatment to suppress relapse after cessation of therapy in patients with chronic hepatitis C: a multicenter randomized controlled trial.

The aim of this study was to determine whether 12 months course of interferon alfa (IFN-alpha) therapy could improve the beneficial effect of IFN in chronic hepatitis C. Eighty-eight patients were treated with natural IFN-alpha for either 28 weeks (45 cases) or 52 weeks (43 cases). Sustained response was achieved in 15 (33.3%) of 45 cases treated for 28 weeks and in 23 (53.5%) of 43 cases treated for 52 weeks. Transient response with relapse of alanine transaminase (ALT) after completion of therapy was observed in 13 cases (28.9%) treated for 28 weeks and in 4 cases (9.3%) treated for 52 weeks. Thus, ALT relapse was suppressed by prolonged IFN treatment. No response was found in 17 cases (37.8%) treated for 28 weeks and in 16 cases (37.2%) treated for 52 weeks, indicating that approximately 38% of the patients with chronic hepatitis C were resistant to IFN therapy even with prolonged treatment. The rate of sustained response was significantly higher in patients with type 2a or 2b than in those with type 1b. Even in type 1b cases, it was higher in the 52-week treatment group than in the 28-week treatment group, and the rate of transient response was lower in the 52-week treatment group, indicating that relapse in type 1b cases was suppressed by prolonged IFN therapy. IFN therapy was not effective for patients with advanced liver fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Serial quantitative analysis of serum hepatitis C virus RNA level in patients with acute and chronic hepatitis C.

To examine changes in the serum level of hepatitis C virus RNA in acute and chronic phases of hepatitis C virus infection, we tested serial serum samples of six patients with acute hepatitis C (posttransfusion: three; sporadic: three) and 11 patients with chronic hepatitis C using a competitive reverse transcription and polymerase chain reaction assay. The internal standard consisted of known amounts of synthetic mutated RNA. No patient with acute hepatitis showed resolution during the follow-up period (24-57 weeks). In posttransfusion cases, titers of hepatitis C virus RNA (log10[hepatitis C virus RNA copies/ml serum]) rose to a high level (7.5-9.5) in the early phase of infection (4-12 weeks after the transfusions) in association with the first serum alanine aminotransferase peaks. Titers of hepatitis C virus RNA then decreased, while serum alanine aminotransferase levels fluctuated with multiple peaks. In sporadic cases, titers of hepatitis C virus RNA had already reached a high level (7.0-7.5) at the first alanine aminotransferase peaks 2-3 weeks after the clinical onset. In chronic hepatitis C virus infection, titers of hepatitis C virus RNA remained high for follow-up periods of 6-12 years in patients with chronic active hepatitis. These results indicate that the replication of hepatitis C virus rose to a high level in the early phase of infection and that a high replicative level of hepatitis C virus might be related with progression of liver disease in the chronic phase of infection.

Acute Disease↗

Hepatitis C virus antibody and hepatitis C virus replication in chronic hepatitis B patients.

We assessed hepatitis C virus infection in 156 chronic hepatitis B patients using second-generation hepatitis C virus antibody (anti-HCV). Active virus replication was further investigated in anti-HCV-positive cases by means of polymerase chain reaction assay for the detection of serum hepatitis C virus RNA. Anti-HCV prevalence was higher in patients negative for hepatitis B e antigen (HBeAg) (10/48, 21%) than in HBeAg-positive patients (10/108, 9%) (p < 0.05), and the reactivity (cut-off index) in anti-HCV enzyme-linked immunosorbent assay of the positive cases was significantly higher in HBeAg-negative patients (4.1 +/- 0.1) than in -positive ones (3.6 +/- 0.6) (p < 0.05). The prevalence of hepatitis C virus RNA in anti-HCV-positive cases was also higher in the HBeAg-negative group (9/10, 90%) than in the -positive group (3/10, 30%) (p < 0.01). Viremia was found in association with high reactivity in anti-HCV ELISA (cut-off index > 3.5) in both groups. Nine (90%) of 10 such cases were viremic in the HBeAg-negative group compared with three (43%) of seven in the HBeAg-positive group (p < 0.05). These results suggest that hepatitis C virus replication may be influenced by hepatitis B virus replicative states, indicating possible interference between hepatitis B and C viruses.

Adult↗