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Biomedical subjects

S Kakumu

Publications and source records attributed to S Kakumu.

At least 127 records · Page 7Linked to original sources
PubMed1990

Gamma-interferon production in response to hepatitis B core protein and its synthetic peptides in patients with chronic hepatitis B virus infection.

The nucleocapsid of hepatitis B virus (HBV) is an efficient immunogen in activating T cells to produce interferon-gamma (IFN-gamma) in patients with chronic HBV infection. We investigated hepatitis B core antigen (HBcAg)-specific T cell recognition, which seems to be implicated in the pathogenesis of chronic liver disease. IFN-gamma production by peripheral-blood mononuclear cells of patients with chronic HBV infection [25 patients with chronic active hepatitis (CAH) and 14 asymptomatic carriers of HBV (ASCs)] was measured by an enzyme-linked immunosorbent assay. P19 polypeptide, which is derived from recombinant HBcAg particle (rHBcAg), increased IFN-gamma production in patients with CAH, but its effect was weaker than that of rHBcAg. P19 had no stimulating effect on T cells from ASCs. The fine specificity of T cell recognition of HBcAg was examined using 8 kinds of synthetic peptides. T cells from the patients who responded against P19 polypeptide recognized the sites within the common sequences of HBcAg and HBeAg (p72-90, P90-99, P108-122 and P126-146). These results suggest that HBcAg and P19 are cross-reactive at the T cell level, and that these T cells recognize the sites within the common sequences of HBcAg and HBeAg in HBV-infected patients.

Adult↗
PubMed1990

Comparisons of peripheral blood and hepatic lymphocyte subpopulations and interferon production in chronic viral hepatitis.

Studies were undertaken to clarify the immunological mechanism in patients with chronic hepatitis C compared with chronic hepatitis B. Phenotypic study by flow cytometry showed that CD8+ T cells and HLA-DR+ cells isolated from liver biopsy specimen were significantly increased in their proportions as compared with those in peripheral blood, while intrahepatic CD4+ T cells were significantly lower than peripheral blood CD4+ T cells in both types of patients with chronic active hepatitis (CAH). Furthermore two-color analysis revealed that CD8+ CD11- and CD3+ HLA-DR+ cells were significantly elevated in liver tissue than in peripheral blood in both patients groups. In in vitro tests, mononuclear cells obtained from the liver of type B and type C CAH had a reduced capacity to produce IFN-gamma in response to pokeweed mitogen, while they produced equal amounts of IFN-alpha under stimulation with Newcastle disease virus as compared with control peripheral blood mononuclear cells. In contrast, spontaneous productions of both IFNs were greater in liver infiltrates of the two patients groups. These results indicate that functionally activated T cells are distributed in a similar manner in the liver of both chronic hepatitis B and C, suggesting that cytotoxic T cell plays a major role in the hepatocellular injury of both groups of patients.

Adult↗
PubMed1990

Recombinant human alpha-interferon therapy for chronic non-A, non-B hepatitis: second report.

Four million units per day of recombinant human alpha-interferon were administered three times weekly for 16 wk to 26 patients with chronic non-A, non-B hepatitis. The efficacy of therapy was assessed by comparing it with the results in the nontreated patients, or with our previous study in which we administered 2 million units per day of interferon. The treatment was discontinued in four patients 8 wk after start of therapy because there was no improvement in serum aminotransferase levels. The remaining 22 patients completed the treatment schedule, and their aminotransferase values showed significant decreases throughout the therapy and during the follow-up period, compared with their baseline levels or the nontreated group. After 3 months of follow-up, normal aminotransferase activities were seen in eight treated patients. In four of these patients, liver histology showed a marked improvement in inflammation and parenchymal cell necrosis. Percent change from pretreatment level of serum 2',5'-oligoadenylate synthetase activity was significantly higher in the aminotransferase-normalized group than in the nonnormalized group during therapy. The present study suggested that a higher dose of alpha-interferon could control the disease activity more effectively in patients with chronic non-A, non-B hepatitis.

Alanine Transaminase↗
PubMed1989

Hepatitis B core antigen-specific IFN-gamma production of peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection.

To evaluate the specificity of cellular immune response to hepatitis B virus (HBV) Ag in patients with chronic HBV infection, we have measured IFN-gamma production and proliferation of PBMC of 16 patients with chronic active hepatitis (CAH), 17 asymptomatic carriers of HBV (ASC), 6 anti-hepatitis B surface (HBs)-positive subjects, and 6 control individuals with ELISA procedure and [3H]thymidine incorporation. There was no significant increase in the mean proliferative response to recombinant HB surface and core Ag (rHBsAg and rHBcAg), nor was IFN-gamma production elicited with rHBsAg in any group. In contrast, PBMC of HBeAg-positive and anti-HBe-positive CAH patients, and anti-hepatitis B "e" Ag (HBe)-positive ASC showed significantly enhanced IFN-gamma production in response to HBcAg, whereas those of HBeAg-positive ASC and anti-HBs-positive subjects did not respond to HBcAg. The maximal response was observed in a 5-day culture with 500 ng/ml of rHBcAg when assessed by stimulation index value. Monocytes did not demonstrate an increased suppressor or helper activity for IFN-gamma production in these patients. T cell subset fractionation revealed that CD4+ cells were main population of IFN-gamma production specific for HBcAg and CD8+ cells did not suppress IFN-gamma production of CD4+ cells. Furthermore, CD4+ cells of HBeAg-positive ASC generated lesser amounts of IFN-gamma than HBeAg-positive CAH patients did. These results show that the measurement of IFN-gamma production is useful to determine cellular immune response to HBV Ag and suggest that IFN-gamma production depends on the helper activity of CD4+ T cells sensitized to HBcAg.

Epitopes↗
PubMed1989

Tumor necrosis factor alpha production by peripheral blood mononuclear cells of patients with chronic liver disease.

We investigated the production of tumor necrosis factor alpha by peripheral blood mononuclear cells of patients with chronic liver disease and its association with hepatitis activity. Tumor necrosis factor alpha production was measured with an enzyme-linked immunosorbent assay. Tumor necrosis factor alpha production by peripheral blood mononuclear cells stimulated with recombinant gamma-interferon of patients with chronic active hepatitis (5.8 +/- 4.0 units per ml, p less than 0.05) and patients with cirrhosis (4.1 +/- 2.1 units per ml, p less than 0.05) was significantly increased when compared with controls (2.5 +/- 1.6 units per ml). Tumor necrosis factor alpha production by peripheral blood mononuclear cells stimulated with a combination of recombinant gamma-interferon and recombinant interleukin 2 of patients with chronic persistent hepatitis (5.8 +/- 3.8 units per ml, p less than 0.05), patients with chronic active hepatitis (8.9 +/- 3.0 units per ml, p less than 0.001) and patients with cirrhosis (6.7 +/- 3.2 units per ml, p less than 0.05) was significantly increased in comparison with controls (3.3 +/- 1.8 units per ml). Tumor necrosis factor alpha production of patients with chronic active hepatitis was significantly higher than that of patients with chronic persistent hepatitis (p less than 0.05). There was a significant correlation (r = 0.5699, p less than 0.005) between tumor necrosis factor alpha production and histologic activity index in patients with chronic persistent hepatitis or chronic active hepatitis. These findings show that tumor necrosis factor alpha production is increased in chronic liver disease and that the increased tumor necrosis factor alpha production is related to hepatitis activity.

Adjuvants, Immunologic↗
PubMed1989

Interferon alpha and gamma positive mononuclear cells and HLA antigen expression on hepatocyte membrane in the liver in chronic type B and non-A, non-B hepatitis.

To evaluate the role of local interferon on pathogenesis in chronic type B and non-A, non-B chronic hepatitis, we examined the cellular localization of interferon alpha and gamma, and the expression of HLA antigens in cryostat liver sections from 33 chronic carriers of HBs antigen and 10 patients with non-A, non-B chronic hepatitis, using an immunoperoxidase procedure with monoclonal antibodies. Infiltrating mononuclear cells were the main cell element staining positive for interferon alpha or gamma. Among type B chronic liver disease, the percentages of both interferon alpha- and gamma-positive mononuclear cells were highest in patients with chronic active hepatitis, and their levels were higher in patients who had serum HBe antigen, indicating that local expression of interferon closely correlates with activity of disease and virus replication. On the other hand, both the frequency of interferon alpha or gamma positive cells, and the intensity of HLA class I antigens on hepatocytes were much lower in patients with non-A, non-B, chronic active hepatitis in comparison with those with type B chronic active hepatitis. These findings suggested that locally produced interferons have role of varying degrees on the host defence mechanism in chronic hepatitis, reflecting disease activity and the etiology of the disease.

Adult↗
PubMed1989

Recombinant human interleukin 1 alpha is cytotoxic for and increases surface expression of HLA-A,B,C antigens of a human hepatoma cell line, PLC/PRF/5.

Our study was undertaken to determine whether human recombinant interleukin 1 alpha (rIL 1 alpha) has any effect on the proliferation and expression of HLA-A,B,C antigens of human liver cell lines. The addition of rIL 1 alpha reduced the cell number of the human hepatoma cell line, PLC/PRF/5. This effect was determined to be cytotoxic, but not growth inhibitory, rIL 1 alpha did not change the number of Chang cell or SK-Hep-1 at a concentration as, high as 25,000 U/ml. rIL 1 alpha enhanced the expression of HLA-A,B,C antigens on PLC/PRF/5, but had no effect on Change cell or SK-Hep-1. Receptor binding studies showed that 125I-rIL 1 alpha bound to PLC/PRF/5 in a specific and saturable manner, but did not bind to Chang cell or SK-Hep-1. Scatchard plot analysis of the binding to PLC/PRF/5 revealed a single type of high affinity binding site with an apparent dissociation constant of approximately 5 x 10(-5) M and the presence of approximately 150 binding sites per cell. These findings suggest that IL 1 alpha may play a role in host defense against some hepatomas as cytotoxic factor and may be an enhancer of expression of HLA-A,B,C antigens on tumor cells.

Antigens, Neoplasm↗
PubMed1989

Effect of interferon alpha, gamma, and tumor necrosis factor alpha on the HLA-A, B, C expression of cell lines derived from human liver.

Our study was undertaken to determine whether human recombinant interferon alpha(rIFN alpha), gamma(rIFN gamma), and tumor necrosis factor alpha(rTNF alpha) exert an effect on the HLA-A, B, C expression of human liver cell lines. The HLA-A, B, C expression was assayed by immunoperoxidase staining and enzyme-linked immunosorbent assay. rIFN alpha and gamma enhanced the HLA-A, B, C expression of the three cell lines tested, Chang cells, SK-Hep-1, and PLC/PRF/5. The activity of rIFN gamma proved more than 8000 times more potent than that of rIFN alpha in Chang cells, 30 times in SK-Hep-1, and 20 times in PLC/PRF/5, respectively. rTNF alpha also enhanced the HLA-A, B, C expression of the three cell lines. The enhancement of HLA-A, B, C expression by rIFN alpha and gamma reached a peak on day 3, and that by rTNF alpha on day 5. These findings suggest that IFN alpha, IFN gamma, and TNF alpha may play similar roles in enhancement of HLA-A, B, C expression of hepatocytes in hepatitis and hepatoma cells.

Cell Line↗
PubMed1989

Distribution of HBcAg in hepatitis B detected by immunoperoxidase staining with three different preparations of anti-HBc antibodies.

To evaluate the role of the expression of hepatitis B core antigen (HBcAg) in liver cell damage the immunoperoxidase staining pattern of cryostat liver biopsy specimens from 16 chronic carriers of hepatitis B surface antigen (HBsAg) was investigated using three different kinds of anti-HBc antibodies. Polyclonal antibody prepared from recombinant HBcAg seemed to be more sensitive in detecting HBcAg than did monoclonal antibody from the same antigen. The topographical distribution of HBcAg detected by these two antibodies was similar, showing a close correlation to the histological activity of disease. Furthermore, the predominant localisation of cytoplasmic HBcAg usually reflected an active and severe ongoing hepatitis. On the other hand, monoclonal antibody prepared from purified Dane particles resulted in the prominent cytoplasmic staining for HBcAg regardless of histological severity of the hepatitis. The quantitative expression and topographical distribution of HBcAg depended on the type of anti-HBc antibodies used.

Adult↗
PubMed1989

Effects of various cytokines on collagen synthesis by normal rat hepatocytes in primary cultures and fibroblasts.

Collagen formation is an important function of liver parenchymal and nonparenchymal cells that may be relevant to the pathogenesis of hepatic fibrosis. In the present study, the effect of various kinds of cytokines and prednisolone on collagen synthesis by hepatocytes obtained from perfused rat livers and confluent human skin fibroblasts were investigated. The cells were cultured in serum-free medium for 24 h with [3H]proline and various additives. The amounts of collagen and noncollagen protein synthesis were calculated from the incorporation of [3H]proline into collagen-sensitive and collagen-resistant proteins. The additions of interleukin 1 alpha, interleukin 1 beta and transforming growth factor alpha enhanced both collagen and noncollagen protein synthesis by hepatocytes as well as by fibroblasts. Transforming growth factor beta also increased both collagen and noncollagen protein synthesis by fibroblasts while it selectively inhibited collagen synthesis by hepatocytes. Interferon preparations and prednisolone showed a selective suppression of collagen synthesis by both cells, indicating that these additives did not affect either cell viability or proliferation during the observed period. These results suggest that collagen synthesis by liver parenchymal cells is either positively or negatively modulated by various kinds of cytokines and hormone.

Animals↗
PubMed1989

Serum levels of alpha-interferon and gamma-interferon in patients with acute and chronic viral hepatitis.

We measured activities of alpha- and gamma-interferon simultaneously in 198 sera of 70 patients with acute and chronic viral hepatitis using specific and sensitive enzyme immunoassay and immunoradiometric assay. The results were compared with those in patients with influenza and in healthy controls. Twelve out of 28 patients with acute viral hepatitis showed positive alpha-IFN and/or gamma-IFN activities. alpha-IFN was detectable throughout the clinical course while gamma-IFN levels rose in the convalescent phase regardless of etiology. Conversely, in patients with influenza, both alpha-IFN and gamma-IFN levels of initial samples tended to be higher than those of late samples. Six out of 12 patients with chronic active type B hepatitis showed increased alpha-IFN and/or gamma-IFN values during acute deterioration with marked elevation of serum alanine aminotransferase. However, the two interferons did not always appear simultaneously, although either was detectable in both acute and chronic hepatitis. Enhanced alpha-IFN or gamma-IFN activity was not found in asymptomatic chronic hepatitis B carriers or in patients with chronic persistent hepatitis and liver cirrhosis with chronic hepatitis B virus infection, with the exception of 2 cases. Our results indicated that circulating multiple IFN species were present during the clinical course in some patients with acute and chronic viral hepatitis.

Acute Disease↗
PubMed1989

Pilot study of recombinant human alpha-interferon for chronic non-A, non-B hepatitis.

Recombinant human alpha-interferon was administered to 15 patients with chronic non-A, non-B hepatitis as a part of a pilot study. Patients received injections of 2 million units per day of interferon three times weekly for 16 wk. The treatment schedule was completed in all but one, whose serum aminotransferase levels were continuously elevated during treatment. In seven of the 15 patients, elevated serum aminotransferase levels decreased rapidly during therapy and eventually fell into the normal or nearly normal range. However, once the therapy was stopped, a prompt return of aminotransferase levels to pretreatment values usually was observed. After 3 months of follow-up, aminotransferase activities remained normal in only two patients in whom liver histology showed marked improvement in intralobular degeneration and focal necrosis of hepatocytes. Anti-interferon antibody was detected in four patients at the end of therapy, and decreased 2',5'-oligoadenylate synthetase activity occurred in two patients and in another with relapsed aminotransferase level. Whether alpha-interferon therapy could control the disease activity in patients with chronic non-A, non-B hepatitis deserves further evaluation in a prospective controlled trial.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

Pre-S proteins in chronic hepatitis B virus infection: markers of active viral infection.

The role of large (pre-S1) and middle (pre-S2) proteins of HBsAg in hepatitis B virus (HBV) infection is not fully known. Therefore, we studied the expression of pre-S proteins in the liver and serum of 26 patients with chronic HBV infection, using immunoperoxidase staining and enzyme immunoassay. Pre-S1 and pre-S2 proteins were detected in a large number of patients in both liver and serum, irrespective of the disease activity. Serial sections showed that most cells positive for HBsAg were also positive for pre-S proteins. The localization of pre-S2 and HBsAg was similar, with cytoplasmic and membranous stainings of hepatocytes, whereas pre-S1 was expressed exclusively in cytoplasm. Serum levels of HBsAg, pre-S1, and pre-S2 of DNA polymerase-positive cases were significantly higher than those of DNA polymerase-negative cases. Membranous display of pre-S2 on hepatocytes was observed more often in DNA polymerase-positive patients, and their serum pre-S2 levels were significantly higher than those without it. The predominant localization of cytoplasmic HBcAg usually was associated with active, ongoing hepatitis. Its expression and DNA polymerase activity were significantly correlated. These results indicate that pre-S proteins in serum and the membranous display of pre-S2 on hepatocytes of patients with chronic HBV infection refect active viral replication, but their expression does not correlate with disease activity.

Hepatitis B↗
PubMed1989

[Usefulness of ultrasonography-guided fine needle aspiration cytology in a case of jejunal leiomyosarcoma].

The patient was a 45-year-old man with the symptoms of abdominal pain and constipation. Laboratory data showed no remarkable changes. Ultrasonic and CT-scan examinations revealed a mass deeply situated in the abdominal cavity. Ultrasonography guided needle aspiration cytology was performed. Obtained specimen showed a large cluster accompanied by numerous smaller clusters, and dispersed single cells. Most of cells were spindle in shape with abundant cytoplasm, and uniform in size. These cells have moderately hyperchromatic nuclei with finely granular pattern, which were round or oval, and have tiny nucleoli. Some cells were binucleated. The nuclear membrane was sharp and well preserved. Giant cells or mitotic figures were not observed. As a result, cytological diagnosis was "suspicious of leiomyosarcoma". The tumor was resected. The specimen consisted of a segment of the jejunum with an irregularly-shaped, and reddish soft first-sized mass continued to jejunum muscle layer. The cut surface of the mass showed central cavitation and necrosis in part. Histological diagnosis was well differentiated leiomyosarcoma originated from the jejunum. The tumor was composed of smooth muscle like cells arranged in bundles with some bizarre multinucleated cells and rare mitotic figures.

Biopsy, Needle↗
PubMed1989

Occurrence of immunohistochemically detected small Mallory bodies in liver disease.

To determine the diagnostic significance of immunohistochemically detected small Mallory bodies (MBs) which are invisible by conventional stainings, we investigated the occurrence of MBs in liver tissue with alcoholic and nonalcoholic liver disease by immunoperoxidase staining with monoclonal anti-MB antibody, anti-NMB-3. In conventional stainings, MBs were detected in only six of 26 (23%) patients with alcoholic liver disease, and nine of 63 (14%) patients with nonalcoholic liver disease. On the other hand, MBs were detected in 20 of 26 (77%) patients with alcoholic liver disease, and 25 of 63 (40%) patients with nonalcoholic liver disease by immunoperoxidase staining. Immunohistochemically detected MBs were shown to possess the ultrastructural characteristics of MBs by immunoelectronmicroscopy in the four specimens. Our result indicates that the small MBs are not rare in nonalcoholic liver disease, and the presence of immunohistochemically detected small MBs is not a good marker of an alcoholic etiology.

Adolescent↗
PubMed1988

Interleukin 2 receptor bearing T lymphocytes in patients with chronic liver disease.

We investigated the role of interleukin 2 receptor expression (IL 2R) on T cell in chronic liver disease. IL 2R was determined by analysing T cell surface Tac antigen with anti-Tac, a monoclonal antibody that binds at or near the binding site for IL 2, using a fluorescence-activated cell sorter. The percentage of Tac+ cells in T cell fraction from peripheral blood mononuclear cells in unstimulated cultures was 7.9 +/- 2.1% (+/- SD) in controls. A similar value was obtained in asymptomatic carriers of HBsAg (ASC), in patients with chronic active hepatitis (CAH) and liver cirrhosis (LC). Upon stimulatin with recombinant IL 2, there was a small but significant increase in Tac+ cells. The percentages of Tac+ cells in IL 2-stimulated cultures were significantly lower in ASC (P less than 0.01), patients with CAH (P less than 0.01) and LC (P less than 0.05) as compared to controls (16.4 +/- 4.4%). Percentages of Tac+ cells after stimulation with phytohemagglutinin P (PHA-P) in ASC and CAH did not differ from controls (74.9 +/- 5.9%). Only patients with LC showed diminished Tac+ cells (P less than 0.01) compared to controls. During a 4-wk course of recombinant IL 2 therapy, a serial study on 5 HBeAg-positive patients with CAH was done, and the results showed that Tac+ cells were significantly diminished 2 wk (P less than 0.01) and 4 wk (P less than 0.05) after starting therapy in comparison with pretreatment levels in IL 2-stimulated cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

An outbreak of foodborne hepatitis A in a factory: a possible shift in age of patients in Japan.

We investigated extensively an outbreak of hepatitis A at a factory in suburban Nagoya. Epidemiological study indicated a foodborne outbreak by a supplier of lunches. Serologically, all the employees younger than 30 years of age had been susceptible to hepatitis A virus, but the highest morbidity was observed in the 40-44 age group. The age difference in morbidity from foodborne hepatitis and susceptible populations suggests a shift in mean patient age linked to a shift in antibody prevalence to hepatitis A virus. In communities where the prevalence started shifting after development of sanitary systems, effective prophylaxis for foodborne hepatitis A will be necessary to prevent the disease in an increasing number of older patients in a few decades.

Adult↗