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Biomedical subjects

C M Chu

Publications and source records attributed to C M Chu.

At least 145 records · Page 8Linked to original sources

Integration of HBV-DNA may not be a prerequisite for the maintenance of the state of malignant transformation. An analysis of 110 liver biopsies.

Hundred and ten liver biopsy specimens from various parts of the world were examined for episomal and integrated HBV-DNA sequences. In 54 patients with HBsAg chronic liver disease episomal HBV-DNA was found in 83% of HBeAg-positive patients, compared to only 22% of patients with anti-HBe. Furthermore episomal HBV-DNA in the latter predominated among the Asians. Integrated HBV-DNA was found only in 5.5% of HBeAg-positive patients but in 16.5% of patients with anti-HBe. In 28 HBsAg-positive patients with hepatoma, episomal HBV-DNA was found in 50% of HBeAg-positive patients but in only 11% of anti-HBe patients. Conversely integrated sequences were less common (25%) in HBe-Ag-positive patients than in anti-HBe patients (50%), giving an overall incidence of integration in this group of 45%. No episomal, and only one case of integrated sequences of HBV-DNA, could be detected among 10 patients with HBsAg-negative hepatoma. In addition neither episomal nor integrated HBV-DNA could be detected in 18 patients with non-HBV-related liver disease. Our data suggests that stable integration of HBV-DNA into the host's genome is not necessarily a prerequisite for the maintenance of the state of malignant transformation but may be necessary for its initiation. Alternatively, the detection of integrated HBV-DNA may represent a 'snap shot' of a random integration event amplified by clonal expansion promoted by other factors.

Base Sequence↗

The role of delta superinfection in acute exacerbations of chronic type B hepatitis.

Serum specimens collected from patients with chronic type B hepatitis during their acute exacerbations were studied with radioimmunoassay for serological markers of delta (delta) agent infection. Serum delta antigen was negative in all 56 hepatitis B e antigen (HBeAg)-positive and 25 anti-HBe-positive acute exacerbations. Two (3.6%) HBeAg-positive and five (20%) anti-HBe-positive acute exacerbations were found to be positive for both IgG anti-delta and IgM anti-delta. The incidence in anti-HBe-positive patients was significantly higher than in HBeAg-positive patients. These results indicated that some of the acute exacerbations, particularly in anti-HBe-positive phase, could be attributed to delta-superinfection. However, acute exacerbations preceding HBeAg/anti-HBe seroconversion were not associated with delta-superinfection.

Hepatitis Antibodies↗

Alpha-fetoprotein changes in the course of chronic hepatitis: relation to bridging hepatic necrosis and hepatocellular carcinoma.

To examine the frequency and significance of alpha-fetoprotein (AFP) elevation, radioimmunoassay for AFP was performed every 3-6 months in a prospective follow-up study on 432 hepatitis B surface antigen (HBsAg)-positive and 105 HBsAg-negative patients with clinicopathologically proven chronic hepatitis. In a period of 6-85 months (mean 26.9 +/- 16.8), AFP elevation (greater than 20 ng/ml) was recorded in 45.6% of the HBsAg-positive patients. In addition, 19.4% of the HBsAg-positive patients had AFP levels greater than 100 ng/ml, with a highest level of 2520 ng/ml in the absence of hepatocellular carcinoma (HCC). All these figures were much greater than those for HBsAg-negative patients (P less than 0.001). Most episodes of AFP elevation were transient, with parallel moderate SGPT elevation (greater than 200 IU/L). The AFP levels in such episodes correlated closely with the presence of bridging hepatic necrosis, only weakly with peak SGPT levels, but not with age, sex or hepatitis B e antigen/antibody status. None of the transient episodes was followed by subsequent development of HCC. On the other hand, AFP elevation (greater than 100 ng/ml) without parallel SGPT elevation could predict the presence of HCC with very high specificity (98.7%). However, the sensitivity was not high enough (66.7%) for one to rely solely on AFP for the detection of HCC at its earlier stage.

Adolescent↗

Gene coding for the late 11,000-dalton polypeptide of the Tian Tan strain of vaccinia virus and its 5'-flanking region: nucleotide sequence.

A late gene coding for a major structural polypeptide of 11,000 daltons from the Tian Tan strain of vaccinia virus was cloned. A comparison of the sequences from Tian Tan and WR strains of vaccinia virus revealed that there were differences in four nucleotides and one amino acid and that there was little homology between the 5'-flanking sequences of the late and the early genes. However, substantial homology was detected between the 5'-flanking sequences of the late genes.

Amino Acid Sequence↗

Studies of circulating immune complexes and lymphocyte subpopulations in childhood IgM mesangial nephropathy.

T cell subsets, serum immunoglobulin (IgM) level, IgM-bearing lymphocytes, and circulating immune complexes (CIC) were studied in 12 children who suffered from IgM mesangial nephropathy (IgMN) during the acute nephrotic phase, in remission and relapse. Frequent relapses were observed in 11 cases, and 1 was partially responsive to steroid treatment. IgMN was diagnosed by the consistent pattern of IgM deposition by all four FITC-labelled antihuman IgM antibodies from rabbits and goats supplied by four different companies and by the 100% positivity of electron-dense mesangial deposits in an identical localization and distribution pattern of kidney biopsy specimen. CIC were detected by the 3.5% polyethylene glycol method. In sera from 12 patients IgM CIC were detected in 8 cases during the acute nephrotic phase. High levels of C3 CIC and C4 CIC were also found in these cases during the acute nephrotic phase. The CIC were undetectable in remission. Only 3 cases were detectable at low levels of IgM CIC during the second relapse. High serum IgM levels and IgM-bearing lymphocytes were noted in these patients. The patients also had a significant increase of OKT8 cells and a decrease in the OKT4/OKT8 ratio during the acute phase and in relapse. Taken together, the immunopathologic and clinical features suggest that IgMN is a disease entity with a chiefly classical pathway activation of complement components. The correlation between the changes of T cell subsets and the disease activity in IgMN suggests that this may serve as a therapeutic and prognostic guide.

Antigen-Antibody Complex↗

Hepatic decompensation associated with hepatitis B e antigen clearance in chronic type B hepatitis.

To examine hepatic decompensation associated with acute exacerbation preceding hepatitis B e antigen clearance in chronic type B hepatitis, 376 patients with chronic hepatitis who were hepatitis B e antigen-positive were prospectively studied for up to 7 yr (mean 25 mo). Among the 165 patients who underwent hepatitis B e antigen clearance, 4 patients experienced hepatic decompensation and one of them eventually developed hepatic encephalopathy and died. The incidence of hepatic decompensation associated with hepatitis B e antigen clearance was 2.4%. We suggest that such an event in previously unrecognized chronic hepatitis B carriers could have been erroneously interpreted as acute or subacute hepatic failure, and that it might have been the result of a stronger enhancement of the host immune response.

Acute Disease↗

Acute exacerbation in hepatitis B e antigen positive chronic type B hepatitis. A clinicopathological study.

During a 6-year (mean 24.5 months) follow-up study of 237 HBeAg-positive patients with biopsy-verified chronic type B hepatitis, 199 episodes of acute exacerbation (SGPT greater than 300 IU/l) were observed in 148 patients. The clinical and laboratory findings of these acute exacerbations were less severe than classic acute viral hepatitis (P less than 0.001) but with remarkable overlapping. The main histological changes of acute exacerbations were those of lobular hepatitis, even with bridging hepatic necrosis which predicted subsequent HBeAg clearance. Anti-HBc IgM was positive in 14.4% of the exacerbations. All of these findings made acute exacerbation of chronic type B hepatitis indistinguishable from acute viral hepatitis aside from chronic clinical history. Hepatitis A virus, delta agent and possibly non-A, non-B virus(es) were responsible for some of the episodes of clinical exacerbations.

Acute Disease↗

Serodiagnosis of acute B hepatitis: comparison between a competitive binding radioimmunoassay and an enzyme linked immunosorbent assay for IgM antibody to hepatitis B core antigen.

The standard radioimmunoassay for anti-HBc (CORAB) was modified for the differential detection of anti-HBc IgM by incorporation of a step in which anti-HBc IgG was preferentially absorbed by Staphylococcus aureus cells (Protein A). The ratio (R) of anti-HBc IgM to total anti-HBc was evaluated by computing the ratio of sample cpm's after and before protein A absorption. The R values of acute B hepatitis ranged from 0.9 to 2.1 (mean 1.3 +/- 0.3) while those of chronic HBsAg carriers ranged from 3.1 to 8.3 (mean 4.9 +/- 1.1). Adopting 2.1 as the upper limit of R value for acute B infection, this modified CORAB was shown to have excellent correlation with enzyme immunoassay, and to be capable of differentiating acute from persistent HBV infection in HBsAg positive patients, and discriminating acute B hepatitis from non-A, non-B hepatitis in HBsAg negative but anti-HBc positive acute hepatitis.

Acute Disease↗

In vitro effect of a bovine thymic extract (thymostimulin) on T-cell differentiation in cord blood lymphocytes.

Cord blood lymphocytes were isolated from 40 normal newborns. The initial 20 samples were used to determine the dose-response curve of bovine thymic extract (Thymostimulin) by the measurement of active T cells. Results showed that the active T cells increased significantly when the Thymostimulin concentration was increased to 50 ng/ml and 100 ng/ml. The remaining 20 samples were divided into three portions and preincubated either with 50 ng and 100 ng of Thymostimulin or without Thymostimulin. The total T cells, active T cells, B cells, T-cell subsets, and lymphoproliferative responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen were determined. The results showed that the active T cells, total T cells, B cells, OKT4 cells, and OKT8 cells were significantly increased after Thymostimulin treatment. The lymphoproliferative responses were also significantly increased. These data strongly support our conclusion that Thymostimulin has a marked stimulating effect on human lymphocyte proliferation and differentiation.

Animals↗

Hepatocellular carcinoma in noncirrhotic patients. A laparoscopic study of 92 cases in Taiwan.

Clinical and laboratory findings of 92 cases of pathologically verified noncirrhotic primary hepatocellular carcinoma (HCC) were analyzed and compared with that of 174 cases of cirrhotic HCC during the same period. Ninety-two cases of noncirrhotic HCC constitute one third of all the cases of HCC. They comprised 74 men (80.4%) and 18 women (19.6%) with a male:female ratio of 4.1. The mean age was 52.0 +/- 14.5 years. Among them, 17.4% had a history of hepatitis; 65.2% were HBsAg positive. Compared with cirrhotic HCC, patients with noncirrhotic HCC had less frequent past history of hepatitis, lower positive rate for HBsAg, higher albumin/globulin ratio, and lower frequency in the elevation of serum alpha-fetoprotein. The results might imply that noncirrhotic and cirrhotic HCC have different pathogenetic backgrounds.

Adolescent↗

Age-specific prevalence and significance of hepatitis B e antigen and antibody in chronic hepatitis B virus infection in Taiwan: a comparison among asymptomatic carriers, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

The age-specific prevalence of hepatitis B e antigen (HBeAg) and its antibody (anti-HBe) were studied by radioimmunoassay, and compared in a large series of patients with chronic hepatitis B virus (HBV) infection, including 268 asymptomatic carriers, 389 chronic hepatitis, 114 liver cirrhosis, and 278 hepatocellular carcinoma (HCC). The prevalence of HBeAg/anti-HBe in asymptomatic carriers and patients with chronic hepatitis correlated closely with age as HBeAg prevalence decreased and anti-HBe prevalence increased with increasing age (P less than 0.0005), and is probably due to high infection rate at young age in Taiwan. The prevalence of HBeAg in patients with both cirrhosis and HCC are much significantly lower and had no correlation with age. Two peaks of age-specific prevalence of HBeAg and anti-HBe were observed in patients with HCC, implicating two patterns of HBV infection in these patients. The difference in the prevalence of HBeAg and anti-HBe might indicate that asymptomatic carriers, chronic hepatitis, liver cirrhosis, and HCC are sequential sequelae of HBV infection.

Adolescent↗

Peripheral T-cell subsets in chronic type B hepatitis: correlation with biochemical and histological activities and hepatitis B e antigen/antibody status.

Peripheral T-cell subsets in 77 patients with hepatitis B surface antigen (HBsAg)-positive chronic liver diseases were studied by indirect immunofluorescence using murine monoclonal antibodies against all peripheral T cells (OKT3), T-helper/inducer cells (OKT4), and T-cytoxic/suppressor cells (OKT8). OKT4/OKT8 ratios were significantly reduced in patients with hepatitis B e antigen (HBeAg)-positive chronic liver diseases, including 28 patients with chronic active hepatitis (CAH) (P less than 0.001) and 15 with chronic persistent hepatitis (CPH) (P less than 0.001). OKT4/OKT8 ratios were significantly lower in 21 HBeAg-negative patients with CAH (P less than 0.05), as compared to those of 17 normal controls, while T-cell subsets in 13 patients with HBeAg-negative CPH were essentially normal. Low OKT4/OKT8 ratios significantly correlated with HBeAg positivity (P less than 0.001) and CAH (P less than 0.05), as assessed with multiple regression. There was a significant negative correlation between OKT4/OKT8 ratios and serum glutamic-pyruvic transaminase (SGPT) levels (r = -0.37; P less than 0.01). It was concluded that in chronic hepatitis B virus infection, low OKT4/OKT8 ratios are closely related to active viral replication and more severe histological and biochemical activity.

Adolescent↗

From the National Institutes of Health. Summary of a meeting on the origin of pandemic influenza viruses.

Influenza type A virus periodically undergoes major antigenic shifts in which the hemagglutinin (HAG) and sometimes the neuraminidase (NA) antigens are replaced by HAG and NA antigens of another subtype. Three such shifts have taken place since the virus was first isolated, and all appear to have occurred in China. The way in which these "new" influenza type A viruses suddenly appear (or reappear) in the human population is not known. At a meeting held in Beijing, China, on November 10-12, 1982, participants discussed the latest findings on the molecular biology of influenza viruses and on aspects of their ecology that may offer insight into the factors responsible for the origin of pandemic influenza viruses. Information obtained in earlier studies has provided some clues about how the antigenic shifts may occur. For example, the H3N2 virus has been found to be a recombinant deriving seven of its eight genes from an H2N2 strain and gene 4 (which encodes for the HAG) from some other virus, possibly an avian influenza virus of the H3 subtype [1-3]. In addition, studies of the genome of the H1N1 virus that appeared in Anshan, China, in 1977 have shown that this virus almost certainly underwent no replication for 27 years. This finding suggests that the virus existed in an animal reservoir during this period [4, 5].

Animals↗

Chronic hepatitis with nonspecific histological changes. Is it a distinct variant of chronic hepatitis?

A longitudinal follow-up study has been undertaken in 62 patients with clinicopathologically verified chronic hepatitis with non-specific reactive histological changes (NSRH) in comparison with 28 patients with chronic persistent hepatitis (CPH), the clinical features of which are quite similar to NSRH. In contrast to the stationary and non-progressive course of CPH, 45.2% of patients with NSRH, either HBsAg positive or negative, ran a fluctuating course with moderate to marked elevation of SGPT (greater than 200 IU/l) In HBsAg-positive patients, only those positive for HBeAg and a few negative for both HBeAg and anti-HBe had fluctuating courses. In addition, patients with apparent clinical and biochemical changes could show histological features of chronic lobular hepatitis (CLH). A few developed chronic active hepatitis and/or cirrhosis on follow-up biopsy. It is concluded that NSRH is a form of chronic hepatitis different from CPH, but similar to or representing a phase of CLH. It is suggested that NSRH should be categorized as CLH in the classification of chronic hepatitis.

Adolescent↗