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Biomedical subjects

R Goldin

Publications and source records attributed to R Goldin.

36 records · Page 2Linked to original sources

Periportal fibrosis secondary to transfusion siderosis in two patients with acquired immune deficiency syndrome (AIDS) treated with zidovudine--a confusing ultrasound appearance.

We present the confusing sonographic features of periportal fibrosis in two AIDS patients who had zidovudine-induced transfusion siderosis of the liver. To our knowledge this has not been previously reported in the literature. The clinical, pathological and sonographic features are described.

Acquired Immunodeficiency Syndrome↗

Dermatitis herpetiformis and primary sclerosing cholangitis.

A patient with dermatitis herpetiformis (DH) developed abnormal liver function tests and was found to have histological features of primary sclerosing cholangitis (PSC) on liver biopsy. The association of DH and PSC has not been previously reported and the high incidence of phenotype HLA B8 and DR3 in these disorders suggests a common genetic predisposition may exist for both diseases.

Bile Ducts↗

Seroprevalence of hepatitis C virus nucleocapsid antibodies in patients with cryptogenic chronic liver disease.

The serological responses to two different hepatitis C virus antigens were studied by enzyme-linked immunosorbent assay in a variety of chronic liver diseases and in healthy blood donors. The study population comprised 97 cases of cryptogenic chronic liver disease (40% with a history suggestive of parenterally transmitted non-A, non-B hepatitis and 60% without such a history), 87 cases of other well-characterized chronic liver diseases and 96 voluntary blood donors. The commercially available C100-3 assay and a new assay utilizing a 22 kD recombinant protein (c22) from the nucleocapsid region of the virus were used for antibody detection. Overall in the non-A, non-B hepatitis group, 77% were positive for anti-c22, 55% were positive for anti-C100-3 and 24% were negative by both tests. In the parenterally transmitted chronic liver disease group, 82% were positive for anti-C100-3 and 90% were positive for anti-c22 (not significant). In the cryptogenic chronic liver disease cases 36% were positive for anti-C100-3 and 67% were positive for anti-c22 (p less than 0.001). Only in one case (a patient with hepatitis B virus infection) was anti-C100-3 detected without concomitant anti-c22. None of the voluntary blood donors had detectable hepatitis C virus antibodies. The new enzyme-linked immunosorbent assay test for anti-c22 would appear to be a more sensitive indicator of chronic hepatitis C virus infection than the existing commercial test, suggesting a useful diagnostic role in both cases of cryptogenic chronic non-A, non-B hepatitis liver disease and for the screening of blood products for prevention of hepatitis after transfusion.

Base Sequence↗

Effect of cyclosporin-A in woodchucks with chronic hepatitis delta virus infection.

Four woodchucks chronically infected with hepatitis delta virus (HDV) were treated with cyclosporin-A (CyA) for 11 weeks. All animals had detectable HDAg in the liver and two of them were also positive for HDAg and HDV-RNA in serum. Reappearance of HDV in serum was noted in one of the two non-viraemic animals and increased viraemia in the two viraemic. HDV-RNA levels became elevated within a week of starting treatment and an inverse relationship between HDV-RNA and WHV-DNA became apparent during the treatment period. With discontinuation of treatment, HDV-RNA levels either returned to pretreatment levels or became negative. The remaining animal showed no return of viraemia during CyA treatment; HDV-RNA remained negative and WHV-DNA levels did not change. Liver biopsies revealed a slight increase in lobular activity during CyA treatment in the animals showing increased viraemia. These data are consistent with the hypothesis that the host immune response exerts a negative control on the level of HDV viraemia and that HDV influences HBV replication independently of the host immune response. In an animal that may have been clearing HDV, immunosuppression did not result in recurrence of viraemia.

Animals↗

Co-expression of markers for hepatitis delta and hepatitis B viruses in human liver.

Delta hepatitis (HDV) infection can only occur in the presence of hepatitis B (HBV) infection, as HDV requires a coat of HBV surface antigen (HBsAg) for assembly of complete virus. A number of studies have examined the variation of HBV markers in serum and liver during establishment of HDV infection, but none has systematically examined the relationship between the two viruses in individual hepatocytes. Liver biopsies from five patients with HDV/HBV infection were stained for HBsAg, HBV core antigen (HBcAg) and hepatitis D (delta) antigen (HDAg). Double immunostaining was performed with a combination of indirect immunoperoxidase and alkaline phosphatase/antialkaline phosphatase techniques. HDV and HBV antigens were expressed in all five liver biopsies. Co-localization of HBsAg was seen in up to 39% of HDAg positive cells, and HBcAg in up to 8% of HDAg positive cells. HBcAg was detectable in approximately 9% of HBsAg positive cells, and HBsAg in approximately 12% of HBcAg positive cells. HDV can replicate without HBV but ultimately requires HBV to produce complete virus and subsequently infect other cells. In this study the majority of HDV positive cells did not appear to contain HBV markers. This might suggest delta virus replication without assembly, or possibly sequential production/assembly of the virus.

Adult↗

A recombinant vaccinia virus expressing hepatitis A virus structural polypeptides: characterization and demonstration of protective immunogenicity.

A recombinant vaccinia virus containing most of the P1 region of hepatitis A virus (HAV) was constructed. Cell lysates of cultures infected with the virus contained HAV proteins detectable by radioimmunoassay. Western blot analysis revealed the presence of a single protein of Mr 60K to 62K, bearing epitopes from structural polypeptides VP4, -3 and -2, and the N terminus of VP1. The size of the protein suggests that at least some of the vaccinia virus thymidine kinase is also expressed. Inoculation of tamarin monkeys with the recombinant virus resulted in the development of a specific anti-HAV immune response which was protective against challenge with a virulent strain of HAV. Recombinant viruses expressing the above region of HAV or the proteins expressed by such viruses may be useful in the development of a vaccine suitable for use in man.

Animals↗

An in situ hybridization, molecular biological and immunohistochemical study of hepatitis delta virus in woodchucks.

The presence of hepatitis delta virus genomic RNA and hepatitis delta antigen was investigated in woodchuck liver and extrahepatic tissues by in situ hybridization using synthetic radiolabeled probes, Northern-blot analysis and immunohistochemical staining for hepatitis delta antigen. Hepatitis D virus RNA and hepatitis delta antigen were detected in the nuclei of infected hepatocytes but in none of the other tissues examined. Northern-blot analysis of total cell RNA confirmed these findings and revealed a series of hepatitis D virus transcripts, including full-length genomic RNA and dimers and trimers of hepatitis D virus RNA that may represent replicative intermediates. Use of single-stranded probes showed genome-size monomers and dimers to be both of genomic and antigenomic polarity, although dimers were found to be predominantly antigenomic. These findings document the strict hepatotropism of hepatitis D virus and support the rolling-circle model of genome replication for this unique, defective RNA virus.

Animals↗

Immunization of woodchucks with recombinant hepatitis delta antigen does not protect against hepatitis delta virus infection.

To assess the role of immunization against hepatitis delta antigen in the prevention of hepatitis delta virus infection, woodchuck carriers of woodchuck hepatitis virus were immunized with a 64 amino acid portion of hepatitis delta antigen from its N-terminal region. The protein was expressed in Escherichia coli and contained a major immunogenic epitope. A significant anti-hepatitis delta response was observed that did not, however, protect the animals from hepatitis delta virus superinfection. Unexpectedly, the period of detectable viremia was longer in the immunized than in the control animals. We conclude that immunization with this recombinant hepatitis delta antigen does not afford protection against subsequent hepatitis delta virus exposure.

Animals↗

Cloning and expression of an immunodominant region of the hepatitis delta antigen.

A cDNA clone prepared from hepatitis delta virus (HDV) RNA extracted from human serum was subcloned in the bacterial expression vector pPL31 to produce a fusion protein consisting of the first 98 amino acids of MS2 polymerase and of 64 amino acids from near the N-terminal region of hepatitis delta antigen (HDAg). The fusion protein was shown to be related to HDAg by a commercial sandwich immunoassay (Abbott) and immunoblotting with human anti-HDAg serum. Antiserum against the fusion protein was raised in rabbits and used to identify HDAg extracted from the serum and liver of an HDV-infected woodchuck and chimpanzee and from the serum of an HDV-infected human, by immunoblotting and immunohistology. A single, major polypeptide of 24K was detected in both serum and liver extracts, with a minor polypeptide of 26K sometimes present. Liver extracts also contained lower Mr polypeptides thought to be degradation products, the major species being 22.5K. The same pattern of staining was obtained with human anti-HDAg serum. Absorption experiments with the expressed protein and cross-competition experiments with the rabbit antiserum suggest that a major immunodominant region of HDAg is present near the N-terminal end of the antigen, between positions 1561 and 1368 on the genome. Both the expressed protein and rabbit antiserum were shown to be good diagnostic reagents.

Amino Acid Sequence↗

Protracted enteric cryptosporidial infection in selective immunoglobulin A and saccharomyces opsonin deficiencies.

Chronic cryptosporidial infection in man usually occurs in those who are immunocompromised. We report a patient with a one year history of bowel symptoms resulting from persistent cryptosporidial infection of the colon. Investigations showed underlying selective IgA and saccharomyces opsonin deficiencies but no evidence of cell mediated immune dysfunction. Both selective immunoglobulin A and opsonin deficiencies are relatively common in the general population and may be a cause of susceptibility to persistent cryptosporidial infection.

Chronic Disease↗

Ankylosing spondylitis and hyperparathyroidism.

An attempt was made to determine whether a relationship exists between ankylosing spondylitis (AS) and hyperparathyroidism (HP). Twenty patients with definite AS, studied for biochemical evidence of HP, did not show consistent abnormalities in serum calcium, phosphorus, alkalinephosphatase, or parathyroid hormone levels or in bone-density measurements. Reviewing roentgenograms of 39 patients with HP showed one patient with sacroiliitis, and one of the 28 hyperparathyroid patients tissue-typed as HLA B27-positive. Both AS and HP are independent entities that have no causative or pathological relationship to each other.

Alkaline Phosphatase↗

Influence of MHC class II genotype on outcome of infection with hepatitis C virus. The HENCORE group. Hepatitis C European Network for Cooperative Research.

BACKGROUND: The outcome of infection with hepatitis C virus (HCV) varies substantially among individuals. Host genetic factors are likely to give rise to some of this variability. Polymorphisms in the MHC class II loci may influence the outcome of HCV infection; however, reports of MHC class II allele associations have been inconsistent. We aimed to confirm these associations in a cohort of European patients with different clinical outcomes. METHODS: The distribution of MHC class II alleles was compared between patients with self-limiting infection (n=85) and matched patients with persistent infection (n=170); between patients with mild (n=321) and severe (n=321) histological injury; and between patients who responded to interferon (n=96) and those who did not (n=192). The results of these comparisons were confirmed with a second-stage study of self-limiting infection (n=52) versus persistent infection (n=152). FINDINGS: Self-limiting HCV infection was associated with HLA-DRB1*1101 (odds ratio 2.14 [95% CI 1.11-4.12]; p=0.013) and HLA-DQB1*0301 (2.22 [1.24-3.96], p=0.004). Persistent HCV infection was associated with HLA-DRB1*0701 (2.04 [1.03-4.17], p=0.027), and HLA-DRB4*0101 (2.38 [1.29-4.35], p=0.002). These results were confirmed in the second-stage study. No significant associations (p<0.05 after Bonferroni correction) were found between MHC class II alleles and severe histological injury or response to interferon therapy. INTERPRETATION: Specific MHC class II alleles influence susceptibility or resistance to persistent HCV infection.

Cohort Studies↗