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Biomedical subjects

J M Vierling

Publications and source records attributed to J M Vierling.

At least 37 records · Page 2Linked to original sources
PubMed1995

Malignant vascular tumors of the liver presenting as liver failure and portal hypertension.

We describe three patients referred for orthotopic liver transplantation with liver failure and portal hypertension who were found to have malignant vascular tumors: two patients with angiosarcoma and one patient with epithelioid hemangioendothelioma. Their clinical presentation mimicked decompensated chronic liver disease. None had tumor masses on computed tomography and ultrasonography. Massive tumor involvement of the liver was identified in the two patients studied by magnetic resonance imaging. Pathological examination of the explanted liver at the time of transplantation in one patient and autopsy in a second patient showed angiosarcoma. Laparoscopic liver biopsies in the third patient showed epithelioid hemangioendothelioma. The vascular origin of the tumor was established by histopathologic examination and confirmed with immunohistochemistry. Malignant vascular tumors of the liver should be included in the differential diagnosis of liver failure of unclear etiology.

Adult↗
PubMed1995

Detection of hepatitis C virus with RNA polymerase chain reaction in fulminant hepatic failure.

The role of hepatitis C virus (HCV) infection in fulminant hepatic failure is controversial. The frequency of serum HCV RNA positivity in previously reported patients with fulminant hepatic failure (FHF) of indeterminate cause ranged from 0 to 12% in the United States and Europe and from 43% to 59% in Asia. We assessed serum HCV RNA using polymerase chain reaction (PCR) and oligoprimers from the 5'UTR of the HCV genome in 26 consecutive patients with FHF. Another laboratory independently performed PCR on 21 of the serum samples using different oligoprimers from the 5'UTR and NS3 region of the HCV genome. Serum HCV RNA was detected in two of seven (28%) patients with hepatitis B, 9 of 15 (60%) with an indeterminate cause, and in none with hepatitis A (n = 2) or drug-induced hepatotoxicity (n = 2). HCV RNA PCR results were concordant between both laboratories in 17 of 21 (81%) of samples. In patients with an indeterminate cause, HCV RNA positivity was significantly associated with the transmission risk factor of low socioeconomic status and Hispanic ethnicity. Eighteen patients underwent liver transplantation (LT) and 15 (83%) survived. Among patients with FHF of indeterminate cause, recurrent or acquired HCV infection after transplantation occurred in three of five (60%) and one of four (25%) patients, respectively. Three of four (75%) patients with hepatitis C virus infection post-LT also developed histologic hepatitis. HCV appears to be the causative agent of a substantial number of cases of FHF classified as indeterminate in the Los Angeles area. Differences in patient populations or risk factors may explain the discordant incidences of HCV infection in FHF observed among different programs.

Adolescent↗
PubMed1995

Simultaneous detection of both hepatitis B virus DNA and hepatitis C virus RNA using a combined one-step polymerase chain reaction technique.

Hepatitis C virus (HCV) RNA polymerase chain reaction (PCR) is widely used for diagnosis of HCV infection and evaluation of therapy. The sensitive hepatitis B virus (HBV) DNA PCR is often reserved for detection of quantities of HBV DNA that are insufficient for hybridization. Application of both PCR techniques is limited by their labor-intensity, potential for contamination, and substantial time required for analysis. To study HCV and HBV infections, occurring alone or in combination, we developed a combined one-step PCR method to detect HCV RNA and HBV DNA in a single serum specimen using oligoprimers from the HCV 5' untranslated region and the HBV preS/S region. Specificity of the HBV and HCV PCR products was confirmed on the basis of their molecular sizes in positive samples, Southern blot hybridization, and negative controls. The sensitivities of the combined PCR were assessed using samples containing a wide range of defined amounts of HBV DNA and HCV RNA and were comparable with those obtained with conventional HBV DNA or HCV RNA PCR methods. The sensitivity of the combined method was further validated by the 100% concordance between results of its HBV and HCV components and those of conventional PCR methods in patients with HBV and/or HCV infections. The combined one-step HBV/HCV PCR is a sensitive, specific, rapid, and cost-effective method, especially suited for epidemiological screening and clinical diagnosis of HBV and HCV infections occurring alone or in combination.

Base Sequence↗
PubMed1995

Recurrence of viral hepatitis after liver transplantation: insights into management.

Recurrence of viral infection and hepatitis is a common problem for patients undergoing LT for hepatitis B or hepatitis C. In patients with hepatitis B who do not receive immunoprophylaxis, recurrence of HBsAg positivity is virtually universal and is usually associated with rapidly progressive hepatitis that jeopardizes long-term patient and allograft survival. HCV infection recurs in 80% to 100% of patients, but only 50% develop histologic features of hepatitis, which are generally mild and do not significantly decrease life survival. Long-term HBIg prophylaxis is currently the only effective strategy to prevent or modify HBV recurrence. At present, there is no effective prophylaxis for recurrence of HCV infection. Preliminary results suggest that interferon therapy may benefit a minority of patients with either recurrent HBV or HCV infection after LT. Hepatitis B should not be regarded as a contraindication for LT. However, until an effective and readily available therapy is developed to prevent recurrence, HBsAg-positive patients should undergo transplantation under experimental protocols. Hepatitis C is also not a contraindication for LT. Although recurrent hepatitis C is usually mild and slowly progressive, severe forms of hepatitis requiring retransplantation have been increasingly reported. Long-term follow-up studies are needed to define the natural history of recurrent HCV infection after LT and its impact on allograft and patient survival.

Antigens, Viral↗
PubMed1994

Acute hepatitis associated with the Chinese herbal product jin bu huan.

OBJECTIVE: To describe the hepatotoxicity associated with ingestion of the Chinese herbal product Jin Bu Huan Anodyne Tablets (Lycopodium, serratum) and to propose possible mechanisms of injury. DESIGN: Retrospective analysis. SETTING: Academic hepatology units and private practice facilities. PATIENTS: Seven previously healthy patients. MEASUREMENTS: Clinical, laboratory, radiologic, and histologic studies. RESULTS: Acute hepatitis occurred after a mean of 20 weeks (range, 7 to 52 weeks) of Jin Bu Huan ingestion and resolved in six patients within a mean of 8 weeks (range, 2 to 30 weeks); another patient is currently improving. Hepatitis was associated with symptoms of fever, fatigue, nausea, pruritus, and abdominal pain and with signs of jaundice and hepatomegaly. Biopsy specimens showed that one patient had hepatitis with eosinophils (consistent with a drug reaction) and the other had mild hepatitis, moderate fibrosis, and microvesicular steatosis. Decreasing the Jin Bu Huan dose in one patient improved liver test results. Reusing Jin Bu Huan in two other patients caused abrupt recrudescence of hepatitis. CONCLUSION: Jin Bu Huan can cause liver injury. Although the hepatotoxic mechanisms are not defined, they may include hypersensitive or idiosyncratic reactions or direct toxicity to active metabolites. Hepatotoxicity caused by herbal products underscores the toxicity caused by herbal products underscores the importance of national surveillance programs and quality control of the manufacture of these products.

Acute Disease↗
PubMed1994

Acute liver failure due to lymphoma. A diagnostic concern when considering liver transplantation.

Lymphomatous involvement of the liver may present as acute liver failure but is an absolute contraindication for liver transplantation. Therefore it is imperative to diagnose such patients since survival in this group is poor and recurrence is high. We describe two patients with acute liver failure referred for liver transplantation whose diagnostic testing revealed hepatic lymphoma. These cases underscore the importance of considering lymphoma in the differential diagnosis of acute liver failure prior to liver transplant.

Adolescent↗
PubMed1994

Molecular diagnostic techniques for viral hepatitis.

The five different viruses that cause human viral hepatitis, A, B, C, D, and E share the unique property of hepatotropism. Identification of the nucleic acid sequences of each of these viruses, coupled with the application of recombinant DNA technology, has resulted in the rapid development of molecular diagnostic techniques. Currently, molecular hybridization and polymerase chain reaction are the major diagnostic techniques for viral hepatitis. This review discusses the molecular biology of the five hepatitis viruses, the principles of molecular biological techniques, and their current and future diagnostic applications.

Algorithms↗
PubMed1993

One-step RNA polymerase chain reaction for detection of hepatitis C virus RNA.

Although detection of hepatitis C virus RNA with polymerase chain reaction has become the standard for diagnosis, extensive application has been thwarted by polymerase chain reaction's labor intensiveness, risk of false-positive results through contamination and time required for individual assays. To minimize these limitations, we developed and validated a one-step hepatitis C virus RNA polymerase chain reaction assay. The one-step method was compared with traditional hepatitis C virus RNA polymerase chain reaction using primers from the highly conserved 5' untranslated region of the hepatitis C virus genome. Variables studied in the one-step method included the source and quantity of reverse transcriptase (RTase), the concentration of MgCl2 and the duration of reverse transcription and complementary DNA amplification cycles. Optimal conditions for the one-step method were obtained with 25 U of reverse transcriptase and 2 mmol/L MgCl2. The one-step method substantially reduced the time required for analysis. The sensitivity of the one-step method was comparable to that of traditional hepatitis C virus RNA polymerase chain reaction using serially diluted RNA extracted from the serum of a hepatitis C virus-infected patient. The specificity of the one-step method was confirmed on Southern-blot hybridization. The results exhibited 100% concordance with results of traditional hepatitis C virus RNA polymerase chain reaction in 50 serum samples, including those of positive and negative controls. In addition, 100% concordance was observed between the two methods' results when sera containing low levels of hepatitis C virus RNA were used.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1992

Up-regulation of intercellular adhesion molecule 1 transcription by hepatitis B virus X protein.

Intercellular adhesion molecule 1 (ICAM-1), a counter-receptor for lymphocyte function-associated antigen 1 on T cells, is critically important to a wide variety of adhesion-dependent leukocyte functions, including antigen presentation and target cell lysis. ICAM-1 expression by hepatocytes is increased in areas of inflammation and necrosis during chronic hepatitis B. Whether induction of ICAM-1 is due to the effect of inflammatory cytokines or involves a direct effect of the hepatitis B virus (HBV) remains unknown. In the present study, transfection of the HBV genome into human hepatoma cell lines resulted in enhanced expression of ICAM-1 protein and RNA in the absence of inflammation. Results of subgenomic transfections indicated that the HBV X protein (pX) induced ICAM-1 expression. Nuclear run-on assays showed that pX induced the ICAM-1 gene by increasing its rate of transcription. Although both pX and interferon gamma induced transcription of ICAM-1, addition of interferon gamma to cells expressing pX did not show an additive or synergistic effect. These results indicate that pX can directly regulate expression of ICAM-1 and may participate in the immunopathogenesis of HBV infection.

Cell Adhesion Molecules↗
PubMed1992

Suppressor function of liver mononuclear cells isolated during murine chronic graft-vs-host disease. II. Role of prostaglandins and interferon-gamma.

Mononuclear inflammatory cells (MC) isolated from the livers and spleens of mice with chronic graft-vs-host disease (CGVHD) to minor histocompatibility antigens (B10.D2----BALB/c) show defective proliferation when stimulated with Con A and LPS. In turn, both CGVHD liver and spleen cells suppress the proliferation of mitogen-stimulated normal spleen cells in a genetically unrestricted manner. The suppressor activity of CGVHD spleen cells is mediated by plastic nonadherent null (natural suppressor) cells and involves a soluble suppressor factor(s). In contrast, the suppressor activity of CGVHD liver cells is mediated by macrophages (M phi). In the current studies we show that the suppressor activity of CGVHD liver cells is also mediated by soluble factors and compare the roles of prostaglandins and interferon (IFN)-gamma in mediating defective proliferation and suppressor activities of CGVHD liver and spleen MC. Monoclonal antibody to IFN-gamma partially reversed the defective mitogen-stimulated proliferation of CGVHD spleen MC but had no effect on proliferative response of CGVHD liver MC. Indomethacin did not alter the low proliferative response of either CGVHD liver or spleen MC. Anti-IFN-gamma inhibited the ability of CGVHD spleen cells to suppress proliferation of Con A and LPS-stimulated B10.D2 spleen cells. In contrast, anti-IFN-gamma resulted in a small decrease in the ability of liver MC to suppress Con A (but not LPS)-stimulated cell proliferation. Indomethacin decreased the ability of both CGVHD liver and spleen cells to suppress Con A-stimulated proliferation but had inconsistent effects on LPS-stimulated proliferation. These results show that IFN-gamma and prostaglandins partially mediate the suppressor activity of CGVHD spleen MC. The suppressor activity of CGVHD liver MC also involves prostaglandins but is relatively independent of IFN-gamma.

Animals↗
PubMed1992

Direct detection of circulating hepatitis C virus RNA using probes from the 5' untranslated region.

Diagnostic testing for hepatitis C virus (HCV) infection currently is based on the presence of anti-HCV antibodies or a positive HCV RNA polymerase chain reaction (PCR) test. Although HCV RNA PCR is a sensitive and specific technique, widespread application is limited. Moreover, HCV RNA PCR is subject to false-positive reactions through contamination and is inherently difficult to standardize and quantitate. To overcome limitations of HCV RNA PCR, we produced both cDNA and riboprobes from a 241 nucleotide sequence of the 5' untranslated region of the HCV genome for slot hybridization. Hybridization was absent using normal human serum, horse serum, or hepatic cellular RNA from noninfected liver. Hybridization occurred predominantly with positive-stranded HCV RNA and was abolished by pretreatment with RNase A. Slot hybridization was performed on serum samples from 60 patients with chronic HCV infection and a positive HCV RNA PCR and 20 patients with liver diseases unrelated to HCV who had a negative HCV RNA PCR. Slot hybridization with cDNA and riboprobes showed concordance with HCV RNA PCR of 95 and 98.3%, respectively. There were no false-positive reactions in controls. The sensitivity of riboprobe hybridization was comparable to that of one stage HCV RNA PCR using 5' untranslated region primers. Riboprobe hybridization with the HCV H strain standard was positive in the dilution corresponding to 10(-6) chimpanzee infectious doses50/ml. The density of the hybridization signals correlated significantly with the mass of an RNA standard extracted from the liver of a patient with HCV infection. The relative quantities of HCV RNA in the sera of selected patients varied and were not correlated with the duration of disease or the histopathological stage. The highest relative quantities were associated with concurrent immunosuppression. We conclude that slot hybridization is a sensitive, specific alternative to HCV RNA PCR that can be directly quantitated using appropriate HCV RNA standards.

Base Sequence↗
PubMed1992

Immune disorders of the liver and bile duct.

Several hepatobiliary diseases appear to be mediated by the host immune response. They can be subdivided into those in which the immune reaction is against an infectious agent such as hepatitis viruses, those in which the immune reaction appears to be against an autoantigen expressed on hepatobiliary cells, and those due to alloimmunity. The existence of autoimmune liver diseases indicates a breakdown in the mechanisms responsible for self-tolerance. In HBV infection, the hepatocellular necrosis appears to be mediated by the host immune response against viral antigens expressed on the membranes of infected hepatocytes. Autoimmune chronic active hepatitis can be subdivided on the basis of differences in circulating autoantibodies. In classic type I autoimmune chronic hepatitis, autoantibodies are directed against non-organ- and non-species-specific antigens. Thus, they are unlikely to be involved in pathogenesis. In contrast, type II autoimmune chronic hepatitis is characterized by antibodies against specific cytochrome P-450 isoenzymes that appear to be expressed on the surface membrane of hepatocytes. Immunogenic cytochrome P-450 also can be induced by drug metabolism and haptenation. This indicates that environmental or medicinal xenobiotics may initiate autoimmune liver damage. Primary biliary cirrhosis is characterized by T-cell-mediated inflammation and destruction of interlobular and septal bile ducts and antibodies specific for epitopes of the 2-oxo-acid dehydrogenase multienzyme complex of mitochondria. The histopathologic lesion NSDC also is observed in alloimmune-mediated diseases such as CGVHD and rejection of liver allografts. PSC may be mediated by an immune response against endothelial cells of the peribiliary capillary plexus, with secondary reactions to bile duct epithelial cell antigens. The pathogenesis of alcoholic liver disease is multifactorial, but one component involves an immune response to acetaldehyde-protein adducts. Secondary sensitization of cell-mediated effector mechanisms, endothelial damage, and secretion of noxious cytokines appear to be involved in pathogenesis.

Autoimmune Diseases↗
PubMed1991

Suppressor function of hepatic mononuclear inflammatory cells during murine chronic graft-vs-host disease. I. Macrophage-enriched cells mediate suppression in the liver.

Murine chronic graft-vs-host disease (CGBHD) to minor histocompatibility antigens (B10.D2----BALB/c) is characterized by inflammatory destruction of intrahepatic bile ducts, scleroderma-like skin lesions, and lymphoid involution. Spleen cells isolated from this model proliferate poorly when stimulated with mitogens. Previous reports indicate defective lymphocyte proliferation in this model is the result of active suppression induced by the graft-vs-host reaction in the spleen and is mediated by Thy 1.2-, sIg-, plastic nonadherent, splenic natural suppressor (NS) cells. To determine whether the intense CGVHD in the liver is associated with induction of suppression, we compared the suppressor activity of hepatic and splenic mononuclear inflammatory cells isolated concurrently during murine CGVHD. Both hepatic and splenic MC suppressed the proliferation of mitogen-stimulated normal spleen cells in a non-MHC, non-Mls restricted manner. T cells contributed to the suppressor activity of both populations. However, the suppressor activity of hepatic MC was mediated largely by a macrophage-enriched population of MC while that of splenic MC was mediated largely by NS cells.

Animals↗
PubMed1990

Disappearing bile ducts: immunologic mechanisms.

In primary biliary cirrhosis, chronic graft-versus-host disease, and chronic liver transplant rejection, immunologic mechanisms appear to cause destruction of intrahepatic bile ducts and consequently may lead to liver failure. Understanding those mechanisms may lead to improved therapy. Recent findings and clinically relevant concepts are discussed.

Antigen-Presenting Cells↗
PubMed1990

Cell surface expression of hepatitis B surface and core antigens in transfected rat fibroblast cell lines.

Hepatocellular necrosis during hepatitis B virus infection is hypothesized to result from host immune responses against either hepatitis B surface antigen or hepatitis B core antigen expressed on the surface membrane of infected hepatocytes. To study the capacity of hepatitis B deoxyribonucleic acid to induce membrane expression of either hepatitis B surface antigen or hepatitis B core antigen in vitro, we assessed transfected rat fibroblast cell lines by indirect immunofluorescence. Rat fibroblasts were transfected with plasmid vectors containing the natural promoters, native enhancer, and uninterrupted sequences of either the Pre S/S gene or core gene. Resulting cell lines produced hepatitis B surface antigen and hepatitis B core antigen/hepatitis B e antigen, respectively. Immunofluorescence microscopy or flow cytometry showed that hepatitis B surface antigen and hepatitis B core antigen were expressed in a granular pattern in the surface membrane of transfected cells. We conclude that surface membrane expression of both hepatitis B surface antigen and hepatitis B core antigen is an intrinsic consequence of expression of either the Pre S/S or core gene.

Animals↗
PubMed1990

Trans-activation of HLA-DR gene by hepatitis B virus X gene product.

Hepatocellular injury during hepatitis B virus (HBV) infection has been postulated to result from a human leukocyte antigen (HLA)-restricted T-lymphocyte host immune response against HBV antigens. Although HLA expression is enhanced in the presence of hepatic inflammation, whether HBV itself can induce HLA expression on infected hepatocytes is unknown. In this study, we demonstrate the induction of HLA-DR expression on human hepatoma cell lines transfected with HBV DNA sequences. The HBV X gene alone was capable of inducing HLA-DR expression. This induction correlated with elevated HLA-DR RNA, and this resulted directly from transcriptional trans-activation of the HLA-DR gene by the HBV X protein. These studies suggest that the HBV X protein can regulate the expression of HLA-DR and thus raise the possibility of participation by the X gene in the immunopathogenesis of HBV infection.

Antigens, Viral↗