Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Porphyria cutanea tarda (PCT) is believed to be associated with reduced hepatic uroporphyrinogen decarboxylase activity and risk factors such as alcohol abuse and medication with oral contraceptives and certain other drugs. Recently it has been suggested that hepatitis C virus (HCV) infection may also be associated with PCT. We have therefore reviewed the prevalence of HCV infection in a series of patients with PCT in the Lothian region of Scotland. We identified 12 patients with PCT, all of whom had abnormal liver function tests. Liver histology revealed chronic active hepatitis in six patients, micronodular cirrhosis in four patients, hepatocellular carcinoma in one patient and normal findings in one HIV positive patient. Out of 12 patients tested, 11 were positive for anti-HCV antibodies by second generation enzyme linked immunosorbent assay (ELISA 2), and by recombinant immunoblot assay (RIBA 2); positive serology was confirmed by polymerase chain reaction (PCR). In a second group of 14 patients with chronic HCV infection matched for age and sex with the PCT patients, all had normal urinary uroporphyrin excretion. We have thus confirmed in Scotland early reports from Spain and Italy that PCT is strongly associated with HCV infection. This could explain the development of inflammatory changes in the liver and progression of liver disease in patients with PCT. Porphyrin metabolism, however, appears normal in patients with chronic HCV infection without PCT.
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PMID:The association of hepatitis C viral infection with porphyria cutanea tarda in the Lothian region of Scotland. 895

Frequently, immunodeficient patients have more than one organ or system affected by opportunistic infection or neoplasia, requiring quick and precise diagnostic investigation. In some situations, different invasive diagnostic procedures may be necessary. Open lung biopsy is sometimes necessary to clarify the pulmonary diagnosis. Laparoscopy may be useful to clarify liver or other peritoneal diseases. Some specific patients might require both procedures. In this way it is proposed that the surgeon, through a microthoracotomy used for the pulmonary biopsy, has access to the diaphragm. A small phrenotomy is performed and then a liver needle biopsy under direct vision. The described technique of simultaneous open lung and hepatic biopsy permits better handling of the needle and hemostasis of the hepatic lesion at the puncture site. This method has been used since 1994 on 16 HIV-positive patients, all having clinical and laboratory manifestations of lung disease associated with liver disease of unknown etiology. No complications related to the method were observed. It is significant that different etiologies for the lung and liver disease were found in 50% of the cases. We conclude that the presented technique is simple, useful, and safe.
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PMID:Hepatic and pulmonary biopsy by mini-thoracotomy and transdiaphragmatic access. 898 49

On September 21-22, 1995, an international meeting entitled "Targeting of Novel Therapeutics to the Liver and GI Tract" was held at the Natcher Conference Center on the campus of the National Institutes of Health. The conference was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases through the Division of Digestive Diseases and Nutrition and Digestive Diseases Interagency Coordinating Committee (DDICC). Section 440A of Public Law 94-562 in 1976 created the DDICC for the purpose of coordinating the digestive disease-related research activities of relevant federal health agencies into a coordinated program aimed at combating digestive diseases. As part of this federal effort, an assessment of the "state of the art" for targeted drug therapeutics to the liver and gene therapy was undertaken through the conference, cochaired by Dr. Mark Zern (Thomas Jefferson Medical College) and Dr. Flossie Wong-Staal (University of California, San Diego, CA). The conference was divided into four sessions: Session I was Vectors and Techniques; Session II was Liver and Metabolic Diseases; Session III was Hepatitis and GI Disease; and Session IV was Approaches for HIV Infection. This summary focuses on the new technologies and the studies directly pertaining to liver disease. Table 1 lists the techniques and their applications. Table 2 describes viral vectors that have been employed for the purpose of hepatic gene therapy. Table 3 summarizes the studies presented as posters at the conference.
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PMID:Hepatic drug delivery and gene therapy. 902 68

The genomes of both bacteria and eukaryotic organisms are known to encode selenoproteins, using the UGA codon for seleno-cysteine (SeC), and a complex cotranslational mechanism for SeC incorporation into polypeptide chains, involving RNA stem-loop structures. These common features and similar codon usage strongly suggest that this is an ancient evolutionary development. However, the possibility that some viruses might also encode selenoproteins remained unexplored until recently. Based on an analysis of the genomic structure of the human immunodeficiency virus HIV-1, we demonstrated that several regions overlapping known HIV genes have the potential to encode selenoproteins (Taylor et al. [31], J. Med. Chem. 37, 2637-2654 [1994]). This is provocative in the light of overwhelming evidence of a role for oxidative stress in AIDS pathogenesis, and the fact that a number of viral diseases have been linked to selenium (Se) deficiency, either in humans or by in vitro and animal studies. These include HIV-AIDS, hepatitis B linked to liver disease and cancer, Coxsackie virus B3, Keshan disease, and the mouse mammary tumor virus (MMTV), against which Se is a potent chemoprotective agent. There are also established biochemical mechanisms whereby extreme Se deficiency can induce a proclotting or hemorrhagic effect, suggesting that hemorrhagic fever viruses should also be examined for potential virally encoded selenoproteins. In addition to the RNA stem-loop structures required for SeC insertion at UGA codons, genomic structural features that may be required for selenoprotein synthesis can also include ribosomal frameshift sites and RNA pseudoknots if the potential selenoprotein module overlaps with another gene, which may prove to be the rule rather than the exception in viruses. One such pseudoknot that we predicted in HIV-1 has now been verified experimentally; a similar structure can be demonstrated in precisely the same location in the reverse transcriptase coding region of hepatitis B virus. Significant new findings reported here include the existence of highly distinctive glutathione peroxidase (GSH-Px)-related sequences in Coxsackie B viruses, new theoretical data related to a previously proposed potential selenoprotein gene overlapping the HIV protease coding region, and further evidence in support of a novel frameshift site in the HIV nef gene associated with a well-conserved UGA codon in the 1-reading frame.
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PMID:Genomic structures of viral agents in relation to the biosynthesis of selenoproteins. 915 12

Assessment of chronic hepatitis C virus infection requires a liver biopsy in most circumstances. There is a reluctance to perform liver biopsy in haemophiliacs because of a perceived risk of haemorrhage, although with adequate factor concentrate replacement in patients without factor concentrate inhibitors it should be safe. We report a 4-year experience of liver biopsy in patients with haemophilia infected with chronic hepatitis C virus. Of 55 patients seropositive for anti-HCV, 35 have undergone liver biopsy; the median age of this group was 33 years (range 13-68). Seven patients had a normal liver. 22 had portal tract inflammation, four with lymphoid aggregates. Mild piece-meal necrosis was observed in only two and no bile duct injury was found. 11 patients had mild mixed micro- and macro-vesicular fat. 19 patients had no evidence of fibrosis despite an estimated median duration of disease of 20 years (range 8-43). In the remaining 16 patients the maximum degree of fibrosis achieved was stage III. Patients with more significant fibrosis could not be identified on the basis of ALT or HCV RNA. There were no complications of liver biopsy in this series. Liver biopsy following a well-defined protocol in chronic hepatitis C virus haemophiliac carriers is safe in the absence of factor concentrate inhibitors. In this young group of patients without HIV infection there was no evidence of significant liver disease despite a considerable duration of disease. Performing liver biopsy allows accurate information to be given to the patient and avoids unnecessary therapy. The relative youth of this group may be important in the light of the benign histology.
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PMID:The role for liver biopsy in haemophiliacs infected with the hepatitis C virus. 935 33

The Mpl ligands are a family of closely related hematopoietic growth factors that bind to the thrombopoietin receptor, c-Mpl. In addition to the endogenous Mpl ligand, thrombopoietin, two recombinant Mpl ligands, recombinant thrombopoietin and pegylated megakaryocyte growth and development factor (PEG-MGDF) are under investigation. Endogenous thrombopoietin regulates most of the normal production of platelets but also is essential for the normal development of other lineages. When recombinant thrombopoietin or PEG-MGDF is administered to normal animals or humans, there is a dose-dependent increase in the platelet count but no effect on leukocytes or erythrocytes. When administered following chemotherapy in animal models or humans, Mpl ligands reduce the duration and sometimes the degree of thrombocytopenia. The Mpl ligands also may be effective in reducing the thrombocytopenia of patients with HIV infection, liver disease, myelodysplasia, or after plateletpheresis.
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PMID:In vivo effects of Mpl ligand administration and emerging clinical applications for the Mpl ligands. 920 31

A prospective study of 74 consecutive HIV patients (mean age, 34 years) at a public hospital in Mumbai, India, found evidence of hepatitis B and C virus, hepatic tuberculosis, and other liver disease. Clinical evaluation, liver function tests, ultrasonography, radioisotope liver scan, hepatitis B and C virus markers, and liver histology were performed. 34 patients (45%) were classified as chronic alcoholics on the basis of a history of consumption of at least 80 g of alcohol daily for at least 5 years and test findings. 59 (80%) had a history of multiple sex partners or encounters with commercial sex workers. 12 patients (16%) were hepatitis B surface antigen-positive and 22 (30%) were positive for hepatitis C virus antibody. Bilirubin, transaminases, and alkaline phosphatase were elevated in 13%, 13%, and 24%, respectively. Liver cirrhosis was present in 5 patients. Hepatitis B virus was detected in 4 patients and dual hepatitis B and C infection was found in another patient. Finally, 5 patients had liver tuberculosis. The mean absolute lymphocyte count was 2521/cu. mm; only 20 had a count indicative of immunosuppression (2000/cu. mm). These findings confirm that hepatic effects are a major feature of HIV infection in India.
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PMID:Spectrum of liver diseases in HIV infection. 935 1

A normal constituent of the human upper respiratory flora, Streptococcus pneumoniae also produces respiratory tract infections that progress to invasive disease at high rates in specific risk groups. The individual factors that contribute to the development of invasive pneumococcal disease in this distinct minority of persons, include immune (both specific and innate), genetic, and environmental elements. Specific defects in host responses may involve age, deficiencies in levels of antibodies and complement factors, and splenic dysfunction. Combinations of these immune defects contribute to the increased rates of invasive pneumococcal disease in patients with sickle cell disease, nephrotic syndrome, neoplasms, and underlying medical conditions such as diabetes and alcoholic liver disease. The number of risk factors are greatest and the rates of invasive disease are highest in patients with HIV-1 infection, which has emerged as a major risk factor for serious S. pneumoniae infection worldwide.
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PMID:Invasive pneumococcal disease in the immunocompromised host. 927 Sep 91

Hepatitis C is the most common cause of post-transfusion hepatitis, as well as of the viral chronic liver disease in the western world. However since it is even more often asymptomatic than HBV, this is not truly recognized. The detection of hepatitis C can only rely on serological and virological methods and require their extensive use in screening programs. Following the molecular identification characterisation of HCV, it became possible to detect virus specific antibodies. The first generation Elisas were limited in their scope and have been replaced by second and third generation tests with better sensitivity and specificity. These assays detect antibodies to several sets of HCV protein including the C22 core, the C33 and C100, which correspond to the non structural regions (NS3 and NS4 respectively). More recently, NS5 proteins have also been added and synthetic peptides have replaced some of the recombinant proteins used initially. In spite of improved sensitivity and specificity, last generation Elisas still require confirmation by supplemental assays which can be of different types (immunoblot or combined Elisas) and include sets of structural and non structural recombinant proteins or peptides. New tests are needed to improve sensitivity and proficiency of this mandatory confirmation procedure. It is unclear at this stage whether the dogma inherited from HIV to request two sets of reactive antibodies will be also warranted by experience in HCV infection. The biggest limitation of present HCV tests is the delayed appearance of anti-HCV following primary infection. Even more worrisome is the fact that 10% of chronic infection with liver disease still remain seronegative, despite circulating HCV RNA in serum and/or liver as well as expressing HCV antigen demonstrable in liver tissue by immunostaining. Such a proportion is even more common in settings with immune deficiencies including organ transplantation and HIV infection. DNA amplification methods, such as PCR or others, must be used in order to demonstrate HCV RNA in combination with reverse transcription steps. This new powerful technology must be however applied under stringent quality control procedures and cannot be yet considered for screening or routine diagnosis although it can detect viremia as early as a week after exposure and help to monitor interferon treatment. During acute hepatitis, the delay in the appearance of anti-HCV hampers acute phase diagnosis. The early detection of HCV RNA in peripheral blood, confirms the diagnosis and opens up therapeutic possibilities. In chronic hepatitis, the diagnosis of seronegative forms may only be resolved by PCR. Moreover, the presence of HCV RNA in peripheral blood represents the only marker of on going viral replication and coincides with the severity of liver damage. During treatment with interferon, the follow up of HCV RNA sequences makes it possible to monitor its efficacy. The search for HCV RNA sequences directly in liver tissue shows that HCV may replicate in the liver in the absence of viremia. The presence of HCV RNA in the liver and the serum of liver transplanted patients is essential for the etiological diagnosis and management of hepatitis and bone marrow failure occurring after transplantation. Epidemiological study using PCR is a major tool in documenting vertical transmission between mother and child. Finally, PCR is important for the analysis of the HCV genome. Thus, in France there are at least three main strains, one close to the US prototype, the other close to the Japanese strain, possibly responsible for a more severe illness, and a third one distinct from the previous two. Two major HCV genotypes, F1 and F2, corresponding to HCV type I and II (USA prototype and Japanese) with prevalence of 45% and 55% respectively, were found in France. F1 infected patients were younger and more often male than F2 group. Nine of 28 patients in F1 genotype infected group had history of drug abuse but none i
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PMID:[Limits of immunoserologic and molecular diagnosis of hepatitis C]. 929 65

The prevalence and the clinical course of hepatitis C virus (HCV) infections were studied in 23 HIV-1-infected children, who were born to 22 mothers with HIV-1/HCV coinfection. During the follow-up only two children (8.7%) showed persistent anti-HCV antibodies and circulating HCV RNA. Both children, who were aged 10 and 10.6 years respectively at the end of follow-up, had chronically-evolving liver disease and autoimmune thrombocytopenia but no signs of progressive HIV disease. Based on our experience, vertically-acquired HIV-1/HCV coinfection is less frequent than is generally reported and may be associated with the development of chronic thrombocytopenia in addition to liver disease. Moreover, perinatal HIV-1/HCV coinfection appears to be associated with a slow progression of HIV disease.
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PMID:Mother to infant transmission of coinfection by human immunodeficiency virus and hepatitis C virus: prevalence and clinical manifestations. 934 91


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