Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three-hundred-eighty-four leprosy patients were clinically examined for sexually transmitted diseases (STD) in north and northeastern India, revealing a high incidence (5.2%) of STD among them. Eighteen males, one female, and one eunuch were found to have chancroid ulcer, gonococcal urethritis, lymphogranuloma inguinale, and primary chancre. Of these patients, only 100, selected randomly, could be screened serologically for STD due to Treponema pallidum, herpes simplex (type 1 and 2), Entamoeba histolytica, hepatitis-associated virus, cytomegalovirus, Chlamydia trachomatis and human immunodeficiency virus (HIV); 100 control sera were included for comparison. In addition, sera from another 133 normal subjects and another 176 lepromatous patients were also screened for HIV antibody. Thus, a total of 233 normal sera and 276 leprosy sera were tested for HIV antibody. Although our leprosy patients have shown significantly high incidences of clinical STD and also high seropositivity against T. pallidum, herpes-simplex viruses types 1 and 2, hepatitis-associated virus, and cytomegalovirus, the search for antibody against HIV was negative. Our clinical and serological data suggest promiscuity in our patient population. The absence of HIV antibody in this high-risk population, however, seems to be an enigma.
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PMID:Sexually transmitted diseases in leprosy patients in north and northeastern India. A futile search for human immunodeficiency virus antibody. 228 Jan 16

Prior to the discovery of the coccobacillus in the lymph nodes of patients with cat-scratch disease by Wear and associates, the diagnosis was based on clinical findings and a nonstandardized skin test. Atypical cases either remained an enigma or were questioned as to accuracy of diagnosis. We present here a case of cat-scratch disease associated with pleural effusion, anicteric hepatitis, and other systemic manifestations confirmed by identification of the coccobacillus. It is the first association with a pleural effusion. With the Warthin-Starry stain, we anticipate a redefinition of this disease. The confirmation of atypical cases will help broaden the clinical spectrum, as well as guide us to consider this diagnosis where its classic manifestations may be absent.
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PMID:Pleural effusion and anicteric hepatitis associated with cat-scratch disease. Documentation by cat-scratch bacillus. 394 95

The entity of chronic hepatitis has long been an enigma, and its treatment confusing. Recent studies have indicated the importance of excluding causes such as drugs, Wilson's disease and alpha 1-antitrypsin deficiency. After excluding such causes, there are 3 major groups--'autoimmune', hepatitis B, and non-A, non-B (NANB) in all of which an immunological basis for pathogenesis exists. The autoimmune group has been subdivided into a milder type (chronic persistent hepatitis) and a more severe type (chronic active hepatitis) on histological grounds. Corticosteroids are indicated in chronic active hepatitis if cirrhosis or bridging necrosis is present. However, corticosteroids are contraindicated in disease due to the hepatitis B virus where chronic active hepatitis correlates with the presence of replicating virus (serum positive for e antigen, DNA polymerase and HBV-DNA), and in such cases antiviral agents and immunomodulation are being studied. Very little is known about NANB hepatitis in the absence of an assay and there may be more than a single agent. In hepatitis B, the development of serological markers, molecular probes (HBV-DNA), natural animal hepatitis with near-identical viruses, and delta antigen (a virus requiring co-infection with hepatitis B) have all extended our knowledge so dramatically that it is hoped that the enigma of chronic hepatitis will be solved when an assay for NANB hepatitis becomes available.
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PMID:Chronic hepatitis. Aetiology and current management. 673 69

The discovery of hepatitis C was the direct result of the landmark discoveries of hepatitis B virus (HBV) and hepatitis A virus (HAV) and their serologies. Screening tests for HAV and HBV made it possible in the mid-1970s to examine cases of transfusion-associated hepatitis (TAH) and to demonstrate that only approximately 25% resulted from HBV and that none were related to HAV. Consequently, approximately 75% of TAH became classified as non-A, non-B hepatitis (NANBH). Subsequently, chimpanzee studies demonstrated that NANBH was a result of a transmissible agent Although it has been difficult to convince clinicians that NANBH was a serious disease because the overt manifestations are generally mild, it gradually became apparent that the NANBH agent often resulted in chronic hepatitis and sometimes evolved into cirrhosis. The NANBH agent remained a virologic enigma for the next decade until researchers at the Chiron Corporation used an ambitious molecular approach on large volumes of high-titer infectious chimpanzee plasma from the Centers for Disease Control and Prevention (CDC). They extracted RNA, cloned it into an expression vector, and screened the expressed product with presumed immune sera. A single positive clone was found in the millions screened, and, within a year, the entire genome was sequenced and the agent was identified as a novel flavivirus--the hepatitis C virus (HCV). Retrospective analysis of pedigreed samples at the National Institute of Health (NIH) showed that 70% to 90% of NANBH cases were HCV related. The impact of HCV blood donor screening has been enormous. The single-antigen first-generation enzyme immunoassay (EIA-1) prevented 40,000 HCV infections within the first year, and the second-generation assay (EIA-2) has actually reduced new transfusion-related HCV infections to almost zero.
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PMID:Discovery of non-A, non-B hepatitis and identification of its etiology. 1065 50

In a 68-year-old woman with severe chronic hepatitis an extensive investigation revealed no other cause than the use of sotalol for 10 months due to atrial fibrillation. Once the use of the medication had been discontinued the patient's symptoms quickly disappeared and the liver function disorders normalised within 5 months. Sotalol is a beta-adrenergic receptor blocking and anti-arrhythmic agent. It is widely used in patients with supraventricular and ventricular arrhythmias. An adverse effect in terms of liver damage is not known. The pathogenesis of the observed hepatitis remained an enigma because sotalol is a hydrophilic substance which is not metabolized by the liver and is cleared by the kidneys unchanged.
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PMID:[Chronic hepatitis ascribed to the use of sotalol]. 1176 6

Great advances has been achieved in the last 10 years in the study of acute and chronic viral hepatitis. The enigma of non-A non-B viral hepatitis was disclosed when C virus was identified and later when E virus was isolated. New viruses has been searched to explain non-A to non-E viral hepatitis, being reported recently G virus. Epidemiology and clinical aspects has been reviewed identifying unusual clinical forms: choletasic and relapsing hepatitis in HAV infection; escape mutants B virus hepatitis in HVB infection; and the silent evolution to chronicity in more than 70% of cases in HVC infection. Diagnostic techniques has been developed to asses serum antibodies and the virus itself. It is important to quantitate the viral particles in the serum before treatment. PCR technique has been used with good results. A and E virus do not remain in the host and permanent inmunity is obtained after infection is resolved. 10% of B and 80% of C viral hepatitis goes to chronicity. So far, the only drug used to treat chronic viral B, D and C hepatitis is interferon alfa, obtaining good response en 40%. Combinations with Rivabirin and increasing the dose, frequency and duration of interferon treatment are in study. lt is a recomendation to treat acute HCV infection with Interferon alfa to prevent chronicity. Vaccines against A and B virus are used, being included in childhood vaccination programs. No HVC vaccine has developed probably to constant virus mutancy. New chalenges are present in this field and in the identification of new hepatitis viruses.
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PMID:[Viral hepatitis: from A to G viruses]. 1216 88

A number of viruses can initiate central nervous system (CNS) diseases that include demyelination as a major feature of neuropathology. In humans, the most prominent demyelinating diseases are progressive multifocal leukoencephalopathy, caused by JC papovirus destruction of oligodendrocytes, and subacute sclerosing panencephalitis, an invariably fatal childhood disease caused by persistent measles virus. The most common neurological disease of young adults in the developed world, multiple sclerosis, is also characterized by lesions of inflammatory demyelination; however, the etiology of this disease remains an enigma. A viral etiology is possible, because most demyelinating diseases of known etiology in both man and animals are viral. Understanding of the pathogenesis of virus-induced demyelination derives for the most part from the study of animal models. Studies with neurotropic strains of mouse hepatitis virus, Theiler's virus, and Semliki Forest virus have been at the forefront of this research. These models demonstrate how viruses enter the brain, spread, persist, and interact with immune responses. Common features are an ability to infect and persist in glial cells, generation of predominantly CD8(+) responses, which control and clear the early phase of virus replication but which fail to eradicate the infection, and lesions of inflammatory demyelination. In most cases demyelination is to a limited extent the result of direct virus destruction of oligodendrocytes, but for the most part is the consequence of immune and inflammatory responses. These models illustrate the roles of age and genetic susceptibility and establish the concept that persistent CNS infection can lead to the generation of CNS autoimmune responses.
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PMID:Virus demyelination. 1270 46

Histological and clinical features of syncytial giant cell hepatitis (GCH) are rarely observed in adults, and the disease has been associated with several autoimmune disorders and drug reactions. We describe here the case of a 62-year-old woman who presented with evidence of severe acute hepatocellular injury and cholestasis. Serum work-up demonstrated antimitochondrial antibodies specific for primary biliary cirrhosis (PBC) autoantigens, whereas markers of viral infection including hepatitis viruses, paramyxovirus and measles virus were negative. Liver histology revealed the presence of multinucleated hepatocellular giant cells in the parenchymal areas surrounding bridging necrosis. Importantly, damaged interlobular bile ducts were also observed within the lymphocyte-infiltrated portal tracts. Further study using transmission electron microscopy demonstrated the presence of filamentous strands and particles resembling paramyxovirus nucleocapsids in the cytoplasm of syncytial giant cells. To our knowledge, this is the first case of PBC with histological and clinical evidence of syncytial GCH in an adult, and we submit that it might provide novel clues in the enigma of PBC pathogenesis.
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PMID:Primary biliary cirrhosis with multinucleated hepatocellular giant cells: implications for pathogenesis of primary biliary cirrhosis. 1689 19

Mature nonstructural protein-15 (nsp15) from the severe acute respiratory syndrome coronavirus (SARS-CoV) contains a novel uridylate-specific Mn2+-dependent endoribonuclease (NendoU). Structure studies of the full-length form of the obligate hexameric enzyme from two CoVs, SARS-CoV and murine hepatitis virus, and its monomeric homologue, XendoU from Xenopus laevis, combined with mutagenesis studies have implicated several residues in enzymatic activity and the N-terminal domain as the major determinant of hexamerization. However, the tight link between hexamerization and enzyme activity in NendoUs has remained an enigma. Here, we report the structure of a trimmed, monomeric form of SARS-CoV nsp15 (residues 28 to 335) determined to a resolution of 2.9 A. The catalytic loop (residues 234 to 249) with its two reactive histidines (His 234 and His 249) is dramatically flipped by approximately 120 degrees into the active site cleft. Furthermore, the catalytic nucleophile Lys 289 points in a diametrically opposite direction, a consequence of an outward displacement of the supporting loop (residues 276 to 295). In the full-length hexameric forms, these two loops are packed against each other and are stabilized by intimate intersubunit interactions. Our results support the hypothesis that absence of an adjacent monomer due to deletion of the hexamerization domain is the most likely cause for disruption of the active site, offering a structural basis for why only the hexameric form of this enzyme is active.
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PMID:Crystal structure of a monomeric form of severe acute respiratory syndrome coronavirus endonuclease nsp15 suggests a role for hexamerization as an allosteric switch. 1740 50

The establishment of a lifelong latent infection after resolution of primary infection is a hallmark of cytomegalovirus (CMV) biology. Primary infection with human CMV is possible any time in life, but most frequently, virus transmission occurs already perinatally or in early childhood. Many years or even decades later, severe clinical problems can result from recurrence of infectious virus by reactivation from latency in individuals who undergo immunocompromising medical treatment, for instance, transplant recipients, but also in septic patients without canonical immunosuppression, and in elderly people with a weakened immune system. The diversity of disease manifestations, such as retinitis, pneumonia, hepatitis, gastrointestinal disease, and others, has remained an enigma. In clinical routine, seropositivity for IgG antibodies against human CMV is taken to indicate latent infection and thus to define a qualitative risk of recurrence, but it is insufficient as a predictor for the quantitative risk of recurrence. Early experimental studies in the mouse model, comparing primary infection of neonatal and adult mice, led to the hypothesis that high load of latent viral genomes is a better predictor for the quantitative risk. A prolonged period of virus multiplication in the immunologically immature neonatally infected host increased the risk of virus recurrence by an enhanced copy number of latent virus genomes from which reactivation can initiate. In extension of this hypothesis, one would predict today that a higher incidence of reactivation events will also fuel the expansion of virus-specific T cells observed in the elderly, a phenomenon known as "memory inflation". Notably, the mouse model also indicated a stochastic nature of reactivation, thus offering an explanation for the diversity and organ selectivity of disease manifestations observed in patients. As the infection history is mostly undefined in humans, such predictions from the mouse model are difficult to verify by clinical investigation, and moreover, such questions were actually rarely addressed. Here, we have surveyed the existing literature for reports that may help to retrospectively relate the individual infection history to the risk of virus recurrence and recrudescent organ disease.
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PMID:Pediatric roots of cytomegalovirus recurrence and memory inflation in the elderly. 3106 89


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