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)

An outbreak of hepatitis caused by hepatitis E virus (HEV) in Abbottabad, Pakistan was traced to fecal contamination of a water system. Of 109 men hospitalized with hepatitis, 104 (95%) had serologic evidence of acute hepatitis E (IgM antibody to HEV [anti-HEV]), three (3%) probably had acute hepatitis E (high titers of IgG anti-HEV without IgM), and two had acute hepatitis A. Among a subset of 44 men with acute hepatitis E from whom three serum specimens were obtained over a four-month period, the anti-HEV IgG geometric mean titers (GMTs) decreased from 1,519 during the outbreak to 657 at four months. The IgM anti-HEV was detected in 40 (91%) of 44 sera obtained at admission (GMT = 533 during acute disease), but in only six (14%) four months later. The prevalence of anti-HEV in this population before the outbreak was estimated to be 30%. The presence of IgG anti-HEV appeared to protect against clinical hepatitis or development of serologic evidence of new infection with HEV. This is the second major epidemic of hepatitis E in the Pakistani military confirmed by an anti-HEV enzyme-linked immunosorbent assay (ELISA). Evidence that pre-existing antibody as measured by this ELISA protects against disease is important for assessment of vaccine development.
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PMID:Epidemic of hepatitis E in a military unit in Abbotrabad, Pakistan. 1251 59

The coronavirus, mouse hepatitis virus strain JHM, causes acute and chronic neurological diseases in rodents. Here we demonstrate that two closely related virus variants, both of which cause acute encephalitis in susceptible strains of mice, cause markedly different diseases if mice are protected with a suboptimal amount of an anti-JHM neutralizing antibody. One strain, JHM.SD, caused acute encephalitis, while infection with JHM.IA resulted in no acute disease. Using recombinant virus technology, we found that the differences between the two viruses mapped to the spike (S) glycoprotein and that the two S proteins differed at four amino acids. By engineering viruses that differed by only one amino acid, we identified a serine-to-glycine change at position 310 of the S protein (S310G) that recapitulated the more neurovirulent phenotype. The increased neurovirulence mediated by the virus encoding glycine at position S310 was not associated with a different tropism within the central nervous system (CNS) but was associated with increased lateral spread in the CNS, leading to significantly higher brain viral titers. In vitro studies revealed that S310G was associated with decreased S1-S2 stability and with enhanced ability to mediate infection of cells lacking the primary receptor for JHM ("receptor-independent spread"). These enhanced fusogenic properties of viruses encoding a glycine at position 310 of the S protein may contribute to spread within the CNS, a tissue in which expression of conventional JHM receptors is low.
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PMID:Enhanced virulence mediated by the murine coronavirus, mouse hepatitis virus strain JHM, is associated with a glycine at residue 310 of the spike glycoprotein. 1297 Apr 10

An hepatic disease caused by a filterable agent carried in leukemic mice is described. Ordinarily the virus remains latent and asymptomatic. If, however, the mice are treated with urethane or methylformamide before and after virus inoculation, the disease becomes manifest and is characterized by extremely marked liver necrosis. Infant mice, a large percentage of weanlings, and adult Bagg albino mice are killed when injected with a filtrate from organs of diseased animals. Adult F1 and Swiss mice show signs of the disease but generally recover. They succumb, however, when simultaneously treated with urethane or methylformamide. By continuing the treatment of consecutive transfer generations an acute disease can be induced which finally kills all adult F1 mice without the treatment. At this stage the original leukemia may be lost. Mice which have recovered from the subacute disease are resistant to the acute disease, and mice injected with the latent form of the agent are immune to the subacute disease. However, even immunized animals lose their resistance if they are treated with urethane. The acute or subacute disease can be reduced to the latent stage by passing the agent through several generations of immunized animals. The relationship of this hepatitis virus of mice to viruses causing similar diseases is discussed, as is the possibility that these agents are closely related, if not identical.
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PMID:Viral hepatitis associated with transplantable mouse leukemia. I. Acute hepatic manifestations following treatment with urethane or methylformamide. 1321 22

Coxiella burnetii causes acute Q fever in humans and occasional chronic infections that typically manifest as endocarditis or hepatitis. Isolates associated with acute disease were found to be distinct from a group of chronic disease isolates by a variety of biochemical parameters and in a guinea pig fever model of acute disease, suggesting a difference in virulence potential. We compared antigenic polypeptides among C. burnetii isolates and found an immunodominant 28-kDa protein in acute group isolates but not in chronic group isolates (T. Ho, A. Hotta, G. Q. Zhang, S. V. Nguyen, M. Ogawa, T. Yamaguchi, H. Fukushi, and K. Hirai, Microbiol. Immunol. 42:81-85, 1998). In order to clone the adaA gene, the N-terminal amino acid sequence of adaA was determined and a 59-bp fragment was amplified from Nine Mile phase I DNA by PCR. The putative gene fragment was used to screen a lambda ZAP II genomic DNA library, and an open reading frame expressing a 28-kDa immunoreactive protein was identified. Sequence analysis predicted a gene encoding an approximately 28-kDa mature protein with a typical signal sequence. The adaA (acute disease antigen A) gene was detected in acute group C. burnetii isolates but not identified in chronic group isolates by PCR and Southern blotting. A typical signal peptide was predicted in adaA, and specific antibody to adaA reacted with the purified membrane fraction of acute group isolates by Western blotting, suggesting that adaA is exposed on the outer surface of C. burnetii. adaA was overexpressed in pET23a as a fusion protein in Escherichia coli to develop anti-recombinant adaA (anti-radaA) specific antibody, which recognized a approximately 28-kDa band in acute group isolates but not in chronic group isolates. In addition, immunoblotting indicates that radaA reacted with sera derived from animals infected with acute group isolates but did not react with sera from animals infected with chronic group isolates. These results support the idea that an adaA gene-targeted PCR assay and an radaA antigen-based serodiagnostic test may be useful for differential diagnosis of acute and chronic Q fever.
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PMID:Identification and characterization of an immunodominant 28-kilodalton Coxiella burnetii outer membrane protein specific to isolates associated with acute disease. 1573 Oct 54

Coxiella burnetii is an obligate intracellular bacterium that causes a worldwide zoonosis, Q fever, and can be misused as a biological warfare agent. Infection in animals (coxiellosis) is mostly persistent. Infection in humans is often asymptomatic, but it can manifest as an acute disease (usually a self-limited flu-like illness, pneumonia, or hepatitis) or as a chronic form (mainly endocarditis, but also hepatitis and chronic fatigue syndrome). C. burnetii infection in pregnant women may result in abortions, premature deliveries, and stillbirths. Infection in nature is maintained and transmitted by ticks as the principal vector and reservoir. Cattle, sheep, and goats are the most important source of human infections. Humans contract C. burnetii infection mostly by aerosol in contact with contaminated environs, wind playing an important factor in spreading the infection. The wide distribution of C. burnetii contributes to a high resistance of its extracellular small cell variant to environmental conditions. Its intracellular large cell variant, adapted to survive under harsh conditions of phagolysosomes, enables long-term survival and persistence of C. burnetii, namely in monocytes/macrophages. Host factors such as underlying disease and cell-mediated immunity play a decisive role in the clinical expression of C. burnetii infection. Complete genome analysis of C. burnetii will certainly contribute to better understanding of the pathogenesis of C. burnetii infection and will improve Q fever diagnosis and immunoprophylaxis.
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PMID:Coxiella burnetii infection. 1648 1

Q fever is a zoonosis with many manifestations. The most common clinical presentation is an influenza-like illness with varying degrees of pneumonia and hepatitis. Although acute disease is usually self-limiting, people do occasionally die from this condition. Endocarditis is the most frequent chronic presentation. Although Q fever is widespread, practitioner awareness and clinical manifestations vary from region to region. Geographically limited studies suggest that chronic fatigue syndrome and cardiovascular disease are long-term sequelae. An effective whole-cell vaccine is licensed in Australia. Live and acellular vaccines have also been studied, but are not currently licensed.
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PMID:Q fever. 1650 66

In this study one spleen-intact dog (A) and two splenectomised dogs (BSE, CSE) were infected with Babesia canis. All animals developed an acute disease characterised by fever, haemoglobinuria and anaemia, the latter being more severe in the splenectomised dogs. Fever and parasitised red blood cells were detected for three days after imidocarb treatment in the splenectomised animals. Haematological abnormalities included regenerative anaemia, thrombocytopenia and leukopenia (due to neutropenia and lymphopenia) in the acute phase, soon followed by leukocytosis, neutrophilia and left shift a few days later. Acute hepatopathy was detected in all dogs with elevated ALT activity, which was more seriously altered in the splenectomised dogs. Diffuse changes in liver structure and hepatomegaly were seen by ultrasonography. Liver biopsy and histology revealed acute, non-purulent hepatitis in the splenectomised dogs. Both splenectomised dogs were successfully cured after collection of 400 ml highly parasitised blood, proving that large-amount antigen production is possible with rescuing the experimental animals. Whole blood transfusion, imidocarb and supportive care with infusions, antipyretics, glucocorticoids and diuretics were applied. The spleen-intact dog clinically recovered after receiving supportive treatment, with no imidocarb therapy. Microbial infections developed in both splenectomised animals (BSE: haemobartonellosis, CSE: osteomyelitis caused by Escherichia coli), probably as a consequence of immunosuppression after splenectomy and glucocorticoid therapy.
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PMID:Clinicopathological changes and effect of imidocarb therapy in dogs experimentally infected with Babesia canis. 1661 23

The diagnostic criteria for autoimmune hepatitis have been codified, and a scoring system can quantify the strength of the diagnosis. Centrilobular (zone 3) necrosis signifies acute disease, and severe acute and fulminant presentations of autoimmune hepatitis are recognized. The absence of symptoms at presentation may identify some patients who do not require treatment, but therapeutic decisions must be based on disease activity not symptoms, especially since 26-70% of asymptomatic patients become symptomatic. Elderly patients have more advanced disease at presentation, but they respond well to treatment. Antibodies to soluble liver antigen/liver pancreas, asialoglycoprotein receptor, actin, and liver cytosol type 1 have prognostic value. Molecular mimicry between viral and self-antigens is the likely basis for the autoimmune response. Susceptibility alleles optimize antigen presentation. Polymorphisms influence immunocyte activation, counter-regulatory actions within the cytokine milieu, and apoptotic pathways for hepatocyte and immunocyte death. Perturbations in the populations of T regulatory cells and natural killer T cells disrupt immune homeostasis. Cyclosporine, mycophenolate mofetil, and budesonide afford new treatment opportunities, and molecular interventions at critical pathogenic pathways are feasible, especially within the cytokine network. Confident animal models of the human disease and a collaborative network of clinical investigators are the requisites for progress.
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PMID:Evolving concepts in the diagnosis, pathogenesis and treatment of autoimmune hepatitis. 1741 44

The Kings College group was the first to describe a clinical syndrome similar to autoimmune hepatitis in children and young adults transplanted for non-immune mediated liver diseases. They coined the term "de novo autoimmune hepatitis". Several other liver transplant centres confirmed this observation. Even though the condition is uncommon, patients with de novo AIH are now seen in most of the major transplant centres. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The most characteristic laboratory hallmark is a marked hypergammaglobulinaemia. Autoantibodies are common, mostly ANA. We described also a case of LKM1-positivity in a patients transplanted for Wilson's disease, however this patients did not develop clinical or histological features of AIH. Development of SLA/LP-autoantibodies is also not described. Therefore, serologically de novo AIH appears to correspond to type 1 AIH. Like classical AIH patients respond promptly to treatment with increased doses of prednisolone and azathioprine, while the calcineurin inhibitors cyclosporine or tacrolimus areof very limited value - which is not surprising, as almost all patients develop de novo AIH while receiving these drugs. Despite the good response to treatment, most patients remain a clinical challenge as complete stable remissions are uncommon and flares, relapses and chronic disease activity can often occur. Pathogenetically this syndrome is intriguing. It is not clear, if the immune response is directed against allo-antigens, neo-antigens in the liver, or self-antigens, possibly shared by donor and host cells. It is very likely that the inflammatory milieu due to alloreactive cells in the transplanted organ contribute to the disease process. Either leading to aberrant antigen presentation, or providing co-stimulatory signals leading to the breaking of self-tolerance. The development of this disease in the presence of treatment with calcineurin inhibitors supports the view held by most specialists in autoimmune hepatitis that these drugs, even though effective in acute disease, are not helpful in the long-term management of autoimmune liver diseases.
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PMID:De novo autoimmune hepatitis after liver transplantation. 1793 Dec 3

The role of CC chemokine receptor 1 (CCR1) in host defense and disease development was determined in a model of viral-induced neurologic disease. Intracerebral (IC) infection of mice with mouse hepatitis virus (MHV) results in an acute encephalitis followed by a chronic demyelinating disease similar in pathology to the disease multiple sclerosis (MS). No increase in mortality was observed during the acute phase of disease following MHV infection of mice lacking CCR1 (CCR1-/-) as compared to wild-type (CCR1+/+) mice. However, by 21 d post-infection, 74% of CCR1-/- mice had succumbed to death compared to only 32% mortality of CCR1+/+ mice, indicating that chemokine signaling through CCR1 significantly (p <or= 0.04) enhanced survival following IC infection with MHV. Increased mortality in CCR1-/- mice was not associated with increased viral recovery from the CNS, although CCR1 deficiency correlated with reduced T-cell accumulation within the CNS during acute, but not chronic, disease. Despite the reduction in T-cell trafficking into the CNS of CCR1-/- mice during acute disease, components of host defense remained unaltered; T-cell effector functions including cytolytic activity and proliferation and the expression of IFN-gamma within the CNS were not significantly different between CCR1+/+ and CCR1-/- infected mice. In addition, macrophage infiltration into the CNS was unaffected in MHV-infected CCR1-/- mice when compared to CCR1+/+ mice. Furthermore, assessment of neuropathology revealed no difference in the severity of demyelination between CCR1-deficient and wild-type mice. Together, these findings reveal that T-cell and macrophage trafficking are not dependent on CCR1 and highlight an important role for CCR1 signaling in promoting survival during chronic MHV infection.
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PMID:CCR1 deficiency increases susceptibility to fatal coronavirus infection of the central nervous system. 1815 33


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