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)

Transgenic mouse lineages were established that carry the normal (M) or mutant (Z) alleles of the human alpha 1-antitrypsin (alpha 1-Pi) gene. All of the alpha 1-Pi transgenic mice expressed the human protein in the liver, cartilage, gut, kidneys, lymphoid macrophages, and thymus. The human M-allele protein was secreted normally into the serum. However, the human Z-allele protein accumulated in several cell types, but particularly in hepatocytes, and was found in serum in tenfold lower concentrations than the M-allele protein. Mice in one lineage carrying the mutant Z allele expressed high levels of human alpha 1-Pi RNA and displayed significant runting (50% of normal weight) in the neonatal period. This lineage was found to have alpha 1-Pi-induced liver pathology in the neonatal period, concomitant with the accumulation of human Z protein in diastase-resistant cytoplasmic globules that could be revealed in the Periodic acid-Schiff reaction (PAS). The phenotype of mice in the strain expressing high levels of the Z allele is remarkably similar to human neonatal hepatitis, and this strain may prove to be a useful animal model for studying this disease.
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PMID:Neonatal hepatitis induced by alpha 1-antitrypsin: a transgenic mouse model. 326 19

Monoclonal antibodies (MoAb) to L3T4 have been used successfully to suppress autoimmunity in murine models for several human autoimmune diseases. To clarify the immunologic and clinical consequences of treatment with anti-L3T4, we examined the effects of chronic administration of anti-L3T4 on the composition of lymphoid organs, the function of lymphocytes, and the histopathology of autoimmune disease in lupus-prone NZB/NZW F1 (B/W) mice. Weekly treatment with anti-L3T4 (2 mg/mouse) from age 5 to 8 months depleted L3T4+ cells from the spleen and lymph nodes, and prevented the development of splenomegaly and lymphadenopathy. The MoAb bound to target cells in the thymus and modulated their expression of the L3T4 antigen but, in contrast to its effect in extrathymic sites, anti-L3T4 did not deplete the target population from the thymus. In fact, after 3 months of therapy, mice that had been treated with anti-L3T4 had much larger thymuses than control mice that had been treated with saline, suggesting that treatment with anti-L3T4 prevented the thymic atrophy that occurs spontaneously in murine lupus. Despite depleting L3T4+ cells from the spleen, treatment with anti-L3T4 did not diminish the response of splenic lymphocytes to T and B cell mitogens, and it augmented splenic natural killer (NK) cell activity. Finally, treatment with anti-L3T4 decreased the diverse histopathologic manifestations of murine lupus. It dramatically reduced glomerular immunoglobulin and complement deposition and diminished lymphocytic infiltration and vasculitis in the kidneys. Treatment also reduced extrarenal immunopathology, including focal hepatitis and salivary gland infiltration. These observations have implications regarding the use of CD4 MoAb in people with autoimmune diseases.
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PMID:Treatment of murine lupus with monoclonal antibody to L3T4. I. Effects on the distribution and function of lymphocyte subsets and on the histopathology of autoimmune disease. 326 85

Using counterimmunoelectrophoresis (CIE), serum antibodies to rabbit thymus extractable antigens were detected in 15% (38/259) of patients with chronic liver disease (CLD) of various aetiologies and 33% (41/124) of patients with miscellaneous connective tissue diseases (CTD). A remarkable diversity of precipitating systems was apparent among cases with the two classes of disorders. All the five systems found in CLD (XR, XR2, SS-B, XR3, XR4) were associated mostly with immunological hepatic disorders. In the 52 autoimmune hepatitis cases, XR was mainly detected (29%), whereas in the 82 primary biliary cirrhosis patients the whole spectrum of reactivities was represented (XR: 11%, XR2: 10%, SS-B and XR3: 2% each, XR4: 1%). XR proved to be closely associated with smooth muscle antibodies (SMA, detected by indirect immunofluorescence on rat kidney sections) both qualitatively and quantitatively. Since all SMA positive sera with anti-actin specificity (SMAT, SMAG) were XR positive and purified actin could absorb out XR CIE reactivity, the hypothesis is made that a cross-reaction occurs between XR antigen and actin epitope(s).
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PMID:Precipitating antibodies to rabbit thymus extractable antigens in chronic liver disease: relationship with anti-actin antibodies. 330 18

We report two sisters with neonatal hemochromatosis (NHC), including the first documented survivor. Characterized by excessive parenchymal iron in liver, pancreas, heart, and other organs, but little iron in the spleen, bone marrow, or other sites of the reticuloendothelial system, NHC is rarely reported and has been uniformly fatal. The first infant (case 1) presented with neonatal hypoglycemia, coagulopathy, and mild hyperbilirubinemia; she rapidly deteriorated and died of multisystem failure. Autopsy showed cirrhosis. Her sister (case 2) presented similarly; liver biopsy showed giant cell hepatitis, which is consistent with idiopathic neonatal hepatitis (INHP). However, iron staining revealed that case 1 had extensive iron deposits in the liver, pancreas, heart, thymus, and bone, but none in bone marrow or spleen. Case 2 had grade 4 liver iron staining, normal bone marrow iron, elevated serum ferritin and transferrin saturation, and HLA-A3 haplotype. At 16 months of age, the growth, development, and serum measures of iron status in case 2 were normal; liver biopsy showed fibrosis, negative iron staining, and normal tissue iron concentration. NHC is compatible with survival, has clinicopathologic features that overlap with INHP, and may frequently be misdiagnosed as INHP. A prospective study is needed to determine the incidence and natural history of NHC--a disorder that may be more common than is currently recognized.
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PMID:Familial neonatal hemochromatosis with survival. 333 84

To better assess the extent of the tissue tropism of mammalian hepadnaviruses, 10 tissues from each of six woodchucks were examined for the presence and state of woodchuck hepatitis virus (WHV) nucleic acids 15 months after experimental WHV infection. The tissues examined were peripheral blood lymphocytes, lymph node, spleen, bone marrow, thymus, pancreas, kidney, ovary, testis, and liver. Tissue samples from three chronically infected animals and three animals with serologic patterns of recovery (serum: WHsAg-, anti-WHs+, anti-WHs+, WHV DNA-) from acute WHV infection were analyzed in parallel by in situ hybridization and Southern and Northern blot techniques. WHV nucleic acids were detected in several individual tissues from each animal examined, although not all tissues in every animal contained WHV. Substantial differences were observed among the various tissues and animals with respect to the frequency, level, and intratissue distribution of WHV nucleic acids, as well as the presence of different viral genomic forms. Active WHV DNA replication was present only in the liver and spleen of the chronically infected animals. No evidence of ongoing WHV DNA replication was found in any of the tissues from the recovered animals. WHV DNA was homogeneously distributed among all hepatocytes in the livers of the chronic carriers. By contrast, WHV DNA in all the extrahepatic tissues, and in the livers of the recovered animals, was detected only in scattered foci of cells.
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PMID:Systemic distribution of woodchuck hepatitis virus in the tissues of experimentally infected woodchucks. 338 68

"Wasting" or "fading" syndromes are common causes of puppy and kitten mortality. Numerous infectious and toxic, metabolic, or nutritional factors could potentially be responsible for wasting and death in young animals. Evidence has been presented that infectious canine hepatitis virus infection, beta-hemolytic streptococcus infection, and feline infectious peritonitis virus infection are responsible for a significant number of deaths due to wasting syndrome. However, many cases of wasting syndrome cannot be attributed to infectious agents or other specific etiologies. The thymus gland warrants special attention when one is evaluating an animal with a wasting syndrome because it is known that, in some species, neonatal thymectomy results in wasting and death. Unfortunately, most reports describing fading syndromes in puppies and kittens do not mention the gross or histologic appearance of the thymus gland at postmortem examination. When examining the thymus gland, one must keep in mind that the thymus may be hypoplastic owing to a congenital or genetic defect in its structure and function or it may be atrophic secondary to whatever is causing the fading syndrome. If a thorough history, clinical examination, and/or postmortem examination do not reveal a cause for the fading syndrome, then defective thymus function should be considered as a possible causative or contributing factor to the fading syndrome. In these cases, therapy designed to replace or improve the defective thymus function should be considered. At least one form of wasting syndrome in puppies (immunodeficient dwarfism) has been found to respond to short-term therapy with a thymus hormone (thymosin fraction 5) or with bovine growth hormone (which is thymotropic) in limited clinical trials. It is possible that other forms of wasting or fading syndromes would also respond to therapy with thymus hormone or growth hormone. Certain thymus hormones (thymopoietin pentapeptide, thymosin alpha 1, facteur thymique serique, and rabbit thymus acetone powder) and bovine growth hormone are commercially available. Before initiating therapy, one should consider that if the cause of the wasting syndrome is genetic, then successful treatment may perpetuate a genetic defect. More research (both basic and clinical) is needed to determine the role of thymus gland dysfunction in fading syndromes of puppies and kittens and if therapy with one or several of the thymus hormones or with growth hormone could reverse the symptoms of wasting.
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PMID:Possible association of thymus dysfunction with fading syndromes in puppies and kittens. 349 4

The immune functions of neonatally thymectomized C3Hf mice exposed only temporarily to thymus function show a progressive decay with time in the absence of the thymus. The immune responses studied at different ages in the range of 100-600 days were: first-set rejection of H-2-compatible and incompatible skin allografts, second-set rejection of skin allografts, capacity of spleen cells to produce graft-versus-host reactions in F(1) hybrids, resistance to infection with mouse hepatitis virus, and response of spleen cells to phytohemagglutinin in vitro. These long-term studies had the purpose of determining the duration of the restoration induced by thymus function when the mice were exposed only temporarily to it. Different models were used but the two basic ones were: (a) mice grafted intraperitoneally at 15 days of age with a syngeneic thymus that was removed surgically at 10, 20, or 30 days after grafting, and (b) mice grafted at 15 days of age with allogeneic strain A thymoma or C57BL thymus, these representing situations in which there is spontaneous rejection of the restoring graft. In all the experimental models used, the animals were restored when tested at 100 days of age, but progressively became immunologically incapacitated at 200-300 days of age. From the more controlled experiments in which the restoring thymus graft was removed surgically, the following conclusions can be drawn. (a) A short exposure to a thymus graft can produce restoration of immune functions in neonatally thymectomized mice, but this restoration is not self-sustaining in the absence of the thymus and declines progressively with age. The decline usually starts at 200-300 days of age. (b) This was especially clear in experiments in which the same animal was tested twice in its lifetime for capacity to produce graft-versus-host reactions; these animals were competent at 100 days and became incompetent at 400 days of age. (c) The shortest period of thymic exposure studied was 10 days; if vascularization of the graft is taken into account, 2-3 days of thymic function are sufficient to produce restoration. (d) The immune decay observed in the thymectomized animals exposed temporarily to thymus was more profound than the physiological decay of immunity observed in control animals of similar age. (e) Of all the tests studied, the response of spleen cells to phytohemagglutinin was to be preserved the longest in animals exposed only temporarily to thymic function. The present results were interpreted in accordance with our previous findings indicating that a population of postthymic cells can be developed by temporary exposure of neonatally thymectomized animals to thymic function, but that this population is not self-sustaining in the absence of thymus and progressively decays by physiological attrition.
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PMID:Studies on thymus function. 3. Duration of thymic function. 440 Jun 98

An effect of replication of certain viruses in murine monocytic macrophages was manifested by depletion of cells through degenerative and necrotizing changes in thymus-dependent areas of lymphoid structures. In mice infected with murine hepatitis virus (MHV-3) or lactate dehydrogenase virus, these changes were transient in mice killed on postinoculation day (PID) 2. To study these morphologic changes due to viral replication, adult Swiss specific-pathogen-free homozygous nude mice (nu/nu) and their heterozygous haired littermates (nu/+) were inoculated with 10(5) LD50 of MHV-3, euthanatized, and necropsied on PID 1, 2, 4, 6, 8, and 10 along with noninoculated controls. The nu/+ and nu/nu mice killed on PID 2 had lymphocytic karyorrhexis and depletion of cells in the thymus-dependent area. In the heterozygote, these characteristic lesions were transient; whereas in the homozygote, lesions persisted and were present in survivors euthanatized and necropsied on PID 16. Although the intensity of lesions due to MHV-3 varied between nu/+ and nu/nu mice, virus titers determined on liver homogenates were similar for the homozygote and heterozygote during acute disease. Nude and nonnude mice given lactate dehydrogenase virus and killed on PID 2 had a transient depletion of lymphocytes; whereas mice given lymphocytic choriomeningitis virus and killed on PID 4 had a similar lesion. Lesions neither occurred when mice were treated with silica before inoculation, indicating that functional monocytic macrophages were required, nor occurred when another virus, herpes simplex virus type 1, was given.
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PMID:Comparison of early splenic changes associated with replication of viruses in murine monocytic macrophages. 632 45

This study evaluated the subchronic (14-day) toxicity of selected (0.2, 1.0, and 4.0 mg/kg) daily subcutaneous injections of diethylstilbestrol (DES) in female (C57B1/6 X C3H)F1 mice. Parameters observed included body and organ weights, gross organ morphology, histopathology, clinical chemistry, and hepatic microsomal enzyme activities. The liver, bone marrow, and thymus are major target organs for DES. Liver enlargement, with associated histopathological changes consistent with mild hepatitis, centrolobular necrosis, and sinusoidal changes were observed. Supporting the histological changes were alterations in serum enzyme levels and microsomal enzyme activity. Bone marrow changes included decreases in the number of cells as well as the number of colony forming units per gram stem cells. Toxicity to the thymus was evidenced by decreased thymic weights and lymphocyte depletion. The hepatic and thymic effects were observed at the lowest (0.2 mg/kg) dose. Although all parameters were not assessed for recovery, those that were evaluated returned to control levels by thirty days after treatment.
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PMID:Subchronic toxicology of diethystilbestrol in the mouse. 662 66

Clinico-morphological study of the liver was carried out in 54 patients with generalized severe myasthenia of 1 1/2-2-year duration. The functional values of the liver were studied before thymectomy and on the 1st post-operation day. Eight liver punctates were examined histologically and electron-microscopically. A picture of nonspecific reactive hepatitis whose clinical manifestations included hyperbilirubinemia, and disorder of the absorbing and excreting functions of the liver was revealed. Ultrastructural signs of cholestasis were found. The observed fibrosis of the organ was accompanied by hypertrophy and hyperplasia of lipocytes but without their manifest transformation into lipofibroblasts . Hypoplasia of hepatocytes was observed in myasthenia which may be due to their thymus-dependent inhibition. The mechanism of disturbance of pigment metabolism in the liver of patients with myasthenia is multi-component and may be associated with disorders in bile evacuation, hematotissue barrier, and probably, structural-functional incompetence of hepatocytes.
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PMID:[Morphologic characteristics of disorders of liver function in myasthenia]. 672 5


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