Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunological disturbances occurring as a result of liver disease have been studied in an animal model of cirrhosis. The mononuclear phagocytic cells of the normal liver phagocytose large amounts of antigen irrespective of whether that antigen is injected directly into the portal or into the systemic circulations. The liver therefore acts as a filter 'in series' and 'in parallel' with the spleen and reduces the immunogenicity of antigens entering the organism by either of these routes. In rats with hepatic cirrhosis, there is a reduction in the capacity of the liver to phagocytose the flagellar antigen of Salmonella adelaide. This results in increased stimulation of splenic lymphoid tissue and in an increased antibody response to this thymus-independent antigen. The increased antigenic stimulus to the spleen may also be responsible for the increased suppressor-cell activity which has been demonstrated in these rats, and may be the mechanism of the diminished cell-mediated immune response both in this animal model of cirrhosis and in the human disease state. These studies suggest that many of the immunological disturbances associated with chronic liver disease may be the result of maldistribution of antigen occurring because of impaired hepatic phagocytic capacity.
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PMID:The immune response in cirrhotic rats. Antigen distribution, humoral immunity, cell-mediated immunity and splenic suppressor cell activity. 1 99

The dynamics of the thymus cell densities was studied during CCl4-induced cirrhogenic hepatopathy. The results show that all thymus compartments take part in immune phenomena occurring in the whole lymphatic system. The maximal intensity of thymus participation is attained in precirrhosis and evolutive cirrhosis. Within the cortical zone, the cell density pyroninophilia and blast-transformed cells increase during the first two months. After two months, there is a decrease of the pyroninophilic elements within the cortical zone, concomitantly with their increase at the medullary level, thus suggesting a migration process of the cells, which change the cortical-medullary ratio.
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PMID:Thymus quantitative morphological changes during CCl4-induced liver cirrhosis. 15 Dec 24

Arteriosclerotic and nonarteriosclerotic rats were treated with carbon tetrachloride (CCL4) to induce cirrhosis of the liver. Massive myocardial infarction was then induced in intact and CCL4-treated animals. During acute necrosis (Days 1 thru 3), animals were killed at 4, 8, 12 and 24 h on Days 1 and 2, and during myocardial repair on Days 4, 5 and 8. During the induction of cirrhosis, animals developed polydypsia, polyuria, and hyperglycemia; during myocardial infarction, the arteriosclerotic + cirrhotic animals developed severe and persistent congestive heart failure, i.e., hydrothorax. Adrenal and thymus gland weights and corticosterone levels indicated that cirrhosis per se increased pituitary--adrenal activity, particularly in arteriosclerotic animals. Enzyme levels of SGOT and SGPT demonstrated severe hepatic damage due to cirrhosis and acute myocardial infarction. Blood triglycerides and cholesterol responded abnormally in cirrhotic animals during acute myocardial ischemia due to their entrapment within hepatic cells. The cirrhotic animals manifested poor myocardial repair with persistent foci of necrosis, calcification, and a high incidence of large, occlusive, atrial thrombi. It is suggested that cirrhosis interferes with lipid metabolism and adrenal steroid conjugation leading to abnormal levels of mineralocorticoids which favor congestive heart failure, poor myocardial repair, and atrial thrombosis.
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PMID:Effect of CCL4-induced cirrhosis on the pathophysiologic course of acute myocardial infarction in nonarteriosclerotic vs arteriosclerotic male rats. 46 16

Hepatic cirrhosis reduced the susceptibility of rats to the induction of tolerance by the oral administration of a protein antigen. Rats with portacaval shunt were rendered tolerant as readily as normal rats. The orally induced state of partial tolerance was shown to be dependent on thymus-dependent lymphocytes: B lymphocytes reacted normally to challenge when injected with T lymphocytes from normal rats. Several factors may contribute to the reduced responsiveness of the cirrhotic rats to the tolerance regime. First, the cirrhotic liver was shown to have a reduced capacity to separate immunogen from tolerogen. Second, because of the reduced phagocytic capacity of the liver, increased quantities of lipopolysaccharide, derived from intestinal microorganisms, enter the blood stream. These substances and products of hepatocyte necrosis have adjuvant activity and may therefore contribute to the changed state of responsiveness of rats with cirrhosis.
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PMID:The immune response in cirrhotic rats. The induction of tolerance to orally administered protein antigens. 108 9

In different forms of chronic hepatitis B, autoantibodies reacting with the epithelium of the basal skin layer (EBSL) and with the epithelium of the cortical and medullary areas of the thymus can be detected by indirect immunofluorescence. The rate of demonstration and the level of these antibodies were established to depend directly on the activity of chronic hepatitis. The data obtained indicate that autoantibodies to EBSL are typical not only for the beginning of the autoimmune process but may also serve as an indicator of the activity of chronic autoimmune disease. The highest titers of the autoantibodies were demonstrated in aggressive hepatitis B associated with liver cirrhosis (in 100% of cases). The data obtained were compared to the liver biopsy findings. Therefore, demonstration of the high titers of autoantibodies can be used without liver biopsy for the diagnosis of liver cirrhosis in hepatitis B.
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PMID:[Autoantibodies against the basement membrane layer of the skin epithelium as an indicator of the activity of the autoimmune process in children with chronic hepatitis B]. 204 86

Delayed cutaneous hypersensitivity was assessed in 120 patients (among them 109 HBsAg positive), with chronic persistent hepatitis, chronic active hepatitis, and compensated as well as decompensated liver cirrhosis by simultaneous application of seven standardized antigens and negative control ("Multitest CMI"). In 21 patients, after 12-24 months the tests were repeated. The sum of indurations of all positive responses ("score") were calculated. Responsiveness measured as results below a normal values was related to the advancing of liver disease (from 13% in chronic persistent hepatitis up to 77% in compensated and 61% in decompensated liver cirrhosis). A comparative analysis (t-Student test) of the arithmetical means of the "scores" revealed statistically significant differences between results obtained in diagnostic groups. It was also dependent from the severity of liver disease. Patients with chronic persistent hepatitis (without specific treatment) and patients with chronic active hepatitis (treated using thymus extract, TFX - "Polfa") has showed an increased "score" values. In contrast to this group, all persons with liver cirrhosis without skin-responsiveness in the first and second tests (anergy) died at the period of 18 months. "Multitest CMI" can be of value in assessing of results of immunotherapy, as well as prognosis of the course of advanced liver disease.
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PMID:[Use of the "Multitest-CMI" in the evaluation of cutaneous delayed hypersensitivity reaction to antigens in patients with chronic diseases of the liver]. 210 Aug 10

We studied in this paper the behavior of immunosuppressive and fibroblast proliferation inhibitory factors in the acute, chronic damage and cirrhotic alteration of the liver. We induced in LEW-rats acute hepatic necrosis by i.v. application of dimethylnitrosamine (DMNA: 35 mg/kg b.wt.) and by i.m. injection of CCl4 (1 ml/kg b.wt., twice a week). After 2-4 weeks we found chronic hepatic damage and after 8-10 weeks liver cirrhosis. As a control, untreated animals were used. Sera and liver factors were prepared from the animals and used for inhibition tests of fibroblast proliferation and MLC reaction. Furthermore, cell count and cell subpopulation of the thymus were determined by monoclonal antibodies (W3/25, OX-8). LF of untreated and DMNA-treated animals exhibited very strong unspecific inhibition effects of fibroblast proliferation and allogenic stimulation. However, with progression of hepatic damage (chronic hepatitis and cirrhosis) both suppressive abilities were gradually reduced. Normal sera showed very slight inhibition of allogenic stimulation but sera of animals with acute hepatic damage showed very strong inhibition. In the 2 weeks of CCl4 treatment, their inhibitory abilities were more than 40%, and with progression of hepatic damage they were gradually reduced. Normal sera or sera of animals with chronic hepatic damage could not suppress the fibroblast proliferation; however, sera of acute hepatic damage inhibited it very strongly. With chronic hepatic damage, the thymus gradually atrophied and, after 10 weeks of CCl4 treatment, it had atrophied completely. Thymocyte differentiation was found only in animals with acute hepatic damage. This suggests that factors which were liberated from the damaged hepatocytes caused differentiation of the thymocytes.
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PMID:Alteration of thymus and of immune regulatory-antifibroblast factors in acute and chronic hepatic damage. 295 51

Using immobilized anti-C3 antibody and an enzyme immunoassay, sera from 26 patients (eight with systemic lupus erythematosus (SLE), four with Hashimoto's thyroiditis, eight haemophiliacs and six with post-hepatitis cirrhosis) containing high levels of circulating immune complexes (IC) were selected. The IC were precipitated with 2.5% polyethylene glycol, washed, treated with acid buffer, neutralized and tested using an enzyme immunoassay in parallel with the original sera for antibody activity against a panel of antigens: human myosin and thyroglobulin, mouse actin and tubulin, calf thymus DNA and trinitrophenyl coupled to bovine serum albumin (TNP/BSA). It was found that all the isolated IC may contain IgG, IgA and IgM antibodies reacting with actin tubulin and TNP/BSA and also, depending upon the disease, antibodies reacting with some of the other antigens of the panel. By comparison to the antibodies present in the original sera, higher titers of antibodies were found in the isolated IC while some antibody specificities not detected in a given serum were occasionally noted in the isolated IC. The antibodies present in the IC seem to possess characteristics similar to those of polyreactive human natural autoantibodies. It is concluded that natural autoantibodies participate actively in the formation of IC found in pathological sera.
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PMID:Enzyme immunoassay analysis of antibody specificities present in the circulating immune complexes of selected pathological sera. 305 7

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

Successful liver allografts were established by combination with allogeneic bone marrow transplantation. When liver tissue of BALB/c (H-2d) or C57BL/6J (H-2b) mice was minced and grafted under the kidney capsules of C3H/HeN (H-2k) mice, it was rejected. However, when C3H/HeN mice were irradiated and reconstituted with T-cell-depleted BALB/c or BALB/c nu/nu bone marrow cells, or with fetal liver cells of BALB/c mice, they accepted both donor (stem-cell)-type (BALB/c) and host (thymus)-type (C3H/HeN) liver tissue. Assays for both mixed-lymphocyte reaction and induction of cytotoxic T lymphocytes revealed that the newly developed T cells were tolerant of both donor (stem-cell)-type and host (thymus)-type major histocompatibility complex determinants. We propose that liver allografts combined with bone marrow transplantation should be considered as a viable therapy for patients with liver disease such as liver cirrhosis and hepatoma.
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PMID:Successful liver allografts in mice by combination with allogeneic bone marrow transplantation. 352 May 75


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