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 major serum antiprotease is alpha 1-antitrypsin (A1AT). Deficiency of A1AT can result in infantile cirrhosis and premature emphysema, both of which have a high degree of morbidity and significant mortality. Although synthesized primarily by the liver, A1AT has been histochemically localized in monocytes and macrophages in vitro and has been shown to be produced in tissue culture of monocyte-macrophage origin. This study was planned to quantitatively and qualitatively assess the in vivo monocyte-macrophage system contribution to serum A1AT. We used bone marrow transplantation (BMT) as an experimental method because there is commanding evidence that after engraftment, the monocyte-macrophage system of the recipient is replaced by that of donor origin. Protease inhibitor (Pi) typing was done on 150 potential BMT recipients and on their potential donors before transplantation. From these initial recipients, 92 eventually underwent transplantation, and 11 recipient-donor pairs, in which each donor's Pi type contained a band not in the recipient's Pi type, were chosen for the study. Six recipients survived beyond 100 days after BMT, and in these cases the donor contained either an S or an M2 band in his or her Pi type not present in the recipient. Using a silver stain method on diluted serum of known M1M2 and MS types, we were able to detect a 2% dilution of the S band and a 25% dilution of the M2 band. When the same method was applied to gels used in typing recipient Pi after BMT, we were unable to detect any contribution to serum A1AT by the donor monocyte-macrophage system.
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PMID:Contribution of monocyte-macrophage system to serum alpha 1-antitrypsin. 304 64

Familial idiopathic nonarteriosclerotic cerebral calcification (FINCC) constitutes a rare but pathologically well defined disorder. Thus far, central nervous system symptoms and signs have been the only recorded expression of this disease. Autosomal dominant and autosomal recessive inheritance have both been postulated as cause. We describe three sibs who had symmetrical cerebral calcifications, but three also had cirrhosis and pulmonary emphysema; two had congenital cerebral aneurysms. All were male and of short stature; they also had delayed development and seizures, and two had other neurologic deficits. One sib died at age 3 years of hepatic failure and portal hypertension. Ruptured cerebral aneurysms led to the death of the other two boys at ages 8 and 13 years. The cerebral calcifications symmetrically involved the basal ganglia and thalami, the dentate nucleus, and the cortical and subcortical areas of the cerebrum. The liver was studied by sequential biopsies in two of the children and in all three by autopsy. Fatty degeneration and portal fibrosis preceded a periportal and micronodular cirrhosis. Severe bilateral pulmonary emphysema was present in one sib at age 12 years, whereas all three had bullae and cysts at autopsy. Ruptured left middle cerebral artery aneurysms were demonstrated in two sibs, and one also had aneurysms of the anterior and posterior communicating arteries. We conclude that in this family FINCC is a complex pleiotropic mendelian mutation, either of autosomal or X-linked recessive nature, whose basic pathogenesis remains unknown but may involve a metabolic defect. This form of FINCC may be a previously undescribed syndrome or a form of FINCC in which extraneural manifestations were previously overlooked.
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PMID:Berry aneurysms, cirrhosis, pulmonary emphysema, and bilateral symmetrical cerebral calcifications: a new syndrome. 313 Aug 69

Alpha 1-Antitrypsin is the principal serum protease inhibitor. In addition to the well-recognized association with early-onset emphysema and cirrhosis, alpha 1-antitrypsin deficiency may be associated with panniculitis. In this article we describe three patients in whom the recognition of certain clinical and histologic features of panniculitis eventually led to the diagnosis of alpha 1-antitrypsin deficiency. Two of our patients were young adults and one was a child. All three had draining, panniculitis, or cellulitis-like lesions at sites of prior trauma. The histopathologic findings were characterized by liquefactive dermal necrosis and collagenolysis of the fibrous septa of the subcutis. The combination of these clinical and microscopic findings should suggest the diagnosis of alpha 1-antitrypsin deficiency panniculitis. The suspicion can be verified by obtaining quantitative serum levels and enzyme phenotyping. The identification of the alpha 1-antitrypsin deficiency state as the cause of a distinct type of panniculitis adds additional evidence for the elimination of the term Weber-Christian disease.
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PMID:Alpha 1-antitrypsin deficiency associated with panniculitis. 325 92

Alpha-1-protease inhibitor (A1PI) exists in over 30 biochemical variants (the Pi system), inherited as autosomal codominant alleles. Homozygotes of Pi type Z have only 10 to 20 percent of the normal serum A1PI concentration and have a high risk of developing pulmonary emphysema. A1PI is an inactivator of polymorph lysosomal elastase, the unopposed action of which may damage the lung. Cigarette smoking is an important additional risk factor. Neonatal hepatitis occurs in 10 to 20 percent of Pi type Z persons, and cirrhosis develops in a number of them in later childhood or in adult life. In heterozygotes of Pi type MZ, pulmonary or hepatic disease may also develop, though they are at lesser risk than type Z homozygotes. Specific A1PI replacement therapy derived from human plasma is now available and has been administered to Pi type Z patients by weekly intravenous infusion without adverse effects. A controlled clinical trial would be desirable, though this would be attended by organizational and economic problems.
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PMID:Natural history of alpha-1-protease inhibitor deficiency. 328 86

alpha(1)-Protease inhibitor (alpha(1)-Pi) deficiency is associated with emphysema, neonatal hepatitis and cirrhosis. The deficiency associated with emphysema has multiple alleles. Cigarette smoke may influence the onset of emphysema in a twofold manner: by overwhelming the concentration of alpha(1)-Pi by increasing elastase release, and by inactivating the alpha(1)-Pi active site through oxidation. alpha(1)-Pi-associated hepatic disease occurs primarily in children with the allele PiZZ, most of whom are asymptomatic although in a small percentage severe obstructive jaundice and fatal junvenile cirrhosis develop. Pharmacologic intervention and alpha(1)-Pi replacement therapy are being tested against alpha(1)-Pi-associated emphysema.
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PMID:Association of alpha 1-antitrypsin deficiency with lung and liver diseases. 332 8

Standardized proportional mortality ratios (PMR) were computed for a population of highway workers. Hazards of highway maintenance work include exposure to solvents, herbicides, asphalt and welding fumes, diesel and auto exhaust, asbestos, abrasive dusts, hazardous material spills, and moving motor vehicles. Underlying cause of death was obtained for 1,570 workers who separated from the California Department of Transportation between 1970 and 1983, and who died in California between 1970 and 1983 (inclusive). Among 1,260 white males, the major findings were statistically significant excesses of cancers of digestive organs (PMR = 128), skin (PMR = 218), lymphopoietic cancer (PMR = 157), benign neoplasms (PMR = 343), motor vehicle accidents (PMR = 141), and suicide (PMR = 154). Black males (N = 66) experienced nonsignificant excesses of cancer of the digestive organs (PMR = 191) and arteriosclerotic heart disease (PMR = 143). Among 168 white females, deaths from lung cancer (PMR = 189) and suicide (PMR = 215) were elevated. White male retirees, a subgroup with 5 or more years of service, experienced excess mortality due to cancers of the colon (PMR = 245), skin (PMR = 738), brain (PMR = 556), and lymphosarcomas and reticulosarcomas (PMR = 514). Deaths from external causes (PMR = 135) and cirrhosis of the liver (PMR = 229) were elevated among white males with a last job in landscape maintenance. White males whose last job was highway maintenance experienced a deficit in mortality from circulatory diseases (PMR = 83) and excess mortality from emphysema (PMR = 250) and motor vehicle accidents (PMR = 196). Further epidemiologic and industrial hygiene studies are needed to confirm the apparent excess mortality and to quantify occupational and nonoccupational exposures. However, reduction of recognized hazards among highway maintenance workers is a prudent precautionary measure.
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PMID:Mortality among California highway workers. 335 85

In order to test the hypothesis that Roman Catholic priests are at low risk for prostatic cancer because of their celibacy, a cohort of 10,026 men who were active or retired diocesan (parish) Roman Catholic priests in the United States on January 1, 1949 were followed until death, leaving the priesthood, or January 1, 1978. The overall standardized mortality ratio (SMR) was 103 and the SMR for cancer of the prostate was 81. Other interesting findings include increased SMRs for cancer of the larynx (147), cirrhosis of the liver (147), and diabetes (182) and decreased SMRs for lung cancer (59), emphysema (26), and suicide (13).
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PMID:Retrospective cohort mortality study of Roman Catholic priests. 340 88

The alpha 1-antitrypsin (AAT) or protease inhibitor (Pi) genetic polymorphism was studied in 144 white, 100 coloured, 104 Indian and 127 black (Northern Sotho) healthy individuals (controls), in the Pretoria area. Their Pi phenotype and gene frequency distributions are compared with world-wide data on other population groups. The severely deficient Pi phenotypes S, Z and SZ jointly attain frequencies of 0.3-0.4% in coloureds and whites; in blacks and Indians the corresponding frequencies are very much lower. The implication for preventive medicine and public health is that in South Africa the sequelae of Pi deficiencies such as cirrhosis of the liver and/or emphysema of the lung are of practical importance in whites and coloureds and much less so in blacks and Indians. In 176 white breast cancer patients studied, the Pi phenotype and gene frequency distributions were found to be similar to those of healthy controls (not statistically significant). Cohorts of other patients were also phenotyped because of their low alpha 1-globulin concentrations in routine serum protein electrophoresis and/or their specific disease condition (cirrhosis of the liver or emphysema of the lung) known to be associated with AAT deficiency. These results are discussed in terms of their significance for family follow-up, genetic counselling and a preventive service. The need to avoid atmospheric pollution, especially cigarette smoke, is emphasised as a major and cost-effective preventive measure.
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PMID:Alpha-1-antitrypsin genetic polymorphism in South Africa. 349 69

By light microscopy and immunoperoxidase methods, morphology and distribution of alpha-1-proteinase inhibitor (Api) cells in the pancreatic islets were studied in seven patients with and in 17 patients without periodic acid-Schiff-positive, diastase-resistant globules in the liver. Five of the seven patients with liver globules had cirrhosis and emphysema, suggesting genetic deficiency of Api, which was confirmed in four by pi phenotyping (blood from one patient was not available). The two remaining patients had only a mild degree of liver fibrosis and mild emphysema and showed a normal MM phenotype. Islet cell hyperplasia and an increased population of Api cells were observed in all five patients with genetic deficiency, compared with the 17 patients without Api deficiency. These morphologic changes were more pronounced in the one homozygous patient than in the heterozygous patients. Nesidioblastosis, ductular proliferation, and atypia of insular cells were seen only in patients with an abnormal phenotype. The increased amount of Api in the islets in the genetic deficiency state may be due to hyperplasia and hypertrophy of Api cells or due to storage of abnormal Api in the preexisting Api cells. The exact stimulus for islet cell hyperplasia and proliferation of Api cells is still unknown.
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PMID:Islet-cell hyperplasia in genetic deficiency of alpha-1-proteinase inhibitor. 351 3

A proportionate mortality ratio (PMR) analysis of all deaths recorded from 1975 to 1985 among New Hampshire white male residents (age 20 years or older) was performed using death certificate information. Among automobile mechanics, the analysis revealed increases in mortality from leukemia (PMR = 178, N = 6); cancers of the oral cavity (PMR = 163, N = 4), lung (PMR = 112, N = 36), bladder (PMR = 169, N = 5), rectum (PMR = 182, N = 4), and lymphatic tissues (PMR = 200, N = 6); and cirrhosis of the liver (PMR = 140, N = 13) and suicide (PMR = 177, N = 22; p less than 0.05). Workers in the gasoline service station industry experienced a leukemia mortality excess (PMR = 328, N = 3; p less than 0.05) as well as increases in deaths from suicide (PMR = 162, N = 4), emphysema (PMR = 245, N = 4), and mental and psychoneurotic conditions (PMR = 394, N = 3). These workers are potentially exposed to a variety of substances including gasoline vapor, benzene, solvents, lubricating oils and greases, and asbestos (from brake and clutch repair) as well as welding fumes and car and truck exhaust. Despite limitations regarding the small number of deaths and methodologic constraints, the results of this analysis suggest that one or more of the exposures experienced by these workers poses a significant carcinogenic risk. More definitive epidemiologic studies are required to determine if the leukemia excess is associated with exposure to benzene, gasoline, or other workplace substances.
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PMID:Proportionate mortality ratio analysis of automobile mechanics and gasoline service station workers in New Hampshire. 361 3


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