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)

We conducted a follow-up study to evaluate mortality among 14,861 workers employed in five facilities producing or using phenol and formaldehyde. More than 360,000 person-years of follow-up accrued. Mortality rates from all causes of death combined were similar to those in the general U.S. population. We observed excesses of cancer of the esophagus, cancer of the kidney, and Hodgkin's disease among workers exposed to phenol, but none of these excesses showed a dose-response relation with exposure to phenol. Excess lung cancer mortality (SMR = 1.2) showed no consistent pattern by any exposure index. Workers exposed to phenol had lower mortality ratios for cancer of the buccal cavity and pharynx, cancer of the stomach, cancer of the brain, arteriosclerotic heart disease, emphysema, disease of the digestive system, and cirrhosis of the liver. Of these, arteriosclerotic heart disease, emphysema, and cirrhosis of the liver were inversely related to duration of phenol exposure and to cumulative phenol exposure levels. Although these inverse associations may be due to chance or uncontrolled confounders, the ability of phenol to interfere with the generation of oxidants in experimental systems suggests that the pattern may have biologic plausibility.
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PMID:Mortality among industrial workers exposed to phenol. 205

Alpha 1-protease inhibitor can exist as over 70 different biochemical variants (the Pi system) which are inherited as autosomal-codominant alleles. The majority of these variants are of no clinical significance. Epidemiologically, the most abundant are Pi types M, S, and Z. Homozygotes of type Z have only 10%-20% of the normal serum concentration of the inhibitor and have an increased risk of developing pulmonary emphysema. Cigarette smoking is the most important risk factor. A minority of Pi Z homozygotes (10%-20%) develop a form of neonatal hepatitis and a proportion of these suffer from liver cirrhosis in adult life. Heterozygotes of Pi type SZ have about one third of the normal serum alpha 1-protease inhibitor concentration but this phenotype does not in itself appear to be a significant emphysema risk factor. Heterozygotes of Pi type MZ are thought to have a moderately increased risk of developing emphysema but only if they smoke; there is also evidence for an increased risk of cirrhosis among subjects of type MZ. No excessive risk appears to be attached to the MS phenotype. Cumulative survival curves have suggested that type Z homozygotes have a poor prognosis but such estimates are based on clinic or hospital patients who already have respiratory symptoms. Calculations based on population frequencies however, suggest that about 90% of the total number of type Z subjects are not accounted for in such surveys. Their whereabouts remains unclear at present; some will undoubtedly have died of liver or lung disease but it is possible that the majority escape and live undetected among the general population.
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PMID:The epidemiology of alpha 1-antitrypsin deficiency. 211 62

The alpha-1-antitrypsin gene is localized to chromosome 14. Numerous genetic variations may occur and some of these result in severely reduced concentration in the serum. The commonest cause of severe deficiency of alpha-1-antitrypsin is the gene-variant Z in the homozygotic form which occurs in one out of 2,000 Danes. Severe deficiency in alpha-1-antitrypsin results in liver symptoms in approximately 10% of the children. Some of these will develop cirrhosis of the liver. In adults at the ages of about 30 to 40 years, gradual development of emphysema occurs and this is earliest and most pronounced in smokers. Adults have also increased frequency of cirrhosis but this is much less pronounced than the development of emphysema. In addition to a number of theoretical therapeutic possibilities, liver transplantation is now possible and this is employed particularly in children with cirrhosis. In young persons with terminal pulmonary insufficiency with anticipated survival for less than one year, heart/lung transplantation or possibly isolated lung transplantation may be considered. An alpha-1-antitrypsin concentrate has been produced. Intravenous dosage once monthly can provide a concentration in the serum for three to four weeks which, as a rule, suffices to prevent emphysema. It is not yet known whether this treatment has any prophylactic effect in cases of developed emphysema. It is to be anticipated that treatment instituted prior to development of emphysema will prevent development of pulmonary disease but the treatment is rather expensive and must, probably, continue throughout life. No controlled investigation of the effect of treatment is available and the range of indications is not defined.
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PMID:[New therapeutic possibilities in alpha 1-antitrypsin deficiency]. 218 56

We have studied the clinical histories and liver biopsy findings in 1951 consecutive adult patients with suspected chronic liver disease, and in four known PiZ-homozygous alpha 1-antitrypsin-deficient patients with emphysema (candidates for lung transplant) and no known liver disease, in order to assess the importance of periportal alpha 1-antitrypsin granules in the liver and their possible causal role in liver disease, and to assess the value of possible screening tests. Periportal granules were found in 30 (1.5 per cent) of the 1951 liver biopsies and in all four known PiZ-homozygous subjects. They were the sole putative aetiological agent in eight of 85 patients (9.4 per cent) with otherwise cryptogenic cirrhosis and present in 2.5 per cent of patients with cirrhosis of known aetiology (alcohol, autoimmune etc.). All but one were Z phenotype (seven homozygotes, 22 heterozygotes). alpha 1-Antitrypsin granules were seen in 12 patients (including three of four lung transplant candidates) with no histological chronic liver disease. Determination of serum alpha 1-antitrypsin levels was quite unhelpful in identifying these patients. This study does not support the concept that periportal alpha 1-antitrypsin granules are necessarily pathogenic, but in some cases they may be causally related to otherwise cryptogenic liver disease. The presence of granules gave no important diagnostic, therapeutic or prognostic information.
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PMID:Alpha 1-antitrypsin granules in the liver--always important? 221 74

This paper attempts to discuss the shape of inequalities in health in the Republic of Ireland by focusing on social class, gender and regional inequalities in health outcomes as shown in annual publications of vital statistics and in various research studies. The Republic of Ireland has a demographic profile of rapid population increase, unique in Europe. While the birth rate is the highest in Europe, the infant mortality rate is relatively low, yet the perinatal mortality rate is relatively high. Attempts are made to analyse social class variations in mortality and morbidity rates but, except for psychiatric care, Irish data on health by social class are scarce. There exist more data on gender inequalities which pinpoint the particular vulnerability of Irish women to ischaemic heart disease and certain types of cancer. Regional analysis of vital statistics reveals the vulnerability of people in urban areas (compared to rural areas) to cancer of the trachea, bronchus and lung, cirrhosis of the liver, tuberculosis of the respiratory system, pneumonia, and bronchitis, emphysema and asthma. In comparison to several European countries, Irish standardized mortality rates were the worst for urban women dying from lung cancer, and for urban men and women, Irish standardized mortality rates were the worst for non-rheumatic heart disease and respiratory tuberculosis. Various studies of morbidity of the elderly clearly reveal the hidden clinical iceberg of symptoms which are not presented to the health care system. Unfortunately, there is relatively little evidence of the health situation of disabled people, the travelling community or the long term unemployed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Health and social inequities in Ireland. 221 9

Alpha 1-protease inhibitor can exist as over seventy different biochemical variants (the Pi system) which are inherited as autosomal codominant alleles. The majority of these variants are of no clinical significance. Epidemiologically, the most abundant are Pi types M, S and Z. Homozygotes of type Z have only 10 to 20% of the normal serum concentration of the inhibitor and have an increased risk of developing pulmonary emphysema. Cigarette smoking is the most important risk factor. A minority of Pi Z homozygotes (10 to 20%) develop a form of neonatal hepatitis and a proportion of these suffer from cirrhosis in adult life. Heterozygotes of Pi type SZ have about one third of the normal serum alpha 1-protease inhibitor concentration but this phenotype does not in itself appear to be a significant emphysema risk factor. Heterozygotes of Pi type MZ are thought to have a moderately increased risk of developing emphysema but only if they smoke; there is also evidence for an increased risk of cirrhosis among subjects of type MZ. No excessive risk appears to be attached to the MS phenotype. Cumulative survival curves have suggested that type Z homozygotes have a poor prognosis but such estimates are based on clinic or hospital patients who already have respiratory symptoms. Calculations based on population frequencies however, suggest that about 90% of the total number of type Z subjects are not accounted for in such surveys. Their whereabouts remains unclear at present; some will undoubtedly have died of liver or lung disease but it is possible that the majority escape and live undetected among the general population.
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PMID:Epidemiology of alpha 1-protease inhibitor deficiency. 234 48

We compared the jobs, estimates of exposures, and mortality experience of short-term (less than or equal to 1 year) and long-term (greater than 1 year) workers from nine plants producing formaldehyde or formaldehyde products. There were few jobs that were filled solely or primarily by newly hired workers. The estimated median level of formaldehyde exposure experienced by short-term workers on their first job was nearly identical to that for long-term workers, although short-term workers were more likely to be in jobs exposed to particulates than were long-term workers. As duration of employment increased, there was little change in the average estimated exposure level of formaldehyde, but the likelihood of being exposed to particulates decreased. Short-term workers had greater risks than long-term workers of dying from diseases of the circulatory system, arteriosclerotic heart disease, emphysema, diseases of the digestive system, cirrhosis of the liver, motor vehicle accidents, suicide and malignant neoplasms, particularly cancers of the stomach, colon, lung, prostate, and brain.
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PMID:Comparison of jobs, exposures, and mortality risks for short-term and long-term workers. 240 25

Alpha-1-antitrypsin (AAT) is the predominant protease inhibitor in human sera. The major physiological role of this inhibitor is to protect elastin fibers in the alveolar structure of the lung from excessive degradation by neutrophil elastase. AAT is synthesized predominantly by hepatocytes, although the AAT gene is expressed to a small degree in the epithelial cells of various tissues. Recent studies have shown that the enhanced liver-specific expression of the AAT gene is controlled by the binding of hepatic nuclear proteins to specific DNA sequences upstream from the structural gene. A variety of mutations within the AAT gene have been identified that result in a partial deficiency or total absence of the inhibitor in sera. Inheritance of a particular combination of these alleles can result in a predisposition towards the development of destructive lung disease. Interestingly, the most common AAT deficiency variant, designated PiZ, causes the mutant protein to accumulate as an insoluble aggregate within the lumen of the hepatic rough endoplasmic reticulum, which is an etiological agent for the development of liver disease. Overall, investigation into the genetic control of AAT has led to an increased understanding of the factors that control hepatic gene expression, as well as mechanisms involved in the pathophysiology of emphysema and liver cirrhosis.
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PMID:Genetic control of human alpha-1-antitrypsin. 269 88

Alpha 1 antitrypsin deficiency predisposes subjects to developing pulmonary emphysema and childhood liver cirrhosis. We have studied restriction fragment length polymorphisms (RFLPs) of the alpha 1 antitrypsin gene in a normal population and a group of patients with pulmonary emphysema. We have identified five RFLPs with eight restriction enzymes. The most frequent polymorphisms have been detected with the enzymes MspI, PstI, and TaqI at frequencies of 46.8%, 6.4%, and 5.0% respectively in the group of normal subjects.
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PMID:DNA polymorphisms of the human alpha 1 antitrypsin gene in normal subjects and in patients with pulmonary emphysema. 287 34

The cirrhosis and hepatocellular carcinoma associated with alpha 1-antitrypsin deficiency has been exclusively reported with the PI Z allele. We present a 63-yr-old white man with emphysema, cirrhosis, and hepatocellular carcinoma. The latter occurred on a background of diffusely distributed hepatocellular dysplasia. Serum protein electrophoresis suggested a deficiency of alpha 1-antitrypsin quantitated at 13% of normal. PI phenotyping showed that he had only the rare PI Mmalton allele, previously associated only with severe lung disease. Family studies demonstrated the distribution of this rare allele. The liver at autopsy displayed well-differentiated hepatocellular carcinoma in addition to alpha 1-antitrypsin deposits in normal, dysplastic, and malignant cells.
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PMID:Diffuse hepatocellular dysplasia and carcinoma associated with the Mmalton variant of alpha 1-antitrypsin. 303 14


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