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)

Between 1992 and 2040, the United States nonwhite elderly population is expected to grow from 3.3 to 14.1 million. In order to assess the implications of this increase on the mortality from neurodegenerative diseases in the United States, we used Census Bureau population estimates to formulate projections of the annual number of deaths from neurodegenerative diseases and from six comparison conditions (liver cirrhosis, colon cancer, lung cancer, cancer of the female breast, multiple sclerosis, and malignant melanoma), assuming that the United States disease-age-gender-specific death rates for 1985-1988 remain constant between 1990 and 2040. We find that neurodegenerative disease mortality increases by 281-524%, depending on the model of population growth used. For the 'middle' population growth model, the increase in annual neurodegenerative disease mortality is 373%. The major component of this increase is the rise in deaths attributed to dementia. For the six comparison diseases, the increases in mortality range from 130 (multiple sclerosis) to 288% (colon cancer). Given the current level of underascertainment of neurodegenerative disease mortality, particularly among minorities, and the conservative nature of the Census Bureau estimates of future population, it is likely that these projections are under-estimates. The implications of these data are discussed.
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PMID:Projected neurodegenerative disease mortality among minorities in the United States, 1990-2040. 809 Feb 60

Between 1990 and 2040, the United States elderly population is expected to grow from 31.6 to 68.1 million. In order to assess the implications of this increase on the mortality from neurodegenerative diseases in the United States, we used Census Bureau population estimates to formulate projections of the annual number of deaths from neurodegenerative diseases and from six comparison conditions (liver cirrhosis, colon cancer, lung cancer, cancer of the female breast, multiple sclerosis, and malignant melanoma), assuming that the United States disease-age-gender-race-specific death rates for 1985-1988 remain constant between 1990 and 2040. We find that neurodegenerative disease mortality increases by 119-231%, depending on the model of population growth used. For the 'middle' population growth model, the increase in annual neurodegenerative disease mortality is 166%. The major component of this increase is the rise in deaths attributed to dementia. For the six comparison diseases, the increases in mortality range from 52 (multiple sclerosis) to 130% (colon cancer). Given the current level of under ascertainment of neurodegenerative disease mortality and the conservative nature of the Census Bureau estimates of future population, it is likely that these projections are underestimates. The implications of these data are discussed.
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PMID:Projected neurodegenerative disease mortality in the United States, 1990-2040. 827 81

We report a 79-year-old man who developed progressive gait disturbance and sensory loss. He had been doing well except for hepatitis B virus hepatitis until 72 years of age when he developed angina pectoris for which aorto-coronary bypass operation was performed when he was 73-year-old (1986). In 1990, he developed pulmonary fibrosis for which prednisolone was prescribed. His liver function deteriorated, and the liver function tests suggested liver cirrhosis. He noted an onset of gait disturbance in the middle of June in 1992 when he was 79-year-old. His gait disturbance deteriorated progressively, and he developed edema and loss of sensation in his both legs. He became unable to walk unassisted in the beginning of July. He fractured his right external malleolus after falling down from a chair. He became unable to stand by himself, and he was admitted to the cardiology service of our hospital on July 18, 1992, and the neurology service was asked to see the patient on July 30 of the same month. The patient was well developed and well nourished man in no acute distress. General physical examination revealed slight jaundice, left carotid bruit, and slight pitting pretibial edema. His temperature was 37.3 degrees C. On neurologic examination, he was alert and mentally sound without dementia. He showed a slight weakness in the facial muscles bilaterally and mild dysarthria and dysphagia, however, the other cranial nerves appeared intact. He was unable to stand unassisted. The muscle tone was hypotonic, however, no focal muscle atrophy was noted, nor was observed fasciculatory twitches.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A 79-year-old man with rapidly progressive tetraparesis]. 829 70

In a study of the disease pattern of the elderly in Rwanda, all patients aged 60 or more, hospitalized in a one-year period at the Medical Department, University Hospital, Butare, were examined prospectively. One hundred and ninety-two patients were included; most were subsistence farmers having a mainly vegetarian diet and living in large families. Infections (37.5% of the patients) and liver cirrhosis (31.8%) were the problems most frequently encountered. Primary hepatocellular cancer was diagnosed in 5.7% of the patients and was the most frequent malignancy. The hospitalized elderly occupied 17.5% of the available beds in the Medical Department. Their disease pattern was different from that of younger patients, making heavier demands on the medical resources. Malaria and upper intestinal inflammation were less frequent in the elderly; liver cirrhosis, primary hepatocellular cancer, pneumonia, prostatic cancer, cardiovascular pathology, chronic renal pathology and chronic lung disease were more prevalent. Several age-related conditions frequently observed in industrialized countries (e.g. coronary heart disease, stroke, gallstones, renal cysts, dementia) were rare. The study thus illustrates the concept of 'secondary aging': to the primary changes induced by the aging process, additional alterations are added which depend upon the environment and the lifestyle, resulting in a varying disease pattern. Health policies thus must take into account that the demographic transition in developing countries may result in a pattern of diseases different from that seen in industrialized countries; care must be taken when transposing data obtained from elderly populations in industrialized countries.
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PMID:The disease pattern of elderly medical patients in Rwanda, central Africa. 841 4

Alcoholism may lead to a great many physical and mental problems in individuals of any age. Elderly alcoholics often have additional problems resulting from the interaction of age related changes in physiology and "heavy" alcohol intake. Some of the more important problems are: Impairment of the immune system with decreased ability to deal with infection or cancer. Increased incidence of hypertension, cardiac arrhythmia, myocardial infarction, and cardiomyopathy. Increased incidence of stroke. Alcohol dementia. Increased incidence of esophageal and other cancers. Cirrhosis and other liver disease. Malnutrition. There seems to be no area in which even moderate alcohol intake is of definite benefit, and some areas in which even small amounts are detrimental.
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PMID:Medical manifestations of alcoholism in the elderly. 875 18

In spite of all the scientific advances of the past few years, proton magnetic resonance spectroscopy of the brain has not attained the status of a routine examination technique with clinically accepted indications. The method should be considered as an additional option to MR imaging for inherited and acquired encephalopathic changes as well as, in future, for localization diagnosis of epilepsies. A proton magnetic resonance spectroscopic investigation without a prior intensive clinical and imaging investigation is not useful. Above all, factors influencing metabolite distribution such as for example, serum osmolality must be known. Methodological prerequisites for the clinical application of proton resonance spectroscopy are, first of all, a high stability of the chosen technique as well as a sufficiently certain quantification of metabolites and the availability of a reference group. The use of short echo times is necessary for the quantification of glutamine and the osmolyte myo-inositol. Indications for individual cases in which clinical investigations and MR topography cannot provide sufficient certainty and spectroscopy can furnish additional information are, in addition to uses in neuropediatrics, the suspicion of Alzheimer's dementia, HIV encephalopathy in early manifestations, and unclarified depressions of consciousness accompanying liver cirrhosis.
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PMID:[Clinical uses of proton magnetic resonance spectroscopy of the brain]. 968 44

The serpins are a family of proteinase inhibitors that play a central role in the control of proteolytic cascades. Their inhibitory mechanism depends on the intramolecular insertion of the reactive loop into beta-sheet A after cleavage by the target proteinase. Point mutations within the protein can allow aberrant conformational transitions characterized by beta-strand exchange between the reactive loop of one molecule and beta-sheet A of another. These loop-sheet polymers result in diseases as varied as cirrhosis, emphysema, angio-oedema, and thrombosis, and we recently have shown that they underlie an early-onset dementia. We report here the biochemical characteristics and crystal structure of a naturally occurring variant (Leu-55-Pro) of the plasma serpin alpha(1)-antichymotrypsin trapped as an inactive intermediate. The structure demonstrates a serpin configuration with partial insertion of the reactive loop into beta-sheet A. The lower part of the sheet is filled by the last turn of F-helix and the loop that links it to s3A. This conformation matches that of proposed intermediates on the pathway to complex and polymer formation in the serpins. In particular, this intermediate, along with the latent and polymerized conformations, explains the loss of activity of plasma alpha(1)-antichymotrypsin associated with chronic obstructive pulmonary disease in patients with the Leu-55-Pro mutation.
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PMID:Inactive conformation of the serpin alpha(1)-antichymotrypsin indicates two-stage insertion of the reactive loop: implications for inhibitory function and conformational disease. 1061 72

Alpha-1-antitrypsin deficiency results from point mutations that distort the structure of the protein to allow a unique protein-protein interaction that we have termed loopsheet polymerisation. Polymers of Z alpha 1-antitrypsin accumulate within hepatocytes to form inclusion bodies that are associated with juvenile cirrhosis and hepatocellular carcinoma. The lack of circulating protein predisposes the Z alpha 1-antitrypsin homozygote to emphysema. This process also occurs in other members of the serine proteinase inhibitor (serpin) superfamily, antithrombin, C1-inhibitor and alpha 1-antichymotrypsin, in association with thrombosis, angioedema and chronic obstructive pulmonary disease, respectively, and we have recently shown that it underlies a novel inclusion body dementia. The interaction provides a useful paradigm for other 'conformational diseases' such as Huntington's disease, Creutzfeldt-Jakob disease and the amyloidoses.
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PMID:Alpha-1-antitrypsin deficiency, the serpinopathies and conformational disease. 1090 27

alpha(1)-Antitrypsin is the most abundant circulating protease inhibitor and the archetype of the serine protease inhibitor or serpin superfamily. Members of this family may be inactivated by point mutations that favor transition to a polymeric conformation. This polymeric conformation underlies diseases as diverse as alpha(1)-antitrypsin deficiency-related cirrhosis, thrombosis, angio-edema, and dementia. The precise structural linkage within a polymer has been the subject of much debate with evidence for reactive loop insertion into beta-sheet A or C or as strand 7A. We have used site directed cysteine mutants and fluorescence resonance energy transfer (FRET) to measure a number of distances between monomeric units in polymeric alpha(1)-antitrypsin. We have then used a combinatorial approach to compare distances determined from FRET with distances obtained from 2.9 x 10(6) different possible orientations of the alpha(1)-antitrypsin polymer. The closest matches between experimental FRET measurements and theoretical structures show conclusively that polymers of alpha(1)-antitrypsin form by insertion of the reactive loop into beta-sheet A.
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PMID:Pathogenic alpha 1-antitrypsin polymers are formed by reactive loop-beta-sheet A linkage. 1092 8

Members of the serpin family of serine proteinase inhibitors play important roles in the inflammatory, coagulation, fibrinolytic, and complement cascades. An inherent part of their function is the ability to undergo a structural rearrangement, the stressed (S) to relaxed (R) transition, in which an extra strand is inserted into the central A beta-sheet. In order for this transition to take place, the A sheet has to be unusually flexible. Malfunctions in this flexibility can lead to aberrant protein linkage, serpin inactivation, and diseases as diverse as cirrhosis, thrombosis, angioedema, emphysema, and dementia. The development of agents that control this conformational rearrangement requires a high resolution structure of an active serpin. We present here the topology of the archetypal serpin alpha1-antitrypsin to 2 A resolution. This structure allows us to define five cavities that are potential targets for rational drug design to develop agents that will prevent conformational transitions and ameliorate the associated disease.
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PMID:Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for rational drug design to prevent conformational disease. 1093 92


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