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 potential promoting and/or complete carcinogenic activity of a methyl group-deficient (MD) diet lacking methionine, choline, vitamin B12, and folate on liver tumor induction in weanling male F344/NCr rats was examined. Each of 50 rats per group received one injection 20 mg diethylnitrosamine [(DENA) CAS: 55-18-5; N-nitrosodiethylamine]/kg body weight at 4 weeks of age, and then each was maintained on a methyl group-adequate (MA) diet for 52 weeks (groups 2 and 5) or on an MD diet for 15 weeks followed by the MA diet for 37 weeks (group 4). Controls received injections of saline and were maintained on the same two respective diet regimens (groups 1 and 3, respectively). Histologic results from sacrifices at 6, 10, 15, 22, 39, and 52 weeks revealed early development of foci of eosinophilic gamma-glutamyltransferase (GGT)-positive hepatocytes by week 6 in DENA-MD diet-treated rats, with subsequent development of a diffuse hyperplasia of hepatocytes, oval cell proliferation, cholangiofibrosis, nodular cirrhosis, and neoplastic nodule (NN) formation and, at 52 weeks, hepatocellular carcinomas (HCC) in 13 of 15 rats. Similar but significantly fewer lesions were observed at slightly later sacrifice times in the livers of saline-MD diet-treated rats, with development of NN in 5 of 12 rats and an HCC in 1 of 12 rats at 52 weeks. DENA-treated rats on MA diets developed relatively few GGT-positive foci, and none developed any neoplastic lesions. Except for basophilic foci, areas and foci of cellular alteration containing glycogen-rich hepatocytes frequently exhibited diminished uptake of injected iron and decreased glucose-6-phosphatase and ATPase contents focally or throughout. This study indicates that a relatively brief exposure of both untreated and DENA-treated weanling rats to a severely MD diet produces classical preneoplastic and neoplastic lesions in their livers.
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PMID:Profound postinitiation enhancement by short-term severe methionine, choline, vitamin B12, and folate deficiency of hepatocarcinogenesis in F344 rats given a single low-dose diethylnitrosamine injection. 659 43

To evaluate the results of jejunoileal bypass for morbid obesity, we studied 100 patients with intact bypasses an average of more than five years after surgery. Mean weight loss at five years was 102.7 lb (46.6 kg) (33 per cent). Although nearly half the patients regained some weight between one and five years after surgery, only 17 per cent regained 20 lb (9 kg) or more. Medical benefits (such as improved glucose tolerance and lowered blood pressure) were maintained at five years, but side effects and complications continued to occur in the late postoperative period. Diarrhea (more than three stools per day) persisted in 58 per cent of the patients, and electrolyte disturbances occurred in over a third. Diminished levels of B12 or folate or both were present in 88 per cent. Twenty-one per cent of the patients had nephrolithiasis, and 20 per cent of those who were at risk required cholecystectomy. Progressive hepatic structural abnormalities occurred in 29 per cent of the patients, and there was a 7 per cent incidence of cirrhosis. Although 81 per cent of the patients had satisfactory results at five years, side effects and complications continued to occur, mandating careful follow-up indefinitely. The risk-to-benefit ratio at five years after surgery seems acceptable, but the continued untoward effects of the bypass in the late postoperative period have led us to abandon this procedure in favor of gastric bypass. Only continued longitudinal follow-up will determine whether on balance jejunoileal bypass represents such a serious long-term health hazard that prophylactic restoration of intestinal continuity is indicated.
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PMID:Jejunoileal bypass for morbid obesity. Late follow-up in 100 cases. 683 18

Anaemias with multivariate pathogenesis are frequently observed in chronic liver diseases. Among our patients 44.4 per cent (132 of 297) had an anaemia. The hepatogenic anaemia which appeared most frequently in patients with liver cirrhosis and carcinoma of the liver was in most cases normochromic (75 per cent), at a small proportion hypochromic (17.4 per cent) and rarely hyperchromic (7.6 per cent). Initial phases of an anaemia were more frequently registered by means of the counting of erythrocytes than by means of the determination of haemoglobin, which is to be traced back to the frequently existing volume macrocytosis. Leptomacrocytes, target cells and acanthocytes are observed as further forms of macrocytes in liver diseases. Among the possible individual factors the more frequently appearing latent and more rarely existing manifest haemolysis prevailed in 82 per cent of the examined patients. A hypersplenism, however, was present only in 24 per cent of the patients, vitamin B12 and folic acid deficiency as well as signs of the ineffective erythropoiesis relatively more infrequently occurred. Additional occult haemorrhages or an increase of the plasma volume may lead to an anaemia in latent haemolysis. As to the diagnosis a basis programme and an enlarged programme are reported on. The therapy has to take into consideration the treatment of the basic disease and the deficiency conditions or disturbances established.
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PMID:[Hepatogenic anemia]. 684 79

Titres and immunoglobulin classes of autoantibodies were examined in 69 male patients with alcoholic liver cirrhosis and the findings were related to particular human leucocyte antigens and serum concentration of testosterone. Both anti-nuclear antibodies (ANA) and smooth muscle antibodies (SMA) were significantly more prevalent in patients with cirrhosis than in sex- and age-matched controls. Antimitochondrial antibodies and liver cell membrane antibody were found in 4% of the patients, and in none of the controls, but this difference was not significant. Patients with HLA-B8 and/or HLA-B12 had higher titres of ANA (n.s.) and SMA (P less than 0.05) than patients without these HLA antigens. Serum concentrations of testosterone were significantly lower in ANA-positive patients than in those negative (P less than 0.05), and a similar tendency was found in SMA-positive patients. With increasing titres of ANA the concentration of testosterone fell. Serum concentration of testosterone correlated inversely (P less than 0.05) with plasma immunoglobulin G and A. It is concluded that both genetic and hormonal factors may influence the humoral immune response in these patients.
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PMID:Autoantibodies, histocompatibility antigens and testosterone in males with alcoholic liver cirrhosis. 697 33

1. Rats were given a purified folate-deficient diet containing 5 g succinylsulphathiazole/kg for 4-5 months in two experiments. Control rats were supplemented with folic acid in the drinking-water. 2. Weight gain was much below normal in the folate-deprived rats after the first month. Very low folate levels were recorded in blood, liver and peripheral nerve (12-33% of control). In the central nervous system, including the cerebrospinal fluid, the folate depletion was less conspicuous (50-80% of control). Only marginal signs of anaemia were found and no signs of neurological dysfunction were detected, using nerve conduction velocity measurement and co-ordination tests. 3. Light and electron microscopy of the folate deficient liver revealed fatty infiltration, and enlargement of liver parenchymal cells, nuclei and nucleoli. There was often a considerable amount of bile ductular cells in the lobuli but no cirrhosis. The morphological changes resembled those observed in choline deficiency. 4. Phospholipid N-methylation in liver was depressed in folate-deficiency. This was probably due to a decreased availability of S-adenosylmethionine caused by the low concentrations of methylated folate in liver. Intraperitoneal administration of methionine did not normalize phospholipid methylation. 5. In folate deficiency the proportion of ethanolamine phosphoglyceride in liver was increased at the expense of choline phosphoglyceride, which is consistent with a decreased phospholipid methylation. Also an increase in liver triacylglycerol was noted, in accordance with the morphological observations. Brain lipid composition was unchanged. 6. After the injection of labelled ethanolamine, isotope accumulated in liver phosphoethanolamine in folate deficiency, probably due to an impairment of the CTP:ethanolaminephosphate cytidylyltransferase (EC 2.7.7.14) reaction. The mechanism of this impairment is discussed. 7. Although the low concentrations of folate was the main nutritional change in the deprived animals, changes with respect to vitamin B12 and maybe also choline cannot be excluded. We conclude that some of the changes in folate deficiency, i.e. fatty liver and decreased biosynthesis of liver phospholipids may be due to a precipitated deficiency of lipotropic agents, whereas other differences may be specific for deficiency of folate per se, such as changes in liver phospholipid fatty acids and some of the morphological aberrations.
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PMID:Effect of experimental folate deficiency on lipid metabolism in liver and brain. 708 22

Female F-344 rats, in contrast to male rats of the same strain, are largely resistant to the hepatonecrogenic and hepatocarcinogenic actions of a diet devoid of choline and restricted in methionine (CD diet). A study was performed to determine whether the resistance would be overcome by feeding a diet devoid not only of choline, but also of methionine, vitamin B12 and folic acid (MGD diet). Three experiments were performed, to compare the degrees of steatosis and cell death and proliferation, and the onset of pre-neoplastic and neoplastic lesions, in the liver of female F-344 rats fed either the CD or the MGD diet. Limited responses were again observed in rats fed the CD diet. On the other hand, feeding the MGD diet resulted in degrees of steatosis and of compensatory mitogenesis comparable to those previously found to occur in male F-344 rats fed the CD diet. It resulted also in the development of a marked cirrhosis, of neoplastic nodules and of hepatocellular carcinomas. The results indicate that in female F-344 rats overall availability of methyl groups may be more critical than the dietary supply of choline in determining the severity and spectrum of hepatopathology. They emphasize also the importance of compensatory mitogenesis in the induction of neoplastic lesions by methyl-group deficient or devoid diets.
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PMID:On the role of compensatory mitogenesis in the hepatocarcinogenicity of choline and multiple-lipotrope devoid diets. 803 19

The effects of vitamin B12 status on growth and tissue selenium distribution were studied in Sprague-Dawley rats chronically exposed to subtoxic levels of selenite. Vitamin B12 status was monitored by urinary methylmalonic acid excretion and by liver and plasma vitamin B12 levels. Selenite absorption was unaffected by dietary level of vitamin B12. A significant (P < 0.05) interaction of vitamin B12 and selenium was found on growth of rats fed vitamin B12 deficient or control diets. In vitamin B12 depleted rats, there were significant histologic changes in the liver that were characterized by micronodules and regeneration, bile duct reduplication, mild cirrhosis, necrosis of individual hepatocytes and other minor histologic changes. There was no gross or histologic evidence of liver toxicity in rats supplemented with vitamin B12. Rats pair-fed 9 mg/kg selenium with vitamin B12 had significantly lower liver and kidney selenium levels and significantly higher blood selenium levels compared to rats fed the diet without vitamin B12. These results are consistent with the hypothesis that vitamin B12 deficiency limits selenium methylation and excretion, resulting in higher tissue selenium levels and subsequent toxicity.
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PMID:Effect of vitamin B12 on performance and tissue selenium content in rats fed sub-toxic levels of selenite. 830 6

We determined the vitamin B12 clearance using an ultrafiltration technique and assessed whether the clearance of this vitamin B12 could be used to estimate the glomerular filtration rate (GFR). Fourteen subjects (5 had renal disease, 7 had diabetes mellitus, one had liver cirrhosis and one had cholelithiasis) divided into two groups were studied (group 1, 5 patients without vitamin B12 preloading; group 2, 9 patients with vitamin B12 preloading). Vitamin B12 clearance was significantly correlated with inulin clearance (r = 0.81, p < 0.001) in group 1; group 2 showed an even better correlation (r = 0.94, p < 0.001) with the presaturated vitamin B12 binding protein. In group 2, the mean inulin and vitamin B12 clearance values do not differ significantly (40.3 +/- 13.6 vs 48.2 +/- 17.2 ml/min), but there was a significant difference between mean inulin and creatinine clearance (40.3 +/- 13.6 vs 64.9 +/- 19.9 ml/min, p < 0.05). In conclusion, vitamin B12 clearance appears to be a more reliable method of estimating GFR than creatinine clearance.
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PMID:Measurement of glomerular filtration rate by free vitamin B12 clearance. 832 13

Two cases of alcoholic cerebellar degeneration with pyramidal sign were reported. Patient 1 with alcohol dependence syndrome was a 46-year-old woman. After the alcohol abuse of about eight years, she complained of gait disturbance. The gait disturbance progressively worsened in about two months and she could not ambulate freely by herself. Neurological examination revealed nystagmus, ataxic and spastic gait, slight weakness and spasticity of the lower extremities, hyperreflexia of the extremities, bilateral Babinski's signs, and incoordination of the lower extremities. Examination of liver function and serum B12 was normal. Cranial CT scan and MRI revealed atrophy of the cerebellar vermis and dorsal part of the cerebellum. Though neurological signs slightly improved after the admission to our hospital and the abstinence from alcohol abuse, ataxic gait and hyperreflexia of the extremities have continued. Patient 2 was a 58-year-old man. He was a heavy drinker, but was not a patient with alcohol dependence syndrome. After the heavy drinking of about 40 years, he complained of gait disturbance. The gait disturbance had progressively worsened in about four months. Neurological examination revealed ataxic gait, hyperreflexia of the lower extremities, and bilateral Babinski's signs. Laboratory examination revealed slight liver dysfunction with minimal GPT and moderate gamma-GTP elevation. Examination of serum B12 was normal. Cranial CT scan and MRI revealed atrophy of the cerebellar vermis. Though bilateral Babinski's signs disappeared after the abstinence from heavy drinking, ataxic gait and hyperreflexia of the lower extremities have continued. Alcoholic myelopathy without hepatic cirrhosis was rarely reported. In the relation of alcoholic cerebellar degeneration to alcoholic myelopathy, our cases are interesting and important.
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PMID:[Alcoholic cerebellar degeneration with pyramidal sign--in relation to alcoholic myelopathy]. 847 68

The cobalamin status of 27 patients suffering from alcoholic cirrhosis and 20 control subjects was analyzed. Plasma cobalamin (p < 0.005), total corrinoids (p < 0.005) and their analogs (p < 0.05) were all significantly elevated in the cirrhosis patients. These differences were due to increased haptocorrin (HC)-bound corrinoid (p < 0.02), which could be explained by a deficient hepatic clearance of cobalamin bound to HC. The increase in the concentration of true cobalamin was greater than that of its analogs. There were positive correlations between cholestasis (serum alkaline phosphatase) and plasma analog concentrations (p < 0.05), HC-bound cobalamin (p < 0.005) and total corrinoids bound to HC (p < 0.005). The plasma concentrations of the indicators of cobalamin deficiency, homocysteine (p < 0.05) and methylmalonic acid (p < 0.001), were increased, which could indicate poor cellular penetration of vitamin B12 or a defect in the activation of the two vitamin-B12-dependent enzymes.
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PMID:Alcoholic cirrhosis and cobalamin metabolism. 901 12


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