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Biomedical subjects

M Rojkind

Publications and source records attributed to M Rojkind.

At least 91 records · Page 5Linked to original sources
PubMed1979

Treatment of cirrhosis with colchicine. A double-blind randomized trial.

As part of a double-blind, randomized, controlled trial to evaluate the effect of colchicine on liver cirrhosis, 43 cirrhotic patients were assigned to either a placebo (20 patients) or a colchicine (23 patients) treatment group. Colchicine 1 mg and an indistinguishable placebo were administered orally on a daily dose 5 days a week. In the colchicine group, 12 were males and 11 females, while in the control group 13 were males and 7 females. The time elapsed between diagnosis and inclusion in the study was 14.1 mo for the controls and 14.5 mo for the patients on colchicine. Mortality related to the liver disease occurred in 4 patients on colchicine and 8 patients on placebo. Although the probability of surviving in the colchicine group was greater than that of the placebo, the difference did not reach statistically significant levels. Of the colchicine-treated patients, in three a remarkable decrease in liver fibrosis was observed in serial biopsies. In two other patients, carcinoma of the liver developed. Six of the survivors on colchicine have improved clinically, noticing disappearance of ascites and edema, as well as a decrease in the size of the spleen. All the survivors on placebo continue to show clinical deterioration. In contrast to the usual drop of serum albumin seen in the cirrhotic patients, those receiving colchicine increased and maintained their serum albumin levels throughout the study. Serum proline values were elevated only in the alcohol cirrhotic patients. Serum alkaline phosphatase increased only in those patients receiving colchicine. The results indicate that in some cases, liver fibrosis could be modified by treatment with antifibrotic drugs. The use of colchicine at present should remain within controlled studies.

Adult↗
PubMed1979

Liver collagen synthesis in schistosomiasis mansoni.

We determined collagen synthetic rates and utilization of key amino acid precursors of collagen in slices of wedge liver biopsy specimens obtained at required surgery from 9 patients with hepatosplenic schistosomiasis and from 4 control patients. The liver specimens from the patients with schistosomiasis showed advanced fibrosis, with histologic evidence of schistosomiasis alone in four, and both schistosomiasis and chronic active hepatitis in five cases. Liver slices were incubated with radioactive proline, arginine and glutamine, using quantitative assay conditions validated earlier for murine schistosomiasis. Collagen peptide synthesis in slices from all nine fibrotic liver specimens was 4- to 25-fold greater than normal and correlated positively with liver collagen content, which was 2- to 5-fold greater than normal. Free proline, an amino acid that may contribute to regulation of collagen peptide synthesis, was increased in six of the nine fibrotic liver specimens, and proline was actively formed from arginine in liver slices from all specimens. These measurements of the initial steps of collagen biosynthesis in fibrotic human liver are quantitatively similar to those previously made of the same processes in experimental animals.

Adolescent↗
PubMed1977

Liver collagen synthesis in murine schistosomiasis.

Collagen synthesis was measured in liver slices obtained from mice with hepatosplenic schistosomiasis. Enlarged fibrotic livers from these mice contained 20 times more collagen than normal. This model of hepatic fibrosis results from an inflammatory granulomatous host response to Schistosoma mansoni ova in portal tracts, rather than from direct lover cell injury as with carbon tetrachloride-induced liver fibrosis. Collagen synthesis, as measured by the formation of labeled protein-bound hydroxyproline, occurred in granulomas isolated from fibrotic livers. Labeled collagen that cochromatographed with type I collagen was extracted with neutral salt solution from liver slices incubated with labeled proline. The free proline pool of the liver was doubled in infected mice; coordinately, liver slices from these animals showed maximal collagen production when the concentration of free proline in the medium was raised to 0.4 mM, the same level measured in the fibrotic livers. Under such conditions, collagen synthesis was at a rate equivalent to the formation of 5.4 nmol of protein-bound hydroxyproline per g liver in 6 h. In comparative incubations in medium containing 0.2 mM proline, fibrotic liver slices produced 16-fold more collagen than normal slices. The proline analogue, L-azetidine 2-carboxylic acid, effectively inhibited synthesis of labeled collagen by fibrotic liver slices. These studies show the synthesis of collagen in a reproducible animal model of the most prevalent form of human liver fibrosis. Difinitition of the controlling factors in this system is of interest for the general problem of fibrosis produced by immunological responses.

Animals↗
PubMed1976

Increase in type I and type III collagens in human alcoholic liver cirrhosis.

Collagen in bulk was isolated in about 30% yield from the livers of normal human beings and from livers of persons with alcholic cirrhosis. Analyzed chemically and examined by electron microscopy, the collagen in each case was shown to consist of two types identical with, or resembling closely, type I and type III collagens of skin. The collagen from normal liver was predominantly type I, whereas, that from cirrhotic livers consisted or approximately equal amounts of the two types. By chromatography on carboxymethyl-cellulose, the type I collagen from the cirrhotic livers showed one alpha2chain and two alpha1 chains. The alpha1 chains were separable from one another, but gel electrophoretic patterns of peptides obtained from them after treatment with CNBr were almost identical, and resembled the pattern obtained with CNBr peptides of the alpha1 chain of rat skin type I collagen. The increased collagen of both types was responsible in part for the observed distortion of the architecture of the cirrhotic livers associated with increased rigidity of the stroma. The predominance of type III collagen in the areas of collapse of architecture where, as shown by others, few fibroblasts are present, suggests that hepatocytes might have an important function in fibrogenesis during the course of liver cirrhosis.

Alcoholic Intoxication↗
PubMed1976

RNA biosynthesis in the chick embryo during development and its relation to collagen synthesis.

A study of RNA synthesis in the legs and wings of chick embryos suggests synthesis of specific RNA's as a function of development. An increase in RNA at day 10 was followed by an increase in collagen synthesis. That RNA had a sedimentation coefficient of 23S and several of the characteristics of mRNA. Thus it appeared to contain a poly A sequence since it was retained on poly U coated-filters, it was not methylated, and its synthesis was not inhibited by low doses of actinomycin D. That RNA was found able to direct protein synthesis in a cell-free system derived from wheat germ. In the presence of that RNA, a small amount of protein was synthesized that migrated in acrylamide gel electrophoresis with the alpha chains of collagen and was partially digested by bacterial collagenase.

Animals↗
PubMed1976

Hepatic fibrosis.

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Amino Acids↗
PubMed1975

Effect of colchicine on collagen, albumin and transferrin synthesis by cirrhotic rat liver slices.

Collagen synthesis was found to be increased in liver slices of rats made cirrhotic by chronic administration of CCl4. The liver function was impaired, as determined by an increased retention of conjugated bilirubin and low serum albumin values. However, when animals received colchicine simultaneously with CCl4, collagen synthesis and deposition were inhibited, and the liver function appeared normal. When a group of rats was made cirrhotic by chronic administration of CCl4, and then kept for 30 days without further treatment, fibrosis persisted and collagen synthesis was very low. However, the liver function was severely impaired. When similar rats received L-azetidine-2-carboxylic acid during the 30-days period following CCl4 administration, there was a slight but not significant improvement in liver function. The collagen synthesis and the extent of fibrosis were similar to the controls. However, if similar rats received colchicine during the 30 days period, collagen synthesis was almost negligible, there was a slight decrease in fibrosis and there was a great improvement in liver function. In all the cirrhotic animals studied, transferrin biosynthesis remained constant.

Animals↗
PubMed1975

Serum free proline and free hydroxyproline in patients with chronic liver disease.

Serum free proline and free hydroxyproline were determined in 71 patients with liver disease and in 62 control subjects. The group with liver disease included 60 patients with liver cirrhosis and 11 with chronic active liver disease. Forty-five of the cirrhotic patients were alcoholics, 9 of which were studied during an episode of alcoholic hepatitis. The control group consisted of 24 healthy volunteers, 19 primary malnourished patients, and 19 severely ill patients without liver disease. The values obtained in normal subjects were quite constant; no differences related to sex or age were detected. In patients with malnutrition, and especially in severely ill patients, the proline values were always below the normal limit. Patients with nonalcoholic cirrhosis or chronic active liver disease had serum proline and hydroxyproline values similar to those of normal subjects. However, the patients with alcoholic liver cirrhosis had proline and hydroxyproline values significantly higher than the normal group. Furthermore, in patients with alcoholic hepatitis the serum free proline values were significantly higher than in the other groups. The results suggest that alcohol might have a direct effect on proline metabolism or facilitate its release from the liver cell.

Adolescent↗