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At least 847 records · Page 47Linked to original sources
PubMed1980

alpha 1-Microglobulin from normal and pathological urines.

alpha 1-Microglobulin was purified from normal and pathological urines. Significant differences were found in the amino acid compositions of the alpha 1-microglobulin isolated from these two sources. In addition electrofocusing of alpha 1-microglobulin from normal urine gave rise to two peaks of equal intensity with rather acidic isoelectric points (3.8 and 4.2), whilst alpha 1-microglobulin from pathological urine showed two peaks in a 1:5 ratio with less acidic isoelectric points (4.2 and 4.7). Further charge heterogeneity was also observed in the second peaks from both sources. The sugar compositions were also established, as well as the N-terminal sequences of the alpha 1-microglobulin of both peaks isolated from normal and pathological urines.

Alpha-Globulins↗
PubMed1985

Cystine depletion by WR-1065 in cystinotic cells. Mechanism of action.

Cystinotic leucocytes and skin fibroblasts incubated with the aminothiol N-(2'-mercaptoethyl)-1,3-propanediamine (WR-1065) exhibited substantial intralysosomal cystine depletion within 2 hr. Wr-2721, the thiol phosphorylated derivative of WR-1065, did not lower cystinotic leucocyte cystine in 1 hr but depleted cystinotic fibroblasts of cystine after 21 hr. Concentrations of cysteamine (beta-mercaptoethylamine) equimolar with those of WR-1065 depleted cystine more rapidly than did WR-1065, but the extent of cystine depletion by WR-1065 approached that for cysteamine when longer periods of incubation or higher concentrations were used. Cystine depletion by WR-1065 was slower for leucocyte lysosomal granular fractions than for whole leucocytes. L-[35S]Cystine-labeled fibroblasts exposed to WR-1065 exhibited new compounds not seen when cells were incubated without WR-1065: WR-1065-cysteine, cysteamine-cysteine and cysteamine-glutathione mixed disulfides. L-[35S]Cystine-loaded lysosome-rich granular fractions from cystinotic leucocytes incubated with WR-1065 formed WR-1065-cysteine mixed disulfide but no cysteamine-cysteine mixed disulfide. We suggest that WR-2721 is dephosphorylated intracellularly to the free thiol, WR-1065, which subsequently is converted to cysteamine by an unknown route. Intracellular cysteamine then enters the lysosome and reacts with free cystine to form cysteamine-cysteine mixed disulfide and cysteine which move into the cytosol and the incubation medium where they participate in further interchange reactions with free thiols present there, namely WR-1065 and glutathione.

Amifostine↗
PubMed1982

Measurement of intracellular amino acids in cultured fibroblasts.

Tissue culture is a valuable tool for the study of cellular amino acid metabolism. However, accurate measurement of intracellular amino acids is difficult. Cells must be washed to remove the culture medium which is rich in amino acids, a procedure which may result in the loss of intracellular amino acids. Collection of the cells of washing and amino acid measurement is further complicated by the adherence of cultured fibroblasts to the culture vessel surface. An uncomplicated, reliable method for the determination of the amino acid content of cultured human diploid fibroblasts is described. The intracellular levels of several amino acids determined by this method are markedly higher than previously reported levels.

Amino Acids↗
PubMed1983

Effects of cysteamine and other thiols on cystine egress from isolated lysosome-rich fractions of cystinotic and normal leucocytes.

After loading isolated normal and cystinotic white blood cell lysosomes with radioactive amino acid methyl esters, egress of the corresponding amino acids was measured in the presence or absence of reducing agents. Cysteamine greatly enhanced disposal of cystine- and, to a lesser extent, cysteine-loaded lysosomes, resulting in final similar rates of radioactive clearance. Cysteamine did not alter leucine egress. Cysteamine comparably accelerated cystine egress from normal and cystinotic lysosomes. Reduced glutathione, ascorbic acid, coenzyme A and acetylcoenzyme A, which are much less effective cystine-depleting agents on intact cystinotic cells than cysteamine, failed to increase egress rates from isolated lysosomes loaded with cystine. We believe this in vitro system can help in the future in evaluating drug efficacy in reducing cystine content in cystinotics in addition to the already existing tissue culture technique.

Amino Acids↗
PubMed1987

Glutathione metabolism in normal and cystinotic fibroblasts.

Intracellular concentrations of glutathione and activities of the enzymes gamma-glutamylcysteine synthetase, glutathione synthetase, and gamma-glutamyl transpeptidase were measured in confluent cultured human fibroblasts cell lines from 14 normal cell lines and four cystinotic cell lines. gamma-Glutamyl transpeptidase had a wide range of variability while the glutathione synthetic enzymes, gamma-glutamylcysteine synthetase and glutathione synthetase, had narrower variations and also exhibited no apparent relationship to glutathione content. No differences in the activities of these enzymes were found between normal and cystinotic cells in confluent cell cultures. The activities of the above enzymes and the cell number and content of glutathione, cystine, DNA, and total protein in two normal and two cystinotic fibroblast cell lines were measured during growth. The following growth-dependency patterns were observed: (1) gamma-glutamylcysteine synthetase activity increased markedly in lag and early log phases in both normal and cystinotic cells and decreased rapidly to low confluent levels thereafter. (2) gamma-Glutamyl transpeptidase showed the same wide range of activity noted at confluency but activities decreased in the log phase of growth, a pattern also seen in cystinotic cells. (3) Glutathione synthetase activity remained relatively constant during growth of normal cells but exhibited a peak of activity during lag and early growth of cystinotic cells. (4) Comparative glutathione levels of normal and cystinotic cells were not significantly different and exhibited similar fluctuations with time. (5) The cystine content of normal and cystinotic cells unexpectedly rose to high levels in the lag phase, then decreased to 0.1 nmol 1/2 cystine/mg protein in normal cells and to 0.3 to 1.2 nmol 1/2 cystine/mg protein in cystinotic cells during the log phase. As confluency was approached, normal cell cystine remained at low levels while cystinotic cell cystine rose to characteristically high levels of 50- to 100-fold greater than normal cells at late confluency. These studies extend our understanding of the regulation of glutathione and cystine content in cultured fibroblasts and suggest that glutathione content is closely controlled throughout the cell cycle in the face of varying activities of its anabolic and catabolic enzymes.

Cell Division↗
PubMed1992

Rapid development of an immunoblastic lymphoma and death in children following cadaveric renal transplantation.

We report on three children who underwent cadaveric renal transplantation and subsequently developed an immunoblastic lymphoma, leading to death in two patients. The development of the lymphoma occurred following a multi-drug immunosuppression regimen ending with monoclonal antilymphocyte (OKT3) treatment for biopsy-proven cellular and vascular acute rejection. These patients represent three of 11 children who received OKT3 treatment for rejection in the last 18 months at this institution. Following the diagnosis of lymphoma, all three patients were treated by transplant nephrectomy, cessation of immunosuppression, and administration of intravenous acyclovir. The first two patients died at 4 days and 4 weeks, respectively, after the definitive diagnosis was made with widespread metastatic disease. The remaining child is a short-term survivor (13 months), free of demonstrable malignancy. Multidrug regimens for immunosuppression have a profound effects on T cell function. These effects, when combined with a primary infection by the Epstein-Barr virus, are implicated in the rapid development of the lymphomas and are responsible for the death of these two children.

Cadaver↗