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Biomedical subjects

R Silber

Publications and source records attributed to R Silber.

At least 91 records · Page 5Linked to original sources
PubMed1983

A spectrophotometric assay for dehydroascorbate reductase.

A simple spectrophotometric assay for dehydroascorbate reductase based on the change in absorbance associated with the formation of ascorbic acid is described. Using a partially purified preparation from spinach leaves, the reaction was found to be linear with time and enzyme concentration. The reaction rate determined by this assay correlated well with that obtained by a high-performance liquid chromatography method. Possible advantages over currently available assays as well as potential applications are discussed.

Ascorbic Acid↗
PubMed1983

Public money, private control: a case study of hospital financing in Oakland and Berkeley, California.

Government support of public and private hospitals in Oakland and Berkeley, California was investigated. The private hospitals received government subsidies amounting to at least 60 per cent of their total revenues. The dollar amount of the subsidies to private hospitals was four and one-half times greater than government expenditures on the public hospital. In Oakland and Berkeley, as in many cities, public medical services have been reduced while both government health expenditures and private hospital revenues have increased sharply. The private hospitals, although all nominally non-profit, exhibit revenue maximizing behavior which results in socially unjust and medically irrational resource allocation. Funds might be found for public hospitals and clinics, and resources allocated more justly and rationally, if government expenditures in the private sector were brought under greater public scrutiny and control.

California↗
PubMed1983

Purification and characterization of actin from normal and chronic lymphocytic leukemia lymphocytes.

Previous studies from this laboratory have shown actin to be a major protein of human lymphocytes (Stark, R., Liebes, L. F., Nevrla, D., and Silber, R. Biochem. Med., 27: 200-206, 1982). We now report the purification to homogeneity and characterization of actin from blood lymphocytes of normal subjects and patients with chronic lymphocytic leukemia. The recovery of the purified protein was about 20%. The properties of the lymphocyte actins were compared to each other and to those of rabbit skeletal muscle actin. Lymphocyte actin consisted of beta and gamma forms in a 2:1 ratio. The Mr 42,000 was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Normal and leukemic lymphocyte actin had similar polymerization properties as assessed by viscosity measurements at 25 degrees and 4 degrees, and the ultrastructural appearance of the filaments was the same. Similar patterns were observed between normal and chronic lymphocytic leukemia actin tryptic digests analyzed by high-performance liquid chromatography. The Vmax of the actin-activated myosin Mg2+ ATPase activity was compared using rabbit skeletal muscle heavy meromyosin and subfragment 1 preparations. The values obtained with rabbit skeletal muscle and normal lymphocyte actin were identical. The Vmax observed with chronic lymphocytic leukemia lymphocyte actin was 70% of that obtained with normal lymphocyte actin. The amount of actin needed to produce half-maximal activation (Kapparent) of heavy meromyosin and subfragment 1 were, respectively, 26 and 25 microM for normal lymphocytes and 18 and 24 microM for chronic lymphocytic leukemia lymphocytes. The anomalous ATP activation by actin did not reflect differences in B-:T-cell subpopulations between chronic lymphocytic leukemia and normal lymphocytes. The possible significance of the observed differences between the myosin Mg2+ ATPase activation by chronic lymphocytic leukemia and normal lymphocyte actin is discussed.

Actins↗
PubMed1983

Adenosine and adenosine analogues are more toxic to chronic lymphocytic leukemia than to normal lymphocytes.

We compared the effect of adenosine and adenosine analogues on the phytohemagglutinin-induced proliferative response of blood lymphocytes from normal subjects and patients with chronic lymphocytic leukemia. As measured by the inhibition of thymidine or leucine incorporation, adenosine was more toxic to chronic lymphocytic leukemia (CLL) than to normal lymphocytes. This difference was not affected by the removal of adherent cells. The patients' B lymphocytes were more susceptible to adenosine toxicity than normal B lymphocytes. Similar responses were noted in T lymphocytes from both sources. Differential susceptibility was also observed with deoxyadenosine and adenosine analogues, including 5'deoxyadenosine. Uridine rescue from adenosine toxicity was observed for normal and CLL lymphocytes. In the presence of uridine, there was no difference in the residual inhibition of CLL as compared to normal lymphocytes. Intact CLL lymphocytes metabolized 14C-adenosine at a much lower rate than normal lymphocytes. While it appears that the greater toxicity of adenosine to CLL lymphocytes reflects the impaired catabolism of this nucleoside by these cells, evidence is presented that this is not the only mechanism underlying the differential susceptibility. These results may serve as the basis for further pharmacologic investigations of adenosine and adenosine deaminase inhibitors in chronic lymphocytic leukemia.

Adenosine↗
PubMed1983

Ribonucleotide content of mononuclear cells from normal subjects and patients with chronic lymphocytic leukemia: increased nicotinamide adenine dinucleotide concentration in chronic lymphocytic leukemia lymphocytes.

The ribonucleotide content of lymphocytes obtained from normal subjects and patients with chronic lymphocytic leukemia (CLL) was determined by means of high-performance liquid chromatography. The levels of normal B- and T-cells were compared to each other as well as those of their CLL counterparts. Unfractionated CLL lymphocytes, predominantly B-cells, had significantly lower levels of adenosine-5'-triphosphate, cytidine-5'-triphosphate, uridine-5'-triphosphate, cytidine-5'-diphosphate, and guanosine-5'-phosphate, while the concentration of nicotinamide-adenine dinucleotide was significantly higher than in normal unfractionated lymphocytes which consisted mainly of T-cells. For enriched populations: (a) CLL B-cells had much lower adenosine-5'-triphosphate (3439 versus 5689) (pmol/1 X 10(7) cells), cytidine-5'-triphosphate (107 versus 313), guanosine-5'-triphosphate (462 versus 978), and uridine-5'-triphosphate (633 versus 1214) than normal B-cells; (b) CLL T-enriched subpopulations had significantly lower ribonucleoside triphosphates, adenosine-5'-triphosphate (3217 versus 5468), cytidine-5'-triphosphate (119 versus 209), guanosine-5'-triphosphate (422 versus 826), and uridine-5'-triphosphate (504 versus 969) than normal T-cells. The lower ribonucleoside triphosphate levels found in unfractionated CLL lymphocytes, therefore, are the result of differences between the CLL and normal B-cells as well as between CLL and normal T-cells. These findings establish a framework for studying the reasons underlying the decreased ribonucleoside triphosphate levels in unfractionated CLL lymphocytes. T-helper and T-suppressor lymphocytes showed similar ribonucleotide patterns. Nucleoside and base levels were significantly higher in normal monocytes than in normal lymphocytes. The only compound found to be increased in the CLL B-lymphocytes when compared to their normal counterparts was nicotinamide-adenine dinucleotide. The level in CLL lymphocytes was 404 versus 209 pmol/10(7) cells for normal B-lymphocytes. No correlation was found between any ribonucleotide levels and the expression of 5'-nucleotidase activity.

B-Lymphocytes↗
PubMed1983

[The problem of anastomosis of the large intestine].

Healing problems following surgery of the colo-rectal junction seem to be due primarily to the blood supply of the anastomosis. Radical resections of the draining lymph system (metastatic road) including the dissection of the inferior mesenteric artery in patients with distal colonic cancer may reduce the blood flow to the oral stump of the anastomosis dramatically. In a retrospective analysis, this kind of resection technique will have a much higher incidence in anastomotic stenosis compared to controls without ligation of the artery. By using the electrical knife versus scalpel or scissors a significant higher damage of the colonic wall in animals and increased healing problems of anastomoses can be expected clinically.

Animals↗
PubMed1983

Relationship of adriamycin concentrations to the DNA lesions induced in hypoxic and euoxic L1210 cells.

Exponentially growing L1210 mouse leukemia cells were incubated with Adriamycin (ADR) under hypoxic (95% N2:5% CO2) or euoxic conditions (95% air:5% CO2) for 1 hr at 37 degrees at a drug concentration ranging from 2.8 X 10(-8) to 2.8 X 10(-4) M, i.e., from levels attained clinically by bolus delivery to the high levels used as an i.p. drug dwell or experimentally, in in vitro conditions. High-pressure liquid chromatography analyses showed diminishing efficiency in drug uptake by the cells as the dose was increased. There were no significant differences between hypoxic and euoxic cells in drug uptake and metabolism. The frequency of DNA protein-associated single-strand breaks and DNA-protein cross-links per 10(6) nucleotides, detected by the alkaline elution technique, increased with the dose in the range of 2.8 X 10(-8) to 2.8 X 10(-6) M in both euoxic and hypoxic cells and declined thereafter. However, the number of DNA lesions relative to a normalized drug level declined steadily, starting with the 2.8 X 10(-7) M concentration. Concentrations greater than 2.8 X 10(-6) M of ADR induced still another type of lesion, direct DNA strand breaks, only in euoxic cells. The results indicate that a common mechanism of interaction between drug and DNA is present in hypoxic and in euoxic cells at low ADR, while an O2-dependent mechanism becomes operational in euoxic cells at high ADR levels.

Animals↗
PubMed1982

Properties of lymphocyte 5'nucleotidase in normal subjects and patients with chronic lymphocytic leukemia.

Heterogeneity for 5'nucleotidase has been demonstrated in chronic lymphocytic leukemia [12]. The enzyme is not detectable in the lymphocytes from the majority of patients with this disorder, but normal and even supranormal levels are found in some cases [17]. In the present studies, the properties of this ecto-nucleotidase were investigated in unhomogenized lymphocytes isolated from the blood of normal subjects and patients with chronic lymphocytic leukemia. The activity was found to have a pH optimum of 8.0-8.5 and a preference of 5'ribo- over 5'deoxyribonucleotides. The enzyme was inactive towards 2',3'AMP. The Km for AMP showed a broad range from 19 to 210 microM in unhomogenized lymphocytes. An unexpected relationship was observed between sp. act. and this Km in that higher Km values were noted with cells from subjects with high lymphocyte 5'nucleotidase sp. act. and low Km values in lymphocyte preparations with low sp. act. When plasma membranes were prepared, a narrow range of low Km values unrelated to sp. act. was noted. The change in Km was not due to Pi concentration or nucleotide effects. The ecto-enzyme was inhibited by alpha, beta-methylene adenosine diphosphate, while cytosol phosphatase activity was not inhibited by this compound. Heat stability studies revealed a 45% loss in 5'nucleotidase activity after incubation for 20 min at 65 degrees C. A comparison of the substrate preference, Km values, effect of inhibitor and subcellular localization revealed no differences between the enzyme from patients with chronic lymphocytic leukemia and from normal subjects. This finding is consistent with the suggestion that the undetectable or supranormal levels observed in the lymphocytes of patients with this disorder stems from variations in the percentage of cells having 5'nucleotidase rather than changes in the enzyme proper.

5'-Nucleotidase↗
PubMed1982

Decreased actin content of lymphocytes from patients with chronic lymphocytic leukemia.

Actin, a major cytoskeletal protein, was quantitated in normal and chronic lymphocytic leukemia lymphocytes. The actin content of normal human blood lymphocytes was 2.2 +/- 0.4 mg/10(9) cells and represented 6.6% +/- 1.8% of the total cellular protein. A significant decrease (p less than 0.001) was noted in chronic lymphocytic leukemia lymphocytes that contained 1.4 +/- 0.3 mg actin/10(9) cells, constituting 4.3% +/- 1.1% of the total protein. Normal T and B cells did not differ in actin content. Reduced actin levels were found in the T as well as in the B lymphocytes of "B-cell" chronic lymphocytic leukemia. The possible importance of the decreased actin level in the anomalous capping response and motility of chronic lymphocytic leukemia lymphocytes is discussed.

Actins↗
PubMed1982

Chlorambucil therapy in hairy cell leukemia: effects on lipid composition and lymphocyte subpopulations.

Two patients with progressive hairy cell leukemia following splenectomy were treated with low-dose daily chlorambucil. Both had an objective hematologic response as determined by a return to normal hematocrit and platelet count. This was also reflected in the mononuclear cell fraction by the normalization of cholesterol content, cholesterol/phospholipid ratio, and the lymphocyte subpopulations. This article confirms previous reports on the efficacy of chlorambucil in this setting and describes some morphological, and biochemical concomitant events.

Aged↗
PubMed1981

Increased ascorbic acid content in chronic lymphocytic leukemia B lymphocytes.

Human lymphocyte extracts analyzed by high-performance liquid chromatography reveal a major UV-absorbing peak that was shown to be ascorbic acid by spectral, chemical, and enzymatic criteria. Because this peak appeared very prominent in the elution profile of chronic lymphocytic leukemia (CLL) lymphocyte extracts, we measured the ascorbic acid content in lymphocytes from the blood of normal subjects and untreated patients with chronic lymphocytic leukemia. A significantly higher concentration of 111 +/- 15.3 nmol per 10(8) cells (mean +/- SEM) was found in CLL lymphocytes than in normal blood lymphocytes, which contained 42.2 +/- 3.3 nmol per 10(8) cells. Selective enrichment with B and T cells showed that this difference was limited to the chronic lymphocytic leukemia B cell, which had a 5- to 15-fold higher content of ascorbic acid than normal B cells had. In contrast, the ascorbic acid level was similar in normal and CLL T cells. The very high ascorbic acid content provides the chronic lymphocytic leukemia B cell with a reducing substance that could react with oxidants or free radicals.

Ascorbic Acid↗
PubMed1981

The diagnostic value of the serum lactic dehydrogenase determination in the evaluation of unexplained thrombocytosis.

Thrombocytosis may reflect a primary myeloproliferative disorder or be a secondary reaction to other pathologic processes. Patients with persistent unexplained thrombocytosis meeting criteria of primary thrombocythemia had elevated levels of serum lactic dehydrogenase, whereas comparable patients with secondary thrombocytosis did not. The findings of an elevated serum lactic dehydrogenase supports the diagnosis of a myeloproliferative syndrome in patients who have unexplained thrombocytosis, and should be useful in the differential diagnosis of this hematologic abnormality.

Adult↗
PubMed1981

Adriamycin damage: in vivo repair by lymphoma cells.

The in vivo repair of ADR-induced cell damage was investigated in the DBA3 transplantable mouse lymphoma. After a single injection of 5 or 15 mg ADR/kg body weight into DBA/2J mice, the survival fraction of clonogens showed a 2.2- to 4.4-fold decrease at 12 or 18 hours post injection and returned to pretreatment levels within 6 hours. These changes were accompanied by the appearance and disappearance of DNA crosslinks and breaks. Because cell division and/or cell loss could not explain the return of clonogens to pretreatment level, the results strongly suggest repair of ADR damage in tumor cells in situ. Such an efficient repair mechanism, responding to a high toxic dose of ADR, constitutes a therapeutically unfavorable event that may contribute to drug resistance.

Animals↗