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Biomedical subjects

R Silber

Publications and source records attributed to R Silber.

At least 109 records · Page 6Linked to original sources
PubMed1981

Electrophoretic mobility distributions distinguish hairy cells from other mononuclear blood cells and provide evidence for the heterogeneity of normal monocytes.

The electrophoretic mobility distributions of hairy cells, normal monocytes. CLL, and normal lymphocytes isolated from blood were determined by electrophoretic light scattering. Values obtained for hairy cells, 1.52 X 10(-4) cm2/V . sec, were indistinguishable from that of normal monocytes. The mobility of CLL lymphocytes was similar to that of normal B cells. After exposure to neuraminidase, hairy cells revealed a homogeneous distribution with a reduced mobility of 0.55 X 10(-4) cm2/V . sec, while normal monocytes showed a heterogeneous distribution of electrophoretic mobilities suggestive of subpopulations. The electrokinetic behavior of hairy cells thus differs from that or normal and CLL lymphocytes before, and from that of monocytes after, treatment with neuraminidase. The hairy cell therefore possesses a distinct pattern of surface charge properties that clearly distinguish it from the circulating B cells, T cells, or monocytes.

B-Lymphocytes↗
PubMed1981

Induction therapy and intensive consolidation with daunorubicin, cytosine arabinoside, and 6-thioguanine in adult acute nonlymphoblastic leukemia.

Twenty-one patients with acute nonlymphocytic leukemia were treated with a regimen including daunorubicin, cytosine arabinoside, and 6-thioguanine and 15 patients (71%) achieved a complete remission. Thirteen of the 15 remissions occurred after a single course of therapy and two after two courses of treatment resulting in a rapid time to complete remission. The time from treatment initiation to complete remission was 21-82 days with a median of 29 days. Nine of the 15 patients who gained a complete remission were then treated with two cycles of consolidation therapy utilizing the three induction drugs in modified dosages to determine the toxicity of a consolidation program. With the doses used in consolidation, pancytopenia regularly occurred but only 5/15 courses were associated with complications of bleeding or infection that required hospitalization. No patient died as a result of consolidation therapy. This study confirms the rapid effectiveness of the induction program which provided equivalent complete remission rates for adults at any age (up to 66 years). The consolidation regimen is now being used in a randomized study to determine whether it contributes to the duration of complete remission.

Acute Disease↗
PubMed1981

Comparison of lipid composition and 1,6-diphenyl-1,3,5-hexatriene fluorescence polarization measurements of hairy cells with monocytes and lymphocytes from normal subjects and patients with chronic lymphocytic leukemia.

In this report, we compare the lipid composition and fluorescence polarization properties of hairy cells with those of monocytes and lymphocytes from normal subjects and of lymphocytes from patients with chronic lymphocytic leukemia. For hairy cells, the cholesterol content was 4.66 +/- 1.49 (S.D.) mumol/10(9) cells, and the cholesterol/phospholipid ratio was 0.60 +/- 0.09. These were significantly higher than the values of normal lymphocytes, (cholesterol content, 2.75 +/- 0.65 mumol; cholesterol/phospholipid ratio, 0.50 +/- 0.07) or of chronic lymphocytic leukemia lymphocytes (cholesterol content, 1.76 +/- 0.43 mumol; cholesterol/phospholipid ratio, 0.44 +/- 0.07). Normal monocyte values (cholesterol content, 5.81 +/- 2.08 mumol; cholesterol/phospholipid ratio, 0.59 +/- 0.06) were similar to those of hairy cells. Using the probe 1,6-diphenyl-1,3,5-hexatriene, the fluorescence polarization value at 25 degrees for hairy cells was 0.302, compared to the value of 0.259 obtained with chronic lymphocytic leukemia lymphocytes. Intermediate values (0.294) were obtained with normal lymphocytes and monocytes. Fluorescence polarization values were higher in hairy cell membranes than in chronic lymphocytic leukemia lymphocyte membranes, indicating a low fluidity in the former cell, compatible with their higher cholesterol content and cholesterol/phospholipid ratio. These studies show that two neoplastic cells, hairy cells and chronic lymphocytic leukemia lymphocytes, differ markedly in membrane fluidity and that a high membrane fluidity does not necessarily occur in neoplasia.

Aged↗
PubMed1981

Protein-associated DNA breaks and DNA-protein cross-links caused by DNA nonbinding derivatives of adriamycin in L1210 cells.

The effects of Adriamycin derivatives on L1210 mouse leukemia cells were studied with the DNA alkaline elution assay. The exposure of exponentially growing cells to approximately equitoxic concentrations of N-trifluoroacetyladriamycin-14-valerate (13.8 microM) and its metabolites, N-trifluoroacetyladriamycin (9.0 microM) and N-trifluoroacetyladriamycinol (43.7 microM), for 1 hr in vitro resulted in a high frequency of protein-associated DNA breaks and DNA-protein cross-links. These effects were comparable to those observed with Adriamycin (2.8 microM) and with adriamycinol (26.9 microM). In contrast to Adriamycin and its metabolite adriamycinol, N-trifluoroacetyladriamycin-14-valerate and its two major metabolites do not bind to DNA. Despite the absence of this direct interaction, N-trifluoroacetyladriamycin-14-valerate and its metabolites produce alterations in DNA comparable with the effects of intercalating agents. No evidence for conversion of N-trifluoroacetyladriamycin-14-valerate to Adriamycin or adriamycinol was found in L1210 cells. The similar effects on DNA macromolecules, observed between intercalating and non-DNA-binding anthracyclines, are consistent with the concept that mechanisms other than direct interaction with DNA play a role in the toxic effects of these compounds.

Animals↗
PubMed1980

Human lymphocyte tubulin. Purification and characterization in normal and leukemic cells.

Tubulin has been purified from human blood and tonsil lymphocytes. Using gel filtration, the molecular weight of human lymphocyte tubulin was estimated to be 119000. The protein was shown to consist of two subunits, with molecular weights of 61000 and 58000 comparable to the alpha and beta polypeptides of human brain tubulin. A partial identity reaction was observed between lymphocyte tubulin and human tubulin when tested by double immunodiffusion against a rabbit anti-human brain tubulin antibody. In the presence of GTP, the purified protein polymerized to form microtubules. Tubulin was localized to the cell's juxtacentriolar region by immunofluorescence and electron microscopy. When assayed by a colchicine-binding assay corrected for time decay, the binding affinity was 1.50 +/- 0.86 . 10(6) M-1 and a level in normal lymphocytes of 1.21 . 10(2) +/- 0.79 g/g of soluble protein was determined. Since chronic lymphocytic leukemia lymphocytes have an anomalous capping behavior as well as an unusual susceptibility to colchicine toxicity, the properties and levels of tubulin were determined in these cells. Similar values were obtained for the level, decay rate, molecular weight, and Ka for colchicine as for normal lymphocytes. Chronic lymphocytic leukemia lymphocytes tubulin polymerized in a normal fashion. It thus appears that a decrease in the quantity for function of tubulin does not account for these anomalies in the chronic lymphocytic leukemia lymphocyte.

B-Lymphocytes↗
PubMed1980

Protein kinases in chronic lymphocytic leukemia.

Experiments were performed to characterize the protein kinase activity in blood lymphocytes from patients with chronic lymphocytic leukemia (CLL). Using histone as a substrate, the average specific activity was 397 pmole/min/mg protein. The Km for ATP was 8 muM and for histone 0.3 mg/ml. The addition of optimal concentrations of cyclic adenosine monophosphate (cAMP) (1 muM) or cyclic guanosine monophosphate (cGMP) (10muM) resulted in a 2.2-fold stimulation in activity but had no effect on the Km for ATP or histone. Most of the properties of the CCL protein kinase were similar to those of the normal lymphocyte enzyme. These include the pH response, substrate affinity, as well as rates of phosphorylation and dephosphorylation. The phosphorylation pattern of endogenous proteins was determined using intact lymphocytes incubated with 32P and cell-free homogenates with AT32P. These results indicate that: (1) the cyclicnucleotide-protein kinase interactions are unimpaired in CLL lymphocytes; and (2) a sharply defined cyclic nucleotide concentration response occurs for CLL (as well as normal) lymphocytes, which may explain the reports of variable inhibitory (and stimulatory) effects on mitogenesis by these agents.

Cyclic AMP↗
PubMed1978

Phase II study of adriamycin and bleomycin in patients with multiple myeloma.

Twenty-seven patients with far-advanced multiple myeloma, resistant to standard agents, were treated with either adriamycin (eight patients) or bleomycin (19 patients). Adriamycin was given iv at a dose of 60 mg/m2 every 3 weeks and bleomycin was administered im at a dose of 15 mg/m2 weekly. Drug toxicity was modest. One partial response was seen with each agent, both occurring in "good-risk" patients.

Aged↗
PubMed1977

Multiple myeloma with cutaneous involvement.

A 49-year-old man with multiple myeloma, IgA type, contracted cutaneous plasmocytomas. No deposits of immunoglobulin were found in the cutaneous tumor by direct immunofluorescence. The case is an unusual manifestation occurring in multiple myeloma.

Fluorescent Antibody Technique↗
PubMed1977

Ulcers of the leg in thalassemia.

Four patients had thalassemia and leg ulcers. In three patients the hematologic diagnosis of thalassemia had not been previously made; the presenting symptom was the leg ulcer. The diagnosis of thalassemia should be considered in patients who have unexplained chronic leg ulcers; the incidence of this complication of thalassemia may be higher than previously reported.

Adult↗
PubMed1976

Biomechanically induced tissue reactions after Al2O3-ceramic hip joint replacement. Experimental and early clinical results.

A biomechanical concept of interface maturation around cement-free implanted alumina-ceramic hip endoprostheses in sheep is explained. Provided there is rigid primary stability of the implant within the bone bed, hard tissue formation along the support areas of the implant is mainly dependent on implant shape and main local stress direction. Three subsequent phases of interface maturation can be distinguished, finally resulting in firm fixation of the implant by mechanical interlocking of supporting bone and ceramic. A new composite alumina-metal hip endoprosthesis for partial cement-free implantation (cup) is presented. The technique, postoperative care, and encouraging early results in 5 patients are demonstrated. A new ceramic femoral component for cement free implantation is proposed.

Acetabulum↗