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Biomedical subjects

R Sharon

Publications and source records attributed to R Sharon.

At least 73 records · Page 4Linked to original sources

Acute leukemia following chemotherapy and radiation therapy--a report of 15 cases.

14 patients developed acute nonlymphocytic leukemia and 1 patient developed Burkitt's leukemia following longterm chemotherapy and/or radiotherapy for other disorders. The main primary disorders included multiple myeloma, Hodgkin's disease, non-Hodgkin's lymphoma and breast carcinoma. Acute leukemia developed earlier in patients treated by chemotherapy with or without radiotherapy than in patients treated by radiotherapy alone (63 months, range 24-132 months; 201 months, range 48 months to 30 years, respectively). 13 patients presented without organomegaly and 8 were pancytopenic. Abnormalities of myeloid and erythroid cell lines were observed in the majority of the patients. A high rate of acute erythroleukemia (5 out of 14) was found. Increased reticulin fibers were found in 3 patients. The leukemia was invariably refractory to treatment with a median survival of 4 months. The possible role of preexisting abnormal marrow structure in the development of therapy-related leukemia is discussed.

Acute Disease↗

ABO incompatibility and reproductive failure. I. Prenatal selection.

An analysis of previous spontaneous abortions and the frequencies of blood-group combinations in mother-child pairs was carried out in 500 gravidae. The rate of previous spontaneous abortions in blood-group-O women whose latest child has blood group B is significantly higher than in all other women. On the other hand, the combination mother B/child AB is rarer than expected, but no increase in the rate of previous spontaneous abortions is obvious among these women. These discrepancies are interpreted as an indication that prenatal selection associated with ABO incompatibility may operate at various stages from fertilization through pregnancy, and that different incompatible combinations may be subject to selection at different stages.

ABO Blood-Group System↗

Erythrocyte Na+, K+ cotransport and blood pressure in identical twins.

The erythrocyte Na+, K+ cotransport system was studied in ten pairs of identical twins. Cation fluxes were remarkably similar in each pair of twins, which supports the concept of a genetic determinant for the cotransport system. There was, however, no apparent correlation between cotransport values and the family history of hypertension.

Adolescent↗

HLA-D "BG" in Israel. A Japanese related allele population and family study.

An homozygous typing cell for a local HLA-D determinant"BG", defined by family study, is described. HLA-D "BG" recognizes a specificity identical to the Japanese HLA-DHO (Dw12). Two families and 102 randomly selected healthy Israeli individuals were typed for the HLA-D "BG" determinant. HLA-D "BG" showed segregation as a single determinant within families. The gene frequency for this allele was 0.045, compared to the frequency of 0.148 for DHO in Japanese. In the Israeli population "BG" is in strong association with HLA-Bw52 (joint occurrence = 7.80%) and DR2 (joint occurrence = 8.80%), resembling the data reported foar DHO (Dw12) in Japan. The frequency of this allele may partially account for the low frequency of HLA-Dw2 in the Israeli population.

Alleles↗

Study of a family with Cerebrotendinous Xanthomatosis. No HLA linkage, but an informative recombination between HLA-B and Bf.

A large family with three children affected with the autosomal recessive disease of Cerebrotendinous Xanthomatosis (CTX) was studied for class I (HLA-A,B,C) and class II antigens (HLA-DR,D,SB), properdin factor B and glyoxalase. The extensive typing revealed an informative cross-over between HLA-B and Bf, indicating that Bf is located centromeric to the HLA-B locus and segregated in this family with HLA-D/DR. The parents in this family were first cousins and their parents were also first cousins. Three of their four haplotypes share B14, BfS, DR1, Dx and SB4 and may be identical by descent. The three affected children carried among them all four parental haplotypes, indicating that close linkage of the CTX locus to HLA is unlikely.

Adolescent↗

Immunogenicity of subcellular fractions and molecular species of MuLV-induced tumors. III. Stimulation of syngeneic antitumor responses by subcellular fractions and molecular species of Moloney virus-induced tumors in CBA and A mice.

YBA, a Moloney virus-induced leukemia in CBA mice, and a relatively weak immunogenic tumor, was screened for the presence of immunogenic antigens. The tumor was subjected to homogenization and subcellular fractionation on sucrose gradients; the immunogenic subcellular fractions underwent further separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The immunogenicity of the subcellular fractions and the SDS-PAGE-isolated molecular species were tested by (their) subcutaneous injection into syngeneic mice and examination of their splenocytes examined against tumor cell and normal cell targets by the chromium release cell-mediated lympholysis assay. Tumor cell homogenates were also separated by SDS-PAGE and tested for immunogenicity without prior fractionation. Splenocytes from mice that had received injections of certain SDS-PAGE-isolated epitopes derived from YBA tumor homogenate or its light and heavy subcellular fractions generated effective cytotoxic responses against YBA target cells after 6 days in vitro cultivation. In contrast, intact YBA tumor cells or non-separated tumor homogenates failed to induce an efficient cytotoxic response. The effector cells induced with the immunogenic SDS-PAGE-isolated epitopes of YBA tumor were specific, since they cytolysed the homologous target cells more efficiently than unrelated target cells or syngeneic normal cells. The activity of these effector cells was affected by varying the effector: target ratio. Augmentation of the cytotoxic responses was obtained when the splenocytes of mice immunized with SDS-PAGE-isolated epitopes of YBA tumor were restimulated in vitro, with the homologous neoplastic cells. Immunogenic SDS-PAGE epitopes were isolated from YAC tumor also (YAC is a Moloney-induced tumor of A mice). The effector cells induced with these separated epitopes were characterized as thymus-derived cells and not as natural killer cells. The results suggest that (1) the molecular repertoire of YBA and YBA tumors contain immunogens that can induce a specific antitumor cell-mediated response; (2) the isolated molecular species injected are more efficient immunogens than the entire, unseparated homogenate sample or a dose of 10(8) intact inactivated tumor cells; and (3) the gel matrix may be responsible for the enhanced cell-mediated response induced against the weakly immunogenic tumor.

Animals↗

Induction of antitumor reactive cells or suppressor cells by different molecular species isolated from the same nonimmunogenic tumor.

The inability of spontaneous and some laboratory-induced tumors to stimulate the immune system has continuously raised the question of the validity of using immunological maneuvers in order to control tumor growth. In this project we suggest that a tumor which is nonimmunogenic still has an immunogenic potential that can be revealed and used in order to stimulate antitumor immunity and consequently tumor destruction. YAC, a Moloney-virus-induced tumor of A mice, failed to stimulate immunological responses. This tumor homogenate was exposed to nonreduced sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). At the end of the electrophoresis, the gels were sliced and injected in sequential order into various groups of A mice. It was found that some of the gel slices (usually with M.W. of 100 K or less) induced cytotoxic responses, whereas other gel slices (usually with M.W. of about 150 K) induced suppressor cells. Similarly, certain gel slices induced cells that inhibited the in vivo tumor growth, whereas others enhanced the in vivo tumor growth. These last two types of cells did not present the same cellular population that mediated the cellular cytotoxicity or the suppressive effects respectively. It was concluded that poorly immunogenic tumor cells do possess immunogenic potential that can be revealed after dissociation between the immunogenic and suppressogenic entities.

Animals↗

Incidence of acetaminophen in donated blood.

Acetaminophen levels were determined in 1,176 sera separated from donated blood. The analysis was performed by both a colorimetric method and by high performance liquid chromatography. 6.12% of the samples contained acetaminophen levels ranging from 18 to 58 microgram/ml. The possible clinical significance of such a high incidence of this drug among healthy blood donors is discussed.

Acetaminophen↗

Applicability and significance of salicylate screening in sera of voluntary blood donors: evaluation of two analytical methods.

Salicylate concentrations in 3819 sera of apparently healthy voluntary blood donors were determined in view of the significance of this drug in the induction of allergic reactions and its possible interference in platelet function. Two hundred and ninety-five sera were found by a modified colorimetric determination to contain salicylates. The colorimetric determination was compared with a high performance liquid chromatography (HPLC) analysis of salicylate-containing sera. Drug concentrations detected were mostly in the range of 20-100 mg/l. Such concentrations have been reported to evoke allergic reactions and to affect the haemostatic action of platelets.

Blood Banks↗

Hairy cell leukemia: defective production of granulocyte-macrophage colony-stimulating factor by peripheral blood cells.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) production by the peripheral blood (PB) cells of hairy cell leukemia (HCL) patients whose PB contained only 2 to 10% hairy cells was studied in an in vitro bone marrow culture system. In addition, the possible inhibitory effect on the growth of normal granulocyte-macrophage colony-forming cells (GM-CFC) by the patients' mononuclear cells or serum was assayed. GM-CSF production by PB cells of HCL patients was 82 +/- 18% (mean +/- sd) lower than its production by normal PB cells. No significant inhibition of normal GM-CFC growth was observed in the presence of patients' PB mononuclear cells or their serum. These findings suggest that in HCL patients the monocyte-macrophage system is defective in its capacity to produce GM-CSF. This defect may play a role in the impaired granulocyte production known to occur in HCL.

Adult↗

Genetics of insulin dependent diabetes mellitus in Israel: population and family study.

The association between insulin dependent diabetes mellitus (IDDM) and the HLA system was studied in two groups of Jewish patients: 50 Ashkenazim and 42 non-Ashkenazim. The pattern of association of HLA-A and B locus antigens was somewhat different from that observed in European Caucasian patients. HLA-B8 had a higher frequency; B15 and Cw3 were rare in the population studied and were less frequent in IDDM patients than in controls. On the other hand, the frequency of A26, B18, and Bw38 was increased in Ashkenazi patients, but not in non-Ashkenazim, who in turn showed an increase for Bw51. Although the association between IDDM and HLA-A and B locus antigens shows a marked variability in different populations, the association with HLA-DR3 and DR4 is constant feature. There was a typical excess of DR3/DR4 heterozygotes in both patient groups. This heterozygote type carries the highest relative risk, followed by DR4/DR4 homozygotes. These data can well be interpreted by a model of two different HLA-linked susceptibility genes, one associated with DR3 and the other one with DR4, that interact so that different genotypes are associated with different levels of penetrance. This model received further support from studies in 15 multiple case families where there is an excess of affected sib pairs sharing two DR antigens.

Adolescent↗

HLA in a selective aldosterone biosynthetic defect due to type 2 corticosterone methyl-oxidase deficiency.

HLA phenotypes were studied in nine Jewish families, originating from Iran, with 18 individuals affected with a selective aldosterone biosynthetic defect and 12 healthy siblings. This disorder is inherited through an autosomal recessive gene and parents were consanguineously related in eight out of nine sibships. Family analysis showed that 18 affected individuals carried 20 different haplotypes and only two patients were homozygous for a haplotype. Yet a peak lod score of 1.128 was obtained for the recombinant fraction of 0.05 and thus linkage to HLA cannot be ruled out.

Aldosterone↗