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Biomedical subjects

R Sharon

Publications and source records attributed to R Sharon.

At least 55 records · Page 3Linked to original sources

Aplastic anemia associated with in vitro inhibition of erythropoiesis by bone marrow-adherent cells.

A patient with aplastic anemia that evolved following pure red cell aplasia is described. Cultures of the patient's marrow cells revealed greatly reduced numbers of primitive (BFU-E) and relatively mature (CFU-E) erythroid progenitors, but normal numbers of multipotential (CFU-GEMM) precursors. The BFU-E/CFU-GEMM and CFU-E/BFU-E ratios in the patient's marrow cell cultures were also reduced. T cell- or antibody-mediated inhibition of in vitro erythropoiesis could not be demonstrated in this patient. However, the patient's marrow-adherent cells suppressed the growth of autologous and allogeneic BFU-E and CFU-E, without influencing the growth of CFU-GEMM. Medium conditioned by the patient's adherent cells failed to inhibit the growth of normal erythroid precursors. Our findings suggest a role for marrow-adherent cells in the pathogenesis of aplastic anemia in this patient.

Adult↗

Experimental autoimmune anemia induced with haptenated syngeneic mouse red blood cells and low dose X-irradiation.

This paper describes an experimental model of autoimmune anemia induced with haptenated syngeneic mouse red blood cells (MRBC). A strain mice immunized with penicillinated MRBC (PEN-MRBC) generated IgM anti-MRBC autoantibody response and a very low level of the corresponding IgG response. The IgG anti-MRBC autoantibody response was augmented when mice were X-irradiated (250 rad) prior to immunization with PEN-MRBC, suggesting that a radiosensitive suppressive mechanism controls the IgG autoantibody response. Both the IgM and the IgG secondary anti-MRBC autoantibody responses emerged in mice that had been injected with PEN-MRBC 2 months before a second PEN-MRBC injection. Low dose X-irradiation (250 rad) of A mice without subsequent immunization induced an early IgG anti-MRBC autoantibody response and late IgM response, suggesting the existence of antierythrocyte autoreactivity in normal animals which is controlled by a radiosensitive suppressor mechanism. The anti-MRBC autoantibody response was not only induced by PEN-MRBC. Multiple injections of A mice with trinitrophenylated MRBC also induced autoantibodies against erythrocytes. The IgG anti-MRBC autoantibody response was associated with anemia, but it is not yet known if the two events are related or independent. Autoantibodies of X-irradiated mice immunized with PEN-MRBC were linearly titrated and partially absorbed with MRBC. Less efficient absorption was achieved with human and sheep red blood cells. Fifty percent of splenocytes from X-irradiated mice injected with PEN-MRBC expressed IL-2 receptor 3 days after the injection, whereas the number of cells expressing this receptor earlier or later was significantly less. The various applications of this autoimmune model are discussed.

Anemia, Hemolytic, Autoimmune↗

Mouse glutathione S-transferase Ya subunit: gene structure and sequence.

A mouse glutathione S-transferase gene encoding the Ya subunit was isolated and sequenced. The gene spans about 11 kb, contains seven exons, and encodes an mRNA of 841 nucleotides. Promoter elements, TATA and CAAT box sequences, were located 32 and 70 nucleotides upstream from the initiation of transcription site. The mRNA coding sequences of the mouse gene were highly homologous to a rat liver Ya mRNA species detected by cDNA cloning. The mouse Ya gene produces a 223-amino-acid polypeptide that differs from the 222-amino-acid rat Ya by 10 amino acid substitutions and a carboxyl terminus Phe-Lys-Ile-Gln instead of Phe-Lys-Phe. A genomic clone containing the last three exons of the rat Ya gene was also isolated, sequenced, and compared with the mouse Ya gene. An extensive sequence conservation (70-80%) in the 50 to 200 bases of introns at the exon-intron junctions as well as in the region beyond the cleavage-polyadenylation site of pre-mRNA was observed.

Amino Acid Sequence↗

Effect of Dead-Sea brine and its main salts on cell growth in culture.

Diluted Dead-Sea brine and solutions of certain of its salts (chlorides and bromides of Na, K and Mg) were found to reversibly inhibit cell proliferation in culture. Bromides were more powerful as inhibitors than their chloride counterparts, and K salts were more effective than those of Na and Mg. KBr had the strongest inhibitory effect, which equalled that of diluted Dead-Sea brine at the same concentration. The favourable results of the Dead-Sea Spa treatment of psoriasis may thus be partly due to the penetration of minerals into the body, via the skin, with subsequent reinforcement of anti-proliferative mechanisms.

Animals↗

Treatment of polycythemia vera with hydroxyurea.

Thirty-six patients with polycythemia vera were treated with hydroxyurea for 12 to 67 months. Nineteen patients were previously treated with other drugs. In the vast majority of patients, an average dose of 1 g/day was sufficient to control hematocrit value and platelet count. Half of the patients experienced relief of pruritus, and two thirds experienced regression of splenomegaly. None of the patients had either thrombotic complications or leukemia. Four patients suffered from mild side effects, which included fever, hyperbilirubinemia, and stomatitis, and were relieved of their symptoms when treatment was stopped. However, two patients experienced renal failure, a possible major complication not described previously.

Aged↗

Determination of ABO blood group zygosity by an antiglobulin rosetting technique and cell-based enzyme immunoassay.

Two methods were employed to determine the zygosity of A and B red cells, the rosetting antiglobulin test and the enzyme-linked immunoadsorbent assay (ELISA) technique. By means of the rosetting antiglobulin test, clear differences between AA and AO as well as BB and BO could be shown; however, this method could not define the variation in the amount of the H antigen as a complimentary means of differentiating AA from AO and BB from BO. The ELISA test could quantitatively estimate the level of expression of H antigen, and using anti-A and anti-B reagents in a simultaneous assay, a specific pattern could be generated for each phenotype. Both rosette and ELISA approaches offer easy and inexpensive means of determining zygosity within the ABO system for use in paternity exclusion.

ABO Blood-Group System↗

Partial response of meningeal myeloma to craniospinal radiotherapy.

Concomitant occurrence of meningeal involvement and thoracic plasmacytoma was observed in a patient with IgA lambda myeloma. Cerebrospinal fluid analysis revealed IgA-lambda paraprotein and pathological plasma cells. CT scan of the chest and lumbar myelogram excluded spinal cord compression. The patient partially responded to craniospinal irradiation but succumbed to rapidly progressive myeloma 20 weeks following diagnosis of meningeal involvement.

Aged↗

Immunological function in osteoporosis.

An imbalance of osteoblastic bone formation and osteoclastic bone resorption is thought to be responsible for the osteoporotic condition. The pathological events leading to this disorder are, in most instances, uncertain. A defect in the ability of osteoporotic patients to respond to foreign histocompatibility antigens in a mixed leukocyte reaction is reported here. The results further show that this defect is due both to a poorly responding lymphocyte population as well as to a suppressor factor in osteoporotic sera. In addition, there is a significant increase in the relative and absolute numbers of T cells in the patients' peripheral blood, while serum IgG, IgA, and IgM remain within the normal range. These findings are discussed in the light of a common immunopathological pathway regulating osteoclastic activity and leading to the osteoporotic condition.

Adult↗

An unusually high incidence of homozygous MM in ankylosing spondylitis.

Blood types of patients admitted to the Hadassah University Hospital with ankylosing spondylitis did not differ significantly from the expected percentages among the Israeli population, except for a very high incidence (92% to 100%) of homozygous MM. Among healthy controls the incidence of homozygous MM was found to be in line with accepted values.

Blood Group Antigens↗

Pseudomonas aeruginosa isolates from different medical institutions.

Patients screened for antibiotic resistance at three different medical institutions yielded 1,597 isolates of Pseudomonas aeruginosa. Most of the isolates were sensitive to amikacin (92.8%), tobramycin (70.6%), gentamicin (59.1%) neomycin (89.4%), azlocillin (84.6%), mezlocillin (83.9%), piperacillin (85.7%), cefsulodin (83.8%) and colistin (98.5%); only 43.8% were sensitive to carbenicillin. In a rehabilitation hospital the frequency of isolates resistant to most of these antibiotics was twice as high than in the two other institutions. The frequency of phenotypes resistant to the combination of carbenicillin and gentamicin was twice as high in the rehabilitation hospital isolates (47.3%) than in the general hospital isolates (28.5%). The frequency of isolates resistant to the combination of aminoglycosides and the new beta-lactam antibiotics is relatively lower than in the former combinations. Serogroup 11 is predominant in the isolates from all three institutions (44%). In carbenicillin- and gentamicin-resistant isolates, 61% were of serogroup 11. On the other hand, in the carbenicillin- and gentamicin-sensitive isolates, serogroup 11 accounted for only 27.2%.

Aminoglycosides↗

The isolation of immunogenic molecular entities from immunogenic and nonimmunogenic tumor homogenates by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).

YAC, a Moloney-virus-induced tumor of A-strain mice, is a nonimmunogenic tumor. Mice injected with the inactivated neoplastic cells and challenged with viable tumor cells did not survive longer than mice that received the challenge dose alone. The homogenate of this nonimmunogenic tumor was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). After electrophoresis, the gel slices containing isolated molecular entities were injected into various groups of mice. The mice were challenged with low doses of viable tumor cells (10-30 cells) and their survival time was recorded. Small but significant numbers of mice injected with apparent 80-90 K SDS-PAGE-isolated molecular entity rejected the tumor or survived longer than the control groups of mice. Spleen cells from mice injected with 80-90 K molecular entity inhibited the YAC tumor cotransferred with them to naive recipients (Winn assay). Spleen cells from mice injected with monoclonal antibody against nonspecific T-cell helper factor and immunized with 80-90 K SDS-PAGE-isolated molecular entity failed to inhibit the tumor growth in naive recipients, indicating that helper T cells are involved in induction of the antitumor resistance. Nylon-wool-passed splenocytes from mice injected with 80-90 K inhibited tumor growth in some of the recipient mice. Spleen cells from these mice treated with anti-Thy-1 and complement also inhibited the tumor growth in some of the recipients, suggesting that the effector cells were both T and non-T cells. C57BL/6 mice immunized with apparent 20 K SDS-PAGE-isolated molecular entity of RBL5 tumor also induced in vivo resistance to the syngeneic viable RBL5 cells, but not to the syngeneic B16 melanoma cells, indicating the specificity of the protective effect. The practical and theoretical implications of these findings are discussed.

Animals↗

DNA repair and induction of plasminogen activator in human fetal cells treated with ultraviolet light.

We have tested human fetal fibroblasts for development associated changes in DNA repair by utilizing nucleoid sedimentation as an assay for excision repair. Among skin fibroblasts the rate of excision repair was significantly higher in non-fetal cells than in fibroblasts derived from an 8 week fetus; this was evident by a delay in both the relaxation and the restoration of DNA supercoiling in nucleoids after irradiation. Skin fibroblasts derived at 12 week gestation were more repair proficient than those derived at 8 week gestation. However, they exhibited a somewhat lower rate of repair than non-fetal cells. The same fetal and non-fetal cells were also tested for induction of the protease plasminogen activator (PA) after u.v. irradiation. Enhancement of PA was higher in skin fibroblasts derived at 8 week than in those derived at 12 week gestation and was absent in non-fetal skin fibroblasts. These results are consistent with our previous findings that in human cells u.v. light-induced PA synthesis is correlated with reduced DNA repair capacity. Excision repair and PA inducibility were found to depend on tissue of origin in addition to gestational stage, as shown for skin and lung fibroblasts from the same 12 week fetus. Lung compared to skin fibroblasts exhibited lower repair rates and produced higher levels of PA after irradiation. The sedimentation velocity of nucleoids, prepared from unirradiated fibroblasts, in neutral sucrose gradients with or without ethidium bromide, indicated the presence of DNA strand breaks in fetal cells. It is proposed that reduced DNA repair in fetal cells may result from alterations in DNA supercoiling, and that persistent DNA strand breaks enhance transcription of PA gene(s).

Cell Line↗

Auto-delayed-type hypersensitivity induced in immunodeficient mice with syngeneic modified self-antigens. II. Suppressor T cells control the autoimmune response.

The control of the autoimmune response to modified self-antigens was explored, using immunodeficient mice injected with syngeneic trinitrophenylated spleen cells (TNP-SC) as an experimental model system. X-irradiated (250 rad) A mice injected with TNP-SC and footpad-challenged 7 to 14 days later with syngeneic lymphoblasts generated a delayed-type hypersensitivity (DTH) response that was expressed by footpad swelling measured 24 h, 48 h and 72 h later. Histopathological examination showed massive inflammatory infiltration in the soft tissues of the limbs with extensive necrosis. This was not observed in X-irradiated mice that received the lymphoblast challenge only. The immunological activity was transferred from the X-irradiated TNP-SC-immunized mice to naive recipients by T cells (Lyt-1+) and not by serum, thus excluding the possibility that the inflammatory reaction is mediated by antibodies. We have previously presented evidence that the differentiation status of the lymphoblasts, and not contaminants from the incubation media, was the determinant factor eliciting the DTH response of immunodeficient mice injected with TNP-SC. Since only syngeneic lymphoblasts were able to elicit the DTH response of immunodeficient mice injected with syngeneic TNP-SC, we suggested that immunological activity was directed against self-antigens, thus expressing an autoimmune reactivity. The ability of immunodeficient mice to generate syngeneic DTH was not restricted to the TNP hapten or to inbred A-strain mice. X-irradiated BALB/c mice injected with syngeneic penicillinated spleen cells and challenged with syngeneic lymphoblasts generated a significant DTH response, in contrast to X-irradiated BALB/c mice exposed to the challenge dose only. X-irradiated A mice injected with syngeneic TNP-SC and simultaneously reconstituted with syngeneic splenocytes failed to generate a DTH response after the lymphoblast challenge, indicating that the syngeneic DTH response is controlled by normal suppressor cells. The suppressor cells were characterized as T cells carrying I-Jk, Lyt-1+, Lyt-2+ and Lyt-3+ antigenic markers. The suppressor cells abrogated the syngeneic DTH response of immunodeficient mice injected with TNP-SC, even when transferred a few days after the induction of immunological activity, but not when transferred 1 h before the lymphoblast challenge, indicating that even the established immunological activity can be restrained. Various immunological aspects of these observations and the significance of the findings in illuminating human autoimmune disorders are considered.

Animals↗

The rosetting antiglobulin test as a means of determining the D zygosity of human red cells.

The erythrocyte-antibody rosetting antiglobulin test was used to determine differences in the expression of various Rh antigens on homozygous and heterozygous Rh positive red blood cells. The rosetting antiglobulin test was able to detect the relative difference in expression of C, c, E and e on homo- and heterozygous red blood cells. Based on these findings, the test was used and found suitable for determining the genotypes of various D positive red blood cells.

Adult↗