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Biomedical subjects

A Bernstein

Publications and source records attributed to A Bernstein.

At least 199 records · Page 11Linked to original sources
PubMed1980

Results of a double-blind controlled study on the use of betamethasone in the prevention of respiratory distress syndrome.

A double-blind controlled study on the prenatal use of betamethasone in the prevention of respiratory distress syndrome (RDS) was carried out on 137 patients from 24 to 34 weeks' gestation. The incidence of RDS was less in the treated group (5%) than in control group (17%). The neonatal mortality rate was lower in the treated group (5%) than in the control group (18%) due to an excess of neonatal deaths in the placebo group.

Betamethasone↗
PubMed1980

Phorbol ester tumor promoters block the transition from the early to the heme-dependent late program of Friend cell differentiation.

In this study, the mechanism of inhibition of differentiation of Friend erythroleukemia cells by the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), has been examined. These studies indicate that some early events associated with Friend cell differentiation, including an early change in 86Rb+ transport and a decrease in cell volume, still occur in the presence of TPA. However, several late events in the program of Friend cell differentiation, including the induction of heme synthesis and the loss of proliferative capacity, are inhibited by TPA. These effects of TPA can be reversed by hemin, which alone does not induce Friend cells to differentiate. The addition of hemin to cultures grown in the presence of inducer plus TPA for several days results in the rapid restoration of hemoglobin synthesis, and also causes a parallel decrease in colony-forming ability. These results suggest that tumor promoters may inhibit only heme-dependent events, rather than the entire program of Friend cell differentiation.

Animals↗
PubMed1980

Demonstration with monoclonal antibody of the glycoprotein nature of Thy-1.2 alloantigen.

Thy-1 antigen present in large amounts on the brain and thymus of mice, exists in two allelic forms, either Thy-1.1 or Thy-1.2. Previous results have shown that Thy-1.1 alloantigen is expressed on a glycoprotein of molecular weight 25 000, therefore referred to as the Thy-1 glycoprotein. However the presence of Thy-1.2 alloantigen on the purified Thy-1 glycoprotein could not be established unequivocally. The present paper demonstrates that Thy-1.2 alloantigen, identified by F7D5 monoclonal antibody, is localized on the Thy-1 glycoprotein. The limited neutralization by the glycoprotein of the reactivity of AKR anti-C3H allosera to thymocytes is explained by the fact that the antiserum contains antibodies to determinants other than Thy-1.2. The alloantisera are shown to react with viral proteins encoded for by endogenous murine leukemia virus and expressed at the surface of Friend cells and thymocytes.

Animals↗
PubMed1979

Cellular regulation in Friend virus induced erythroleukemia. Studies with anemic mice of genotype Sl/Sld.

Genetically anemic SI/SI(d) mice have been shown previously to have a defective hematopoietic environment which prevents extensive erythroid differentiation of normal hematopoietic stem cells and also confers resistance to the erythroleukemia-inducing virus, Friend spleen focus-forming virus (SFFV). In this study, we show that the relative resistance of SI/SI(d) mice to transformation by SFFV is not due to the inability of SFFV to replicate, nor is it because SFFV cannot transform erythroid cells, in the spleens of these mice. Injection of syngeneic +/+ mouse spleen cells, previously infected in vivo with SFFV, into secondary SI/SI(d) recipients resulted in marked splenic enlargement, and the appearance of large numbers of erythropoietin (Epo)-independent erythroid colonies in plasma clot culture. The cellular proliferation observed in these SI/SI(d) secondary recipients appeared to be due to infection and transformation of host SI/SI(d) cells rather than the growth of possible tumor colony-forming units (TCFU) present in the infected +/+ spleens, because preirradiation of the SI/SI(d) recipients abolished the splenomegaly and appearance of Epo- independent erythroid colonies. Furthermore, prior irradiation (1,200 rads) of donor spleen cells from SFFV-infected +/+ mice only slightly reduced spleen focus formation in unirradiated SI/SI(d) recipients. The conclusion that SI/SI(d) target cells could be infected and transformed by SFFV was confirmed directly by injecting a high titered preparation of SFFV into SI/SI(d) mice. SI/SI(d) mice were not absolutely resistant to infection or transformation by SFFV. Nevertheless, cells from the spleens of SFFV-infected mice were unable to form tumor colonies (TCFU) in irradiated SI/SI(d) recipients, suggesting that TCFU are either present at an undetectably low frequency in these spleens, or that they are still subject to the regulatory influences of the Steel locus.

Anemia↗
PubMed1979

The role of heme in the regulation of the late program of Friend cell erythroid differentiation.

The addition of a chemical inducer, such as dimethylsulfoxide (DMSO), to cultures of mouse Friend erythroleukemic cells results in the induction of a number of late erythroid events, including the accumulation of globin mRNA, the inducation of hemoglobin synthesis, the appearance of erythrocyte membrane antigens (EMA), and the cessation of cell division. The experiments presented in this study demonstrate that heme is necessary but not sufficient for the loss of proliferative capacity associated with DMSO-induced Friend cell differentiation, whereas the accumulation of globin mRNA and EMA can occur in the absence of heme synthesis or heme itself. These conclusions were reached by selectively inhibiting heme synthesis in DMSO-treated cells in two independent ways: (i) Inducible cells were treated with 3-amino-1,2,4-triazole (AT), a drug which inhibits the induction of heme synthesis in Friend cells in a dose-dependent manner. Treatment of inducible Friend cells with 1.5% DMSO for five days caused the plating efficiency in methyl cellulose to decrease to 1% of that in untreated cultures. However, treatment of the cells with DMSO plus AT almost totally prevented this decrease in plating efficiency. The addition of exogenous hemin, which alone had no significant effect on plating efficiency, largely reversed the effect of AT in DMSO-treated cells, reducing the plating efficiency to below 5%. In contrast to the marked effects of AT on the proliferative capacity of differentiating Friend cells, the levels of globin mRNA and EMA were only partially decreased in cells treated with DMSO plus AT, compared to cells treated with DMSO alone. (ii) The relationship between heme synthesis, terminal cell division, and the induction of globin mRNA was investigated further through the use of non-inducible Friend cell variant clones. One such non-inducible clone, M18, appears to be a phenotypic analog of inducible cells treated with DMSO plus AT. Clone M18 did not accumulate heme or hemoglobin, as detected by benzidine staining, nor lose its proliferative capacity in response to DMSO. However, globin mRNA was induced by DMSO in this clone. Treatment of clone M18 with DMSO plus hemin overcame the block in hemoglobin accumulation suggesting that M18 has a defect in the induction of heme biosynthesis. In addition, exposure of M18 cells to DMSO plus hemin caused a gradual decrease in plating efficiency which was not due to non-specific toxicity. Prior incubation of M18 cells in DMSO for three to five days was necessary before hemin caused a rapid loss of proliferative capacity. Thus, these results, in agreement with the AT studies on inducible Friend cells and previous studies on the induction of EMA in clone M18, indicate that there may be both heme-dependent and heme-independent events in the program of Friend cell differentiation.

Amitrole↗
PubMed1979

Fv-2 locus controls expression of Friend spleen focus-forming virus-specific sequences in normal and infected mice.

We have recently demonstrated that normal hemopoietic cells express RNA sequences that are homologous to sequences specific for the Friend erythroleukemia virus genome [Bernstein, A., Gamble, C., Penrose, D. & Mak, T. W. (1979) Proc. Natl. Acad. Sci. USA 76, 4455-4459]. In this communication, we report that the Fv-2 locus, the major genetic determinant controlling host susceptibility to erythroleukemia induction by Friend leukemia virus, also controls the expression of endogenous sequences related to the replication-defective component of Friend leukemia virus, Friend spleen focus-forming virus (SFFV), in normal uninfected mice. Two independent congeneic pairs of mice [C57BL/6 (B6) and B6.S; B6 and B6.C(H-7(b))], differing only in a small region of the mouse genome including the Fv-2 locus, were used for this purpose. In both cases, molecular hybridization analysis indicated that the presence of SFFV-related RNA sequences in normal mice was associated with the Fv-2(s) allele: bone marrow or spleen cellular RNA from Fv-2(rr) B6 mice contained no detectable SFFV-related sequences, whereas their congeneic Fv-2(ss) pairs contained relatively high levels of these RNA sequences. The absence of these RNA sequences in Fv-2(rr) mice was not due to deletion of these sequences from the DNA of Fv-2(rr) mice. Repopulation of lethally irradiated Fv-2(rr) mice with syngeneic Fv-2(rr) bone marrow cells did not lead to any increase in the levels of these SFFV-related RNA sequences, suggesting that the expression of these sequences is still reduced or inhibited in actively cycling Fv-2(rr) hemopoietic cells. Infection with Friend leukemia virus resulted in the appearance of high levels of RNA homologous to SFFV-specific sequences in the leukemic spleens of B6.S (Fv-2(ss)) mice, whereas these cellular RNA sequences could not be detected in the spleens of Friend virus-infected B6 (Fv-2(rr)) mice. The demonstration that the same gene locus controls both the expression of exogenous SFFV-specific sequences and erythroleukemia induction by Friend leukemia virus suggests that these sequences may be necessary for erythroleukemic transformation. In addition, the finding that the Fv-2 gene locus controls the expression of endogenous SFFV-related sequences suggests that these sequences may also be involved in normal hemopoiesis.

Animals↗
PubMed1979

Presence and expression of Friend erythroleukemia virus-related sequences in normal and leukemic mouse tissues.

The nature and distribution of sequences related to the murine erythroleukemia virus, Friend spleen focus-forming virus (SFFV), have been analyzed by using a radioactive cDNA probe specific for the SFFV genome (cDNA(sff)). From the proportion of high molecular weight viral [(32)P]RNA which hybridized to cDNA(sff), it was estimated that these sequences represent about 50% of the SFFV genome, indicating a genetic complexity of about 3300 nucleotides. cDNA(sff) hybridized extensively (80-95%) to SFFV virion RNA and to cellular RNA from murine and rat cells productively or nonproductively infected with SFFV. Only background homology was detected between cDNA(sff) and viral RNA from a number of murine [Friend murine leukemia virus (MuLV), Moloney-MuLV, and Kirsten sarcoma virus] and nonmurine (Rous sarcoma virus, feline leukemia virus, baboon endogenous virus, and Mason-Pfizer mammary tumor virus) retroviruses. Limited homology was also detected to a number of murine xenotropic and mink cell focus-inducing viruses (20-35%) as well as Rauscher leukemia virus (50%). Nucleotide sequences homologous to cDNA(sff) were also detected in the DNA of normal cells of several mouse strains as single or a few copies per cell. Thermal denaturation analysis indicated that duplexes formed between cDNA(sff) and normal DBA/2J cellular DNA have a reduction in melting temperature of 2 degrees C when compared with the dissociation of hybrids between cDNA(sff) and homologous sequences in SFFV-infected mouse spleen cell DNA. Examination of cellular RNA from uninfected mouse cells indicated that SFFV-related RNA sequences were also expressed in varying degrees in different tissues of adult DBA/2J mice. The highest amounts were observed in cells from bone marrow and spleen, whereas considerably lower amounts were found in cells from the thymus and kidney. No SFFV-related sequences could be detected in RNA extracted from liver, muscle, or fibroblasts. The presence of these SFFV-related sequences in normal, uninfected mouse cell DNA and their differential expression in hematopoietic tissues suggest that these sequences may be an integral part of the program of both normal and leukemic hematopoietic cell differentiation.

Animals↗
PubMed1978

In vitro sensitization of thymocytes. Role of H-21 I region determinants and cell-free mixed leukocyte culture supernates in generation of cytotoxic responses.

Stimulation of thymocytes in vitro by spleen cells differing for the entire H-2 complex leads to a significant proliferative response without a significant cell-mediated lympholysis (CML) response. Addition of soluble cell-free supernates (SF), (taken from a 7-day mixed leukocyte culture) enables these cultures to develop CML response. For optimal CML response, the SF has to be added within 48 h of onset of cultures. Although with spleen cells as responding cells, SF could quantitatively replace I-region different stimulating cells for generation of CML responses, with thymocytes as responding cells, stimulation with I-region cells appeared obligatory for the generation of CML responses. The implications of these findings are discussed.

Animals↗