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Biomedical subjects

Y Weinstein

Publications and source records attributed to Y Weinstein.

At least 19 recordsLinked to original sources
PubMed1992

Elevated activities of protein kinase C and tyrosine kinase correlate to leukemic cell aggressiveness.

We report a linkage between cell aggressiveness, protein kinase C (PKC) activity, tyrosine kinase (PTK) activity and serum requirement. We used 2 leukemic cell lines induced by Moloney murine leukemia virus (MLV). One line was highly aggressive (BS-24-1) and required low serum concentrations (3%) for optimal growth in comparison to the less aggressive line (RO2T) that needed 10% serum for optimal growth. The more malignant cells exhibited higher PKC and PTK activity. This activity was independent of serum concentration between 0.01-10%. In contrast, the weakly malignant cells need a high serum concentration (10%) for optimal PKC or PTK activity. Immunoblot analysis revealed a higher level of PKC protein in the BS-24-1 cells than in the RO2T cells. Serum induction of PKC activity did not change the amount of PKC protein in the cytosol or the membrane fractions, indicating post-translational mechanism regulation of PKC. We suggest that the aggressiveness of BS-24-1 resulted from its ability to become independent of growth regulation by serum factors, via autocrine stimulation of PKC and PTK.

Animals↗
PubMed1992

Oligoclonality of Moloney leukemias.

Induction of leukemia by non-transforming retroviruses results in the appearance of various hematopoietic tumors. It is believed that these tumors are monoclonal. In this work, the clonal nature of Moloney leukemia virus (MoLV)-induced tumors was studied. Two genetic parameters were used in order to identify leukemic clones: the pattern of the proviral integration sites and the rearrangement of the T-cell receptor complex (TCR). In more than 60% of the mice, different leukemic clones populated tumors developed in different organs of the same animal. Genotypic analysis of cell lines derived from a leukemic organ revealed that the tumor is composed of more than one clone. Phenotypic analysis of subclones which were derived from a monoclonal cell line showed variability in the expression of the Thy 1.2 and MHC antigens. The results indicate that MoLV-induced tumors are of oligoclonal nature. Each leukemic organ contains a mixture of leukemic clones, of which one is dominant.

Animals↗
PubMed1991

Effect of an iron supplement on body iron status and aerobic capacity of young training women.

Serum iron deficiency has a high incidence in female athletes. We investigated the effects of a daily oral iron supplement, (160 mg) administered during an intensive 7-week physical training programme, on body iron status, and the maximal aerobic capacity (VO2max) of 13 women (group A) compared to 15 who took a placebo (group B). The subjects were 19 years old. Blood samples were obtained before training began and on days 1, 7, 21 and 42 of training. They were analysed for packed cell volume (PVC) and for haemoglobin (Hb), 2,3-diphosphoglycerate (2,3-DPG), haptoglobin, iron and ferritin concentrations. The VO2max was measured on days 0, 21 and 42 of training. Following 21 days of training Hb, PCV and ferritin were significantly higher (P less than or equal to 0.01) in group A compared to group B. Over the training period Hb rose by 9.3% and 2.4% in groups A and B, respectively. At the end of training 66% of group B exhibited ferritin concentrations below 10 ng.ml-1, while none of group A had such low values. Mean VO2max of group A had increased by 7.5% following 21 days of training (P less than or equal to 0.01) and by 15.3% after 42 days. No appreciable increase in VO2max had occurred in group B by day 21 (significantly lower than VO2max of group A; P less than or equal to 0.05), however by day 42 it had increased by 14.3% (P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Reexamination of Stewart's quantitative analysis of acid-base status.

To provide experimental verification to Stewart's quantitative approach to acid-base analysis, the effects of acute maximal treadmill exercise (VO2max test) on venous acid base status were studied in 17 male subjects aged 18-23 yr. Venous CO2 tension (PCO2) total plasma proteins ([PTOT]), [H+], and concentrations of strong ions [( Na+], [K+], [Cl-] and lactate ion concentration ([La-]) were measured before and within 1 min post-exercise. Mean post-exercise PCO2, [PTOT], [K+], and [La-] were significantly higher than the corresponding pre-exercise values (P less than 0.05), there was a strong tendency for a significant change in [Na+] (P less than 0.056), and no changes were found in [Cl-]. Changes in venous acid-base status were analyzed quantitatively by applying relevant physicochemical theory. Altered values measured in the independent variables ([PTOT], PCO2, and net strong ion difference, [SID]) were used to calculate the corresponding changes in the dependent quantities. Comparison of individual measured and calculated values for the only one of these that is normally measured, ([H+]), yielded the theoretically expected agreement. PCO2 and [SID] changes accounted for most [H+] changes. These results demonstrate the usefulness of the quantitative approach (i.e., [H+]-PCO2 diagram) in the analysis and in understanding of plasma acid base changes with exercise and in clinical situations.

Acid-Base Equilibrium↗
PubMed1990

Changes in the coding sequence of the H-2Dk gene of metastatic cells that might account for immunogenic abnormality of its encoded antigen.

In previous studies we have demonstrated that metastatic cells, derived from T-10 fibrosarcoma, express an immunogenically abnormal H-2Dk glycoprotein which is involved in manifesting their metastatic phenotype. In the present study we show that these cells contain a remarkably high level of H-2Dk specific mRNA. Moreover, by cloning cDNA of this gene and analyzing its nucleotide sequence, we found 4 single nucleotide changes. Two of them did not change the encoded amino acids, whereas the others resulted in two amino acid substitutions in the alpha-2 domain of the protein product that might account for its immunogenic abnormality.

Amino Acid Sequence↗
PubMed1990

Cloning, characterization and sequence of a novel 59-kDa protein of Chlamydia trachomatis.

Chlamydia trachomatis (Ct) serovar L2 DNA was partially digested with BamHI, ligated with plasmid vector pBR325 and used to transform Escherichia coli JMB83. Recombinant colonies were screened for their ability to synthesize chlamydial (chl) proteins by dot immunoblot and by in vitro transcription translation assays. A clone, B1, expressing a 59-kDa protein was further characterized, and the encoding gene was subcloned in the expression vector, pKK223-3, containing the tac promoter. Elevated levels of the 59-kDa protein were produced in E. coli in the presence of the lac inducer, IPTG. Sequencing identified one long open reading frame encoding a polypeptide of 59,075 Da (59 kDa). The partially purified 59-kDa protein was recognized by sera from patients with chl infections as shown in immunoblotting. In addition, the 59-kDa protein was located in the sarcosyl-soluble fraction of chl lysates. When used as a DNA probe in dot hybridization assays, the clone encoding the 59-kDa protein showed high homology to all serovars of Ct and four strains of Chlamydia psittaci. The cloned 59-kDa protein is neither related to the 60-kDa heat-shock protein found in many strains of bacteria, nor to the Cys-rich sarcosylinsoluble protein described in other studies of chlamydia.

Amino Acid Sequence↗
PubMed1990

Competition among leukemic cells.

We investigated competition among leukemic cells induced by Moloney murine leukemia virus (MoLV) in order to understand the mechanisms involved in the generation of leukemia. We used six leukemic cells lines from Balb/C mice infected with MoLV. Each line had a unique genetic marker which enabled us to trace it in mixtures of cells either in vivo or in vitro. The markers were a unique rearrangement of T-cell receptors, the integration sites of the retrovirus and rearrangements in the Pim-1 oncogene. A mixture of two cell lines (1:1) injected into intact Balb/C mice usually produced a monoclonal tumor originating from one cell line. In most cases, the cell lines that were aggressive in vivo were also dominant in mixing experiments in vitro. In some lines, we could correlate the aggressiveness of the tumor to its superior growth rate and lower requirement for serum factors in vitro. In others, this correlation did not hold, and we assumed that host factors like the immune system contribute to the malignant potential of the leukemic cell.

Animals↗
PubMed1989

Interleukin 3 (IL-3) induces transcription from nonrearranged T cell receptor gamma loci in IL-3-dependent cell lines.

The expression of the murine TCR-gamma genes was examined in a series of IL-3-dependent and growth factor-independent cell lines. All of the IL-3-dependent cell lines, but none of the IL-3-independent lines, expressed high levels of one or more of the gamma genes but did not express the TCR-beta genes. None of the cell lines expressing the gamma loci contained detectable genomic gamma gene rearrangements. Sequencing of cDNA clones from two of the cell lines demonstrated that transcription was from nonrearranged gamma loci based on the presence of sequences in the cDNAs that are found immediately 5' of the J gamma 4 and J gamma 2 genes. The expression of gamma transcripts was dependent upon IL-3 and no transcripts were detectable within 6-8 h after the removal of IL-3. Readdition of IL-3, but not granulocyte CSF, resulted in the reappearance of gamma transcripts within 30 min. The results demonstrate that IL-3 regulates the expression of nonrearranged gamma loci. Since expression is required for rearrangement, it can be hypothesized that IL-3 may influence the ability of lymphoid/myeloid progenitors to commit to the T cell lineage.

Animals↗
PubMed1989

Activation of the c-H-ras proto-oncogene by retrovirus insertion and chromosomal rearrangement in a Moloney leukemia virus-induced T-cell leukemia.

A rearrangement of the c-H-ras locus was detected in a T-cell line (DA-2) established from a Moloney leukemia virus-induced tumor. This rearrangement was associated with the high-level expression of H-ras RNA and the H-ras gene product, p21. DNA from DA-2 cells transformed fibroblasts in DNA transfection experiments, and the transformed fibroblasts contained the rearranged H-ras locus. The rearrangement involved one allele and was present in tissue from the primary tumor from which the cell line was isolated. Cloning and sequencing of the rearranged allele and comparison with the normal allele demonstrated that the rearrangement was complex and probably resulted from the integration of a retrovirus in the H-ras locus between a 5' noncoding exon and the first coding exon and a subsequent homologous recombination between this provirus and another newly acquired provirus also located on chromosome 7. These events resulted in the translocation of the coding exons of the H-ras locus away from the 5' noncoding exon region to a new genomic site on chromosome 7. Sequencing of the coding regions of the gene failed to detect mutations in the 12th, 13th, 59th, or 61st codons. The possible reasons for the complexity of the rearrangement and the significance of the activation of the H-ras locus to T-cell transformation are discussed.

Alleles↗
PubMed1988

Iron deficiency caused by 7 weeks of intensive physical exercise.

The present study was designed to evaluate the effect of an intensive physical training program involving both isometric and isotonic activities on the body iron status of 8 females and 11 males (age 20 +/- 1 year). The training was carried out over a 7 week period and included 8 h of varying physical activities each day. Venous blood samples were obtained from the subjects prior to the beginning of the training, on day 2 and in weeks 2, 4, 6 and 7 of the program. Blood samples were analyzed for iron, ferritin and hemoglobin (Hb) concentrations, total iron binding capacity (TIBC) and red blood cell count (RBC). Iron levels of males and females decreased 65% after 2 weeks of training (p less than 0.001). At the end of the training program 5 males and 6 females had lower than normal iron values (less than 13.4 mumol.l-1). TIBC increased 25% in women and 18% in men following 2 and 4 weeks of training (p less than 0.001) and remained at this elevated level throughout the training period. Ferritin levels decreased 50% in both sexes after 4 weeks of exercise (p less than 0.05) and remained at this level until the end of the training. Hb and RBC decreased 8-10% in both sexes during the training period. In two of the women anemia occurred after 4 weeks of training. The development of latent iron deficiency in a substantial number of participants after a relatively short period of training is uncommon and may reflect the high intensity of exercise required in this program.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Down-regulation of natural killer cell activity in MoLV leukemogenesis: evidence for tumor-cell-mediated suppression.

The role of natural killer (NK) cells in retrovirus-induced leukemogenesis was studied. These cells which do not require prior sensitization are considered as a part of the body's defense system against tumor development and spread. Neonate BALB/c mice infected with Moloney murine leukemia virus (MoLV) develop leukemia within 3-6 months. The MoLV-infected mice showed a progressive loss of endogenous and augmented NK activity, correlated with the development of the leukemic state. Mixing of spleen cells from tumor-bearing mice with NK-augmented splenocytes resulted in suppression of NK activity. In addition, mixing of T cell lines isolated from MoLV-induced tumors with augmented splenocytes also resulted in the down-regulation of NK cell activity. The present study demonstrates that tumor cells from leukemic organs and leukemic T cell lines can actively suppress NK cell function. It is postulated that after MoLV infection the progression of virus-transformed T cells to a fully developed tumor depends on the ability of these cells to down-regulate NK cell activity and thus escape immune surveillance.

Animals↗
PubMed1988

Alterations in lymphokine secretion during leukemogenesis.

The production of interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 3 (IL-3) and granulocyte/macrophage colony stimulating factor (G/M-CSF) by preleukemic and leukemic spleen cells from Balb/c mice infected with Moloney leukemia virus (MoLV) was examined. During the development of the leukemia, the secretion of IL-1 and IL-2 significantly decreased, while the secretion of IL-3 and G/M CSF was not affected and was even enhanced. In addition, a 10 fold increase in the number of colony forming units in cultures (CFU-C) was found in the leukemic spleen indicating a shift in hematopoiesis from the bone marrow (BM) to the spleen. The low levels of IL-2 found in the conditioned medium of Concanavalin A (Con A) activated leukemic spleen cells could not result from active consumption of IL-2 by the cells, pointing to a genuine defect in IL-2 production. This failure of IL-2 secretion could be partially overcome by the addition of phorbol 12 beta-myristate 13 alpha-acetate (PMA) to the cells but not by the addition of IL-1. The defect in IL-2 production and the enhancement in IL-3 and G/M-CSF production may be of significance in the progression of preleukemic cells to autonomous malignant cells.

Animals↗
PubMed1987

Sequential expression in the nervous system of c-myb and VIP genes, located in human chromosomal region 6q24.

Vasoactive intestinal peptide (VIP) is a major neuropeptide involved in multiple functions such as vasodilation, smooth-muscle relaxation, sweat secretion, gastrointestinal peristalsis, pancreatic function, and brain activity. In view of the multiple roles associated with VIP, it is important to understand its gene regulation. We have recently isolated the human VIP gene and determined its structure. By in situ hybridization techniques we have now localized this gene to the long arm of chromosome 6, 6q24, a chromosomal region that has been shown previously to contain the coding sequences for the nuclear protooncogene c-myb. Genes found in close proximity to each other on the chromosome are often functionally related and, as VIP is primarily expressed in the nervous system, we investigated the possible correlation of c-myb to VIP in neuronal tissue. A sharp peak of c-myb mRNA was observed in the hippocampus of 3-day-old rats, preceding the peak of VIP mRNA that occurs in this brain area at 8 days of age. Thus, the protooncogene c-myb may be associated with events in brain development occurring prior to the appearance of elevated concentrations of VIP.

Animals↗
PubMed1987

Insertion and truncation of c-myb by murine leukemia virus in a myeloid cell line derived from cultures of normal hematopoietic cells.

A retroviral insertion into the c-myb gene, which resulted in a 3' truncation, was found in an in vitro-derived myeloid cell line. The retroviral insertion occurred at precisely the same nucleotide at which another murine leukemia virus insertion occurred in an in vivo-induced myeloid leukemia. These findings suggest that comparable events may be required for the derivation of myeloid cell lines in vitro and for induction of myeloid leukemia in vivo.

Base Sequence↗
PubMed1987

Characterization of mouse thymocyte subpopulations by the enzymatic marker 20-alpha-hydroxysteroid dehydrogenase: differential responses to IL-1 and IL-2.

The responses of thymocytes to Concanavalin A (Con A), and interleukin 1 (IL-1), interleukin 2 (IL-2) and phorbol myristate acetate (PMA) were investigated. The enzyme 20-alpha-hydroxysteroid dehydrogenase (20 alpha SDH) was used as a marker to distinguish between various populations of activated thymocytes. Thymocytes that were selected in Con A + pure or crude IL-2 expressed high 20 alpha SDH activity, while those that were selected in Con A + recombinant IL-1 (rIL-1) or crude IL-1, or Con A + PMA expressed low 20 alpha SDH activity. Both groups proliferate in response to Con A and had IL-2 receptors. After selection, the enzymatic phenotype was stable even if the cells were transferred from Con A + IL-2 to Con A + PMA (or IL-1) or vice versa. A third group was selected from thymocytes that were cultured in PMA + T cell growth factor (TCGF). This group expressed low levels of 20 alpha SDH, had IL-2 receptors, but did not respond to Con A. This paper demonstrates that 20 alpha SDH can be used as an enzymatic marker to distinguish between subpopulations of activated T cells, which have not been previously detected by the conventional surface markers.

Aldehyde-Lyases↗