Biomedical subjects

M Bar-Eli

Publications and source records attributed to M Bar-Eli.

At least 19 recordsLinked to original sources

PubMed1992

Evidence for a structurally homologous Rh-like polypeptide in Rhnull erythrocytes.

Human Rhnull red blood cells fail to react with Rh antibodies, indicating that these cells are either devoid of Rh protein or, like other species, possess antigenically distinct variants. To determine whether Rhnull cells possess an Rh-like polypeptide, 32-kDa proteins from D--, rr, and Rhnull cells were labeled with the cysteine-specific probe, 125I-labeled pyridyldithioethylamine. Size comparisons of labeled proteins in Triton X-100-solubilized membranes from Rh-bearing and Rhnull cells showed similar sedimentation coefficients and Stoke's radii. Immunoprecipitated Rh(D) from D-- cells, Rh(c) from rr cells, and purified 32-kDa proteins from Rhnull cells were digested with alpha-chymotrypsin and examined by high-performance liquid chromatography and by two-dimensional iodopeptide mapping. Analysis of 125I-labeled chymotryptic fragments from immunoprecipitated Rh(D) and Rh(c) showed the labeled peptides from both phenotypes to be virtually identical. High-performance liquid chromatography profiles and iodopeptide maps of 32-kDa Rhnull proteins yielded patterns identical to 32-kDa proteins isolated from D-- cells and rr cells with the exception of one missing 125I-labeled peptide. Further analysis of the Rh-related fragments from Rhnull cells showed significant homology with immunoprecipitated Rh(D) and Rh(c). DNA sequence analysis of cysteine-encoding regions from Rh-bearing and Rhnull cells showed complete identity. These data suggest that Rhnull red blood cells, although serologically distinct, possess an Rh-like protein that is structurally very similar to Rh(D) and Rh(c).

Amino Acid Sequence↗

PubMed1992

A crisis related analysis of perceived spectators' behavior in competition.

Spectator behavior in competition is analyzed in terms of spectators' response (positive or negative), or lack of response in reaction to a player's action, or which is independent of a player's action, in a home or away game. This study investigated the perceived contribution of these variables to extreme psychological arousal states (crisis, noncrisis). Forty-eight elite ball-game players responded to a questionnaire asking them to estimate the occurrence probability of the Bayesian combinations among these variables under crisis and noncrisis conditions. An RM-ANOVA procedure revealed that under the crisis condition a negative response, an unsuccessful action, and a home game were rated as more probable, whereas under the noncrisis condition the reverse would be true. The athlete's psychological state was more strongly related to spectator response than to game location or athlete's action. Results are discussed theoretically in reference to the crisis construct.

Arousal↗

PubMed1991

Abnormalities of the retinoblastoma gene in the pathogenesis of acute leukemia.

The retinoblastoma-susceptibility (Rb) gene is an antioncogene that is frequently altered in retinoblastomas, sarcomas, and some epithelial tumors. We examined the structure of the Rb gene by Southern blotting in 215 cases of leukemias and lymphomas of diverse phenotype and in 15 leukemic cell lines. In selected cases Rb protein expression was examined with specific monoclonal antibodies. Structural abnormalities of the Rb gene with absent protein expression were frequent in all types of human acute leukemia, but were particularly common (27% incidence) in M4 and M5 myeloid leukemia with monocytic differentiation and in Philadelphia chromosome (Ph1)-positive leukemia of lymphoid phenotype (11% to 29% incidence). Changes in Rb were observed early in the transition to acute leukemia in cases of myelodysplastic syndrome and in the accelerated phase of chronic myelocytic leukemia in transition to blast crisis. In one case, molecular changes in Rb could be correlated with leukemia remission and relapse. We conclude that the Rb antioncogene is commonly involved in the evolution of human acute leukemias, particularly in those of a monocytic phenotype and in lymphoid leukemia in which there is an antecedent alteration of the Ph1 chromosome.

Acute Disease↗

PubMed1991

Correlation between molecular and clinical events in the evolution of chronic myelocytic leukemia to blast crisis.

A patient with typical Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia (CML) was studied during sequential phases of disease: (1) initial chronic phase; (2) myeloid blast crisis; (3) second chronic phase; and (4) accelerated disease. A point mutation in the coding sequence of the p53 gene first appeared concomitantly with the blast crisis and then disappeared with the re-establishment of a second chronic phase. The chromosomal concomitant of the molecular alteration was a deletion of 17p. These observations suggest that abnormalities of the p53 anti-oncogene are temporally related to the clinical progression of some cases of CML and are probably responsible for the development of blast crisis in these cases.

Adult↗

PubMed1991

The spectrum of molecular alterations in the evolution of chronic myelocytic leukemia.

DNA from 135 patients with chronic myelogenous leukemia (CML) at various clinical stages and Philadelphia (Ph1) chromosome positive acute lymphoblastic leukemia was investigated for alterations in a variety of proto-oncogenes which have been implicated in the evolution of CML from its chronic phase to blast crisis. The most common genetic change found in the evolution of typical Ph1 chromosome positive CML to blast crisis was an alteration of the p53 gene involving either a rearrangement, a deletion, or a point mutation in the coding sequence of the gene. Alterations of the p53 gene were found in the myeloid and the rare megakaryocytic variant of blast crisis but were absent in the lymphoid leukemic transformants. Gross structural alterations were seen in 11 of 54 (20%) of myeloid or unknown phenotypes of blast crisis and in only 1 of 44 chronic phase cases. Eight examples of mutations in the open reading frame of the p53 gene at codons 49, 53, 60, 140, 202, 204, 238, and 239 were observed in blast crisis patients. Mutations in the N-RAS gene were rare in typical blast crisis (2 of 27 cases) but were found in megakaryocytic and Ph1 negative myeloid blast crisis. We concluded that heterogeneous alterations in the p53 gene and occasionally in the N-RAS genes accompany the evolution of chronic phase CML to blast crisis.

Blotting, Northern↗

PubMed1990

The pattern of mutational involvement of RAS genes in human hematologic malignancies determined by DNA amplification and direct sequencing.

DNA from 161 patients with various forms of hematologic malignancies were investigated for mutations in exons 1 and 2 of the N-RAS, K-RAS and Ha-RAS gene by direct sequencing of DNA amplified in vitro by the polymerase chain reaction. Mutations involving either codons 11, 12, or 13 of the N-RAS gene were identified in 18 of the 161 patients. The relative frequencies of N-RAS gene mutations in these hematologic disorders was as follows: acute myelogenous leukemia (AML), 15%; acute lymphoblastic leukemia (ALL), 14%; myelodysplastic syndromes, 24%; and myeloid and lymphoid blast crisis of chronic myelogenous leukemia (CML), 3%. No correlation was observed between the presence of mutations and cytologic features or immunophenotype of these malignancies. Mutations involving codons 12 or 13 were equally prevalent, with a glycine to aspartic acid substitution being the most frequently encountered change. A single T-ALL case had a codon 11 mutation resulting in substitution of alanine with threonine. We failed to find mutations in exons 1 and 2 of the K-RAS or Ha-RAS genes in any case except a single AML with a mutation in codon 61 of the K-RAS gene. Also, no mutations were identified in chronic phase of CML, chronic lymphocytic leukemia. Ph1 positive ALL, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma. These results indicate that RAS mutations, especially those involving exon 1 of the N-RAS gene, are frequent only in a subset of hematologic malignancies.

Adolescent↗

PubMed1990

A splicing mutation accounts for the lack of p53 gene expression in a CML blast crisis cell line: a novel mechanism of p53 gene inactivation.

Alterations of the p53 anti-oncogene have recently been found to occur frequently in the blast crisis of chronic myelocytic leukaemia. The p53 gene may be altered by gross structural alterations or by point mutations in the coding sequence. We now report a novel mechanism of gene inactivation in a blast crisis cell line where a mutation in a splice donor site at the 5' end of the fifth intron of the gene interrupts RNA processing and gene expression.

Base Sequence↗

PubMed1990

Anxiety, self-control and shooting performance.

55 rifle shooters were administered state-trait anxiety and self-control questionnaires. Shooting performance was recorded on 7 competitive occasions. Analysis indicated shooting performance is dependent more on anxiety state than on anxiety trait and self-control. Highly skilled shooters were less anxious and performed better across all competitions than moderately skilled shooters but did not differ on self-control and anxiety trait. The assumption that increased anxiety negatively affects performance through the mediation of self-control should be further studied.

Adaptation, Psychological↗

PubMed1989

The relationship between MHC antigen expression and metastasis.

From the studies summarized here a complex picture of the role played by MHC products in determining tumorigenicity and metastasis is emerging. In order to be able to understand this relationship better, it is necessary to consider several factors. 1. Each tumor system or neoplastic tissue is unique, and its behavior reflects the influence of cell-specific characteristics, as well as its ability to modulate other cells and tissues--including cells belonging to the immune system--and also to be modulated by other cells and soluble factors. 2. Since metastasis formation is a multistep process in which only small subpopulations of tumor cells with complex and defined phenotypes are able to colonize secondary tissues, elimination of even one single phenotypic component of this structured process can easily reverse the metastatic capacity of the cells. Acquisition of metastatic ability, on the other hand, would be a more difficult task, since any new characteristic expressed by the cells or induced experimentally, such as gene transfection or results of IFN treatment, must be expressed in a temporal manner and in concert with other cellular characteristics. Therefore, an experimental protocol measuring a specific element in determining metastasis can easily produce conflicting results, depending on the type of cells and genetic background of the host studied. 3. The level of specific MHC products on tumor cells is one among many other cell characteristics that may determine the metastatic potential of cells. Moreover, each of the class 1 MHC products, and the relationship among them, including other than the classical K, L, or D products (Brickell et al., 1983), should be regarded as independent entities, with possible different regulatory roles in cell-cell recognition, in a general sense, which may be involved in determining invasiveness and homing as well as recognition by the immune system. 4. Both specific T-cell and nonspecific natural mediated immunity (which is much less understood) are involved in the selection of the metastatic cell population. 5. Immunogenicity of tumors is not necessarily determined by high levels of MHC antigen expression; it is also dependent on the level of TSA. Thus, immunoselection mediated by T lymphocytes during metastasis formation could be directed against both MHC and TSA antigens. Therefore, low expression of MHC antigens by metastatic cells as a result of immunoselection is not always observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Alterations in the p53 gene and the clonal evolution of the blast crisis of chronic myelocytic leukemia.

Molecular mechanisms responsible for the clinical progression of chronic myelocytic leukemia to its accelerated phase or to blast crisis have not been defined. We found alterations of the p53 gene (p53 is a 53-kDa nuclear protein) including deletions and rearrangements in 8 of 34 patients in blast crisis and 1 of 4 patients in the accelerated phase, but in only 1 of 38 patients in the chronic phase of chronic myelocytic leukemia. Only two other examples of p53 gene alterations were found among 203 patients with hematologic malignancies and solid tumors. Transcripts of the p53 gene were uniformly found in chronic-phase cells, but gene expression was variable in blast crisis, and transcripts were reduced or undetectable in 10 of 16 patients. Heterogeneous alterations in the structure and expression of the p53 gene appear to be relatively frequent in blast crisis and may be involved in the evolution of disease.

Blast Crisis↗

PubMed1989

N-RAS mutations in T-cell acute lymphocytic leukaemia: analysis by direct sequencing detects a novel mutation.

A novel mutation of the N-RAS gene of T-ALL blast cells was detected by a direct sequencing of in vitro amplified exon-1 of the N-RAS gene. Threonine (ACA) was substituted for alanine (GCA) at codon 11. This mutation would have been overlooked by conventional probe hybridization techniques. A search for other mutations in N-RAS exon-1 in T-ALL revealed a codon 13 mutation substituting aspartic acid (GAT) for glycine (GGT) in one of 18 patients. No mutations at codon 12 were detected.

Base Sequence↗

PubMed1989

Analysis of N-RAS exon-1 mutations in myelodysplastic syndromes by polymerase chain reaction and direct sequencing.

Mutations in codons 12 or 13 of the first exon of the N-RAS gene have been reported in myelodysplastic syndromes (MDS) in frequencies that vary between 9% and 40% depending on the techniques used in analysis. Gene amplification and direct sequencing provides the only unambiguous method of detecting those mutations that induce amino acid alterations. Using this technique, we analyzed 21 MDS patients for mutations in exon-1 of N-RAS. Codon 12 mutations substituting aspartic acid (GAT) for glycine (GGT) were found in four cases, and a codon 13 mutation substituting alanine (GCT) for glycine (GGT) was detected in one patient. We conclude that N-RAS exon-1 mutations in one patient. We conclude that N-RAS exon-1 mutations producing amino acid changes occur in about 20% to 25% of MDS cases.

Anemia, Refractory, with Excess of Blasts↗

PubMed1989

Direct sequencing analysis of exon 1 of the c-K-ras gene shows a low frequency of mutations in human pancreatic adenocarcinomas.

We have applied direct dideoxy sequencing of DNA fragments amplified in vitro by the polymerase chain reaction to the detection of mutations in exon 1 of the c-K-ras gene in human pancreatic adenocarcinomas. Four fresh frozen primary tumors, one metastatic tumor, and twelve formalin-fixed paraffin embedded tumors were analysed. Only three cases showed a possible mutation in codon 12 in a small population of cells, in contrast to the high frequency reported for this alteration with the RNAase A protection assay and allele-specific oligoxynucleotide hybridization. No major difference in sensitivity was found between DNA sequence analysis, and the latter method. Our results suggest that if c-K-ras mutations are indeed present in pancreatic adenocarcinomas at the high frequency reported by others, they must be confined to a small fraction of the cell population to escape detection by direct sequencing. Such a phenomenon would have implications for c-K-ras mutations in the pathogenesis of pancreatic adenocarcinomas.

Adenocarcinoma↗

PubMed1989

Game standings and psychological crisis in sport: theory and research.

Individual psychological crisis in competitive situations negatively affects motor performance. Psychological crisis development is probabilistically defined for every moment of the competition. This study estimates the effect of game standings defined interactively by three components: direction of lead, tendency, and event's expectancy, upon crisis vulnerability of a basketball player. Twenty-eight top basketball experts responded to a 'Game Standing Questionnaire' in which they were asked to assess probabilistically the relevance of game standings to crisis development. The Bayesian likelihood ratio was applied to these estimates. Results revealed that game standings have a considerable diagnostic relevance with regard to the development of an individual competitive psychological crisis. Furthermore, a negative tendency, a lead by the opposing team, and an unexpected event are more likely to occur under crisis conditions than under non-crisis conditions. Various aspects related to the validation and the practical applicability of the study are discussed.

Arousal↗

PubMed1988

NK sensitivity, H-2, c-K-ras proto-oncogene expression and metastases: analysis of the metastatic potential of H-2 gene transfected fibrosarcoma cells.

The transformation of a potentially neoplastic cell into an autonomous highly malignant and metastatic tumor cell involves a multifactorial cascade of events. This will eventually lead not only to the emergence of a tumor cell with an unlimited potential of replication, but more important will contribute to its ability to ignore and evade homeostatic immune and non-immune regulatory mechanisms. Specifically, those mechanisms which may restrict and direct its growth, dissemination, patterns of differentiation and interaction with the cellular and humoral factors comprising its environment. However, many different factors may contribute to a highly invasive and malignant phenotype. It is obvious that one should expect that a cardinal role should be assigned to alterations in those factors which contribute to the capacity of the malignant cells with its environment at the cell membrane level, which in turn is dependent on the concerted functional expression of specialized membrane associated components (i.e. receptors, cyto adhesion molecules (CAM's), histocompatibility antigens, GAP junction complexes, extracellular matrix components, etc.). In the present studies, we have investigated the contribution of three major factors, which maybe the cause or result of alterations at the level of the cell membrane: MHC encoded antigen expression, susceptibility to the cytolytic activity of NK cells and enhanced expression of the c-K-ras proto-oncogene, as to their development of metastatic capacity of a malignant cell. To address these questions, we used metastatic (IE7) and non-metastatic (IC9) variants of the murine 3-methylcholanthrene induced T-10 fibrosarcoma. Using this system, the following major conceptually important observations were made: A. The restoration by transfection of the expression of membrane associated H-2K encoded glycoproteins abrogates the metastatic capacity of the highly metastatic tumor cell clone, IE7, irrespective of the degree of susceptibility to NK or c-K-ras oncogene expression. This reduction in metastatic capacity is followed by a significant decrease in its tumorigenicity which is concomitant with its ability to induce in vivo potent H-2K restricted CTL's. These results clearly indicate that H-2K region encoded molecules play no apparent role in determining the susceptibility of tumor cells to NK cells, and yet their loss or aberrant expression is a cardinal event in tumor progression towards metastatic capacity, a fact which is supported by similar observations achieved in other murine models (18).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

Alterations of class I HLA genes in human colon cancers.

Alterations of HLA class I genes were found in 3 of 12 human colon cancers. Rearrangements in HLA class I genes were observed in 2 cancers and amplification of HLA-coding genes was observed in 1 cancer. All 3 cancers were at an advanced stage. No examples of amplification or rearrangement in the HLA genes were found in 10 other tumours of diverse types. No alterations in the beta 2-microglobulin gene were observed in 22 human solid tumours included in this study. The association between alterations in HLA genes and proto-oncogenes in these tumours is discussed.

Adenocarcinoma↗

PubMed1988

Influence of H-2K transfection on susceptibility of fibrosarcoma tumor cells to natural killer (NK) cells.

In this study, we have used the T-10 fibrosarcoma tumor cells to further analyze the relationship between metastatic competence, expression of H-2K antigens and susceptibility to lysis by virus augmented NK cells in vitro. Our results show an inverse correlation between metastatic properties of the original T-10 clones, IC9 and IE7, and susceptibility in vitro to lysis by virus-augmented NK cells. Restoration by transfection of expression of H-2K genes (H-2Kb or H-2Kk) led to the alteration of the metastatic phenotype of the tumors cells, yet had minor influence on the putative susceptibility of these clones to NK. These observations suggest that expression of MHC gene products, while affecting metastases, does not exclusively determine sensitivity to NK cells.

Animals↗

PubMed1988

Time phases and the individual psychological crisis in sports competition: theory and research findings.

A conceptual model of the development of an athlete's individual psychological crisis during competition has recently been proposed and applied to basketball. In this article the diagnostic value of the time dimension with regard to such a process of crisis development is investigated. The relevance of six time phases for the diagnosis of individual psychological crisis during the competition is discussed in detail. The present study was conducted on 28 basketball experts who completed a 'phases of competition' questionnaire using the components of the Bayesian likelihood ratio (diagnostic value) for each phase. Results revealed that time limits can be determined unanimously and that the proposed phases do have a considerable diagnostic relevance as predicted on theoretical grounds. Various aspects related to the validation and the practical applicability of the present research are briefly discussed.

Basketball↗