Biomedical subjects

M Einat

Publications and source records attributed to M Einat.

10 recordsLinked to original sources

PubMed1997

Induction of thermotolerance in chickens by temperature conditioning: heat shock protein expression.

Broiler chicks were conditioned by exposure to heat stress early in life to elucidate physiological mechanisms and possible involvement of the known heat shock proteins (HSPs) in the induction of thermotolerance. Chicks were exposed to 36 +/- 1 degree C; 70-80% relative humidity (rh) for 24 hours at the age of 5 days. During conditioning, weight gain was depressed. Due to accelerated growth during the postconditioning period, a complete compensation for lost weight gain was achieved by the conditioned group. At the age of 42 days, challenge with acute heat stress of 35 +/- 1 degree C; 25-30% rh resulted in a large increase in cloacal temperature of the control chickens and by a more moderate increase in the conditioned chickens. Mortality during the thermal challenge was significantly higher in the control chickens than in the conditioned ones. Conditioning at an early age resulted in reduced plasma triiodothyronine (T3) concentration and hemodynamic changes (significant decrease in heart weight and hematocrit). The synthesis rate of 70 and 90 kDa HSPs during the first hour of heat challenge, accelerated gradually in control chickens, whereas in the conditioned chickens it accelerated only after 3 hours and in a more moderate response. These results suggest that HSP's response does not play a major role in the conditioning-induced mechanism leading to acquisition of thermotolerance in chickens.

Acclimatization↗

PubMed1997

Human umbilical cord blood myeloid progenitor cells are relatively chemoresistant: a potential model for autologous transplantations in HIV-infected newborns.

Vertical transmission from mother to child occurs in 15-39% of women infected with the human immunodeficiency virus (HIV). Stem cell transplantation has recently been suggested as a potential therapy for patients with HIV infection. We have examined the possible advantages of human cord blood (HUCB) stem cells over bone marrow (BM) stem cells in the treatment of HIV-infected newborns. HUCB myeloid progenitors were found to be statistically more resistant to interferon-alpha (IFN-alpha), cytarabine (ARA-C), and eilatin than BM myeloid progenitor cells grown with IL-3 (P < 0.05). HUCB treated with IFN-alpha, ARA-C, and eilatin demonstrated a significantly higher capacity for self-renewal manifested by delta assay following 7 days in liquid culture. We, therefore, suggest that HUCB purged by anti-HIV drugs may be a source for autologous transplantation in HIV-infected newborns.

Antiviral Agents↗

PubMed1996

Synergistic effects of interleukin-11 with other growth factors on the expansion of hematopoietic progenitors from normal individuals and chronic myeloid leukemia patients resistant to treatment with cytosine arabinoside or eilatin.

Interleukin-11 (IL-11) is a novel cytokine that has been shown to stimulate human hematopoietic progenitors including the CD34+ CD33- DR- early progenitors. IL-11 has little effect on its own but it synergizes with other hematopoietic growth factors. We investigated the recovery of human myeloid progenitors incubated with IL-11 alone or in combination with other cytokines, including stem cell factor (SCF), interleukin-3 (IL-3) and granulocyte macrophage colony-stimulating factor (GM-CSF) following their in vitro treatment with ARA-C (10(-9) M) or Eilatin (10(-7) M). IL-11 in combination with IL-3 and GM-CSF markedly increased CFU-C colony growth pre- and post-ARA-C or Eilatin incubation from CML and normal individual bone marrow (BM) cells. Similarly, IL-11 alone or in combination with other cytokines increased cell recovery following 7-day suspension culture. A decrease in BCR/ABL fusion product was observed (by FISH analysis) after incubation of BM cells from CML patients in liquid culture for 7 days with 10(-9) M ARA-C or 10(-7) M Eilatin in the presence of IL-11 alone or in combination with other cytokines. These results indicate that following cytoreductive therapy IL-11 may enhance to a greater extent the growth of normal myeloid progenitors than the malignant clone and may, therefore, be of clinical importance for CML patients treated with chemotherapeutic agents.

Animals↗

PubMed1995

Eilatin: a novel marine alkaloid inhibits in vitro proliferation of progenitor cells in chronic myeloid leukemia patients.

We examined the effect of Eilatin, a novel marine product, on the survival of human myeloid progenitor cells (CFU-C) isolated from normal individuals and from 12 patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) in chronic phase and blastic crisis. We compared its effect to the effect of interferon-alpha (IFN-alpha) and cytosine arabinoside (Ara-C). Eilatin, IFN-alpha, and Ara-C inhibited the proliferation of CFU-C from normal individuals and CML patients in a dose-dependent manner. The percent survival of colony-forming units from bone marrow (BM) of seven CML patients in chronic phase exposed for 16 hours to Eilatin (10(-7) and 10(-6) M), IFN-alpha (500 U/mL), or Ara-C (10(-9) M and 10(-8) M) was found to be statistically lower (p < 0.05) than the percent survival of myeloid progenitors from normal individuals. A 16-hour exposure of CD34+ cells isolated from peripheral blood (PB) of three CML patients in blastic crisis and from BM of two patients in chronic phase to Eilatin 10(-7) M, IFN-alpha 500 U/mL, Ara-C 10(-9) M resulted in a marked inhibition in the ability of the cells to proliferate in liquid culture and a reduction in CFU-C content. Using fluorescent in situ hybridization (FISH), we evaluated detection of the BCR/ABL fusion product in the CD34+ cells. All five patients were 100% Ph+ at diagnosis. BCR/ABL translocations were detected in 94.6 +/- 0.6% of CD34+ cells after growth in liquid culture for 7 days. The level of BCR/ABL fusion signals detected after exposure of CD34+ cells for 16 hours to Eilatin 10(-7) M, IFN-alpha 500 U/mL, or Ara-C 10(-9) M were 54.5 +/- 5%, 63.6 +/- 5%, and 70 +/- 4%, respectively (mean +/- SE, n = 5). Our data indicate that Eilatin, a substance isolated from the Red Sea purple tunicate Eudistoma sp., has an antileukemic effect against in vitro Ph+ cells and may be used in conjunction with currently available agents for ex vivo purging of BM and/or PB of CML patients in conjunction with autologous bone marrow transplantation.

Adolescent↗

PubMed1995

Potent antileukemic activity of the novel agents norsegoline and dibezine.

We examined the effect of norsegoline, a natural marine product, and dibezine, a synthetic product, on the survival of human myeloid progenitor cells [colony-forming unit-cells (CFU-C)] from normal individuals and from 10 patients with Philadelphia-positive chronic myelogenous leukemia (CML) in chronic phase and blastic crisis. We compared their effect to the effect of IFN-alpha. Norsegoline, dibezine, and IFN-alpha inhibited the proliferation of CFU-C in a dose-dependent manner. The number of CFU-C from bone marrow (BM) of five CML patients in chronic phase exposed for 16 h to norsegoline (10(-8)-10(-6)M), dibezine (10(-8)-10(-6)M), and IFN-alpha (500 units/ml) was found to be statistically lower (P < 0.05) than the number of CFU-C derived from normal individuals. A 16-h drug exposure of CD34(+) cells isolated from the peripheral blood of three CML patients in blastic crisis and from BM of two patients in chronic phase resulted in a marked inhibition in the ability of the cells to proliferate in liquid culture and a reduction in CFU-C content. Using the fluorescent in situ hybridization technique, we evaluated detection of the BCR/ABL fusion product in the CD34(+) cells. All five patients were 100% Philadelphia positive at diagnosis. BCR/ABL translocations were detected in 94.6 +/- 0.6% of cells following their growth in liquid culture for 7 days. Following exposure of CD34(+) cells to norsegoline, dibezine, or IFN-alpha, BCR/ABL fusion signals could be detected in 73 +/- 11%, 66.5 +/- 4. 7%, and 66.0 +/- 2.5% of cells from BM and 72.3 +/- 5%, 68.8 +/- 7%, and 60.6 +/- 6.8% of peripheral blood, respectively. Our data indicate that norsegoline and dibezine have in vitro an antileukemic effect against Philadelphia-positive cells and may be used in conjunction with currently available agents for ex vivo purging of BM and/or peripheral blood of CML patients in conjunction with autologous bone marrow transplantation.

Adolescent↗

PubMed1991

Homeobox genes in mouse development.

Following the discovery of the homeobox as a conserved sequence in developmentally important genes of Drosophila, a plethora of such sequences have been identified in evolutionarily distant organisms. Among mammals, the mouse homeobox genes have been studied most intensively with a hope of deciphering basic mechanisms of embryonic development. The genomic arrangement of many mouse homeobox genes is similar to the organization of the Drosophila genes, suggesting that they arose as a consequence of gene duplication and divergence from a primordial cluster during evolution. Homeobox genes encode proteins that may form a part of the autoregulatory and transregulatory network specifying positional value in the embryo. Supporting this view, the more diverged members of this growing family function as transcription factors, some of which regulate the expression of tissue-specific genes. Mouse homeobox genes are expressed during embryonic development in a spatially restricted manner and alterations in their expression pattern can disrupt embryonic development. The implications of these findings will be discussed in the context of the role of homeobox genes in the embryonic development of Drosophila and other organisms.

Amino Acid Sequence↗

PubMed1989

Nucleotide sequence analysis of human abl and bcr-abl cDNAs.

The complete nucleotide sequence of human abl RNA containing exon Ia was determined. It spans 5598 nucleotides and codes for a protein of 1130 amino acids. The 3' untranslated region contains two short open reading frames and multiple ATTT(A) motifs characteristic of short lived mRNAs. Computer analysis of the abl protein predicts four domains distinct with regard to surface probability and chain flexibility. Nucleotide analysis of the abl segment within a bcr-abl cDNA cloned from the K562 cell line indicated no further alterations within the coding region. A bcr-abl construct containing this segment transformed, together with c-myc, RAT-1 cells and produced a highly active tyrosine kinase.

Amino Acid Sequence↗

PubMed1988

Transfection of fibroblasts with activated c-myc confers resistance to antigrowth effects of interferon.

The Go/G1 to S transition in growth factor-stimulated Balb/c 3T3 fibroblasts is efficiently blocked by interferons (IFNs). In the present communication we studied whether deregulated expression of exogenously introduced c-myc changes the growth sensitivity to type I IFNs (alpha + beta). Constructs that link the two coding exons of c-myc to the long terminal repeat (LTR) of Ha-MS virus were introduced into the 3T3 fibroblasts. The steady state levels of exogenous c-myc mRNA in the individual stable clones were 3-10 fold higher than the endogenous mRNA levels in non transfected Balb/c 3T3 cells. The expression directed from the c-myc-construct was found to be completely resistant to inhibition by IFN while it was still partially responsive to addition or depletion of growth factors. To test the possible phenotypic changes after this genetic manipulation, the cell cycle distribution of individual c-myc-transfected clones was analyzed during the growth factor controlled transition from resting phase to proliferating state. We find that entry into S phase of the c-myc-transfected clones became completely resistant to inhibition by low IFN concentrations which blocked this process in the parental cell line and the control clones. It is concluded that deregulated expression of c-myc resulting from substitution of the authentic promoters and the first c-myc exon with a viral promoter reduces the sensitivity of synchronized fibroblasts to the antimitogenic effects of IFN.

Animals↗

PubMed1985

Inhibitory effects of interferon on the expression of genes regulated by platelet-derived growth factor.

The G0/G1 to S transition in quiescent BALB/c 3T3 cells stimulated by serum growth factors can be specifically blocked by the administration of interferon (IFN) to the system. In the present communication, we studied whether IFN inhibits the early events in the G0/G1 phase that are initiated by the platelet-derived growth factor (PDGF). The results show that IFN inhibits most of the PDGF-mediated increase of c-myc, ornithine decarboxylase, and beta-actin mRNAs measured 3 hr after stimulation. c-fos mRNA levels are reduced by IFN as early as 20 min after exposure of the quiescent cells to PDGF. The expression of several genes that belong to the competence gene family is, therefore, inhibited by IFN and this could account for the failure of the IFN-treated cells to enter into the S phase when growth factors present in the platelet-poor plasma are added. We also report that the PDGF-mediated increase in the uptake of deoxyglucose is not impaired by IFN, thus suggesting that the early effects of IFN on gene expression do not result from inhibition of binding of PDGF to its cell-surface receptors. Unlike the direct stimulatory effect of PDGF, which is not sensitive to cycloheximide, the inhibitory effect of IFN on c-myc mRNA levels depends in part on protein synthesis. We propose that a putative product of one of the IFN-induced genes could mediate the decrease in expression of the PDGF-regulated gene family.

Animals↗

PubMedDate not supplied

Close link between reduction of c-myc expression by interferon and, G0/G1 arrest.

It has recently been reported that c-myc is an inducible gene, regulated directly by growth signals which promote proliferation and expressed in a cell-cycle dependent manner. Because various leukaemic cell lines express high levels of c-myc messenger RNA, it was of interest to discover whether the gene could be down-regulated in these cells by a growth inhibitor such as interferon (IFN). We show here that in Daudi Burkitt's lymphoma cells, IFN-alpha produces a five- to sevenfold reduction in c-myc mRNA through a decreased rate of c-myc gene transcription. By isolating a growth-resistant Daudi cell variant that had escaped from this down-regulation, we provide the first clear link between reduction of c-myc mRNA and the IFN-mediated G0/G1 arrest characteristic of Daudi cells. Furthermore, by screening other cell lines, we demonstrate the heterogeneity of human leukaemic cells with respect to these criteria. Thus, IFN-alpha fails to reduce the c-myc mRNA and to change the cell-cycle distribution in HL-60 and U937 cells, although normal induction of other IFN-regulated activities takes place. The latter group of cells shows a decline in c-myc gene expression when they become arrested in the G0/G1 phase as part of their terminal differentiation.

2',5'-Oligoadenylate Synthetase↗