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Y Weinstein

Publications and source records attributed to Y Weinstein.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1986

Modulation of protein kinase C and Ca2+ lipid-independent protein kinase in lymphoma induced by Moloney murine leukemia virus in BALB/c mice.

We investigated the possible role of protein kinase C (PKC) in the progression of Moloney murine leukemia virus (Mo-MuLV)-induced lymphoma in BALB/c mice. Mice injected with Mo-MuLV on the first day after birth developed lymphoma within 1 1/2-3 months. The development of lymphoma was characterized by a gradual increase in the number of spleen cells. However, no analogous changes could be detected in the thymuses of these mice, although cells of both organs were found to be virus producers as early as 3-4 weeks after inoculation. PKC activity, which was assayed in extracts of spleen and thymus cells, declined gradually during the development of lymphoma. Concomitantly with this decline, a progressive appearance of Ca2+/lipid-independent protein kinase activity was observed. TPA treatment of intact cells from normal mice reduced the level of soluble PKC activity, while inducing Ca2+/lipid-independent phosphorylation. By contrast, TPA had no effect on these enzymatic activities in cells derived from leukemic mice. Spleen enlargement caused by injection of a non-leukemogenic inflammatory agent such as mineral oil was ineffective in this respect, suggesting that the PKC-Ca2+/lipid-independent protein kinase modulation is associated with the virally induced leukemogenesis.

Animals↗
PubMed1986

Establishment and characterization of a novel bone-marrow-derived macrophage-like accessory cell line.

An accessory cell line, designated line A, was generated from bone marrow stem cells which differentiated in vitro in response to colony-stimulating factor (CSF) in substratum cultures. The cells were found to constitutively secrete large amounts of CSF, the activity of which was neutralized by anti-CSF-1 antibodies. Cells of line A and its supernatants potentiate the suboptimal response of thymocytes to PHA, manifesting an interleukin-1 (IL-1)-like activity. Culture fluids of this line also reconstitute the response to T cell mitogens of spleen cells depleted of adherent accessory cells. It was also found that cells of line A bear low levels of surface Ia, and they efficiently present soluble antigen to proliferating memory T cells. Constitutive prostaglandin secretion, which sometimes masks antigen-presenting capacity, was also demonstrated. Cells of line A are poorly phagocytic, do not secrete lysozyme, and lack Fc and complement receptors. However, they manifest strong cytoplasmic nonspecific esterase staining and an ectoenzyme profile resembling that of elicited inflammatory macrophages. In addition, the cell surface antigen Mac-2 was demonstrated, while stainings with anti-Mac-1 and anti-Mac-3 were negative. Thus, line A may represent a unique subpopulation of immunoregulatory accessory cells, the features of which are discussed.

Animals↗
PubMed1986

Influence of temperature on the CO2 dissociation curve of the turtle Pseudemys scripta.

Carbon dioxide dissociation curves were constructed for blood of Pseudemys scripta. These were shifted by temperature and CCO2 was inverse to temperature at common PCO2. CO2 capacitance coefficients for oxygenated and deoxygenated blood (beta oxy, beta deoxy) were inverse to temperature at reported in vivo arterial PCO2's as was the Haldane effect. Data for in vivo PCO2 and Hb saturation of pulmonary arterial and venous blood allowed determination of effective beta which closely reflected values of beta oxy and beta deoxy at different temperatures. This indicates an influence of curve shape on beta eff at in vivo PCO2's. A high degree of correlation was found between air convection requirement (liters of gas ventilated per mmol CO2 produced) and beta eff at different temperatures. The inverse relationship between beta eff and temperature strongly influenced perfusive conductance of CO2 (Gperf = Vb X beta) and contributes to the temperature-independent stability of ventilatory to perfusive conductance ratio and the CO2 content of the animal. The influence of variable curve shape and Haldane effects must be considered as determinants of beta eff in the quantitative assessment of CO2 transport in this species.

Animals↗
PubMed1986

Truncation of the c-myb gene by a retroviral integration in an interleukin 3-dependent myeloid leukemia cell line.

Among a series of myeloid leukemia cell lines, one (NFS-60) was found to have a rearrangement of the c-myb locus. The rearrangement involved the integration of a retrovirus into the region of the gene corresponding to the sixth exon of the avian c-myb locus. The insertion is associated with the production of a truncated RNA and the introduction of a terminator codon at the juncture of the long terminal repeat and the c-myb locus. The properties of the NSF-60 cells were compared with those of other myeloid cell lines, and the known sequence of differentiation induced by interleukin 3. Similar to other myeloid cell lines, the NFS-60 cells do not terminally differentiate in response to interleukin 3, granulocyte/macrophage, or granulocyte colony-stimulating factor suggesting that the cells are transformed with regard to their ability to differentiate. The NFS-60 cells are totally dependent on interleukin 3 for growth and maintenance of viability in vitro but also proliferate in response to granulocyte colony-stimulating factor. The properties of the cells support the concept that the c-myb protooncogene is involved in the control of normal differentiation of hematopoietic cells.

Animals↗
PubMed1986

Analysis of interleukin 1 mediated radioprotection.

The potential value of interleukin 1 (IL-1) containing supernatants as a radioprotective agent was evaluated. It was found that the response of irradiated thymocytes to mitogens was partially restored if IL-1 containing supernatants was included in the culture medium immediately after irradiation. A delay of 24 h in the addition of IL-1 and mitogen abrogated the radioprotection effect. Under the same conditions IL-2 containing supernatants were effective, suggesting that the dose modifying effect of IL-1 acts through induction of IL-2 elaboration. The results of the present study may be important in cases where it is necessary to restore depressed immune response resulting from irradiation accidents or radiotherapy.

Animals↗
PubMed1985

Interleukin 3.

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20-Hydroxysteroid Dehydrogenases↗
PubMed1985

Blood respiratory properties in pigeons at high altitudes: effects of acclimation.

Many birds thrive at high altitudes where environmental temperatures are low. Previous studies have shown that tolerance of and acclimation to hypoxia involve cardiopulmonary and hematological adaptations. We investigated blood respiratory properties during exposure to simulated high altitude (hypobaric hypoxia) and low temperature in unanesthetized resting pigeons (Columbia livia, mean mass 0.38 kg). A control group (C) and a group acclimated to 7 km above sea level (ASL) in a hypobaric chamber at 25 degrees C (HA group) were used. All were acutely exposed to altitudes through 9 km ASL at 5 or 25 degrees C. Arterial and mixed venous blood gas tensions and O2 and CO2 content during steady state decreased with increased altitude, whereas blood lactate increased in both groups at both temperatures. Acute high-altitude exposure did not affect hematocrit, hemoglobin concentrations, or O2 carrying capacity, but at any altitude these were all greater in HA than in C birds. At 5 degrees C blood pH increased with altitude in controls but remained unchanged in HA birds. At 25 degrees C in both groups mean intracellular pH did not change, averaging 6.97, whereas extracellular (venous) pH increased with altitude. At the highest altitudes tissue O2 extraction was virtually complete in both groups. Acclimation changed blood O2 and CO2 combining properties in ways likely to improve gas transport at high altitudes. The previously unreported shifts in blood respiratory and acid-base properties with acclimation indicate that innate extrapulmonary adaptations contribute to avian hypoxia tolerance.

Acid-Base Equilibrium↗
PubMed1985

Interleukins 2 and 3 regulate the in vitro proliferation of two distinguishable populations of 20-alpha-hydroxysteroid dehydrogenase-positive cells.

The ability of interleukin 2 (IL 2), interleukin 3 (IL 3), and granulocyte/macrophage colony-stimulating factor (GM-CSF) to induce the proliferation of cells from thymus, spleen, or bone marrow was examined and compared with their ability to induce expression of the enzyme 20-alpha-hydroxysteroid dehydrogenase (20 alpha SDH). In the thymus, the peanut agglutinin agglutinated cells (PNA+) lacked 20 alpha SDH and showed no detectable response to IL 2, IL 3, or GM-CSF in either proliferation or induction of 20 alpha SDH. In contrast, the PNA nonagglutinated (PNA-) subpopulation expressed 20 alpha SDH and proliferated in response to Con A and/or IL 2. The responding cells that could be expanded in vitro with IL 2 expressed high levels of 20 alpha SDH. Neither IL 3 nor GM-CSF in the presence or absence of Con A had a demonstrable effect on the PNA- population. In cultures of bone marrow cells, both IL 3 and GM-CSF induced proliferation, whereas IL 2 had no effect on proliferation in the presence or absence of Con A. Thy-1-depleted bone marrow cells, expanded in tissue culture with IL3, contained cells that co-expressed Thy-1 and 20 alpha SDH. In contrast, cells proliferating in vitro to GM-CSF did not expressed Thy-1 or 20 alpha SDH. In cultures of normal splenic lymphocytes, two populations of cells capable of expressing 20 alpha SDH were detected. One population could be expanded in vitro with IL 2 and Con A, whereas the second was responsive to IL 3. In spleens from athymic mice, only the latter cells were detected. These results demonstrate that IL 3 and IL 2 responsiveness distinguishes two populations of 20 alpha SDH cells. The relevance of these observations to the possible relationship of IL 3 and IL 2 in T cell differentiation is discussed.

20-Hydroxysteroid Dehydrogenases↗
PubMed1985

Effect of radiation on the production of interleukins and T-lymphocyte activities.

The effect of 0-400 rad 60Co gamma-ray doses on distinct steps in the process of murine T-cell activation by concanavalin A (Con A) was investigated. When C57BL/6 spleen cells were stimulated immediately after irradiation, production of interleukin-1 (IL-1) and interleukin-2 (IL-2) was not impaired. Concomitantly, the display of IL-2 receptors in Con A-induced reactivity to IL-2 was not affected. The proliferative response was markedly diminished by increasing doses of radiation. The effect of radiation was found to depend not only on the delivered dose but also on the time interval between irradiation and stimulation of the lymphoid cultures. When the mitogenic stimulus was delayed for 24 hours following irradiation, IL-1 production was not diminished, whereas IL-2 production was impaired by doses greater than 200 rad. The proliferative response was diminished to a markedly higher degree as compared to the degree it was diminished in cell cultures stimulated by Con A immediately after irradiation. IL-2 production and the proliferative response to Con A of irradiated cell suspensions, cultured without mitogen for 24 hours post irradiation, were also assessed after adjustment for cell death. In this case, an impairment in IL-2 production that was dose dependent was apparent, but still the levels of IL-2 secreted by 400-rad irradiated cells reached high levels. In contrast, the proliferative response to Con A could not be restored. When T-cell growth factor was added concomitantly with Con A to irradiated cell cultures, a radioprotective effect could be observed.

Animals↗