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Biomedical subjects

Y Weinstein

Publications and source records attributed to Y Weinstein.

At least 91 records · Page 5Linked to original sources
PubMed1977

Interferon inhibition of lymphocyte mitogenesis.

Interferon inhibits the early phase of mitogenic action of Concanavalin A on lymphocytes as measured by incorporation of labelled precursors in RNA, DNA or protein. There was no evidence for a role of cyclic AMP in the process of inhibition. Dialysis of interferon against high salt and urea did not separate cell inhibitory activity from antiviral activity. Thus, these results are compatible with the possibility that the antiviral and cell inhibitory activities are in the same molecule. However, further purification of the interferon will be required to verify this assumption.

Animals↗
PubMed1977

Fractionation of lymphocytes involved in the generation of cell-mediated cytotoxicity over insolubilized conjugated histamine columns.

Spleen cells from normal BALB/c mice were cultured in vitro with irradiated C57BL/6 stimulating cells. Five days later the T cell-mediated cytotoxic activity of the effector cells was assessed with a 51Cr-release assay that used H-2bEL-4 tumor cells as targets. Before the BALB/c responding lymphocytes were sensitized they were fractionated by passing the spleen cells over insolubilized histamine rabbit serum albumin Sepharose columns (H-RSA-S) or over rabbit serum albumin Sepharose (RSA-S) control columns. Fractionation of cells over the H-RSA-S columns depleted or significantly reduced the cytotoxic potential of the unretained cells. All cytotoxic potential was recovered when the cells that adhered to the H-RSA-S were eluted from the columns. In contrast, no effect on responsiveness was detected after the cells had been fractionated over the control column. The loss of response potential by the cells that did not adhere to H-RSA-S could not be accounted for by removal of macrophages nor by the concentration of cells with suppressor activity in the effluent. These cell fractionation studies raise the possiblity but do not prove that cytotoxic precursor cells may express amine receptors that could be responsible for their retention by insolubilized histamine columns.

Animals↗
PubMed1977

20alpha-hydroxysteroid dehydrogenase: a T lymphocyte-associated enzyme.

20alpha-Hydroxysteroid dehydrogenase (20alpha-SDH), an enzyme which reduces progesterone to 20alpha-dihydroprogesterone, was found to be associated with T lymphocytes. 20alphaSDH activity was present in spleen cells bearing theta antigen, spleen cells nonadherent to nylon wool (T lymphocyte-enriched population), and in thymocytes. Almost no enzymatic activity was found in bone marrow cells from normal mice and in spleen cells from neonatally thymectomized or athymic nude mice. T cell mitogens (PHA and Con A), but not the B cell mitogen LPS, induced high levels of enzymatic activity 48 hr after addition to spleen cell cultures. The level of 20alphaSDH activity in lymphocytes was age dependent. At the age of 4 weeks 20alphaSDH activity in thymocytes, spleen cells, and lymph node lymphocytes was 3 to 5 times higher than at 8 and 16 weeks. Progesterone (5.0 X 10(-7) M) was found to inhibit thymocyte proliferation after exposure to mitogens, but not 20alpha-dihydroprogesterone (10(-6) M). 20alpha SDH may protect the embryonic thymocytes against high concentrations of progesterone.

20-alpha-Dihydroprogesterone↗
PubMed1976

Control of immune responses by cyclic AMP and lymphocytes that adhere to histamine columns.

Mixed lymphocytes from human peripheral blood, murine spleens, lymph nodes or thymus glands have pharmacologically specific receptors for histamine, beta mimetic catecholamines and prostaglandins. When these cells are exposed to the panoply of drugs mentioned above, their intracellular cyclic AMP concentrations increase. The biologic consequences of such an increase were at first elusive. Now we know that the immune potential of some murine spleen cells may be modulated and the release of lysosomal enzymes and histamine from human leukocytes may be inhibited. This paper concentrates on the effects that manipulation of cells with amine receptors has on their immune function. Recent studies have revealed that a subpopulation of splenic suppressor T cells responds to increases in its cyclic AMP content by reversing its suppressive effects on the humoral antibody response. When these T cells are removed from the murine cell population by their differential adherence to insolubilized conjugates of histamine with albumin, the remainder of the cells are more responsive to sheep cell antigen, as tested by transferring the spleen cells together with the antigen into lethally irradiated recipient animals. The suppressor T cells that adhere to the insolubilized conjugates of histamine-albumin (called histamine-rabbit serum albumin-Sepharose, or HRS) are Ia positive, they appear to have receptors for histamine, beta adrenergic amines and prostaglandins of the E series, and when stimulated by these agents their in vivo and in vitro suppressor actions are reversed. The reversal seems quantitatively dependent on cyclic AMP accumulation. Receptors for the amines and prostaglandins are found on the T cell precursors of cell mediated immunity. They develop on some T effector cells in selected models of allogeneic target cell lysis. The receptors also appear to develop on selected B cells once these cells become committed to antibody production. The distribution of receptors on all leukocytes has not been adequately studied nor has their full potential in the immune response been studied in detail.

Animals↗
PubMed1975

Specific mitogenic activity of 8-Br-guanosine 3',5'-monophosphate (Br-cyclic GMP) on B lymphocytes.

8-Br-cyclic GMP has been found to be a specific B cell mitogen; it triggers athymic nude mice spleen cells and "B mice" spleen cells, nylon adherent, anti-theta and complement-treated cells to proliferate. It does not stimulate thymocytes or purified T cells. The kinetics of the response to Br-cyclic GMP and LPS are almost identical. The mitogenic effect of LPS and Br-cyclic GMP is additive when the two mitogens are given together to cells. Spleen cells (C3H/HeJ strain) that did not respond to LPS were triggered by Br-cyclic GMP to make DNA. In order to achieve maximal stimulation by Br-cyclic GMP, the drug had to be in contact with the cells for more than 24 hr. Br-cyclic GMP was found to be mitogenic for spleen cells from five different mouse strains, but not for human leukocytes. DB-cyclic AMP was found to inhibit the DNA synthesis of T lymphocytes after they interacted with Con A; DB-cyclic AMP had no effect on the ability of the B lymphocytes to be transformed by LPS. The differential effects of cyclic nucleotides on B vs. T lymphocytes are discussed.

Animals↗
PubMed1974

Hemolytic plaque formation by leukocytes in vitro. Control by vasoactive hormones.

Histamine, beta-adrenergic amines, and prostaglandins inhibited hemolytic plaque formation by splenic leukocytes from immunized mice. The same agents had previously been shown to prevent both the IgE-mediated release of histamine from human basophils and the immunologically specific cytolytic activity of murine lymphocytes, through stimulation of the production of cyclic AMP in leukocytes. We therefore tested the hypothesis that cyclic AMP might mediate an inhibitory effect of these drugs by comparing the ability of these agents to inhibit plaque formation with their effects on cyclic AMP accumulation in leukocytes. In splenic cells from three mouse strains, the dose-dependent effects of these agents of cyclic AMP correlated with their inhibition of plaque formation. Beta- but not alpha-adrenergic agonists were effective in both systems, and the effects of isoproterenol were inhibited by propranolol. Histamine was approximately equipotent with isoproterenol in both systems. Two prostaglandins (E(1) and E(2)) were effective in both systems, but prostaglandin F(2alpha) was not. Dibutyryl cyclic AMP, a lipid-soluble analog of the endogenous nucleotide, inhibited plaque formation by cells of all three strains. Theophylline, an inhibitor of cyclic AMP degradation, inhibited plaque formation slightly, but potentiated the effects of histamine, isoproterenol, and the prostaglandins on both cyclic AMP accumulation and plaque formation. Finally, cholera enterotoxin, a potent activator of adenyl cyclase, produced a delayed inhibition of plaque formation and a parallel increase in leukocyte cyclic AMP content; both effects of the toxin were blocked by canine antitoxin. These results suggest that leukocyte cyclic AMP may act as a "second messenger" to suppress plaque formation in vitro. The inhibitory effects of hormones and cyclic AMP on plaque formation are strikingly similar to their effects on in vitro models of immediate and cell-mediated hypersensitivity. The physiologic significance of these findings is not yet known.

Animals↗
PubMed1974

Separation of specific antibody-forming mouse cells by their adherence to insolubilized endogenous hormones.

Spleen cells from mice immunized with sheep red cells were separated by differential adherence to insolubilized histamine, catecholamines, and prostaglandins. The hormones were insolubilized by linking them to Sepharose beads through a protein carrier. We measured hemolytic plaque formation (per million splenic leukocytes) of cells which passed through columns of hormone-carrier-Sepharose beads (i.e., those cells that failed to bind). As compared with control (no column) cells, the number of plaque-forming cells was substantially reduced by passage through histamine, epinephrine, isoproterenol, and prostaglandin-E(2) columns. Plaque-forming cells were not significantly reduced by passage through carrier Sepharose (another control) or norepinephrine- and prostaglandin-F(2alpha)-carrier Sepharose columns. Thus, the ability of an insolubilized hormone preparation to subtract plaque-forming cells roughly correlated with the presence of pharmacologic receptors for the corresponding free hormones, as judged by stimulation of cyclic AMP accumulation in the same cells, reported previously. Both 19S and 7S plaque-forming cells were subtracted by columns prepared from pharmacologically active hormones, but none of the insolubilized hormones stimulated accumulation of intracellular cyclic AMP. The cell membrane phenomenon that allows adherence to a given hormone-carrier-bead column may be identical with the cell receptor.

Animals↗
PubMed1973

Specific leukocyte receptors for small endogenous hormones. Detection by cell binding to insolubilized hormone preparations.

Receptors for small endogenous hormones on human leukocytes were studied by insolubilizing the hormones and incubating them with the cells. Histamine, norepinephrine, and prostaglandin E(2) (PGE(2)) were conjugated to either of two types of carrier: (bovine or rabbit) serum albumin or a random copolymer of DL-alanine and L-tyrosine. The conjugates were linked to agarose beads (Sepharose) and the resultant drug-conjugate-beads were incubated with leukocytes. Norepinephrine (when linked to its carrier via glutaraldehyde) and histamine preparations bound the majority of leukocytes. The binding appeared to be specific for the hormones tested. For example, the binding by histamine-rabbit serum albumin-Sepharose was prevented or reversed by high concentrations of histamine and histamine antagonists, but not by catecholamines or their pharmacologic antagonists. Similarly, binding of cells to the norepinephrine conjugate was inhibited by some catecholamines and propranolol, but not by histamine or histamine antagonists. Conjugates of norepinephrine linked via carbodiimide did not bind cells. The protein or copolymer carriers did not contribute to binding per se. The hormone-protein-conjugates bound more cells than the hormone-polymer conjugates. The former (unlike the free amines) failed to stimulate accumulation of cyclic AMP in leukocytes. The norepinephrine linked to polymer via glutaraldehyde, however, did stimulate leukocyte cyclic AMP accumulation, possibly because of the flexibility of the polymer. Columns of the various Sepharoses were used to determine the distribution of receptors to each hormone in mixed leukocyte populations. The majority of cells appeared to have receptors for both histamine and norepinephrine (bound through glutaraldehyde). Receptors to prostaglandins may have been detected by the column procedure, but their distribution could not be quantitated. The approach described provides a means to separate leukocytes on the basis of what are likely to be preformed receptors to small endogenous hormones, and to study the physiologic importance and function of the receptors.

Alanine↗