Search PubMed⌕ Search

Biomedical subjects

Y Weinstein

Publications and source records attributed to Y Weinstein.

At least 73 records · Page 4Linked to original sources

Sex-associated differences in the regulation of immune responses controlled by the MHC of the mouse.

The immunologic potential of T lymphocytes and antigen-presenting cells (APC) from male and female mice were compared. Lymphocytes from female mice or from male mice that cannot produce and respond to testosterone (Tfm/y) were more reactive than male lymphocytes to alloantigens in MLR. Spleen cells from Tfm/y mice equipped with estrogen implants showed a higher responsiveness than control Tfm/y to alloantigens. The removal of suppressive adherent cells or the addition of T cell growth factor (TCGF) enhanced the proliferative activity of the cells in the MLR. The responsiveness of female cells to alloantigens, however, remained superior to that observed in male cells. Similarly, in the presence of TCGF, thymocytes from female mice react more effectively than male cells in MLR. In addition, Con A-stimulated spleen cells from female mice produce more interleukin 2 (IL 2) than do spleen cells from males or female mice treated with testosterone. Lymphocytes from immunized mice were tested for their ability to respond to soluble antigens (KLH and OVA) in vitro. Again, female immunocompetent cells respond more vigorously than male cells or cells originating in female mice with testosterone implants. APC from female spleen were more efficient than male APC in initiating a secondary response in primed lymphocytes from either males or female mice. Moreover, castration of male mice enhanced, and treatment of female mice with androgen reduced, the efficiency of antigen presentation. In conclusion, these data suggest that female cells are superior to male cells in immunologic functions that are known to be associated with reactions to and recognition of histocompatibility antigens, i.e., antigen presentation and MLR. Furthermore, our present data indicate that the differential reactivity of immunocytes between male and female mice depends on the hormonal balance of the animal.

Animals↗

Radiosensitivity of isolated subsets of human lymphocytes (E+, OKT4+, OKT8+): protective role of monocytes and monokines.

The sensitivity of human peripheral blood T lymphoid populations to 60Co ionizing radiation was investigated. Dose-response values were determined for populations that are commonly identified by their ability to form spontaneous rosettes with sheep red blood cells (E+ cells), helper T lymphocytes (OKT4+ cells) and suppressor T lymphocytes (OKT8+ cells). OKT4+ and OKT8+ T cell subsets were negatively selected by complement (C)-mediated cytolysis using the C fixing OKT4 and OKT8 monoclonal antibodies (MoAb). The irradiation-induced damage was assessed by the lymphoblast transformation test, using the polyclonal T cell mitogen, phytohaemagglutinin (PHA) and the OKT3 MoAb. (The OKT3 antibodies are mitogenic for T cells only in the presence of monocytes). No significant differences were evident between dose-response values of E+, OKT4+ and OKT8+ lymphoid subpopulations when using PHA as a mitogen. On the other hand, when OKT3 was used to trigger resting irradiated peripheral blood T lymphocytes, e.g. E+ cells, OKT3 stimulated T cells proved to be markedly radioresistant as compared to PHA stimulated cell cultures. This was found to result from the fact that purified T cell cultures were co-cultured with non-irradiated monocytes when OKT3 was employed as a motogen. Similarly co-culturing of irradiated E+, OKT4+ and OKT8+ cells with non-irradiated autologus monocytes partially corrected the irradiation damage, regardless of the mitogen employed. More important, however, was the observation that macrophage derived supernatants containing (interleukin-1) IL-1 could confer a high degree of radioprotection on irradiated E+ cells. It is concluded that monocytes and monocyte products partially protect against irradiation damage.

Antibodies, Monoclonal↗

Effects of testosterone metabolites and of anabolic androgens on the bone marrow and thymus in castrated female mice.

Effects of metabolites of testosterone and of anabolic androgens on bone marrow and thymus of ovariectomized mice were studied. Steroids contained in capsules made of silastic tubing were implanted on the day of castration or were injected at the day of castration (Noralone and T.P.), lymphatic organs were examined two weeks later. It was found that testosterone, 5 alpha-DHT, 3 alpha-diol, Dianabole, T.P., and Noralone caused increases in the relative number of large cells and in activity of 20 alpha SDH in bone marrow. Concomitantly, these steroids caused a marked reduction in thymus cell number and an increase in the responsiveness of the thymus cells to Con A and PHA. The steroid 3 beta-diol increased marrow cell 20 alpha SDH activity but did not affect the thymus cell number. Other steroids tested, Ad-dione 3 alpha or 3 beta-androsterone, 5 beta-DHT, epitestosterone, and progesterone had no effect on thymus or bone marrow.

20-Hydroxysteroid Dehydrogenases↗

Distribution of preleukemic cells in fractionated bone marrow of mice.

Separation of preleukemic cells (having the potential to develop further into overt T-cell leukemias) from bone marrow cell populations was attempted. Donor mice of preleukemic bone marrow included C57BL/6 mice inoculated intrathymically with D-RadLV or AKR/J mice carrying spontaneous preleukemic cells among their bone marrow cells. Fractionation of bone marrow cells suspended in bovine serum albumin (BSA) by equilibrium density centrifugation or by velocity sedimentation at 1 g unit gravity using discontinuous density gradient of Ficoll was applied. The leukemogenic potential of the separated bone marrow fractions was tested by evaluating leukemia development following their transfer into appropriate recipients. No enrichment of D-RadLV-induced preleukemic cells was found in any of the four bone marrow fractions obtained following separation on BSA gradient. Separation of D-RadLV-induced preleukemic cells was afforded by using the Ficoll gradients. Preleukemic cells were located mainly among four out of 21 fractions tested, consisting mostly of 10 to 14 micrometers size cells. In contrast, preleukemic cells from AKR donors were distributed among most of the separated fractions. It is suggested that these variable results may reflect homogeneity or heterogeneity of progenitor target cells undergoing transformation.

Animals↗

Modulation of endometrial lymphocyte response in menstrual cycle of fertile women.

Endometrial lymphocytes were isolated in two groups of fertile women, 17 of them normal and seven with various clinical problems. In order to study their immunological properties, endometrial and blood lymphocytes were cultured with either phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed (PW), or purified protein derivative (PPD). Lymphocyte response was assayed by tritiated thymidine incorporation. The percent of T cells was estimated by E-rosette formation. In the normal fertile group, endometrial lymphocyte response to PHA and to Con A was found to correlate with the days of menstrual cycle, rising in a linear fashion between days 9 and 24. In the group with clinical problems, no correlation was noted. In neither group were endometrial lymphocyte responses to PW or PPD or percent of endometrial lymphocyte rosette formation influenced by the menstrual cycle. The modulation of endometrial lymphocyte response to PHA or to Con A stimulation in normal fertile women during the menstrual cycle seems unrelated to the number of T cells.

Adult↗

Stimulation of prostaglandin E production by concanavalin A in isolated Graafian follicles.

Addition of Concanavalin A (Con A) to isolated rat Graafian follicles induced prostaglandin E (PGE) production after 2 h of incubation. PGE synthesis continued throughout 24 h culture period. Cyclic AMP accumulation was noted after 6 h of incubation with Con A. .Aspirin, indomethacin and flufenamate prevented both the stimulation of PGE production and of cyclic AMP accumulation by Con A; antibodies to PGE prevented the cyclic AMP production. These studies indicate that the interaction of Con A with the follicle results in PGE production. It seems that besides the known pathway for the induction of PGE synthesis in the ovarian follicle, via elevation of intracellular cyclic AMP, an additional pathway, via an external signal which is independent of cyclic AMP exists.

Animals↗

Expression of 20 alpha-hydroxysteroid dehydrogenase in the mouse marrow cells: strain differences, thymic effect on enzymatic activity, and possible localization in pre T lymphocytes.

The enzyme 20 alpha-hydroxysteroid dehydrogenase (20 alpha SDH) was studied in bone marrow cells from various strains. The bone marrow cells of congenitally athymic (nude) and normal BALB/C mice consisted of 2 subpopulations of nucleated cells, larger cells of 10-14 microns and smaller cells of 7 microns in size. About 75% of the 20 alpha SDH activity was located in the larger cells. Bone marrow cells from young neonatally thymectomized or congenitally athymic mice had an increase portion of big cells and contained twice as much 20 alpha SDH activity as control mice. Liver cells from 1-day-old mice and spleen cells from mice lethally irradiated and bone marrow reconstituted, both of which contained primarily stem cells, erythroid, myeloid and pre B lymphocytes, had essentially no 20 alpha SDH. Following stimulation with PHA marrow cells from athymic nude mice responded to the mitogen in terms of [3H]thymidine incorporation and stimulation of 20 alpha SDH activity. Bone marrow cells after stimulation with PHA were labelled with fluorescein conjugated anti-theta antibodies. With the aid of fluorescence activated cell sorter (FACS II) it was found that the fluorescent cells had 2.5-5 fold more 20 alpha SDH activity than the unlabelled cells. The results support the suggestion that the 20 alpha SDH activity is located in the marrow pre T lymphocytes.

20-Hydroxysteroid Dehydrogenases↗

In vivo T-lymphocyte response against spontaneous reticulum cell neoplasms in SJL/J mice.

The properties of lymphocytes associated with reticulum cell neoplasms (RCN) (type B) occurring spontaneously in SJL/J mice were examined. The activity of 20 alpha-hydroxysteroid dehydrogenase (20 alpha-SDH) was used as a marker for activated T-cells. High levels of this enzyme were found in cell suspensions of tumors taken from 6- to 7-month-old mice. Treatment of the cells derived from tumorous organs with anti-theta serum and complement resulted in a loss of the 20 alpha-SDH activity; this indicated that T-lymphocytes populate the RCN. The activated T-cells in the neoplastic tissue were larger than small lymphocytes. In the more advanced stage of tumor growth seen in 1-year-old mice, the percentage of malignant reticulum cells was low and the neoplastic tissue showed low levels of 20 alpha-SDH activity. Tumor cells irradiated in vitro triggered syngeneic lymphocytes to proliferate in tumor-lymphocyte mixed cultures. The T-cell proliferative response measured by [3H]thymidine incorporation was accompanied by a marked increase in 20 alpha-SDH activity. The spleen cells taken from mice bearing old tumors that showed marked fibrosis did not respond to T- and B-cell mitogens. Histologically, the structure of the spleen was preserved, with few or no tumor cells. Spleen cells from age-matched healthy mice responded to mitogens.

20-Hydroxysteroid Dehydrogenases↗

Segregation of human peripheral blood lymphocytes according to their affinity for insolubilized histamine. Principal differences between males and females.

An attempt was made to investigate the possible existence of differences in the composition of peripheral blood lymphocytes between males and females. Using affinity chromatography of human peripheral mononuclear cells on insolubilized histamine together with staining by fluoresceinated histamine-rabbit serum albumin (HRSA) we revealed that males possess a significantly higher proportion of mononuclear cells which bind to HRSA. These results are also reflected in sex-related differences in proliferative responses of the HRSA-non-adherent mononuclear cell population to T cell-dependent mitogens antigens and allogeneic mononuclear cells.

Animals↗

Stimulation of resistance to tumor growth of athymic nude mice pretreated by combined local hyperthermia and X-irradiation.

Host resistance to tumor growth was studied in athymic nude mice of C57BL background. Animals were pretreated in the left hind leg by local hyperthermia, local X-irradiation, or combined local hyperthermia and X-irradiation. Twenty-four hr posttreatment, the animals were inoculated with the metastatic Lewis lung carcinoma tumor. Half of the animals in each group were inoculated in the pretreated leg and animals of the other half of the group were inoculated in the contralateral untreated leg. An increase of 30 to 45% in life span was achieved in normal and nude mice pretreated by combined local hyperthermia and irradiation. The increase in life span was similar in animals inoculated in the pretreated leg or in the untreated contralateral leg. These results indicate that T-lymphocytes are not involved in the protection against tumor growth.

Animals↗

20 alpha hydroxysteroid dehydrogenase (20 alpha SDH) activity in New Zealand mice T lymphocytes and bone marrow cells: effect of age, sex, and castration.

The activity of 20 alpha hydroxysteroid dehydrogenase (20 alpha SDH), a T lymphocyte-associated enzyme, was measured in fetal liver, thymus, spleen, and bone marrow cells from NZB, NZW, and (NZB X NZW)F1 (B/W) mice. There was an age-dependent increase of 20 alpha SDH activity in bone marrow cells, and a decrease in thymocytes and splenic T lymphocytes. Treatment with anti-theta and complement did not reduce the 20 alpha SDH activity of bone marrow and fetal liver cells, but reduced the activity of spleen cells. PHA stimulates both 20 alpha SDH activity and thymidine incorporation in splenic, bone marrow, and fetal liver lymphocytes. The results suggest that the enzyme in the bone marrow and fetal liver is located in pre-T lymphocytes. Enzymatic activity in bone marrow cells taken from female B/W mice (older than 7 months) was 40 to 20% lower than in male mice. Orchidectomy, but not ovariectomy, caused a significant decrease in thymocyte 20 alpha SDH activity. Orchidectomy depressed and ovariectomy enhanced 20 alpha SDH activity of bone marrow cells. The 20 alpha SDH activity of fetal liver cells from B/W mice was twice as high as in either parent strain. No 20 alpha SDH activity was found in fetal liver cells taken from BALB/C SJL or C57BL/6 mice. A model is proposed to explain the age- and sex-related changes in 20 alpha SDH activity of pre-T and T lymphocytes in healthy and pathologic conditions.

20-Hydroxysteroid Dehydrogenases↗

Participation of a histamine-Sepharose-adherent subpopulation of human mononuclear cells in the production of leucocyte migration inhibition factor (LIF) in healthy children.

The separation of mouse splenic T lymphocytes into distinct subpopulations by fractionation on histamine-rabbit serum albumin Sepharose (H-RSAS) columns has been described. The H-RSAS-adherent T cells have been attributed regulatory functions associated with B cell activity, T cell-mediated cytotoxicity and the secretion of mediators such as immuno-interferon. The possibility that H-RSAS-adherent T cells exert a similar regulatory effect on an in vitro parameter of T cell-mediated immunity was investigated by assaying the production of leucocyte migration inhibition factor (LIF) in human blood samples, using the agarose droplet method. Phytohaemagglutinin (PHA) and BCG-purified protein derivative (PPD) were used as stimulants of LIF secretion which was measured as a percentage of inhibition of linear leucocytic migration. In normal individuals a highly significant (P less than 0.001) decrease was demonstrated in the production of LIF by peripheral blood leucocytes depleted of H-RSAS-adherent cells. Migration inhibition dropped from 36 +/- 11.7% to 21.2 +/- 12.9% in eighteen cases tested with PHA and from 29.3 +/- 11.7% to 17.2 +/- 9.8% in twelve cases tested with PPD. These results suggest the existence of a lymphocytic subpopulation involved in LIF production which expresses histamine receptors.

Cell Adhesion↗

Impairment of the hypothalamo-pituitary-ovarian axis of the athymic "nude" mouse.

Pituitary and serum levels of LH and FSH and hypothalamic GnRH content were measured in acyclic, congenitally athymic (nu/nu) female mice. No significant differences were found between athymic and normal dioestrous mice of the same age (3 months). The serum LH level of the athymic mouse failed to increase 6 days after ovariectomy, but increased in response to injection of GnRH. The results suggest that the athymic nude mice suffer from impairment of hypothalamic control of the pituitary.

Animals↗