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Biomedical subjects

M Borysenko

Publications and source records attributed to M Borysenko.

At least 19 recordsLinked to original sources

Stress-induced decline in immune responsiveness in C3H/HeJ mice: relation to endocrine alterations and tumor growth.

We examined the effect of rotation-induced stress on (1) growth of lymphosarcoma tumors; (2) interleukin-2 (IL-2) production; (3) T cell subset distribution; and (4) cytotoxic T cell (CTL) function. In addition, we examined the levels of corticosterone and beta-endorphin as possible mediators of stress-induced immune alterations. Rotation stress induced progressive lymphosarcoma growth, while unstressed mice showed tumor regression after 2 weeks of growth. IL-2 production and CTL activity in stressed animals were significantly lower than controls during the first 2 weeks after initiation of stress. Spleen lymphocytes from stressed and control mice bearing the L3T4 antigen (helper/inducer T cell marker) remained unchanged, while in peripheral blood such cells decreased in stressed but not control animals. This latter pattern was also observed in Lyt 2 positive (suppressor/cytotoxic) cells of both spleen and peripheral blood. Corticosterone levels were elevated for an extended period following initiation of stress, while beta-endorphin levels remained similar to those of the controls. Although these data do not directly establish a causal link between immunoinhibition and tumor growth, they clearly demonstrate that stress inhibits a number of cell-mediated immune functions that may be relevant in this regard.

Animals

Development and histogenesis of the thymus in dog. A light and electron microscopical study.

The development of the thymus was studied with histological, transmission electron microscopic (TEM) and histochemical methods in 100 dog fetuses (beagle), between day 19 of gestation and day 21 after birth. Thymus development could be divided in three stages: 1/Formation of epithelial palisades; 2/Initiation of lymphopoiesis; 3/Differentiation of the medulla and Hassall's bodies (HB). The epithelial anlagen were seen at day 23 of gestation showing the characteristic palisade structure of the endodermally derived epithelium. Ten days later the beginning of lymphoiesis and the reticularization of the epithelial cells could be seen. The first HB could be found at day 38 when cortical-medullary differentiation is recognized. The histochemical observation demonstrated a rich content of PAS positive coarse granules in the cytoplasm of reticulo-epithelial (RE) cells. On the other hand, the HB showed a diffuse PAS positive reaction. The ultrastructural investigations demonstrated the presence of desmosomes connecting RE cells to one another. Desmosomes were not found between RE and lymphocytes. The growth of the developing thymus into the mesenchymal matrix resulted in the lobulation of the organ by connective tissue cells and fibers. The first mast cells were seen at day 35 of gestation, most abundantly in the interlobular connective tissue (ICT) although a few were present in the cortex and somewhat more in the medulla, near the HB. At the end of development small groups of neutrophil cell precursors appeared in the ICT and the cortex. Cysts were not present up to day 21 after birth.

Animals

Decline of natural killer cell target binding and lytic activity in mice exposed to rotation stress.

We examined the effect of rotation-induced stress on the percentage distribution of NK-YAC-1 target-binding cells and natural killer (NK) cell activity from splenic lymphocytes of C3H/HeJ mice. Following a 6-day stress regimen, we observed a marked decline in both the percentage of target-binding cells and in NK cell activity. This decline was first evident 13 days after initiation of stress and persisted for 2 weeks. Our data indicate that intermittent rotation stress over a 6-day period results in a delayed but persistent deleterious effect on NK-YAC-1 target binding and NK cell activity.

Animals

Effect of delta 9-THC on brain and plasma catecholamine levels as measured by HPLC.

The effects of chronic administration of delta 9-tetrahydrocannabinol (delta 9-THC) on the plasma and brain catecholamine (CA) levels were measured using high performance liquid chromatography-electrochemical detection (LC-EC) system. Intact male rats were injected daily with vehicle (50 microliter oil) or with delta 9-THC (3 mg/kg body wt) over a period of 25 days. Trunk plasma and tissue from preoptic area (POA) and mediobasal hypothalamus (MBH) were collected and catecholamine levels were detected by LC-EC system coupled to an electronic integrator. Alumina extract of tissue and plasma samples, spiked with the internal standard (dihydroxybenzylamine), were injected into the LC-EC system; the CA were chromatographed and eluted within 12 minutes using sodium phosphate buffer as the mobile phase. delta 9-THC treatment resulted in a significant decrease in plasma and MBH levels of norepinephrine (NE), epinephrine (E), POA levels of NE; and significant increases in MBH levels of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC). Our study indicates for the first time that delta 9-THC treatment significantly alters not only the POA and MBH CA levels, but also the plasma CA levels.

3,4-Dihydroxyphenylacetic Acid

Effects of acute and subchronic delta 9-tetrahydrocannabinol administration on the plasma catecholamine, beta-endorphin, and corticosterone levels and splenic natural killer cell activity in rats.

The effect of acute (1 day) or subchronic (25 days) treatment with delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent of marihuana, on plasma norepinephrine (NE), epinephrine (E), corticosterone, beta-endorphin (beta-end), and splenic natural killer (NK) cell activity of the rat was studied. Groups of animals received subcutaneously, either THC in corn oil + saline (3 mg THC/kg); oil + saline; or THC + naloxone (2 mg naloxone/kg and 3 mg THC/kg). Acute injection of THC with or without naloxone did not significantly change plasma levels of NE, E corticosterone, beta-end, or the NK cell activity. However, subchronic treatment with THC significantly reduced plasma levels of NE, E, corticosterone, and NK cell activity, compared to controls. The plasma beta-end levels were significantly elevated in the THC-treated animals. In the THC + naloxone group of animals, the plasma hormone levels (corticosterone and beta-end) were similar to control levels and the NK cell activity was significantly higher than in THC-treated animals. These results indicate that subchronic exposure to THC results in suppression of splenic NK cell activity. The interaction of THC with the endogenous opiate system appears to be a contributing factor leading to the NK cell suppression in rats. A direct suppressive action of THC or its metabolites on the NK cell is not ruled out by this study.

Animals

Surface immunoglobulin on granular and agranular leukocytes in the thymus and spleen of the snapping turtle, Chelydra serpentina.

Spleen and thymus suspensions from the turtle, Chelydra serpentina were examined by indirect immunofluorescence and found to contain both agranulocytes and granulocytes positive for surface Ig. Among the splenic agranulocytes , 50% of the lymphocyte and monocyte population was positive for surface Ig. In the thymus only 7% of the thymocytes were positive. Ninety-two percent of the granulocytes, composed primarily of basophils and eosinophils, were positive for surface Ig in both the thymus and spleen. The presence of surface immunoglobulins on turtle splenic leukocytes was confirmed by sheep red blood cell (SRBC) immunization studies. Basophils, lymphocytes and monocytes from immunized turtles formed SRBC rosettes, while eosinophils from immunized turtles were found to specifically phagocytose SRBC. Splenic leukocytes from control turtles did not phagocytose or rosette with SRBC. This study demonstrates that indirect immunofluorescent techniques can be used to identify surface immunoglobulin on turtle granulocytes as well as agranulocytes .

Animals

Turtle lymphocyte surface antigens in chelydra serpentina as characterized by rabbit anti-turtle thymocyte sera.

Spleen and thymus suspensions from the turtle, Chelydra serpentina were examined by indirect immunofluorescence with a rabbit anti-turtle thymocyte serum (RATT). After the species-specific antibodies had been absorbed out, the antisera labeled all lymphocytes in the thymus and spleen. The specificity of RATT for thymocytes was greater than the specificity for splenic lymphocytes. The presence of two antigens, one thymus specific, TS, and another shared by both thymocytes and splenic lymphocytes, LS, is suggested. The TS antigen was absent from a minor subpopulation of turtle thymocytes and may represent a mature population of T-like cells in the thymus.

Animals

Anti-immunoglobulin induced histamine release from naturally abundant basophils in the snapping turtle, Chelydra serpentina.

The dose response, temperature sensitivity, time course and calcium dependency of histamine release from snapping turtle basophils treated with rabbit anti-turtle immunoglobulin (RATIg) sera was explored. This investigation indicated that the level of histamine release induced by RATIg was dependent upon the concentration of RATIg with concentrations of 350 mcg/ml inducing optimal release. In addition, release was temperature dependent with release increasing over a temperature range of 10 degrees C to maximal at 27 degrees C. Release was also dependent on the length of exposure to RATIg. Release increased steadily over a time period of 0 to 30 minutes with the higher concentrations of RATIg inducing the most rapid release. Basophil-histamine release was also found to be calcium dependent. This study indicates that the snapping turtle basophil possesses similar characteristics to that of its mammalian counterparts. It is proposed that the very wide temperature range over which turtle basophils release histamine is an important feature in he immune resistance of this ectothermic animal.

Animals

Academic stress, power motivation, and decrease in secretion rate of salivary secretory immunoglobulin A.

The effect of academic stress on immune function, as measured by the rate of secretion of salivary secretory immunoglobulin A (s-IgA), was studied prospectively in 64 first-year dental school students. Perceived stress and s-IgA secretion rate were measured five times--during an initial low-stress period, three high-stress periods coinciding with major examinations, and a final low-stress period. The s-IgA secretion rate was significantly lower in high-stress than low-stress periods for the whole group. In addition, personality characteristics differentiated patterns of s-IgA secretion rates. Students characterised by a great need to establish and maintain warm personal relationships secreted more s-IgA at each point than did all other subjects. The s-IgA secretion rates of those with a high inhibited need for power continued to decline through the final low-stress period rather than recovering as in all other subjects.

Adult

Naturally abundant basophils in the snapping turtle, Chelydra serpentina, possess cytophilic surface antibody with reaginic function.

Basophils constitute 50 to 63% of the blood leukocytes in Chelydra serpentina, the snapping turtle. Immunoglobulin (Ig) on the surface of the turtle basophil was detected by indirect immunofluorescence by using an IgG fraction from rabbit anti-turtle Ig serum (RATIg) and a fluoresceinated goat anti-rabbit antibody incubated at 4 degrees C. However, when the cells were incubated with RATIg at 22 degrees C, the basophil number, as determined by Wright's stain and neutral red counts, decreased dramatically. This morphologic evidence of degranulation was directly proportional to the antiserum concentration. Degranulation also correlated with cell histamine release (r = 0.73). In other experiments, turtle basophils were found to express antigen-specific surface Ig after immunization with sheep red blood cells (SRBC). Washed basophils from immunized turtles formed basophil-SRBC rosettes in vitro. Basophils from control turtles did not. Basophil-SRBC rosettes could also be induced by in vitro passive sensitization by preincubation of normal turtle basophils in the SRBC immune turtle sera. This study shows clearly that the turtle basophil has an immune capacity analogous to the mammalian basophil/mast cell. This study also contains the first direct evidence for the existence of reaginic antibody (or antibodies) in an ectothermic vertebrate. Finally, C. serpentina is proposed as a unique animal model for the study of basophil function.

Animals

Epinephrine-induced changes in the distribution of lymphocyte subsets in peripheral blood of humans.

We have previously demonstrated that mitogen responsiveness of mononuclear cells (MNC) from peripheral blood is reduced after a single injection of epinephrine to human subjects. The purpose of the present study was to characterize the relative distributions of MNC subsets after epinephrine administration using monoclonal antibodies and conventional cell markers. The absolute number of circulating MNC increased 64% within 30 min after injection of epinephrine, and returned to baseline by 2 hr. Analysis of MNC subsets revealed that there were no changes in the relative percentages of total T lymphocytes [T3+ cells, or neuraminidase-treated sheep red blood cell rosettes (EN-rosettes)], B lymphocytes (B1+, or cells with surface-bound immunoglobulin), or monocytes (by morphologic criteria) after epinephrine administration. The percentage of inducer T cells (T4+) declined at 30 and 60 min postinjection. Overall, the percentage of suppressor/cytotoxic T cells (T8+) did not change after injection of epinephrine; however, analysis of individual subjects revealed opposing responses of this subset. The T4:T8 ratio was 2.19 before injection, declined to 1.56 at 60 min, then increased to 3.10 2 hr postinjection. The percentage of natural killer/killer cells (HNK-1+) increased from a baseline of 15.5% before epinephrine injection to 29.6% at 30 min postinjection, then declined to 11.4% at 2 hr. Therefore, the administration of physiologic doses of epinephrine results in changes in the relative proportions of lymphocyte subsets in peripheral blood, in addition to reduced mitogen responsiveness as reported previously.

B-Lymphocytes

Decrease in mitogen responsiveness of mononuclear cells from peripheral blood after epinephrine administration in humans.

A single subcutaneous injection of 0.2 mg epinephrine into healthy human subjects caused a transient lymphocytosis in peripheral blood. Mononuclear cells (MNC), isolated at various times after epinephrine administration, were cultured in the presence of mitogens. The blastogenic responses to pokeweed mitogen (PWM) and phytohemagglutinin (PHA) were significantly reduced for up to 60 min post-epinephrine (p less than 0.05); the response to concanavalin A (Con A) was reduced in the 15-min samples only. All responses returned to pre-injection levels by 120 min post-injection. Removal of adherent monocytes from MNC isolates before culture did not restore normal mitogen responsiveness. When MNC were cultured in the absence of mitogens, there was no difference in survival between pre- and post-epinephrine samples. Incubation of untreated MNC for 2 hr or 18 hr in vitro with various concentrations of epinephrine (10(-5) to 10(-1) mg/ml) had no effect upon the subsequent blastogenic response to mitogens. Other workers have reported that epinephrine administration causes alterations in the composition of the circulating lymphocyte pool. Taken together, these data suggest that the reduction in mitogen responsiveness after epinephrine is the result of changes in the distribution of lymphocyte subclasses in peripheral blood.

Adult

Stress, behavior, and immunity: animal models and mediating mechanisms.

Research with animal model systems demonstrates a causal relation between stress and disease susceptibility. The physiological sequelae of stressful stimulation vary with type of stressor, chronicity, and perceived control. Different patterns of endocrine secretion are thus associated with specific behavioral parameters. The immune system is regulated at several levels: genetic, cellular, hormonal, and neuronal. Stress and behavioral factors can modulate both cell-mediated and humoral immunity by impacting on the latter three levels of regulation. Both corticosteroids and catecholamines, released as part of the response to aversive stimulation, profoundly inhibit immune responsivity by binding directly to the lymphocyte surface or by releasing secondary mediators that increase the function of suppressor lymphocytes. In addition, there are direct neuroanatomical connections between the hypothalamus and lymphoid organs. Subtle changes in experimental design have yielded significant differences in results that have increased understanding of intermediary mechanisms. Such research complements psychoneuroimmunological and behavioral epidemiological studies in humans.

Animals

Stress and dental caries in the rat.

The stress of crowding and exposure to inescapable electric shock increased both the incidence and the severity of dental caries in rats housed in a conventional animal facility. Male Osborne-Mendel rats were inoculated intraorally with cariogenic bacteria, fed a high-sucrose diet, and housed in either a conventional or a sheltered facility. Rats in both housing conditions were subdivided into control and stress groups. At the end of the 56-day trial period, stressed rats from conventional housing had a significant increase in both incidence and severity of dental caries in comparison to their controls. In contrast, stressed rats from sheltered housing had a trend toward increased cariogenesis which reached significance in only one of five scores. These rats also failed to gain weight comparable to their controls, making it possible that stress-induced reduction in appetite partially offset stress-induced exacerbation in cariogenesis.

Animals

Ultrastructural analysis of normal and immunized spleen of the snapping turtle, Chelydra serpentina.

In the ultrastructural comparison of normal, unimmunized spleens with immunized spleens at key intervals after antigenic stimulation with keyhole limpet hemocyanin (KLH), we noted cellular and cytological features which reflect the cellular kinetics of the primary immune response, particularly with respect to plasma cell production. Although lymphoblasts and mature plasma cells are present in the white and red pulp, respectively, intermediate stages of the plasma cell line are rarely found in normal spleen. Following antigenic challenge, we found a marked increase in lymphoblasts in the white pulp, most of them containing short segments of rough endoplasmic reticulum suggesting initial differentiation toward plasma cells. Following an apparent migration of cells from the white to the red pulp, we found plasma cells in various stages of maturation in the red pulp cords and sinuses. The ultrastructural features of these cells reflect the differentiation of lymphoblasts into mature plasma cells. Both immature and mature plasma cells usually possess dilated cisternae of rough endoplasmic reticulum, suggesting that they are capable of producing and storing a secretory product, presumably antibody. We also noted a large number of immature macrophages and monocytes in immunized spleens. These cellular events and their cytological characteristics are compared to those described in other vertebrate classes.

Animals

Changes in spleen histology in response to antigenic stimulation in the snapping turtle, Chelydra serpentina.

Proliferative and migratory changes of lymphoid cells in the spleen were observed in turtles stimulated with KLH and maintained at 30 degrees C. Small foci of pyroninophilic lymphoblasts were first seen in the white pulp at about day 5. Progressive enlargement of these centers continued and peaked by days 8-12. By days 15-20 the white pulp returned to a normal (unimmunized) state, while the number of pyroninophilic cells, primarily plasma cells, increased markedly in the red pulp. At days 22-25, the number of plasma cells returned to normal levels and the spleen appeared normal for the remainder of the 60 day observation period. These events suggest that at 30 degrees C, the turtle is capable of a strong and prompt proliferative response in the white pulp sheaths, followed by migration and differentiation of lymphoblasts into plasma cells, in the red pulp. Observations of pyroninophilic cells in sinuses, venules and veins of the spleen and a concomitant depletion of cells in red pulp, further suggest a migration from the spleen to other sites. Following a second antigenic challenge, at day 60, no significant histological changes were observed at 30 degrees C. Nor were any changes observed following primary or secondary antigenic challenge, in animals maintained at 10 degrees C. These findings are discussed with regard to immunological memory and low temperature immunosuppression in ectothermic vertebrates.

Animals