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Biomedical subjects

R Glaser

Publications and source records attributed to R Glaser.

At least 19 recordsLinked to original sources
PubMed1992

Prolactin synthesized and secreted by human peripheral blood mononuclear cells: an autocrine growth factor for lymphoproliferation.

Prolactin has been shown to have an immunoregulatory role in the rodent immune response. A prolactin-like molecule has also been found in mouse splenocytes and a human B-lymphoblastoid cell line. We have evaluated whether human peripheral blood mononuclear cells (PBMCs) synthesize and/or secrete prolactin. We used the polymerase chain reaction (PCR) to generate a 276-base-pair prolactin product from human PBMCs, and Southern blot analysis confirmed that it was related to prolactin. Western blotting using a polyclonal antibody to prolactin indicated that cell extracts prepared from human PBMCs contained a high molecular mass (60-kDa) immunoreactive prolactin. To determine whether this PBMC prolactin was being secreted, we developed a highly sensitive and specific hormonal enzyme-linked immunoplaque assay. With this assay, we were able to detect human prolactin secretion from concanavalin A (Con A)- or phytohemagglutinin-stimulated PBMCs but not from unstimulated PBMCs. We next sought to determine whether this secreted prolactin could function as an autocrine growth factor in lymphoproliferation. We observed that anti-human prolactin antiserum significantly inhibited human PBMC proliferation in response to Con A or phytohemagglutinin. We conclude that a prolactin-like molecule is synthesized and secreted by human PBMCs and that it functions in an autocrine manner as a growth factor for lymphoproliferation.

Base Sequence↗
PubMed1992

Solid-state structure of orphenadrine hydrochloride and conformational comparisons with diphenhydramine hydrochloride and nefopam hydrochloride.

The solid-state structure of (+-)-orphenadrine hydrochloride [(CH3)2NCH2CH2OCH(o-CH3C6H4)(Ph).HCl], a skeletal muscle relaxant drug, was determined by single-crystal X-ray diffraction analysis. Orphenadrine hydrochloride gave crystals belonging to the monoclinic P2(1)/n space group, and at low temperature (92 K), the following parameters were found: a = 6.923 (4), b = 7.508 (5), c = 33.22 (3) A, V = 1720 (3) A3, Z = 4, R(F) = 0.109, and Rw(F) = 0.131. Data were collected from poor crystalline material because of the low volume of the needle-shaped crystals (0.025 x 0.025 x 0.15 mm3). A molecular mechanics model was calculated by using an input structure based on atomic coordinates of the crystallographically determined molecular structure. The resulting molecular mechanics model and the structure determined by X-ray crystallography have the same molecular conformation. Whereas both solid-state (+-)-orphenadrine hydrochloride and diphenhydramine hydrochloride [(CH3)2NCH2CH2OCH(Ph)2.HCl] have synclinal N-C-C-O and antiperiplanar NC-C-O-CAr2 torsion angles, the former has a helical arrangement for Ar2CH, as expected, and the phenyl rings in the latter are disposed in a nonhelical, "open-book" arrangement.

Diphenhydramine↗
PubMed1992

Decreased herpes simplex viral immunity and enhanced pathogenesis following stressor administration in mice.

Mild electric footshock stress was delivered during the dark portion of a 12:12 h light:dark cycle to C57BL/6 female mice that were infected with herpes simplex virus-type 1 (HSV). The studies were designed to correlate viral titer with both humoral and cell-mediated immune responses to HSV infection. Footshock was observed to result in decreased HSV-specific immunity. The numbers of leukocytes in spleens and draining popliteal lymph nodes of footshocked mice were depressed compared to both apparatus control and home cage control mice. A significant suppression of the HSV-specific cytotoxic T lymphocyte (CTL) response was observed in both the spleen and popliteal lymph nodes of footshocked mice. Serum IgM anti-HSV antibody titers were also depressed in footshocked mice. These changes were shown to be correlated with significantly increased viral titers in footshocked mice compared to control mice. These data demonstrate that administration of a relatively mild stressor is associated with depressed HSV-specific cellular and humoral immunity and is associated with increased pathogenicity.

Animals↗
PubMed1992

Quantitative association between altered plasma esterified omega-6 fatty acid proportions and psychological stress.

Medical students (MS) tested during the first year of medical school showed both greater stress on the Brief Symptom Inventory and lower plasma proportions of total esterified arachidonic acid (AA, C20:4n-6), and its omega-6 fatty acid (FA) precursor, linoleic acid (C18:2n-6) than control laboratory workers. This association suggests that omega-6 FA metabolism may be affected during stress. Low AA values might result from depletion of plasma stores for immunoregulatory prostenoids formation or from modification of metabolic pathways by cortisol or other cytokine compounds implicated in stress. Values for other major FA and the omega-3 neuronal metabolic substrate, docosahexaenoic acid (DHA, C22:6n-3) were similar between students and controls. The clear preservation of the omega-3 FA pathway suggests their programmed availability for neuronal function during stress. Since plasma FA proportions may affect immune cell membrane function(s), we suggest that altered values of plasma FAs may be an important component of the physiological effects of psychological stress.

Anxiety↗
PubMed1992

Psychoneuroimmunology: can psychological interventions modulate immunity?

There is ample evidence from human and animal studies demonstrating the downward modulation of immune function concomitant with a variety of stressors. As a consequence, the possible enhancement of immune function by behavioral strategies has generated considerable interest. Researchers have used a number of diverse strategies to modulate immune function, including relaxation, hypnosis, exercise, classical conditioning, self-disclosure, exposure to a phobic stressor to enhance perceived coping self-efficacy, and cognitive-behavioral interventions, and these interventions have generally produced positive changes. Although it is not yet clear to what extent these positive immunological changes translate into any concrete improvements in relevant aspects of health, that is, alterations in the incidence, severity, or duration of infectious or malignant disease, the preliminary evidence is promising.

Arousal↗
PubMed1991

Effects of pyrroloisoquinoline enantiomers ((+)- and (-)-McN-5652-Z) on behavioral and pharmacological serotonergic mechanisms in rats.

A behavioral syndrome consisting of 5-hydroxytryptamine (5-HT)-dependent behaviors (e.g. forepaw treading, retropulsion and splayed hindlimbs) as well as hyperthermia occurred after bilateral injection of the (6S, 10bR)-(+)-enantiomer of McN-5652-Z into the cerebral ventricles in pargyline-treated rats. Both the behavioral syndrome and hyperthermia produced by (+)-McN-5652-Z were counteracted by parachlorophenylalanine or ketanserin. The (6R, 10bS)-(-)-enantiomer of McN-5652-Z influenced neither behavior nor body temperature. The enantiomers of McN-5652-Z differed also in their ability to inhibit ex vivo binding of paroxetine in rat frontal cortex and hypothalamus, in vitro uptake of 5-HT in rat blood platelets, and 5-HT-induced contraction of rat vascular smooth muscle, with (+)-McN-5652-Z being most active. No difference was observed between the effects of (+)- and (-)-McN-5652-Z on 5-HT metabolism by rat brain monoamine oxidase. Molecular models of N-protonated enantiomers having a cis B,C-ring juncture and a B-ring chair conformation were differentiated using a hypothetical model of the 5-HT uptake area. The findings indicate that the enantiomers of McN-5652-Z are useful tools for studying the stereoselectivity of behavioral and pharmacological effects exerted by serotonergic neurotransmission.

Animals↗
PubMed1991

The influence of chlorpromazine on the potential-induced shape change of human erythrocyte.

The effect of chlorpromazine (CPZ) on the shape of human erythrocytes with different values of transmembrane potential (TMP) was investigated. The shape of red blood cells with negative values of the TMP remained unchanged after the formation of stomatocytes by chlorpromazine, while cells with positive TMP showed a characteristic time course of shape change during the incubation with CPZ. Experiments with vanadate show that this might be due to a difference in the activity of the phospholipid-translocase at different values of TMP.

Chlorpromazine↗
PubMed1991

Restraint stress differentially affects anti-viral cellular and humoral immune responses in mice.

Physical restraint administered to C57BL/6 mice significantly altered the inflammatory response to influenza virus infection and depressed anti-viral cellular immunity. Restraint-stressed animals showed a pattern of reduced mononuclear cell infiltration and lung consolidation which coincided with elevated plasma corticosterone levels. Furthermore, cellular immunity to virus was significantly depressed; interleukin-2 secretion was reduced by 96% and 59% in the mediastinal lymph nodes and spleens, respectively, as compared to a non-restrained group. However, the magnitude of the humoral immune response to influenza virus was unaffected by restraint stress. Anti-viral IgG antibody levels in restrained/infected mice did not differ when compared to a non-restrained/infected control group 14 days post-infection.

Animals↗
PubMed1991

Characterization of two monoclonal antibodies to Epstein-Barr virus diffuse early antigen which react to two different epitopes and have different biological function.

Five monoclonal antibodies (mAbs) were identified using immunofluorescence that were specific for the Epstein-Barr virus (EBV) encoded 52/50 kDa early antigen (EA-D) protein complex. Evidence to suggest that these mAbs react with the same 52/50 kDa EA-D protein was obtained by Western blotting, immunoprecipitation and ELISA. Two of the mAbs, 90E2 and 214A9, neutralized EBV DNA polymerase activity. The 214A9 mAb also inhibited the activity of bacteriophage T4 DNA polymerase while the 90E2 mAb did not. These data suggest that the 90E2 and 214A9 mAbs recognize two different epitopes on the 52/50 kDa EA-D protein. The high frequency of recovery of hybridomas producing anti 52/50 kDa EA-D mAbs suggest that this protein may have an important role in EBV pathogenesis/replication.

Animals↗
PubMed1991

Stress-induced suppression of herpes simplex virus (HSV)-specific cytotoxic T lymphocyte and natural killer cell activity and enhancement of acute pathogenesis following local HSV infection.

Stressful events suppress a broad spectrum of both humoral and cellular immunological responses. However, studies of the effects of stress on the development of specific antiviral immune responses have not been reported. We have utilized an established murine model of an acute, local footpad Herpes simplex virus type 1 (HSV-1) infection to study the effect of restraint stress on the generation of HSV-specific cytotoxic T lymphocytes (CTL) and natural killer (NK) cell activity. Lymphoproliferative responses in the popliteal lymph nodes following footpad infection as well as the generation of HSV-specific CTL and NK cell activity were depressed in restrained mice compared to infected, unrestrained controls. Frequency analyses of HSV-specific pre-CTL indicated that suppression of the CTL response occurred early in the sequence of events that precedes the generation of functionally lytic CTL and was not mediated by a diminished IL-2 response. Although restrained mice exhibited fewer lymphocytes in the popliteal lymph nodes, the subset distribution was the same as that in the unrestrained controls. Furthermore, stress-induced immunosuppression resulted in a higher titer of infectious HSV at the site of infection. Overall, these findings provide evidence that physiological changes associated with restraint stress can influence the immune response to a specific viral infection and alter the course of viral pathogenesis.

Animals↗
PubMed1991

Stress-related activation of Epstein-Barr virus.

Herpesviruses characteristically persist in a latent state in the body over the lifetime of an individual. Under certain conditions, any one of the herpesviruses can be reactivated. The mechanisms underlying the establishment of latent virus infection or viral reactivation are not well understood; however, it is known that the cellular immune response plays a very important role in the maintenance of latency and in virus reactivation. One of the factors thought to be associated with the reactivation of latent herpes-viruses is psychological stress. Using an examination stress model with medical student subjects, we previously demonstrated the reactivation of latent Epstein-Barr virus (EBV), as measured by increases in antibody titers. In this follow-up study using the same group of medical students, we found evidence for incomplete reactivation of latent EBV, with only selective expression of the latent virus genome.

Adult↗
PubMed1991

Stress-induced effects on cell-mediated innate and adaptive memory components of the murine immune response to herpes simplex virus infection.

Using a murine model, we have previously shown that restraint stress is able to suppress the development of herpes simplex virus (HSV)-specific cytotoxic T lymphocytes (CTL) and natural killer (NK) cell activity in the popliteal lymph nodes following local footpad infection. These studies of the primary cell-mediated immune response to HSV infection have been extended to examine the effects of a similar stressor on the development of HSV-specific memory CTL (CTLm) following local and systemic HSV infection. In addition, the effect of stress on HSV-specific CTLm localization and proliferation in the popliteal lymph node following reexposure to HSV was investigated. Lastly, the ability to stimulate HSV-specific CTLm to the lytic phenotype under conditions of restraint stress was examined. Restraint stress did not inhibit the generation of HSV-specific CTLm. However, restraint stress inhibited the ability to activate CTLm to the lytic phenotype. In HSV seropositive mice (primed prior to stress), restraint stress prevented the in vivo activation and/or migration of HSV-specific CTLm in the popliteal lymph nodes. These findings demonstrate that activation of HSV-specific immunological memory can be inhibited by physiological changes associated with stress. Such immune inhibition may provide a possible mechanism for the development of recrudescent herpetic disease.

Animals↗
PubMed1991

The effect of restraint stress on the kinetics, magnitude, and isotype of the humoral immune response to influenza virus infection.

The stress of physical restraint has been shown to modulate the cellular immune response during a viral infection. We have studied the effects of stress on the humoral immune response during infection by influenza virus. Restraint stress altered the kinetics of the antibody response; seroconversion in the IgG and IgA isotypes was delayed in virus-infected C57BL/6 mice subjected to repeated cycles of physical restraint. However, the magnitude and isotype of the mature antibody response were unaffected during the plateau phase; no significant differences were observed between restrained/infected and nonrestrained/infected mice. Thus, the time during infection at which the antibody response was measured was a significant variable in the study of stress-induced alterations of the host's response to a replicating viral antigen. While restraint stress did not significantly affect the magnitude or class of the humoral response, it did alter the kinetics of response.

Animals↗
PubMed1991

A comparison of Epstein-Barr virus specific proteins expressed by three Epstein-Barr virus isolates using specific monoclonal antibodies.

Monoclonal antibodies (MAbs) were prepared in mice inoculated with a nasopharyngeal carcinoma Epstein-Barr virus (NPC-EBV) producer lymphoblastoid cell line (NPC-LC). When the 214A9 MAb was used to study the expression of the 52/50-kD early antigen in NPC-LC, B95-8, and HR-1 cells, no difference was found. The same results were obtained with the 343D12 MAb which is to a 125-kD virus capsid antigen protein. However, the 244G11 MAb detected an EBV membrane antigen (MA) with a molecular weight of 220 kD in both B95-8 and HR-1 cells, but reacted with a 250-kD MA protein in the NPC-LC cells. Similar results were obtained with the 201D6 MAb which reacted with a MA polypeptide with a molecular weight of 220/200 kD in HR-1 and B95-8 cells and one of 250/200 kD in NPC-LC cells. The data suggest that there may be differences in at least two MA proteins synthesized by the NPC-EBV isolate as compared with the prototype HR-1 and B95-8 EBV isolates.

Animals↗
PubMed1991

The influence of academic stress and season on 24-hour concentrations of growth hormone and prolactin.

Stress has been considered a physiological regulator of GH and PRL secretion in humans. The stressors used in studies have often been extreme. The influence of commonplace stressors on the endocrine system has not been clarified. Therefore, to better define the role of commonplace stressors on GH and PRL secretion, we evaluated the effect of examination stress on GH and PRL secretion in 37 male medical students. We performed hourly sampling for 24 h for GH and PRL 4 weeks before, during exam week, and 2 weeks after major examinations in the fall and spring of their first year. Stress, as evaluated by the Perceived Stress Scale (PSS), increased as expected during examination weeks, but there was no correlation between the PSS scores and mean day or night GH and PRL secretion. Twenty-four-hour GH and PRL secretion was not significantly altered during examinations in either fall or spring. A significant seasonal influence, however, was noted on GH secretion, with both daytime and nocturnal GH secretion being consistently higher in the Fall than in the Spring. We conclude that examination stress does not significantly influence mean daytime or nocturnal GH and PRL concentrations. We suggest that serum GH and PRL levels may not be significantly altered in man by commonplace stressors. Also, seasonal effects may be operative in the control of human GH secretion.

Adult↗
PubMed1991

The influence of valinomycin induced membrane potential on erythrocyte shape.

In addition to previous observations indicating that membrane potential changes generated by various Donnan- and Nernst-potentials lead to erythrocyte shape transformations, we show in this paper that diffusion potential change, induced by valinomycin, governs erythrocyte shape transformations. In low KCl-medium valinomycin, transferring the positive Nernst-potential into a negative diffusion potential, transforms stomatocytes into echinocytes. Using modified erythrocytes with a reversed K/Na ratio, even positive diffusion potentials can be induced by valinomycin. In these cases, stomatocytes can be generated by valinomycin. It is shown that, additionally, valinomycin in large concentrations is itself stomatocytogenic, and that the fluorescent dye diS-C3-(5) also induces stomatocytes. This, however, is a side effect which does not contradict the potential dependence of shape transformation. Using non washed erythrocytes, resuspended in plasma, valinomycin, inducing negative diffusion potential, transforms most erythrocytes to echinocytes despite the stomatocytogenic effect of albumin.

Albumins↗
PubMed1990

Expression of the Epstein-Barr virus genome in a nasopharyngeal carcinoma epithelial tumor cell line.

An epithelial tumor cell line was recently established from a biopsy specimen of a nasopharyngeal carcinoma (NPC), and designated HONE-I. Uncloned (parental) HONE-I and HONE-I clone (C)-40 cells were found to contain latent Epstein-Barr virus (EBV). Expression of the latent EBV genome in HONE-I C-40 cells has been examined. It was possible to detect a small percentage of cells spontaneously synthesizing EBV early antigen (EA) and virus capsid antigen (VCA) by immunofluorescence (IF). In addition, the EBV nuclear antigens (EBNA-I and EBNA-2), as well as the EBV latent membrane protein (LMP) were detected in the HONE-I cells. Attempts were made to induce the latent EBV genome in these cells with iododeoxyuridine (IUdR). We observed a significant increase in the number of EA/VCA-positive cells, an increase in EBV DNA, the synthesis of virus particles, and the rescue of infectious virus after treatment of HONE-I C-40 cells with IUdR. The HONE-I C-40 cells should facilitate studies of the expression and regulation of the EBV genome in NPC epithelial tumor cells, which have not previously been available.

Antigens, Viral↗