Biomedical subjects

R Glaser

Publications and source records attributed to R Glaser.

At least 73 records · Page 4Linked to original sources

PubMed1995

Temporal relationships and IL-2 dependency of prolactin-induced lymphocyte proliferation.

Recombinant preparations of human prolactin (hPRL) and interleukin 2 (hIL-2) as well as monoclonal antibodies to these growth factors were used to study the synergistic interaction of PRL and IL-2 in Nb2 rat lymphoma lactogen-dependent cells. It was shown that IL-2 stimulated Nb2 cell proliferation in lactogen-free culture medium. Experiments with short-term exposure to growth factor demonstrated that PRL was required only during the initial 12 h of incubation while IL-2 was mitogenic regardless of the time it was added. Antibody to IL-2 partially inhibited both PRL- and IL-2-induced proliferation whereas antibody to PRL significantly decreased PRL but not IL-2-induced proliferation. These findings suggest that the complete mitogenic effect of PRL on Nb2 cells requires stimulation of IL-2 production.

Animals↗

PubMed1995

Influence of academic stress and season on 24-hour mean concentrations of ACTH, cortisol, and beta-endorphin.

We investigated the influence of a common stressful event, i.e., academic examinations, on the 24-h mean concentration of adrenocorticotropic hormone (ACTH), cortisol, and/or beta-endorphin. In addition, we evaluated the effect of season on the endocrine response to this stressor. We studied medical students (n = 55), screened for a variety of health and life style factors, from three consecutive medical school classes 1 month before, during, and 2 weeks following examinations. Hourly blood samples were obtained from an indwelling catheter and two serum pools were made (0800-2200h = day and 2300-0700h = night). Examinations produced a significant (p < .001) increase in perceived stress scores. In addition, we found a significant (p < .001) effect of examination stress on the increase in mean daytime but not nocturnal ACTH levels during autumn, but not during the spring. In contrast, the examination stress did not significantly affect day or night mean cortisol levels from baseline to examination week. We further divided the students by whether their perceived stress scores increased during examination week and fell during recovery (Group 1) or whether their perceived stress scores did not follow the expected pattern (Group 2). We found that in the Group 1 students who perceived the most stress, cortisol levels significantly increased (p < .001) from baseline to examination. Therefore, the nature of the stressor and the state of the responder were of equal importance in the observed cortisol response during examinations among these students. Further, academic stress had no significant effect on beta-endorphin levels. Finally, we found that the mean day and night ACTH levels were higher (p < .001) in the spring than in the fall; a seasonal influence on cortisol and beta-endorphin concentrations, however, was not observed. In summary, we have demonstrated that stress associated with the taking of examinations produces a dissociation among mean 24-h levels of ACTH, cortisol, and beta-endorphin. In addition, daytime cortisol levels increased during examinations only in the group of students whose perceived stress scores increased. Further, a seasonal influence on ACTH secretion was suggested by these results with higher levels observed in the spring than in the fall.

Adrenocorticotropic Hormone↗

PubMed1995

Individual differences in cardiac sympathetic control predict endocrine and immune responses to acute psychological stress.

Potential mechanisms coordinating individual differences in cardiovascular reactivity and endocrine and immune responses to acute psychological stress were examined. Twenty-three young, healthy women performed a mental arithmetic challenge while measures of cardiovascular, endocrine, and immune function were assessed. Results revealed that the acute stressor was associated with changes in the cardiovascular, endocrine, and immune systems. More important analyses revealed that individual differences in cardiovascular reactivity predicted stress-induced cortisol changes. Furthermore, cardiac sympathetic control, as indexed by preejection period, was specifically related to changes in natural killer cell activity. These results suggest that distinct physiological pathways are activated in response to acute psychological stress.

Adolescent↗

PubMed1995

Appraisal support predicts age-related differences in cardiovascular function in women.

The influence of appraisal support on age-related differences in cardiovascular function was examined. Resting assessments of heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory sinus arrhythmia (RSA), and preejection period were obtained from 45 young and 20 elderly women. Consistent with prior research, results revealed that the elderly women had higher blood pressure and lower RSA than the young women. More important, appraisal support predicted age-related differences in SBP and DBP: Age predicted elevated blood pressure for women low in appraisal support, whereas age was unrelated to blood pressure for women high in appraisal support. These preliminary data suggest that appraisal support may be an important predictor of long-term physiological function and health.

Adolescent↗

PubMed1995

Hormonal modulation of Epstein-Barr virus replication.

Among the various factors thought to be associated with the reactivation of latent herpesviruses is psychological stress. An increase in levels of 'stress hormones' such as glucocorticoids occurs in individuals who are stressed and previous studies have shown that glucocorticoid hormones can reactivate latent Epstein-Barr virus (EBV) in vitro. In this study, we confirm that the EBV genome in latently infected lymphoblastoid cells can be reactivated with two glucocorticoid hormones, hydrocortisone and dexamethasone. In addition to hydrocortisone and dexamethasone, we also found that other hormones of the hypothalamic-pituitary-axis (corticotropin-releasing factor and adrenocorticotropin hormone but not epinephrine and norepinephrine) as well as somatostatin can enhance the lytic replication of the HR-1 strain of EBV in superinfected cells. These results suggest that multiple endocrine interactions may be involved in stress-induced reactivation/replication of latent EBV.

Adrenocorticotropic Hormone↗

PubMed1995

A symmetric analysis of paired rankings with application to temporal patterns of hormonal concentration.

Mallows (1957, Biometrika 44, 114-130) introduced a simple model to describe the distribution of subjects' rankings of the items from some fixed set. Both Feigin (1992, in Probability Models and Statistical Analyses for Ranking Data, 75-91. New York: Springer-Verlag) and Critchlow and Verducci (1992, Journal of the Royal Statistical Society, Series C 41, 17-29) have considered an asymmetric extension of this model, designed to analyze the distribution of subjects' post-treatment rankings, conditional on their pretreatment rankings. Here a symmetric extension is introduced and is used to analyze the joint distribution of paired rankings associated with the patterns of prolactin hormonal response of wife-husband pairs during the course of a marital conflict. Locally most powerful tests are developed to check for independence of the wife and husband responses, and for differences in their divergence from a theoretical pattern of response. Additionally, conditional on the rankings of one group (e.g., the wives), the locally most powerful test of an affinity for the theoretical pattern in the other group (e.g., the husbands) turns out to be closely related to the test given by Critchlow and Verducci.

Adult↗

PubMed1994

Solid-state stereochemistry of (-)-scopolamine hydrobromide sesquihydrate, a new polymorph of the anticholinergic drug.

The solid-state structure of (-)-scopolamine hydrobromide sesquihydrate was determined by single-crystal X-ray diffraction analysis at low temperature. (Nr,C alpha-S)-(-)-Scopolamine hydrobromide sesquihydrate gives crystals belonging to the tetragonal space group P4(3)2(1)2, and at 180 K: a = 11.870(4), c = 26.193(3) A, V = 3691(1) A3, Z = 8, R(F) = 0.062, and Rw(F) = 0.059. Thermogravimetric analysis afforded a total weight loss of approximately 6%, consistent with a loss of 1.5 molecules of water and in accord with the sesquihydrate stoichiometry found by single-crystal X-ray crystallography. The unit cell dimensions, molecular structure, basic packing arrangement [minus the full water molecule], and the crystal system are all the same as that of the P4(1)2(1)2 hemihydrate form [R(F) = 0.09] reported earlier by Pauling and Petcher. This suggests that the previously reported "hemihydrate" description of the structure should be reconsidered. In addition to partial dehydration of the sesquihydrate crystal, non-observance of the eight water molecules might have arisen from their relatively large thermal motions at ambient temperature coupled with a lack of sufficient data versus the number of variable parameters. The phenyl ring syn-to-oxirane arrangement in the sesquihydrate form is the same as that in the corresponding crystalline methyliodide quaternary ammonium salt and in (-)-(Ns,C alpha-S)-hyoscyamine [atropine] hydrobromide, but differs from the elongated anti-to-oxirane arrangement in anhydrous (Nr,C alpha-S)-(-)-scopolamine hydrobromide.(ABSTRACT TRUNCATED AT 250 WORDS)

Crystallography, X-Ray↗

PubMed1994

Plasma cortisol levels and reactivation of latent Epstein-Barr virus in response to examination stress.

In this study, we explored the possibility that glucocorticoid hormones, known to increase under stress, might be one component of the mechanism involved in induction of latent Epstein Barr virus (EBV). We obtained blood samples from 45 male medical students during examinations and approximately 3-4 weeks before the examinations (baseline) and measured antibody titers to EBV and plasma cortisol levels. We found reproducible changes in EBV, virus capsid antigen (VCA) antibody titers, with higher antibody titers observed in the examination blood samples consistent with the reactivation of latent virus. However, we found no evidence that day and night plasma cortisol values across the sampling points changed significantly from baseline to examinations. Therefore, academic stress did not elevate cortisol levels, but increases in EBV VCA antibody titers were still observed. The data suggest in these subjects that other neuropeptides or hormones were involved in the induction of latent EBV.

Adult↗

PubMed1994

Dielectric spectroscopy of human erythrocytes: investigations under the influence of nystatin.

When placed in rotating electric fields red blood cells show a typical electrorotation spectrum with antifield rotation in the lower and cofield rotation in the higher frequency range. Assuming a spherical cell geometry, however, dielectrical parameters were obtained that differ from those measured by independent methods. Dielectrophoresis and, in particular, electrorotation yielded lower membrane capacitance values than expected. Introduction of an ellipsoidal model with an axis ratio of 1:2 allowed a description that proved to be consistent with dielectrophoresis and electrorotation data. For control cells an internal conductivity of 0.535 S/m, a specific membrane capacitance of 0.82 x 10(-2) F/m2, and a specific conductance of 480 S/m2 were obtained. The first characteristic frequency (frequency of fastest antifield rotation) and the related rotation speed can be measured quite quickly by means of a compensation method. Thus it was possible to follow changes of dielectric properties on individual cells after nystatin application. Ionophore-membrane interaction caused cell shrinkage in parallel to a decrease of the first characteristic frequency and rotation speed. Analysis of data revealed a decrease of the internal conductivity that is not only caused by ion loss but also, to a large extent, by a strong increase of hindrance because of shrinkage. Ionophore-induced membrane permeabilities can be calculated from volume decrease as well as from electrorotational data. In no case can these permeabilities count for the high membrane-AC conductivity that is attributed to the band-3 anion exchanging protein. The membrane-AC conductance was found not to be decreased for cells in Donnan equilibrium, which had leaked out almost completely.

Biophysical Phenomena↗

PubMed1994

A biobehavioral model of cancer stress and disease course.

Approximately 1 million Americans are diagnosed with cancer each year and must cope with the disease and treatments. Many studies have documented the deteriorations in quality of life that occur. These data suggest that the adjustment process is burdensome and lengthy. There is ample evidence showing that adults experiencing other long-term stressors experience not only high rates of adjustment difficulties (e.g., syndromal depression) but important biologic effects, such as persistent downregulation of elements of the immune system, and adverse health outcomes, such as higher rates of respiratory tract infections. Thus, deteriorations in quality of life with cancer are underscored if they have implications for biological processes, such as the immune system, relating to disease progression and spread. Considering these and other data, a biobehavioral model of adjustment to the stresses of cancer is offered, and mechanisms by which psychological and behavioral responses may influence biological processes and, perhaps, health outcomes are proposed. Finally, strategies for testing the model via experiments testing psychological interventions are offered.

Adaptation, Psychological↗

PubMed1994

Chronic stress, social support, and persistent alterations in the natural killer cell response to cytokines in older adults.

To address the long-term physiological consequences of chronic stressors, 14 continuing or current family caregivers of Alzheimer's disease (AD) patients, 17 former AD caregivers, and 31 control subjects were compared. Continuing and former caregivers did not differ on depressive symptomatology or perceived stress; both groups were significantly more depressed and stressed than controls. Furthermore, continuing and former caregivers did not differ in the response of NK cells in vitro to recombinant interferon-gamma and recombinant interleukin-2, and both groups had a significantly poorer response to these cytokines than controls. The physiological and psychological consequences of chronic stressors may persist well beyond the cessation of the actual stressor.

Aged↗

PubMed1994

Characterization of neutralizing monoclonal antibodies directed against Staphylococcus aureus alpha-toxin.

A panel of neutralizing murine monoclonal antibodies (MAbs) against Staphylococcus aureus alpha-toxin has been established, using formaline-inactivated alpha-toxin as an immunogen. Five independent groups of neutralizing epitopes have been identified representing five functionally important structures in the toxin molecule. Because none of the antibodies binds to overlapping decapeptides representing the toxin sequence or to bromocyanogen cleavage products of alpha-toxin, they may all bind to conformational epitopes. Nevertheless, they all bind to monomeric alpha-toxin in a Western blot. Three of the antibodies bind to the toxin monomer in an enzyme-linked immunosorbent assay (ELISA) in the presence, but not in the absence, of detergent. These epitopes are not accessible in hexameric toxin; two of them may represent the contact sites of the toxin monomers upon hexamerization and one is related to a structurally important glycine-rich central hinge region. Two different antibodies bind to monomeric toxin in an ELISA in the presence and absence of detergent and their epitopes are present more than once on oligomeric toxin; they bind strongly to hexameric toxin in a Western blot. The binding properties of the antibodies to alpha-toxin in different assay systems are summarized in an epitope model, which describes the presence of neutralizing domains in the different conformational steps required for pore formation.

Animals↗

PubMed1994

The effects of an acute psychological stressor on cardiovascular, endocrine, and cellular immune response: a prospective study of individuals high and low in heart rate reactivity.

High and low reactors were preselected on the basis of their heart rate reactivity to a speech stressor in a prescreening session. In the main study, subjects were exposed to a mental arithmetic plus noise stressor. Cardiovascular activity was recorded during baseline and stressor, and blood was drawn prior to and following the stressor for endocrine and immune assays. Results revealed that the stressor decreased the blastogenic response to concanavalin A and increased natural killer cell numbers and cytotoxicity, absolute numbers of CD8+ T-lymphocytes, norepinephrine and epinephrine levels, heart rate, and blood pressure responses. In addition, cortisol and natural killer cell cytotoxicity responses to the stressor differentiated individuals high versus low in heart rate reactivity. These results suggest that the interactions among the autonomic nervous system, endocrine system, and immune system are not only amenable to psychophysiological analysis but that such analyses may play an important role in illuminating underlying mechanisms.

Adolescent↗

PubMed1994

Platelet alpha 2-adrenergic receptor binding and the effects of d-amphetamine in boys with attention deficit hyperactivity disorder.

Presynaptic inhibitory alpha-adrenergic receptors are involved in regulating the release of norepinephrine (NE) through a negative feedback mechanism mediated by NE. Increased alpha2-adrenergic receptor activity suggests decrease NE release and activity, while decreased alpha2-adrenergic activity suggests increase NE release and activity. A large body of evidence suggests the involvement of a disturbance in NE activity in the pathophysiology of attention deficit hyperactivity disorder (ADHD) in childhood. Platelet alpha2-adrenergic receptor binding was compared in 23 boys aged 7-12 with the diagnosis of ADHD and 11 normal controls. The ADHD boys tended to have lower levels of alpha2-binding than controls. The administration of d-amphetamine in a double-blind placebo-controlled crossover design did not have any effect on alpha2-receptor binding in ADHD boys. Nonresponders to d-amphetamine had the lowest alpha2-receptor binding compared to responders and controls. These findings suggest a normal alpha2-adrenergic activity in ADHD boys responders to d-amphetamine and a possible increase in NE release in ADHD boys nonresponders to d-amphetamine due to decreased alpha2-adrenergic receptors.

Attention Deficit Disorder with Hyperactivity↗

PubMed1993

Spontaneous development of a chromosomal translocation 5;14 in an Epstein-Barr-virus-associated B-cell lymphoma in a SCID mouse.

C.B-17 SCID mice were inoculated with human peripheral blood leukocytes (PBLs) from normal Epstein-Barr virus (EBV)-seropositive and -seronegative donors. Confirmation of a functioning human immune response was demonstrated by the detection of human antibody after inoculation with rotavirus, tetanus toxoid, or EBV. One group of animals inoculated with PBLs from an EBV-seropositive donor developed immunoblastic lymphomas approximately 9 weeks after transplantation. Confirmation of the species and sex of origin of the tumor cells was established using a spontaneous cell line prepared from the tumor. At passage I, the tumor-cell line (AGTI) showed 15% of the metaphases with a translocation involving chromosomes 5 and 14. A lymphoblastoid cell line (AGLCL) established from the same PBLs from the same donor at the time of inoculation of the mice had a normal female karyotype. The AGLCL and a clone of AGTI cells were analyzed for rearrangement of immunoglobulin heavy chain (IgH) genes; both cell lines showed rearrangement of both IgH alleles. The results outlined in this report suggest that a spontaneous chromosomal translocation involving chromosome 14 occurred in normal PBLs in the SCID mouse.

Animals↗

PubMed1993

Solution- and solid-state structures of N-desmethylnefopam hydrochloride, a metabolite of the analgesic drug.

The solid-state structure of (+/-)-N-desmethylnefopam hydrochloride (1), a metabolite of the analgesic drug, was determined by single-crystal X-ray diffraction analysis. Compound 1 gave crystalline prisms belonging to the orthorhombic Pcab space group, and at ambient temperature (293 K), a = 9.939(2), b = 14.479(1), c = 20.148(3) A, V = 2899.5(8) A3, Z = 8, R(F) = 0.045, and Rw(F) = 0.025. The benzoxazocine ring of crystalline 1 is twisted into the boat-flattened (chair) [BfC] conformation, the phenyl ring resides in a relatively sterically unhindered exo-type ring position, whereas the O atom and NCH2Ar occupy sterically hindered positions between "boat" and "chair" regions. Dissolution of BfC crystalline 1 in CD2Cl2 solvent affords a dynamic conformational equilibrium (involving the putative twist-chair-flattened (chair) conformer) as shown by line broadening and weighted time-averaged vicinal coupling constants [-OCH2CH2N- segment] in the 1H NMR spectrum. The solution-state weighted time-averaged 50(1) degrees O-CH2-CH2-N dihedral angle, calculated by the R-ratio method, shows that the BfC conformation is the major contributor to time-averaged structure.

Analgesics↗

PubMed1993

Solid-state stereochemistry and activity of 3-methylnefopam diastereomers: manipulation of eight-membered ring conformations in analogues of the non-narcotic analgesic drug.

The solid-state structures of (+/-)-(1R,3S,5S)/(1S,3R,5R)- and (+)/(-)-(1R,3R,5R)/(1S,3S,5S)-3-methylnefopam hydrochloride, epimeric 3-methyl derivatives of the non-narcotic analgesic drug, were determined by single-crystal X-ray diffraction analyses. (+/-)-(1R,3S,5S)/(1S,3R,5S)-3-Methylnefopam hydrochloride gave crystals belonging to the monoclinic space group P2(1)/c, and at ambient temperature, a = 7.993(2), b = 34.376(4), c = 11.785(2) A, beta = 93.06 degrees, V = 3234(2) A3, Z = 8, R(F = 0.070, and Rw(F) = 0.053. (+)/(-)-(1R,3R,5R)/(1S,3S,5S)-3-Methylnefopam hydrochloride gave chiral crystals belonging to the orthorhombic space group P2(1)2(1)2(1), and at 92 K, a = 9.261(2), b = 10.280(2), c = 16.668(4) A, V = 1587(1) A3, Z = 4, R(F) = 0.034, and Rw(F) = 0.035. The two molecules in the asymmetric unit of the (1R,3S,5S)/(1S,3R,5R)-racemic modification had twist-chair-(flattened chair) [TCfC] conformational geometries for the eight-membered ring. Both molecules are virtually identical as shown by a root mean squares fit of 0.077 A in the superimposition of all nonhydrogen atoms in both molecules. The (+)/(-)-(1R,3R,5R)/(1S,3S,5S)-epimers were found in the same boat-(flattened chair) [BfC] conformation previously noted for crystalline nefopam hydrochloride. The TCfC and BfC eight-membered ring conformations of the two 3-methylnefopam diastereomers differ in the -N+H(CH3)CH2CH-fragment chair or boat arrangement vis-a-vis the adjacent flattened region. In both 3-methyl diastereomers, the C(3)-methyl group was disposed in an equatorial orientation, the phenyl group resided in an exo-position, and the -OCH(Ph)-o-C6H4- fragment occupied the flattened region of the eight-membered ring.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

PubMed1993

Stress-induced modulation of the primary cellular immune response to herpes simplex virus infection is mediated by both adrenal-dependent and independent mechanisms.

A murine model of herpes simplex virus (HSV) infection was used to examine the role of the adrenal gland in restraint stress-induced suppression of viral immunity. Adrenal-dependent mechanisms were important for suppressing the generation of HSV-specific cytotoxic T lymphocytes (CTL) but not the associated diminished lymphadenopathy in response to local HSV infection. While exogenous corticosterone administration alone was unable to suppress lymphadenopathy and CTL generation in adrenalectomized mice, an adrenal-independent mechanism induced by restraint stress functioned in synergy with corticosterone to suppress lymphadenopathy and CTL development. These results suggest that both adrenal-dependent and independent mechanisms contribute to stress-induced modulation of HSV immunity.

Adrenal Glands↗