Biomedical subjects

W B Malarkey

Publications and source records attributed to W B Malarkey.

At least 37 records · Page 2Linked to original sources

PubMed1996

Delayed diagnosis of psychological erectile dysfunction because of the presence of macroprolactinemia.

Idiopathic hyperprolactinemia can be found in men with either normal or low serum testosterone (T) levels. The explanation for the differing effects on T of similar PRL levels has not been found. Macroprolactinemia, as a clinical entity, has been reported mostly in women. These macromolecules are biologically less active and/or are transported less easily across the capillary bed than the 22-kDa molecules. Therefore, women with elevated PRL levels retain normal menses and fertility. We studied six men, aged 28-53 yr (mean, 45 yr), in whom hyperprolactinemia was initially considered to be the cause of their erectile dysfunction. PRL levels ranged from 25-92 ng/mL (normal, 2-15 ng/mL), but T and gonadotropin levels were normal, suggesting that PRL was not disrupting gonadotropin and gonadal steroid function. The results of magnetic resonance imaging studies of the pituitary gland were normal. Separation by Sephadex G-100 column chromatography showed a predominance (85-90%) of big (60 kDa) and big big ( > 150 kDa) PRL, in contrast to the predominance of 22-kDa PRL in normal subjects. Nocturnal tumescence testing was normal, supporting the diagnosis of psychogenic impotence in these subjects, and potency returned after counseling. Hence, the biologically inactive macroprolactinemia did not cause any organic derangement in erectile function. It further obscured and delayed the appropriate diagnosis and treatment of these individuals.

Adult↗

PubMed1995

Slowing of wound healing by psychological stress.

There is evidence that psychological stress adversely affects the immune system. We have investigated the effects of such stress, caused by caring for a relative with Alzheimer's disease, on wound healing. We studied 13 women caring for demented relatives (mean age 62.3 [SE 2.3] years) and 13 controls matched for age (60.4 [2.8] years) and family income. All subjects underwent a 3.5 mm punch biopsy wound. Healing was assessed by photography of the wound and the response to hydrogen peroxide (healing was defined as no foaming). Wound healing took significantly longer in caregivers than in controls (48.7 [2.9] vs 39.3 [3.0] days, p < 0.05). Peripheral-blood leucocytes from caregivers produced significantly less interleukin-1 beta mRNA in response to lipopolysaccharide stimulation than did controls' cells. Stress-related defects in wound repair could have important clinical implications, for instance for recovery from surgery.

Aged↗

PubMed1995

The reliability and validity of a structured interview for the assessment of infectious illness symptoms.

Respiratory infections are the leading cause of morbidity in community populations. We developed a structured interview based on the Health Review (Rose et al., Psychosom. Med. 40: 142-165, 1978) to provide a simple method for periodic assessment of infectious illness, particularly upper respiratory infections. Congruence between interview data and physician diagnoses demonstrated excellent agreement regarding the presence or absence of an infection. Subjects who showed a clinically significant increase in antibody titers to an influenza virus vaccine reported fewer than half as many respiratory infections in the subsequent year as subjects who did not show a significant response. Interrater and test-retest reliabilities were satisfactory. These data support the reliability and validity of this method of assessing infectious illnesses.

Aged↗

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

A PCR-derived, non-isotopic labeled prolactin cRNA probe suitable for in situ hybridization.

We have developed a novel vector-free method for the synthesis of nonisotopic (digoxigenin) labeled prolactin (PRL)-gene specific cRNA probe based on the direct in vitro transcription of DNA template amplified by polymerase chain reaction (PCR). The T7 and T3 RNA polymerase promoters were incorporated into the amplified DNA by including the promoter sequences in the '5 end of the oligonucleotides used to prime the PCR. These promoters allowed the subsequent transcription of digoxigenin labeled antisense and sense cRNA probes from the amplified DNA. We successfully utilized these probes to detect specific PRL mRNA in human pituitary and decidua tissues by in situ hybridization (ISH) which can provide identification and localization of PRL-gene expression at a single cell level. This approach avoided time consuming steps which required subcloning of target DNA into the vectors that contains bacteriophage RNA polymerase promoter as well as the need for radioactive materials. This non-isotopic ISH procedure takes less than 72 h from specimen preparation to microscopic analysis and should prove to be useful for molecular biological studies of hormones and clinical diagnosis.

Base Sequence↗

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

The dissociation of catecholamine and hypothalamic-pituitary-adrenal responses to daily stressors using dexamethasone.

The hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) systems are implicated in the human stress response. One characterization of these systems is that they are nonspecific in their response, but differ in activation threshold and time course. Additionally, they have been found to be affected commonly by strong metabolic stressors and infusions of CRH, and a hypothesis has been developed primarily from animal research that CRH stimulates both the HPA and SAM systems. To determine whether CRH was significantly involved in tonic as well as psychological stress-induced catecholamine levels in man, we infused 24 normal male undergraduate students with either saline (n = 12) or dexamethasone (DEX; n = 12) and evaluated their subsequent plasma levels of ACTH, cortisol, epinephrine (EPI), and not epinephrine (NEPI). DEX produced a dramatic decrease in ACTH and cortisol levels, but no significant changes in EPI or NEPI occurred over a 4-h sampling interval. After the administration of math and speech stressors in a controlled laboratory setting, DEX inhibited the ACTH and cortisol release that was noted in the saline group, but stress-induced increases in EPI and NEPI were comparable in both groups. Thus, our study suggests that there is a difference in the neural pathways for tonic and stress-induced stimulation of the SAM and HPA systems.

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

Stress-induced changes attributable to the sympathetic nervous system during experimental influenza viral infection in DBA/2 inbred mouse strain.

The murine model of influenza viral infection was used to evaluate the effects of restraint stress on pathogenesis and survival in the DBA/2 inbred strain of mice. Restraint stress has been associated with an enhanced probability of survival during influenza infection in this strain of mouse. Previous studies suggested that the protective mechanism(s) of stress on mortality might be attributable to elevated levels of circulating glucocorticoids. Subsequent work demonstrated that corticosterone levels alone could not account for the enhanced survival seen in the DBA/2 mice. The present studies examined the role of catecholamines in behavioral stress during influenza infection. It appears that glucocorticoids may play a primary role in trafficking and restriction of inflammation, while catecholamines may play role in limiting activation of virus-specific effector cells. The studies presented here suggest that the interplay between these two physiological response mechanisms needs to be coordinated to optimize development of the immune response to an infection.

Animals↗

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

High atrial natriuretic peptide concentrations blunt the pressor response during cardiopulmonary resuscitation in humans.

OBJECTIVE: To determine the relationship of circulating atrial natriuretic peptide concentrations to the pressor response to high-dose epinephrine in patients undergoing cardiopulmonary resuscitation (CPR) for cardiac arrest. DESIGN: Prospective study. PATIENTS: Fourteen normothermic, adult, prehospital and emergency department patients suffering unexpected cardiac arrest. INTERVENTION: Patients received high-dose epinephrine (0.2 mg/kg) i.v. when standard advanced cardiac life support (including multiple 1-mg dosages of epinephrine) failed to result in return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: Cardiac arrest patients were separated into those patients with and without detectable serum atrial natriuretic peptide concentrations, and were termed the "low atrial natriuretic peptide" and "high atrial natriuretic peptide" groups, respectively. Their aortic pressure response to high-dose (0.02 mg/kg) epinephrine was compared. The proportion with positive assays was compared with a group of healthy control subjects. Fourteen patients were studied. Eight patients had low serum atrial natriuretic peptide concentrations and six patients had high circulating atrial natriuretic peptide concentrations. The mean concentration in the high atrial natriuretic peptide group was 151 +/- 82 pg/mL. The proportion with positive assays (six of 14 patients) was greater than in the group in spontaneous circulation (three of 29 patients) (p = .002). The maximal increase in the aortic relaxation-phase pressures after high-dose epinephrine was 9 +/- 7 torr (1.2 +/- 0.9 kPa) in the low atrial natriuretic peptide group and 0 +/- 5 torr (0 +/- 0.7 kPa) in the high atrial natriuretic peptide group (p = .03). The maximal increase in the aortic compression pressures after high-dose epinephrine was 17 +/- 13 torr (2.3 +/- 1.7 kPa) in the low atrial natriuretic peptide group and 2 +/- 10 torr (0.3 +/- 1.3 kPa) in the high atrial natriuretic peptide group (p = .03). Thus, pressor responses after high-dose epinephrine administration were observed in patients in the low atrial natriuretic peptide group, but this response was absent in patients in the high atrial natriuretic peptide group. CONCLUSIONS: Cardiac arrest patients receiving CPR have higher circulating atrial natriuretic peptide concentrations than healthy subjects. High serum atrial natriuretic peptide concentrations may antagonize the vasopressor response to epinephrine. Blocking this effect of atrial natriuretic peptide may improve outcomes in patients suffering cardiac arrest.

Adult↗

PubMed1993

Mechanisms of action of long-acting analogs of somatostatin.

The prolactin secreting rat pituitary tumor cell line, GH3, expresses high affinity receptors for both vasoactive intestinal peptide (VIP) and somatostatin (SS14). VIP induces prolactin secretion by GH3 cells, an action which is antagonized by SS14. This in vitro model was used to examine the mechanism of action of two synthetic somatostatin analogs, D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-OH (octreotide; SMS 201-995) and cyclo(aminoheptanoyl-Phe-D-Trp-Lys-Thr (benzyl)) (cyclic pentapeptide; CPP). Octreotide and CPP bind to the pituitary somatostatin receptor with lower affinity than does SS14 (KD = 1.3 +/- 1.1; 80 +/- 29; 211 +/- 107 nM for SS14, octreotide and CPP, respectively). SS14 and octreotide were equally effective as inhibitors of VIP-mediated accumulation of cAMP (40% and 45% inhibition, respectively, P < 0.01). SS14 and octreotide also inhibited forskolin-mediated accumulation of cAMP (42% and 40% inhibition of cAMP production, respectively; P < 0.01). The inhibitory action of somatostatin and octreotide on both VIP- and forskolin-mediated cAMP accumulation was blocked by pre-treatment of GH3 cells with pertussis toxin (P < 0.001). Neither SS14 nor octreotide affects the apparent affinity of VIP for its specific receptors on GH3 cells; thus, the inhibitory action of SS14 and octreotide appears to be mediated at the locus of the G-protein-adenylate cyclase complex. In contrast, CPP inhibited VIP-mediated cAMP accumulation slightly, but had no effect on forskolin-mediated cAMP production. Pertussis toxin did not attenuate CPP affects on VIP-mediated cAMP accumulation. However, pre-incubation of GH3 cells with CPP decreased the apparent affinity of receptors for VIP, suggesting that effects of CPP are attributable to interference with VIP binding rather than inhibition at the G-protein-adenylate cyclase complex.

Amino Acid Sequence↗

PubMed1993

The influence of age on endocrine responses to ultraendurance stress.

BACKGROUND: Aging produces significant changes in the human endocrine system. This study was designed to determine if elderly and younger individuals differ in various endocrine measures before and after ultraendurance stress. METHODS: Sixteen young and 19 older subjects competing in a world championship triathlon had blood samples acquired for 13 hormones before, immediately after the event, and 18 hours into recovery. RESULTS: Following the triathlon, almost every hormone level increased. Significantly higher basal circulating levels of dihydroepiandrosterone sulfate (DHEA-S) and thyroid stimulating hormone (TSH) were found in 20-year-old individuals, whereas higher levels of norepinephrine (NEPI) and sex hormone binding globulin (SHBG) were found in the 50- to 74-year-old group. Older subjects had lower postexercise levels of EPI, DHEA-S, GH, and PRL and higher postexercise levels of estradiol than younger individuals. Similarity in pre- and postrace weights as well as Hgb and Hct levels suggested that dehydration, while present, did not significantly contribute to the endocrine changes. CONCLUSIONS: Ultraendurance stress produced dramatic increases in all but one of the hormones evaluated. Whether frequent exercise can alter the endocrine changes that occur with aging cannot be answered by this study. It is clear, however, that when comparisons are made with young active individuals, frequent exercise does not eliminate the differences in basal concentrations of TSH, DHEA-S, SHBG, and NEPI or exercise-induced release of estradiol, GH, and PRL that occur with aging.

Adult↗

PubMed1993

Exercise training and dietary carbohydrate: effects on selected hormones and the thermic effect of feeding.

To determine relationships among dietary carbohydrate, aerobic exercise training, the thermic effect of food (TEF), and hormonal responses to feeding, 8 trained and 7 sedentary men consumed diets providing 15, 45, or 75% of energy as carbohydrate for 5 days. On Day 6, metabolic rate was measured before as well as 30, 60, 90, and 120 min after an 868-kcal liquid test breakfast. Blood was sampled hourly during Day 5 and during each metabolic rate measurement. The trained group had a larger TEF (40 +/- 2.4 vs. 31 +/- 3.0 kcal/2 hrs), greater insulin sensitivity, and greater plasma prolactin and cortisol levels. As carbohydrate in the treatment diet increased, carbohydrate utilization and thyroid stimulating hormone were higher and thyroxine was lower, but TEF was not significantly different. After the test meal, trained individuals had a higher TEF but the carbohydrate content of the treatment diet did not influence TEF.

Adolescent↗

PubMed1993

Growth hormone secretion by human peripheral blood mononuclear cells detected by an enzyme-linked immunoplaque assay.

In order to evaluate the secretion of GH from human peripheral blood mononuclear cells (PBMC) and its possible role as a modulator of lymphoproliferation, we have developed a hormonal enzyme-linked immunoplaque assay. This assay captures GH between a monoclonal and polyclonal antibody. This is followed by adding substrate and a horseradish peroxidase-conjugated antibody against the polyclonal antibody which produces violet colored plaques where GH has been secreted. This assay is sensitive, specific, highly reproducible, and can detect picogram quantities of GH. Using this assay we have detected GH secretion from approximately 1% of human PBMC under unstimulated conditions. Regression analysis showed a linear relationship between the number of cells plated and the number of GH plaques formed. Therefore, GH plaques were formed by single cells or its progeny and did not represent aggregation of secreting cells. Preincubation of PBMC with cycloheximide, a protein synthesis inhibitor, completely abolished the formation of GH plaques which suggests that the PBMC were responsible for the synthesis of the secreted GH. In addition, we have also observed that stimulation of human PBMC with T-cell mitogens, Concanavalin A and PHA and the cytokine IL-2 led to significant increases in GH plaque area and number whereas stimulation with LPS, a B cell mitogen, was ineffective. The PHA and IL-2 induced increase in plaque number suggests that they can recruit noncommitted lymphocytes to actively secrete GH which raises the possibility that this secreted GH may serve as a growth factor in T cell proliferation. We conclude that this immunoplaque assay may be useful in evaluating the secretion of other peptides from human immune cells.

Cells, Cultured↗

PubMed1992

Human thymocytes secrete luteinizing hormone: an autocrine regulator of T-cell proliferation.

There is evidence that there may be bidirectional communication between immune and gonadotropin producing cells. In the present study we describe the secretion and function of an LH like peptide secreted from the human thymus. Serial dilutions of thymic extracts obtained from surgically removed thymic tissues displaced I125 LH from LH antiserum parallel to that produced by pituitary LH. Thymic LH was detected as early as 10 days of age and maximal concentrations were noted at 5 months. Utilizing a sensitive and specific hormonal enzyme linked immunoplaque assay developed in our laboratory, we were able to detect LH secretion from unstimulated human thymocytes. Neutralizing endogenously released LH in PHA stimulated thymocytes with LH antiserum significantly inhibited thymidine incorporation. We conclude that an LH-like peptide is secreted by human thymocytes which acts as an autocrine co-mitogen in lymphoproliferation.

Cell Division↗

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↗