Showing papers by "Virginia Commonwealth University published in 1988"

Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens

Abstract: Alterations in brain serotonergic function have been implicated in the mechanism of action of LSD, mescaline, and other similarly acting hallucinogenic drugs of abuse such as STP (2,5-dimethoxyphenylisopropylamine; DOM). In order to test the hypothesis that the mechanism of action of LSD and phenylisopropylamine hallucinogens is through stimulation of a specific brain serotonin receptor sub-type, the affinities of these compounds for radiolabelled 5-HT2, 5-HT1A, 5-HT1B, and 5-HT1C receptors have been determined using recently developed in vitro radioligand binding methodologies. The 5-HT2 receptor was labelled with the agonist/hallucinogen radioligand 3H-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine). The 5-HT1A, 5-HT1B, and 5-HT1C receptors were labelled with 3H-OH-DPAT, 3H-5-HT, and 3H-mesulergine, respectively. In general, the phenylisopropylamines displayed 10–100 fold higher affinities for the 5-HT2 receptor than for the 5-HT1C receptor and 100–1000 fold higher affinities for the 5-HT2 receptor than for the 5-HT1A or 5-HT1B receptor. There was a strong correlation between hallucinogenic potencies and 5-HT2 receptor affinities of the phenylisopropylamines (r=0.90); the correlation coefficients for the 5-HT1A, 5-HT1B, and 5-HT1C were 0.73, 0.85, and 0.78, respectively. Because there is no evidence that 5-HT1A-selective or 5-HT1B-selective agonists are hallucinogenic and because the phenylisopropylamines are potent hallucinogens, a 5-HT2 receptor interaction is implicated and supports our previous suggestions to this effect. A secondary role for 5-HT1C receptors cannot be discounted at this time. These results, when integrated with other receptor pharmacological information, indicate that an important component of the mechanism of action of LSD and the phenylisopropylamine hallucinogens is through stimulation of brain 5-HT2 receptors.

Protection against acute lethal viral infections with the native steroid dehydroepiandrosterone (DHEA)

Abstract: A significant protective effect of a native adrenal steroid, dehydroepiandrosterone (DHEA), was demonstrated in studies of two lethal viral infection models in mice: systemic coxsackievirus B4 and herpes simplex type 2 encephalitis. The steroid was active either by long-term feeding or by a single subcutaneous injection. A closely related steroid, etiocholanolone, was not protective in these models. Histopathological analysis, leukocyte counts, and numbers of spleen antibody forming cells in the coxsackievirus B4 model suggests that DHEA functions by maintaining or potentiating the immune competence of mice otherwise depressed by viral infection. DHEA was not effective in genetically immunodeficient HRS/J hr/hr mice and did not demonstrate antiviral activity in vitro. While the molecular basis for DHEA's effect on the immune system is not known, studies by others suggest that it may counteract the stress related immunosuppressive effects of glucocorticoids stimulated by viral infection. Because DHEA is a native steroid that has been used clinically with minimal side effects, the utility of DHEA in the therapeutic modulation of acute and chronic viral infections including the acquired immune deficiency syndrome deserves intensive study.

Idealism, Relativism, and the Ethic of Caring

Abstract: In this study, we investigated Gilligan's (1982) theory of moral thought Two hundred sixteen American college students (73% women and 205% black) completed two questionnaires designed to measure individual differences in personal moral philosophies Analyses indicated that individuals who endorsed an ethic of caring also tended to have higher scores on the idealism scale of the Ethics Position Questionnaire, r = 53 Caring was also slightly correlated with the rejection of moral relativism, r = - 13 Individuals who espoused highly idealistic but nonrelativistic personal moral philosophies most strongly endorsed an ethic of caring Sex differences among these students were conspicuously absent

Pretreatment with phencyclidine, an N-methyl-D-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury.

Abstract: This study examined the effects of pretreatment with phencyclidine (PCP), a selective N-methyl-d-aspartate (NMDA) antagonist, on behavioral and physiologic responses of the rat to experime...

Finite element methods for parabolic and hyperbolic partial integro-differential equations

Abstract: On formule plusieurs methodes de Galerkin a temps discret pour des equations integrodifferentielles paraboliques

Macrophage-mediated myelin-related mitogenic factor for cultured Schwann cells

Abstract: Conditioned medium from cultured peritoneal macrophages that have phagocytosed a myelin membrane fraction is mitogenic for cultured Schwann cells. Production of the mitogenic supernatant was time- and dose-dependent with a maximal Schwann cell-proliferative response from supernatants after 48-hr incubation of cultured macrophages with myelin-enriched fraction (200 micrograms of protein per ml). The response was specific for myelin membrane: supernatants derived from macrophages incubated with axolemma, liver microsomes, polystyrene beads, or lipopolysaccharide were not mitogenic. Lysosomal processing of the myelin membrane was necessary for the production of the mitogenic factor, which was shown to be heat labile and trypsin sensitive. There was no species specificity because myelin membranes isolated from the central and peripheral nervous systems of rat, bovine, and human were equally potent in eliciting mitogenic supernatant. However, supernatants derived from central nervous system myelin membranes were two to three times more mitogenic than those obtained from peripheral nervous system fractions of the same species. Previous observations that myelin is mitogenic for cultured Schwann cells may, in part, involve the intermediate processing of myelin by macrophages that are present in Schwann cell cultures. These results suggest that macrophages play a crucial role in Schwann cell proliferation during Wallerian degeneration.

Production and clearance of lactate from brain tissue, cerebrospinal fluid, and serum following experimental brain injury

Abstract: Lactate dynamics in the brain, cerebrospinal fluid (CSF), and serum were studied in 20 chloralose-anesthetized cats following fluid-percussion trauma. Brain lactate and brain tissue pH were measured by hydrogen-1 and phophorus-31 magnetic resonance spectroscopy. The CSF, arterial, and cerebrovenous serum lactate levels as well as serum glucose concentration were quantified. In the six sham-operated control animals, brain, CSF, cerebrovenous, and arterial lactate levels as well as brain pH remained at normal values. In the five animals in the mild-trauma group (1.6 atm), brain and CSF lactate levels were moderately elevated, although the brain pH and serum lactate content remained at control values. Severe trauma (3.1 atm) in nine cats produced an 82% increase in the brain lactate index and a reduction in brain tissue pH (7.02 +/- 0.02 to 6.95 +/- 0.02; mean +/- standard error of the mean), indicating brain tissue acidosis caused by excessive lactate accumulation. Brain lactate levels reached a peak 1 1/2 hours after severe trauma, then steadily decreased to normal levels by 8 hours posttrauma. Maximum increases of CSF and arterial lactate levels (from 1.4 +/- 0.2 to 4.1 +/- 0.4 and from 1.6 +/- 0.2 to 4.1 to 0.6 mmol/liter, respectively) were observed 15 minutes after trauma, and the values decreased during the next 2 hours. The response was biphasic, with a secondary rise observed in both CSF and serum lactate levels during the remaining 4 hours of the experiment. The difference between the arterial and venous lactate levels (A-Vlact) gradually increased and reached a peak 2 hours postinjury (from -0.05 +/- 0.10 to -0.41 +/- 0.09 mmol/liter). The results of this study show that the production of lactate in brain tissue, CSF, and blood increased in proportion to the severity of the injury. The observation that lactate levels in blood and CSF are maximum immediately following impact while brain lactate and A-Vlact are gradually increasing suggests that the brain-tissue production of lactate fails to account for the rapid appearance of lactate in CSF and blood. It is speculated that the initial elevation of CSF lactate values reflects the systemic response of trauma, and the secondary rise of CSF lactate levels following severe trauma is due to slow seepage of lactate produced by brain tissue into the CSF space. These studies are the first to describe the temporal profile of brain lactate production and eventual clearance by CSF and blood in fluid-percussion injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Pial arteriolar vessel diameter and CO2 reactivity during prolonged hyperventilation in the rabbit.

Abstract: ✓ Hyperventilation reduces intracranial pressure (ICP) acutely through vasoconstriction, but its long-term effect on vessel diameter is unknown. In seven rabbits with a cranial window implanted 3 weeks earlier, the effect of prolonged hyperventilation on vessel diameter was studied. Anesthesia was maintained for 54 hours with a pentobarbital drip (1 mg/kg/hr). The pH, CO2, and HCO3− levels were measured in arterial blood and cisterna magna cerebrospinal fluid (CSF). The diameter of 31 pial arterioles was measured with an image splitter. After baseline measurements, pCO2 was reduced from 38 to 25 mm Hg and allowed to return to 38 mm Hg for 10 minutes every 4 hours. There was an initial vasoconstriction of 13%, which progressively diminished by 3% every 4 hours. Thus, by the 20th hour, vessel diameters at a pCO2 of 25 mm Hg had returned to slightly above baseline values obtained at a pCO2 of 38 mm Hg. The temporary return of pCO2 to 38 mm Hg every 4 hours caused vasodilation: 12% at 4 hours, gradually incre...

An Examination of the Factor Structure and Convergent and Discriminant Validity of the SCL-90R in an Outpatient Clinic Population

Abstract: This study investigated the factor structure of the SCL-90R using an outpatient psychology clinic population. Six relatively homogeneous and stable factors were identified: Depression, Somatization, Anger-Hostility, Paranoid-Psychoticism, Phobic Anxiety, and Obsessive-Compulsive. However, a principal component analysis revealed that the first factor accounted for a large percentage of the variance, suggesting that this instrument measures a general dimension of psychopathology. In addition, significant correlations between the SCL-90R symptom dimensions and both the BDI and several MMPI scales were found. The results of the study lead to questions regarding the utility of the SCL-90R.

Sjögren-Larsson syndrome. Impaired fatty alcohol oxidation in cultured fibroblasts due to deficient fatty alcohol:nicotinamide adenine dinucleotide oxidoreductase activity.

Abstract: Lipid metabolism was studied in cultured skin fibroblasts from patients with the inherited disorder, Sjogren-Larsson syndrome (SLS). Intact SLS fibroblasts incubated in the presence of [1-14C]palmitate accumulated more radioactive hexadecanol than did normal cells, whereas incorporation of radioactivity into other cellular lipids was unaltered. The hexadecanol content of SLS fibroblasts was abnormally elevated. Hexadecanol accumulation was not due to increased fatty alcohol synthesis nor its deficient utilization for glycerol ether synthesis. The half-life of intracellular hexadecanol loaded into SLS fibroblasts was increased (70 min) compared with normal (15 min), and intact SLS fibroblasts showed impaired oxidation of [14C]-hexadecanol to fatty acid. Fatty alcohol:NAD+ oxidoreductase, the enzyme catalyzing this reaction, was deficient in SLS fibroblasts. Mean total activity in SLS fibroblasts (n = 5) was 13% of that in normal fibroblasts, and palmitoyl CoA-inhibitable activity was 1% of normal. Fibroblasts from two obligate SLS heterozygotes had enzyme activities intermediate between that in normal fibroblasts and individuals with SLS. These results suggest that the primary defect in SLS is deficiency of fatty alcohol:NAD+ oxidoreductase. SLS represents the first inherited disorder in man associated with an isolated abnormality in fatty alcohol metabolism.

Role of peptide conformation in the rate and mechanism of deamidation of asparaginyl residues.

Abstract: The tetrapeptides Val-Asn-Gly-Ala and N-acetyl-Val-Asn-Gly-Ala undergo deamidation of the asparaginyl residue at pH 7.0 at similar rates. However, they form different products. The N-acetyl peptide gave a 3:1 ratio of N-acetyl-Val-isoAsp-Gly-Ala and N-acetyl-Val-Asp-Gly-Ala, respectively. The nonacetylated peptide gave no detectable amounts of these products but rather gave a cyclic peptide formed from the nucleophilic displacement of the asparaginyl side chain amide by the amino terminus of valine. This compound was slowly inverted at carbon 2 of the asparaginyl residue. At pH values above 7.5, the nonacetylated peptide also underwent deamidation to form Val-isoAsp-Gly-Ala and Val-Asp-Gly-Ala in the 3:1 ratio. Proton NMR spectra of the acetylated and nonacetylated tetrapeptides show that below pH 7.5 they have very different preferred conformations, and it is these different conformations which result in the different mechanisms of deamidation. Above pH 9.0, both peptides have similar conformations and deamidate by the same mechanism to give equivalent products. Neither mechanism of deamidation was subject to general base catalysis by the buffer. These results suggest that deamidation rates of the asparaginyl-glycyl sequence in proteins will vary according to the conformation of the peptide backbone of each respective protein. The results also show that asparaginyl residues which are penultimate to the amino terminus can react to form an N-terminal-blocked seven-membered ring.

The dynamic relations among interpersonal behaviors: a test of complementarity and anticomplementarity.

Abstract: On the basis of the positions of behaviors relative to one another in the interpersonal circle, the principles of complementarity and anticomplementarity specify how people's behaviors influence one another in interpersonal interactions. Pairs of undergraduate women (1 subject, N = 80, and 1 confederate) collaborated for 16 min to create and agree on stories for two pictures. Confederates performed scripted roles that emphasized one of eight interpersonal behaviors. Behaviors were coded into eight categories, and the relative effect of each confederate behavior on each subject behavior was determined. Using the geometric properties of the interpersonal circle, vectors were calculated that identified the relative impact of each confederate stimulus behavior on the overall pattern of subject responses. Results were consistent with the dynamic relations among interpersonal behaviors that complementarity and anticomplementarity propose and demonstrated that how a person behaves toward another systematically and profoundly affects how the other behaves toward the person.

CONVICTED RAPISTS' PERCEPTIONS OF SELF AND VICTIM:: Role Taking and Emotions

Abstract: This article is an attempt to bridge the gap between feminist structural explanations for rape and the social psychological mechanisms that make it possible for some men in patriarchal societies to feel neutral about sexual violence toward women. The concept of role taking is used to analyze the perceptions of self and victim held by 79 convicted rapists. Men who defined their behavior during sexual encounters as rape saw themselves from the perspective of their victim through reflexive role taking, had inferred their victims' experience through synesic role taking, and used this awareness to further their plan of action. Men who did not define their behavior as rape did neither reflexive nor synesic role taking and appeared incapable of understanding the meaning of sexual violence to women. The majority of both groups did not experience role-taking emotions, that is, guilt, shame, or empathy, which symbolic interactionists posit are the mediators of self-control. I argue that the gender imbalance of powe...

A statistical approach to the construction and analysis of isobolograms

Abstract: Current statistical procedures used in the construction of isobolograms do not use recent advances in mathematical statistics. The variability in the experimental data is either ignored or incompletely accounted for in the analyses. The decision procedures currently used to characterize the type of interaction between two agents do not permit the determination of the level of statistical significance associated with a given conclusion. Furthermore, the often formidable sample size is not exploited in the current isobologram methodology. Statistical techniques exist that may be used to construct isobolograms and decision procedures with a reliable level of significance. An isobologram is a contour of constant response of the underlying dose-response surface. Consequently, response surface methods (RSM) are useful in the estimation and analysis of isobolograms. The interaction between ethanol and chloral hydrate in female ICR mice was evaluated using the RSM approach by fitting the logistic model to quantal...

Use of dehydroepiandrosterone to improve immune response

Abstract: The steroid hormone dehydroepiandrosterone (DHEA), when administered by feeding or by subcutaneous injection, significantly improves the host response to viral infection. Experimental animal data shows that, with infection (100,000 plaque forming units/animal) of a human coxsackievirus B4 strain, which causes mortality in about 90% of infected animals, mortality was reduced to 37% when animals were treated with DHEA. Moreover, DHEA induced an 80% elevation in the number of antibody forming cells, particularly in cells forming gamma globulin M (early antibodies), and gamma globulin G (secondary antibodies). This elevation in the number of antibody forming cells was evident only in DHEA treated and virus infected animals, but not in uninfected animals treated with DHEA or in infected animals not treated with DHEA. In virus infected and DHEA treated animals there was also an elevation in the number of monocyte cells, the particular white blood cell associated with a resistance to this infection. This elevation was not observed in hormone treated uninfected animals. This observation shows that DHEA can be used to up regulate the host immune response to virus infection, by increasing the number of antibody forming cells, elevating the number of white blood cells associated with resistance to virus infection and markedly reducing virus induced mortality. Virus (antigen) has to present in order to demonstrate the up regulation of immunity by the hormone.

Circumferential pressure probe

Abstract: A probe for measuring circumferential pressures inside a body cavity. In the preferred embodiment, a urodynamic pressure measurement probe for evaluating human urinary sphincter function is disclosed. Along the length of the probe are disposed a multiplicity of deformable wall sensors (15) which typically comprise support tube sections (55) with flexible side wall areas (57, 16). These are arranged along the length of the probe in two areas, one just proximal to the tip (13) for the sensing of fluid pressure inside the bladder, and five in a sensing section (14) which is positioned within the urethra at the point at which the urinary sphincter constricts to control the flow of urine. The remainder of the length of the probe comprises multiple rigid support tube sections (10) interspersed with flexible support tube sections in the form of bellows (58) to provide flexibility.

Effects of race and periodontal status on antibody reactive with Actinobacillus actinomycetemcomitans strain Y4

Abstract: Higher levels of serum antibody reactive with Actinobacillus actinomycetemcomitans strain Y4 (AAY4) have been demonstrated in localized juvenile periodontitis than in other forms of periodontal diseases. However, in studies which reported the racial distribution of the clinical groups, a predominantly black juvenile periodontitis population has been compared with a non-periodontitis control population that was predominantly white. The purpose of this study was to determine the effect of race (black or white) on antibody reactivity to AAY4 for subjects with clinical diagnoses of adult periodontitis (AP), non-periodontitis (NP), juvenile periodontitis (JP) and severe generalized periodontitis in young adults (SP). A radioimmunoassay (RIA) was utilized to detect and quantitate antibody to AAY4. Within clinical groups of NP, JP and SP a higher prevalence of seropositive black subjects than white subjects was found. The association between a high prevalence of positive antibody responses to AAY4 in JP subjects compared to NP subjects still exists, but was reduced compared to previous reports. White non-periodontitis subjects, used as control subjects in previous reports, were found to have a significantly lower frequency of seropositivity to AAY4 than black non-periodontitis subjects. This relationship held whether the periodontatly healthy subject was ascertained from a family with a JP or SP family member or was ascertained solely on the basis of a diagnosis of non-periodontitis. The difference in the prevalence of seropositivity to AAY4 between JP and SP subjects was entirely due to the racial composition of the two groups, as nearly half the SP subjects were white compared with only 15% of the JP subjects. Thus, antibody reactivity to AAY4 was found to be related to both clinical diagnosis and race.

Prospective study of microbial colonization of the nose and skin and infection of the vascular access site in hemodialysis patients.

Abstract: We conducted a prospective study of nasal and skin floras in 71 patients receiving chronic hemodialysis. We wished to determine whether a sterile skin preparation technique was more effective than a clean technique in removing microorganisms from the skin of the vascular access site. We also examined the effect of administration of antibiotics and status of patient hygiene on microbial flora. The presence of Staphylococcus aureus in the nose had a low predictive value for the simultaneous presence of the microorganism on the skin. The status of skin colonization can be accurately assessed only by culture of the skin. Sterile technique was no more effective at removing microorganisms from skin than was clean technique. Antibiotics significantly affected nasal flora but not skin flora. S. aureus was significantly more likely to remain on the skin after application of an antiseptic in patients with poor hygiene than in patients with good hygiene (P = 0.002). Patients with poor hygiene also had a significantly higher concentration of S. aureus on the skin of the vascular access site after application of antiseptic than patients with good hygiene (P = 0.005). We found no evidence to support a change from clean to sterile technique for skin preparation, but improvement in personal hygiene may be an effective strategy for prevention of vascular access infections.

Combined pretrauma scopolamine and phencyclidine attenuate posttraumatic increased sensitivity to delayed secondary ischemia.

Abstract: Fasted Wistar rats were given a mild level of traumatic brain injury (TBI) and then subjected to 6 min of transient forebrain ischemia 24 h posttrauma. One group was given simultaneous 1 m...

Mentoring Women in Academia

Abstract: We investigated faculty and graduate students' judgments about mentoring women in academia. Overall ratings of important characteristics of mentors were similar to those reported in empirical and descriptive literature. Differences in the women's ratings were not related to demographic characteristics. However, women who were seeking mentors, had mentors, or had been mentors for others, did have different evaluations of this relationship.

Black Battered Women: Practice Issues:

Abstract: Although domestic violence occurs among all racial/ethnic groups, regardless of socioeconomic background, little attention has been paid to black battered women. The authors discuss six culturally ...