scispace - formally typeset
Search or ask a question

Showing papers by "Virginia Commonwealth University published in 1986"


Journal ArticleDOI
TL;DR: The authors attempt to demonstrate that genes and the environment can interact in several interesting and potentially subtle ways, that these interactions can be expressed in simple models from which clear empirical predictions can be generated, and that elucidation of the etiology of psychiatric disorders will require the consideration of both genetic and environmental risk factors.
Abstract: The authors present three major models for the joint effect of genes and environment on liability to psychiatric illness: additive effects of genotype and environment, genetic control of sensitivity to the environment, and genetic control of exposure to the environment. Each model is illustrated by several examples, including a quantitative one. The authors attempt to demonstrate that genes and the environment can interact in several interesting and potentially subtle ways, that these interactions can be expressed in simple models from which clear empirical predictions can be generated, and that elucidation of the etiology of psychiatric disorders will require the consideration of both genetic and environmental risk factors.

509 citations


Journal ArticleDOI
TL;DR: Data gathered in Australia and England on the social attitudes of spouses and twins are largely consistent with a genetic model for family resemblance in social attitudes and there is substantial assortative mating and little evidence of vertical cultural inheritance.
Abstract: Data gathered in Australia and England on the social attitudes of spouses and twins are largely consistent with a genetic model for family resemblance in social attitudes. There is substantial assortative mating and little evidence of vertical cultural inheritance.

403 citations


Journal ArticleDOI
TL;DR: Thiothixene seems to have more than an antipsychotic effect, and a subdiagnosis defined by those symptoms that are drug-responsive, some of which are not included in current diagnostic criteria is suggested.
Abstract: • Fifty outpatients with borderline and/or schizotypal personality disorder were randomly allocated to thiothixene (Navane) or placebo treatment that was continued for 12 weeks. The mean daily dosage of thiothixene hydrochloride in the final week of the study was 8.7 mg, a lower dosage than is used in outpatient schizophrenics. Significant drug-placebo differences were found, regardless of diagnosis, on "illusions," "ideas of reference," "psychoticism," "obsessivecompulsive symptoms," and "phobic anxiety," but not on "depression." Thiothixene seems to have more than an antipsychotic effect. Since response to treatment studies are a means for reformulating diagnostic concepts, we suggest a subdiagnosis defined by those symptoms that are drug-responsive, some of which are not included in current diagnostic criteria. Patients with borderline and schizotypal disorder without the foregoing symptoms probably would not profit from thiothixene and might needlessly be placed at risk for adverse drug effects.

205 citations


Journal ArticleDOI
TL;DR: In this paper, the relationship between negative events and disorder was moderated by gender, the types of events experienced, and anticipated change in the psychosocial environment, highlighting the importance of the use of standardized and psychometrically sound measures of life events, social support, and psychological disorder.
Abstract: Relationships among major life events, perceived social support, and psychological disorder were assessed in a sample of older adolescents. Negative life events and satisfaction with social support were significantly and independently related to a range of psychological symptoms. Further, the relationship between negative events and disorder was moderated by gender, the types of events experienced, and anticipated change in the psychosocial environment. The importance of the use of standardized and psychometrically sound measures of life events, social support, and psychological disorder is highlighted.

205 citations


Journal ArticleDOI
TL;DR: It is concluded that HLj is related by structure, function, and some regulatory characteristics to rat P-450j and rabbit P- 450 LM3a, cytochromes critical for metabolism of several clinically relevant cytotoxic and carcinogenic agents.
Abstract: Through the use of monospecific antibodies directed against hepatic cytochrome P-450j, an enzyme induced in rats treated with ethanol or isoniazid, we have purified from human liver the related cytochrome P-450 termed HLj. HLj resembles rat P-450j and P-450 LM3a, the homologous cytochrome in rabbit liver, in its NH2-terminal amino acid sequence, in being in highest concentration in liver microsome samples prepared from two patients intoxicated by ethanol and one patient given isoniazid, and in catalyzing the metabolic activation of the procarcinogen N-nitrosodimethylamine. Furthermore, each of nine human liver RNA samples contained a species of mRNA hybridizable to a cloned HLj cDNA. We conclude that HLj is related by structure, function, and some regulatory characteristics to rat P-450j and rabbit P-450 LM3a, cytochromes critical for metabolism of several clinically relevant cytotoxic and carcinogenic agents.

179 citations


Journal ArticleDOI
TL;DR: It is concluded that macrolide antibiotics induce P-450p, the most rapidly turning over cytochrome yet reported, by stimulating its synthesis indirectly and by blocking its degradation, significantly.

175 citations


Journal ArticleDOI
TL;DR: The theoretical and practical advances of measurements of cerebral blood flow over cerebral angiography, especially in comatose patients are stressed, and the role of measurement of cerebralBlood flow in the clinical management of vasospasm is discussed.

156 citations


Journal ArticleDOI
TL;DR: It is concluded that HLp is a human representative of a conserved glucocorticoid-inducible cytochrome P-450 gene family whose mechanism of induction involves accumulation of HLp mRNA.
Abstract: HLp is a human liver cytochrome P-450 that is immunochemically related to the glucocorticoid-inducible liver cytochrome P-450p in the rat and its homologue in the rabbit, P-450 LM3c. To investigate the structure and regulation of HLp, we used a monoclonal antibody that recognizes purified HLp to screen a human liver cDNA library in lambda gt11. We isolated and sequenced two overlapping cDNA clones that span the entire 2011 bases of an mRNA that codes for a protein of 504 amino acids. The predicted amino-terminal amino acid sequence of this protein is identical to the first 20 residues determined from purified HLp. HLp mRNA shares more than 70% sequence homology with related proteins from the rat and rabbit but less than 40% homology with other published cytochrome P-450 genes. Moreover, Southern blot analysis of human and rat genomic DNA revealed 50 and 60 kilobases of DNA, respectively, hybridizable to the HLp cDNAs. Blot analysis of human liver RNA from five patients revealed major (2.2 kilobase) and minor (3.0 kilobase) bands that hybridized to HLp cDNAs. The apparent concentration of these hybridizable mRNAs as well as the amounts of immunoreactive HLp protein in microsomes from the same liver were increased in a dose-dependent relationship in three patients who received dexamethasone, a potent glucocorticoid. Furthermore, in samples of RNA and of microsomes isolated from cultures of a human hepatoma cell line (Hep G2) incubated for 120 hr in medium containing dexamethasone, there was a 6-fold induction of the two mRNA species hybridizable to HLp cDNAs and a 3-fold induction of immunoreactive HLp protein as compared to the values for cultures incubated in steroid-free medium. We conclude that HLp is a human representative of a conserved glucocorticoid-inducible cytochrome P-450 gene family whose mechanism of induction involves accumulation of HLp mRNA.

145 citations


Journal ArticleDOI
TL;DR: Oleic acid inhibited C26:0 synthesis in ALD fibroblasts by 58% and total fatty acid synthesis by 68 to 78% and inhibition of saturated VLFA synthesis by oleate may be useful in treating ALD.
Abstract: Monounsaturated fatty acids, especially oleic acid (C18:1), decreased the content of saturated very-long-chain fatty acids (VLFA) in cultured skin fibroblasts from patients with adrenoleukodystrophy (ALD) and controls. When confluent ALD fibroblasts were incubated with oleic acid for 5 days in lipid-free medium, which eliminates uptake of exogenous VLFA, the mean cell content of C26:0 was decreased by 33.7 +/- 10.1%. Oleic acid inhibited C26:0 synthesis in ALD fibroblasts by 58% and total fatty acid synthesis by 68 to 78%. Therefore, the elevated C26:0 levels in ALD cells may be lowered by inhibiting fatty acid biosynthesis, and inhibition of saturated VLFA synthesis by oleate may be useful in treating ALD.

138 citations


Journal ArticleDOI
TL;DR: The effects of two levels of fluid-percussion brain injury on cerebral blood flow (CBF) and pial arteriolar diameter were investigated in cats and changes in the diameter of pialarterioles were significantly correlated with posttraumatic changes in CBF.
Abstract: ✓ The effects of two levels of fluid-percussion brain injury on cerebral blood flow (CBF) and pial arteriolar diameter were investigated in cats. Regional CBF was measured using the radioactive microsphere technique. Experimental brain injury resulted in changes in arterial blood pressure, CBF, and pial arteriolar diameter that were related to the severity of the injury. Low-level injury (1.88 ± 0.11 atm, mean ± standard error of the mean) resulted in a slight transient increase in CBF which had returned to preinjury levels by 30 minutes. High-level injury (2.68 ± 0.19 atm) resulted in larger, statistically significant (p < 0.01) increases in whole-brain CBF, decreases in cerebrovascular resistance, and increases in pial arteriolar diameter 1 minute postinjury. One hour after injury, CBF had returned to preinjury levels while cerebral perfusion pressure was significantly (p < 0.01) reduced. There was no evidence of reduced CBF in any region studied. Pial arterioles dilated during the posttraumatic hyperte...

138 citations


Journal ArticleDOI
01 Jan 1986-Stroke
TL;DR: The results show that viscosity changes must result in compensatory readjustments of vessel diameter, but that these adjustments do not occur where autoregulation to pressure changes is known to be defective.
Abstract: There is still considerable controversy regarding the influence of blood viscosity upon CBF. We have measured CBF with microspheres in 23 cats. Autoregulation was disturbed in the left caudate nucleus by microsurgical occlusion of the left middle cerebral artery. Induced hypertension or hypotension was used and i.v. mannitol (1 g/kg) administered. In all cats blood viscosity decreased an average of 16% at 15 minutes and, in 16 cats, increased 10% at 75 minutes post-mannitol. CBF in the right caudate was 79 +/- 6 ml/100g/min, in the left 38 +/- 6 (p less than 0.001). Only minor changes of CBF occurred in areas with presumed normal autoregulation, including the right caudate, in conjunction with pressure or viscosity changes. In the left caudate CBF decreased 21% with hypotension and 18% with higher viscosity, more than on the right (p less than 0.01 and p less than 0.2, respectively). CBF increased in the left caudate 56% with hypertension and 47% with lower viscosity, again much more than on the right (p less than 0.001 and p less than 0.01, respectively). In the other area which is (nearly) exclusively supplied by the middle cerebral artery of the cat, i.e., the ectosylvian cortex, results were similar to those in the caudate nucleus. These results show that viscosity changes must result in compensatory readjustments of vessel diameter, but that these adjustments do not occur where autoregulation to pressure changes is known to be defective. The adjustments to viscosity changes might be called blood viscosity autoregulation of CBF. We hypothesize that pressure autoregulation and blood viscosity autoregulation share the same mechanism.

Journal ArticleDOI
TL;DR: Analysis of 50 mother-child dyads, including children from 4 to 10 years of age, revealed that the behaviors emitted by mother and child are likely to influence the child's ability to tolerate the medical experience.
Abstract: Maternal influences on children's fear and coping behaviors during a medical examination were studied in a pediatric outpatient clinic using the Dyadic Prestressor Interaction Scale (DPIS) to measure anticipatory reactions just prior to contact with the physician. Analysis of 50 mother-child dyads, including children from 4 to 10 years of age, revealed that the behaviors emitted by mother and child are likely to influence the child's ability to tolerate the medical experience. Maternal use of distraction and low rates of ignoring were associated with lower child distress and increased prosocial behaviors. Children's active exploration of the situation was more likely to occur when mothers provided their children with information, and was less likely when mothers reassured their children. Maternal reassurance of children and overt maternal agitation were associated with more maladaptive child responses. Age trends were also found in interactive patterns. Younger children were more likely to receive reassurance from mothers when they showed attachment. There was a stronger association between mother's information giving and child's exploring for children under 5 years, 9 months of age. Results supported the usefulness of the DPIS for investigation of child management techniques in this situation. Theoretical extension to attachment and stranger-approach situations was made. Suggestions for future studies to clarify the reciprocity of interactions or to determine causal direction between mother and child behaviors, as well as to evaluate the specificity or generality of these findings, were provided.

Journal ArticleDOI
TL;DR: In this article, the concept of a shape index derived from the molecular graph was expanded to include two additional indexes derived from counts of one-path and three-path fragments, leading to shape indexes of 1K and 3K.
Abstract: The concept of a shape index derived from the molecular graph previously described, has been expanded to include two additional indexes derived from counts of one-path and three-path fragments. Algorithms have been derived using the original model of defining two limiting structures and quantitating any intermediate structural shape relative to these two. Counts of one-path fragments and three-path fragments lead to shape indexes of 1K and 3K. The information encoded in each has been extracted in terms of shape attributes. The concept that molecular shape can be viewed as a sum of isolated attributes is put forward and a partial series is presented based on the indexes developed to date. Several examples of QSAR applications are presented where two of these shape indexes are revealed to encode enough information to give good correlations.


Journal Article
TL;DR: It is concluded that, in man, there is a cytochrome P-450 family composed of two isozymes that are immunochemically and structurally related to the 3-methylcholanthrene-inducible family observed in several other species.
Abstract: The rat 3-methylcholanthrene-inducible family of liver cytochromes P-450 contains two proteins (P-450c and P-450d) that are immunochemically related, possess 68% total sequence homology, and are induced by a number of toxic or carcinogenic compounds. To determine whether equivalent isozymes of hepatic cytochrome P-450 are expressed in humans, as they are in several mammalian species, we performed immunoblot analyses on microsomes prepared from 14 human liver specimens and found that each one contained a 52.5-kDa protein (termed HLd) that reacted with antibodies specific for rat P-450d. In addition, one specimen contained a 54-kDa protein (termed HLc) that reacted with antibodies specific for rat P-450c. HLd was purified through the use of immunoaffinity chromatography and was found to be 56% homologous to rat P-450d and 61% homologous to the equivalent isozyme in the rabbit (P-450 LM4) through their first 18 NH2-terminal amino acids. Finally, levels of immunoreactive HLd varied more than 10-fold among these patients but were unrelated to the patients' drug treatments, smoking habits, or amount of immunoreactive HLp, a human liver cytochrome P-450 related to the glucocorticoid-inducible family of rat cytochromes P-450. We conclude that, in man, there is a cytochrome P-450 family composed of two isozymes (HLc and HLd) that are immunochemically and structurally related to the 3-methylcholanthrene-inducible family observed in several other species.

Journal ArticleDOI
TL;DR: Results indicate a significant but small tendency for older adults to underrate low and overrate higher intensity contact heat compared with younger adults, and similarities in pain perception were stronger than differences among the age groups.
Abstract: The effect of age on pain sensitivity is unclear. Some studies suggest a loss of pain perception with age, whereas other studies indicate either no change or an increase in pain sensitivity with age. The present study assessed perceived intensities of six levels of painful contact thermal stimuli (43 degrees C, 45 degrees C, 47 degrees C, 48 degrees C, 49 degrees C, and 51 degrees C). Magnitude estimation procedures were used, and participants were instructed to provide separate ratings for the perceived sensory intensity and the perceived unpleasantness (affective intensity) of the thermal stimuli during separate sessions. Middle-age adults showed the lowest sensory sensitivity and greatest affective pain ratings. Although results indicate a significant but small tendency for older adults to underrate low and overrate higher intensity contact heat compared with younger adults, similarities in pain perception were stronger than differences among the age groups.

Journal ArticleDOI
TL;DR: It is concluded that this four-item decision rule derived at the Medical College of Virginia, Richmond, transported well to a different patient population and would have been useful in identifying patients with pharyngitis who had a high likelihood of throat cultures positive for group A streptococci.
Abstract: Use of existing decision rules could improve management of streptococcal pharyngitis, but the validity of such rules outside their original patient population is not known. We applied a four-item decision rule derived at the Medical College of Virginia, Richmond, to 516 patients at the University of Nebraska, Omaha, to test how accurately it would predict outcome of throat culture. After correction for differences in the prevalence of a positive culture (17% in Virginia, 26% in Nebraska), the rule closely predicted the frequency of positive cultures in five subgroups based on the presence of clinical findings. We conclude that this rule transported well to a different patient population and would have been useful in identifying patients with pharyngitis who had a high likelihood of throat cultures positive for group A streptococci.


Journal ArticleDOI
TL;DR: In this article, the size differences among heteroatoms and carbon atoms in different valence states are taken into account in the 2Kα shape index, which is calculated as a function of non-hydrogen atom count.
Abstract: The molecular shape index, previously described, has been extended to take into account the size differences among heteroatoms and carbon atoms in different valence states. In the algorithm for the shape index, 2K, calculated as a function of the non-hydrogen atom count, the count value of non-C sp3 atoms is modified by a term α. The value of α is derived from the covalent radius of an atom relative to the radius of C sp3. Several examples of the use of the atom-specified shape index, 2Kα, in biological studies are presented.

Journal ArticleDOI
TL;DR: The effects of Ca2+ ion on the structure of thrombin-derived and reptilase-derived fibrin gels formed at various ionic strengths were studied turbidimetrically.
Abstract: The effects of Ca2+ ion on the structure of thrombin-derived and reptilase-derived fibrin gels formed at various ionic strengths were studied turbidimetrically. For both enzymes clotting times were shorter, final gel turbidities were higher and fibre mass/length ratios were increased as the ionic strength was lowered. The addition of 5 mM-Ca2+ augmented each of these effects for any given ionic strength. In the thrombin system, Ca2+ increased the final gel turbidity from 0.04 to 0.26 A632.8 at ionic strength 0.15. Under identical conditions in the reptilase system, the final gel turbidity increased from 0.03 A632.8 in the absence of Ca2+ to 0.345 A632.8 in the presence of 5 mM-Ca2+. In the thrombin system, fibre mass/length ratios increased from 0.4 X 10(12) to 6.9 X 10(12) Da/cm in the absence of Ca2+, and from 4.4 X 10(12) to 7.9 X 10(12) Da/cm in the presence of Ca2+, as the ionic strengths were decreased from 0.15 to 0.08 and to 0.11 respectively. In the reptilase system, the mass/length ratios increased from 0.9 X 10(12) to 5.8 X 10(12) Da/cm in the absence of Ca2+, and from 4.8 X 10(12) to 8.7 X 10(12) Da/cm in the presence of Ca2+, as the ionic strengths were decreased from 0.15 to 0.08 and to 0.10 respectively. At ionic strengths below 0.10, the presence of 5 mM-Ca2+ caused precipitation and macroscopic aggregation of fibrinogen upon the addition of either enzyme. In the presence of 5 mM-Ca2+, the fibres composing thrombin-induced and reptilase-induced gels were virtually identical.

Journal ArticleDOI
TL;DR: No relationship was found between life stress and injury, indicating that previous findings for football players were not duplicated for intercollegiate volleyball players.
Abstract: The present study examined whether male and female National Collegiate Athletic Association (NCAA) Division I intercollegiate volleyball players with high life stress would be at greater risk for the occurrence of injury. Life stress was measured with the Social and Athletic Readjustment Rating Scale (SARRS) and the Athletic Life Experiences Survey (ALES). Regardless of how the data were analyzed (injured v noninjured, high stress v low stress, severity of injury), no relationship was found between life stress and injury, indicating that previous findings for football players were not duplicated for intercollegiate volleyball players. Also, different levels of coping resources among volleyball players did not mediate the life stress to injury rate but did differentiate injured from noninjured players.

Journal ArticleDOI
TL;DR: An empirical analysis of the diffusion patterns of five surgical procedures shows innovation tends to be more likely to occur in markets in which the more generous payers predominate, and the marginal effects of payer mix are small compared to effects of location and hospital characteristics, such as size and teaching status.

Journal ArticleDOI
TL;DR: The observation that TCDD could directly suppress the antibody response by spleen cells from DBA/2 mice, at concentrations comparable to those required to suppress the B6C3F1 mice, suggested that the effect on the B-lymphocyte was atypical of the profile of activity (i.e., dependence on the Ah locus) previously reported to characterize the effects of dioxin in other systems.

Journal ArticleDOI
TL;DR: In this paper, the authors investigate whether using learning contracts in higher education enhances adults' readiness and competencies for self-directed learning and find that the use of learning contracts has little impact on developing readiness for selfdirectedness, but does have some impact on learning competencies.
Abstract: The purpose of this study was to investigate whether using learning contracts in higher education enhances adults' readiness and competencies for self-directed learning. One hundred and sixty-three students from six universities, enrolled in graduate courses in adult education where learning contracts were employed, were given pre and posttests to measure any significant gain in their competencies and readiness for self-directed learning. Findings suggest that the use of learning contracts has little impact on developing readiness for self-directedness, but does have some impact on developing competencies for self-directed learning.


Journal ArticleDOI
TL;DR: It was suggested that stress management procedures involving teaching of problem-focused coping strategies and provision of social support would be most effective for this population of severe cases of genital herpes infection.

Journal ArticleDOI
TL;DR: Diminished interferon titers occurred in HSV-2- Infected animals treated with Δ9-THC in doses exceeding 15 mg/kg when compared to virus-infected animals given the diluent.
Abstract: This study was undertaken to determine the effect of delta 9-tetrahydrocannabinol (delta 9-THC) on polyinosinic:polycytidylic acid [poly(I):poly(C)]-induced, and on herpes simplex virus type 2 (HSV-2)-induced, alpha/beta interferon in the B6C3F1 mouse. Animals were administered delta 9-THC, or the diluent, intraperitoneally for 4 consecutive days or at various time intervals prior to administration of the interferon inducer. Poly(I):poly(C) or HSV-2 was injected intravenously on Day 4. Animals receiving poly(I):poly(C) and treated with delta 9-THC at doses ranging from 5 to 100 mg/kg exhibited significantly lower titers of interferon than mice given poly(I):poly(C) and the diluent. Diminished interferon titers occurred in HSV-2-infected animals treated with delta 9-THC in doses exceeding 15 mg/kg when compared to virus-infected animals given the diluent. This suppression of early interferon persisted through 24 hr.

Journal ArticleDOI
TL;DR: In this article, posttraumatic creatine kinase-BB isoenzyme (CKBB) activity and lactate concentration in ventricular cerebrospinal fluid (CSF) have been studied in 29 patients with severe head injuries.
Abstract: ✓ The posttraumatic creatine kinase-BB isoenzyme (CKBB) activity and lactate concentration in ventricular cerebrospinal fluid (CSF) have been studied in 29 patients with severe head injuries. The CKBB activity reaches its maximum a few hours after trauma, and has a monoexponential drop with a half-time of approximately 10 hours. Ventricular CSF lactate concentration continues to rise in patients with a poor outcome, and decreases only slowly and inconsistently in most of the other patients. Thus, increase of lactate in the ventricular CSF is not, like CKBB, a direct one-stage consequence of the trauma but is due to continuous production from a derangement of metabolism caused by the trauma. Since even higher ventricular CSF lactate levels can be survived when not caused by head injury, and since no significant pH changes were related to the ventricular CSF lactic acidosis in these artificially ventilated patients, it is concluded that ventricular CSF lactic acidosis is indicative of a severe, although not...


Journal ArticleDOI
TL;DR: In this article, a comparison of rapists' attitudes toward women, violence and rape with that of other felons reveals that their rape relevant attitudes are more extreme than those of other criminals.
Abstract: Literature in the area of rape has been dominated by the psychiatric perspective leading to the view of rape as an individualistic, ideosyncratic and psychopathological problem. This leads to a conception of the rapist as a special criminal who is somehow different from his fellow prisoners. This paper proposes to study rapists as emotionally average men who have been socialized to view aggressive sexual behavior as appropriate in various situations. A comparison of rapists’ attitudes toward women, violence and rape with that of other felons reveals that their rape relevant attitudes are more extreme. It is proposed that the prevailing rape myths that exist in the society at large serve the function of providing excuses and justifications for rapists.