Showing papers by "Virginia Commonwealth University published in 1985"

Identification of an inducible form of cytochrome P-450 in human liver

Abstract: It has not yet been determined whether human liver contains inducible cytochromes P-450 similar to those that catalyze the oxidative metabolism of foreign substances in animals. We carried out immunoblot analyses of liver microsomes isolated from eight patients and found that each contained a cytochrome P-450, termed HLp, that reacted with antibodies directed against P-450p, a rat liver cytochrome that is inducible by the anti-glucocorticoid pregnenolone-16 alpha-carbonitrile, by glucocorticoids, by anti-seizure drugs, and by such macrolide antibiotics as triacetyloleandomycin. In the two patients who received dexamethasone and anti-seizure medications and in the one patient who was given triacetyloleandomycin, the concentrations of immunoreactive HLp and the ability to demethylate erythromycin and/or to convert triacetyloleandomycin to a metabolite that forms a spectral complex with cytochrome P-450 heme (catalytic properties unique to P-450p in rat liver) were significantly higher as compared to the values for patients who received no inducing drugs. We purified HLp to homogeneity and found that it was immunochemically related to P-450p and to its homologue in the rabbit (LM3c), actively demethylated erythromycin in a reconstituted system, exhibited electrophoretic mobility identical to that of P-450p, and shared 57% homology in its NH2-terminal amino acid sequence with that of a pregnenolone-16 alpha-carbonitrile-inducible rat cytochrome P-450. We conclude that HLp is a human representative of the multigene family of the glucocorticoid-inducible cytochromes P-450.

Identification of the cytochrome P-450 induced by macrolide antibiotics in rat liver as the glucocorticoid responsive cytochrome P-450p

Abstract: We administered triacetyloleandomycin (TAO) to rats and found that this macrolide antibiotic is the most efficacious inducer of liver microsomal cytochrome P-450 (P-450) examined to date. Liver microsomes prepared from TAO-treated rats contained greater than 5.0 nmol of P-450/mg of protein and a single induced protein as judged by analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This protein comigrated with P-450p, the major form of P-450 induced in liver microsomes of rats treated with pregnenolone-16 alpha-carbonitrile (PCN) or dexamethasone (DEX). On immunoblots of such gels developed with antibodies to P-450p, the TAO-induced protein reacted strongly as a single band. There was strict parallelism between the amount of immunoreactive P-450p in liver microsomes prepared from untreated rats or from rats treated with phenobarbital, TAO, DEX, or PCN, the ability of these microsomes to catalyze conversion of TAO to a metabolite which forms a spectral complex, and the ethylmorphine and erythromycin demethylase activities. Antibodies to P-450p specifically blocked microsomal TAO metabolite complex formation and ethylmorphine and erythromycin demethylase activities. Moreover, anti-P-450p antibodies completely immunoprecipitated solubilized TAO metabolite complexes prepared by detergent treatment of liver microsomes obtained from TAO-treated rats. Finally, we found that the major form of P-450 isolated from liver microsomes of TAO-treated rats and purified to homogeneity was indistinguishable from purified P-450p as judged by molecular weights, spectral characteristics, enzymatic activities, ability to bind TAO, peptide maps, and amino-terminal amino acid sequences. We concluded that, in addition to glucocorticoids, macrolide antibiotics are specific inducers of P-450p.

Superoxide generation and reversal of acetylcholine-induced cerebral arteriolar dilation after acute hypertension.

Abstract: The appearance of superoxide anion radical in cerebral extracellular space during and after acute hypertension induced by intravenous norepinephrine was investigated in anesthetized cats equipped with cranial windows. Superoxide was detected by demonstrating the presence of superoxide dismutase-inhibitable reduction of nitroblue tetrazolium. The superoxide dismutase-inhibitable rate of reduction of nitroblue tetrazolium was 4.1 +/- 1.61 nM/min per cm2 during hypertension and 4.55 +/- 0.62 nM/min per cm2 one hour after hypertension had subsided. During norepinephrine administration in the absence of hypertension, the superoxide dismutase-inhibitable rate of reduction of nitroblue tetrazolium was 0.44 +/- 0.17 nM/min per cm2. The reduction of nitroblue tetrazolium during hypertension was also inhibited by prior treatment of the brain surface with phenylglyoxal at pH 10, to induce irreversible inhibition of the anion channel. The results show that acute hypertension is associated with the generation of superoxide which enters the extracellular space of the brain via the anion channel. Following hypertension, the sustained vasodilation caused by acute hypertension was inhibited significantly by topical application of superoxide dismutase and catalase, showing that it was due in part to superoxide and other radicals derived from it. The vasodilator response of cerebral arterioles to topical acetylcholine was converted to vasoconstriction following acute hypertension, and restored to vasodilation following topical application of superoxide dismutase and catalase. The results show that superoxide and other radicals generated after acute hypertension interfere with acetylcholine-induced endothelium-dependent vasodilation, probably because they destroy the endothelium-derived relaxant factor.

A Shape Index from Molecular Graphs

Abstract: A numerical index of molecular shape has been derived from the graph of the non-hydrogen molecular skeleton. The index is based on the count of 2-bond fragments in a graph relative to the maximum number possible in the isomeric star graph and the minimum number in the isomeric linear graph. In this initial study all non-hydrogen atoms and all bonds are considered equal. The 2κ index describes the molecular shape in relationship to the star and linear graph and is normalized to the number of atoms. Applications are presented for shape similarity estimation, cavity filling ability and QSAR analyses.

“Riding the Bull at Gilley's”: Convicted Rapists Describe the Rewards of Rape

Abstract: In this paper we argue that the popular image of rape, a nonutilitarian act committed by a few "sick" men, is too limited a view of sexual violence because it excludes culture and social structure as pre-disposing factors. Our data come from interviews with 114 convicted, incarcerated rapists. Looking at rape from the perspective of rapists, we attempt to discover the function of sexual violence in their lives; what their behavior gained for them in a society seeming prone to rape. Our analysis reveals that a number of rapists used sexual violence as a method of revenge and/or punishment while others used it as a means of gaining access to unwilling or unavailable women. In some cases, rape was just a bonus added to burglary or robbery. Rape was also a recreational activity and described as an "adventure" and an "exciting" form of impersonal sex which gained the offender power over his victim(s).

Demonstration in multiple species of inducible hepatic cytochromes P-450 and their mRNAs related to the glucocorticoid-inducible cytochrome P-450 of the rat.

Abstract: We have recently demonstrated that P-450p, a form of rat liver cytochrome P-450 inducible by steroids such as dexamethasone and pregnenolone-16 alpha-carbonitrile, by the macrolide antibiotic triacetyloleandomycin, and by phenobarbital, is immunochemically related to and shares 73% NH2-terminal amino acid sequence homology with rabbit cytochrome LM3c. Extending this interspecies comparison we now report that liver microsomes prepared from the rabbit, hamster, gerbil, and mouse contain inducible cytochromes P-450 that resemble P-450p in: (a) converting triacetyloleandomycin to a metabolite that forms a distinct spectral complex with cytochrome P-450 heme, (b) catalyzing the demethylation of erythromycin, and (c) reacting on immunoblots with antibodies directed against P-450p or LM3c. These three characteristics changed in parallel within treatment groups of a given species receiving different inducers of cytochrome P-450. However, there were striking qualitative and quantitative interspecies differences in the responses to inducers. For example, rifampicin was the most efficacious inducer of LM3c in the rabbit and yet was not at all an inducer of P-450p in the rat whereas pregnenolone-16 alpha-carbonitrile, an inducer in the rat, failed to induce LM3c in the rabbit. Immunoblot analysis of these microsomes revealed in each species except the rabbit a single immunochemically related protein. A second immunoreactive protein was present in microsomes from male and female and rifampicin- and dexamethasone-treated female rabbits. Two cloned cDNAs, which hybridized to a species of liver mRNA directing the synthesis of P-450p in a cell-free translation system, were used to probe Northern blots of liver RNAs. These revealed a single band of hybridizable mRNA in each species (except RNA from the rabbit which gave no signal even under conditions of reduced stringency) that was induced in qualitative proportions to that of the accumulated immunoreactive protein. We conclude that P-450p appears to be conserved in evolution and is represented in each of the species tested by one or more immunochemically related proteins which exhibit similar catalytic activities to those of P-450p.

Validity Estimates for the Career Decision-Making Self-Efficacy Scale.

Abstract: The results of concurrent and discriminant validity studies only partially supported the construct validity of the Career Decision-Making Self-Efficacy Scale, and the use of individual subscales pr...

Multi-Project Scheduling: Analysis of Project Performance

Abstract: Application of heuristic solution procedures to the resource-constrained, multi-project scheduling problem is analyzed under equal and unequal penalties. The performance of ten scheduling rules is categorized with respect to four project summary measures, namely, resource-constrainedness, location of the peak requirements, and problem size. It is shown that the choice of a scheduling rule can be based upon the resource-constrainedness, problem size, and penalty. These results are based on scheduling, in detail, over 3000 multi-project scheduling problems, each containing three projects and from 24 to 66 activities.

Linking Teacher and Student Learning Styles with Student Achievement and Attitudes.

Abstract: The authors present an innovative model for economic education research on teaching methods at the university level. The results suggest that student achievement and attitudes toward economics might be improved by a better match between the teaching style of instructors and the learning style of students.

Individual Differences in Information Integration During Moral Judgment

Abstract: An ethical ideologies model based on relativism and idealism was tested. Subjects judged the morality of an individual who produced a mildly or extremely positive or negative consequence by conforming to or violating a common moral norm. As predicted, an averaging model with differential weights accounted for situationists' (high relativism and idealism) and absolutists' (low relativism and high idealism) judgments; conformity to norms was discounted when the consequence was extremely negative or positive. In contrast, subjectivists' (high relativism and low idealism) judgments conformed to an averaging model; a mildly positive consequence lowered moral judgments of conforming actions. whereas a mildly negative consequence tended to raise moral judgments of nonconforming actions. Last, exceptionists' (low relativism and idealism) judgments were influenced equally by conformity and consequence. These individuals generally combined data in a strictly linear, additive fashion; the more positive the consequence or the greater the conformity of the action to a moral norm, thc more positive the moral judgment.

Physics of small metal clusters: Topology, magnetism, and electronic structure.

Abstract: The electronic structure of small clusters of lithium atoms has been calculated using the self-consistent-field, molecular-orbital method. The exchange interaction is treated at the unrestricted Hartree-Fock level whereas the correlation is treated perturbatively up to second order by including pair excitations. This is done in two steps, one involving only the valence electrons and the other including all the electrons. A configuration-interaction calculation has also been done with all possible pair excitations. The equilibrium geometries of both the neutral and ionized clusters have been obtained by starting from random configurations and using the Hellmann-Feynman forces to follow the path of steepest descent to a minimum of the energy surface. The clusters of Li atoms each containing one to five atoms are found to be planar. The equilibrium geometry of a cluster is found to be intimately related to its electronic structure. The preferred spin configuration of a cluster has been found by minimizing the total energy of the cluster with respect to various spin assignments. The planar clusters are found to be less magnetic than expected by Hund's-rule coupling. For three-dimensional clusters, however, the magnetism is governed by Hund's rule. The effect of correlation has been found to have decisive influence on the equilibrium topology and magnetism of the clusters. The binding energy per atom, the energy of dissociation, and the ionization potential of the clusters are compared with experiment and with previous calculations. The physical origin of the magic numbers and the effect of the basis functions on the calculated properties have also been investigated.

Menarcheal status and parent-child relations in families of seventh-grade girls.

Abstract: The associations between menarcheal status and several child-rearing and outcome variables were examined for mother-daughter and father-daughter dyads. All variables were assessed with questionnaires as an extension of earlier observational studies. Analyses were conducted via multiple regression analyses wherein menarcheal status was treated as a continuous variable and was entered into the regression equation as a set of power polynomial terms. The results indicated that most of the significant relations occurred for the mother-daughter dyad, and most of these relations were curvilinear. When menarche occurs at or around the modal time, changes in parent-child relations may be best thought of as temporary perturbations, but when menarche occurs early the effects may persist.

A Supported Work Approach to Competitive Employment of Individuals with Moderate and Severe Handicaps

Abstract: This article describes the key features of a supported work approach to providing vocational placement and support to persons with moderate and severe handicaps in competitive employment settings. This approach is based on an ongoing longitudinal study of persons with mental retardation who are competitively employed through the Rehabilitation Research and Training Center at Virginia Commonwealth University. The importance of competitive employment is emphasized and the four major components of the supported work approach (job placement, job-site training, ongoing monitoring, and follow-up) are outlined in detail. Specific proposals are made for integrating a supported work approach into community-based adult services and secondary special education programs.

Regional brain metabolite levels following mild experimental head injury in the cat

Abstract: ✓ Glucose, adenosine triphosphate, phosphocreatine, and lactate levels in the cortex, striatum, diencephalon, hippocampus, cerebellum, and brain stem were measured in cats 1 hour after they were subjected to low-level (2 atm) fluid-percussion injury. Following injury, there was a mild but significant increase in lactate levels in the majority of regions studied. The hippocampus exhibited the highest percentage increase in lactate (fourfold). The cortical area directly under the trauma device showed a threefold lactate increase, while there was a twofold increase in other brain regions studied. Although there were consistent decreases in phosphocreatine levels, these decreases were significant only in the hippocampus (p < 0.05). Glucose levels in all brain regions studied were no different from control levels at the time of study. The unchanged glucose levels, together with previous studies of identically injured cats showing that cerebral blood flow was unimpaired, suggest that excess lactate was not a co...

The Beavers‐Timberlawn Model of Family Competence and the Circumplex Model of Family Adaptability and Cohesion: Separate, but Equal?

Abstract: An empirical examination of the association between instruments measuring the Beavers-Timberlawn Model of family competence and the Circumplex Model of adaptability and cohesion is presented. Even when triangulated measures were utilized to control for the divergent methods of data collection traditionally employed to operationalize these models of family health, family competence as measured by the Beavers-Timberlawn Family Evaluation Scales was either minimally (mothers) or not associated at all (fathers and children) with balanced and thereby optimal dimensions of adaptability and cohesion as measured by the Family Adaptability and Cohesion Evaluation Scales. Methodological and substantive explanations for the surprising lack of association between measures of these two prominent family assessment models are explored and short- and long-range implications for the growth and practice of family therapy are discussed.

Free-floating Iliofemoral Thrombus: A Risk of Pulmonary Embolism

Abstract: • We retrospectively evaluated the risk of pulmonary embolism in hospitalized patients with venographically proved iliofemoral deep vein thrombosis (DVT). Venograms and clinical records of 78 patients with iliofemoral DVT were reviewed and the proximal intraluminal thrombus was characterized as free-floating (>5-cm nonadherent segment) or occlusive (no free-floating elements). The incidence of pulmonary embolism confirmed by high-probability radioisotope ventilation-perfusion lung scanning within ten days following venography was 9% (7/78) and was associated with 60% (3/5) free-floating and 5.5% (4/73) occlusive phlebographic criteria (P .05). Patients with iliofemoral DVT that met free-floating criteria are at significant risk for pulmonary embolism, despite the administration of heparin. (Arch Surg1985;120:806-808)

Clinical findings in four children with biotinidase deficiency detected through a statewide neonatal screening program.

Abstract: Four children with biotinidase deficiency were identified during the first year of a neonatal screening program for this disease in the Commonwealth of Virginia. Two unrelated probands were identified among the 81,243 newborn infants who were screened. In addition, two siblings of one of these infants were found to be affected. Both probands had mild neurologic symptoms at two and four months, respectively, and the two older children had more severe neurologic abnormalities, cutaneous findings, and developmental delay at two and three years of age. However, none of the affected children had acute metabolic decompensation. Previous studies have shown that the administration of biotin to affected children can be a lifesaving procedure that can reverse acute symptoms and prevent irreversible neurologic damage. Our findings demonstrate that subtle neurologic abnormalities may appear as early as at two months of age and that developmental abnormalities may occur even in the absence of episodes of overt metabolic decompensation. Since screening and treatment are both inexpensive and effective and the incidence of the disease is well within the range of that of other metabolic diseases for which screening is performed, biotinidase deficiency should be added to the group of metabolic diseases for which screening is done in the neonatal period.

Pubertal Status and Parent-Child Relations in Families of Seventh-Grade Boys

Abstract: Associations between global ratings of pubertal status and several child-rearing and outcome variables were examined for mother-son and father-son dyads. All variables were assessed with questionnaires in an attempt to confirm and demonstrate the robustness across methods of earlier observational studies. In anticipation of curvilinear effects, multiple regression analyses, wherein pubertal status is treated as a continuous variable and is entered into the regression equations as a set of power polynomial terms, were employed. Significant relations between pubertal status and outcome variables were found for the mother-son (but not for the father-son) dyad and most relations were quadratic. These results are similar to those of earlier observational studies in that temporary perturbations occur in mother-son relations at or near the peak of pubertal growth. No statistically significant effects of socioeconomic status upon relations between pubertal status and the family interaction variables were found.

Infant auditory perception: Tonal masking

Abstract: The results of an earlier study ( Olsho, 1984 ) indicated that 5- to 8-month-old infants were relatively better at discriminating among high-frequency pitches than low. In the present study, sensory and nonsensory explanations for that effect were evaluated by examining infants' performance in a task requiring similar sensory processing but differing in the demands placed on processes such as memory. Infants' ability to resolve frequency was tested using a tonal masking paradigm, the psychophysical tuning curve. Twenty-four infants were tested at probe frequencies ranging from 500 to 4000 Hz; a group of young adults served as a comparison. Masked and unmasked thresholds were estimated using the visually reinforced head turn procedure in conjunction with an adaptive psychophysical method. Although infants' tuning curves fell below those of adults (indicating poorer performance), the widths and slopes of the infants' curves were not different from the adults'. Moreover, the difference between age groups remained constant across probe frequencies. These findings imply that by 5 months of age, the infant's ability to resolve sound frequency is similar to the adult's.

Transition from School to Work for Individuals with Severe Handicaps: A Follow-Up Study.

Abstract: The present study assessed the employment status of 117 transition age young adults with moderate, severe, or profound mental retardation in Virginia. Data were collected by trained interviewers on variables related to employment level, wages earned, types of jobs, assistance available in job identification, and so forth. The findings of this study indicated high unemployment rates of almost 88%, with only 14 of the 117 persons holding competitive jobs in nonsheltered work environments. Wage accumulation was very limited. Implications of these results and other similar studies for future programming are then discussed.

Student Satisfaction with Field Placement

Abstract: Students' perceptions of their field placements rarely are taken into account in the literature on field practicum and supervision. This survey of MSW students at a southern university examines factors associated with student satisfaction with field agency, field instructor, and field learning. The survey covers student and agency characteristics, learning goals and structure, supervision, and school-agency linkages. Students associated the quality of supervision and relevance of learning most highly with satisfaction in their placement experiences. Being treated as a professional in the agency, school-agency linkages, student characteristics, and amount of time engaged in specific social work activities were found not to be major factors in student satisfaction with field work.

The relationship of anxiety to childhood depression.

Abstract: In order to investigate the relationship between anxiety and depression in emotionally disturbed children, 30 hospitalized inpatient children were individually administered the Children's Depression Inventory (CDI), the Children's Manifest Anxiety Scale-Revised (CMAS-R), and the State-Trait Anxiety Inventory for Children (STAIC). Results indicated a significant relationship between CDI scores, the CMAS-R and its factors, and the STAIC. Correlations between the various factors of anxiety and depression suggest a complex relationship between the two constructs. Stepwise regression analyses indicated further the complexity of this relationship. Results were discussed in terms of the possible differential role which the different anxiety factors play in depression.

Malocclusion, masticatory muscle, and temporomandibular joint tenderness

Abstract: The Angle classification of occlusion, as well as occlusal contacts determined at retrusion, mediotrusion, laterotrusion, and protrusion were recorded from 298 dental students. Various masticatory muscles and the TM joints were palpated simultaneously for tenderness. No significant relationships were observed between (1) tenderness and Angle class or (2) tenderness and any occlusal contact. In relation to a slide between retruded contact position and intercuspal position: measurements for (a) vertical and (b) horizontal displacements, but not (c) lateral deflection, were greater in Class I students without tenderness than in Class I students with tenderness.