Showing papers by "Virginia Commonwealth University published in 1991"

Survival in Patients with Primary Pulmonary Hypertension: Results from a National Prospective Registry

Abstract: Objective To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival. Design Registry with prospective follow-up. Setting Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart, Lung, and Blood Institute. Patients Patients (194) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988. Measurements At diagnosis, measurements of hemodynamic variables, pulmonary function, and gas exchange variables were taken in addition to information on demographic variables, medical history, and life-style. Patients were followed for survival at 6-month intervals. Main results The estimated median survival of these patients was 2.8 years (95% Cl, 1.9 to 3.7 years). Estimated single-year survival rates were as follows: at 1 year, 68% (Cl, 61% to 75%); at 3 years, 48% (Cl, 41% to 55%); and at 5 years, 34% (Cl, 24% to 44%). Variables associated with poor survival included a New York Heart Association (NYHA) functional class of III or IV, presence of Raynaud phenomenon, elevated mean right atrial pressure, elevated mean pulmonary artery pressure, decreased cardiac index, and decreased diffusing capacity for carbon monoxide (DLCO). Drug therapy at entry or discharge was not associated with survival duration. Conclusions Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables: mean pulmonary artery pressure, mean right atrial pressure, and cardiac index. Such an equation, once validated prospectively, could be used as an adjunct in planning treatment strategies and allocating medical resources.

Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial

Abstract: ✓ There is still controversy over whether or not patients should be hyperventilated after traumatic brain injury, and a randomized trial has never been conducted. The theoretical advantages of hyperventilation are cerebral vasoconstriction for intracranial pressure (ICP) control and reversal of brain and cerebrospinal fluid (CSF) acidosis. Possible disadvantages include cerebral vasoconstriction to such an extent that cerebral ischemia ensues, and only a short-lived effect on CSF pH with a loss of HCO3− buffer from CSF. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM), which has shown some promise in experimental and clinical use. Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation (PaCO2 35 ± 2 mm Hg (mean ± standard deviation): control group), hyperventilation (PaCO2 25 ± 2 mm Hg: HV group), or hyperventilation plus THAM (PaCO2 25 ± 2 mm Hg: HV + THAM group). Stratification into subgroups of patients with motor score...

Cerebral circulation and metabolism after severe traumatic brain injury: the elusive role of ischemia.

Abstract: Although experimental and pathological studies suggest an important role for ischemia in the majority of fatal cases of traumatic brain injury, ischemia has been a rare finding in most clinical studies of cerebral blood flow (CBF) in head-injured patients. The hypothesis of the present study was that cerebral ischemia occurs in the first few hours after injury, but that CBF measurements have not been performed early enough. Early measurements of CBF (by the 133Xe intravenous method) and arteriovenous oxygen difference (AVDO2) were obtained in 186 adult head-injured patients with a Glasgow Coma Scale score of 8 or less, and were correlated with neurological status and outcome. During the first 6 hours after injury, CBF was low (22.5 +/- 5.2 ml/100 gm/min) but increased significantly during the first 24 hours. The AVDO2 followed the opposite course; the decline of AVDO2 was most profound in patients with low motor scores, suggesting relative hyperemia after 24 hours. A significant correlation between motor score and CBF was found in the first 8 hours after injury (Spearman coefficient = 0.69, p less than 0.001), but as early as 12 hours postinjury this correlation was lost. A similar pattern was found for the relationship between CBF and outcome. Cerebral blood flow below the threshold for infarction (CBF less than or equal to 18 ml/100 gm/min) was found in one-third of the studies obtained within 6 hours, the incidence rapidly decreasing thereafter. A low CBF after 24 hours was not generally associated with a high AVDO2, and was probably a reflection of low oxidative metabolism rather than frank ischemia. In 24 patients, a CBF of 18 ml/100 gm/min or less was found at some point after injury; the mortality rate was significantly higher in this subgroup, and survivors did worse. In some cases, ischemia was successfully treated by reducing hyperventilation or inducing arterial hypertension. These results support the above hypothesis, and suggest that early ischemia after traumatic brain injury may be an important factor determining neurological outcome. Moreover, these data indicate that early hyperventilation or lowering of blood pressure to prevent brain edema may be harmful.

The genetic epidemiology of bulimia nervosa.

Abstract: OBJECTIVE The authors seek to clarify, from both an epidemiologic and genetic perspective, the major risk factors for bulimia nervosa and to understand the relationship between narrowly defined bulimia and bulimia-like syndromes. METHOD Personal structured psychiatric interviews were conducted with 2,163 female twins from a population-based register. Psychiatric disorders were assessed using DSM-III-R criteria. RESULTS Lifetime prevalence and risk for narrowly defined bulimia were 2.8% and 4.2%, respectively. Including bulimia-like syndromes increased these estimates to 5.7% and 8.0%, respectively. Risk factors for bulimia included 1) birth after 1960, 2) low paternal care, 3) a history of wide weight fluctuation, dieting, or frequent exercise, 4) a slim ideal body image, 5) low self-esteem, 6) an external locus of control, and 7) high levels of neuroticism. Significant comorbidity was found between bulimia and anorexia nervosa, alcoholism, panic disorder, generalized anxiety disorder, phobia, and major depression. Proband-wise concordance for narrowly defined bulimia was 22.9% in monozygotic and 8.7% in dizygotic twins. The best-fitting model indicated that familial aggregation was due solely to genetic factors with a heritability of liability of 55%. A multiple threshold model indicated that narrowly defined bulimia nervosa and bulimia-like syndromes represented different levels of severity on the same continuum of liability. CONCLUSIONS The liability to fully syndromal bulimia nervosa, which affects around one in 25 women at some point in their lives, is substantially influenced by both epidemiologic and genetic risk factors. The same factors that influence the risk for narrowly defined bulimia also influence the risk for less severe bulimia-like syndromes.

Marked Protection by Moderate Hypothermia after Experimental Traumatic Brain Injury

Abstract: These experiments examined the effects of moderate hypothermia on mortality and neurological deficits observed after experimental traumatic brain injury (TBI) in the rat. Brain temperature was measured continuously in all experiments by intraparenchymal probes. Brain cooling was induced by partial immersion (skin protected by a plastic barrier) in a water bath (0 degrees C) under general anesthesia (1.5% halothane/70% nitrous oxide/30% oxygen). In experiment I, we examined the effects of moderate hypothermia induced prior to injury on mortality following fluid percussion TBI. Rats were cooled to 36 degrees C (n = 16), 33 degrees C (n = 17), or 30 degrees C (n = 11) prior to injury and maintained at their target temperature for 1 h after injury. There was a significant (p less than 0.04) reduction in mortality by a brain temperature of 30 degrees C. The mortality rate at 36 degrees C was 37.5%, at 33 degrees C was 41%, and at 30 degrees C was 9.1%. In experiment II, we examined the effects of moderate hypothermia or hyperthermia initiated after TBI on long-term behavioral deficits. Rats were cooled to 36 degrees C (n = 10), 33 degrees C (n = 10), or 30 degrees C (n = 10) or warmed to 38 degrees C (n = 10) or 40 degrees C (n = 12) starting at 5 min after injury and maintained at their target temperatures for 1 h. Hypothermia-treated rats had significantly less beam-walking, beam-balance, and body weight loss deficits compared to normothermic (38 degrees C) rats. The greatest protection was observed in the 30 degrees C hypothermia group.(ABSTRACT TRUNCATED AT 250 WORDS)

Behavioral, biochemical, and molecular modeling evaluations of cannabinoid analogs.

Abstract: Numerous cannabinoids have been synthesized that are extremely potent in all of the behavioral assays conducted in our laboratory. An important feature in increasing potency has been the substitution of a dimethylheptyl (DMH) side chain for the pentyl side chain. Our previous studies have shown that (−)-11-OH-Δ8-THC-dimethylheptyl was 80–1150 times more potent than Δ9-THC. Stereospecificity was demonstrated by its (+)- enantiomer which was more than 1400–7500 times less potent. A related series of DMH cannabinoid analogs has recently been synthesized and preliminary evaluations reported here. (−)-11-OH-Δ9-THC-DMH was found to be equipotent with (−)-11-OH-Δ8-THC-DMH. The aldehyde (−)-11-oxo-Δ9-THC-DMH was 15–50 times more potent than Δ9-THC. Surprisingly, (−)-11-carboxy-Δ9-THC-DMH was also active, being slightly more potent than Δ9-THC. In the bicyclic cannabinoid series, the length and bulk of the side chain were found to be equally important. Aminoalkylindoles, which are structurally dissimilar from classical cannabinoids, have been found to exhibit a pharmacological profile similar to Δ9-THC. Though not extremely potent in vivo, they appear to represent an entirely new approach to studying the actions of the cannabinoids. The structural diversity and wide-ranging potencies of the analogs described herein provide the opportunity to develop a pharmacophore for the cannabinoids using molecular modeling techniques.

Nonenzymatic deamidation of asparaginyl and glutaminyl residues in proteins.

Abstract: Some asparagine and glutamine residues in proteins undergo deamidation to aspartate and glutamate with rates that depend upon the sequence and higher-order structure of the protein. Functional groups within the protein can catalyze this reaction, acting as general acids, bases, or stabilizers of the transition state. Information from specific proteins that deamidate and analysis of protein sequence and structure data bases suggest that asparagine and glutamine lability has been a selective pressure in the evolution of protein sequence and folding. Asparagine and glutamine deamidation can affect protein structure and function in natural and engineered mutant sequences, and may play a role in the regulation of protein folding, protein breakdown, and aging.

Validation of bioanalytical methods.

Abstract: Validation of bioanalytical methods used to generate data for pharmacokinetic and bioavailability studies is approached by a variety of techniques and is subject to many different methods of interpretation. This Review puts the various techniques into perspective and discusses pitfalls which may occur in interpretation of validation data. Recovery studies, standardization techniques, and selectivity/specificity are discussed with regard to the intrinsic value of various techniques that are used in validation. Models used for analytical calibration curves are explained in terms of their validity and limitations, along with a presentation of the most common ways to validate the model. Analytical sensitivity and detection limits are presented and discussed with regard to the usefulness of the various definitions. Appropriate means of testing precision and accuracy, the most important factors in assessing method quality, are presented. Stability and ruggedness testing are discussed along with a presentation of ways to assess data acceptability on a daily run basis.

The microflora of periodontal sites showing active destructive progression

Abstract: 20 adult periodontitis (AP) subjects were examined every 2 to 4 months and microbiological samples were collected and cultured when 2 mm or more loss of attachment (active sites) was detected by 2 examiners. Similar sites in which no progressive destruction was observed (control sites) also were sampled in the same subjects. By lambda-analysis, there was no statistically significant difference in floras of active (42 sites from 12 subjects) and control (36 sites from 12 subjects) sites or between the floras of the active and control sites and of 63 samples from 22 AP subjects that were examined previously in a cross-sectional study. By paired t test, no microbial species had a significantly greater association with active than with control sites. The only species that were detected in one or more samples from all subjects with active sites were Wolinella recta, Fusobacterium nucleatum, and Peptostreptococcus micros. Porphyromonas gingivalis and 9 other taxa were isolated from one-half or more of the persons with active sites. The composition of microbiological floras of all periodontitis samples was statistically significantly different from that of subjects with healthy gingiva. The composition of microfloras of sites in subjects with naturally-occurring gingivitis was intermediate between that of subjects with healthy gingiva and that of active and control sites in AP subjects.

Efficacy and cost effectiveness of adjuvant chemotherapy in women with node-negative breast cancer: A decision-analysis model

Abstract: Background. In 1988 the National Cancer Institute issued a Clinical Alert that has been widely interpreted as recommending that all women with node-negative breast cancer receive adjuvant chemotherapy. Acceptance of this recommendation is controversial, since many women who would not have a recurrence would be treated. Methods. Using a decision-analysis model, we studied the cost effectiveness of chemotherapy in cohorts of 45-year-old and 60-year-old women with node-negative breast cancer by calculating life expectancy as adjusted for quality of life. The analysis evaluated different scenarios of the benefit of therapy: improved disease-free survival for five years, with a lesser effect on overall survival (base line); a lifelong benefit from chemotherapy; and a benefit in disease-free survival with no change in overall survival by year 10. The base-line analysis assumed a 30 percent reduction in the relative risk of recurrence for five years after treatment. Results. For the 45-year-old woman, t...

Toward a multicultural model of the stress process.

Abstract: Stress and coping models are potentially useful frameworks for multicultural counseling and research because of their focus on the effects of social environmental factors on human functioning. This article attempts to expand a “standard” model of the stress process (Lazarus & Folkman, 1984) to include a number of culture-relevant dimensions. Cultural factors are discussed that influence each component of the stress model including (a) the types and frequency of events experienced, (b) appraisals of the stressfulness of events, (c) appraisals of available coping resources, (d) selection of coping strategies, and (e) manifestations of adaptational difficulties. Implications of the expanded model for both research and counseling practice are discussed. Los modelos de estres y la adaptacion al estres tienen la potencia para ser cuadros utiles en la consejeria e investigacion multicultural por su enfoque sobre los efectos de factores ambientales sociales en la funcion humana. Este articulo intenta extender un modelo “normal” del proceso de estres (Lazarus y Folkman, 1984) para incluir un numero de dimensiones culturalmente pertinentes. Se discuten los factores culturales que influyen en cada componente del modelo de estres, incluyendo: los tipos y la frequencia de los eventos experimentados, la apreciacion del nivel de estres de acontacimientos, la apreciacion de los recursos de adaptacion disponibles, la seleccion de estrategias de adaptacion, y las manifestaciones de dificultades de adaptacion. Se discuten las implicaiones del modelo extendido para la investigacion y la practica de consejeria.

Magnetic behavior of clusters of ferromagnetic transition metals.

Abstract: The effective magnetic moments of small iron and cobalt clusters have been calculated by assuming that the clusters undergo superparamagnetic relaxation The effective moments per atom are found to be much below the bulk values, even at low temperatures (100 K) They increase with particle size and the applied magnetic field, and are in good agreement with recent beam experiments on ${\mathrm{Fe}}_{\mathit{N}}$ and ${\mathrm{Co}}_{\mathit{N}}$ clusters We also provide the first realistic estimates of the true magnetic moments in small ${\mathrm{Co}}_{\mathit{N}}$ clusters The present studies cast doubt on the recent theoretical interpretation of the observed reduced magnetic moments in small clusters compared to bulk as being due to melting of surface spins

Negotiating reality after physical loss: hope, depression, and disability.

Abstract: The utility of different reality negotiation strategies among 57 persons who had traumatically acquired severe physical disabilities was examined. It was predicted that a sense of goal-directed determination ("agency"; Snyder, 1989) would predict lower depression and psychosocial impairment scores soon after injury. To meet the demands of rehabilitation and social integration, however, it was hypothesized that a sense of ability to find ways to meet goals ("pathways") would predict lower depression and psychosocial impairment among persons who had been disabled for a longer period. The expected interaction was significant in the prediction of psychosocial impairment but not of depression. The sense of pathways was predictive of impairment and depression regardless of the time since injury. Results suggest that in the reality negotiation process the different components of hope as defined by Snyder have salient effects on perceptions of ability to function in social capacities.

Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo.

Abstract: The intravenous administration of heparin to patients before open heart surgery reduced ristocetin cofactor activity by 58% (P less than 0.01, t test), and this impairment of von Willebrand factor-dependent platelet function was closely related to plasma heparin levels (r2 = 0.9), but not to plasma von Willebrand factor (vWF) levels. We hypothesized that heparin may inhibit vWF-dependent platelet hemostatic functions by directly binding vWF in solution and interfering with vWF-GpIb binding. Using the in vitro techniques of ristocetin-induced platelet agglutination, fluorescent flow cytometric measurement of vWF-platelet binding, and conventional radioligand binding assays we observed that heparin inhibited both vWF-dependent platelet function and vWF-platelet binding in a parallel and dose-dependent manner. Heparin also inhibited platelet agglutination induced by bovine vWF and inhibited the binding of human asialo-vWF to platelets in ristocetin-free systems. The inhibitory potency of heparin was not dependent upon its affinity for antithrombin III, but was molecular weight dependent: homogeneous preparations of lower molecular weight were less inhibitory. Heparin impairment of vWF function may explain why some hemorrhagic complications of heparin therapy are not predictable based on techniques for monitoring the conventional anticoagulant effects of heparin.

Stability and change in the u.s. public's knowledge of politics

Abstract: The U.S. public's current knowledge about politics is compared with levels of knowlege in the 1940s and 1950s. Fourteen questions asked by Gallup on various surveys from 1945 to 1957 were included on a larger survey of political knowledge conducted by telephone in 1989 with a randomly selected sample of 610 adult U.S. residents. On 8 of the 14 items, the percentage answering correctly in 1989 was higher than in the earlier surveys (by 4-15 points). One item showed an increase of 1 percent, two were down 1 percent, and three others declined by 5 percent, 9 percent, and 10 percent. When level of education is controlled, however, levels of knowledge appear to have declined for most of the items. A reanalysis of some of the original Gallup data is used to estimate the effectiveness of schools in transmitting political information in 1989 compared with the earlier years. An informed citizenry is an implicit requisite for any theory of democracy. However, public opinion surveys of the 1940s and 1950s consistently demonstrated the average citizen's limited knowledge concerning public affairs and the basic workings of parties, politics, and government (Berelson, Lazarsfeld, and McPhee 1954; Campbell et al. 1960; Converse 1962, 1964; Lazarsfeld, Berelson, and Gaudet 1944). In 1962 and 1963 Erskine published four articles in Public Opinion Quarterly cataloging how informed the American citizenry was on a host of political and public concerns (Erskine 1962, 1963a, 1963b, MICHAEL X. DELLI CARPINI is assistant professor of political science at Barnard College, Columbia University. SCOTT KEETER is associate professor of political science at Virginia Commonwealth University. This research was supported by grants from Virginia Commonwealth University and Barnard College and by the Virginia Commonwealth University Survey Research Laboratory. Some of the data were made available through the Inter-University Consortium for Political and Social Research (ICPSR) and the Roper Center for Public Opinion Research. Neither ICPSR nor the Roper Center is responsible for the analyses and interpretations presented here. We wish to thank Stephen Earl Bennett and the anonymous referees for their helpful comments on earlier versions of this article. Public Opinion Quarterly Volume 55 583-612 C 1991 by the American Association for Public Opinion Research All rights reserved 0033-362X/91/5504-0002$02.50 This content downloaded from 207.46.13.25 on Mon, 12 Sep 2016 04:27:47 UTC All use subject to http://about.jstor.org/terms 584 Michael X. Delli Carpini and Scott Keeter 1963c). The articles brought together national survey questions asked from 1947 through 1962. Since the late 1950s the number and range of political knowledge questions asked on national surveys have declined precipitously. Using a national telephone survey, we have replicated several of the items reported by Erskine to document what, if any, changes have occurred in the U.S. public's political knowledge. First we summarize extant research on political knowledge, pointing out its conclusions as well as the shortcomings that result from a relative lack of current data. Next we discuss the design and validity of our survey and examine the willingness of respondents to complete a survey devoted mainly to a test of political knowledge. We then turn to the Gallup polls used in our comparisons, explaining adjustments that are necessary due to sampling bias. We follow with a comparison of marginals for 14 knowledge questions. Finally, we explore the changes in political knowledge (and lack thereof) in light of societal changes in educational achievement.

The effect of angle and flow rate upon hemodynamics in distal vascular graft anastomoses: a numerical model study.

Abstract: Flow in distal end-to-side anastomoses of iliofemoral artery bypass grafts was simulated using a steady flow, three-dimensional numerical model. With the proximal artery occluded, anastomotic angles were varied over 20, 30, 40, 45, 50, 60 and 70 deg while the inlet Reynolds numbers were 100 and 205. Fully developed flow in the graft became somewhat skewed toward the inner wall with increasing angle for both Reynolds numbers. Separated flow regions were seen along the inner arterial wall (toe region) for angles > or = 60 deg at Re = 100 and for angles > or = 45 deg at Re = 205 while a stagnation point existed along the outer arterial wall (floor region) for all cases which moved downstream relative to the toe of the anastomosis with decreasing angles. Normalized shear rates (NSR) along the arterial wall varied widely throughout the anastomotic region with negative values seen in the separation zones and upstream of the stagnation points which increased in magnitude with angle. The NSR increased with distance downstream of the stagnation point and with magnitudes which increased with the angle. Compared with observations from chronic in vivo studies, these results appear to support the hypothesis of greater intimal hyperplasia occurring in regions of low fluid shear.

The family history method: whose psychiatric history is measured?

Abstract: Objective: The family history method, in which an informant is asked about the history of psychiatric illness in relatives, is widely used in psychiatric research. Previous research has examined the influence on family history information of characteristics of the relative. In this report, the authors seek to clarify the impact on family history reporting of the psychiatric history ofthe informant. Method: Both members offemale twin pairs from a population-based twin registry were asked about the history of major depression, generalized anxiety disorder, and alcoholism in their mother and father. The authors examined twin pairs discordant for each ofthe three diagnoses and predicted that the affected twin would report higher rates ofthe same disorder in her parent than would the unaffected twin. Results: Twins with a history of major depression or generalized anxiety disorder but not twins with alcoholism were significantly more likely to report the same disorder in their parents than were their unaffected co-twins. Conclusions: For major depression and generalized anxiety disorder, a family history diagnosis appears to reflect the psychiatric history of both the relative and the informant. Caution may be needed in the interpretation of results based on the family history method, although the magnitude of this problem may be attenuated by the use of multiple informants. (AmJ Psychiatry 1991; 148:1501-1504)

The anion paradox in sodium taste reception: resolution by voltage-clamp studies

Abstract: Sodium salts are potent taste stimuli, but their effectiveness is markedly dependent on the anion, with chloride yielding the greatest response. The cellular mechanisms that mediate this phenomenon are not known. This "anion paradox" has been resolved by considering the field potential that is generated by restricted electrodiffusion of the anion through paracellular shunts between taste-bud cells. Neural responses to sodium chloride, sodium acetate, and sodium gluconate were studied while the field potential was voltage-clamped. Clamping at electronegative values eliminated the anion effect, whereas clamping at electropositive potentials exaggerated it. Thus, field potentials across the lingual epithelium modulate taste reception, indicating that the functional unit of taste reception includes the taste cell and its paracellular microenvironment.

Prediction tree for severely head-injured patients

Abstract: Prediction tree techniques are employed in the analysis of data from 555 patients admitted to the Medical College of Virginia hospitals with severe head injuries. Twenty-three prognostic indicators are examined to predict the distribution of 12-month outcomes among the five Glasgow Outcome Scale categories. A tree diagram, illustrating the prognostic pattern, provides critical threshold levels that split the patients into subgroups with varying degrees of risk. It is a visually useful way to look at the prognosis of head-injured patients. In previous analyses addressing this prediction problem, the same set of prognostic factors (age, motor score, and pupillary response) was used for all patients. These approaches might be considered inflexible because more informative prediction may be achieved by somewhat different combinations of factors for different patients. Tree analysis reveals that the pattern of important prognostic factors differs among various patient subgroups, although the three previously mentioned factors are still of primary importance. For example, it is noted that information concerning intracerebral lesions is useful in predicting outcome for certain patients. The overall predictive accuracy of the tree technique for these data is 77.7%, which is somewhat higher than that obtained via standard prediction methods. The predictive accuracy is highest among patients who have a good recovery or die; it is lower for patients having intermediate outcomes.

Risk aversion and rent-seeking: An extension and some experimental evidence

Abstract: Theoretical investigations indicate that the risk attitudes of individuals will effect the amount of rent that can be assumed to be dissipated by rent-seeking activities. Following this line of investigation we extend Hillman and Katz's work to a small numbers case and demonstrate that the degree to which a monopoly rent is dissipated is dependent upon the structure of the risk attitudes of two risk averse individuals.

Formulations for delivery of drugs by metered dose inhalers with reduced or no chlorofluorocarbon content

Abstract: Aerosol formulations for use in metered dose inhalers are disclosed which include 1,1,1,2-tetrafluoroethane alone and in combination with other compounds as well as various hydrocarbon blends. The density, vapor pressure, flame extension characteristics, dispersability of medicant, dissolvability of surfactant, respirable fraction, and compatibility elastomer seals for the aerosol formulations have been examined. The aerosol formulations are attractive alternatives to chlorofluorocarbon based aerosols since they do not deplete the ozone layer.

The effects of prototype-based biases on leadership appraisals: A test of leadership categorization theory.

Abstract: Leadership categorization theory suggests that leaders who display characteristics and abilities that match observers' schematic conception of an effective leader will be more favorably evaluated t...

The Electrotopological State: An Atom Index for QSAR

Abstract: A new characterization of atoms in molecules is introduced as the electrotopological state index, which combines both the electronic character and the topological environment of each skeletal atom in a molecule. The electrotopological state (E-state) of a skeletal atom is formulated as an intrinsic value Ii plus a perturbation term ΔIi, arising from the electronic interaction within the molecular topological environment of each atom in the molecule. The atom intrinsic value, for first row atoms, is expressed as I = (δv + 1)δ, in which δv and δ are the counts of valence and sigma electrons, respectively, for the atom in the molecular skeleton. The E-state, Si, for atom i is defined as Si = Ij + ΔIj, where the influence of other atoms on atom i, ΔIi, is given as Σ(Ij — Ij)/rij2; rij is the graph separation between atoms i and j, counted as number of atoms, including i and j. Information in the electrotopological state is revealed by examples of various types of organic structures, including skeletal branching and heteroatom variation. The relation of the E-state value to NMR chemical shift is demonstrated for a series of carbonyl compounds. QSAR examples are given for hydrazide inhibition of MAO and for receptor binding of β-carbolines. These examples reveal the power of this approach to QSAR using atom level indexes, computed directly from molecule connection tables, in which it is possible to identify atoms and regions in the molecule which are important for activity.

Sequence and structure determinants of the nonenzymatic deamidation of asparagine and glutamine residues in proteins.

Abstract: The rates of deamidation of Asn and Gln residues in peptides and proteins depend upon both the identity of other nearby amino acid residues, some of which can catalyze the deamidation reaction of the Asn and Gln side chains, and upon polypeptide conformation. Proximal amino acids can be contiguous in sequence or brought close to Asn or Gln side chains by higher order structure of the protein. Local polypeptide conformation can stabilize the oxyanion transition state of the deamidation reaction and also enable deamidation through the beta-aspartyl shift mechanism. In this paper, the environments of Asn and Gln residues in known protein structures are examined to determine the configuration and identity of groups which participate in deamidation reactions. Sequence information is also analyzed and shown to support evolutionary selection against the occurrence of certain potentially catalytic amino acids adjacent to Asn and Gln in proteins. This negative selection supports a functional role for deamidation in those non-mutant proteins in which it occurs.

Cariogenicity of Streptococcus mutans V403 glucosyltransferase and fructosyltransferase mutants constructed by allelic exchange.

Abstract: Streptococcus mutans produces several enzymes which metabolize sucrose. Three glucosyltransferase genes (gtfB, gtfC, and gtfD) and a single fructosyltransferase gene (ftf) encode enzymes which are important in formation of exopolysaccharides. Mutants of S. mutans V403 carrying single and multiple mutations of the gtfB, gtfC, gtfD, and ftf genes recently have been constructed by allelic exchange in our laboratory. Using selected strains from this panel of mutants, we examined the importance of water-insoluble glucan, water-soluble glucan, and fructan production in cariogenicity while controlling for the effects of strain and species variability. Genetic and biochemical characterization of mutants and assays of glucosyltransferase and fructosyltransferase activities were performed to ensure that the phenotypes of strains coincided with deficiencies predicted by genotype. The young gnotobiotic rat model of cariogenicity was used to assess virulence of the wild-type strain and isogenic mutants. Mutant strains were less virulent than the wild type in almost every location examined for caries on tooth surfaces and level of involvement of lesions (depth and severity). Inactivation of either gtfB and gtfC or ftf dramatically reduced virulence; the subsequent inactivation of gtfD did not enhance the effect of reduced virulence.

Personality hardiness, ways of coping, social support and burnout in critical care nurses.

Abstract: Hardiness, ways of coping, social support and burnout in 103 critical care nurses were addressed in this study Work-related and nonwork-related social support and hardiness were negatively related to burnout Use of emotion-focused coping was positively correlated with burnout while hardiness was negatively related to the use of emotion-focused coping and positively related to both types of social support After controlling for working nights, social support, hardiness, emotion-focused coping and problem-focused coping accounted for 44% of the variance in burnout scores

Evaluating FACES III and the Circumplex Model: 2,440 Families†

Abstract: Previous evaluations of the Circumplex Model's curvilinear hypothesis using FACES instruments have yielded conflicting results. A review of the different research procedures and samples used in those investigations revealed that none of the studies had samples large and/or heterogenous enough to test the curvilinear hypothesis adequately. The present study evaluates the curvilinear hypothesis of family functioning and the concurrent validity of FACES III with a sample of optimal size (N = 2,440 families) and diversity. The lack of support for the curvilinear hypothesis in this "greenhouse" sample is explained by different findings for the two FACES III subscales. There was no relationship between the study's measures of well-being and the adaptability subscale and a linear relationship between these measures and the cohesion subscale. Implications of these findings for the continuing use of the FACES III and for the Circumplex Model of Marital and Family Systems are discussed.

Hypercholesterolemia in long-term survivors of heart transplantation: an early marker of accelerated coronary artery disease.

Abstract: Coronary artery disease remains a significant long-term problem for survival after heart transplantation. Hyperlipidemia is a known risk factor for coronary artery disease in the general population, but the role of hyperlipidemia in cardiac allograft recipients has not been elucidated. To study this problem, we retrospectively reviewed 38 heart transplant recipients who survived more than 3 years after surgery and looked at age, development of diabetes, drug protocol, and development of hypercholesterolemia for a possible correlative or predictive value to the development of early coronary artery disease after heart transplantation. Eleven patients were identified as having coronary disease by the third year after transplantation. High-risk cholesterol values (in milligrams per deciliter) at 6 months after heart transplantation were defined as follows: for ages 10 to 20, 190; 20 to 30, 220; 30 to 40, 240; 40+, 260. We found a strong predictive value with high-risk lipid profiles (p less than 0.01) for the development of coronary artery disease by the third year. No significance was found for a low-risk value, the development of diabetes, or hypertension. All patients below the age of 20 years had coronary artery disease by the third year after transplantation. We conclude that a high-risk cholesterol value at 6 months after transplantation is a strong predictor for development of accelerated coronary artery disease and early graft failure. This has major implications for management of hyperlipidemia in the cardiac allograft recipient.

Sjögren-Larsson syndrome. Deficient activity of the fatty aldehyde dehydrogenase component of fatty alcohol:NAD+ oxidoreductase in cultured fibroblasts.

Abstract: Sjogren-Larsson syndrome (SLS) is an inherited disorder associated with impaired fatty alcohol oxidation due to deficient activity of fatty alcohol:NAD+ oxidoreductase (FAO). FAO is a complex enzyme which consists of two separate proteins that sequentially catalyze the oxidation of fatty alcohol to fatty aldehyde and fatty acid. To determine which enzymatic component of FAO was deficient in SLS, we assayed fatty aldehyde dehydrogenase (FALDH) and fatty alcohol dehydrogenase in cultured fibroblasts from seven unrelated SLS patients. All SLS cells were selectively deficient in the FALDH component of FAO, and had normal activity of fatty alcohol dehydrogenase. The extent of FALDH deficiency in SLS cells depended on the aliphatic aldehyde used as substrate, ranging from 62% of mean normal activity using propionaldehyde as substrate to 8% of mean normal activity with octadecanal. FALDH activity in obligate SLS heterozygotes was partially decreased to 49 +/- 7% of mean normal activity using octadecanal as substrate. Differential centrifugation studies in fibroblasts indicated that this FALDH enzyme was largely particulate; soluble FALDH activity was normal in SLS cells. Intact SLS fibroblasts oxidized octadecanol to fatty acid at less than 10% of the normal rate, but oxidized free octadecanal normally, suggesting that the FALDH affected in SLS is chiefly involved in the oxidation of fatty alcohol to fatty acid. These results show that the primary enzymatic defect in SLS is the FALDH component of the FAO complex, which leads to deficient oxidation of fatty aldehyde derived from fatty alcohol.