Showing papers by "University of Pittsburgh published in 1993"

Nonexponential relaxations in strong and fragile glass formers

Abstract: Deviations from thermally activated and from exponential response are typical features of the vitrification phenomenon and previously have been studied using viscoelastic, dielectric, calorimetric, optical, and other techniques. Linear response data from literature on about 70 covalent glass formers, ionic melts, supercooled liquids, amorphous polymers, and glassy crystals are surveyed. Except for orientational glasses and monohydric aliphatic alcohols a distinct but broad correlation of non‐Debye behavior with non‐Arrhenius relaxations is found. Within the broad trend several groups of materials, distinguished by their respective molecular complexity, can be identified and are shown to exhibit narrow correlations. At a given degree of deviation from Arrhenius behavior externally imposed stresses are relaxed with a departure from exponential behavior which is stronger the more the molecular or atomic subunits of the glassforming material are interconnected with each other.

Entrepreneurship and the concept of fit: A model and empirical tests

Abstract: This paper reports the results of a study designed to investigate entrepreneurship and 'fit' in small and medium sized high technology manufacturing firms. A normative model of fit has been developed, which including the variables of entrepreneurial style, organizational structure, and mission strategy, determines a measure of the firm's fit with its environment. The normative model of fit proposed here is based on variables and relationships found to be important in previous empirical studies. Data on environmental turbulence, entrepreneurial style, organization structure, mission strategy, and financial performance were collected from 82 manufacturing firms. A measure of fit was calculated for each firm. Findings indicate that performance among firms was positively related to the measurement of fit. In short, fit is an important construct for firm success. Implications include prescriptive guidance to assist practitioners in diagnosing and correcting 'misfit' for individual firms.

Stress and immunity in humans: a meta-analytic review.

Abstract: This article presents a meta-analysis of the literature on stress and immunity in humans. The primary analyses include all relevant studies irrespective of the measure or manipulation of stress. The results of these analyses show substantial evidence for a relation between stress and decreases in functional immune measures (proliferative response to mitogens and natural killer cell activity). Stress is also related to numbers and percent of circulating white blood cells, immunoglobulin levels, and antibody titers to herpesviruses. Subsequent analyses suggest that objective stressful events are related to larger immune changes than subjective self-reports of stress, that immune response varies with stressor duration, and that interpersonal events are related to different immune outcomes than nonsocial events. We discuss the way neuroendocrine mechanisms and health practices might explain immune alteration following stress, and outline issues that need to be investigated in this area.

Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans

Abstract: Direct gene transfer offers the potential to introduce DNA encoding therapeutic proteins to treat human disease. Previously, gene transfer in humans has been achieved by a cell-mediated ex vivo approach in which cells from the blood or tissue of patients are genetically modified in the laboratory and subsequently returned to the patient. To determine the feasibility and safety of directly transferring genes into humans, a clinical study was performed. The gene encoding a foreign major histocompatibility complex protein, HLA-B7, was introduced into HLA-B7-negative patients with advanced melanoma by injection of DNA-liposome complexes in an effort to demonstrate gene transfer, document recombinant gene expression, and determine the safety and potential toxicity of this therapy. Six courses of treatment were completed without complications in five HLA-B7-negative patients with stage IV melanoma. Plasmid DNA was detected within biopsies of treated tumor nodules 3-7 days after injection but was not found in the serum at any time by using the polymerase chain reaction. Recombinant HLA-B7 protein was demonstrated in tumor biopsy tissue in all five patients by immunochemistry, and immune responses to HLA-B7 and autologous tumors could be detected. No antibodies to DNA were detected in any patient. One patient demonstrated regression of injected nodules on two independent treatments, which was accompanied by regression at distant sites. These studies demonstrate the feasibility, safety, and therapeutic potential of direct gene transfer in humans.

Inflammation, immunoregulation, and inducible nitric oxide synthase

Abstract: Nitric oxide (NO), the molecule of the year 1992, is gaining recognition as an important biological mediator. Its multitude of physiologic and pathophysiologic functions result from both a wide distribution of synthesis and diverse mechanisms of action. Besides its functions as a potent vasodilator and neurotransmitter, NO is important in inflammation and immunity. Both beneficial and detrimental consequences of induced synthesis have been discovered. Information is now accumulating on the regulation and function of induced NO. The recent cloning of human inducible NO cDNA should assist in defining the role of inducible NO in human physiology and pathophysiology.

Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes.

Abstract: Nitric oxide is a short-lived biologic mediator for diverse cell types. Synthesis of an inducible nitric oxide synthase (NOS) in murine macrophages is stimulated by lipopolysaccharide (LPS) and interferon gamma. In human hepatocytes, NOS activity is induced by treatment with a combination of tumor necrosis factor, interleukin 1, interferon gamma, and LPS. We now report the molecular cloning and expression of an inducible human hepatocyte NOS (hep-NOS) cDNA. hep-NOS has 80% amino acid sequence homology to macrophage NOS (mac-NOS). Like other NOS isoforms, recognition sites for FMN, FAD, and NADPH are present, as well as a consensus calmodulin binding site. NOS activity in human 293 kidney cells transfected with hep-NOS cDNA is diminished by Ca2+ chelation and a calmodulin antagonist, reflecting a Ca2+ dependence not evident for mac-NOS. Northern blot analysis with hep-NOS cDNA reveals a 4.5-kb mRNA in both human hepatocytes and aortic smooth muscle cells following stimulation with LPS and cytokines. Human genomic Southern blots probed with human hep-NOS and human endothelial NOS cDNA clones display different genomic restriction enzyme fragments, suggesting distinct gene products for these NOS isoforms. hep-NOS appears to be an inducible form of NOS that is distinct from mac-NOS as well as brain and endothelial NOS isozymes.

Elevated Levels of Transforming Growth Factor α and Epidermal Growth Factor Receptor Messenger RNA Are Early Markers of Carcinogenesis in Head and Neck Cancer

Abstract: The squamous mucosa of patients who develop head and neck cancer is “condemned” or predisposed to disregulated growth as reflected by the high incidence of synchronous and metachronous primary tumors. We hypothesized that transformed and nontransformed mucosa from head and neck cancer patients would produce increased levels of transforming growth factor α (TGF-α) and its cell surface receptor, the epidermal growth factor receptor (EGFR), thereby contributing to this predisposition. Using molecular biological techniques, we examined the incidence and mechanism of TGF-α and EGFR overproduction in tumors and histologically normal mucosa excised from patients with squamous cell carcinoma of the head and neck (SCCHN) to test this hypothetical mechanism of field cancerization. Northern blot hybridization was used to evaluate the frequency of increased TGF-α and EGFR mRNA production in tissue excised from 24 patients with SCCHN and 10 cell lines compared with 7 control patients without cancer or a history of alcohol and tobacco use. Southern blot hybridization was used to examine for gene amplification. In patients with SCCHN, TGF-α mRNA was elevated by a mean of 5-fold in 95% of histologically “normal” mucosa samples ( P = 0.001) and by a mean of 5-fold in 87.5% of tumors ( P = 0.0001) while EGFR mRNA was elevated by a mean of 29-fold in 91% of histologically normal mucosa specimens ( P = 0.0005) and by a mean of 69-fold in 92% of tumors ( P = 0.0005), compared with mRNA levels in control normal mucosa. In 10 SCCHN cell lines, TGF-α mRNA was increased by a mean of 16-fold and EGFR mRNA levels were increased by a mean of 77-fold. Increased production of TGF-α and EGFR mRNA in the histologically normal mucosa of patients at risk for a primary or secondary head and neck cancer may serve both as a marker for malignant transformation and as a target for preventive therapies.

Psychiatric risk factors for adolescent suicide: A case-control study.

Abstract: Objective The objective of this study was to determine the psychiatric risk factors for adolescent suicide. Method Sixty-seven adolescent suicide victims were compared with 67 demographically matched community controls. Psychiatric disorder was assessed in suicide victims using a psychological autopsy protocol and in controls using similar semistructured psychiatric interviews. Risk factors were quantified by use of the odds ratio (OR), that is, the relative frequency of the occurrence of a given condition in the suicides compared with the controls. Results The most significant psychiatric risk factors associated with adolescent suicide were major depression (OR = 27.0), bipolar mixed state (OR = 9.0), substance abuse (OR = 8.5), and conduct disorder (OR = 6.0). Substance abuse was a more significant risk factor when comorbid with affective illness than when alone (OR = 17.0 versus 3.3). The majority of depressed suicide victims had a primary affective disorder (82%). A significant minority (31%) of depressed suicide victims had been depressed less than 3 months. Previous suicide attempts, suicidal ideation, and homicidal ideation also were associated with adolescent suicide. Conclusions The development of effective treatments for youth who fit the above-noted risk profiles should be given high priority. J. Am. Acad. Child Adolesc. Psychiatry , 1993, 32, 3:521–529.

Determining the rotational alignment of the femoral component in total knee arthroplasty using the epicondylar axis.

Abstract: The posterior condylar surfaces of the femur are routinely used as the reference for the rotational orientation of the femoral component during most primary total knee arthroplasties. The purpose of this investigation was to identify a clearly discernible, reproducible secondary anatomic axis useful for determining the rotational orientation of the femoral component when the posterior condylar surfaces cannot be used. Seventy-five embalmed anatomic specimen femurs were studied. A surgical epicondylar axis was defined as the line connecting the lateral epicondylar prominence and the medial sulcus of the medial epicondyle

Binge eating disorder: its further validation in a multisite study.

Abstract: Binge eating disorder (BED) is a new eating disorder that describes the eating disturbance of a large number of individuals who suffer from recurrent binge eating but who do not regularly engage in the compensatory behaviors to avoid weight gain seen in bulimia nervosa. This multisite study of BED involved 1,785 subjects drawn from 18 weight control programs, 942 subjects from five nonpatient community samples, and 75 patients with bulimia nervosa. Approximately 29% of subjects in weight control programs met the criteria for BED. In the nonpatient community samples BED was more common than purging bulimia nervosa. The validity of BED was supported by its strong association with (1) impairment in work and social functioning, (2) overconcern with body/shape and weight, (3) general psychopathology, (4) significant amount of time in adult life on diets, (5) a history of depression, alcohol/drug abuse, and treatment for emotional problems.

Some conceptual and statistical issues in analysis of longitudinal psychiatric data. Application to the NIMH treatment of Depression Collaborative Research Program dataset.

Abstract: L studies have a prominent role in psychiatric research; however, statistical methods for analyzing these data are rarely commensurate with the effort involved in their acquisition. Frequently the majority of data are discarded and a simple end-point analysis is performed. In other cases, so called repeated-measures analysis of variance procedures are used with little regard to their restrictive and often unrealistic assumptions and the effect of missing data on the statistical properties of their estimates. We explored the unique features of longitudinal psychiatric data from both statistical and conceptual perspectives. We used a family of statistical models termed random regression models that provide a more realistic approach to analysis of longitudinal psychiatric data. Random regression models provide solutions to commonly observed problems of missing data, serial correlation, time-varying covariates, and irregular measurement occasions, and they accommodate systematic person-specific deviations from the average time trend. Properties of these models were compared with traditional approaches at a conceptual level. The approach was then illustrated in a new analysis of the National Institute of Mental Health Treatment of Depression Collaborative Research Program dataset, which investigated two forms of psychotherapy, pharmacotherapy with clinical management, and a placebo with clinical management control. Results indicated that both person-specific effects and serial correlation play major roles in the longitudinal psychiatric response process. Ignoring either of these effects produces misleading estimates of uncertainty that form the basis of statistical tests of hypotheses.

Cytokines, endotoxin, and glucocorticoids regulate the expression of inducible nitric oxide synthase in hepatocytes.

Abstract: Nitric oxide (NO.) is a short-lived mediator which can be induced in a variety of cell types and produces many physiologic and metabolic changes in target cells. The inducible or high-output NO. synthase (NOS) pathway was first characterized in macrophages activated by lipopolysaccharide (LPS) and interferon gamma (IFN-gamma). Hepatocytes also express an inducible NOS following exposure to the combination of endotoxin (LPS) and tumor necrosis factor (TNF), interleukin 1 (IL-1), and IFN-gamma. In this study, to identify which of these cytokines, if any, was acting to induce the gene expression for hepatocyte NOS, we measured the levels of rat hepatocyte NOS mRNA by Northern blot analysis after stimulation by various combinations of endotoxin and cytokines in vitro. We found the mRNA for hepatocyte NOS to be a single band at approximately 4.5 kilobases which was maximally up-regulated (approximately 70-fold) by the combination of TNF, IL-1, IFN-gamma, and LPS. Abundance of NOS mRNA peaked 6-8 hr after stimulation and then declined by 25% at 24 hr. Unstimulated hepatocytes in vitro showed only a trace mRNA band after prolonged autoradiographic exposure. As single agents, TNF and IL-1 were the most effective inducers of hepatocyte NOS mRNA. Combinations of two or three stimuli revealed strong synergy between TNF, IL-1, and IFN-gamma. The increased mRNA levels correlated with elevated nitrogen oxide release and cGMP levels in the culture supernatants. Dexamethasone and cycloheximide inhibited induction of mRNA for hepatocyte NOS in a dose-dependent fashion. The addition of NG-monomethyl-L-arginine had no effect on mRNA levels but effectively blocked NO. formation. The inducible hepatocyte NOS mRNA was also detected in rat hepatocytes following chronic hepatic inflammation triggered by Corynebacterium parvum injection in vivo. These data demonstrate that the inducible NOS is functional in rat hepatocytes both in vitro and in vivo and that this pathway is under complex control. Endotoxin and inflammatory cytokines act synergistically to up-regulate gene expression for hepatocyte NOS, whereas glucocorticoids down-regulate the mRNA.

A methodology for controlling the size of a test suite

Abstract: This paper presents a technique to select a representative set of test cases from a test suite that provides the same coverage as the entire test suite. This selection is performed by identifying, and then eliminating, the redundant and obsolete test cases in the test suite. The representative set replaces the original test suite and thus, potentially produces a smaller test suite. The representative set can also be used to identify those test cases that should be rerun to test the program after it has been changed. Our technique is independent of the testing methodology and only requires an association between a testing requirement and the test cases that satisfy the requirement. We illustrate the technique using the data flow testing methodology. The reduction that is possible with our technique is illustrated by experimental results.

Development and Validation of the Biphasic Alcohol Effects Scale

Abstract: Alcohol produces stimulant and sedative effects, and both types of effect are thought to influence drinking practices. This article describes the development and preliminary validation of the Biphasic Alcohol Effects Scale (BAES), a self-report, unipolar adjective rating scale designed to measure both stimulant and sedative effects of alcohol. An initial pool of 12 stimulant and 12 sedative items was derived from previous alcohol effect measures, and from descriptors of intoxication generated by subjects during interviews conducted on both the ascending and descending limbs of the blood alcohol curve. This item pool was administered to a sample of sober college students twice, with a 2-week inter-test interval. Items that were difficult to comprehend, or that had high ratings or low test-retest reliability, were eliminated, resulting in a seven-item stimulant subscale and a seven-item sedative subscale. These subscales showed high internal consistency in a sober state, which was not improved by additional item deletion. The data from this study also provided a basis for revising the instructions for the BAES. The new 14-item instrument was then given to 30 male and 12 female nonalcoholics on the ascending and descending limbs of the blood alcohol curve, after the administration of either 0.75 ml/kg alcohol (males) or 0.65 ml/kg alcohol (females). Internal consistency was high for both BAES subscales on both limbs of the blood alcohol curve (Cronbach's alpha = 0.85 to 0.94), and was not improved by additional item deletion. Factor analyses conducted on both limbs of the blood alcohol curve supported the proposed factor structure of the BAES.(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental pathways in disruptive child behavior

Abstract: Developmental sequences in disruptive behavior from childhood to adolescence are traced retrospectively and prospectively in two community samples of boys. Three developmental pathways are distinguished: (a) an early authority conflict pathway, consisting in sequence of stubborn behavior, defiance, and authority avoidance; (b) a covert pathway, consisting of minor covert behaviors, property damage, and moderate to serious forms of delinquency; and (c) an overt pathway, consisting of aggression, fighting, and violence. The overlap among the three disruptive pathways is examined. Those boys who escalated in the overt pathway were more likely to escalate in the covert pathway than boys escalating in the covert pathway showing an escalation in the overt pathway. Escalation in the authority conflict pathway was not associated with escalation in either the overt or the covert pathways. Boys' rate of self-reported delinquency was highest for those in triple pathways (covert-overt-authority conflict) or in certain dual pathways (covert-overt, covert-authority conflict). However, by age 16 the highest rate of offending was displayed by those in the triple pathways. The rate of violent offenses was also highest for those in the triple pathways and for those in the overt and covert pathways. Results from the rate for court petitions largely supported these findings. Lowest rates of offending were observed for boys in the overt and authority conflict pathways. Implications are discussed for clinical practice and future research.

Introspecting about Reasons can Reduce Post-Choice Satisfaction

Abstract: This study tested the prediction that introspecting about the reasons for one's preferences would reduce satisfaction with a consumer choice Subjects evaluated two types of posters and then chose one to take home Those instructed to think about their reasons chose a different type of poster than control subjects and, when contacted 3 weeks later, were less satisfied with their choice When people think about reasons, they appear to focus on attributes of the stimulus that are easy to verbalize and seem like plausible reasons but may not be important causes of their initial evaluations When these attributes imply a new evaluation of the stimulus, people change their attitudes and base their choices on these new attitudes Over time, however, people's initial evaluation of the stimulus seems to return, and they come to regret choices based on the new attitudes

Ultrasound-assisted cannulation of the internal jugular vein. A prospective comparison to the external landmark-guided technique.

Abstract: BACKGROUNDCentral venous access is an essential part of patient management in many clinical settings and is usually achieved with a blinded, external landmark-guided technique. The purpose of this study is to evaluate whether an ultrasound technique can improve on the traditional method.METHODS AND RESULTSWe prospectively evaluated an ultrasound-guided method in 302 patients undergoing internal jugular venous cannulation and compared the results with 302 patients in whom an external landmark-guided technique was used. Ultrasound was used exclusively in an additional 626 patients. Cannulation of the internal jugular vein was achieved in all patients (100%) using ultrasound and in 266 patients (88.1%) using the landmark-guided technique (p < 0.001). The vein was entered on the first attempt in 78% of patients using ultrasound and in 38% using the landmark technique (p < 0.001). Average access time (skin to vein) was 9.8 seconds (2-68 seconds) by the ultrasound approach and 44.5 seconds (2-1,000 seconds) by ...

Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study

Abstract: ObjectivePreviously, we documented that mild hypothermia (34°C) induced immediately with reperfusion after ventricular fibrillation cardiac arrest in dogs improves functional and morphologic cerebral outcome. This study was designed to test the hypothesis that a 15-min delay in the initiation of coo

Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic-pituitary-adrenal axis

Abstract: Interleukin 6 (IL-6) is a pleiotropic cytokine produced by the cells of immune and nonimmune origin. Increased production of IL-6 is associated with disturbances of homeostasis, such as trauma, sepsis, or inflammatory diseases. Endotoxemia, tissue injury, or immune inflammatory reactions as well as physical or psychological stress are known to cause increased production of IL-6. We have confirmed this by showing that rats exposed to electric footshock, physical restraint, or a conditioned aversive stimulus have increased levels of plasma IL-6. Interestingly, the kinetics of the increase in plasma IL-6 resembled that of increase in plasma corticosterone. As no detectable endotoxin was found in the plasma samples from stressed and nonstressed rats and there is no evidence of tissue damage and inflammation in situations of restraint or conditioned aversive stimulus, a nonimmune origin of IL-6 is possible. Thus, the releasing of IL-6 into plasma may be under the regulation of neural and endocrine responses to...

Emotional/Behavioral Problems in Clinic and Nonclinic Children: Correspondence Among Child, Parent and Teacher Reports

Abstract: This study examined the correspondence among child, parent and teacher reports, in rating emotional and behavioral problems of 98 community nonpatients and 64 clinically referred children (ages 6-13). The mean ratings differed significantly for the three sources and for the two samples, and there were a few significant interactions. Correlations of the scores between sources, especially parents and teachers, were in the moderate range and were not significantly different from one another. Informant correspondence was higher for externalizing than internalizing problems in both patient and nonpatient samples, and was higher for nonpatients than patients. In general, informant agreement was higher for cases characterized by lower family stress and higher child acceptance, among other clinical variables.

The use of moderate therapeutic hypothermia for patients with severe head injuries: a preliminary report

Abstract: Animal research suggests that moderate therapeutic hypothermia may improve outcome after a severe head injury, but its efficacy has not been established in humans. The authors randomly assigned 40 consecutively treated patients with a severe closed head injury (Glasgow Coma Scale score 3 to 7) to either a hypothermia or a normothermia group. Using cooling blankets and cold saline gastric lavage, patients in the hypothermia group were cooled to 32 degrees to 33 degrees C (brain temperature) within a mean of 10 hours after injury, maintained at that temperature for 24 hours, and rewarmed to 37 degrees to 38 degrees C over 12 hours. Patients in the normothermia group were maintained at 37 degrees to 38 degrees C during this time. Deep-brain temperatures were monitored directly and used for all temperature determinations. Intracranial pressure (ICP), cerebral blood flow (CBF), and cerebral metabolic rate for oxygen (CMRO2) were measured serially for all patients. Hypothermia significantly reduced ICP (40%) and CBF (26%) during the cooling period, and neither parameter showed a significant rebound increase after patients were rewarmed. Compared to the normothermia group, the mean CMRO2 in the hypothermia group was lower during cooling and higher 5 days after injury. Three months after injury, 12 of the 20 patients in the hypothermia group had moderate, mild, or no disabilities; eight of the 20 patients in the normothermia group had improved to the same degree. Both groups had a similar incidence of systemic complications, including cardiac arrhythmias, coagulopathies, and pulmonary complications. It is concluded that therapeutic moderate hypothermia is safe and has sustained favorable effects on acute derangements of cerebral physiology and metabolism caused by severe closed head injury. The trend toward better outcome with hypothermia may indicate that its beneficial physiological and metabolic effects limit secondary brain injury.