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Biomedical subjects

S L Brown

Publications and source records attributed to S L Brown.

At least 109 records · Page 6Linked to original sources

Stimulation of migration of human aortic smooth muscle cells by vitronectin: implications for atherosclerosis.

OBJECTIVE: Migration of smooth muscle cells into the neointima has been implicated in atherogenesis. Vitronectin, a serum factor that promotes cell spreading and attachment, accumulates in atherosclerotic human tissues. The aim of this study was to determine the role of vitronectin and its receptor (integrin alpha V beta 3) in migration of smooth muscle cells. METHODS: Human aortic smooth muscle cell migration was studied in modified Boyden chambers. Expression of vitronectin receptor was determined by northern blotting of receptor mRNA and immunoprecipitation of receptor protein. RESULTS: Vitronectin dose dependently increased smooth muscle cell migration by an amount comparable to that induced by platelet derived growth factor, (PDGF)-BB. Antiserum to alpha V beta 3 diminished vitronectin driven migration. Northern blot analysis showed low constitutive expression of alpha V and beta 3 mRNA by smooth muscle cell and rapid induction with transforming growth factor beta (TGF-beta) and thrombin. Immunoprecipitation confirmed increased synthesis of the alpha V beta 3 vitronectin receptor complex by TGF-beta or thrombin. Smooth muscle cells pretreated with TGF-beta or thrombin showed increased vitronectin driven migration. cAMP suppressed induction of migration, but inhibition of protein kinase C increased it. CONCLUSIONS: These results show that vitronectin-induced human aortic smooth muscle cell migration is mediated by alpha V beta 3 vitronectin receptor and expression of the receptor is induced by TGF-beta and thrombin, which in turn induce vitronectin driven, vitronectin receptor modulated smooth muscle cell migration.

Arteriosclerosis↗

Granulocyte colony-stimulating factor "mobilized" peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy.

Hematopoietic growth factors have been used to accelerate engraftment after bone marrow transplantation and to "mobilize" peripheral blood progenitor cells (PBPC). We report on the data in 85 consecutive patients with Hodgkin's disease who were treated in a single institution using different methods to obtain PB progenitor cells. Use of granulocyte colony-stimulating factor for mobilization resulted in a significantly accelerated time to recovery of granulocytes (10 days v 12 days, P < .01) when compared with "nonmobilized" PBPC recipients. Similarly, use of mobilized PBPC resulted in a significantly accelerated time to platelet engraftment (13 days v 30 days, P < .001) when compared with "nonmobilized" recipients. Moreover, there was a statistically significant difference in total costs in favor of the group receiving "mobilized" PBPC.

Adolescent↗

Correlates of suicide and violence risk in an inpatient population: coping styles and social support.

Forty-six suicidal psychiatric inpatients were compared with 44 nonsuicidal psychiatric inpatients on measures of suicide risk, violence risk, impulsivity, feelings of anger, social support, and eight coping styles. The two groups were similar on demographic variables, but the suicidal patients were higher on the suicide risk scale, the violence risk scale, the impulsivity scale, and feelings of anger. Suicidal patients were significantly less likely to use the coping style of minimization to deal with life problems. A negative correlation was found between the social support measure and both suicide risk and violence risk. Three coping styles were found to correlate negatively with violence risk, but none with suicide risk. Coping styles were found to be a better predictor of violence risk than of suicide risk. It was also found that the more variables included in the predictor equation, the higher the correlation with the risk measures.

Adaptation, Psychological↗

Headache and cortisol responses to m-chlorophenylpiperazine are highly correlated.

The serotonin receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the release of cortisol and prolactin, and induces migraine-like headaches. We have studied the neuroendocrine and headache responses to m-CPP in 8 subjects with migraine and 10 normal subjects. Each subject underwent two challenge tests, one with 0.25 mg/kg PO of m-CPP and the other with placebo, administered in a double-blind crossover format. Serial measurements of serum cortisol, prolactin, and m-CPP levels were made at 30-min intervals for 210 min following ingestion of the medication. The incidence and severity of headache was assessed by a structured telephone interview after each test. We confirmed that m-CPP stimulates the release of cortisol and prolactin, and may induce headache, in both migraine subjects and normal controls. The cortisol response as well as ratings of headache severity and duration directly correlated with plasma levels of m-CPP. There were highly significant associations between the cortisol response and both headache severity and duration, independent of m-CPP plasma levels. We did not find statistically significant differences between the migraine and normal subjects in terms of their neuroendocrine or headache responses to m-CPP.

Adult↗

Radiofrequency capacitive heaters: the effect of coupling medium resistivity on power absorption along a mouse leg.

A capacitive radiofrequency source in conjunction with a temperature-controlled electromagnetic coupling medium has the potential of delivering uniform heating distributions in a mouse leg for experimental studies to investigate the use of hyperthermia as a treatment for cancer. The system has been adopted by a number of groups who have confirmed that uniform temperatures can be achieved in the presence of blood flow along a one-dimensional line which extends between the plates across the leg. In this paper, a simple mathematical model is presented and verified experimentally to demonstrate that parallel-plate capacitive radiofrequency heaters produce an inherent absorbed power distribution along the leg which is determined by the impedances across the loads. Hence, the thicker or thinner regions of the leg can be preferentially heated by using a coupling medium with lower or higher salinity, respectively. Uniform power absorption along the mouse leg required that the coupling medium had equivalent electrical properties to those of tissue.

Animals↗

Suicide and violence associated with panic attacks.

Several studies have indicated that patients with panic attacks have a higher rate of suicide attempts as well as deaths from suicide. Additionally, several investigators have presented case reports of individuals manifesting suicidal and violent behaviors directly and temporally associated with panic attacks. We report on four additional cases and suggest that these findings may explain, in part, the increased rate of suicidal behavior among patients with panic attacks found by some investigators. Furthermore, these case reports offer preliminary evidence that the relationship between violent behavior and the panic state may be clinically significant and deserving of further elucidation.

Adult↗

The relationship of personality to mood and anxiety states: a dimensional approach.

This study evaluates the relationship of personality to mood and anxiety states in a sample of 50 psychiatric out patients. In order to overcome arbitrariness inherent in categorical diagnoses of affective, personality and anxiety disorders, we use a dimensional approach to personality, mood and anxiety. According to our results, mood and anxiety states affect personality domains differentially. Namely, relatively large portions of personality and behavior, such as higher-order traits of novelty seeking and reward dependence, seem independent from mood and anxiety states. In contrast, the higher-order dimension of harm avoidance and its corresponding lower-order traits reflect changes in mood and anxiety to a much greater extent. Both the likelihood that large portions of personality may be independent from current mood and the likelihood that some precisely delineated personality domains tend to change simultaneously with current mood may improve our understanding of the relationship of personality to emotionality and affective disorders.

Adult↗

Localization and characterization of serologic epitopes on HLA-A2.

A panel of cells expressing 68 different mutant HLA-A2 genes was generated by site-directed mutagenesis and DNA-mediated gene transfer in order to define the regions of class I MHC molecules that contribute to the epitopes recognized by mAb. Each of the variant HLA-A2 molecules differed from HLA-A2.1 by a single amino acid substitution. The substitutions were located in both the alpha-helices and beta-strands of the alpha 1 and alpha 2 domains, and included residues that are highly polymorphic and that are conserved. All but five of the variant HLA-A2 molecules were expressed at levels that ranged from approximately 25%-100% the levels found for HLA-A2.1. The remaining five variants had no detectable expression and all involved substitutions at highly conserved residues. Eleven mAbs with specificities that ranged from highly HLA-A2 specific to monomorphic were analyzed for their ability to bind the variant HLA-A2 molecules. The results demonstrate that the binding of five of 11 mAbs could be mapped to the alpha 1 and alpha 2 domains. MA2.1 was the only antibody mapped to the alpha 1 domain. CR11-351 and A2,A28M1 recognized an overlapping epitope at the amino terminal end of the alpha 2-helix, and PA2.1 and BB7.2 recognized an overlapping epitope that includes the carboxy terminus of the alpha 2-helix and a turn on one of the underlying beta-strands. These results demonstrate that positions located on the surface of the molecule, but not within the peptide-binding cleft of the molecule, are important in serological specificities.

Cross Reactions↗

Developmental toxicity of CI-921, an anilinoacridine antitumor agent.

CI-921, an anilinoacridine compound active against leukemic and solid tumors, was evaluated for potential developmental toxicity. Intravenous injections of CI-921 in dextrose were given to female Sprague-Dawley rats (0.1, 0.5, and 1.0 mg/kg) on Gestation Days (GD) 6-15 and to female New Zealand White rabbits (0.1, 1.0 and 2.0 mg/kg) on GD 6-18. Appropriate vehicle and untreated controls were included. Maternal and fetal parameters, including external, visceral, and skeletal malformations and variations, were assessed. Treatment of rats with 1.0 mg/kg resulted in maternal toxicity, manifested as reduced body weight gain and food consumption during and after treatment. Reduced fetal body weight, an increased incidence of stunted fetuses, malformations of the axial and appendicular skeleton, microphthalmia, and an increased number of anatomical variations (including anomalies of the axial skeleton and apparent hydronephrosis) also occurred in rats at 1.0 mg/kg. Treatment of rabbits resulted in no apparent maternal toxicity. However, reduced fetal body weight, agenesis of the azygous lobe of the lung, and an increased incidence of variations of the axial skeleton occurred at 2.0 mg/kg in rabbits. These results indicate that CI-921, at the highest dose tested in each species, produced developmental toxicity in the presence of maternal toxicity in rats, but in the absence of maternal toxicity in rabbits.

Abnormalities, Drug-Induced↗

Self-help smoking cessation materials.

Smoking-cessation campaigns and services use printed self-help materials as a major medium for assisting smokers to quit. Such materials are associated with abstinence rates of up to 20% at 12-month follow-ups. Adherence to the specific content of self-instructional programs can be poor, but higher levels of reported adherence may be associated with a greater likelihood of cessation. Personalized cessation materials do not enhance cessation rates, but social support and minimal levels of personal contact do. Research is needed to identify which specific components of these programs are effective, how adherence may be promoted and how materials may be used in conjunction with other interventions--particularly cost-effective forms of counselling and social support.

Humans↗

Correlates of Tridimensional Personality Questionnaire Scales with selected Minnesota Multiphasic Personality Inventory Scales.

The pattern of correlations between selected MMPI scales and the scales of the Tridimensional Personality Questionnaire were examined in a convenience sample of 88 patients who had received both tests. Time between tests (usually less than one year) did not affect the correlations, but MMPI response-set variables (L, F, K, F-K) did. The Tridimensional Personality Questionnaire harm avoidance scale and subscales had many correlates on the MMPI. The Novelty seeking scale and subscales showed a number of moderate correlations with a smaller number of MMPI scales; these correlations did not significantly exceed the correlations with MMPI response-set variables. The Tridimensional Personality Questionnaire reward dependence scale and subscales had few, if any, significant MMPI correlates. It was also noted that no Tridimensional Personality Questionnaire scales were related to MMPI repression factor scores.

Adolescent↗

Factors influencing the thermosensitivity of two rodent tumors.

When SCCVII or KHT tumors (150 mm3) growing in the dorsum of the hind feet of mice were heated in a water bath at 44 degrees C for 60 min, the local control rate was 75 or 5%, respectively. To investigate factors responsible for the differential thermosensitivity between SCCVII and KHT tumors, the intratumor temperature distributions during heating and the thermosensitivities of the tumor cells were studied. Significant temperature heterogeneity was observed in heated tumors. The thermal dose distribution during heating for the sensitive SCCVII tumors was found to be more homogeneous than that for the resistant KHT tumors. For cells grown and heated in culture, SCCVII and KHT cells had similar thermosensitivities. However, when heated in vivo, both SCCVII and KHT cells were more sensitive than their counterparts grown in culture and SCCVII cells were more sensitive than KHT cells. If cells dispersed from the tumors were cultured in medium for 6 h and then heated, both types of cells became as resistant as cells grown in culture. One possible reason for tumor cells to be more sensitive to heating in vivo than in vitro, the temperature of unheated tumors, was examined. It was found that the temperature in the same region in unheated tumors varied temporally by several degrees with an average temperature of 31-32 degrees C. We found no evidence that the temperature during tumor growth could greatly influence the thermosensitivity of the tumor cells. Our findings indicate that a more homogeneous distribution of temperature in the tumor during heating and higher in vivo thermosensitivity of the tumor cells are characteristics of the more heat-sensitive tumor.

Animals↗