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Biomedical subjects

S L Brown

Publications and source records attributed to S L Brown.

At least 127 records · Page 7Linked to original sources
PubMed1991

Smokers unlikely to quit.

Data from a population survey were used to examine the relationships of the number and the duration of previous smoking cessation attempts with current confidence and perceived difficulty of quitting, beliefs about reasons for current smoking and for previous relapses, and preferences for different forms of assistance with cessation. There were significant positive relationships between the duration of previous cessation attempts and perceived difficulty and between the number of previous cessation attempts and confidence. Those who had made more cessation attempts and who had been able to abstain for less than a week were more likely to attribute both relapse and current smoking to uncontrollable factors such as addiction. There were no relationships between cessation attempts and preferences expressed for personalized, or any other, forms of assistance with cessation. These results support the proposition that multiple and short-duration smoking-cessation attempts are related to reduced optimism regarding future cessation.

Adult↗
PubMed1991

Correlates of risk of suicide in violent and nonviolent psychiatric patients.

OBJECTIVE: This study was designed to identify variables that correlate with the risk of suicide in two patient groups that differ mainly in their level of expressed aggression. METHOD: Twenty-eight psychiatric patients with a history of violent behavior who were in a forensic psychiatric facility were tested and compared to 28 psychiatric inpatients without a history of violence who were admitted to a large municipal hospital. Measures used included a battery of self-report questionnaires, with acceptable reliability and validity, that provided indices of risk of suicide, risk of violence, impulsivity, anger, anxiety, and various mood states. RESULTS: The two groups, matched on demographic variables and overall risk of suicide, differed significantly on the measured risk of violence. The two groups showed similar patterns of correlations between risk of suicide and such variables as risk of violence, anger, fear, state and trait anxiety, lack of impulse control, suspiciousness, and rebelliousness. They differed in the correlation between suicide risk and depression. In the nonviolent patients there was a high correlation between risk of suicide and sadness; in the violent patients there was no correlation between these variables. CONCLUSIONS: The low correlation between sadness and risk of suicide in the violent patients, and the low prevalence of affective disorder diagnoses in these patients compared to other patients, suggests that suicidal risk should be managed differently in highly violent patients than in others.

Adult↗
PubMed1990

Interrelationships among anxiety, aggression, impulsivity, and mood: a serotonergically linked cluster?

Serotonin abnormalities appear to be related to a variety of psychopathological dimensions such as anxiety, depressed mood, impulsivity, and aggression dysregulation. We hypothesized that the psychopathological dimensions related to serotonin would be significantly intercorrelated since they seem to have a common biological basis. Sixty psychiatric inpatients were examined on a series of psychometric tests measuring suicidality, violence potential, impulsivity, depressive mood, and anxiety. The scores on all of these measures tended to be significantly correlated with one another. These findings support the additional hypothesis that biological markers may be more closely related to basic psychological dimensions than to nosological categories.

Adult↗
PubMed1990

Nosological tunnel vision in biological psychiatry. A plea for a functional psychopathology.

Classical nosology has been the major cornerstone of biological psychiatric research; finding biological markers and eventually causes of disease entities has been the major goal. Another approach, one we have designated as "functional," seems possible, attempting to correlate biological variables with psychological dysfunctions, the latter being considered to be the basic units of classification in psychopathology. We have pursued this route for many years, and based on the resulting findings we formulated the following hypothesis. Signs of diminished dopamine, serotonine, and noradrenaline metabolism, as have been found in psychiatric disorders, are not disorder-specific, but rather are related to psychopathological dimensions; i.e., hypoactivity/inertia; increased aggression/anxiety and anhedonia, independent of the nosological framework in which these dysfunctions occur (van Praag et al. 1990). In this paper only the 5-HT data have been discussed. Implications of the functional approach for psychiatry are discussed, including a shift from nosological to functional application of psychotropic drugs. Functional psychopharmacology will be dysfunction-oriented and therefore inevitably geared towards utilizing drug combinations. This prospect is hailed as progress, both practically and scientifically.

5-Hydroxytryptophan↗
PubMed1990

Receptor-mediated endocytosis of low-density lipoprotein by cultured human glomerular cells.

Lipoproteins might be involved in the pathogenesis of glomerular damage. Uptake of low-density lipoprotein (LDL) by cultured human glomerular cells has been studied using LDL, labelled with the fluorescent probe 1,1'-dioctadecyl-3,3,3'3'-tetramethyl-indocarbocyanine perchlorate (diI). Cells have been characterised using phase-contrast microscopy, monoclonal antibodies and lectins. Differentiated glomerular epithelial cells, epithelial-like cells and mesangial cells all took up diI-LDL. Uptake was specific for LDL, of high affinity and inhibited by excess unlabelled LDL, heparin and preloading the cells with cholesterol. Binding of diI-LDL to the cell surface was restricted to discrete areas which were arranged in linear arrays on mesangial cells. Endocytosis of surface-bound diI-LDL occurred within 3 min and breakdown of internalised diI-LDL within 30 min. These results indicate that cultured human glomerular cells take up LDL by receptor-mediated endocytosis.

Cells, Cultured↗
PubMed1990

Monoamines and abnormal behaviour. A multi-aminergic perspective.

Classical nosology has been the cornerstone of biological psychiatric research; finding biological markers and eventually causes of disease entities has been the major goal. Another approach, designated as 'functional', is advanced here, attempting to correlate biological variables with psychological dysfunctions, the latter being considered to be the basic units of classification in psychopathology. Signs of diminished DA, 5-HT and NA metabolism, as have been found in psychiatric disorders, are not disorder-specific, but rather are related to psychopathological dimensions (hypoactivity/inertia, increased aggression/anxiety, and anhedonia) independent of the nosological framework in which these dysfunctions occur. Implications of the functional approach for psychiatry include a shift from nosological to functional application of psychotropic drugs. Functional psychopharmacology will be dysfunction-orientated and therefore geared towards utilising drug combinations. This prospect is hailed as progress, both practically and scientifically.

Arousal↗
PubMed1989

Developmental regulation of membrane and secretory Ig gamma 2b mRNA.

To better understand the developmental regulation of membrane and secretory forms of Ig Heavy chain mRNA, mutations were made in a gamma 2b gene in vitro and assayed for their expression in cell lines representative of early and late stages of B cell development. Processing of the gamma 2b mRNA did not change with the amount of message produced, demonstrating that the production of predominantly secretory mRNA in plasma cells is not the consequence of increased message synthesis. The length of the intron between the secretory and membrane exons was found to affect the relative expression of secretory and membrane mRNA, but this effect was also observed in non-lymphoid cells, suggesting that the intron "gradient effect" does not identify the processing reaction which is regulated during B cell differentiation. Deletion of the signals for the splice from CH3 to the membrane exons resulted in the exclusive production of secretory mRNA irrespective of the developmental stage of the recipient cell, suggesting that this splice reaction plays a role in regulating these mRNA, and that competition between the two polyadenylation sites does not dictate the relative expression of the two forms of message. Appropriate ratios of the two forms were produced from a 2.3-kbp fragment of the gamma 2b gene containing the secretory cleavage and membrane splice signals in the context of a different transcription unit. These results suggest that the changes in the relative expression of secretory and membrane gamma 2b mRNA during B cell development are mediated by a competition between cleavage at the secretory polyadenylation and splicing from CH3 to the membrane exons.

Animals↗
PubMed1989

Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha interferon.

Idiotypes are distinct clonal markers for B-cell lymphomas. Previously we reported the use of anti-idiotype antibodies in the therapy of patients with B-cell malignancies. Because synergy was demonstrated with the addition of alpha interferon to anti-idiotype antibodies in a murine lymphoma model, we performed a clinical trial combining these two agents. Here we provide an update of the original trial of anti-idiotype antibodies alone and report the outcome of the new combination trial. In 16 treatment courses of anti-idiotype antibodies alone there were seven partial responses and one complete response. In 12 courses of combination anti-idiotype antibody and alpha interferon there were two complete responses and seven partial responses. Substantial tumor regressions occurred with minimal toxicity in both trials even in patients refractory to conventional chemotherapy. Tumor specimens obtained at the time of disease progression often contained a preponderance of idiotype-negative lymphoma cells, suggesting that anti-idiotype antibody treatment exerted a strong antitumor effect against antigen-positive cells. Anti-idiotype antibodies have reproducible objective antitumor activity in B-cell lymphoma. The addition of alpha interferon may improve the initial rate of response to this treatment. Strategies that deal effectively with idiotype-negative lymphoma cells should improve the extent and duration of these responses.

Antibodies, Anti-Idiotypic↗
PubMed1989

Regulation of the production of secretory and membrane immunoglobulin during lymphocyte development.

An area of great controversy in molecular immunology is the mechanism by which the differential expression of secretory and membrane immunoglobulin heavy chain is regulated during B cell development. Since the changes in expression of the two proteins are determined largely by the steady state levels of the mRNAs that encode them, recent work has focused on the regulation of the expression of the two messages. This problem is central to understanding humoral immunity, with the specific antigen driven switch from antibody as receptor to antibody as secreted product and may be of direct relevance to some forms of the common variable immunodeficiency syndrome. In addition, numerous other genes have been shown to be regulated by alternative RNA processing. Since its beginnings, research in immunology has brought about profound changes in our view of biology. Jenner's landmark experiment, inducing a minor illness to prevent a major one, showed that the body's future susceptibility to a particular disease could be manipulated. More recently the demonstration that immunoglobulin V, D, and J gene segments, originally spread over many kilobases (kbs) in the genome, must be assembled to form a functional heavy chain gene has shattered both the concept of a genome fixed at fertilization and the "one gene, one protein" rule. The alternative processing of heavy chain transcripts to produce secretory and membrane forms of immunoglobulin has demonstrated how the same gene can give rise to proteins with alternative structures. Since the discovery of the role of alternative RNA processing in heavy chain mRNA synthesis, numerous other cellular genes have been shown to be regulated by modulation of RNA processing pathways.

Animals↗
PubMed1989

Interleukin-2 induction of ACTH secretion: presence of an interleukin-2 receptor alpha-chain-like molecule on pituitary cells.

Pituitary cells were shown to release corticotropin (ACTH) in response to interleukin-2 (IL-2) and to express a protein that is related to the alpha-chain of the IL-2 receptor (IL-2R). The alpha-chain-like molecule was bound by a rat monoclonal antibody to the murine IL-2 receptor as well as to IL-2. Sodium dodecylsulfate-polyacrylamide gel electrophoretic analysis of the affinity-purified material from pituitary cells demonstrated a protein which was similar to that which was isolated from activated splenocytes. Thus, IL-2 and its receptor may be one of several hormone-receptor pairs utilized by both the immune and neuroendocrine systems for intersystem communication.

Adrenocorticotropic Hormone↗
PubMed1989

Topically active carbonic anhydrase inhibitors. 1. O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide.

A series of O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide (4, L-643,799) was prepared and the potential utility of each series member as a topically active inhibitor of ocular carbonic anhydrase was determined. In vitro studies showed these esters to be substrates for ocular esterases which liberate 4 during corneal translocation. The most interesting series member, 2-sulfamoyl-6-benzothiazolyl 2,2-dimethylpropionate (22, L-645,151), acting as a prodrug form of 4, was found to enhance delivery through the isolated albino rabbit cornea by 40-fold when compared to the parent phenol 4. Studies in rabbits revealed that 22 is a potent topically active ocular hypotensive carbonic anhydrase inhibitor.

Animals↗
PubMed1988

Lymphocyte beta-adrenergic receptor binding in panic disorder.

Lymphocyte beta adrenergic receptor binding using [125I]CNP was determined in patients with panic disorder (N = 4) or agoraphobia with panic attacks (N = 17) and age- and sex-matched healthy subjects (N = 22). The patients showed a significantly lower number of beta-adrenergic receptor binding sites and a significantly higher affinity of binding than healthy subjects. A past or present history of major depression in the patients did not alter these findings. These results are consistent with a growing body of knowledge implicating noradrenergic dysfunction in the pathophysiology of panic anxiety.

Adrenergic beta-Agonists↗