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Biomedical subjects

S Swartz

Publications and source records attributed to S Swartz.

17 recordsLinked to original sources
PubMed2001

Discovery of heterocyclic ureas as a new class of raf kinase inhibitors: identification of a second generation lead by a combinatorial chemistry approach.

Heterocyclic ureas, such as N-3-thienyl N'-aryl ureas, have been identified as novel inhibitors of raf kinase, a key mediator in the ras signal transduction pathway. Structure-activity relationships were established, and the potency of the screening hit was improved 10-fold to IC(50)=1.7 microM. A combinatorial synthesis approach enabled the identification of a breakthrough lead (IC(50)=0.54 microM) for a second generation series of heterocyclic urea raf kinase inhibitors.

Proto-Oncogene Proteins c-raf↗
PubMed1995

Changing diagnoses in Valkenberg Asylum, Cape Colony, 1891-1920: a longitudinal view.

This paper will examine changes made to diagnoses of patients admitted to Valkenberg Asylum, Cape Colony, during the period 1891-1920, in order to illustrate the ambiguous and shifting relationship between psychiatric theory and practice, in this colonial setting. The diagnostic profiles of Valkenberg patients make clear that the distinction between manic-depression and dementia praecox, established in theory by the end of the first decade of this century, was by no means clearly perceived by asylum practitioners. Racial attitudes affected diagnostic practice; these will be outlined. Valkenberg's case records will be used to illustrate interactions between the patient's history, race and gender, classificatory changes, and ambiguous presentation of symptoms. These records add an important diachronic perspective to the synchronic perspective contained in annual reports and lunacy registers. The implications of diagnostic changes for research which attempts retrospective diagnosis will be explored.

Colonialism↗
PubMed1994

Issues in the analysis of psychotic speech.

Debate on the locus of dysfunction in psychotic speech or thought disorder continues. Research in the area tends to reflect researchers' assumptions about the relationship between language and thought, and these determine the nature of the methodologies used. The circularity of argument produced in this way is inevitable, while fully contextualized comprehensive descriptions of interactions with psychotic patients are lacking. This article outlines a method of analysis which will yield basic descriptions, and produce data readily comparable to naturally occurring conversation. It includes consideration of context, conversation analysis, cohesion analysis, and tone-unit analysis. A crucial feature of the method is serious attention paid to the role of the listener in the creation of misunderstandings in conversations with psychotic speakers.

Antisocial Personality Disorder↗
PubMed1989

Multiple mechanisms of target cell disintegration are employed in cytotoxicity reactions mediated by human natural killer cells.

The rate of disintegration of target cells subsequent to lytic programming by human peripheral blood natural killer (NK) cells was investigated using a quantitative calcium pulse technique. The rate of this initial calcium-independent target cell disintegration was indicative of a first-order decay process for programmed target cells with a calculated half-life of less than 3 min. This initial, rapid disintegration phase was independent of the overall cytotoxic activity of the lymphocyte preparation tested. Moreover, initial rates of target cell disintegration were comparable for target cell lines that exhibit up to 6-fold differences in overall susceptibility to natural cytotoxicity. In these studies we also consistently observed very slow, calcium-independent disintegration of additional target cells following apparent completion of the rapid disintegration process. Using a 51Cr release assay and K-562 target cells, the kinetics of this slow disintegration process were examined and found to be similar for donors exhibiting up to a 2-fold difference in overall cytotoxic activity and independent of the concentration of programed target cells. Whereas the initial rapid disintegration mechanism was independent of temperature over the range of 10-37 degrees C, the slow disintegration mechanism exhibited a direct dependence on the incubation temperature. Furthermore, we observed that supernatants obtained after the termination of lytic programing by ethylene diaminetetraacetic acid could effect the slow lysis of fresh NK-susceptible target cell lines. These results support the utilization of at least two distinct mechanisms for target cell lysis by human NK cells.

Adult↗
PubMed1987

Talk about talk: metacommentary and context in the analysis of psychotic discourse.

This paper presents an analysis of an interview with a manic patient at a time when her discourse seemed incoherent. It addresses itself to the interface between discourse and context, and argues that adequate contextualization of discourse can render incoherent speech more understandable. Appraisal of context and analysis of metacommentary--speakers' references to the ongoing talk--makes apparently incoherent discourse intelligible, and gives access to the patient's experience of her illness. The implications of discourse analysis for psychiatric research are explored. General goals for discourse analysis in psychiatric settings are suggested, and strengths and weaknesses of the approach discussed.

Adult↗
PubMed1987

Inhibition of captopril-induced renin release by angiotensin II.

The angiotensin-converting enzyme inhibitor (CEI) captopril has been shown to elevate plasma renin activity (PRA) and prostaglandin E2 levels, and to lower blood pressure and angiotensin II (AII) levels. Renin is secreted in both active and inactive forms; however, the interrelationship of these forms and responses to captopril are unclear. We proposed to determine if PRA rise induced by captopril is due primarily to release from AII inhibition, and if inactive renin is converted to active renin when PRA increases. Seven normal volunteers were given captopril, 50 mg orally, while on a moderately sodium-restricted diet (35 mEq/day). Changes in PRA and total and inactive renin, as well as prostaglandin E2, were measured. Then, on two different occasions, the captopril dose was preceded or followed by infusion of AII, to negate changes in AII induced by CEI. The dose of AII was obtained by dose-response infusion until a minimal increase in blood pressure occurred. Active renin increased with captopril alone, from 8.2 to 48.3 ng/ml/h by 90 min (p less than 0.01). AII completely blocked the rise in PRA induced by captopril, whether given before or after captopril. Inactive renin did not decline as active renin increased over the 90-min study. Therefore, the PRA rise induced by captopril is mediated through a fall in AII levels and loss of feedback on renin-secreting cells. The rise in PRA comes from secretion of active renin rather than conversion from inactive renin.

Adult↗
PubMed1985

Diuretics versus calcium-channel blockers in systemic hypertension: a preliminary multicenter experience with hydrochlorothiazide and sustained-release diltiazem.

The safety and efficacy of sustained-release diltiazem 120 to 180 mg, 2 times a day, were compared with hydrochlorothiazide 25 to 50 mg, 2 times a day, and the combination of diltiazem and hydrochlorothiazide in 56 patients with mild to moderate hypertension (supine diastolic blood pressure between 95 and 114 mm Hg) using a placebo-controlled, parallel-design protocol. Data from an additional 21 patients were evaluated for safety only. The data reported herein represent the preliminary experience from a larger 200-patient multicenter study. All patients received placebo for 4 weeks, followed by either hydrochlorothiazide or diltiazem titrated to achieve a diastolic blood pressure reduction of greater than or equal to 10 mm Hg to reach a goal supine diastolic blood pressure of less than 90 mm Hg. Patients not achieving the treatment goal received hydrochlorothiazide plus diltiazem. At week 14, on maintenance monotherapy, diltiazem and hydrochlorothiazide produced comparable reductions in blood pressure from placebo baseline (160.3 +/- 24.3/101.7 +/- 5.5 to 145.2 +/- 24.1/89.8 +/- 7.4 mm Hg with diltiazem, 156.0 +/- 15.6/103.7 +/- 4.7 to 134.1 +/- 12.5/89.2 +/- 9.5 mm Hg with hydrochlorothiazide, p less than 0.001 for both). Diltiazem and hydrochlorothiazide achieved goal blood pressure in 42% and 45% of patients, respectively. The effects in responders were sustained for 6 months. In patients who did not achieve the treatment goal, 63% responded to diltiazem plus hydrochlorothiazide.No clinically significant postural hypotension was observed on any regimen. Heart rate was slightly lower with diltiazem than with hydrochlorothiazide. Adverse effects were minimal with diltiazem, hydrochlorothiazide and diltiazem plus hydrochlorothiazide but more hypokalemia occurred with hydrochlorothiazide.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1984

Immunoregulation in hypersensitivity pneumonitis: phenotypic and functional studies of bronchoalveolar lavage lymphocytes.

We examined the immunologic phenotype and function of bronchoalveolar lymphocytes isolated from 4 pigeon breeders who developed symptoms of hypersensitivity pneumonitis on exposure to pigeons, and 6 asymptomatic but equally exposed individuals. Similar numbers of bronchoalveolar lymphocytes were found in symptomatic breeders compared with the asymptomatic, and the percent of T11, T4, and T8 bearing cells as well as the T4/T8 ratios were similar in both groups. Despite these similarities, the groups had significantly different functional activity. Bronchoalveolar lymphocytes from symptomatic breeders demonstrated a marked (p less than 0.001) increase in blastogenic activity to both phytohemagglutinin and pigeon serum stimulation when compared with asymptomatic breeders. In addition, enriched bronchoalveolar T-cells suppressed the response of autologous preincubated peripheral blood lymphocytes to both phytohemagglutinin and pigeon serum in the asymptomatic compared with the symptomatic breeders. These studies suggest a discrepancy between the phenotype and function of immunoregulatory T-cell subsets in bronchoalveolar lavage lymphocytes in pigeon breeder's disease, and support a role for functional immunoregulatory imbalances in the pathogenesis of hypersensitivity pneumonitis.

Adult↗
PubMed1983

Mechanisms of hypnotic and nonhypnotic forgetting.

Subjects participated in two experimental sessions designed to study laboratory-induced amnesia, one using a standard hypnosis paradigm and one using a non-hypnotic directed-forgetting paradigm. Two independent sources of variation were derived from the hypnotic amnesia data: retrieval inhibition and inhibition release. In the nonhypnotic directed-forgetting procedure, some items were cued to be forgotten shortly after presentation and some were cued to be remembered. At test, the subjects were asked to recall both the to-be-remembered and the to-be-forgotten items. Over 39% of the variance in the recall of the to-be-forgotten items could be accounted for by the inhibition and release constructs obtained with hypnosis. These relations between the two procedures were not mediated by verbal ability or cognitive style (field independence). We concluded that the mechanisms of forgetting involved in laboratory demonstrations of hypnotic and nonhypnotic amnesia are related, and the implication is that some of them are the same, namely, retrieval inhibition and inhibition release. We also argued that the possible demand characteristics that accompany the hypnosis procedure are not apparent with the nonhypnotic procedure. Therefore, the relationships observed in the present results were taken as evidence that hypnotically induced amnesia is not entirely the result of subjects' reactions to demand characteristics.

Amnesia↗
PubMed1978

Dietary assessment of coal miners in southern Illinois.

A survey was conducted in southern Illinois with a population of 46 coal miners and ex-coal miners ranging in age from 42 to 86 years. All the subjects were suffering from some degree of respiratory insufficiency. Three 24-hr dietary recalls were obtained from each participant and the mean daily intakes of 11 nutrients and calories were calculated by computer. Selected hematological analyses of blood were performed. Dietary intakes of calcium, vitamin A, and vitamin C were lowest within the population sample. The mean blood values indicative of iron status were within normal range. Physical inactivity among some of the miners accompanied by inadequate calcium intakes could predispose them to calcium-related skeletal infirmities. Inadequate intakes of vitamin A by the majority of subjects were particularly significant in this population. The role of vitamin A in maintaining healthy epithelial tissues is discussed and its possible association with a coal miner's susceptibility to pulmonary complications resulting from chronic exposure to coal dust. The results emphasize the value of assessing the nutritional status of individual coal miners and the need for personal dietary counseling.

Adult↗