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Biomedical subjects

H B Kaplan

Publications and source records attributed to H B Kaplan.

At least 37 records · Page 2Linked to original sources

Stability of psychological symptoms: drug use consequences and intervening processes.

We integrate aspects of coping response, impaired ability, and motivational explanations for the causes and consequences of drug abuse, all which were cast previously as competing or alternative paradigms. We projected a model of 1) continual daily drug use as a consequence of early adolescent psychological symptoms and 2) continual daily drug use as an influential variable in maintaining or exacerbating these symptoms over the young adult life-course. Gender, race, and education also were modeled explicitly according to their presumed theoretical importance. Finally, we modeled contemporaneous factors such as physical health and employment status as the common consequences of the shared independent variables in order to reduce bias in the estimated structural relationships. We found that continual daily drug use is significantly dependent on early psychopathology and increases psychological symptoms significantly. Daily proximate drug use has direct negative effects on education. Education, in turn, improves both mental and physical symptoms significantly. During young adulthood, psychological symptoms are related significantly to contemporaneous unemployment and physical health limitations; thus modeling these symptoms as common consequences reduces potentially biased estimates of the effect of shared independent variables.

Adaptation, Psychological↗

Methodological problems in the study of psychosocial influences on the AIDS process.

Recent psychosocial research on the onset and course of AIDS is reviewed toward the goal of identifying major methodological problems in carrying out such research. The problems are identified as related to guiding theoretical statements, sampling plans, validity of measurement models, and analytic strategies. Increased understanding of the onset and course of AIDS will depend on the speed and effectiveness with which the methodological problems are addressed.

Acquired Immunodeficiency Syndrome↗

Explaining adolescent drug use: an elaboration strategy for structural equations modeling.

We report a series of analyses designed to estimate increasingly elaborated theoretical models that explain adolescent drug use. Each of the successive elaborations adds a theoretical construct to the explanatory model in order to increase our understanding of drug use by specifying in greater detail the nature of the structural relationships among the latent variables. The more detailed specification is accomplished by 1) specifying new direct effects that increase explained variance in drug use, 2) decomposing direct effects through the interpolation of hypothesized intervening variables, 3) specifying antecedents of variables that modify their direct effects, and 4) exposing suppressor effects. Where indicated, we evaluate alternative explanations of the observed relationships. We do this by controlling for common antecedent effects to reduce spuriousness or by examining different specifications of causal linkages among the explanatory constructs.

Adolescent↗

Overproduction and purification of the luxR gene product: Transcriptional activator of the Vibrio fischeri luminescence system.

Expression of Vibrio fischeri luminescence genes requires an inducer, termed autoinducer, and a positive regulatory element, the luxR gene product. A plasmid containing luxR under control of a tac promoter was engineered to overproduce this gene product. The overproduced luxR gene product was active in vivo, and its apparent monomeric molecular weight was indistinguishable from that of the protein encoded by luxR under control of its own promoter (M(r) 27,000). The new tac-luxR construct directed the synthesis of large quantities of the luxR gene product in induced Escherichia coli cells lacking other lux genes. In the presence of the other lux genes, overexpression of the tac-luxR construct was not detected. The overproduced luxR gene product, which formed cytoplasmic inclusion bodies, was purified and used in subsequent studies. Nonequilibrium pH gradient electrophoresis indicated that the protein was basic, and the amino-terminal 15 amino acids were sequenced. DNA-binding activity was detected by membrane filter binding assays; under the conditions used, the binding was not lux DNA-specific. Binding of tritium-labeled autoinducer to the luxR gene product was not detected, and autoinducer enhancement of the binding of the luxR gene product to DNA could not be detected reproducibly.

Journal Article↗

Complement activation during systemic lupus erythematosus. C3a and C5a anaphylatoxins circulate during exacerbations of disease.

To determine whether activated complement components appear in the circulation of patients with systemic lupus erythematosus (SLE), we measured C5a and C3a by radioimmunoassay. Mean C5a concentration in the plasma of acutely ill SLE patients was 46.0 ng/ml, compared with 17.1 ng/ml in normal controls (P less than 0.01). Mean C3a concentration in patients with severe disease was 526 ng/ml, compared with 134 ng/ml in controls (P less than 0.01). In patients with moderately active SLE, the mean C3a concentration, but not the mean C5a concentration, was also elevated. In addition, C3a was elevated in 15 or 21 patients with active SLE, whereas low levels of C3 or C4 were noted in only 7 of these 21 patients. We conclude that the measurement of complement-derived anaphylatoxins may be useful in the management of patients with SLE. In addition, we suggest that these circulating mediators may contribute to the pathogenesis of vascular injury in patients with the disease.

Complement Activation↗

Diffusion of autoinducer is involved in regulation of the Vibrio fischeri luminescence system.

The enzymes for luminescence in Vibrio fischeri are induced by the accumulation of a species-specific metabolite (autoinducer) in the culture medium. Tritium-labeled autoinducer was used to study the mechanism of autoinduction. When 3H-autoinducer was added to suspensions of V. fischeri or Escherichia coli, cellular concentrations equaled external concentrations. For V. fischeri, equilibration of 3H-autoinducer was rapid (within 20 s), and greater than 90% of the cellular tritium remained in unmodified autoinducer. When V. fischeri or E. coli cells containing 3H-autoinducer were transferred to autoinducer-free buffer, 85 to 99.5% of the radiotracer escaped from the cells, depending on the strain. Concentrations of autoinducer as low as 10 nM, which is equivalent to 1 or 2 molecules per cell, were sufficient for induction, and the maximal response to autoinducer occurred at about 200 nM. If external autoinducer concentrations were decreased to below 10 nM after induction had commenced, the induction response did not continue. Based on this study, a model for autoinduction is described wherein autoinducer association with cells is by simple diffusion and binding of autoinducer to its active site is reversible.

4-Butyrolactone↗

Self-derogation and adjustment in the community: a longitudinal study of psychiatric patients.

The authors assessed the symptoms and role performance of a group of psychiatric inpatients 1 year after their discharge to determine their level of adjustment in the community. Level of self-derogation at the time of discharge was consistently found to predict the level of adjustment. The occurrence of stressful life events was also predictive of symptoms but was not found to be significantly related to role performance. The chronicity of the disease was unrelated to adjustment. The change in self-derogation level and its ability to predict community adjustment is interpreted in terms of reestablishing the patient's belief in his or her own worth and efficacy.

Follow-Up Studies↗

Crisis treatment in a day hospital. Impact on medical care-seeking.

The cost-effectiveness of a day hospital program is documented by examining the utilization of medical and psychiatric services before and after a time-limited following crisis-presentations. Patients in crisis have been shown to have increased need for services following a crisis. In contrast, medical-care events decreased for the population treated in the day hospital. The results, with respect to reduction of medical care were greatest for those patients judged to have benefited from the psychiatric interventions.

Adolescent↗

Effects of non-steroidal anti-inflammatory agents on human neutrophil functions in vitro and in vivo.

Human blood neutrophils exposed to appropriate stimuli aggregate, degranulate and generate superoxide anion (O2-). These responses are anteceded by mobilization of membrane-associated calcium, monitored as a decrease in fluorescence of cells preloaded with chlortetracycline (CTC). We studied the effects, both in vitro and in vivo, of non-steroidal anti-inflammatory agents (aspirin, indomethacin, ibuprofen and piroxicam) on these neutrophil responses to three stimuli: a chemoattractant, N-formyl-methionyl-leucyl-phenylalanine (FMLP); a tumor promotor, phorbol myristate acetate (PMA); and a lectin, concanavalin A (Con A). The effects of these drugs were compared with those of two polyenoic inhibitors of arachidonate metabolism: eicosatrienoic acid (ETI) and eicosatetraynoic acid (ETYA). The pattern of inhibition of neutrophil functions varied both with inhibitor and the nature of the stimulus. Thus, aspirin, piroxicam, ETYA and ETI inhibited neutrophil aggregation, degranulation, and O2- generation in response to FMLP, whereas ibuprofen inhibited only aggregation and degranulation and indomethacin only inhibited aggregation. None of the agents inhibited aggregation or degranulation induced by PMA or Con A: only piroxicam inhibited O2- generation in response to PMA or Con A. ETI and ibuprofen inhibited decrements of CTC fluorescence induced by FMLP, but whereas ETI inhibited the CTC response to PMA or Con A, ibuprofen was without effect. The agents had varying effects on binding of the stimulus [( 3H]FMLP, [3H]Con A), but these did not correlate with neutrophil responses to the ligands. Neutrophils from subjects taking therapeutic doses of ibuprofen, indomethacin, or piroxicam showed profiles of inhibited responses to FMLP similar to those observed with these agents in vitro. These data suggest that, although non-steroidal anti-inflammatory agents may inhibit discrete neutrophil functions both in vitro and in vivo, their effects do not duplicate those of polyenoic inhibitors of arachidonate metabolism. Moreover, since the susceptibility of neutrophils differed not only with respect to each inhibitor, but also to the stimulus, it is unlikely that all neutrophil responses are necessarily linked by a common pathway that is blocked by inhibitors of arachidonic acid metabolism.

5,8,11,14-Eicosatetraynoic Acid↗

Generation of C5-derived peptides and other immune reactants in the sera of patients with systemic lupus erythematosus.

Activated complement components and immune complexes cause neutrophil aggregation in vitro and in vivo. We have previously demonstrated that sera of patients with active systemic lupus erythematosus (SLE) provoke the aggregation of normal neutrophils in vitro. In this study the serum or plasma of 4 such patients was fractionated on Sephadex G-75. In 3 patients neutrophil aggregating activity (NAA) was detectable in fractions which coeluted with reference C5-derived peptides (estimated molecular radius of 17,000). The activity of these fractions was inhibitable by antibodies to human C5. All patients also had activity that coeluted with reference immune complexes. In addition, material of apparent molecular radius under 12,000 that contributed to the neutrophil aggregating activity of SLE sera was detected. In separate experiments increased levels of C5a desarg were demonstrated during active disease by means of radioimmunoassay. These findings suggest that multiple neutrophil aggregants circulate during the course of active SLE. The formation of intravascular leukoaggregates may contribute to endothelial injury in this disease.

Antigen-Antibody Complex↗

Effects of diagnosis and treatment history on relapse of psychiatric patients.

Of 400 patients followed up for 1 year after release from the hospital, 34% were readmitted during that year. For schizophrenic patients the readmission rate was 49%, and for nonschizophrenic patients it was 21%. Rate of rehospitalization was positively related to number of prior hospitalizations, cumulative months of prior hospitalization, and duration of illness, but the relationship varied between the schizophrenic and nonschizophrenic groups. In contrast to the findings of Linn and associates, in this study prior hospitalization of nonschizophrenic patients markedly increased the likelihood of rehospitalization.

Adolescent↗

The roles of degranulation and superoxide anion generation in neutrophil aggregation.

Human neutrophils when exposed to appropriate stimuli aggregate, generate O(2) and secrete lysosomal constituents. To determine whether a causal relationship may exist between these responses neutrophils were exposed to either N-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, or the two calcium ionophores, A23187 and prostaglandin Bx. Each agent elicited all of the above responses. The concentrations required to elicit the aggregation of 30 . 10(6) neutrophils/ml were comparable to that required for O(2) generation or lysozyme release. In a series of experiments designed to dissociate these responses, cells were suspended in a concentration too dilute (3 . 10(6) neutrophils/ml) to permit aggregation to occur. O(2) generation and lysozyme release was measurable and varied in a dose-dependent fashion to the concentration of stimulus. In a second series of experiments, neutrophils were treated with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid to inhibit degranulation without affecting O(2) generation. Aggregation was inhibited in a parallel fashion with lysozyme release. When detectable O(2) was removed from the medium by superoxide dismutase and catalase, aggregation and lysozyme release unaffected showing that aggregation can not be due to the presence of O(2) or its products in the extracellular medium. Neither aggregation of resting cells nor augmentation of fMet-Leu-Phe-induced aggregation was observed when cells were exposed to either supernatants of degranulated neutrophils or constituents of specific granules (lysozyme, lactoferrin). Kinetic analysis showed that in the absence of cytochalasin B degranulation preceded aggregation, while in its presence aggregation preceded degranulation.

Cell Aggregation↗