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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 199 records · Page 11Linked to original sources

OKT3 monoclonal antibody plasma levels during therapy and the subsequent development of host antibodies to OKT3.

OKT3 levels and the presence of human antibodies to OKT3 were determined in the plasma of 66 patients receiving OKT3 monoclonal antibody (5 mg i.v. daily) for the treatment of acute renal allograft rejection. Plasma 24-hr trough levels of OKT3 rose over the first three days and then remained in a steady state over the remainder of the 14-day period of OKT3 therapy, with a mean level of 902 +/- 71 ng/ml (mean + SEM). On termination of OKT3 therapy plasma levels of OKT3 dropped to very low levels after 3 days. Host antibodies, usually of low titer, developed in a number of patients, usually 2-3 weeks after the start of OKT3 therapy. 37/43 patients (86%) who received OKT3 alone developed IgG anti-OKT3 antibodies; 9/23 patients (39%) who received Cytoxan in addition to OKT3 developed IgG anti-OKT3 antibodies, a significantly lower (P = 0.0002) incidence. The present regimens permitted maintenance of adequate levels of circulating OKT3 for 2 weeks, a sufficient time to reverse acute renal allograft rejection in most patients.

Antibodies, Anti-Idiotypic↗

Cognitive profiles of some subtypes of learning disabled adults.

Test profiles of 100 learning disabled adults were analyzed in an attempt to determine if patterns of learning disability subtypes which have been identified in children also persist into adulthood. On the basis of Wide Range Achievement Test reading and arithmetic grade level scores, subjects were classified into one of three subgroups. The classification resulted in finding 32 subjects who were substantially better at reading than arithmetic, 17 who were better at arithmetic than reading, and the remaining 51 with less than a 1.5-year grade level discrepancy between reading and arithmetic. Subgroup membership was used as the independent variable in a series of one-way analyses of variance which tested for differences in performance patterns on the Wechsler Adult Intelligence Scale and components of the Halstead-Reitan Neuropsychological Test Battery. While results support the view that most learning disabled individuals do not have specific disabilities, results suggest that it is possible to identify relatively small specific subtypes similar to those previously identified in learning disabled children, with some doing well at reading but poorly at arithmetic, and others doing very poorly at reading but relatively better, but not normally, at arithmetic. Cognitive testing of the first of these two specific subtypes revealed particular deficits in visual-spatial, nonverbal problem solving and complex psychomotor tasks. The second subtype did better on tasks of that type, but poorly on linguistic tasks.

Journal Article↗

Thymus hormones do not induce proliferative ability or cytolytic function in PNA+ cortical thymocytes.

A variety of thymus hormone preparations, as well as drugs known to perturb cell differentiation, were tested for their ability to induce nonfunctional cortical thymocytes to become functional precursor cells. Murine cortical thymocytes, defined as the high peanut agglutinin (PNA) binding or as the low H-2K, major [86%] thymocyte subpopulation, were isolated by fluorescence-activated cell sorting. Their function was assessed in a high cloning efficiency, growth factor saturated, concanavalin A-stimulated limit-dilution culture system, determining the number of precursors of extended clones (PTL-p), or determining with a lectin-mediated tumor-lysis readout the number of precursors of cytolytic clones (CTL-p). The hormone preparations tested were crude or partially purified culture supernatants from thymus "epithelial" monolayers (TES), soluble extracts of thymic nonlymphoid tissue (STF), semipure thymus humoral factor (THF), and the pure peptides thymopoietin 32-36 (TP5) and "facteur thymique sérique" (FTS). These preparations were either added directly to the limit dilution cultures, or were first preincubated with the cells, which were then subjected to limit-dilution culture. In no case did the hormone preparations cause any increase in the level of PTL-p or CTL-p in the PNA+ or low H-2K thymocyte population, even though a conversion of only a few percent to functional cells could have been detected. Two possible explanations are considered. One is that the main function of these materials is to control post-thymic peripheral T cells, rather than to induce intrathymic differentiation. Another is that the typical cortical thymocyte is beyond the stage at which thymocytes can be induced by hormones, a view that is strengthened by the failure of either 5-azacytidine or the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate to activate these cells. In this latter explanation the true intrathymic target of hormone action may be an earlier, and very minor, thymus subpopulation.

Animals↗

The economic costs of schizophrenia. Implications for public policy.

The direct and indirect costs associated with schizophrenia in Australia were calculated using the incidence approach and compared with similar costings of myocardial infarction in Australia and the United States. In Australia schizophrenia affects one-twelfth as many people as does myocardial infarction, yet costs half as much. This is because the stream of costs associated with each case of schizophrenia is six times the stream of costs associated with myocardial infarction. To illustrate the utility of this costing approach, the information was used to estimate the cost-benefit ratio likely to follow the introduction of social intervention strategies. The information also showed that Australian support for research in schizophrenia is inadequate when compared with that for myocardial infarction and quite out of proportion to the cost of schizophrenia to the community.

Adolescent↗

Thymopoietin to thymopentin: experimental studies.

Thymopoietin is a polypeptide hormone of the thymus consisting of 49 amino acids. The pentapeptide thymopentin (TP-5) Arg-Lys-Asp-Val-Tyr, corresponding to amino acids 32-36 of thymopoietin, appears to represent the active site of thymopoietin in that it has all the biological activities of the native hormone. Thymopoietin is secreted by epithelial cells of the thymus and is pleiotropic in action, affecting neuromuscular transmission, induction of early T cell differentiation and immune regulation. The immuno-regulatory actions of thymopentin on peripheral T cells are mediated by intracellular cyclic GMP elevations in contrast to the intracellular cyclic AMP elevations induced in precursor T cells that trigger their further differentiation to T cells. Thymopoietin and thymopentin have the biological characteristics of being immunonormalizing in a number of animal model systems of immune dysbalance. These include immune dysbalances induced by thymectomy or the thymic involution associated with aging or by other procedures in thymus-intact animals. The normalizing action of thymopentin, whether the immune dysbalance be in the direction of hyper- or hyporesponsiveness, points to its potential utility in human diseases characterized by immune dysbalance.

Animals↗

Thymopentin: stability considerations and potency by various routes of administration.

Thymopentin, the synthetic pentapeptide Arg-Lys-Asp-Val-Tyr corresponding to amino acids 32-36 of thymopoietin, was rapidly degraded in human plasma (T 1/2 = 30 s) and this was shown to be due to proteolytic enzymes in plasma. The biological potency of thymopentin varied greatly with the route of administration, a finding possibly related to its short half-life. Intravenous infusion provided the most potent and bolus intraperitoneal injection the least potent mode of administration. Thus the route and rate of administration are critical factors in determining the effective dose being received by the animal.

Action Potentials↗

Structural requirements for the biological activity of thymopentin analogs.

Thymopentin, the synthetic pentapeptide Arg-Lys-Asp-Val-Tyr, corresponds to residues 32-36 of the thymic hormone thymopoietin. Thymopentin, like thymopoietin, induces intracellular cGMP elevations in the human T-cell line, CEM. Thymopentin also displaces radiolabeled thymopoietin from a receptor glycoprotein prepared from CEM cells, provided that a nonapeptide corresponding to thymopoietin is added to block thymopoietin binding to an additional binding site. Twenty nine analogs with single position substitutions were synthesized by solid-phase or classical solution synthesis, and are evaluated in these assays. All analogs that were active gave positive effects in both assays. A number of substitutions were tolerated at positions 2, 4, and 5, but there was an absolute requirement for L- or D-Arg at position 1 and L- or D-Asp at position 3 to maintain biological activity.

Amino Acid Sequence↗

OKB7, a monoclonal antibody that reacts at or near the C3d binding site of human CR2.

OKB7, an IgG2 mouse monoclonal antibody, binds to the C3d receptor (CR2) of human B lymphocytes in or near the active site of the receptor. OKB7 precipitates the same molecule as monoclonal antibodies B2 and HB-5 which have previously been reported to react with the C3d receptor at epitopes distant from the active site. The epitope recognized by OKB7 is distinct from those bound by B2 and HB-5 as shown in competitive binding experiments and is near the complement binding site since OKB7 blocks EAC3d rosetting at concentrations as low as 1 microgram/ml in the absence of cross-linking antibodies.

Animals↗

Relationships between neuropsychological and psychopathological dimensions in male alcoholics.

A study was conducted of the relationships between psychopathology and neuropsychological deficit in chronic alcoholic patients who had received the Minnesota Multiphasic Personality Inventory (MMPI), the Halstead-Reitan Neuropsychological Test Battery, and the Wechsler Adult Intelligence Scale (WAIS). Classification of the MMPIs by code type resulted in the formation of groups of 10 subjects with normal MMPIs, 19 subjects with MMPI profiles suggestive of depression, and 10 subjects with profiles suggestive of psychosis. Analysis of covariance was performed for various Halstead-Reitan scores; the only significant findings emerged for several of the verbal subtests of the WAIS. The group with psychotic MMPIs did substantially more poorly on these measures than the other groups. It was concluded that depressed alcoholics do not show greater neuropsychological deficit than do individuals with no significant psychopathology other than alcoholism. However, alcoholics with MMPI profiles that suggest psychosis differ from the other groups studied with regard to certain verbal abilities.

Adult↗

Pentazocine.

Published clinical studies and extensive experience has shown that pentazocine, the first of the practical agonist/antagonist analgesics, is a potent analgesic with wide application in clinical medicine. It has been shown to have a spectrum of pharmacological activity which has qualitative differences from pure opiate agonists and these have important implications in clinical medicine. Pentazocine can provide analgesia as great as the opiates including morphine and meperidine, but does not have the same effect on mood. It is, therefore, less effective than the opiates in those situations where an anxiolytic effect is desired. Conversely, it produces less CNS depression in particular with regard to respiratory depression and nausea and vomiting. It also does not have the same potential for producing hypotension. The parenteral administration of pentazocine produces rapid strong analgesia which is of less duration than with morphine or meperidine. The oral administration of pentazocine is less predictable with regard to response but in appropriate patients it is capable of providing a similar degree of analgesia to that achieved with parenteral pentazocine. The dependence liability of pentazocine is substantially less than that with the opiates, and where abuse of parenteral pentazocine alone has taken place, it has usually been in medical and paramedical personnel seeking a support for inadequate personalities. Though physical and psychic dependence to parenteral pentazocine is undoubtedly possible, its incidence is extremely low with regard to the extent of the therapeutic use of pentazocine.

Aged↗

Statistical relationships and discriminative accuracy of the Halstead-Reitan, Luria-Nebraska, and Wechsler IQ scores in the identification of brain damage.

Ninety-two patients (46 brain-damaged and 46 control) were administered both the Halstead-Reitan and Luria-Nebraska Neuropsychological Batteries and the WAIS. The relationship between the Luria and the Halstead Battery was assessed using a common metric, T scores, and also by comparing impairment ratings for both batteries. Diagnostic screening accuracy was compared using discriminative functions and by computing the percentage of brain-damaged and control cases falling above and below the combined group medians. Results of the discriminative analyses were also compared with those obtained using only IQ scores from the WAIS. Findings support the comparability of the two neuropsychological test batteries with respect to diagnostic screening accuracy and the extent to which they measure level of impairment. Interestingly, equivalent discrimination between organic and control subjects was obtained using WAIS IQ scores. However, differences in the instruments did emerge on an individual case basis.

Adult↗