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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 397 records · Page 22Linked to original sources

Hematopoietic thymocyte precursors: IV. Enrichment of the precursors and evidence for heterogeneity.

A method has been developed for the enrichment of the hematopoietic precursors of thymocytes from spleen and bone marrow cells. Up to 40-fold enrichments were obtained resulting in preparations in which as few as 10(5) cells produced prompt repopulation of the thymus of an irradiated mouse. Precursor cells from bone marrow appear to contain the enzyme terminal deoxyribonucleotidyl transferase (Tdt), an agent suggested as a potential somatic mutator. This enzyme (Tdt) was not detectable in any spleen cell preparation examined, including one in which a 40-fold enrichment of thymocyte precursors had been produced. This is the first difference reported between the splenic and bone marrow precursors of thymocytes.

Animals↗

Cognitive and perceptual differences between schizophrenics and organics.

Distinguishing between brain-damaged and schizophrenic patients remains a significant clinical problem. However, substantive and methodological difficulties have led to discouragement and consequent loss of interest in this area of differential diagnosis. Several models for making this distinction were proposed: cognitive, empirical-psychometric, attentional motivational, neuropsychological and information processing. In evaluating these models, three persistent methodological problems were identified: diagnostic inaccuracy, inadequate sampling, and difficulty in interpretation of the subject's performance. Various suggestions were made for resolving these difficulties through such means as equating samples for level of deterioration, utilizing modern, objective diagnostic techniques in the selection of samples, comparing subtypes of brain damage and schizophrenia, and using test procedures that have been shown to assess dispositional characteristics of the conditions under study, rather than their epiphenomena. It was suggested that recent substantive findings, mainly those involving neurological deficit in schizophrenia and detection of major behavioral differences among various subtypes of schizophrenia and brain damage, could be used in attempts to resolve the differential diagnostic problem under discussion. It was suggested that resolution of the methodological problems posed in combination with new substantive data concerning schizophrenic and brain-damaged patients may set the stage for a new start for investigating an old problem.

Attention↗

Age, thymic involution, and circulating thymic hormone activity.

Circulating thymic hormone activity and thymic histology were studied in patients undergoing open heart surgery. Plasma thymic hormone activity was measured using a bioassay based upon thymocyte antigen induction on null mouse lymphocytes. Activity was highest at 15-30 yr of age and declined thereafter, being negligible after the sixth age decade. The age-related decline of circulating thymic hormone activity correlated, in general, with progressive thymic involution. However, hormone activity was detected in plasma from some cases with advanced involution, suggesting that the normal young thymus may have considerable functional reserve.

Adolescent↗

Performance of brain-damaged, schizophrenic, and normal subjects on a visual searching task.

Goldstein, Rennick, Welch, and Shelly (1973) reported on a visual searching task that generated 94.1% correct classifications when comparing brain-damaged and normal subjects, and 79.4% correct classifications when comparing brain-damaged and psychiatric patients. In the present study, representing a partial cross-validation with some modification of the test procedure, comparisons were made between brain-damaged and schizophrenic, and brain-damaged and normal subjects. There were 92.5% correct classifications for the brain-damaged vs normal comparison, and 82.5% correct classifications for the brain-damaged vs schizophrenic comparison.

Adult↗

Thymopoietin enhances the allogeneic response and cyclic GMP levels of mouse peripheral, thymus-derived lymphocytes.

The action of the purified thymic factor, thymopoietin, on populations of post-thymic lymphocytes has been studied. Thymopoietin, at concentrations as low as 1.5 ng/ml, uniquely enhanced the proliferative response of peripheral T cells from lymph node and spleen to allogeneic stimulation. Enhancement of the allogeneic response (MLR) was not produced by several polypeptide hormones, including insulin, ACTH, HCG, or Ubiquitin. Treatment of spleen cells with anti-Thy-1 antiserum almost completely abolished the MLR. Thymopoietin's stimulatory effects could not reverse this. Thymopoietin treatment of Thy-1+-enriched spleen cell populations enhanced the MLR even when thymopoietin was removed as early as 2 min after incubation with responding cells. The interaction of thymopoietin with peripheral Thy-1+ cell populations produced a rapid and transient rise in cyclic GMP levels and slightly decreased cyclic AMP levels. These results suggest that thymopoietin interacts with one or more Thy-1+ subpopulations and that this interaction involves early changes in cyclic nucleotide metabolism.

Animals↗

Mode of action of levamisole.

Levamisole is a heterocyclic compound that is an effective antihelminthic agent and is also immunoregulatory. Its likely immuno-regulatory mode of action is by mimicry of the thymic hormone thymopoietin. Chemically, levamisole may form a thymopoietin-mimetic tertiary structure, stimulate lymphocytes by its imidazole component, or be metabolized to O.M.P.I., a reducing compound which affects radical scavenging in multiplying lymphocytes. Physiologically, thymopoietin affects many components of the immune system including both neutrophils, macrophages, and lymphocytes and its therapeutically important actions are probably targeted at stimulation of phagocytosis and stimulation of regulatory T cells to restore homeostasis in a perturbed immune system.

Animals↗

Nuclear magnetic resonance studies of the denaturation of ubiquitin.

The effects of pH, temperature and guanidine hydrochloride concentration on the structure of ubiquitin, a polypeptide which can activate adenylate cyclase and can mimic thymopoietin induced differentiation of prothymocytes, were monitored using nuclear magnetic resonance spectroscopy. This relatively small polypeptide (molecular weight of 8541) exhibits a remarkable stability towards pH and temperature changes. At 7 M guanidine hydrochloride concentration, the structure of ubiquitin is essentially a random coil.

Guanidines↗

Circulating thymic-hormone activity in congenital immunodeficiency.

Circulating thymic-hormone activity was assayed by measuring Thy 1-2 antigen induction on null lymphocytes from athymic mice incubated with human plasma or serum. Plasma from 19 normal children aged under 10 had inductive activity equivalent to 10-6-16-2 ng thymopoitin/ml. Plasma from 15 infants were severe combined immuno-deficiency, 2 of whom had appreciable immunoglobulin synthesis, and from 2 infants with DiGeorge syndrome had little or no inductive activity. Successful reconstitution with thymus or bone-marrow grafts and with red-cell infusions (if adenosine-deaminase deficiency is present) was followed by a rise in circulating thymic-hormone activity.

Agammaglobulinemia↗

Bioassay determinations of thymopoietin and thymic hormone levels in human plasma.

Thymopoietin is a thymic hormone that induces differentiation of thymocytes from precursor cells which arise in hemopoietic tissues. This paper describes a sensitive in vitro assay for the induction of Thy 1.2 antigen on null lymphocytes from germ-free athymic (nu/nu) mice. The sensitivity and specificity of the bioassay were increased by adding high concentrations of ubiquitin (a nonspecific inducer) to the induction incubations. The bioassay was sufficiently sensitive to detect thymopoietin at less than 0.25 ng/ml. A dose-response relationship was shown between thymopoietin concentration and the percentage of cells induced to express Thy 1.2 antigen. When normal human plasma was assayed, induction was registered with activity corresponding to thymopoietin at greater than 1 ng/ml in plasma from infants or young adults. Activities in the thymopoietin range of 0.25 ng/ml were registered with plasma from healthy subjects over 50 years of age. Thymectomy was followed by loss of this inductive activity from the plasma. This bioassay permits clinical studies on T (thymus-derived) cell inducers released by the human thymus into the circulation.

Adult↗