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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 433 records · Page 24Linked to original sources

Antigenic and functional evidence for the in vitro inductive activity of thymopoietin (thymin) on thymocyte precursors.

Thymopoietin, a polypeptide hormone isolated from bovine thymus, induced in vitro the differentiation of prothymocytes to cells with the antigenic and functional characteristics of intrathymic thymocytes. These changes included the acquisition of the differentiation antigens TL and Thy-1 (theta) and the ability to respond to the mitogen Con-A. Thymopoietin appears to be highly speicfic in inducing the prothymocyte to be highly specific in inducing the prothymocyte to thymocyte differentiation and does not affect the pluripotential stem cell measured by the colony forming assay (CFU-S), the erythropoietin-sensitive cell or B-cells. Experiments are in progress to determine whether additional hormonal inductive signals are required to complete the differentiation of an immunologically competent T-cell.

Animals↗

The Papago psychology service: a community mental health program on an American Indian reservation.

A community psychology service run by the Papago Indian tribe and staffed largely by Papago Indians who have been trained as mental health workers is described. This service is unique among mental health services for Indians in that the tribe has complete control of the funds for the service and sets its own policies. It was developed for a rather traditional Indian group, and the culture, the traditions, and the wishes of the Papago community were respected. Consultation with medicine men was built into the program from the start, and adaptation of mental health techniques to fit the culture is stressed. Before this clinic was established, few mental health resources were directly available to the reservation. Similar to other Indian tribes, the Papagos are economically disadvantaged, with an unemployment rate of over 50%, low educational attainment, and very high rates of alcoholism, suicide, and vehicular accidents. The topics covered are the tribe's view of health programs for its people, the present Papago community and traditional means of treatment, traditional psychotherapy adapted to Papago culture, the indigenous Papago mental health worker, and the non-Indian professional consultant.

Administrative Personnel↗

The amino acid sequence of thymopoietin II.

The amino acid sequence of bovine thymopoietin II is presented. This T cell differentiating hormone of the thymus is a single 49 amino acid polypeptide chain of 5562 daltons. There is microheterogeneity at the C terminus with approximately two thirds of the molecules lacking the C terminal arginine found on the remaining molecules. Determination of the primary structure of thymopoietin II was facilitated by a long automated sequenator run on thymopoietin II coupled to 2-isothiocyanonaphthalene-4,8-disulfonic acid (NITC), tryptic cleavage of maleated thymopoietin II to yield the overlapping C terminal peptide, and efficient manual sequencing of this peptide using benzene extractions to minimize extractive losses of peptide.

Amino Acid Sequence↗

Chemical synthesis of a peptide fragment of thymopoietin II that induces selective T cell differentiation.

Thymopoietin is a polypeptide hormone of the thymus that consists of a 49 amino acid polypeptide chain of 5562 daltons. A peptide corresponding to positions 29-41 of bovine thymopoietin II was synthesized by the Merrifield solid-phase technique. This peptide was shown to have a purity (correct sequence) of 96% by amino acid and C terminal analyses and by a complete determination of the amino acid sequence by manual Edman degradations. It displayed a selectivity of action similar to that of thymopoietin itself, inducing the differentiation of T lymphocytes but not of complement receptor (CR+) B lymphocytes. Although a number of substances induce the differentiation of both T cells and CR+B cells under the conditions of assay in vitro, only thymopoietin and the synthetic peptide described in this report have been shown to induce the differentiation of T cells selectively. Our data establish that the key residues involved in the active site of thymopoietin are present within a synthetic polypeptide which constitutes a minor portion of the amino acid sequence of thymopoietin. Since this peptide had 3% activity by comparison with thymopoietin, the tertiary structure of thymopoietin may be required for optimal configuration of the active site to produce full biological activity.

Amino Acid Sequence↗

Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells.

A polypeptide of 8500 molecular weight is described that induces the differentiation of T (thymus-derived) cell and B (bone-marrow-derived) cell immunocytes in vitro, apparently via beta-adrenergic receptors and adenylate cyclase activation. This polypeptide shows a high degree of evolutionary conservation, exhibiting close structural, functional, and immunological similarity when isolated from such diverse origins as cells of mammals and higher plants. This polypeptide was detected in animal cells, yeast, bacteria, and higher plants, and so may well be a universal constituent of living cells.

Adenylyl Cyclases↗

Similarities and differences between psychological deficit in aging and brain damage.

This study compared education matched young brain-damaged, young nonbrain-damaged, old brain-damaged and old nonbrain-damaged groups on a battery of measures of cognitive, perceptual, and motor skills. By means of a factor analysis, the 26 original measures were reduced to four, called nonverbal memory, language ability, motor ability, and psychomotor problem solving. Factor scores were obtained for each of these measures and were subjected to a linear discriminant analysis; 48.3% of the cases were correctly classified. Plotting of the canonical variable suggested that the first discriminant function separated the young nonbrain-damaged group from the others, but did not discriminate well otherwise. The second discriminant function was noncontributory. Multi-variate analysis of variance produced significant main effects for the "age" and "brain damage" factors, but the interaction term was nonsignificant. Inspection of the cell means indicated that the four measures interacted differentially with age.

Adult↗

Thymus-repopulating capacity of cells that can be induced to differentiate to T cells in vitro.

It was established previously that committed precursors of T cells, which reside in bone marrow and spleen and lack T cell surface differentiation antigens, can be induced by thymopoietin and certain other agents to differentiate rapidly in vitro into T cells bearing typical surface antigens, including Thy-1 and TL (Komuro-Boyse assay). To relate this differentiative step observed in vitro to physiologic events in vivo, a system was devised to trace the migration of precursor cells to the thymus, and their maturation to T cells. Lethally irradiated mice of a TL- strain received spleen cells from TL+ hybrids i.v., and the TL+ population of the thymus was enumerated 13 to 20 days later. Donor TL+ cells first became detectable at 13 days and increased thereafter. Preliminary tests showed that cells capable of migrating to the thymus have a similar density to the cells that are inducible in the Komuro-Boyse assay, this being lower than that of mature of T cells. The thymus-repopulating properties of the donor spleen population were not affected by: 1) pre-treatment in vitro with thymus extract or thymopoietin, which initiates differentiation of T cells precursors, nor b) pre-treatment with anti Thy-1 serum plus complement, which eliminates differentiated T cells. But pre-treatment a) and b) applied in sequence markedly reduced the capacity of spleen cells to repopulate the thymus. These results can be interpreted as follows: induction of Thy-1-TL- precursor cells (pro-thymocyte) in vitro yields Thy-1+TL+ cells (early thymocytes) which have not yet lost their property of repopulating the thymus; therefore, thymus-repopulation was not depleted by treatment a) alone, which induced Thy-1 +TL+ cells, nor by treatment b) alone, which did not affect thymus-repopulation by Thy-1-TL- cells, although treatments a) plus b) did eliminate the newly induced Thy-1+TL+ cells and thus impaired repopulation of the thymus. We conclude that the cell which responds to thymopoietin in the Komuro-Boyse assay by expressing the T cell surface phenotype is the same cell (pro-thymocyte) that normally migrates in vivo from hemopoietic tissues to the thymus and is there induced by thymopoietin to express the phenotype of an early T cell.

Animals↗

Induction of T-cell differentiation in vitro by thymin, a purified polypeptide hormone of the thymus.

Thymin, a purified polypeptide isolated from bovine thymus, was shown to induce the expression of differentiation antigens characteristic of thymocytes [TL and Thy-1 (theta)] when incubated in vitro with mouse bone marrow or spleen cells. This induction occurred in 5-10% of the cells from bone marrow after a 2-hr incubation with subnanogram concentrations of thymin. The induced cells expressed more TL and Thy-1 (theta) antigens than average normal thymocytes.

Animals↗