Search PubMed⌕ Search

Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 379 records · Page 21Linked to original sources
PubMed1979

A synthetic pentapeptide with biological activity characteristic of the thymic hormone thymopoietin.

The pentapeptide arginyl-lysyl-aspartyl-valyl-tyrosine, corresponding to amino acid residues 32--36 in thymopoietin, was synthesized. In vitro, this pentapeptide induced the differentiation of murine prothymocytes to thymocytes and inhibited differentiative induction of cells of the B lineage. This combination of actions is presently unique to the parent molecule thymopoietin. In vivo, the pentapeptide reduced the high numbers of autologous rosette-forming cells normally present in the spleens of athymic mice; this also is a property of thymopoietin. These results suggest that this readily synthesized pentapeptide corresponds to an active site of thymopoietin and might serve as a therapeutic substitute for thymopoietin.

Amino Acid Sequence↗
PubMed1979

Myasthenia gravis, thymectomy and serum thymic hormone activity.

Serum thymic hormone activity was measured in 36 patients with myasthenia gravis and in 10 control subjects from each age decade. In all 25 patients under 50 years of age results were within, or close to, the normal range. Activity at levels considered normal for juveniles was detected in 10 of the 11 older patients whereas levels normally decline in older subjects. One week after thymectomy, 13 of 17 patients (76 per cent) had no demonstrable serum thymic hormone activity. However, 10 months or longer after thymectomy only five patients (30 per cent) lacked thymic hormone activity in the serum. There was a significant correlation between clinial improvement and sustained lowering of serum thymic hormone activity after thymectomy.

Adolescent↗
PubMed1979

Separation of functional subsets of human T cells by a monoclonal antibody.

A monoclonal antibody was produced to human peripheral blood T cells. This hybridoma antibody, termed OKT4, was reactive by indirect immunofluorescence with only 55-60% of the peripheral blood T cell population (OKT4+) and unreactive with normal B cells, null cells, and macrophages. The OKT4- T cell population contained the previously described TH2+ subset that has been shown to contain cytotoxic/suppressor cells. With cell-sorter separation of OKT4+ and OKT4- cells, it was shown that these T cell subsets were functionally discrete. Both gave proliferative responses with concanavalin A, alloantigens, and phytohemagglutinin although OKT4+ cells were much more responsive to the latter. OKT4+ cells alone responded to soluble antigens whereas OKT4- cells alone were cytotoxic after alloantigenic sensitization of unfractionated T cells. However, both OKT4+ and OKT4- cells were required during sensitization for optimal development of cytotoxicity. These data suggest that the OKT4+ subset represents a helper population and that the OKT4- subset contains the cytotoxic effector population. OKT4 could be a valuable reagent for determining alterations of these functional subsets in human diseases.

Antibody Specificity↗
PubMed1979

Short in vitro half-life of thymopoietin32--36 pentapeptide in human plasma.

Thymopoietin32--36 (TP5) is a synthetic pentapeptide that has the biological activity of its parent molecule, the 49 amino acid thymic hormone thymopoietin. Tritiated thymopoietin32--36 (3 /-TP5) was prepared by reductive tritiation of dibromotyrosyl-TP5. The stability of 3 H-TP5 in human plasma was studied by analyzing samples by thin-layer chromatography at different time points and quantitating the radioactivity associated with TP5 (Arg-Lys-Asp-Val-Tyr) and its tyrosyl-containing breakdown products (Lys-Asp-Val-Tyr, Asp-Val-Tyr, Val-Tyr, Tyr). In plasma (but not in saline) the pentapeptide was rapidly degraded (apparent t1/2 approximately 30 seconds) with the corresponding appearance of radioactivity associated with the other tyrosyl-containing reference compounds. These data imply that the pentapeptide, which is active in vivo, may rapidly trigger changes in responsive cells; sustained circulating levels may not be required for activity.

Adult↗
PubMed1979

Cognitive and affective responses to lithium in patients with organic brain syndrome.

The authors describe a series of patients with organic brain syndrome who showed a dramatic clinical response to lithium carbonate therapy. None of the patients had been diagnosed as manic-depressive. Most had extensive psychiatric treatment experiences and had been given both affective and cognitive diagnoses. Six of the eight patients also qualified for the diagnosis of alcoholism. They had been treated with a wide variety of psychotherapeutic medications. Lithium was found to be rapidly and dramatically effective in patients with static lesions of the central nervous system who showed a combination of dementia and agitated depression.

Affect↗
PubMed1979

Angel dust use in an outpatient setting--clinical profile and implications for treatment.

The study attempts to identify two populations of 20 young people who are self-reporting marijuana use in one group and angel dust in the other. We have examined these populations and evaluated them on a series of variables in an attempt to discover whether there are significant differences between them and, if so, whether there is in fact a clinical profile which may be descriptive of nonacute reactions to angel dust. Results indicate that there are significant differences on variables that distinguish angel dust users in an outpatient setting.

Adolescent↗
PubMed1979

Survey research and the silent majority.

A survey conducted at the New York University Dental Center demonstrated that significant differences exist between patients who are ready participants in research efforts and those who require the more persistent attention of the researcher. In addition, patients who were questioned while in treatment emphasized different reasons for selecting a dental school for treatment than did those patients who were interviewed prior to beginning treatment. The importance of collecting data from a truly random sample of patients is stressed and elaborated with reference to the marketing implications of the results. Strategies for patient recruitment and retention require knowledge that is complete and does not suffer from systematic absences in the data base. Careful data collection methods are described and advocated.

Academic Medical Centers↗
PubMed1979

Early stages of human marrow lymphocyte differentiation: induction in vitro by thymopoietin and ubiquitin.

To study early stages of human lymphocyte differentiation, bone marrow cells were physically separated according to their density and size by gradient centrifugation and then velocity sedimentation. The isolated cell fractions were incubated with putative inducing agents and then assayed for their expression of an array of surface differentiation markers. The inducing agents used were two polypeptides, thymopoietin (Tp) and ubiquitin (Ub), and the cyclic nucleotide, dibutyril cyclic 3'5' adenosine monophosphate (cAMP). Tp, Ub, and cAMP each induced the ability to form sheep erythrocyte rosettes by small lymphocytes, which may thus represent T cell precursors. Ub and Tp induced rosette formation with mouse erythrocytes on lymphocytes of more heterogenous size, which may be "early" B cell precursors. Ub alone could induce surface IgM expression on small lymphocytes, which might be "late" B cell precursors. Both Tp and Ub induced Fc receptors on small lymphocytes. Complement receptors could not be induced on marrow lymphocytes by Tp, Ub, or cAMP. A number of lymphocyte precursors can thus be identified by their physical characteristics and their ability to respond to particular soluble factors with the expression of new differentiation markers.

Adult↗
PubMed1979

A novel lymphocyte differentiating factor in serum of patients with mycosis fungoides and Sezary syndrome.

Sera from 13 patients with mycosis fungoides and 2 with Sezary syndrome were tested for activity that induces lymphocyte differentiation. Induction of Thy-1.2 antigen and surface immunoglobulin were used, respectively, to measure T- and B-cell differentiation. The indicator cells were null lymphocytes from the spleens of congenitally athymic nude mice. Normal serum induced some T-cell but no B-cell differentiation. The T-cell-inducing activity was ascribed to thymic hormone and declined with advancing age. A totally different pattern emerged with patient serum. T-cell-inducing activity was significantly more active than in normal serum (p less than 0.001). This activity did not decline with advancing age and was not inhibited by a concentration of ubiquitin, which blocks nonspecific beta-adrenergic induction. B-cell-inducing activity was also present. This novel serum factor (or factors) is a potent inducer of T- and B-lymphocyte differentiation and is associated with neoplastic lymphoproliferation of the T-cell series.

Adult↗
PubMed1979

Further characterization of the human inducer T cell subset defined by monoclonal antibody.

Evidence is presented that the OKTA+ T cell subset in man, defined by a monoclonal hybridoma antibody, provides help for B lymphocyte differentiation in a PWM driven system. Both B cell proliferation and intracytoplasmic immunoglobulin synthesis are facilitated by OKT4+ and not by OKT4- T cells. Given earlier studies demonstrating that OKT4+ T cells were necessary for generation of T cytotoxic cells and the present study that OKT+ T cells are necessary for the differentiation of B cells, it would appear that the OKT+ population is the major human T helper (inducer) subset.

Animals↗
PubMed1979

Encopresis in adolescence: two case studies.

Encopresis is an underreported psychopathological symptom of adolescence, not necessarily defining a specific diagnostic entity. The two cases presented offer an opportunity to evaluate encopresis occurring in markedly different adolescent pathological entities and developmental backgrounds. The first patient presented a longitudinal life course wherein toilet training and fecal considerations were prominent throughout his development. Indeed, this young man had such areas of cohesive functioning, as to be appropriately considered within the range of characterological pathology, severe, though it may be. In marked contrast, the second patient's encopresis represented but a small part of a totally encompassing psychotic disintegration.

Adolescent↗
PubMed1979

Increased blood-brain barrier permeability to tetracycline in rabbits under dysbaric conditions.

Alteration of the blood-brain barrier (BBB) by dysbaric exposure may have relevance in several areas of hyperbaric medicine. Drugs administered to persons exposed to dysbaric conditions, e.g., divers, compressed air workers, may penetrate the brain in amounts that could produce toxic or undesirable effects. Modification of the BBB may also have pathogenetic implications in decompression sickness. Furthermore, increased BBB permeability to certain potentially useful antitumor agents, antibiotics, and other compounds under dysbaric conditions may provide the basis for a new therapeutic approach. This report concerns the influence of dysbaric exposure on BBB permeability to an antibiotic. Tetracycline (5-40 mg/kg) was intravenously injected in 22 experimental rabbits (subjected to air compression-decompression) and 17 controls (kept at ambient pressure). Fluorescence microscopy and spectrometry revealed significantly greater tetracycline concentrations in 72.7% of the experimental brains. With the 5 mg/kg dose, the mean tetracycline concentrations was 0.17 micrograms/g in control brains and 0.33 micrograms/g in experimentals. These results indicate that dysbaric exposure increases BBB permeability to tetracycline. It appears that BBB alteration is related to intravascular gas bubbles but is independent of the development of decompression sickness. The conclusions of this investigation are pertinent to brain pharmacotherapy and may provide some new insight into the mechanism of decompression sickness. They also point to potential risks connected with drug administration under dysbaric conditions that can alter BBB permeability.

Animals↗
PubMed1978

Immunological studies of aging. IV. The contribution of thymic involution to the immune deficiencies of aging mice and reversal with thymopoietin32-36.

Aged mice preferentially lose the capacity to make IgG and high affinity PFC after immunization with the T-dependent antigen DNP-BGG. We have found that thymectomy accelerates the appearances of these immune deficiencies associated with aging. When splenocytes from old mice are transferred to young lethally irradiated, syngeneic mice and the recipients immunized 7 wk later, the number of IgG and high affinity PFC was increased compared to the response of old splenocytes transferred to young thymectomized mice. These immune deficiencies of aged mice were also reversed when old mice were treated with thymopoietin in vivo or splenocytes from old mice were incubated with thymopoietin before adoptive transfer to young irradiated, thymectomized syngeneic mice. The T-cell independent response to DNP-Ficoll was less impaired than the T-cell dependent response to DNP-BGG in old animals. These data suggest that a decline in thymic function that occurs during aging may contribute to the immunological deficiencies of old animals.

Aging↗
PubMed1978

Chemical synthesis of a hexadecapeptide segment of ubiquitin that activates adenylate cyclase and induces lymphocytes to differentiate.

A hexadecapeptide corresponding to positions 59--74 of ubiquitin was synthesized and purified. The peptide was characterized by its mobility in TLC and electrophoresis, amino acid sequence and composition, and molar rotation. The peptide possessed approximately 40% activity compared with native ubiquitin in each of 3 biological assays in vitro: a) thymocyte induction, b) B cell induction and c) elevation of intracellular cyclic AMP levels in sarcoma 180 cells.

Adenylyl Cyclases↗
PubMed1978

The generation and regulation of lymphocyte populations: evidence from differentiative induction systems in vitro.

Results with a dual assay, for the induction of Thy-1+ T cells and of CR+ B cells from marker-negative precursors, confirm that thymopoietin is at present the only known selective inducer of prothymocytes. In contrast, various inducers, including ubiquitin, are active in both assays. Pharmacological evidence indicates that there are different cellular receptors for ubiquitin and thymopoietin. Prothymocytes and pro-CR+ B cells compose two distinct populations in bone marrow and spleen; their distribution in density gradients is different, and elimination of either population enriches the other proportionately. There are no noteworthy differences between induction of these two populations in regard to (a) kinetics, (b) dependence on temperature and protein synthesis, (c) activation by cAMP, and (d) inhibition by cGMP. The opposite inductive effects of cAMP and cGMP were corroborated by the use of pharmacological agents that raise or lower the levels of intracellular cyclic nucleotides. In contrast, a third induction assay, which monitors acquisition of the PC+ surface phenotype, indicates that this differentiative step, the last known for B cells, is initiated by cGMP and inhibited by cAMP. Induction of PC is also inhibited by thymopoietin, signifying that the inductive selectivity of thymopoietin is not due to restriction of its receptors to the T lineage cells. Rather it seems that receptors for thymopoietin occur also on PC-inducible and other B cells, although in this case geared biochemically to inhibition rather than expression of the succeeding gene program. This suggests a role for thymopoietin in the coordinated interregulation of lymphocyte classes, in addition to its better-known function as the thymic inducer of prothymocytes. Present data conform to a general scheme in which the cyclic nucleotides cAMP and cGMP, and agents that affect intracellular levels of these mediators, influence reciprocally the early and late (functional) phases of lymphocyte differentiation as a whole, while thymopoietin influences reciprocally the differentiation of the B and T classes of lymphocyte.

Animals↗