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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 343 records · Page 19Linked to original sources
PubMed1981

Suppression of human T-cell mitogenesis and E-rosette formation by the monoclonal antibody OKT11A.

OKT11A, a monoclonal anti-human T-cell antibody was studied for its in vitro effects on lymphocyte functions. At a concentration as low as 10 ng/ml, OKT11A significantly suppressed T-cell proliferation induced by OKT3, purified protein derivative (PPD), tetanus toxoid and allogeneic non-T cells. Total inhibition of proliferation was noticed at concentrations of 1-10 microgram OKT11A/ml. The antibody was only fully effective when added to stimulated cell cultures within the first 2 hr of the culturing period. OKT11A also blocked total and active sheep erythrocyte (E)-rosette formation by T lymphocytes: this activity closely paralleled the suppression of proliferative response. Quantitative studies on the binding of 125I-labelled IKT11A indicated that an average of 2 x 10(4) antibody molecules were bound per T cell. Taken together, these findings show that OKT11A recognizes a sparsely represented T-cell surface determinant that is associated with the inhibition of mitogenic responsiveness and E-rosette formation. Furthermore, our data imply that the E-rosette receptor of T cells is involved in the regulation of immune functions.

Animals↗
PubMed1981

The human thymic environment.

Selected combinations of antisera labelled with different fluorochromes were used to explore the cellular interactions in the human thymic cortex and the medulla. In the early fetal thymus the cortical epithelial cells and an apparently more mobile medullary interdigitating cell population expressed large amounts of Ia-like (HLA-DR) and moderate amounts of HLA-A,B,C antigens while the lymphoid cells in the cortex expressed human T lymphocyte and cortical thymocyte antigens but were Ia-, HLA-A,B,C-. This arrangement is maintained in the infant thymus. The terminal deoxynucleotidyl transferase enzyme is first generated in cortical thymocytes (around the 17th week of gestation) and appears in bone marrow precursor cells later. In the infant thymus the lymphoid populations could be classified, according to their reactivity pattern with the new monoclonal antibodies of the OKT series, into three cell types: putative prothymocytes, typical cortical thymocytes and medullary thymocytes. Among the medullary population the majority showed the phenotype of the "inducer" cell and a minority showed that of "suppressor-cytotoxic" cells. The thymic medulla (and interdigitating cells in peripheral lymphoid organs) may predominantly contribute to the generation of "inducer" T lymphocytes.

Animals↗
PubMed1981

Improvement of natural killer activity and of T cells after thymopoietin pentapeptide therapy in a patient with severe combined immunodeficiency.

The case of an 18-month-old child, affected by malnutrition, severe interstitial pneumonia and immunological abnormalities is reported. Since the age of 10 months, the infant suffered from severe recurrent infections and failure to thrive. Immunological studies revealed a striking decrease of T lymphocytes and of natural killer (NK) function. Serum immunoglobulins, salivary IgA, natural isohaemagglutinins, Fc-IgG receptor-bearing cells and suppressor T lymphocytes were absent, together with an impaired de novo DNA synthesis after PHA, Con A, PWM and Cowan I strain from Staphylococcus aureus stimulation. In vitro incubation of the patient's lymphocytes with TP-5, a thymopoietin-derived synthetic pentapeptide, resulted in improvement of sheep rosettes, Fc-IgG receptor-positive lymphocytes and NK activity. The child was therefore treated with TP-5 for 8 months and his clinical condition improved as well as the number of T cells, Fc-IgG-positive lymphocytes and NK function. However, humoral immunity remained persistently depressed. We suggest that this child could be classified as affected by 'late-onset severe combined immunodeficiency'. In vitro assays with thymic hormones or synthetic drugs that mimic the action of thymic hormones should be performed and this therapy could be applied in the treatment of some of these heterogeneous syndromes, especially when an immunological reconstitution with bone marrow or fetal graft cannot be attempted.

Antigens↗
PubMed1980

Effects of cyclosporin A on suppressor and inducer T lymphocytes in primary biliary cirrhosis.

There is a significant decrease in the ratio of inducer (helper) to suppressor T lymphocytes in the peripheral blood of patients with primary biliary cirrhosis (PBC). These changes are not seen in other forms of cholestatic liver disease, but are similar to those described in chronic graft-versus-host disease. Cyclosporin A treatment increased the proportion of suppressor A lymphocytes and improved liver function in 6 patients with PBC. This indicates that cyclosporin A is an immunoregulatory drug. Unfortunately nephrotoxicity precluded long-term use.

Cyclosporins↗
PubMed1980

Solution conformation of thymopoietin32-36: a proton nuclear magnetic resonance study.

The aqueous solution conformation of Arg-Lys-Asp-Val-Tyr (TP5), corresponding to positions 32-36 of the thymic hormone thymopoietin has been investigated by proton nuclear magnetic resonance (NMR). This pentapeptide fragment retains the biological activity of the parent protein, viz., induction of selective differentiation of T lymphocytes. All the observed NH and CH resonances of TP5 have been assigned, and the solution conformation of this peptide has been investigated by analysis of chemical shift variations with pH, vicinal NH-C alpha H coupling constant data, and amide hydrogen exchange rates. The latter were measured in H2O by using a combination technique consisting of the transfer of solvent saturation and saturation recovery NMR experiments. The data are compatible with the assumption of a highly motile dynamic equilibrium among different conformations for TP5. A comparison of the amide hydrogen exchange rates of the pentapeptide with that of solvated model compounds shows that Val4-NH is significantly shielded from the solvent. In addition, the chemical shift variations with pH suggest that the guanidino-N epsilon H of arginine is associated with one of the carboxylate groups. These observations provide specific boundary conditions for the construction of molecular models of the conformation(s) of TP5 in aqueous solution.

Fourier Analysis↗
PubMed1980

Improved radioimmunoassay technique for measuring serum thymopoietin.

An improved radioimmunoassay technique for measuring serum thymopoietin has been developed which obviates the spurious displacements previously obtained with serum samples, and increases sensitivity to 20 pg. Key improvements involved further purification of labeled thymopoietin, sequential incubations to enhance sensitivity and the use of charcoal-treated serum blanks to render controls and unknown samples comparable to the standard curve.

Animals↗
PubMed1980

Physical-chemical properties of ubiquitin.

The secondary structure of ubiquitin, the environment of its single tyrosine residue and its potential for interacting noncovalently with histone 2A or DNA, have been probed by circular dichroism (CD), ultraviolet absorbance, fluorescence and ancillary techniques. The results indicate that ubiquitin has a stable secondary structure containing only a low percentage of alpha-helix or beta-sheet. The ubiquitin tyrosine has an elevated pKa arising from the influence of a spatially proximate carboxylate which also causes a marked quenching of the tyrosine fluorescence at neutral pH; the influence of this carboxylate is lost when the protein is unfolded in 7 M guanidine. No evidence has been obtained for the presence of allosteric noncovalent interactions between free ubiquitin and either histone 2A or purified unfractionated DNA. The results suggest that one function of ubiquitin (or of the ubiquitin segment of protein A24) may be to interact with a chromatin component other than histone 2A or DNA, and/or that ubiquitin functions within 2A as a steric blocking group of a region of the nucleosome.

Animals↗
PubMed1980

An inhibitor of thymic hormone activity in serum from patients with lymphoblastic leukemia.

Serum from 21 patients with lymphoblastic leukemia, five with myeloblastic leukemia and 30 age matched control subjects tested for thymic hormone activity in an assay that measures the induction of T cell surface antigen. This activity was subnormal in serum from 10 of 16 patients with untreated lymphoblastic leukemia (p less than 0.001) but was within the normal range when the leukemia was in remission. Low inductive activity was associated with an inhibitor of T cell induction which was less than 30,000 daltons in molecular size and interfered with induction by purified thymopoietin plus a high concentration of ubiquitin or by normal serum alone.

Antigens, Surface↗
PubMed1980

Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage.

A series of monoclonal antibodies was used to define three discrete stages of human intrathymic T-cell differentiation. The earliest stage was confined to <10% of thymocytes, which were.reactive with both OKT9 and OKT10. Subsequently, approximately 70% of human thymocytes acquired a thymocyte-restricted antigen, OKT6, lost OKT9 antigen, and expressed reactivity with OKT4 and OKT5. These last two monoclonal antibodies were previously shown to define inducer (helper) and cytotoxic/suppressor populations, respectively, in peripheral blood. The OKT4(+), OKT5(+), OKT6(+) "common" thymocyte population represents the majority of thymocytes and accounts for more than 70% of thymocytes. With further maturation, thymocytes lose OKT6 reactivity, segregate into OKT4(+) and OKT5(+) subsets, and acquire reactivity with OKT3 (and OKT1). This latter stage corresponds to the more functionally mature subset. The possible relationship of acute lymphoblastic leukemia of T-cell lineage to these proposed stages of intrathymic differentiation was determined. Analysis of 25 tumor populations showed that 21 could be related to one or another differentiative stage. The majority (15/21) were derived from an early thymocyte or prothymocyte subpopulation, 5/25 were derived from a common thymocyte subpopulation, and 1/25 was derived from a mature (OKT3(+)) subpopulation. These data suggest that is it now possible to define stages of T-cell differentiation that can be related to T-cell malignancies in humans.

Antibodies, Neoplasm↗