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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 307 records · Page 17Linked to original sources
PubMed1982

Biochemical characterization of a differentiation antigen shared by human epidermal langerhans cells and cortical thymocytes.

Previous immunofluorescent studies have shown that differentiation antigens recognized by the monoclonal antibody (OKT6) are present on the external membranes of human epidermal Langerhans cells, cortical thymocytes and some cultured T cell lines. In the present investigation, the biochemical characteristics of the OKT6 recognized antigens derived from these three sources were compared. Following immunoprecipitation with OKT6, a single band with an approximate molecular weight of 52,000 daltons was identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (under both reducing and nonreducing conditions) in the detergent lysate of radioiodinated normal epidermal cells. A molecule with the same apparent molecular weight was immunoprecipitated from thymocytes and cultured MOLT-3 (T cell-acute lymphoblastic leukemia) cells. However, a low molecular weight protein of approximately 10,000 daltons was coprecipitated from these MOLT-3 cells. No electrophoretically identifiable antigens were precipitated from peripheral lymphocytes or monocytes with OKT6. These observations further distinguish Langerhans cells from classical monocytes, indicate that these cells express a membrane antigen otherwise characteristic of cortical thymocytes, and suggest the potential usefulness of the monoclonal antibody, OKT6, in further investigations of the functions and ontogeny of Langerhans cells.

Animals↗
PubMed1981

Proton NMR investigation of Ln3+ complexes of thymopoietin 32-36.

The pentapeptide Arg-Lys-Asp-Val-Tyr (TP5) is a biologically active fragment of thymopoietin, the thymic hormone that induces selective T-cell differentiation. The formation of lanthanide(III) complexes of TP5 is demonstrated through the observation of Tb3+ fluorescence enhancement. The equilibria, stoichiometry and solution conformation of the La3+, Pr3+ and Yb3+ complexes of TP5 have been investigated using NMR spectroscopy. In addition, the dissociation constants of two methyl ester analogs of TP5 have been studied. Evidence is presented supporting an interaction between the arginine guanidino N epsilon H and the aspartate carboxylate of TP5. Binding of Ln3+ appears to be accompanied by a disruption (or weakening) of this interaction and a concomitant increase in the 180 degrees rotamer population for the aspartate carboxylate group. The observed trends in the magnitudes of the dissociation constants and the rotamer populations appear to suggest that, although a significant amount of monodentate complexes may also exist, the metal ion binds predominantly to both carboxylates in a bidentate fashion.

Amino Acids↗
PubMed1981

Rheumatoid arthritis: a disease of T-lymphocyte/macrophage immunoregulation.

In rheumatoid arthritis the synovial membrane has many of the characteristics of a hyperactive, immunologically-stimulated lymphoid organ. The basis of this hyperactivity is poorly understood. Highly specific antisera to human Ia-like (HLA-DR) antigens and monoclonal antibodies (OKT series) to various T-lymphocyte subsets were used to analyse both the normal and the rheumatoid synovium and to compare it with normal lymph nodes. In rheumatoid arthritis the synovium acquires an infiltrate with microanatomical similarities to the paracortical area of the lymph node. Large, very strongly HLA-DR-positive macrophage-like interdigitating cells form close contacts with the OKT4+ (inducer-type) T-cells, while the OKT8+ population (T-cells of suppressor-cytotoxic type) between the macrophage-OKT4+ cell clusters is scanty (T4/T8 ratio = 9:1). By contrast, in the lymph node there are more OKT8 T-cells interspersed between the HLA-DR+ interdigitating cells and OKT4+ cells (T4/T8 ratio = 2:1). The large interdigitating cells and the OKT4+ T-cell population may be mutually stimulatory. In the absence of efficient suppression this stimulation may lead to activation of B-lymphocytes and oligoclonal or polyclonal immunoglobulin synthesis, as is found in the synovial membrane in rheumatoid arthritis.

Antibodies, Monoclonal↗
PubMed1981

Complete amino acid sequences of bovine thymopoietins I, II, and III: closely homologous polypeptides.

Complete amino acid sequences were determined for thymopoietins I and II (revision), isolated from bovine thymus, and for thymopoietin III, a newly identified polypeptide isolated from bovine spleen. Thymopoietin III (TP-III) is a 49 amino acid monomeric peptide that shows minor microheterogeneity at residue 34. The three thymopoietins have largely identical sequences yet some distinct differences, suggesting very recent evolution from a common gene. The complete amino acid sequences are (Formula: see text).

Amino Acid Sequence↗
PubMed1981

Use of monoclonal antibodies to T-cell subsets for immunologic monitoring and treatment in recipients of renal allografts.

Using monoclonal antibodies and flow cytometry, wer serially monitored lymphocyte subpopulations in renal-allograft recipients treated with either conventional immunosuppression or a monoclonal antibody. In 29 patients given conventional suppression, highly significant correlations between changes in T-cell subsets and rejection were noted. Normal or elevated ratios of OKT4 (helper/inducer) to OKT8 (suppressor/cytotoxic) cells were associated with rejection unless the donor was HLA identical or the total number of T cells was extremely low. In patients with low ratios, rejection seldom occurred. Two patients treated with OKT3 monoclonal antibody for acute rejection had rapid disappearance of OKT3-reactive cells from the peripheral blood and prompt reversal of rejection. The use of monoclonal antibodies allows the precise determination of changes in T-cell subsets and promises the development of therapeutic protocols that can be designed to manipulate selected lymphocyte populations.

Antibodies↗
PubMed1981

Functional analysis of human T cell subsets defined by monoclonal antibodies. IV. Induction of suppressor cells within the OKT4+ population.

In this report, we explored the functional heterogeneity within the OKT4+ subset of human T cells. Evidence was obtained that although in vitro pokeweed mitogen-activated OKT4+ cells can function as radioresistant helper cells, these activated OKT4+ cells could also exert potent feedback suppression. Despite the induction of suppressor cells after pokeweed mitogen activation, the OKT4+ population maintains its original OKT3+, OKT4+, nd OKT8- surface phenotype. The suppressor cells contained within the activated OKT4+ population were found to be radiosensitive. Importantly, the suppression mediated by activated OKT4+ cells required the presence of radiosensitive cells contained within the resting OKT4+ population. Taken together, these results suggest that the OKT4+ subset of human T cells contains cells that can be activated to differentiate into suppressor cells independent of OKT8+ cells.

Antibodies↗
PubMed1981

Proton nuclear magnetic resonance study of an active pentapeptide fragment of ubiquitin.

The aqueous solution conformation of Tyr-Asn-Ile-Gln-Lys (UB5) corresponding to positions 59-63 of the polypeptide, ubiquitin, has been investigated by proton NMR. Like the parent protein, UB5 induces nonspecifically both T and B lymphocyte differentiation. The various NH and CH resonances of this pentapeptide have been assigned, and its solution conformation has been probed through a study of chemical shift variations with pH, temperature dependence of amide hydrogen chemical shifts, vicinal NH--C alpha H and C alpha H--C beta H2 coupling constant data, and amide hydrogen-exchange rates. The latter were measured in H2O by using a combination of 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 this peptide. The various secondary amide hydrogens remain essentially exposed to the solvent. The temperature-dependence study of the amide hydrogen chemical shifts also did not reveal any strong internal hydrogen bonds. A rotamer population analysis of tyrosine and asparagine side chains suggests that two of the rotomers are predominantly populated for each of these residues. From these results, a picture emerges of the dynamic conformation of UB5 in aqueous solution.

Chromosomal Proteins, Non-Histone↗
PubMed1981

Effect of the TP5 analogue of thymopoietin on the rejection of male skin by aged and thymectomized female mice.

Although young adult C3H/HeJ (C3H) females do not reject C3H male skin grafts, C3H females older than 1 year commonly do so, as also do many thymectomized, young adult C3H females. Therapy with TP5, a synthetic pentapeptide analogue of thymopoietin which has biological properties of the parent molecule, substantially reduced the capacity of aged C3H females and of thymectomized, young C3H females to reject C3H male skin.

Aging↗
PubMed1981

Creating a useful panel of anti-T cell monoclonal antibodies.

Monoclonal antibodies to human T lymphocyte surface markers were produced by cell fusions between splenocytes from mice, immunized with T lineage cells, and mouse myeloma cells. Our approaches to immunization, clone selection and analysis of the resultant monoclonal antibodies with similar reactivities were produced. In one example, we found that several distinct monoclonal antibodies identified the same T inducer subset yet, apparently, recognized epitopes of the differentiation antigen(s) on these cells.

Animals↗
PubMed1981

OKT3 induces suppressor cells for mixed lymphocyte and PHA mitogenic responses in human peripheral lymphocytes.

Human peripheral lymphocytes pretreated with the Orthoclone monoclonal anti-T cell antibody OKT3 for 48 h markedly suppressed the proliferative response of autologous lymphocytes in one-way MLC and the mitogenic response to PHA. The ability to induce suppression is specific to OKT3 since other monoclonal antibodies to human T cells (OKT1, OKT4 and OKT8) did not elicit similar responses, OKT3 is mitogenic but further proliferation of OKT3 pretreated lymphocytes was not required for the suppression of autologous lymphocytes since mitomycin-C treated cells were fully effective. Kinetic studies indicated that pretreatment of lymphocytes with OKT3 for 24 h was sufficient to induce marked inhibition of the mitogenic response of autologous lymphocytes to PHA whereas suppression in MLC was not observed until lymphocytes were pretreated for 48 h. These studies support the previous observations that OKT3 may be reacting with an important molecule on the T cell surface and that interaction of OKT3 with this molecule induces profound functional changes.

Antibodies, Monoclonal↗