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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 235 records · Page 13Linked to original sources
PubMed1984

Immunoassay for bovine serum thymopoietin: discrimination from splenin by monoclonal antibodies.

A polyclonal rabbit anti-bovine thymopoietin antiserum was used to develop a radioimmunoassay and sandwich enzyme-linked immunosorbent (ELISA) assay for the thymic hormone thymopoietin. Both assays showed slightly less sensitivity for the closely related splenic hormone splenin (SP) than thymopoietin (TP) and markedly less sensitivity for the human as compared with the bovine polypeptides. A number of murine monoclonal antibodies specific for bovine thymopoietin were generated; they were unreactive with bovine splenin and were also unreactive with human thymopoietin and splenin. A sandwich ELISA using these monoclonal anti-TP antibodies together with polyclonal rabbit anti-TP was specific for bovine thymopoietin and measured 300-500 ng/ml thymopoietin in bovine serum. Similar approaches are being pursued to develop an immunoassay for thymopoietin in human serum.

Animals↗
PubMed1984

Thymopoietin radioreceptor assay utilizing lectin-purified glycoprotein from a biologically responsive T cell line.

Radiolabeled thymopoietin that was biologically active and of high specific activity was prepared by a novel technique involving protection of free amino groups, selective excision of the protected N-terminal prolyl group with post-proline cleaving enzyme, reaction of the newly exposed alpha-amino group with a highly radioiodinated compound, and deprotection and purification of the polypeptide. Binding of this radiolabeled thymopoietin was not demonstrable by conventional techniques with cells, cell membranes, or solubilized cell membranes, apparently due to the presence of active proteases in these preparations. A glycoprotein with thymopoietin binding properties was prepared by lectin purification from the detergent-solubilized membranes of CEM cells, a human T cell line that responds to thymopoietin in vitro with increases in intracellular cyclic GMP. Presumably this procedure separated the thymopoietin binding protein from membrane proteases, thus permitting the development of a radioreceptor assay. Evidence is presented that the thymopoietin binding protein represents a thymopoietin receptor that is probably related to the mediation of immunoregulatory actions of thymopoietin on a subset of peripheral T cells.

Binding, Competitive↗
PubMed1984

Cooperativity of thymopoietin 32-36 (the active site) and thymopoietin 38-45 in receptor binding.

Thymopoietin is a 49 amino acid polypeptide hormone of the thymus whose biological activity is reproduced by the synthetic pentapeptide thymopentin, corresponding to amino acids 32-36. Thymopentin requires the addition of an octapeptide corresponding to thymopoietin 38-45 for full competition with native thymopoietin in a radioreceptor assay with receptor derived from the human T-cell line CEM. Thus thymopoietin appears to bind to its receptor on T-cells by two regions (32-36 and 38-45). Thymopentin alone is biologically active and induces elevations of intracellular cyclic GMP. Whilst occupancy of the adjacent site by thymopoietin 37-45 does not of itself cause an elevation of intracellular cyclic GMP this peptide is not biologically silent as it does enhance the potency of thymopentin.

Amino Acid Sequence↗
PubMed1984

Distinct epitopes on the T8 molecule are differentially involved in cytotoxic T cell function.

The present report attempts to determine if there are distinct epitopes on the T8 molecule that are involved in class I-restricted cytotoxic T lymphocyte (CTL) function. A panel of 9 monoclonal antibodies (OKT8A,B,C,E,F,G,H,I, and OKT5) was produced and all antibodies were shown to bind to the T8 molecule. This panel of antibodies was employed to characterize the distribution of distinct epitopes on the T8 molecule and to block the activity of class I-specific influenza virus-immune and allo-immune CTL effector function. Significant differences in the ability of the anti-T8 antibodies to block CTL function were observed: OKT8C and T8F blocked best (49 and 55% respectively); OKT8A,E,G,H,I, and OKT5 blocked less well (24-31%); and OKT8B blocked marginally (11%). There was no correlation between the capacity of the antibodies to block CTL function and their heavy chain isotype. Competitive binding of the different OKT8 antibodies to the cell surface and differential trypsin sensitivity of the epitopes recognized by the antibodies indicated that OKT8C and T8F were located on topographically distinct regions of the T8 molecule. These results indicate that specific epitopes on the T8 molecule are involved in CTL function, and that there could be more than one functional site on the molecule.

Animals↗
PubMed1984

Contrasting biological activities of thymopoietin and splenin, two closely related polypeptide products of thymus and spleen.

Thymopoietin, a 49 amino acid polypeptide hormone of the thymus discovered by its effect on neuromuscular transmission, was later shown to induce T-cell differentiation and to affect immunoregulatory balance. A radioimmunoassay for thymopoietin revealed a crossreaction with a product found in spleen and lymph node but not other tissues. This product, named splenin, differs from thymopoietin only in position 34, aspartic acid for bovine thymopoietin and glutamic acid for bovine splenin. Synthetic pentapeptides corresponding to residues 32-36, called thymopentin and splenopentin, reproduce biological activities of thymopoietin and splenin, respectively. Thus thymopoietin and thymopentin affect neuromuscular transmission and induce the phenotypic differentiation of T precursor cells in vitro while inhibiting phenotypic differentiation of B cells. Splenin and splenopentin, in contrast, do not affect neuromuscular transmission, and they induce both T- and B-cell precursors.

Amino Acid Sequence↗
PubMed1984

Relationships between language skills as assessed by the Halstead-Reitan battery and the Luria-Nebraska language-related factor scales in a nonaphasic patient population.

The study involved a comparison between language tests derived from the Halstead-Reitan and Luria-Nebraska neuropsychological test batteries. Language-related measures from each battery were entered into a factor analysis based on a sample of 150 nonaphasic neuropsychiatric patients. Five factors were extracted and were named Academic Achievement, Basic Skills, Verbal Intelligence, Auditory Discrimination, and Comprehension of Syntactical Relations. Measures from both the Halstead-Reitan and Luria-Nebraska loaded on most of these factors. A canonical correlation analysis revealed a strong relationship between the Halstead-Reitan and Luria-Nebraska measures. However, it was noted that interpretation of this relationship must be qualified by the association found between the measures used and educational achievement.

Adult↗
PubMed1984

Contrasting effects of thymopentin and splenopentin on the capacity of female mice to reject syngeneic male skin.

The TP-5 pentapeptide analog of thymopoietin and the SP-5 pentapeptide analog of splenin, which differ only in substitution of Glu for Asp and represent positions 32-36 of the parent molecules, were compared for effects on the capacity of C3H/HeJ female mice to reject C3H/HeJ male skin (the H-Y rejection response). The actions of these TP-5 and SP-5 analogs of respective thymic and splenic products were already known to differ in other functional systems, neuromuscular and immunological, in vitro and in vivo. The H-Y rejection response of young thymus-intact female mice was heightened by TP-5 and by SP-5. Neither TP-5 nor SP-5 affected the raised H-Y rejection response of splenectomized female mice. Whereas TP-5 lowered the raised H-Y rejection response of thymectomized female mice, as reported elsewhere, SP-5 did not. Thus, not only do these structurally very similar immunoregulators differ in their particular functions, but the overall effect of these functions in vivo depends on the immune status of the recipient.

Animals↗
PubMed1984

Treatment of acute graft-versus-host disease with monoclonal antibody OKT3. Clinical results and effect on circulating T lymphocytes.

Eight recipients of a bone-marrow graft from HLA-identical, MLR-nonreactive sibling donors who had developed grade II-IV acute graft-versus-host disease (aGVHD), were given 14 consecutive daily injections of 5 mg of a murine anti-T-cell monoclonal antibody (MCA) called OKT3. Four patients with grade II aGVHD showed a complete response; two patients with grade II had a partial response, and two patients (one with grade II and one with grade IV) showed no improvement at all. The main side effect was a high spiking fever after the first injection. T cells were monitored with monoclonal antibodies, indirect immunofluorescence, and flow cytometry. Circulating T3+ T cells dropped to virtually zero within 1 hr following the first injection. Low numbers of E-rosetting cells were still demonstrable during OKT3 therapy. During the second week of treatment, T-cell markers (T3, T4, T8) started to increase again, in spite of excess antibody in the circulation. At that time, T cells showed weaker fluorescence with OKT3 than before OKT3 therapy, suggesting modulation of the T3 antigen. After cessation of OKT3 therapy, T cells reached pretreatment levels within one week. None of the six patients studied developed anti-mouse-Ig antibodies. These results suggest that OKT3 therapy is effective in limited aGVHD. The absence of anti-mouse-Ig antibody formation may allow repeated courses of MCA that may add to their therapeutical potential.

Acute Disease↗
PubMed1984

The incidence of schizophrenia in New South Wales, Australia. A psychiatric register study.

Age-specific estimates of the incidence of schizophrenia in NSW, Australia, have been made using two methods, one based on a psychiatric register and the other based on routinely collected hospital morbidity data. Similar results were obtained by both methods. The estimates lie towards the bottom of the range of incidence estimates of schizophrenia that have been published for some other countries, and are lower than estimates from a number of U.S. studies. The diagnostic criteria of schizophrenia employed by Australian psychiatrists conform closely to DSM-III criteria.

Adolescent↗
PubMed1984

Functional analysis of human T cell subsets defined by monoclonal antibodies. VI. Distinct and opposing immunoregulatory functions within the OKT8+ population.

In the present study, we investigated the immunoregulatory potential of OKT8+ cells after in vitro activation. Initial studies had demonstrated that the T cell marker OKT4 identifies T cell sets containing helper cells, whereas OKT8 reacts with the suppressor and cytotoxic T cell effectors. More detailed analysis of the OKT4+ subset, however, demonstrated that there is functional heterogeneity in the OKT4+ population. The evidence for this heterogeneity arose from studies on (1) the relative radiosensitivities of the distinct immunoregulatory functions of cells contained within this set, and, (2) the effects of the state of activation of this population on immune function. For example, OKT4+ cells included radiosensitive helper cells, radioresistant helper cells, and radiosensitive inducers of suppressor cells. Furthermore, after activation, the OKT4+ population also contained cells capable of suppressing B cell differentiation. Since activation of the OKT4+ population results in the emergence of cells with counterbalancing immunoregulatory properties, it was of interest to determine whether the state of activation of the OKT8+ population influences the immunoregulatory potential of this subset. In the experiments reported here E+ cells were cultured with pokeweed mitogen (PWM) for 60-70 h and then thoroughly depleted of OKT4+ cells, leaving OKT8+ cells. The ability of the PWM-activated OKT8+ cells (first culture) to exert suppressive activity was determined by adding graded numbers of these cells to fresh autologous OKT4+ cells and B cells. The cell mixtures were cultured in the presence of PWM for 5 days and then assayed for plaque-forming-cell (PFC) activity by the reverse hemolytic plaque assay. Our studies demonstrate that activation of OKT8+ cells results in the emergence of cells with apparently counterbalancing immunoregulatory properties. Activated nonirradiated OKT8+ cells consistently suppressed B cell immunoglobulin production. However, the immunoregulatory function mediated by irradiated activated OKT8+ cells is highly dependent on the magnitude of the helper activity obtained with fresh OKT4+ cells. Thus, irradiated activated OKT8+ cells suppressed the generation of PFC only when the level of helper activity was optimal. However, when the level of help was not optimal, no suppressor activity was observed; rather, under these conditions, irradiated activated OKT8+ cells amplify the PFC response. We would emphasize that the amplification function of irradiated OKT8+ cells depends strictly on the presence of fresh OKT4+ cells. Irradiated activated OKT8+ cells alone are not helper cells, since addition of these cells to B cells thoroughly dep

Antibodies, Monoclonal↗
PubMed1984

The T4 surface antigen is involved in the induction of helper function.

The OKT4 monoclonal antibody reacts with a 62K m.w. glycoprotein present on a subset of human T cells with the capacity to help or induce B cell differentiation. The present studies were undertaken to determine whether the T4 molecule itself plays any role in the helper function mediated by T4+ cells. Using a series of monoclonal antibodies (OKT4, OKT4A-E), which react with distinct noncompeting epitopes of the T4 molecule, we found that OKT4A and OKT4E, but not OKT4, antibodies inhibited the induction of B cell differentiation by T4+ cells. This inhibition was apparent when using nonirradiated or irradiated T4+ cells, and was noted over a wide range of concentrations. Importantly, inhibition occurred only if the antibody was present during the first 24 hr of cell culture, and the presence of antibody did not alter the kinetics of induction of B cell differentiation. Thus, these data suggest that the T4 molecule plays an early, critical role in cellular interactions required for helper cell function.

Antibodies, Monoclonal↗
PubMed1984

Biologic functions of the OKT1 T cell surface antigen. I. The T1 molecule is involved in helper function.

The OKT1 (Leu-1) monoclonal antibody reacts with a 69 KD glycoprotein that is present on only a fraction of functionally mature thymocytes but is maintained on most peripheral T cells. In the study presented, we examined the role of this surface molecule in T cell function. We found that addition of the OKT1 antibody to B cells and autologous T4+ cells markedly enhances B cell differentiation. This enhancement was apparent when nonirradiated or irradiated T4+ cells but not T8+ cells were used. Moreover, the OKT1 antibody as well as the OKT1 F(ab')2 fragment enhanced B cell differentiation in a dose-dependent fashion. It is important to note that perturbation of the T1 molecule with OKT1 in the presence of autologous E- cells causes the rapid release of molecules that trigger B cells to proliferate and differentiate into Ig-secreting cells. These data when considered together suggest that OKT1 reacts with a T cell membrane determinant or a complex that is intimately involved in the execution of helper function on OKT4+ cells.

Antibodies, Monoclonal↗
PubMed1984

Thymopoietin pentapeptide (thymopentin, TP-5) in the treatment of rheumatoid arthritis. A compilation of several short- and longterm clinical studies.

Thymopentin (TP-5), the active side of thymopoietin, was shown to affect immunoregulation. The effect of this drug in the treatment of rheumatoid arthritis (RA) was evaluated. Three trials were performed: a six month double-blind trial comparing TP-5 administered subcutaneously to placebo at 3 different dosages, an open longterm study in which the same dosage of the drug was administered subcutaneously, and a shortterm (3 weeks) double-blind trial in which the drug was given intravenously at a high dosage (100 mg/day). In none of these 3 studies were statistically significant improvements registered in the TP-5 treated patients, although there were important improvements in individual patients. Serious side effects were not encountered, but the majority of patients did not improve or were withdrawn because of ineffectiveness. The beneficial effect of TP-5 on the clinical evolution of RA, reported elsewhere, could not be confirmed by these studies.

Arthritis, Rheumatoid↗
PubMed1984

Distribution of antigens defined by OKB monoclonal antibodies on benign and malignant lymphoid cells and on nonlymphoid tissues.

Monoclonal antibodies OKB1, OKB2, OKB4 and OKB7 have been previously shown to detect distinctive antigens displayed on B, but not on T, lymphocytes. Benign and malignant lymphoid cells were investigated for their reactivity with these antibodies in cell suspension by indirect immunofluorescence and in cryostat tissue sections by the avidin-biotin complex immunoperoxidase technique. Fetal liver pre-B cells and pre-B and common type acute lymphoblastic leukemia cells isolated from 15 patients were OKB1-OKB2+OKB4-OKB7-. All mature lymphoid tissue B cells and the neoplastic cell surface immunoglobulin-positive (SIg+) B cells isolated from each of 47 B cell neoplasms were OKB2+. OKB1 and OKB7 were expressed by interfollicular, follicular center, and many, but not all, mantle zone B cells. OKB4 was expressed by follicular center cells, but not by mantle zone or interfollicular B cells. The neoplastic SIg+ B cells isolated from 45 of 47 B cell malignancies were OKB1+OKB4+, and those isolated from 45 of 46 B cell malignancies were OKB7+. The neoplastic B cells of one mantle zone lymphoma were OKB1-, of one small lymphocytic cell lymphoma were OKB7-, of one large cell lymphoma were OKB4-, and of one small lymphocytic cell lymphoma with a monoclonal gammopathy were OKB1-OKB4-. Normal and myeloma plasma cells were OKB-. The malignant T cells isolated from 12 T cell neoplasms were OKB2-OKB4-, but were OKB1+ and/or OKB7+ in 3 cases. Thus, the OKB antibodies appear to detect distinctive antigens that may be expressed at different stages of B cell differentiation. In addition, OKB4 reacted with selected renal and respiratory epithelium, and OKB2 reacted with a wide range of epithelial tissues. The OKB antibodies should prove useful in the investigation of B cell differentiation and may aid in the identification and characterization of lymphoproliferative malignancies with significant therapeutic and prognostic differences not identifiable by conventional histopathologic and immunologic methods.

Animals↗
PubMed1983

Stability of human lymphocyte differentiation antigens when stored at room temperature.

The development of monoclonal antibodies to human differentiation antigens and cytofluorographs have added a new dimension to immune monitoring. However, the technology is such that regionalization will most likely occur. We have demonstrated that human lymphocyte antigens OKT3, OKT4, OKT8 and OKT11 are stable in blood samples stored in ACD at room temperature for less than 72 h. This will allow samples to be analyzed in regional centers.

Antibodies, Monoclonal↗
PubMed1983

Cell membrane perturbation of resting T cells and thymocytes causes display of activation antigens.

Three human lymphocyte antigens recognized by monoclonal antibodies OKIa1, OKT9, and OKT10 were found to be minimally represented on resting peripheral T cells (all three) and thymocytes (OKIa1 and OKT9). These antigens, which are present on "activated" T cells, were promptly displayed on "resting" T cells or thymocytes following cross-linking of surface-bound monoclonal antibody by horse alpha-mouse IgG. These experiments suggested that membrane perturbations may induce the expression of certain antigens that are normally present in an unexpressed form in resting cells.

Antibodies, Monoclonal↗