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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 253 records · Page 14Linked to original sources
PubMed1983

Thymopoietin pentapeptide treatment of primary immunodeficiencies.

26 patients with primary immunodeficiencies (3 infants with severe combined immunodeficiency [SCID] 3 with DiGeorge syndrome, 6 with T-cell defect or SCID with B cells, 4 with common variable hypogammaglobulinaemia and associated T-cell defect, 5 with ataxia-telangiectasia, and 5 with hyper-IgE syndrome) were treated with thymopoietin pentapeptide (TP-5) at a dose of 0 . 5 mg/kg daily for 2 weeks and then 3 times a week at 0 . 5 mg/kg for 10 weeks, 3 patients with DiGeorge syndrome and 3 with primary T-cell defect demonstrated pronounced clinical and immunological improvement during treatment. None of the patients with SCID and 3 of 6 patients with SCID with B cells or primary T-cell defect showed any clinical or immunological changes during therapy. In 5 patients with ataxia-telangiectasia clinical manifestations and immunological tests were unchanged by TP-5. Abnormality of T cells in cases of hyper-IgE syndrome was not corrected by TP-5 treatment.

Adolescent↗
PubMed1983

Five epitopes of a differentiation antigen on human inducer T cells distinguished by monoclonal antibodies.

A series of mouse monoclonal antibodies reacting with human T cells of the helper/inducer subclass, OKT4, 4A, 4B, 4C, and 4D, have been reported. Using double-fluorescent staining and complement-mediated depletion, it was shown that the antigen(s) recognized by OKT4, 4A, 4B, 4C, and 4D antibodies are present on the same cell. Using FITC-labeled OKT4, 4A, 4B, 4C and 4D, a lack of competition between the antibodies for their epitopes was shown. Immunoprecipitation of the antigen recognized by each antibody yielded a molecule of approximately 60,000-62,000 Da. Sequential precipitation with several antibodies resulted in a minimum of additional precipitated antigen following removal of the first antigen. Capping of cell surface antigen with OKT4, followed by staining with OKT4, 4A, 4B, 4C, or 4D, indicated that the epitopes for all five antibodies co-cap. A sandwich ELISA assay using OKT4 and the other antibodies showed that molecules binding to OKT4A, 4B, 4C, and 4D also bound OKT4. It can therefore be concluded that monoclonal antibodies OKT4, 4A, 4B, 4C, and 4D recognize distinct epitopes present on a molecule of approximately 60-62,000 Da on human helper/inducer T cells.

Animals↗
PubMed1983

Patterns of antigenic expression on human monocytes as defined by monoclonal antibodies.

A series of seven monoclonal antibodies directed at determinants on human peripheral blood monocytes were produced and characterized. The antibodies were separated into three groups based on cell distribution and percentages of monocytes bearing antigen. Hybridoma antibodies, termed OKM1, OKM9, and OKM10, recognized antigen(s) expressed on the majority of adherent monocytes, null cells, and granulocytes. The second group, comprising OKM5 and OKM8, reacted with most adherent monocytes and platelets. OKM3 and OKM6, comprising a third group of antibodies, reacted with a subpopulation of adherent monocytes and platelets. OKM antibodies were not expressed on lymphocytes, thymocytes, and lymphoblastoid cells, with the exception of OKM3 which reacted with three B-cell lines. SDS gels of immunoprecipitates formed with OKM antibodies yielded the following tentative molecular weight results: OKM1 and OKM9 antigens appeared to be 160,000 (nonreduced) and 170,000 (reduced); OKM10 precipitated two polypeptides of 170,000 and 115,000 (reduced); OKM5 and OKM8 precipitated a single polypeptide of 88,000 (reduced, nonreduced); OKM6 antigen appeared to be 116,000 (nonreduced) and 130,000 (reduced).

Animals↗
PubMed1983

Withdrawal seizures in black and white alcoholic patients: intellectual and neuropsychological sequelae.

An investigation was made of whether black alcoholics have a different response to having withdrawal seizures than white alcoholics, in terms of cognitive and other neuropsychological deficits. In a previous study it was found that white alcoholics with histories of withdrawal seizures did not demonstrate neuropsychological differences from white alcoholic patients without such histories. However, the apparently higher incidence of withdrawal seizures among blacks noted during screening of subjects for this study raised the question of whether the consequences of the seizure history might be different among blacks. The Halstead-Reitan Neuropsychological Test Battery was administered to 22 white and 20 black alcoholic inpatients. Half of each group had a history of withdrawal seizures while the other half did not. The results of the study indicated that on several tests, there were significant differences between black patients with and without seizure histories, but that was not the case for the white patients. Various possible causes for this finding are discussed.

Adult↗
PubMed1983

Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies.

We have obtained four monoclonal antibodies, IB4, OKM1, OKM9, and OKM10, all directed against the C3bi receptor of human monocytes and macrophages (M phi). Two criteria were used to determine the specificity of these antibodies. First, culture surfaces coated with the antireceptor antibodies caused specific down modulation of C3bi receptor activity on M phi adherent to these substrates. Second, receptor protein purified by using IB4 or OKM1 retained the ability to bind selectively to C3bi-coated erythrocytes. Each of the antibodies recognizes a distinct epitope on the C3bi receptor; they do not compete with one another for binding to monocytes. Further, when immobilized on a solid support, each of the antibodies binds a molecule from M phi lysates that can simultaneously bind one of the other monoclonal anti-C3bi receptor antibodies. OKM10 binds and masks the ligand-binding site of the C3bi receptor, while IB4, OKM1, and OKM9 bind to sites remote from the C3bi binding site. All four antibodies immunoprecipitated polypeptides of Mr 185,000 and 105,000 from 125I-surface-labeled M phi. IB4 also precipitates polypeptides of Mr 185,000, 153,000, and 105,000. We conclude that the C3bi receptor of human M phi is a complex composed of two polypeptides, Mr 185,000 and 105,000. We have identified monoclonal antibodies reacting with four distinct antigenic determinants of this complex. The determinant recognized by antibody OKM10 is at or near the ligand-binding site of the receptor. The determinant recognized by antibody IB4 is shared by at least two other leukocyte surface proteins.

Animals↗
PubMed1983

Effects of in vivo administration of monoclonal antibodies specific for human T cell subpopulations on the immune system in a rhesus monkey model.

Monoclonal antibodies specific for human T cell subsets have been tested for their immunosuppressive effect in a rhesus monkey skin graft model. Rhesus monkeys were injected i.v. daily with antibodies specific for helper T cells (OKT4 and 4A), for cytotoxic/suppressor T cells (OKT8A), or all peripheral T cells (OKT11A), and they received an allogeneic skin graft one or two days after the initial antibody treatment. The OKT4, 4A, and 11A antibodies prolonged skin graft survival, but OKT8A did not. All animals were carefully monitored regarding levels of T cell subsets and antibody formation to the injected monoclonal antibody. The relevant T cell subset was not eliminated from the circulation when OKT4 and OKT4A antibodies were given separately. The OKT4+ cells remained in the circulation coated with antibody. OKT4+ cells could no longer be demonstrated when both OKT4 and 4A were given simultaneously. However, this difference in effect on the OKT4+ cells did not influence skin graft survival time. All animals receiving monoclonal antibody treatment developed antimouse-Ig antibodies after 10 to 13 days of treatment, which presumably counteracted the effect of the antibodies. From these data it appears that the rhesus monkey is a useful animal model in which to investigate the potential of monoclonal antibodies against human lymphocyte subpopulations to modify and regulate the immune response in an orderly fashion.

Animals↗
PubMed1983

Thymopoietin-like substance in human skin.

A heterologous antithymopoietin (anti-TP) antibody was used to determine whether a TP-like molecule is present in the epidermis, since such factors have been postulated to play a part in known T cell-epidermal cell interaction. Examination of cytocentrifuge smears of freshly separated human epidermal cells stained by indirect immunofluorescence revealed that 8-14% of these cells possessed cytoplasmic reactivity with the anti-TP antibody. Similarly, 2-5% of human epidermal cells, maintained in tissue culture for 2-8 weeks, showed cytoplasmic staining with the anti-TP antibody. Double-labeling immunofluorescence studies, with the anti-TP antibody and a monoclonal antibody specifically reactive with Langerhans cells (OKT6), demonstrated that cells possessing this TP-like substance were not Langerhans cells. In situ studies of 4-microns frozen sections of normal human skin indicated that the cell population which possesses the TP-like substance is the basal layer of keratincoytes in the epidermis.

Fluorescent Antibody Technique↗
PubMed1983

Allogeneic bone marrow transplantation: the monitoring of granulocyte macrophage colonies following the collection of bone marrow mononuclear cells and after the subsequent in-vitro cytolysis of OKT3 positive lymphocytes.

Marrow nucleated cells from eight normal allogeneic donors was layered on Ficoll-Metrizoate to isolate the mononuclear cell fraction. The cells were then washed to remove Ficoll-Metrizoate and coagulation factors prior to resuspension in a balanced salt solution and the addition of the murine anti-human T-lymphocyte monoclonal antibody OKT3 and rabbit complement. The procedures were assessed for their effect on mononuclear cell viability (mean recovery 84.4%); the ability of the cells to proliferate granulocyte-macrophage colonies (mean recovery 57.4%); the in-vitro T-lymphocytolysis (mean 75.7%) and the removal of rabbit complement (greater than 99%). Following marrow transplantation with this treated mononuclear fraction the mean day to recovery of greater than or equal to 1.0 X 10(9)/l leucocytes was 20 d, with three patients developing greater than or equal to Grade II acute graft versus host disease (GvHD). Thus, treatment of donor marrow with OKT3 and complement in a large volume system was not detrimental to subsequent engraftment, nor effective in complete T-lymphocytolysis, nor in prevention of severe GvHD.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1983

Comparative efficacy of various routes of administration of thymopentin (TP-5) with consideration of degradative mechanisms.

Thymopoietin (originally termed TP-5 and now called thymopentin) is a synthetic pentapeptide that can reproduce the biological activity of the 49 amino acid thymic hormone thymopoietin. The efficacy of various routes of administration of thymopentin was studied in mice and guinea pigs using an electromyographic assay as an end point to determine biological activity. In mice, the threshold dose necessary for a significant response when compared to controls was 0.03 mg/kg (mpk) for i.v. (intravenous) injection and 0.3 mpk for both i.p. (intraperitoneal) and s.c. (subcutaneous) injection. For the guinea pig, 0.03 mpk produced a significant response when compared to controls when injected either i.v. or s.c.; 0.3 mpk was required for a significant response for i.n. (intranasal) administration and 0.6 mpk for i.p. injection. When saline or plasma was injected, it produced no change in the electromyographic response. In plasma the pentapeptide is rapidly degraded by proteolytic enzymes. Treatment of plasma with specific enzyme inhibitors followed by incubation with thymopentin or thymopoietin confirmed that serine protease and aminopeptidase M-like enzymes are responsible for the rapid inactivation of thymopentin in plasma, as measured by the electromyographic response.

Animals↗
PubMed1983

Thymopentin (TP-5) potency in vivo is enhanced by slow infusion.

The in vivo activity of thymopentin in guinea pigs was assessed electromyographically 18 h after intravenous or subcutaneous injections or infusions ranging over varying periods of time. The lowest threshold dose required to establish a positive effect was obtained with a 30-60 min i.v. infusion (0.38-0.75 micrograms/kg) and we found that we needed X 5 times this dose with 30 min s.c. infusion, X 10 this dose with 10 min i.v. or s.c. infusion, X 200 this dose with bolus IV injection and X 400 this dose with bolus s.c. injection. The marked increase of potency of thymopentin with infusion should be considered in designing clinical regimens.

Animals↗
PubMed1983

A mental health consultation program to the police.

The growing interface between psychiatric staff and the police as a result of the latter's involvement with disturbed patients released into various communities has intensified the need for appropriate police orientation and desensitization to these patients. This article describes a program that grew out of the need of the police for involvement with psychiatric staff, once their resistance had been overcome. The use of videotapes and role playing diminished the anxiety of the police, allowed their better and more rational judgments to come forth when faced with such patients, and increased their empathy. Another goal of the program was to get the police to see that a more reflective and restrained approach to patients, as distinguished from an aggressive, action-oriented approach, was just as demanding of their professionalism and could be more effective and safer in the management of these patients.

Community Mental Health Services↗
PubMed1983

Classification of human lymphocytes and monocytes with the OK series of monoclonal antibodies.

Membrane antigens expressed by either peripheral blood B cells, monocytes, or activated T cells have been identified by monoclonal antisera. OKB1, OKB2, OKB4, and OKB7 react with all or most circulating Smlg+ cells and have differential effects on the generation of plaque forming cells in the reverse hemolytic plaque assay. Of the new monocyte antibodies, OKM5 displays more restricted specificity for monocytes than the previously described OKM1, whereas OKM3 and OKM6 define monocyte subsets. In addition, several new T-cell "activation" antigens have been identified that differ in their expression depending on the nature of the triggering stimulus. These reagents should be of diagnostic and perhaps therapeutic utility.

Animals↗
PubMed1983

Detection by ELISA of shed cell-surface molecules in serum.

Monoclonal antibodies OKT9 and OKT9A, which recognize distinct epitopes on the transferrin receptor, were used to develop a sandwich enzyme-linked immunosorbent assay (ELISA) for this molecule. A 115,000 dalton molecule was detected in serum which probably represents a proteolytic cleavage fragment of the 186,000 dalton (dimer of two 93,000 chains) found on the cell surface of replicating cells. Serum levels of the shed transferrin receptor in human sera may be studied by means of this assay.

Animals↗
PubMed1983

Possible involvement of the T4 molecule in T cell recognition of class II HLA antigens: evidence from studies of proliferative responses to SB antigens.

The T4 molecule has been identified as a marker of human T cell differentiation, but the function of this molecule remains to be defined. We have investigated its possible functional involvement in T cell proliferative responses to class II HLA antigens encoded by the recently described SB locus. The responses of SB-primed cells (specific for each of four different SB antigens) were studied with the use of two proliferation-inducing stimuli, SB antigen or TCGF. The proliferative responses to both stimuli were found to be mediated by T4+, T8- cells. Monoclonal antibodies against some epitopes on the T4 molecule (OKT4A and OKT4B) substantially blocked antigen-stimulated proliferative responses; antibodies against other epitopes of the T4 molecule (OKT4, T4C, T4D) blocked less well. Inhibition of SB-specific proliferation by antibodies to the T4 molecule was maximal only when the antibodies were incubated with the responder cells before the addition of stimulator cells. Proliferative responses of SB-primed cells stimulated with TCGF alone were not inhibited by any of the OKT4-related antibodies, but were completely inhibited by the anti-Tac monoclonal antibody, which reacts with the TCGF receptor. These results lend further support for the hypothesis that the T4 molecule is involved in T cell recognition of and/or activation by class II HLA antigens. We suggest that 1) the T4 molecule binds a nonpolymorphic epitope on class II HLA molecules, and 2) this interaction may facilitate, but not be an obligate requirement for, T cell activation by class II antigens.

Adult↗
PubMed1983

Functional subsets of human monocytes defined by monoclonal antibodies: a distinct subset of monocytes contains the cells capable of inducing the autologous mixed lymphocyte culture.

The induction of most immune responses requires the close cooperation between T cells and antigen-presenting cells (APC), presumably of monocyte/macrophage (M phi) lineage. To characterize human APC further, we used two monoclonal antibodies, OKM1 and OKM5, to isolate and identify M phi subsets. OKM1 has been described and recognizes cell surface antigens on most M phi and granulocytes. OKM5 recognizes cell surface determinants present on the majority of human M phi but does not recognize other hematopoietic cell types. A small subset of peripheral blood M phi is OKM1-OKM5+. Human peripheral blood E- cells were separated into OKM1+ and OKM1- subsets by a rosetting technique utilizing anti-Ig-coated red cells. The capacity to present self antigens in the autologous mixed lymphocyte culture (AMLC) resided predominantly within the E-OKM1- subset, even if surface membrane Ig-positive cells were eliminated. Similar experiments showed that the ability to stimulate in AMLC was contained in the E-OKM5+ population and in fact resided primarily within the E-OKM1-OKM5+ subset. All of these subsets were able to trigger allogeneic T cells to proliferate. The capacity of these APC subsets to present soluble antigens (mumps, tetanus toxoid) was also examined. The data demonstrated that although the majority of these APC are E-OKM1+, E-OKM1-OKM5+ cells can also present foreign antigen. Taken together, these data suggest OKM1 and OKM5 can be used to isolate two functionally distinct human M phi subsets. One subset (E-OKM1+) is capable of presenting soluble antigens but shows minimal ability to trigger AMLC. The other subset (E-OKM1-OKM5+) can also present soluble antigens but is the predominant subset that can trigger AMLC.

Animals↗
PubMed1983

Interaction of thymopoietin peptides with the specific receptor of facteur thymique serique (FTS).

The capacity of ubiquitin (UB) and thymopoietin II (TP) related peptides (TP 5 and TP 13) to interfere with the specific binding of [3H]FTS on intact 1301 cells or on 1301 plasma membrane preparations was studied. All 3 peptides significantly inhibited the binding of [3H]FTS to its receptors on intact 1301 cells at concentrations 20 to 100 times higher than FTS itself. Conversely, none of the 3 peptides provided a significant inhibition of the specific [3H]FTS binding to plasma membrane preparations of 1301 cells compared to control peptides. These contrasted results suggest that TP-related peptides and, to a lesser degree, UB may share the same target cells with FTS and interfere with FTS effects on T cells, but this interaction probably does not involve direct high affinity binding to the FTS receptors.

Animals↗
PubMed1983

The application of monoclonal antibodies to the characterization and diagnosis of lymphoid neoplasms: a review of recent studies.

Twenty-three T-cell neoplasms were divided, according to their reactivity with the OKT monoclonal antibodies as follows: Fourteen neoplasms of diverse histopathology expressed the OKT3+ OKT4+ phenotype, commonly associated with the helper T-cell subset; seven histologically similar lymphoblastic neoplasms expressed diverse phenotypes consistent with various stages of intrathymic differentiation and two neoplasms expressed the uncommon OKT3+ OKT10+ phenotype. Thus, T-cell neoplasms are divisible into phenotypes that correspond to normal stages of T-cell differentiation and functionally distinct T-cell subsets. Benign and malignant lymphoid cells were investigated in cell suspension and in cryostat tissue sections for their reactivity with OKB1, OKB2, OKB4, and OKB7, monoclonal antibodies known to detect distinctive B lymphocyte antigens. Fetal liver pre-B cells, cases of pre-B acute lymphoblastic leukemia, and common-type acute lymphoblastic leukemia were OKB2+ but unreactive with the other OKB antibodies. All mature lymphoid tissue B cells and 47/47 surface immunoglobulin (SIg)-positive B-cell neoplasms were OKB2+. Interfollicular, follicular center, and many, but not all, mantle zone B cells were OKB1+ OKB7+. Follicular center B cells were OKB4+ but mantle zone and interfollicular B cells were OKB4-. 45/47 SIg+ B-cell neoplasms were OKB1+ OKB4+. 45/46 SIg+ B-cell neoplasms were OKB7+. Benign and myeloma plasma cells were OKB-. T-cell neoplasms were OKB2- OKB4- but were occassionally OKB1+ and OKB7+. The OKB antibodies appear to detect distinctive antigens that may be expressed at different stages of B-cell differentiation.

Animals↗