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Biomedical subjects

A L Goldstein

Publications and source records attributed to A L Goldstein.

At least 145 records · Page 8Linked to original sources
PubMed1983

Measurement of thymosin alpha 1 by disassociation microELISA.

A disassociation microELISA was devised for the estimation of thymosin alpha 1, a chemically characterized thymic polypeptide isolated from bovine thymosin fraction 5. Antiserum to synthetic thymosin alpha 1 was raised in rabbits. Thymosin alpha 1 in liquid phase competed with a solid-phase-bound thymosin alpha 1 for this highly specific antibody. The method is specific, sensitive, reproducible and capable of detecting as little as 100 pg/ml of thymosin alpha 1.

Animals↗
PubMed1983

Solid-phase synthesis of thymosin beta 4: chemical and biological characterization of the synthetic peptide.

The chemical synthesis of thymosin beta 4 using a solid-phase procedure has been accomplished. The synthetic product was found to be homogeneous on paper electrophoresis at pH 6.5, high-performance liquid chromatography on a reversed-phase column, and isoelectric focusing using polyacrylamide gels. The synthetic material was also shown to be identical with the natural thymosin beta 4 by tryptic peptide mapping, amino acid compositional analyses, and polyacrylamide gel isoelectric focusing. Biologically, synthetic thymosin beta 4 was found to be as active as the natural compound in a terminal deoxynucleotidyltransferase induction assay and in a macrophage migration inhibition assay. The proposed structure of the peptide hormone was thus confirmed by a chemical synthesis.

Amino Acid Sequence↗
PubMed1983

Immunological studies of male homosexuals with the prodrome of the acquired immunodeficiency syndrome (AIDS).

Homosexual patients who mainly had the prodrome of the syndrome of opportunistic infection and Kaposi's sarcoma were studied immunologically. Patients showed diminished delayed hypersensitivity to recall antigens, diminished lymphocyte blastogenic responses, a suppressor cell for lymphocyte proliferative responses, low helper cells and an inverted helper:suppressor ratio. The patients had low levels of adherent monocytes. NK cell activity and antibody dependent cellular cytotoxicity were normal. Virtually all patients showed elevated serum thymosin alpha 1 levels and elevated serum lysozyme levels. The most consistent findings were the low helper cells, inverted helper:suppressor ratio and elevated serum thymosin alpha 1 and lysozyme. The patients with the prodrome should be subjected to therapeutic research with immunorestorative drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Increased thymic hormone responsive suppressor T lymphocyte function in chronic active hepatitis.

Mitogen-induced suppressor T lymphocyte function was evaluated in patients with chronic active hepatitis (CAH). The in vitro effect of the biological response modifier, thymosin fraction 5, on the suppressive activity of peripheral blood mononuclear cells (PBM) was also assessed. Suppressor cell activity was significantly decreased in patients with CAH when compared to controls (P less than 0.001). In the absence of the inducing mitogen, thymosin-treated PBM from both patients and controls promoted enhancement of tritiated thymidine uptake by cocultured allogeneic lymphocytes. When thymosin-treated mononuclear cells were mitogen-activated; patients, but not the controls, showed a marked increase in suppressor activity (P less than 0.001). These results indicate that the polypeptides contained in thymosin fraction 5 can promote a helper effect in patients and controls. Furthermore, PBM from patients with CAH contain a subset of lymphocytes that can express a suppressive function following thymosin treatment. We conclude that thymosin fraction 5 can promote an in vitro restoration of suppressor T cell function in patients with CAH.

Adolescent↗
PubMed1983

Modulation of endogenous prostaglandins by thymosin-alpha 1 in lymphocytes.

The effects of thymosin-alpha 1 on the stimulation of specific release of prostaglandin E2 (PGE2) from splenic lymphocytes and thymocytes were studied. Experiments were also performed to study in parallel the absolute levels of thymosin-alpha 1 in the blood and the induction of serum FTS activity and of azathioprine sensitivity of spleen cells from adult thymectomized (ATx) mice. A significant difference in the release of PGE2 between normal splenocytes and splenocytes from ATx mice was observed. Thymosin-alpha 1 at certain concentrations was able to stimulate PGE2 release from lymphocytes of ATx mice while inhibiting release in lymphocytes of normal mice. Also, thymocytes were stimulated to release PGE2 after incubation with alpha 1 in a manner similar to that seen in spleen cells of ATx mice. Approximately the same concentrations of alpha 1 was found to also correct the low azathioprine sensitivity of splenocytes from ATx mice. Determinations of FTS-like activity in the blood and the pharmacokinetics of alpha 1 after administration of this synthetic molecule show a clear dissociation. A maximum peak of alpha 1 activity was obtained after 1 hr, while maximal FTS-like activity was observed after 24 hr. The inhibition of the induction by alpha 1 of FTS-like activity and of Thy 1.2 antigen by indomethacin suggests that the action of alpha 1 requires prostaglandin biosynthesis.

Animals↗
PubMed1983

Lipogenesis in primary cultures of adipoblasts derived from genetically obese Zucker rats.

Adipocyte precursor cultures prepared from the epididymal fat pads of genetically obese (fa/fa) and lean (Fa/Fa) Zucker rats grow similarly in culture. Addition of enriched medium (EM) containing human serum, insulin, and glucose stimulated lipid filling of the adipocyte precursors in both cultures. However, [3H] H2O incorporation into total lipids, fatty acid synthetase and lipoprotein lipase activities, and cytosolic protein contents are all decreased in the fa/fa compared with the Fa/Fa cultures. Substitution of lean or obese rat serum for human serum in the enriched medium does not alter the decreased lipogenic capacity of the fa/fa adipocyte precursor cultures.

Adipose Tissue↗
PubMed1983

Enhancement of murine thymocyte cytotoxic T cell responses by thymosin.

Incubation of murine thymocytes with thymosin Fraction 5 (F5) results in a twofold enhancement of the cytotoxic T lymphocyte response (CTL). The assay exhibits requirements for optimal concentrations of thymosin (100 micrograms/ml) and optimal responder/stimulator ratios. Enhancement of CTL activity can be demonstrated in several responder/stimulator strain combinations. The data indicate that thymosin F5 acts via the responder thymocyte population rather than the stimulator cells, since comparable effects were obtained using nude spleen stimulator cells devoid of mature T cells. This system provides a useful bioassay for identifying the component peptides of thymosin F5 which promote thymocyte differentiation and/or maturation and for elucidating the mechanisms of action of the biologically active thymosin peptides.

Animals↗
PubMed1983

Thymosin fraction 5 does not accelerate reconstitution of immunologic reactivity after human marrow grafting.

More than 1 year is required for immunologic function to recover following human marrow grafting. In an attempt to shorten the time required for immunologic reconstitution, 14 patients were treated with thymosin fraction 5 after transplantation. Two died before administration of thymosin could be completed. In the remaining 12 patients, immunologic studies were compared to those of patients who were transplanted but did not receive thymosin. While five patients had transient elevation of in vitro lymphocyte blastogenesis during thymosin treatment, results of other immunologic studies from patients treated with thymosin were similar to those from patients not treated. The subsequent development of graft-versus-host disease, major or minor infection, and leukaemic relapse was not different between the groups. Six patients are alive and five are well without problems; one has chronic graft-versus-host disease. We conclude that thymosin fraction 5 administered as described was not toxic. Although modifying some immunological parameters, thymosin did not appear to alter the incidence of graft-versus-host disease, infection or leukaemic relapse or to accelerate immunologic reconstitution.

Adolescent↗
PubMed1983

Increased circulation of T lymphocytes bearing surface thymosin alpha 1 in patients with myasthenia gravis: effect of thymectomy.

We studied the interaction of the thymic hormone thymosin alpha 1 with peripheral blood B and T lymphocytes in patients with myasthenia gravis (MG), using antibodies against thymosin alpha 1 in an immunofluorescence technique. Eleven of 16 patients with symptomatic MG had an increased number of T lymphocytes bearing surface thymosin alpha 1 (T alpha 1); 5 patients with asymptomatic disease had normal levels of T alpha 1. In six young adults with symptomatic MG who subsequently responded to thymectomy, the number of T alpha 1 cells returned to normal 1 month after thymectomy. Because levels of T alpha 1 correlated with symptoms and thymosin alpha 1 specifically recruits helper T cells, our findings suggest that T alpha 1 may play an immunoregulatory role in the pathogenesis of MG. Determination of T alpha 1 levels may prove to be helpful in assessing residual thymic activity after thymectomy.

Fluorescent Antibody Technique↗
PubMed1983

Thymosin peptides and lymphokines do not directly stimulate adrenal corticosteroid production in vitro.

There is developing evidence that certain thymosin peptides and lymphokines produce a transient increase in steroid hormones when introduced systemically. Conversely, the repressive effect of adrenocortical steroids on the immune system is well documented. In the present study, the direct effect of certain components of the immune system on steroid output by rat adrenal fasciculata cells was tested. With this system, there was no direct steroidogenic effect of either the partially purified thymosin fraction 5, or any of the purified peptide components tested (thymosin alpha 1, alpha 7, or beta 4). These peptides also did not synergize the cellular response to ACTH, nor did they induce cAMP production by a ACTH- and NaF-responsive adrenal membrane preparation. Supernatants from Con A-stimulated spleen cells, which were demonstrated to contain lymphokine activity, and partially purified mouse interferon were also without a significant direct or synergistic effect on steroidogenesis by adrenocortical cells. These results suggest that the steroidogenic response to these peptides observed in vivo may be mediated by the central nervous system.

Adrenal Cortex↗
PubMed1983

Leukocyte subset analysis and related immunological findings in acquired immunodeficiency disease syndrome (AIDS) and malignancies.

Cell surface marker analyses conducted on human peripheral blood lymphoid cells have proven extremely useful in the diagnosis of immunodeficiency and the diagnosis and staging of malignancies. In this paper we have focused on the ratio of helper to suppressor cells in patients with the acquired immune deficiency syndrome and in patients with malignancy. In thirty-three patients with the acquired immune deficiency syndrome, the majority showed an inverted helper:suppressor ratio, elevated serum thymosin alpha 1, and elevated serum lysozyme levels. The inverted ratio was due to a deficiency in T-helper cells. The inverted helper:suppressor ratio was associated with functional suppressor cell activity that was seen in 12 out of 21 patients examined. Patients' lymphocytes were found to suppress the PHA, pokeweed mitogen, and concanavalin-A responses of normal subjects' lymphocytes. The suppression also correlated with impaired lymphocyte proliferative responses among the patients' cells themselves. Because of these findings, the helper:suppressor ratio was studied in patients with solid tumors, lymphoma, acute leukemia, chronic lymphocytic leukemia, and hairy cell leukemia. Approximately 30% of these patients have an inverted helper:suppressor ratio. However, in ten out of 30 patients with chronic lymphocytic leukemia and in three out of 45 patients with lymphoma, the helper:suppressor ratio was elevated, being greater than 3.0. The significance of these findings is as yet to be explored, but it is suggested that an inverted helper:suppressor ratio in patients with malignancy may relate to an advanced stage of disease or a poor prognosis. Documentation of this point will require further study.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Immunological characterization of homosexual males.

To help clarify the nature and pathogenesis of the syndrome of severely opportunistic infection associated with immune deficiency in young homosexual males, we investigated the immunological characteristics of a group of 33 young homosexual men. These young men all had the prodrome to the syndrome which included a history of multiple sexual partners and multiple sexually transmitted diseases. In addition, they all had a past history of mild to moderate viral, bacterial, parasitic, or fungal infections and had used recreational drugs. Within this group of patients, there were five men who had Kaposi's sarcoma. Compared to the 21 normal heterosexual individuals, the homosexual men were found to be anergic to a battery of recall antigens (52% versus 19%); to be hyporesponsive to mitogen stimulation (pokeweed, 30.7 x 10(-3) versus 65.3 x 10(-3) cpm, p less than or equal to 0.005; concanavalin A, 32.2 x 10(-3) versus 60.1 x 10(-3) cpm, p less than or equal to 0.006); and to have lower helper T-cells (18% versus 34.6%, p less than or equal to 0.01), inverted helper:suppressor T-cell ratios (0.85 versus 1.92, p less than or equal to 0.01), and an elevated serum thymosin alpha 1 level (1473 versus 524 pg/ml, p less than or equal to 0.001). These data suggest that the immunological defect precedes the syndrome. The mechanism of this phenomenon is unclear; however, the repeated viral infection combined with drug usage may be responsible. The five patients with Kaposi's sarcoma were compared as a group to the other patients without cancer and found to be more severely immunodeficient. This suggests that the immune suppression by the malignant disease is superimposed on the preexisting deficiency.

Adult↗
PubMed1983

Demonstration of abnormalities in expression of thymic epithelial surface antigens in severe cellular immunodeficiency diseases.

Thymic epithelium from three patients with severe cellular immunodeficiency diseases were compared with age-matched normal thymic epithelium using three markers of human thymic epithelium and antibodies against thymosin alpha 1, thymopoietin, and thymosin beta 4. We have previously shown that normal thymic epithelium reacts with antibodies against GQ gangliosides (antibody A2B5) and binds tetanus toxin (TT). In addition, some areas of normal thymic epithelium express human Thy-1 antigen. We found thymic epithelium in patients with severe cellular immunodeficiency diseases to be different from normal subjects. Two children with severe combined immunodeficiency disease (SCID) had thymic epithelium that bound anti-GQ ganglioside antibody but, unlike in normals, did not bind TT. The patient with severe cellular immunodeficiency and normal serum immunoglobulins (Nezelof syndrome) had thymic epithelium that bound TT but, unlike normal thymic epithelium, did not react with anti-GQ ganglioside antibody. Thymic epithelium from both SCID and Nezelof syndrome patients contained thymosin alpha 1, thymopoietin, and thymosin beta 4 and expressed human Thy-1 antigen. In contrast to SCID thymus rudiments, Nezelof thymus contained numerous (though fewer than normal) lymphocytes with mature T cell surface antigens. Thus, using these probes of human thymic epithelium, we have demonstrated heterogeneous defects in thymic epithelial surface marker expression in severe primary cellular immunodeficiency diseases. These defects presumably reflect abnormalities of in vivo thymic epithelial maturation.

Antibodies, Monoclonal↗
PubMed1983

Immunomodulation of murine B16 melanoma metastasis: thymosin, thymectomy and irradiation.

Thymosin, a product of the endocrine system, was used to further define the effects of immunomodulation of metastasis. Adult thymectomized C57BL/6 mice, 4 wk post-irradiation (400 R) had a decrease in the number of pulmonary metastasis (compared to controls) following tail vein injection of 5 X 10(4) B16 melanoma cells. Thymosin fraction 5 (fr. 5) administration (200 micrograms/mouse, 3 times weekly beginning 2 days post-thymectomy) returned the number of metastasis to the nonthymectomized values. Thymosin treatment of sham-operated, sham-operated irradiated, or thymectomized nonirradiated mice did not significantly elevate the number of metastases compared to the respective controls. Variant tumors which have an increase in metastasis following thymectomy and irradiation were also used. Thymosin administration reversed the effects of thymectomy in such variants, resulting in a decrease in metastasis. Metastases in thymosin-treated control mice were not significantly altered. A role for the thymus in metastasis via an endocrine product (thymosin) is suggested by these studies. Since thymosin did not increase metastasis in intact mice with tumors, further clinical trials with thymosin in cancer patients are not counterindicated by our results. These experiments confirm that thymosin fr. 5 is an important probe of the immunoendocrine events involved in tumor growth and metastasis.

Animals↗