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Biomedical subjects

A L Goldstein

Publications and source records attributed to A L Goldstein.

At least 109 records · Page 6Linked to original sources
PubMed1985

MicroELISA method for measurement of human serum thymosin alpha 1.

A microELISA for the estimation of human serum thymosin alpha 1 is described. In this assay, antibody to thymosin alpha 1 is pre-incubated with the standard or serum at 4 degrees C. Unbound antibody in the liquid-phase then binds with solid-phase thymosin alpha 1. The method is sufficiently sensitive for measuring serum levels of thymosin alpha 1 and highly reproducible. The serum levels measured with the microELISA are comparable to serum levels of thymosin alpha 1 determined by the previously described radioimmunoassay for thymosin alpha 1.

Antibody Specificity↗
PubMed1985

T-cell abnormalities after mediastinal irradiation for lung cancer. The in vitro influence of synthetic thymosin alpha-1.

The effects of mediastinal irradiation (RT) on the numbers and functions of purified peripheral blood T-lymphocytes from patients with locally advanced non-small cell lung cancer were evaluated. The patients were candidates for a randomized trial to evaluate the immunorestorative properties of synthetic thymosin alpha-1. Twenty-one patients studied before RT did not exhibit any significant difference in T-cell numbers or function compared to age-matched healthy subjects. However, 41 patients studied within 1 week after completing RT exhibited significant depressions of E-rosette-forming cells at 4 degrees C (E4 degrees-RFC)/mm3, E-rosette-forming cells at 29 degrees C (E29 degrees-RFC)/mm3, OKT3/mm3, OKT4/mm3, and OKT8/mm3 (P = 0.0001); total T-cell percentages (%OKT3, P = 0.01); and T-cell proliferative responses in mixed lymphocyte cultures (MLR) (P = 0.01) and to the mitogen phytohemagglutinin under suboptimal conditions (P less than or equal to 0.03). Nine patients studied before and after RT showed a significant increase in OKT4/OKT8 (P = 0.01) following RT. A short-term in vitro incubation with thymosin alpha-1 could enhance MLR of T-cells in 12 of 27 patients with post-RT abnormalities. In 13 patients who were treated with placebo, the RT-induced depression of T-cell numbers and function persisted for at least 3 to 4 months. In addition, in 12 patients progressive decreases developed in %E4 degrees-RFC, %OKT3, %OKT4, and OKT4/OKT8, which always preceded clinical relapse. This study indicates that mediastinal RT results in prolonged depletion of circulating T-cells, alterations of T-cell subset proportions, and intrinsic T-cell functional deficiencies. This patient population provides a uniformly immunosuppressed group of subjects with which to evaluate the immunorestorative effects of thymosin alpha-1 or other biologic response modifiers.

Adult↗
PubMed1985

Modulation of thymosin beta 4 by estrogen.

The endocrine thymus produces several hormone-like peptides (generically termed thymosins) which control development of the thymic-dependent lymphoid system and participate in the process of immune regulation. In addition, recent literature supports the hypothesis that gonadal steroids in general and estrogens in particular affect the immune system. To determine whether steroid hormones modulate secretion of thymic peptides, basal concentrations of thymosins alpha 1 and beta 4 were determined by radioimmunoassay in morning blood samples from 87 women in various clinical states. Basal concentrations of thymosin alpha 1 were similar in all women sampled. Basal levels of thymosin beta 4 were similar in normal women during the early follicular phase, women with premature ovarian failure, postmenopausal women not receiving estrogen, and individuals with gonadal dysgenesis. However, the marked variability of basal levels in premature ovarian failure and in postmenopausal women suggests that these groups are quite heterogeneous. Thymosin beta 4 concentrations were reduced in castrated women not receiving estrogen and were decreased more in both postmenopausal women and castrated women who were on chronic estrogen therapy. These data suggest that estrogens can modulate the circulating levels of thymosin beta 4 but not of thymosin alpha 1. We do not yet know whether sex steroids modulate secretion of other thymic peptides.

Adult↗
PubMed1985

Receptors for thymosin alpha 1 on mouse thymocytes.

Thymosin alpha 1 is able to act in vitro to stimulate T-cell precursors and to induce surface markers. The initial mechanism by which alpha 1 activates T cells could be the binding of alpha 1 to cell membranes. Using a specific anti-alpha 1 antibody and an indirect immunofluorescence procedure it was found that thymosin alpha 1 binds to the surface of a large portion of murine lymphocytes. Furthermore, thymocytes have been fractionated into immature and mature subpopulations by using the peanut agglutinin (PNA) technique. It was found that PNA+, immature cells showed specific receptors for alpha 1 on the cell membrane.

Animals↗
PubMed1985

Mechanism of action of thymosin. II. Effects of aspirin and thymosin on enhancement of IL-2 production.

Recent studies have shown that thymosin fraction 5 (TF5) enhances production of interleukin-2 (IL-2) by phytohemagglutinin (PHA)-stimulated normal human peripheral blood mononuclear leukocytes (PBL). In this study we sought to determine whether this effect of TF5 might be mediated via the cyclooxygenase or lipoxygenase pathways. Our studies demonstrate that aspirin, an inhibitor of the cyclooxygenase pathway, given in vivo, or added to cultures in vitro, results in two-fold increased IL-2 production by PHA-stimulated PBL. This increase is comparable to that seen when PBL are cultured in vitro with TF5. When aspirin and TF5 are added simultaneously to PBL in the presence of PHA, an additive response is seen. An inhibitor of the lipoxygenase pathway, 15-hydroxyeicosatetraenoic acid, did not significantly change IL-2 production by PBL or influence the enhancement by TF5. Augmentation of IL-2 production by aspirin and/or TF5 was prevented by monocyte depletion of the PBL population. These results are interpreted as demonstrating (a) that TF5 and aspirin augment, by distinct mechanisms, IL-2 production by normal human PBL, (b) that the effects of both of these agents are mediated directly or indirectly via a monocyte population and (c) that aspirin, in addition to its analgesic and anti-inflammatory properties, may act as a modulator of immunological responsiveness, either alone or in combination with other biological response modifiers such as thymosin.

Aspirin↗
PubMed1985

Thymosin beta 4.

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Amino Acid Sequence↗
PubMed1985

Thymosins, lymphokines, and the immunology of aging.

Recent data point to a significant role for thymosins, lymphokines, and other soluble mediators in the senescence of the immune response that occurs with aging. In recent years, considerable progress has been made in the isolation and physiochemical characterization of several of these soluble mediators. We are now beginning to define the mechanisms by which these molecules regulate and mediate immune responses. In this paper we review the properties of the best characterized thymic hormones and lymphokines and focus on the role of the endocrine thymus in modulating immune responses. Of particular interest is the recent observation that thymosin fraction 5 can enhance production of interleukin-2 (IL-2) and colony-stimulating factor (CSF), and that IL-2 production, but not CSF production, is selectively diminished in aging mice. Several of the products of the immune system also can act as neuroactive immunotransmitters and modulate a number of neuroendocrine responses. Current studies point to an important role for these molecules in modulating neuroendocrine function, suggesting a broader role for the endocrine thymus in the aging process.

Aging↗
PubMed1985

Evidence that thymosins and other biologic response modifiers can function as neuroactive immunotransmitters.

An increasing amount of data supports the hypothesis that there are bidirectional circuits between the central nervous system (CNS) and the immune system. Soluble products that appear to transmit information from the immune compartment to the CNS include thymosins, lymphokines, and certain complement proteins. Opioid peptides, adrenocorticotropic hormone (ACTH), and thyroid-stimulating hormone (TSH) are additional products of lymphocytes that may function in immunomodulatory neuroendocrine circuits. It is proposed that the term "immunotransmitter" be used to describe molecules that are produced predominantly by cells that comprise the immune system but that transmit specific signals and information to neurons and other cell types. Examples would include thymosin alpha 1 and beta 4, lymphocyte-derived ACTH, TSH, and beta-endorphin, interleukin 1, interferon as well as certain other lymphokines and cytokines. The evidence that certain thymosin peptides can serve as immunotransmitters by modulating the hypothalamic-pituitary-adrenal and gonadal axes will be discussed.

Adrenocorticotropic Hormone↗
PubMed1985

Mechanism of action of thymosin. I. Thymosin fraction 5 increases lymphokine production by mature murine T cells responding in a mixed lymphocyte reaction.

The effect of thymosin on the murine thymocyte mixed lymphocyte response was studied. Thymosin fraction 5 (TF5) caused a two- to threefold enhancement of the proliferative response and production of IL 2 when murine thymocytes were cultured with alloantigenic stimulator cells. Production of a second lymphokine, CSF, was increased up to sevenfold. The target cell for thymosin was a mature T cell, because the PNA- subpopulation of thymocytes, as well as peripheral lymph node lymphocytes, responded to culture with TF5 and alloantigen by enhanced proliferation and lymphokine production. The active component of TF5 appears to be one or more as yet unidentified peptides, because neither of the well-characterized TF5 component peptides, alpha 1 or beta 4, were active. After incubation with TF5 in primary culture, cells remaining after 10 to 14 days were increased both in number and in secondary response to alloantigen, as measured by lymphokine production. These results suggest that TF5 contains one or more biologically active components which can modulate mature T cell activity and lymphokine production, and which provide the basis for understanding some of the previously reported diverse effects of thymosin.

Animals↗
PubMed1985

Adipoblasts from the Zucker fafa rat.

In vitro experiments using both primary fetal hepatocyle cultures and adipoblast cultures have demonstrated that the presence of the fa gene is associated with decreased synthetic capacity, when compared to wild-type cultures. These results are in contrast to the elevated lipogensis and lipoprotein-lipase activities found in vivo in young adult obses (fafa) Zucker rats compared to their lean littermates. These studies used adipoblast cultures to address three possible explanations for these in vitro-in vivo differences: 1) FaFa and fafa adipoblast cultures represent different cell populations with intrinsically different abilities to differentiate, ie, to lipid-fill. 2) The decreased synthetic capacities in fafa vs FaFa adipoblast cultures are specific to cultures derived from the epididymal pad. 3) Cultured adipoblasts produce factor(s) that affect adipoblast differentiation in vitro. Results indicate that 1) the rate of differentiation is slower in fafa than in FaFa adipoblasts 2) there are depot-related differences in lipid metabolism, but these differences do not negate the in vitro association between the fa gene and decreased synthetic capacity and 3) FaFa epididymal-derived adipoblasts produce a factor(s) that affects inguinal-derived adipoblast differentiation and/or growth in vitro. Thus it is important to take both the site of cell origin and culture conditions into consideration when using in vitro systems as an approach to understanding complex in vivo disorders, such as obesity in the Zucker fafa rat.

Adipose Tissue↗
PubMed1985

Comparison of the effects of thymosin and other thymic factors on modulation of interleukin-2 production.

Thymosin fraction 5 (TF5) enhances interleukin-2 (IL-2) production by human peripheral blood mononuclear leukocytes (PBL) when cocultured in the presence of phytohemagglutinin (PHA). This important biological activity of TF5 is not due to the presence of two previously well-characterized component peptides, thymosin alpha 1 and thymosin beta 4, but rather to a new, still to be identified component of TF5. Comparison of TF5 with other well-defined thymic preparations and peptides indicates that this biological activity is unique to TF5 and a closely related extract prepared from porcine thymus tissue. Using a standard human PBL cell population obtained by leukopheresis and cryopreservation, it should now be possible to establish a reproducible bioassay for the isolation and characterization of one or more components of TF5 with the property of enhancing PHA-induced IL-2 production by human PBL.

Animals↗
PubMed1985

Elevated levels of gamma amino butyric acid (GABA) in the thymus gland during the immune response.

Innervation of the mammalian thymus gland by both cholinergic and catecholaminergic neuronal projections has been documented. The present results reveal that the inhibitory neurotransmitter, gamma amino butyric acid is also present in the mouse thymus and that it is significantly elevated following challenge with a T-cell dependent antigen. A possible immunomodulatory role for the neurotransmitter is discussed.

Adjuvants, Immunologic↗