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Biomedical subjects

A L Goldstein

Publications and source records attributed to A L Goldstein.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effects of cholesterol and 25-hydroxycholesterol on smooth muscle cell and endothelial cell growth.

Auto-oxidation products of cholesterol may play a role in atherogenesis. In order to determine whether cholesterol or 25-hydroxycholesterol, a cholesterol auto-oxidation product, affected growth of vessel wall cells, sparse and confluent cultures of rabbit thoracic aorta smooth muscle cells and human umbilical vein endothelial cells were exposed to these compounds for 88 hr. The compounds were administered at 10(-4), 10(-5), 10(-6) or 10(-7) M in either ethanol or fetal bovine serum (FBS) vehicle. Cells were counted electronically, and the results were expressed as the percent growth in experimental vs control wells. Cholesterol did not inhibit cell growth under any experimental condition. 25-Hydroxycholesterol had the following effects: inhibited confluent smooth muscle cell growth at 10(-4) M in ethanol vehicle only; inhibited sparse smooth muscle cell growth in a dose-related manner at 10(-4), 10(-5) and 10(-6) M in ethanol vehicle, but in FBS vehicle inhibited at only 10(-4) and 10(-5) M; inhibited confluent human umbilical vein endothelial cells at 10(-4) M in ethanol vehicle only; and inhibited sparse human umbilical vein endothelial cell growth at 10(-4) and 10(-5) M in ethanol vehicle only. Thus, rabbit aortic smooth muscle cell growth was more sensitive to inhibition by 25-hydroxycholesterol than human umbilical vein endothelial cell growth was.

Animals↗
PubMed1988

Immunohistochemical studies in human thymomas. Localization of thymosin and various cell marker.

Forty five human thymomas were studied immunohistochemically using antibodies to thymosin x-1, thymosin beta-3, cortical epithelium of human thymus (UH-1), mouse thymic nurse cells (Th-3) and Leu-7. Most thymomas were found to contain thymosin x-1 (80%) and thymosin beta-3 (89%). Also used in the study were a new monoclonal antibody (UH-1), which reacts with the epithelial cells forming a meshwork in the cortex of the normal newborn thymus and Leu 7, which reacts with subcapsular epithelial cells in the outer thymic cortex. The combined use of UH-1 and Leu-7 was found to identify neoplastic epithelial cells of thymic cortical origin in thymomas. Approximately 80% (37/45) of the thymomas in the present study reacted with Leu-7, UH-1 or both antibodies, and were thus considered to be derived from cortical thymic epithelium. Of the eight thymomas which were negative with both Leu-7 and UH-1, four were histologically of mixed type characterized by the formation of epithelial cell islands. All four of these thymomas were positive with thymosin and were therefore considered to be of medullary origin. Ten of the thymoma were associated with myasthenia gravis; all were positive with UH-1 and were consider to be of cortical origin.

Antibodies, Monoclonal↗
PubMed1988

Thymosin fraction 5 (TF5) stimulates secretion of adrenocorticotropic hormone (ACTH) from cultured rat pituitaries.

In vivo administration of a partially purified thymic hormone-containing extract of the thymus gland, TF5, causes an increase in serum glucocorticoids. The lack of a direct effect of TF5 on adrenal corticosterone secretion suggests that it is mediated at the level of the pituitary. Cultured rat pituitary monolayers were used to determine if the effect is mediated by stimulation of ACTH secretion from the pituitary. Two lots of TF5, BPP100 and C114080-01, caused a dose dependent secretion of ACTH from cultured pituitary monolayers. There was a synergistic effect when the cells were treated with both TF5 and corticotropin-releasing factor (CRF). Immunoneutralization studies were done in which the cells were treated with TF5 or CRF and an antibody to CRF. The antibody completely blocked CRF induced ACTH release, but had no effect on TF5 stimulated ACTH release, suggesting that the activity is not due to a CRF-like peptide in TF5. A number of peptides isolated from TF5, and certain other peptides produced by the immune system were evaluated for their ability to stimulate ACTH secretion. These included thymosin (TSN) alpha 1, alpha 11, and beta 4, prothymosin alpha (PT alpha, thymopoeitin 5 (TP5), factuer thymique serique (FTS), interferon alpha (INF alpha), INF gamma, interleukin 1 (IL-1), and interleukin 2 (IL-2). None of these factors had any effect on pituitary ACTH secretion. These results demonstrate that some peptide component of TF5 causes an increase in serum corticosteroids by stimulating pituitary ACTH release.

Adrenocorticotropic Hormone↗
PubMed1988

Improved ELISA to measure thymosin alpha 1: comparison of whole and absorbed antisera.

An improved microELISA to measure thymosin alpha 1 (T alpha 1) is described which uses a rabbit antibody against T alpha 1 that has been absorbed with a synthetic C-14 fragment of T alpha 1. This assay is compared to the previous assay which used the whole antisera. The antibodies to T alpha 1 are preincubated with the standard or human sera overnight at 4 degrees C, then incubated for an additional 24 h in microtiter plates coated with T alpha 1. Using the whole antiserum, the average T alpha 1 level was 2480 +/- 1110 (mean +/- S.D.) pg/ml by ELISA and 2360 +/- 870 pg/ml by radioimmunoassay (RIA) in eight different samples of human cord sera. Using the N-specific absorbed antiserum the mean T alpha 1 level was 11,800 +/- 4800 pg/ml by ELISA and 10,600 +/- 5200 pg/ml by RIA. Recoveries of exogenously added T alpha 1 are complete (109 +/- 25% for whole and 108 +/- 15% for absorbed antisera). The absorbed antiserum has an increased affinity for the amino acid terminal region of T alpha 1 and the T alpha 1 values by use of absorbed antisera are significantly higher (3-5 x) than those measured using the whole antisera. Thus, the absorbed antisera produces an ELISA which is more sensitive and specific for serum thymosin alpha 1.

Antibodies↗
PubMed1988

Influences of aging and dietary restriction on serum thymosin alpha 1 levels in mice.

Influences of age (3 wk, 2, 7, 19, or 26 mo), long-term dietary restriction (DR) started at 3 wk of age, and acute fasting state on serum thymosin alpha 1 (T alpha 1) levels were measured by radioimmunoassay in female mice from a long-lived strain. The average T alpha 1 level was highest (approximately 60 ng/ml) at 3 wk and fell sharply such that 2 mo old mice fed either normal (N, approximately 80% of ad libitum intake) or restricted (R, approximately 50% of ad libitum intake) diets averaged approximately 20 ng/ml. Any age-related declines after 2 mo of age were mild and statistically significant only for R mice bled 2-4 h (but not 24-48 h) post-feeding. T alpha 1 levels were lower in group R than in group N mice in one experiment at 19 mo of age but not in another at 26 mo. The decline with age in serum T alpha 1 levels is mainly a very early life event for mice of this hybrid strain and appears uninfluenced by DR. T alpha 1 levels are variably reduced by DR later in life.

Age Factors↗
PubMed1988

Differential activity of thymosin peptides (thymosin fraction 5) on plasma thyrotropin in female rats of different ages.

Thymosin fraction 5 (TF-5), a partially purified thymic preparation, has been previously shown to have luteinizing-hormone-releasing-hormone-releasing activity in perfused rat hypothalamus as well as an in vivo stimulatory effect on the pituitary-adrenal axis in prepubertal monkeys. We report here the effect of TF-5 on the plasma levels of several hormones in female rats of different ages. Conscious free-moving Sprague-Dawley rats carrying an indwelling atrial cannula received a single dose of 5 mg/kg body weight of either bovine serum albumin (BSA) or TF-5 via cannula. In young (3-4) months and old (25 months) rats, thymosin induced a marked reduction of plasma thyrotropin (TSH) which was significantly greater than the normal circadian decline observed in the BSA-treated controls. Senescent females (34 months) displayed high basal levels of TSH which showed little circadian rhythmicity and did not respond to TF-5. Thyroxine (T4), triiodothyronine (T3), corticosterone, and prolactin levels were not affected by TF-5 at the dose levels tested. An age-dependent decrease in basal plasma levels of T4 but not T3 was observed in both BSA- and TF-5-treated rats. Young females given up to 10 mg BSA/kg body weight (i.v.) and noninjected controls had similar levels of the above hormones up to 3.5 h after BSA injection. These results suggest that the thymus has an inhibitory action on TSH in the rat, which is not mediated by the thyroid gland. Our results also suggest an age-related desensitization of the TSH system to thymic influence in this species.

Aging↗
PubMed1988

Effect of thymic hormones on interleukin 2 synthesis by lymphocytes from HIV-positive pre-AIDS subjects.

The PHA-induced synthesis of interleukin 2 (IL-2) by peripheral blood lymphocytes (PBL) from 9 normal and 8 pre-AIDS individuals was evaluated. IL-2 content in supernatant fluids of PBL cultures derived from pre-AIDS patients was only around 20% of that found in normal PBL cultures. The addition of two thymic preparations, thymosin faction 5 and TFX-Polfa, to PHA-stimulated PBL cultures from pre-AIDS patients caused significant increase of IL-2 content in cultures. Thymosin alfa 1 was ineffective in this respect. However, thymic factors corrected only partially the defective IL-2 synthesis by PBL from pre-AIDS patients increasing it to ca. 35% of value for normal PBL. The findings suggest the potential of PBL from pre-AIDS patients to respond in vitro to enhancing activity of thymic hormones.

HIV Seropositivity↗
PubMed1988

Cultured human endothelial cells treated with recombinant leukocyte A interferon. Tubuloreticular inclusion formation, antiproliferative effect, and 2',5' oligoadenylate synthetase induction.

Cultured human umbilical vein endothelial cells and human thoracic aorta endothelial cells were treated with 500, 1,000, and 2,000 IU/ml of recombinant leukocyte alpha-interferon for 2, 4, and 7 days. Tubuloreticular inclusions developed in treated human umbilical vein endothelial cells and human thoracic aorta endothelial cells. The size and number of tubuloreticular inclusions observed correlated with the dose and duration of treatment. Interferon treatment inhibited the rate of proliferation of both human umbilical vein endothelial cells and human thoracic aorta endothelial cells in a dose- and duration-dependent manner. Induction of the interferon-associated enzyme, 2'-5' oligoadenylate synthetase, also occurred. Since the endothelium is exposed to endogenous interferon present in certain pathologic conditions and to exogenous interferon administered in the treatment of several neoplastic or viral diseases, there is an increased need to understand the various effects of interferon on the endothelial cell.

2',5'-Oligoadenylate Synthetase↗
PubMed1988

Enzyme immunoassay measurement of thymosin beta 4 in human serum.

An enzyme immunoassay (EIA) for measurement of human serum thymosin beta 4 is described. Antiserum to synthetic thymosin beta 4, raised in rabbits, is incubated with a standard or serum. The unbound antibody in liquid-phase then binds with solid-phase thymosin beta 4. The EIA is both sensitive and accurate and is capable of detecting as little as 2.5 ng/ml thymosin beta 4 in serum. No cross-reactivity was observed with common serum proteins or other putative thymic hormones. High-performance liquid chromatography of serum samples reveals a single thymosin beta 4 peak that corresponds to the authentic thymosin beta 4 peak in the standard. Human serum levels range from 3 to 82 ng/ml in 142 healthy adult human volunteers. Newborn cord serum levels of thymosin beta 4 are lower than in adults.

Alkaline Phosphatase↗
PubMed1987

Modulation of human natural killer cell cytotoxic activity, lymphokine production, and interleukin 2 receptor expression by thymic hormones.

Thymic hormone preparations have been shown to modulate natural killer (NK) activity in vivo in mice. We have investigated the effects of thymosin fraction 5 (TF5) on the in vitro NK cell activity of highly purified human large granular lymphocytes (LGL). The results indicate that TF5 but not kidney fraction 5 (a preparation used as control) is able to enhance the spontaneous NK activity of normal LGL. In addition, TF5 exhibited additive effects with recombinant interferon-alpha in enhancing NK activity in vitro. TF5 also enhanced interleukin 2 production and interleukin 2 receptor expression as well as interferon-gamma production in mitogen-stimulated LGL. Thymosin-alpha 1, a synthetic polypeptide originally isolated in its native form from TF5, also exhibited enhancing effects on LGL activities, suggesting that it is the active species in TF5. These results indicate that thymic hormones might regulate NK activity through the induction of lymphokine production and receptor expression by LGL.

Cells, Cultured↗
PubMed1987

Thymosin fraction 5 stimulates the release of prolactin from cultured GH3 cells.

Thymosin fraction 5, a bovine thymus preparation, has recently been implicated in the regulation of neuroendocrine function. The purpose of the present study was to investigate the effects of thymosin fraction 5 treatment upon the GH3 rat pituitary cell line. Thymosin fraction 5 stimulated prolactin (PRL) release from these cells in a dose and time dependent manner. These results suggest that a product of the endocrine thymus may regulate the release of PRL.

Dose-Response Relationship, Drug↗
PubMed1987

Effect of thymosin immunostimulation with and without corticosteroid immunosuppression on chimpanzee hepatitis B carriers.

Carriers of hepatitis B surface antigen (HBsAg) are at a high personal risk of developing chronic hepatitis, cirrhosis, and primary hepatocellular carcinoma, and they pose a potential health threat to others. Accordingly, erradication of the carrier state is an important therapeutic goal. Several categories of drugs have been evaluated for this purpose, with, at best, limited success. The immune stimulants constitute a drug group considered to have potential benefit, since altered cell-mediated immunity (CMI) appears to have a pathogenic role in the perpetuation of the carrier state. One such immune stimulant is the thymic hormone, thymosin, which is known to enhance suppressor T-cell activity. We therefore examined its possible therapeutic role by evaluating its effect on four chronic HBsAg- and hepatitis B e antigen (HBeAg)-positive chimpanzees. After baseline biochemical, serological, immunological, and histochemical studies were conducted, all four chimpanzees received parenteral thymosin for a period of 10-14 weeks; two of them were pretreated for 4 weeks with corticosteroids. All four were then reevaluated in the same manner at regular intervals during the 14-week period. Neither immunosuppression nor immunostimulation significantly affected biochemical, serological, or histological measures. Indices of CMI were altered, however: both T4 and T8 cells increased with thymosin treatment, although the T4/T8 ratio declined because of the relatively greater increase of the T8 than of the T4 cells. Thymosin did not affect the mitogen assays. Thus, while immunostimulation with thymosin did slightly alter CMI, it had no affect on the HBsAg carrier state or on measures of chronic hepatitis, even when preceded by corticosteroid immunosuppression.

Animals↗
PubMed1987

Thymosin fraction 5 stimulates secretion of immunoreactive beta-endorphin in mouse corticotropic tumor cells.

In addition to reconstituting immune competence, the thymus gland preparation, thymosin fraction 5 (TSN-5), has recently been shown to stimulate secretion of hormones from the hypothalamic-pituitary adrenal axis in vivo and from pituitary corticotropes in vitro. The purpose of the present study was to investigate the effects of TSN-5 on secretion of immunoreactive beta-endorphin (i beta-E) by mouse corticotropic tumor cells. The release of i beta-E by AtT-20 pituitary tumor cells was increased in a dose-dependent manner by concentrations of 30-600 micrograms/ml of TSN-5, whereas concentrations greater than 1,000 micrograms/ml were increasingly less effective in stimulating secretion. TSN-5 (600 micrograms/ml) significantly stimulated i beta-E release within 7 min; maximal secretory responses (up to 275% of control release) occurred by 4 hr. The secretory response of AtT-20 cells to 600 micrograms/ml TSN-5 (37.9 +/- 2.0 vs. 16.1 +/- 1.0 ng i beta-E/ml/4 hr, mean +/- SE) was similar in magnitude to release evoked by 0.1 microM corticotropin-releasing factor (CRF). Combining TSN-5 and CRF treatments increased secretion of i beta-E to nearly 600% of control levels, an effect greater than an additive influence of the two independent treatments. Whereas CRF treatment reduced the levels of i beta-E in AtT-20 cell extracts after 24-hr treatment by 45% (231.8 +/- 24.7 vs. 417.2 +/- 17.8 ng i beta-E/mg protein, CRF vs. vehicle treatments, respectively), TSN-5 did not significantly alter cellular hormone content. Neither TSN-alpha 1 nor TSN-beta 4, two of the component peptides of TSN-5, affected basal or CRF-stimulated release of i beta-E, indicating that an unidentified constituent(s) is corticotropic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Immune-neuroendocrine interactions during aging: age-dependent thyrotropin-inhibiting activity of thymosin peptides.

Thymosin fraction 5 (TF-5), a partially purified thymic preparation, has been previously shown to have luteinizing hormone-releasing hormone (LH-RH)-releasing activity in perfused rat hypothalamus as well as in vivo stimulatory effect on the pituitary-adrenal axis in prepubertal monkeys. We report here the effect of TF-5 on the TSH-thyroid axis in young (3 months) and old (25 months) Sprague-Dawley male rats. Conscious free-moving animals carrying an indwelling atrial cannula received a single dose of 5 mg/kg body wt. of either bovine serum albumin (BSA) or TF-5 via the cannula. In the young rats, TF-5 induced a marked reduction of plasma thyrotropin (TSH) which was significantly greater than the normal circadian decline observed in the BSA-treated controls. The old males displayed high basal levels of TSH which showed no circadian rhythmicity, and did not respond to TF-5. Thyroxine (T4), triiodothyronine (T3), corticosterone, and prolactin levels were not affected by TF-5 at the dose levels tested. The old rats had significantly lower basal levels of T4, but not T3, than their young counterparts. The synthetic peptides thymosin alpha-1 and serum thymic factor, which are components of TF-5, had no effect on the above hormones when injected in doses up to 5 micrograms/kg body wt. Acute thymectomy in 3-month-old males induced a significant increase in basal levels of TSH without affecting plasma T4 or T3. These results suggest that the thymus has an inhibitory action on TSH in the rat, which is not mediated by the thyroid gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1987

Effect of partial testosterone replacement or thymosin on anti-DNA in castrated (NZB X NZW)F1 males.

Castration of young (3-week-old) but not older (3-month-old) male (NZB X NZW)F1 mice was associated with autoantibody production similar to that of untreated female littermates. The castration-induced disease provided a unique model for the evaluation of therapeutic modalities during the first 9 months of life. Castrated male (NZB X NZW)F1 mice were treated with either long-term thymosin (fraction 5) or testosterone for different periods of time. Continuous testosterone replacement abolished the autoimmune disease-accelerating effects of castration at 3 weeks. Brief treatment during either the early or the later periods of life of castrated (NZB X NZW)F1 males was insufficient to prevent accelerated anti-DNA production. Thymosin treatment, when started at the time of castration and continued through life, abolished the rise in anti-DNA. These studies suggest that androgens work throughout the first 7 months of life of the mouse to suppress anti-DNA and that lack of androgens for a relatively brief period allows anti-DNA production to be initiated. Once initiated it cannot be completely suppressed. The cellular basis of the fixed aspect of this process is unknown. A possible role of the thymus is suggested by the ability of thymosin to suppress anti-DNA.

Animals↗
PubMed1987

In vitro effects of thymosin and lithium on lymphoproliferative responses of normal donors and HIV seropositive male homosexuals with AIDS-related complex.

The in vitro effects of thymosin fraction 5 (TF5) and lithium chloride (LiCl) on the ability of peripheral blood mononuclear cells (PBMC) obtained from 37 normal male donors and 33 male patients with AIDS-related complex (ARC) to respond to alloantigenic stimulation (mixed leukocyte reaction, MLR) and to produce interleukin 2 (IL-2) in response to mitogens were studied. TF5 significantly increased MLR responses in normal donors (P less than 0.01) and in a group of 33 ARC patients with depressed cellular immunity (P less than 0.05). Similar effects were observed when LiCl was added to the MLR assays in both the normal and the ARC patient groups. Furthermore, TF5 and LiCl exhibited additive immunoenhancing properties. In 10 normal donors TF5 enhanced phytohemaggutinin (PHA)-induced IL-2 production as well as IL-2 production in response to pokeweed mitogen (PWM) (P less than 0.02). TF5-mediated enhancement of IL-2 production by PBMC obtained from ARC patients was observed in response to both mitogens, i.e., PHA and PWM. Additionally, LiCl increased PHA-induced IL-2 production in both normal subjects and ARC patients. LiCl and TF5 together had an additive effect in the enhancement of IL-2 production in both groups of subjects. Our data extend previous observations regarding the immunoregulatory activities of TF5 and LiCl and provide evidence that PBMC obtained from ARC patients have the potential to respond in vitro to these agents. The significance of these findings is discussed.

AIDS-Related Complex↗