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Biomedical subjects

D Goldstein

Publications and source records attributed to D Goldstein.

At least 181 records · Page 10Linked to original sources
PubMed1989

Effects of type I and II interferons on cultured human breast cells: interaction with estrogen receptors and with tamoxifen.

The combined effects of tamoxifen, a competitive inhibitor of estrogen, and type I or II interferons on the proliferation of several human breast cancer cell lines in vitro were examined. Additive antiproliferative effects were observed with interferons and tamoxifen, in two estrogen receptor positive cell lines, MCF-7 and T-47D. In MCF-7 cells neither beta ser interferon, gamma interferon, nor alpha 6 interferon were able to significantly alter estrogen receptor levels. Antigrowth activities of beta ser interferon and gamma interferon in an estrogen receptor negative cell line, HS578T, were equivalent to those in estrogen receptor-positive cell lines. Consistent with the antiproliferative effects of interferons, high affinity beta ser interferon receptors and interferon inducible 2'5'-oligoadenylate synthetase were present in both MCF-7 and HS578T cell lines. Thus steroid hormone receptor status did not influence the antiproliferative effects of interferons on breast carcinoma cells in vitro.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

Selective interferon-induced enhancement of tumor-associated antigens on a spectrum of freshly isolated human adenocarcinoma cells.

Freshly isolated cells from patients with pleural or peritoneal effusions cytologically diagnosed as adenocarcinoma (n = 43), malignant nonepithelial neoplasms (n = 10), and benign (n = 8) were analyzed for expression of constitutive levels of the tumor antigens TAG-72 [recognized by monoclonal antibody (MAb) B72.3] and carcinoembryonic antigen (CEA) (recognized by MAb COL-4) as well as the class I and class II major histocompatibility (MHC) antigens, and the ability of human interferons (Hu-IFNs) to enhance cell surface expression of those antigens as measured by MAb binding. Both type I and type II IFNs enhanced the expression of TAG-72 and CEA and altered the level of expression of the MHC antigens. Comparative studies of three different Hu-IFNs (IFN-alpha A, IFN-beta ser, and IFN-gamma) revealed that IFN-gamma was the most potent in augmenting either B72.3 or COL-4 binding. Unlike the IFN-gamma -mediated induction of the class II human leukocyte antigens, the change in tumor antigen expression consisted of enhanced constitutive antigen expression; de novo induction of either TAG-72 or CEA could not be achieved by either type I or type II IFN. Of 43 effusions isolated from different adenocarcinoma patients, 42 (97.7%) expressed either CEA or TAG-72, and treatment with Hu-IFN increased the level of expression of either antigen in 36 of 42 samples (85.7%). These studies demonstrate the augmentation of tumor-associated antigens on human carcinoma cells isolated from serous effusions by Hu-IFNs which may be used to enhance the targeting of conjugated MAbs to human carcinoma lesions.

Adenocarcinoma↗
PubMed1989

Effect of sustained pharmacologic vitamin E levels on incidence and severity of retinopathy of prematurity: a controlled clinical trial.

The incidence and severity of retinopathy of prematurity (ROP) as affected by vitamin E prophylaxis at pharmacologic serum levels (5 mg/dl) were evaluated in a double-masked clinical trial of infants with a birth weight less than or equal to 2000 gm or a gestational age less than or equal to 36 weeks. The infants were enrolled by age 5 days and randomly assigned to receive parenterally administered, and later orally administered, free alpha-tocopherol (vitamin E) or its placebo. Study medication was continued until retinal vascularization was complete or active ROP had subsided, except in infants with a diagnosis of severe disease, in whom vitamin E was substituted for study medication. Acute ROP data were collected on 755 infants. Logistic regression analysis, with control for immaturity, oxygen exposure, and other illness risk factors, showed a decrease in incidence of ROP in vitamin E-treated infants (p = 0.003, all infants; p = 0.035, infants weighing less than or equal to 1500 gm at birth). Among the 424 infants weighing less than or equal to 1500 gm at birth, the age at enrollment influenced treatment effect (age day 0 to 1, p = 0.006 (n = 288) vs age day 2 to 5, p greater than 0.1 (n = 136]. Overall, 77.6% of infants with ROP had mild disease. Moderate to severe ROP was confined to infants weighing greater than or equal to 1500 gm at birth (25 given placebo, 25 given vitamin E), with progression to severe disease in nine placebo-treated versus three vitamin E-treated infants (p = 0.048). The incidence of severe ROP per se was not significantly decreased (all birth weights, p = 0.086; less than or equal to 1500 gm birth weight, p = 0.080); the sample size was too small, however, to assess this end point adequately. An increased incidence of sepsis and late-onset necrotizing enterocolitis was found among vitamin E-treated infants weighing less than or equal to 1500 gm at birth who received study medication for greater than or equal to 8 days (p = 0.006). Because most ROP is mild in degree and regresses completely, the risk/benefit ratio of pharmacologic prophylaxis for ROP is unfavorable. Treatment of moderate and severe ROP with vitamin E above physiologic serum levels (greater than 3 mg/dl) appears promising and should be further investigated. The interpretation of cicatricial outcome was confounded by the small number of patients involved and by subsequent treatment of severe ROP in placebo-treated infants with vitamin E.

Age Factors↗
PubMed1989

Double-blind randomized cross-over trial of dexamethasone and prochlorperazine as anti-emetics for cancer chemotherapy.

A double-blind randomized cross-over trial of dexamethasone and prochlorperazine as adjunctive anti-emetics with cancer chemotherapy was undertaken. The drugs were compared for cisplatin, doxorubicin and several other chemotherapy regimens. A total of 44 eligible patients were analysed. Assessment was made by questionnaire answered by the patient 24 h after the chemotherapy. The parameters compared were period of time for nausea and vomiting, number of vomiting episodes, degree of somnolence and insomnia and overall preference. In all cases there was no significant difference for either drug in its ability to suppress emetic effects. Neither drug gave adequate protection against cisplatin-containing regimens. We conclude that dexamethasone alone is equivalent to the more standard dopamine antagonists.

Adult↗
PubMed1989

Human chorionic gonadotropin and free subunits' serum levels in patients with partial and complete hydatidiform moles.

Serum levels of hCG and its free subunits were measured in patients with partial and complete hydatidiform moles and in women with normal 10-week pregnancies. whereas complete moles had higher levels of percent-free beta-hCG than partial moles (2.4 versus 1.0; P less than or equal to .005), partial moles had higher levels of percent-free alpha-hCG than complete moles (0.85 versus 0.17; P less than or equal to .005). Normal 10-week pregnancies had lower levels of both percent-free beta-hCG and percent-free alpha-hCG than partial moles (0.40 versus 1.0, P less than or equal to .005 and 0.27 versus 0.85, P less than or equal to .005, respectively). Percent-free beta-hCG and beta-hCG levels did not distinguish which patients with complete mole were more likely to develop persistent post-molar tumor. The trophoblastic cells in complete and partial moles differ significantly in the manner in which they secrete the free subunits of hCG.

Chorionic Gonadotropin↗
PubMed1989

Diagnosis of stress-related hyperprolactinemia. Evaluation of the hyperprolactinemia rest test.

It remains controversial whether two or three random estimations of prolactin (PRL) concentration obviate the need for special testing to rule out stress-related hyperprolactinemia. In order to clarify this issue, we measured PRL, cortisol, and growth hormone (GH) in serial blood samples obtained under resting conditions (HPR test) in 70 women who had had high PRL levels in two or more random blood samples. Twenty out of 70 women were found to have stress-related hyperprolactinemia, and 11 of the 20 would have been misdiagnosed by using only three random samples. Cortisol levels from the HPR test indicated stress-related pituitary adrenal reactivity in all groups, including the idiopathic (N = 30) and prolactinoma (N = 20) groups. However, PRL secretion in response to stress--a downward trend as a function of time--was evident only in the stress-related hyperprolactinemia group. These results suggest that a limited HPR test (ie, serial PRL determinations at 0, 30, and 60 min) is a valuable and simple measure to identify stress-related hyperprolactinemia in order to avoid diagnostic pitfalls and unnecessary treatment.

Adolescent↗
PubMed1988

Differential production of human chorionic gonadotropin and free subunits in gestational trophoblastic disease.

Serum levels of human chorionic gonadotropin (hCG) and its free subunits (alpha hCG and beta hCG) were determined by means of highly sensitive and specific monoclonal and antipeptide-based monoclonal immunoradiometric assays. During normal pregnancy, the beta hCG to hCG ratio appears constant at approximately 0.5% after 5 weeks of gestation. In contrast, gestational choriocarcinoma was characterized by absolute serum beta hCG levels varying from three to 280 times greater than the maximum values observed during pregnancy and by exceedingly high beta hCG to hCG ratios. In complete hydatidiform mole, this ratio was intermediate between normal pregnancy and choriocarcinoma. The ratios of free beta hCG to hCG will distinguish normal from complete molar pregnancy (p less than 10(-8)), hydatidiform mole from choriocarcinoma (p less than 10(-4)), and choriocarcinoma from normal pregnancy (p less than 10(-8)) with high probability. Finally, it was found by means of the high sensitivity hCG immunoradiometric assays (less than 0.02 ng/ml) that this assay predicted very early tumor recurrence in patients with gestational choriocarcinoma.

Adult↗
PubMed1988

Down-regulation of an abundant cellular protein associated with tumor progression.

Alteration of gene expression in neoplastic cells can be detected by two-dimensional gel electrophoresis. This study reports the altered synthesis of an abundant cellular protein, p29, accompanying tumorigenic transformation of immortalized fibroblasts induced by transfection with oncogenic DNA. Cell lines derived from morphologically transformed foci synthesized p29 at 60-75% reduced levels compared with untransformed parental cells. Upon inoculation into syngeneic immunocompetent animals, transformed cells gave rise to tumors which were excised and established in culture. The amount of p29 in both focal and tumor-derived lines was inversely correlated with the latent period for tumor formation. In cell lines with a tumor latency of 12-20 days, the level of p29 was decreased by 90-99%. In rapidly tumorigenic cells with a short latency (3-6 days), p29 synthesis was not detectable. These data demonstrate that p29 may be a sensitive and reliable marker for tumor progression of fibroblasts.

Animals↗
PubMed1988

Guanine nucleotide-dependent inositol trisphosphate formation in chick heart cells.

Stimulation of muscarinic receptors in dissociated embryonic chick heart cells promotes the hydrolysis of the phosphoinositides resulting in accumulation of the breakdown products inositol trisphosphate, bisphosphate, and monophosphate (InsP3, Insp2, and InsP, respectively). [3H]InsP3 and [3H]InsP2 are significantly elevated within 10 seconds of carbachol addition, while there is a lag in the accumulation of [3H]InsP. The time courses of the formation of the inositol phosphates suggest that carbachol activates a polyphosphoinositide-specific phospholipase C resulting in the formation of InsP3, which is subsequently metabolized to InsP2 and InsP. High-performance liquid chromotography analysis demonstrates the formation of both naturally occurring InsP3 isomers (Ins-1,4,5-P3 and Ins-1,3,4,-P3) and of inositol tetrakisphosphate (InsP4) as well. To investigate whether a guanine nucleotide-binding protein couples receptor stimulation to phosphoinositide (PI) hydrolysis in the heart, we developed a saponin-permeabilized cell preparation that would allow external manipulation of the intracellular guanosine triphosphate (GTP) concentration. In the permeabilized cell preparation, guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) stimulates the accumulation of [3H]InsP, [3H]InsP2, [3H]InsP3, and [3H]InsP4. The effect of GTP gamma S is half-maximal at 1 microM and maximal above 100 microM. In contrast, GTP gamma S is ineffective in promoting PI hydrolysis in the nonpermeabilized cell except at high concentrations. Other guanine nucleotides also lead to the accumulation of [3H]InsP in the permeabilized cell, while 5'-adenylylimidodiphosphate does not. Carbachol also stimulates PI hydrolysis in the permeabilized cell preparation although it is less effective than in the intact cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Contributions of benzodiazepines to cancer therapy.

We have reviewed the therapeutic effects of benzodiazepines employed as adjuncts to cancer treatment. These agents have been used primarily for alleviating or attenuating situational anxiety, insomnia, chemotherapy-induced nausea and vomiting, and anticipatory nausea and vomiting. Situational anxiety not corrected by psychosocial support, symptom control, or time may be successfully treated with benzodiazepines. Procedure-related anxiety, for example, that related to bone marrow biopsy, venipuncture, intrathecal therapy, and the insertion of subclavian and femoral catheters, is a serious problem that may be alleviated by the use of benzodiazepines. Insomnia not caused by a depression serious enough to warrant treatment with a tricyclic antidepressant also may be successfully treated with benzodiazepines. Many clinicians have found benzodiazepines to be useful adjuncts to a cancer chemotherapy regimen because of their anxiolytic, sedative, and amnesic properties and also because of their suspected antiemetic properties when these drugs are used in conjunction with known antiemetic agents. The ability of lorazepam to induce antegrade amnesia has proved particularly useful in alleviating anticipatory nausea and vomiting connected with repeated courses of cytotoxic chemotherapy. Furthermore, since benzodiazepines are relatively safe drugs, their continued and probably expanded uses as cancer therapy adjuncts can be anticipated.

Anti-Anxiety Agents↗
PubMed1988

Elevation of cytoplasmic calcium concentration stimulates hydrolysis of phosphatidylinositol bisphosphate in chick heart cells: effect of sodium channel activators.

The sodium channel activators veratridine and batrachotoxin, the sodium ionophore gramicidin, and the calcium ionophore ionomycin stimulated phosphoinositide breakdown, as indicated by the increased accumulation of [3H]inositol monophosphate in embryonic chick heart cells. The levels of [3H]inositol trisphosphate and [3H]inositol bisphosphate were also increased by veratridine, indicating that there was increased hydrolysis of phosphatidylinositol bisphosphate by phospholipase C. The response to veratridine required both extracellular sodium and calcium, suggesting that calcium entry via Na/Ca exchange might activate phospholipase C. Fluorescence measurements with fura-2 confirmed that the sodium agents greatly increased the cytoplasmic calcium concentration. Veratridine (100 microM) increased cytoplasmic calcium from 94 +/- 4 nM to 862 +/- 103 nM, giving a maximal calcium increase in about 2 min. Batrachotoxin (1 microM) induced an even greater increase in calcium but required a longer time. Gramicidin also induced a large increase in cytoplasmic calcium which was maximal within 0.5 min. To directly test the calcium dependency of phospholipase C, we permeabilized the chick heart cells with saponin and monitored the production of inositol phosphates at different calcium concentrations. Raising the calcium concentration from 3 to 1000 nM increased the accumulation of [3H]inositol phosphates by nearly 4-fold with a half-maximal effect at about 200 nM calcium. The guanine nucleotide guanosine-5'-O-(3-thio)triphosphate (GTP gamma S) also stimulated accumulation of the InsPs and the response to (GTP gamma S) was potentiated by increasing the calcium concentration. The data suggest that the effect of the sodium agents on phosphoinositide hydrolysis results from an elevation of intracellular calcium which increases GTP-dependent phospholipase C activity. Thus, drugs or other conditions that elevate cytoplasmic calcium in heart cells may increase the hydrolysis of membrane phosphoinositides.

Animals↗
PubMed1987

Effects of gamma-interferon on the endocrine system: results from a phase I study.

Interferon causes profound biological changes when given to patients with cancer and many of these could not be predicted from in vitro or animal model systems. We documented significant changes in hormonal levels for a group of 18 patients who were participants in a Phase I gamma-interferon trial. Adrenocorticotropic hormone, cortisol, and growth hormone were all significantly elevated 2 h after treatment with gamma-interferon, with cortisol and adrenocorticotropic hormone returning to base line by 24 h. A placebo group failed to show this change, suggesting a specific interferon effect. Possible mechanisms for these findings and implications for the use of interferons are discussed.

Adrenocorticotropic Hormone↗
PubMed1987

Corticotropin-releasing factor (CRF) produces analgesia in humans and rats.

The analgesic activity of corticotropin releasing factor (CRF) was determined in a clinical model and in the rat hot plate test. Patients administered CRF reported significantly less postoperative pain than patients pretreated with placebo. In rats, injection of CRF resulted in a significant analgesia which was comparable in both intensity and duration to a 300 times greater molar dose of morphine. These findings suggest that endogenous CRF may play a physiologic role in modulating pain when released under conditions of stress.

Analgesia↗
PubMed1987

Chemotherapy influencing the course of nephrotic syndrome in colonic carcinoma.

A 50-year-old man presented with the Nephrotic Syndrome (NS). Subsequent investigations showed this to be due to a membranous glomerulonephritis. He was found to have a primary colonic carcinoma with extensive intra-abdominal spread. He was treated with 5-fluorouracil (5FU) with excellent resolution of the NS for a period of 6 months. The disease eventually progressed and the NS recurred on cessation of chemotherapy. This is the first report of such a response to 5FU of which we are aware and emphasizes the usefulness of palliative chemotherapy even in 'resistant' solid tumors when they are complicated by the NS.

Adenocarcinoma, Mucinous↗
PubMed1987

Acquired immune deficiency syndrome presenting as bone marrow and mediastinal cryptococcosis.

Disseminated cryptococcosis developed as the first manifestation of the acquired immune deficiency syndrome in a previously healthy Haitian man. Following presentation with a febrile illness that included massive mediastinal and peripheral lymphadenopathy, the patient died of overwhelming pulmonary, visceral, and meningeal cryptococcosis.

Acquired Immunodeficiency Syndrome↗