Intraamniotic infection with Candida albicans associated with a retained intrauterine device. A case report.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
D Goldstein
Publications and source records attributed to D Goldstein.
Evidence for the elevation of serum carcinoembryonic antigen and tumor-associated glycoprotein-72 levels in patients administered interferons.
Sera were collected from 111 patients diagnosed with adenocarcinoma or nonadenocarcinoma malignancies who received different schedules of interferon (IFN)-gamma or IFN-beta ser alone or in combination. Serum carcinoembryonic antigen (CEA) and tumor-associated glycoprotein-72 (TAG-72) antigen levels were measured to determine whether interferon could enhance the tumor shedding and, thereby, the serum level of either tumor antigen. Less than 10% of the sera samples from patients diagnosed with nonadenocarcinoma malignancies (e.g., hairy cell leukemia, melanoma) had positive titers of TAG-72 or CEA, and interferon neither increased nor resulted in the appearance of either tumor antigen in those sera. In contrast, 59.2% and 75.4% of the patients with adenocarcinoma had positive serum levels of TAG-72 and CEA, respectively, prior to interferon. IFN-gamma and IFN-beta ser alone or in combination significantly increased serum TAG-72 or CEA in approximately 65% of those patients. The results suggest that interferon administration to patients with adenocarcinoma can result in increased serum levels of selected tumor-associated antigens used in the diagnosis of malignancy. These preliminary findings may be important in the development of new strategies to obtain more sensitive tumor antigen serum assays for the diagnosis and monitoring for disease progression of adenocarcinoma.
Adenocarcinoma↗
Induction of antibodies to the envelope protein of the human immunodeficiency virus by immunization with monoclonal anti-idiotypes.
Anti-idiotypes that possess the internal image of antigen can induce protective humoral immunity toward microbes. Herein we demonstrate antigen mimicry by monoclonal anti-idiotypes of a distinct epitope of the human immunodeficiency virus (HIV) envelope protein that is defined by a synthetic peptide. This peptide, corresponding to amino acid residues 503-535 (peptide 503-535) of HIV-1 IIIB gp160, induced antibodies in three mammalian species that interacted with HIV-1 gp120 and inhibited in vitro syncytium formation caused by HIV-1, IIIB and MN isolates. Three monoclonal anti-idiotypes were generated against rabbit anti-gp120 antibodies specific for peptide 503-535. These anti-idiotypes recognize an interspecies cross-reactive idiotype expressed on mouse, chimpanzee, baboon, rabbit, and human anti-gp120 antibodies specific for peptide 503-535. The interaction with the cross-reactive idiotype is inhibited by synthetic peptide and HIV-1 gp160. Furthermore, rabbits immunized with the monoclonal anti-idiotypes produced antibodies that also bind HIV-1 gp120 and gp160 and recognized the epitope defined by peptide 503-535.
Amino Acid Sequence↗
Quantitative protein changes in metastatic versus primary epithelial ovarian carcinoma.
Primary and metastatic ovarian carcinomas from six patients were obtained during primary exploratory laparotomy. Tumor cells were synthetically radiolabeled with [35S]methionine. Radiolabeled cellular proteins of the primary and metastatic cells were examined by two-dimensional polyacrylamide gel electrophoresis followed by autoradiography. Computer assisted analysis of the resultant autoradiograms revealed that the amounts of only two proteins, p35 and p36, were consistently and significantly decreased in the metastatic tumor cells. No other consistent differences in protein synthesis between primary and metastatic tumors were detected.
Down-Regulation↗
Effects of interferon beta ser and transforming growth factor beta on prostatic cell lines.
The effect of interferon beta ser (IFN beta ser) on the growth of three prostatic cancer cell lines DU-145, PC-3 and LNCaP was studied. IFN beta ser inhibited growth of anchorage dependent semiconfluent monolayers and anchorage dependent colony formation of both DU-145 and PC-3 in a dose dependent manner but had no effect on LNCaP. Transforming growth factor beta (TGF beta 1) inhibited proliferation of DU-145 and PC-3 cells in 1% but not 8% fetal calf serum. The combination of TGF beta 1 and IFN beta ser was additive in its effects on growth. Neither epidermal growth factor (EGF) nor transforming growth factor alpha (TGF alpha) reduced the antiproliferative effect of IFN beta ser on these cells. These antiproliferative effects were reproduced in studies on primary epithelial cell cultures derived from prostate specimens with various pathologies. The potential use of IFN beta ser in combination with hormonal therapy to delay the development of hormone refractory tumors is discussed.
Cell Count↗
Advances in drug delivery and targeting.
This review covers a variety of techniques aimed at improving the specificity of delivery of both biologic and cytotoxic agents to tumor tissue while sparing normal tissue. The major areas reported on include further attempts to increase the ability of monoclonal antibodies, both conjugated and unconjugated, to target tumor tissue. It also examines the early clinical trials of liposomes as carriers of both biologics and cytotoxics and the potential problems of this modality. A number of studies in the area of regional drug delivery, including intraperitoneal, intravesical, intra-arterial, and intratumor, highlight the many clinical problems still to be resolved. Improved targeting of antitumor agents to sites of malignant disease appears likely over the next decade judging by the recent developments we review. Although much clinical and laboratory research will be required to achieve this goal, the likely directions appear to be established.
Antibodies, Monoclonal↗
Characterization of an experimental autoimmune dementia model in the rat.
Alzheimer's disease (AD) and other age-related cognitive deficits are associated with autoimmune phenomena. We recently showed that AD sera contain IgG that binds specifically to the heavy molecular weight neurofilament protein (NF-H) of Torpedo cholinergic neurons. We presently examined the behavioral effects of the induction of such antibodies in rats by prolonged immunization with Torpedo cholinergic NF-H. Immunohistochemical studies revealed the accumulation of IgG in the septum and hippocampus and in white matter tracts of these rats. T-maze alternation and discrimination tests revealed that immunization impaired the short-term working memory of the rats but had no effect on their reference memory. This impairment in short-term memory was reversed by treatment with the acetylcholinesterase inhibitor physostigmine. This animal model, termed experimental autoimmune dementia (EAD), may replicate immunologically induced pathogenic processes in AD.
Alzheimer Disease↗
Prolonged interleukin-2 (IL-2) treatment can augment immune activation without enhancing antitumor activity in renal cell carcinoma.
Preliminary studies involving small numbers of patients have suggested that interleukin-2 (IL-2) administered by continuous infusion in repetitive weekly cycles using doses of 3 x 10(6) U/M2/day is immunologically active and can induce tumor responses in patients with renal cell carcinoma. This study was designed to examine both the immunological and clinical effects of prolonged infusion IL-2 given by repetitive weekly cycles; first at moderate doses for 4 weeks as an impatient followed by lower doses of IL-2 for up to 5 months. Prolonged IL-2 treatment was investigated because previous studies revealed that patients had a return to their baseline immune status within 4 weeks after completing IL-2 treatment. Twenty-five patients (including 18 with renal cell carcinoma) were treated with one of two regimens utilizing IL-2 as sole therapy. These regimens were designed to induce augmented and prolonged immune activation based upon in vitro and in vivo data. Though patients on both arms of the study demonstrated sustained lymphocytosis, increase in numbers of natural killer cells, and induction of lymphokine-activated killer activity with prolonged IL-2 administration, only 1 out of the 18 patients with renal cell carcinoma demonstrated a sustained partial antitumor response to therapy. Furthermore, several patients demonstrated profound immune activation, without any evidence of tumor regression. The lack of clinical responses in these patients showing marked activation of LAK cytotoxicity suggests that other variables must also influence the likelihood of antitumor effects for patients receiving IL-2 therapy.
Adult↗
Financial analysis critical to physician alliances.
Although physician support programs have gained in popularity in recent years, organizations must be careful to select the most effective mix of physician relations programs. A healthcare financial manager can help create a productive physician alliance program by analyzing physicians as strategic business units, providing financial and analytical support for program assessment, screening programs for legal risks, and assessing an alliance program's risks in terms of antifraud and abuse legislation, tax laws, and private inurement issues.
Financial Management, Hospital↗
Cellular dry mass during macrophage development in malignant lymphoma.
In order to throw light on known mononuclear phagocyte disturbances in malignant lymphoma, scanning and integrating microinterferometry was employed to measure dry mass in developing mononuclear phagocytes after 0, 2, 4 and 6 days of suspension culture, using cells from 19 healthy subjects, 19 patients with Hodgkin's disease and 17 with non-Hodgkin's lymphoma. Analysis of variance showed that highly significant increases in dry mass (approximately twofold) occurred over the six-day period. No significant differences were found between the subject groups, nor were any attributable to age or sex. In terms of their dry mass, mononuclear phagocytes from lymphoma patients undergo developmental changes in suspension culture that are similar to normal, but a comparison with earlier cell volume studies suggests that differences in cellular water content may be present.
Adult↗
Inhibition of hormone-dependent and independent breast cancer cell growth in vivo and in vitro with the antiestrogen toremifene and recombinant human interferon-alpha 2.
The antiproliferative action of the antiestrogen toremifene and recombinant human interferon-alpha 2a (IFN-alpha 2a) were examined on human breast cancer cell lines grown in culture and in the athymic mouse. Solid tumors grew from an inoculation of a 99:1 ratio of hormone dependent (MCF-7) and hormone independent (MDA-MB-231) breast cancer cells without estrogen administration. However, estradiol supplementation significantly increased the rate of tumor growth. The daily administration of 1.35 x 10(6) U of recombinant human IFN-alpha 2a resulted in a marked rduction of tumor growth in both estradiol-treated and non-treated mice. Toremifene administration (130 micrograms/day from a sustained release preparation) markedly inhibited estradiol stimulation of mouse uterine weight and partially reduced estradiol-stimulated tumor growth. The combination of IFN-alpha 2a (1.35 x 10(6) u/day) with toremifene (130 micrograms/day) reduced estradiol-stimulated growth much below that of toremifene alone but not below that seen with interferon alone. Toremifene (10(-10)-10(-6) M) did not inhibit the growth of hormone-independent MDA-MB-231 breast cancer cells in vitro whereas it did inhibit the growth of hormone-dependent MCF-7 cells in phenol red containing media. IFN-alpha 2a (1-10,000 u) inhibited the growth of both MCF-7 and MDA-MB-231 cells in culture; however, MCF-7 cells were approximately 10-fold more sensitive to interferon inhibition. This was consistent with the MCF-7 cells showing a greater sensitivity to interferon than MDA-MB-231 cells in the induction of 2'5'-oligoadenylate synthetase.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Endocrine and behavioral responses to psychological stress in hyperandrogenic women.
Stress has been implicated in the physiopathology of the ovarian androgenic syndrome. To explore further this notion, we compared the behavioral and endocrine responses to a mental stressor between women with hyperandrogenism (n = 13) and normals (n = 11). The standardized psychological stimulus produced higher levels of anxiety in the hyperandrogenic group than in controls. The endocrine (cortisol, prolactin, growth hormone, beta-endorphin) responses poststressor were definitely dissociated. Both groups showed a comparable anticipatory stress cortisol-secretion response. The cortisol release was greater following the mental stressor in the hyperandrogenic group than in the normals. Thus, hyperandrogenic women appear to have an abnormally affected pituitary-adrenal activation, which may play a role in the pituitary-ovarian disruption characteristic of the ovarian androgenic syndrome.
Adult↗
Phase II trial of carboplatin in soft-tissue sarcoma.
As part of the Eastern Cooperative Oncology Group program for the assessment of new drugs in sarcomas, a Phase II trial of carboplatin was performed in patients who had received no more than one prior chemotherapy regimen. A total of 50 patients received either 400 mg/m2 or 320 mg/m2 depending on whether they had received prior radiotherapy. A response rate of 16% (95% confidence interval 6-32%) occurred in the 37 patients who had received doxorubicin as their only prior systemic therapy. Three of the six responses were complete and persisted for 7 to 34 months. In contrast none of the 13 patients who received carboplatin after initial progression on doxorubicin and subsequent progression on interferon alpha responded. The overall response rate was therefore 12% (95% confidence interval 5-24%). Toxicity was primarily hematologic, with 14 patients having Eastern Cooperative Oncology Group (ECOG) grade 3 toxicity and no grade 4 or 5 toxicities. In view of the number of complete responses, carboplatin should be studied further in untreated patients with advanced soft tissue sarcoma.
Adult↗
Sex differences in visual-spatial ability: the role of performance factors.
Two studies were designed to explore the role of performance factors as sources of the frequently noted higher male scores on visual-spatial ability tests. In the first study, the mental rotations test (MRT) was administered to male and female college students of equally high quantitative ability (based on SAT math scores). Although males had significantly more correct responses on the test than did females, their advantage was eliminated when the ratio of correct responses to items attempted was used as the dependent measure. In the second study, the same test was administered to new groups of male and female college students. In this sample, the males had significantly higher SAT math scores. The MRT was administered under standard, timed conditions and under untimed conditions. Both raw and ratio scores were calculated. With SAT math score as the covariate, analyses of covariance indicated that males demonstrated higher performance in the timed, raw-score condition but not in the untimed or in the ratio-score conditions. The theoretical and social policy implications of these studies are discussed.
Adolescent↗
Phase I studies of recombinant interferon-gamma.
A phase I study of the effects of intravenous administration of interferon-gamma on 31 patients was performed. The effects of dose, schedule, and chronic administration were studied. In the first phase of the study, a dose range of 0.01-500 MU/m2 (0.0002-25 mg/m2) was tested and we found the maximum tolerated dose to be 400 MU/m2; the dose-limiting toxicity with this preparation was hypotension. In the second phase, three different schedules of administration were tested. There were no significant differences in toxicity between a 20 min, a 4 h, or a 24 h infusion of 60 MU/m2 (3 mg/m2). In the third phase, patients received chronic administration of either 1 or 30 MU/m2. Patients given 30 MU/m2 twice a week for 4 weeks showed more symptoms--fever, nausea, and orthostasis--than those treated with 1 MU/m2. No significant changes were seen in natural killer cell activity, antibody-dependent complement cytotoxicity, or monocyte cytotoxicity at any dose. Maximal stimulation of 2',5'-oligodenylate synthetase occurred at low doses (12 MU/m2). Depressed bone marrow colony formation for CFU-GM, BFU-E, and CFU-GEMM in vivo was noted. No objective antitumor responses were noted. This preparation of recombinant interferon-gamma can be given in doses as high as 400 MU/m2. Chronic administration would appear to be limited to 30 MU/m2. However, lower doses may give maximal biologic responses. These studies provide further information on the biologic effects of a wide dose range and a variety of schedules of recombinant interferon-gamma.
2',5'-Oligoadenylate Synthetase↗
Repetitive weekly cycles of interleukin 2: effect of outpatient treatment with a lower dose of interleukin 2 on non-major histocompatibility complex-restricted killer activity.
Fifteen patients with advanced malignancy who had failed conventional therapy were entered into a protocol consisting of 1 inpatient mo of repetitive weekly cycles of interleukin 2 (IL-2) at 3 x 10(6) units/m2/day by constant infusion for the first 4 days of each week. This was followed by IL-2 administered on an outpatient basis at the same schedule but at a dose of 1 x 10(6) units/m2/day for the next 1 to 6 mo. Nine patients had renal carcinoma, four had melanoma, and two had lymphoma. Thirteen patients completed the induction month, and ten patients completed greater than or equal to 1 mo of outpatient therapy. Only one patient had therapy discontinued because of toxicity due to IL-2. No major toxicities occurred during outpatient therapy. After 1 mo of IL-2 at 3 x 10(6) units/m2/day, profound changes similar to those previously documented were seen in peripheral blood lymphocyte (PBL) counts (4.7-fold increase), lymphokine-activated killer activity (16-fold increase), and the percentage of PBL with natural killer-associated markers including a 3.6-fold increase in the percentage of PBL expressing the Leu 19 (NKH-1) marker, a 3.7-fold increase in Leu 11 (FcIgGR), and a 3.0-fold increase in Leu 17 (OKT10). These indicators of IL-2 effect all remained elevated relative to the baseline at the end of 1 and 2 mo of outpatient therapy at the lower dose. However, lymphokine-activated killer activity and Leu 17 percentage were significantly reduced relative to the effect of the higher induction dose. PBL taken from patients while receiving maintenance therapy showed strong and rapid responses to IL-2 in vitro, confirming the in vivo effects of prolonged IL-2 treatment. Nevertheless, there were no complete or partial antitumor responses seen. This study demonstrates that an immunologically active dose of IL-2 can be given long term as outpatient therapy with tolerable toxicity and results in highly IL-2-responsive "primed" lymphokine-activated killer cells.
Adult↗
Muscarinic receptor activation of phosphatidylcholine hydrolysis. Relationship to phosphoinositide hydrolysis and diacylglycerol metabolism.
We examined the relationship between phosphatidylcholine (PC) hydrolysis, phosphoinositide hydrolysis, and diacylglycerol (DAG) formation in response to muscarinic acetylcholine receptor (mAChR) stimulation in 1321N1 astrocytoma cells. Carbachol increases the release of [3H]choline and [3H]phosphorylcholine ([3H]Pchol) from cells containing [3H]choline-labeled PC. The production of Pchol is rapid and transient, while choline production continues for at least 30 min. mAChR-stimulated release of Pchol is reduced in cells that have been depleted of intracellular Ca2+ stores by ionomycin pretreatment, whereas choline release is unaffected by this pretreatment. Phorbol 12-myristate 13-acetate (PMA) increases the release of choline, but not Pchol, from 1321N1 cells, and down-regulation of protein kinase C blocks the ability of carbachol to stimulate choline production. Taken together, these results suggest that Ca2+ mobilization is involved in mAChR-mediated hydrolysis of PC by a phospholipase C, whereas protein kinase C activation is required for mAChR-stimulated hydrolysis of PC by a phospholipase D. Both carbachol and PMA rapidly increase the formation of [3H]phosphatidic acid ([3H]PA) in cells containing [3H]myristate-labeled PC. [3H]Diacylglycerol ([3H]DAG) levels increase more slowly, suggesting that the predominant pathway for PC hydrolysis is via phospholipase D. When cells are labeled with [3H]myristate and [14C]arachidonate such that there is a much greater 3H/14C ratio in PC compared with the phosphoinositides, the 3H/14C ratio in DAG and PA increases with PMA treatment but decreases in response to carbachol. By analyzing the increase in 3H versus 14C in DAG, we estimate that the DAG that is formed in response to PMA arises largely from PC. Muscarinic receptor activation also causes formation of DAG from PC, but approximately 20% of carbachol-stimulated DAG appears to arise from hydrolysis of the phosphoinositides.
Arachidonic Acid↗
Human biologic response modification by interferon in the absence of measurable serum concentrations: a comparative trial of subcutaneous and intravenous interferon-beta serine.
The effect on a range of biologic responses of interferon-beta serine (IFN-beta ser), administered by either the sc or the iv route, was examined in 16 patients. Despite the absence of IFN in the serum of 13 of 16 patients after sc administration, biologic changes associated with IFN administration occurred. Significant increases in peripheral mononuclear cell surface proteins were evident. Monocyte human leukocyte antigen-DR (HLA-DR) showed a 23% increase in mean fluorescent intensity (P = .04) and a 9% increase in percentage of positive cells (P = .02); lymphocyte OKT10 had an 11% increase in percentage of positive cells (P less than .0001) and a 26% increase in mean fluorescent intensity (P = .002). Natural killer cell activity against the Change target increased by 125% (P = .004). Intracellular activity of 2',5'-oligoadenylate synthetase increased 297% at 24 hours and 226% at 48 hours (P less than .0001). Significant increases in serum concentrations of beta 2 microglobulin (24% at 24 hr and 27% at 48 hr, P less than .0001) and neopterin (85%, P = .0001 and 165%, P = .00001) were observed. These alterations after sc administration were similar quantitatively to those resulting from the same dose of IFN-beta ser given iv. Thus, serum IFN concentrations did not have to be measurable for IFN-beta ser to exert biologic activity. The different effects of two dose levels, 45 X 10(6) IU and 180 X 10(6) IU, also were compared independent of route. The higher dose resulted in greater increases over baseline of 2',5'-oligoadenylate synthetase activity (344% vs. 145% at 24 hr; 231% vs. 83% at 48 hr) and serum neopterin concentrations (185% vs. 99% at 24 hr; 271% vs. 153% at 48 hr). For all the other parameters, there was no significant difference between the two doses.
2',5'-Oligoadenylate Synthetase↗