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Biomedical subjects

S Paul

Publications and source records attributed to S Paul.

At least 289 records · Page 16Linked to original sources
PubMed1984

Adriamycin, cyclophosphamide, and etoposide (VP-16-213) in extensive-stage small cell lung cancer.

A three-drug regimen composed of adriamycin, 50 mg/m2 and cyclophosphamide, 500 mg/m2 administered on day 1; and VP-16-213, 50 mg/m2 days 1-5, with courses repeated at 3-week intervals, was studied in 24 consecutive patients with extensive-stage small cell lung cancer (SCLC). Twelve of 33 patients (36%) evaluable for toxicity developed life-threatening marrow suppression and 12% died of septicemia following the first course of treatment. Eleven of 24 patients (46%) with extensive disease achieved an objective response and only one was classified as a complete response. Survival was related to performance status and metastatic site but was not influenced by tumor response. The present study is distinctive from that of previous reports of the same or similar three-drug regimen in that the response rate is lower and toxicity is substantial. Nonetheless, survival as measured by median duration (7.9 months) and proportion alive at 1 year (35%) is comparable to that of previous reports.

Adult↗
PubMed1984

A novel chemically induced animal model of human anxiety.

The ethyl ester of beta-carboline-3-carboxylic acid (beta-CCE) has a high affinity for benzodiazepine receptors and can antagonize some of the pharmacologic actions of benzodiazepines in rodents. Administration of beta-CCE (2.5 mg/kg) to chair-adapted, male rhesus monkeys (7-9 kg) elicited a behavioral syndrome characterized by extreme agitation, head and body turning, distress vocalization and other behaviors which might be termed 'anxious'. Concomitant increases in plasma cortisol, epinephrine, norepinephrine, heart rate, and mean arterial blood pressure were observed. Pretreatment of animals with the benzodiazepine receptor antagonist Ro 15-1788 (5 mg/kg) antagonized the behavioral, endocrine, and somatic changes produced by beta-CCE, but did not elicit any significant changes in these parameters when administered alone. Thus, administration of beta-CCE to primates may be a reliable and reproducible model of human anxiety and, as much, may prove valuable for studying the postulated role of 'stress' or 'anxiety' in a variety of human disorders. In toto, these results strongly suggest that benzodiazepine receptors not only mediate the pharmacologic actions of benzodiazepines, but may also subserve both the affective and physiologic expression of anxiety.

Animals↗
PubMed1984

Immunological aspects of pathological pregnancy (infertility immunology).

As, theoretically, any of the many mechanisms that appear to operate in normal pregnancy to maintain maternofetal immunologic balance could be altered in pathologic pregnancy, a detailed study of the known immunological aspects of pathological pregnancy is given. After looking into the parental genetic heterozygosity and fertility, a good explanation of the antifetal immunoresponse by the pregnant mother including the antibody formation is shown. The placental transport versus trapping of immunoglobulins is described in detail and it is also shown that the placenta is a source of a number of agents that inhibit cell-mediated immunity (HCG, HPL and steroids). These substances may affect a local inhibition of maternal cell-mediated immunity in the vicinity of the trophoblast. The placenta serves as an effective barrier for transfer of immunocompetent maternal lymphocytes to the fetus. The paramount role of the trophoblast as a barrier, while itself escaping immunologic destruction, calls for further studies.

Antibody Formation↗
PubMed1983

Antagonism of the anxiolytic action of diazepam and chlordiazepoxide by the novel imidazopyridines, EMD 39593 and EMD 41717.

The imidazopyridines EMD 35993 and EMD 41717 antagonized the anticonflict actions of diazepam and chlordiazepoxide in rodent models which are predictive for anxiolytic action in man. In contrast to other described benzodiazepine antagonists, these compounds did not antagonize either the anticonvulsant or muscle relaxant properties of either benzodiazepine. Both EMD 39593 and EMD 41717 competitively inhibit the binding of [3H]diazepam to brain membranes, but do not exhibit regional differences in potency. These observations suggest that both EMD 39593 and EMD 41717 display some selectivity in antagonizing the anxiolytic properties of benzodiazepines, and as such may be useful tools in identifying neuronal substrates of anxiety.

Animals↗
PubMed1983

Enzyme-linked immunosorbent assays for sperm antibody detection and antigenic analysis.

Enzyme-linked immunosorbent assays for estimation of antibodies against human sperm and for determination of antigenic reactivity of spermatozoal proteins were established. Sperm immobilized on PHA-coated microtiter plates or solubilized spermatozoal antigens adsorbed on poly(L)-lysine coated microtiter plates were used as the solid phase. Assay of sperm antibodies was performed by incubation of the test samples with the solid phase followed by incubation with anti-Ig conjugated to peroxidase. Sigmoidal antibody dilution curves were obtained with rabbit and mouse anti-sperm sera. The ELISA was effectively used to screen production of anti-sperm antibodies by mouse myeloma x splenocyte hybridomas. The sensitivity of this ELISA for sperm antibodies was more than 1000-fold greater than the classical tray sperm immobilization test, and was comparable in sensitivity to a radioimmunoassay using 125I-labeled protein A as the tracer. Sperm immobilized on PHA-coated plates exhibited significantly greater antigenic reactivity in both the ELISA and RIA compared with methanol fixed sperm. In a competitive inhibition ELISA, linear Logit-log dose-response curves were obtained with detergent solubilized spermatozoal antigens. The assay was used to monitor the purification of the solubilized spermatozoal antigens by chromatofocussing; a more than 60-fold increase of antigenic potency of purified sperm antigen compared with unfractionated sperm extract was evident in the competitive ELISA.

Animals↗
PubMed1983

Two-dimensional electrophoresis of peptides from human-CHO cell hybrids containing human chromosome 21.

Peptide expression influenced by human chromosome 21 was examined by comparing two-dimensional electrophoretograms of a human-hamster hybrid cell containing human chromosome 21 with its parent hamster cell and a revertant of the hybrid which had segregated the chromosome 21 genes for SOD-1, GARS, and a cytotoxic cell-surface antigen. Certain peptides were found in the hybrid but not in the hamster cell. Some, but not all, of these peptides segregated with markers for chromosome 21. Hamster peptides were also found which apparently were suppressed in the hybrid. Finally, one peptide was identified which was unique to the revertant cell. These findings may be of potential relevance to Down's syndrome.

Animals↗
PubMed1983

Cancer chemotherapy via ambulatory infusion pump.

One hundred twenty-four patients with metastatic malignancy were treated with four different single agent infusion programs by constant intravenous infusion for 30 or more days. Drug was administered via a tunneled subclavian line by a battery-driven peristaltic pump (Cormed model ML6) on an ambulatory basis. This schedule allowed for increased cumulative drug dose for 5-Fu, decreased tolerated dose for vinblastine, and comparable doses for adriamycin and mitomycin-C relative to that delivered with the standard intermittent bolus schedule. Therapeutic effects were observed for three of four drugs studied: 5-Fu 13/31 colorectal cancer; adriamycin 7/29; and vinblastine 4/12, including 2/4 melanoma. Adverse effects were significantly reduced, particularly with regard to gastrointestinal toxicity, but also in adriamycin-associated cardiac effects and hair loss. Phase III comparative trials of intermittent bolus therapy with protracted infusion therapy are in progress for 5-Fu in advanced colorectal cancer and for adriamycin in specific tumors. Ambulatory pump infusion (API) chemotherapy is technically feasible and has improved patient tolerance to chemotherapy while demonstrating similar, if not comparable, antitumor effects.

Ambulatory Care↗
PubMed1983

Constant infusion schedule for adriamycin: a phase I-II clinical trial of a 30-day schedule by ambulatory pump delivery system.

Eighteen patients received a continuous intravenous infusion of adriamycin for 14-60 days in a phase I study in which the dose rates were escalated from 2 mg/sq m/day to 5 mg/sq m/day to establish the optimal dose to be delivered over a 30-day period. The drug was delivered via a tunneled subclavian catheter by a portable infusion pump (Cormed model ML-6) primed to provide a volume of diluted drug of 10 cc/day. Leukopenia and stomatitis were observed at 4 mg/sq m/day doses or greater in 50% of courses. At doses less than 4 mg/sq m/day, only 3/17 courses (18%) were associated with stomatitis. Partial alopecia developed in all patients, but less than 50% of scalp hair was affected. The cumulative dose of continuous infusion adriamycin at 30 days is comparable to the dose delivered by standard bolus intermittent schedules (60-90 mg/sq m g 21 days), but the adverse drug effects are eliminated or substantially reduced. Cardiac toxicity was assessed in selected patients treated to 450 mg/sq m or greater by cardiac biopsy and/or gated pool studies. No histopathologic lesions were noted in 3 patients receiving 450 mg/sq m or greater. The recommended daily dose rate of adriamycin in this protracted infusion regimen is 3 mg/sq m/day. The phase II study of this schedule and dose rate in 38 additional patients (a total of 52 evaluable patients) demonstrated objective responses in 1/9 soft tissue sarcoma, 1/3 mesothelioma, 1/3 hepatoma, and 2/13 breast cancer. Phase III studies of the protracted continuous infusion schedule for adriamycin are indicated in that clinical activity is demonstrated at a substantial reduction in toxicity. Pharmacologic studies expanding the existing data base are also necessary.

Adult↗
PubMed1983

Phase I study of continuous venous infusion of floxuridine (5-FUDR) chemotherapy.

Floxuridine (5-FUDR) was administered by continuous venous infusion using an ambulatory portable pump in a phase I study designed to establish the optimal (maximal) daily dose rate to deliver a minimum of 14 days of drug therapy. The major determinant of toxicity was dose rate rather than cumulative dose. Patients receiving greater than 0.15 mg/kg/day developed dose-limiting diarrhea at 7-14 days (median, 10), while patients receiving 0.1-0.125 mg/kg/day were treated for 18-78 days without adverse effects. The recommended daily dose rate for continuous-infusion schedules of 14 days is 0.15 mg/kg/day.

Drug Evaluation↗
PubMed1982

Blockade of 3-carbomethoxy-beta-carboline induced seizures by diazepam and the benzodiazepine antagonists, Ro 15-1788 and CGS 8216.

The benzodiazepine antagonists Ro 15-1788 and CGS 8216 blocked the clonic and tonic convulsions elicited by 3-carbomethoxy-beta-carboline (beta-CCM). The PD50 values for Ro 15-1788, CGS 8216, and diazepam were: 2.0, 0.6, and 2.0 mg/kg, respectively. Neither Ro 15-1788 nor CGS 8216 potentiated the effect of a threshold convulsant dose of beta-CCM. Moreover, these benzodiazepine antagonists neither attenuated nor potentiated the tremorigenic actions of another beta-carboline, harmaline. Diazepam, however, considerably reduced the tremorigenic actions of this drug.

Animals↗
PubMed1982

Inhibition of [3H]diazepam and [3H]3-carboethoxy-beta-carboline binding by irazepine: evidence for multiple "domains" of the benzodiazepine receptor.

The binding of [3H]diazepam and [3H]3-carboethoxy-beta-carboline was examined in rat brain synaptosomal membranes treated with irazepine, an alkylating benzodiazepine. Under incubation conditions that resulted in a 25-33% reduction in the Bmax of [3H]diazepam binding, only modest (less than 8.5%) reductions in the Bmax of [3H]3-carboethoxy-beta-carboline were observed. The differential effects of irazepine on the binding of these two compounds may be explained by the presence of multiple areas or "domains" on the benzodiazepine receptor.

Animals↗
PubMed1982

Effect of anti-HCG sera on purified syncytiotrophoblast from full-term human placenta.

Heterologous anti-HCG and anti-beta-HCG sera failed to effect complement-dependent lysis of purified 51chromium-labeled syncytiotrophoblast in vitro. The progesterone synthetic activity of syncytiotrophoblast was also preserved in the presence of the anti-HCG sera. Binding of the anti-HCG antibodies to the syncytiotrophoblast was demonstrated in an immunofluorescence test. The potential of the anti-HCG sera to participate in complement dependent lysis of other HCG-bearing cell types was revealed using BeWo cells as the targets; 53%-68% of the latter were killed by exposure to anti-HCG sera and complement. The possible mechanism(s) whereby syncytiotrophoblast resists damage by the anti-HCG sera are considered.

Antibodies↗
PubMed1982

Lysis of placental syncytiotrophoblast by allogenic leukocytes in vitro: effects of neuraminidase and chorionic gonadotropin.

51chromium-labeled syncytiotrophoblasts purified from human placentae were lysed by allogenic leukocytes in vitro. The extent of syncytiotrophoblast lysis was dependent upon the dose of the leukocytes, occurred after a lag period of 42 h, and was inhibited by excess of unlabeled syncytiotrophoblasts. Autologous leukocytes failed to lyse syncytiotrophoblasts. Neuraminidase pretreatment of the syncytiotrophoblasts significantly enhanced their lysis by leukocytes. HCG failed to influence the extent of lysis of untreated syncytiotrophoblasts but significantly reduced the lysis of neuraminidase-treated targets. The significance of these observations in relation to the "immunologic privilege" of the trophoblast in vivo is discussed. (Am J Reprod Immunol. 1982; 204-207.)

Chorionic Gonadotropin↗
PubMed1982

Unmasking by neuraminidase of specific chorionic gonadotrophin binding activity of human placental syncytiotrophoblast.

Purified human placental syncytiotrophoblast consistently failed to bind specifically to 125I-labelled hCG. Treatment of the syncytiotrophoblast with neuraminidase resulted in the ability to bind 125I-labelled hCG that was displaceable by excess of unlabelled hCG. Neuraminidase treatment removed 73.8% of the total neuraminic acid of syncytiotrophoblast. The specific binding of 125I-labelled hCG increased linearly with increasing amount of neuraminidase-treated syncytiotrophoblast, was saturable and had a Ka = 1.6 x 10(7) M-1. Excess of GH, prolactin, placental lactogen or insulin did not inhibit the binding, whereas LH did so completely and FSH partly.

Chorionic Gonadotropin↗