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Biomedical subjects

G Braunstein

Publications and source records attributed to G Braunstein.

34 records · Page 2Linked to original sources
PubMed1990

Photodynamic therapy of choriocarcinoma transplanted to the hamster cheek pouch. I. Intraperitoneal photosensitization.

Human choriocarcinoma (JEG-3) cells were transplanted into the cheek pouch of hamsters and treated with photodynamic therapy. Twenty-four hours after intraperitoneal injection of the photosensitizer dihematoporphyrin ether (DHE), 20 tumors were illuminated with 100 J/cm2 of 630-nm light from an argon pumped dye laser. Contralateral tumors served as controls. Dihematoporphyrin ether alone had no effect on tumor growth, while laser light in the absence of DHE resulted in complete regression in 3 tumors (17%), and partial regression in 4 of 18 tumors (22%), possibly due to hyperthermia, P greater than 0.10. Using the combination of DHE plus light (photodynamic therapy) complete tumor regression was noted after a single treatment in 11 of 20 tumors (55%, mean tumor volume 279 mm3) and in 7 of 7 tumors (100%) after a second treatment. Two of 20 tumors were not retreated. Therefore, 18 of 20 tumors (90%) were grossly destroyed by one or two photodynamic treatments. Contralateral control tumors continued to grow to a median volume of 990 mm3 (chi 2 = 26.30, P less than 0.0001). Choriocarcinoma transplanted into the hamster cheek pouch is highly responsive to photodynamic therapy.

Animals↗
PubMed1988

[RU 41740: mode of action on the respiratory system].

Alveolar macrophages are issued from circulating monocytes and stand at the cross-road of all antixenic defences of the lung. They are obtainable for in vitro studies by alveolar lavage, and their properties have been determined during the last few years. Synthesis activity and secretion of inflammation mediators, enzymes, enzyme inhibitors, free radicals and factors of cell co-operation are responsible for the defence of the lungs. The phagocytic activities of alveolar macrophages and their ability to promote cell co-operation make them cells that are capable of antigenic presentation, a fundamental step in the development of immunological defence mechanisms. The effectiveness of RU 41740 in respiratory infections is due to its action on deep lung cells, and in particular alveolar macrophages. This compound has been shown to recruit cells (which is a sign of macrophage activation), to increase enzymatic activities, phagocytosis and release of free radicals and to promote interleukine 1 secretion. These activities have been demonstrated in in vitro studies as well as in animal and human studies.

Adjuvants, Immunologic↗
PubMed1988

Multiple markers for lung cancer diagnosis: validation of models for localized lung cancer.

Sera from 71 patients with localized lung cancer, from 70 normal controls, and from 73 patients with benign lung diseases were analyzed for 10 substances to detect lung cancer: ferritin, lipid-bound sialic acid, total sialic acid, beta 2-microglobulin, lipotropin, the alpha and beta subunits of human chorionic gonadotropin, calcitonin (two assays), parathyroid hormone, and carcinoembryonic antigen (CEA). Individual markers were studied, and optimal combinations of markers were sought for discriminating patients with localized lung cancer from normal controls and from patients with benign lung disease. Both logistic regression and recursive partitioning methods for discrimination were tried. The best rules involved only CEA and ferritin for discriminating patients with lung cancer from normal controls, and CEA and age for discriminating patients with lung cancer from those with benign lung diseases. The performance of these rules was validated on an independent serum panel containing sera from 56 patients with localized lung cancer, 75 normal controls, and 75 patients with benign lung diseases. Three rules designed to achieve 95% specificity against normal controls attained 14%-36% sensitivity for localized lung cancer in the validation panels, whereas three rules designed to achieve 95% specificity against benign lung diseases attained 30%-39% sensitivity. Some aspects of potential clinical applications are discussed.

Age Factors↗
PubMed1988

Evidence that the histamine sensitivity and responsiveness of guinea-pig isolated trachea are modulated by epithelial prostaglandin E2 production.

1. Guinea-pig isolated tracheal preparations in which the epithelium had been removed exhibited a greater contractile response to histamine (intact: 1.91 +/- 0.12 g; n = 6 and rubbed: 2.76 +/- 0.15 g; n = 11; P less than 0.001). The histamine sensitivity (pD2 value) of these preparations was also significantly greater (intact: 4.80 +/- 0.04 and rubbed: 5.40 +/- 0.08; P less than 0.01). 2. Indomethacin suppressed the basal tone of both intact and rubbed preparations but was more effective in the former tissues (intact: -0.70 +/- 0.14 g; n = 22 and rubbed: -0.17 +/- 0.05 g; n = 12; P less than 0.02). 3. Arachidonic acid (AA; 10 microM) suppressed the basal tone of intact tissues but contracted such preparations following indomethacin treatment (1.7 microM; 30 min). However, in rubbed tissues AA (10 microM) induced a contraction which was attenuated following indomethacin treatment. 4. Prostaglandin E2 (PGE2; 0.01 and 0.1 microM) suppressed the basal tone of intact preparations and always evoked contraction of rubbed tissues. Following indomethacin treatment PGE2 (0.01 and 0.1 microM) generally evoked spasm of intact and rubbed tissues while at higher concentrations (1 microM) relaxant effects were observed. 5. Removal of the epithelium did not alter the relaxant effect of PGE2 (pD2 value) on histamine (50 microM)-contracted tissues (intact: 6.86 +/- 0.08 and rubbed: 7.10 +/- 0.3; n = 4; P greater than 0.1). 6. In rubbed preparations treated with indomethacin, PGE2 (0.01 and 0.1 microM) evoked spasm. However, when added to preparations contracted with 5 microM histamine, PGE2 always caused relaxation. 7. The release of immunoreactive PGE2 by rubbed preparations during histamine and/or AA stimulation was significantly less than that produced by intact stimulated tissues. 8. Exogenous PGE2 (0.01-1 microM) decreased the maximal response and sensitivity of rubbed tracheal preparations to histamine. 9. These results suggest that release of an epithelial derived cyclo-oxygenase product, namely PGE2, may regulate basal tone, histamine response and sensitivity of the guinea-pig isolated trachea.

Animals↗
PubMed1988

Local cellular and humoral responses to antigenic and distilled water challenge in subjects with allergic rhinitis.

We studied nasal responses to allergen, saline, and distilled water aerosol in 7 subjects with allergic rhinitis to determine whether they caused a similar release of mediators and influx of inflammatory cells into the nasal lumen. The subjects were challenged first with allergen and then with aerosols of distilled water and of normal saline in random order on separate days. We measured nasal airway resistance (Rn) by posterior rhinomanometry, measured the concentrations of protein, histamine, leukotrienes (LT) B4, C4, and D4, and platelet-activating factor (PAF-acether) and performed total and differential cell counts in nasal lavage fluid obtained before and after each challenge. Allergen challenge provoked a 2-fold or greater increase in nasal airway resistance in all subjects (mean increase = 12.2-fold). This response was associated with significant increases in protein, histamine, LTB4, and sulfidopeptide leukotrienes. 2-lyso-PAF-acether increased significantly, indicating activation of phospholipase A2, but PAF-acether was detected in only one subject. The total cell count increased from 55 +/- 44 x 10(3)/ml to 200 +/- 168 x 10(3)/ml; polymorphonuclear neutrophils increased from 11 +/- 22 x 10(3)/ml to 108 +/- 96 x 10(3)/ml, and eosinophils increased from 1.3 +/- 1.8 x 10(3)/ml to 10.6 +/- 15.3 x 10(3)/ml (p less than 0.05). Saline insufflation provoked insignificant changes in mean Rn, in the levels of protein and all inflammatory mediators, and in the number and types of cells in nasal lavage fluid. Distilled water insufflation also provoked an insignificant increase in mean Rn, but there was a 14-fold increase in one subject.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Cushing's syndrome due to ectopic proopiomelanocortin gene expression by islet cell carcinoma of the pancreas.

Expression of proopiomelanocortin (POMC) was studied in a male patient with Cushing's syndrome and ectopic production of ACTH by a pancreatic carcinoma. Plasma ACTH levels (greater than 200 pg/ml) were elevated, and elevated serum cortisol and urinary free cortisol were partially suppressed to 25% of basal levels by high-dose dexamethasone. Petrosal and jugular vein sampling did not yield a gradient of ACTH. Immunohistochemical staining of tumor tissue removed at pancreatectomy was positive for ACTH and beta endorphin, and negative for corticotropin-releasing factor (CRF). Tumor cells cultured in vitro secreted ACTH and beta-endorphin, which comigrated with their respective radiolabeled standards on gel chromatography. Hydrocortisone suppressed in vitro ACTH secretion and CRF (100 nM) stimulated ACTH by 50% during 72 hours of incubation. Agarose gel electrophoresis of poly-(A) mRNA extracts of tumor tissue followed by hybridization with 32P-cDNA for POMC revealed 2 distinct RNA species. The major RNA species (about 1.0 kb) was smaller than authentic pituitary POMC mRNA (about 1.1 kb); a larger precursor band also was visualized, suggesting either processing or degradation of tumor-POMC mRNA. Cytoplasmic dot blot hybridization of tumor mRNA with POMC cDNA yielded a positive signal with increasing amounts of RNA blotted. Immunohistochemistry and radioimmunoassay (RIA) of ACTH, in vitro regulation of ACTH secretion, and expression of POMC mRNA species by this tumor document expression of the human POMC gene by an islet carcinoma associated with Cushing's syndrome.

Adenoma, Islet Cell↗
PubMed1986

Multiple markers for lung cancer diagnosis: validation of models for advanced lung cancer.

Sera from 171 patients with advanced lung cancer, from 110 normals, and from 123 subjects with benign respiratory diseases were analyzed for 10 substances to detect lung cancer: ferritin, lipid-bound sialic acid, total sialic acid, beta 2-microglobulin, lipotropin, the alpha and beta subunits of human chorionic gonadotropin, calcitonin (two assays), parathyroid hormone, and carcinoembryonic antigen. Individual markers were studied, and optimal combinations of markers were sought for discriminating lung cancer patients from normals and from patients with benign lung disease. Numerous methods for combining the markers were examined, but the methods of logistic regression and recursive partitioning were finally adopted. The best discrimination rules we could find used only carcinoembryonic antigen (CEA) and total sialic acid (TSA). The performance of these rules was validated on an independent serum panel containing sera from 68 patients with advanced lung cancer, from 40 normals, and from 52 patients with benign respiratory disease. The combination rules based on TSA and CEA performed better than a rule based on CEA alone. Logistic discrimination rules with TSA and CEA that were designed to have 95% specificity achieved 54% sensitivity for discriminating advanced lung cancer from normal controls and 52% sensitivity for discriminating advanced lung cancer from controls with benign disease. Some aspects of clinical applicability are discussed, including planned studies for localized lung cancer and the requirement for further testing in specific clinical settings.

Aged↗
PubMed1984

Insulin receptors and placental proteins in normal and gestational-diabetic pregnancies.

We studied 125I-insulin binding to monocytes and plasma levels of two trophoblastic proteins from 38 pregnant patients with varying degrees of carbohydrate intolerance, including 10 pregnant controls (PC), 17 Class A diabetics (A), 6 Class B diabetics - prior to insulin therapy (B-noRx) and 5 different Class B diabetics studied 1-6 weeks following initiation of insulin therapy (B-Rx). All studies were performed in the second half of pregnancy. In comparison to six age- and weight-matched nonpregnant controls (NPC), insulin binding to monocytes was somewhat higher in both PC and A. B.noRx patients had significantly lower tracer binding than did PC (0.71 +/- 0.3 vs 2.6 +/- 0.6%/10(7) cells, p less than 0.01). Insulin treatment of Class B patients restored insulin tracer binding levels to above normal. Levels of human placental lactogen (HPL) were significantly elevated in B-noRx patients compared to PC and A and were lowered to levels comparable to normal in insulin-treated B patients. A highly significant inverse relationship existed between HPL levels and the tracer binding of insulin for all patients studied (r = -0.52, p less than 0.005). Elevations of pregnancy-specific beta 1 glycoprotein were observed in patients with mild carbohydrate intolerance (A) as well as Bno-Rx, but were comparable to normal in those B-patients receiving insulin therapy. There were no significant differences of insulin binding or receptor number in the patient groups in the postpartum state. This further supports the hypothesis that placental factors may be responsible for the insulin binding defects seen in gestational diabetes.

Female↗
PubMed1981

The significance of 1-131 scan dose in patients with thyroid cancer: determination of ablation: concise communication.

Twenty-four patients with differentiated thyroid cancer were studied with diagnostic I-131 neck chest scans after having undergone bilateral subtotal thyroidectomy and initial I-131 therapy with either 30- or 100-mCi doses. With an endogenous stimulation protocol, follow-up studies were performed with neck and chest scans using 2 and 10 mCi I-131. A 400% increase in sensitivity was found with a 10-mCi dose relative to a 2-mCi dose. Comparison with therapeutic doses of 30 and 100 mCi resulted in further increases in the detection of residual iodine-avid tissue. We conclude that a 2-mCi or lower dose of I-131 is inadequate in evaluating residual iodine-avid tissue visually in patients with thyroid cancer. The study does not answer the critical question of whether it is necessary to treat a patient presenting a negative 2-mCi but a positive 10-mCi scan. It may be appropriate to define ablation visually as well as clinically, with further studies directed toward determining a treatment rationale in this patient population.

Adenocarcinoma↗
PubMed1975

A simple radioimmunoassay for unconjugated estriol in pregnancy plasma.

A simple and specific radioimmunoassay (RIA) for the measurement of plasma or serum unconjugated estriol (E3) in pregnancy is described for general laboratory use. Two different antibodies utilized had low cross-reaction to estrone (E1) and estradiol-17 beta (E2). With either of these antibody reagents, a method was designed that requires only an extraction step using a specific solvent mixture of ethyl acetate and n-hexane (3:2, v/v), one-hour incubation with working antibody, and separation of bound from free E3 by ammonium sulfate. Standard curves useful in the range of 0 to 2,000 pg. were obtained. This assay, requiring only 0.05 ml. of plasma, can be completed within 4 hours. The sensitivity of this RIA was 10 pg. The intra- and interassay coefficients of variation (CV) were 5.0 and 9.4 per cent, respectively. When E3 determinations by this method are compared with RIA values by a more complicated technique using Celite column chromatography, the results are not significantly different. There was a good correlation between our RIA and a standard urine E3 determination (n = 137, r = 0.82, p less than 0.001). Using our simplified method, the mean plasma E3 during pregnancy were 1.0 +/- 0.6 ng. per milliliter at 10 weeks, 2.3 +/- 0.6 ng. per milliliter at 20 weeks, 6.5 +/- 1.4 ng. per milliliter at 30 weeks, and 16.5 +/- 5.1 ng. per milliliter at term. Since the serum RIA reflects changes in free E3 which has a shorter half-life than conjugated E3, this rapid and simple method is attractive as an approach to monitor fetal-placental function.

Estriol↗
PubMedDate not supplied

Testosterone therapy in women: a review.

Female sexual dysfunction is a complex problem with multiple overlapping etiologies. Androgens play an important role in healthy female sexual function, especially in stimulating sexual interest and in maintaining desire. There are a multitude of reasons why women can have low androgen levels with the most common reasons being age, oophorectomy and the use of oral estrogens. Symptoms of androgen insufficiency include absent or greatly diminished sexual motivation and/or desire, that is, libido, persistent unexplainable fatigue or lack of energy, and a lack of sense of well being. Although there is no androgen preparation that has been specifically approved by the FDA for the treatment of Women's Sexual Interest/Desire Disorder or for the treatment of androgen insufficiency in women, androgen therapy has been used off-label to treat low libido and sexual dysfunction in women for over 40 y. Most clinical trials in postmenopausal women with loss of libido have demonstrated that the addition of testosterone to estrogen significantly improved multiple facets of sexual functioning including libido and sexual desire, arousal, frequency and satisfaction. In controlled clinical trials of up to 2 y duration of testosterone therapy, women receiving androgen therapy tolerated androgen administration well and demonstrated no serious side effects. The results of these trials suggest that testosterone therapy in the low-dose regimens is efficacious for the treatment of Women's Sexual Interest and Desire Disorder in postmenopausal women who are adequately estrogenized. Based on the evidence of current studies, it is reasonable to consider testosterone therapy for a symptomatic androgen-deficient woman with Women's Sexual Interest and Desire Disorder.

Adult↗
PubMedDate not supplied

[Research on inflammatory mediators in asthma: new therapeutic approaches].

During the National Meeting of Clinical Pharmacology (Giens 1998), the working group exchanged information and examined the new therapeutic approaches to inflammation in asthma. The group performed a state of the art review of the current research on mediators of bronchial inflammation to determine new pharmacological targets of therapeutic interest. An update on the development of potential drugs acting on these targets was established. Specificities related to asthma in terms of evaluation and development of anti-inflammatory drugs were discussed. The place of pharmaco-economy in the development of anti-asthmatic drugs was specified.

Anti-Asthmatic Agents↗