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Biomedical subjects

R Paul

Publications and source records attributed to R Paul.

At least 235 records · Page 13Linked to original sources

Effect of prostaglandin inhibitor and oestrogen on climacteric symptoms and serum free fatty acids.

Oestradiol and naproxen were compared in a double-blind, cross-over study of 20 women suffering from climacteric symptoms. Subjective symptoms were assessed before and after treatment. In addition, serum levels of prostaglandin precursors and of certain other free fatty acids were determined. Oestradiol was found to have a slightly more pronounced effect than naproxen on symptoms and on fatty acid levels. Nevertheless, a large number of the patients reported significant alleviation of their symptoms on naproxen. Some of the climacteric symptoms may thus be mediated by prostaglandins. In most patients the fatty acid levels decreased after treatment with both substances, but there were two exceptions. It is suggested that there may be two separate types of metabolic response to these drugs.

Climacteric↗

Imaging of canine cancers with 18F-2-fluoro-2-deoxy-D-glucose (FDG) suggests further applications for cancer imaging in man.

18F-2-fluoro-2-deoxy-D-glucose (FDG) is a novel radiopharmaceutical that has gained much interest as a cancer-seeking agent. In this paper two cases of histologically verified canine cancer, an osteosarcoma and a mammary carcinoma, are presented. After an intravenous bolus injection of FDG, accumulation of radioactivity over the neoplastic lesion was followed with a computer-guided specially collimated gamma camera. Ratios of radioactivity between tumour and control areas at 30 min were 2.8 and 2.2 for the osteosarcoma and the mammary carcinoma, respectively. In the osteosarcoma, which was imaged for 3 h, this ratio remained essentially stable. It is reasonable to assume that FDG will be suitable for cancer imaging in man.

Animals↗

Steroid receptors and response of ovarian cancer to cytostatic drugs in vitro.

Samples of 21 ovarian cancers were assayed for oestrogen receptor (ER) and progesterone receptor (PR) content, and the response in vitro to treatment with a combination of doxorubicin, diacetyldian hydrogalactitol and cisplatin was determined. The number of living cells after drug exposure was estimated by a new ATP-bioluminescence method and the tumours were considered responsive if cell survival was less than or equal to 50% of the value in a corresponding control culture. Of the 16 tumours that responded to drug exposure, nine were ER-positive, seven ER-negative and eight were PR-positive, eight PR-negative. The mean percentages of surviving cells ranged from 22.2% in PR-negative tumours to 30.9% in PR-positive tumours. There were no differences in the response rates or in the degree of response to the cytostatics in terms of either receptor status or tumour histology. The results were also compared with those obtained in the same tumour samples exposed to hormones, tamoxifen and medroxyprogesterone acetate. The average response of all tumours was better to cytostatics than to hormones (P less than 0.05); this was particularly marked in the ER-negative tumours. Cytostatics may be preferable to hormones as the primary drug treatment for ovarian cancers but steroid-receptor determinations appear not to help in formulating the optimum drug treatment.

Adult↗

A ganglioside antigen on the rat pancreatic B cell surface identified by monoclonal antibody R2D6.

In an attempt to identify B cell specific antigens, we have generated a mouse monoclonal antibody, R2D6, which is directed against plasma membranes of rat pancreatic B cells but against no other pancreatic cells. R2D6 crossreacted with mouse and guinea pig B cells, but not with human or dog. The B cell specificity of R2D6 was utilized in fluorescence-activated cell sorting to prepare highly enriched separate populations of viable pancreatic islet B cells and A cells. R2D6 also recognized adrenal chromaffin cells, secretory cells in the anterior pituitary, and the myenteric plexus of the gastrointestinal tract. Trypsin, chymotrypsin, papain, ficin, and pronase had no effect on R2D6-binding to dissociated rat islet cells. However, neuraminidase treatment of intact cells reduced R2D6-binding by 75%. The antigen recognized by R2D6, Ag(R2D6), could be quantitatively extracted from rat islets by dichloromethane/methanol (2:1) and, after drying, was soluble in methanol alone as well as in phosphate-buffered saline. When the dichloromethane/methanol extract (DME) was bound to polyvinylchloride microtiter plates, antigenic activity was retained and remained insensitive to pronase. In this solvent-extracted form, antigenic activity was totally destroyed by neuraminidase. Therefore, sialic acid is either an integral part of, or is related sterically to the binding site (epitope) for R2D6. In high performance thin-layer chromatographs of the DME, developed in 60:40:9 chloroform/methanol/2.5 N ammonia, Ag(R2D6) migrated with a relative mobility (Rf) of 0.54 +/- 0.07 (n = 3), which was a position nearly coincident with the purified brain ganglioside, GD1a. The antigen bound to DEAE-Sephacel, was not inactivated by mild treatment with base (which hydrolyzes phospholipids) and eluted in ganglioside fractions upon C18 Sep-Pak and upon silicic acid chromatography. Hence, the solubility characteristics, enzyme sensitivities, and behavior of Ag(R2D6) in four chromatography systems are consistent with its identification as a ganglioside.

Animals↗

Copper and zinc in pre-eclampsia.

Twenty uncomplicated pregnancies, 10 parturients with mild and 10 parturients with severe pre-eclampsia, all with uncomplicated deliveries, were studied. Maternal and umbilical cord serum were checked for copper and zinc by the proton-induced X-ray emission (PIXE) method; maternal serum protein, hemoglobin and estriol were determined as well. Maternal zinc and copper values were lower, whereas the umbilical cord serum copper level was higher in the group with severe pre-eclampsia as compared with the controls. Maternal zinc was also lower in mild pre-eclampsia than in the controls. The possible causes of these changes are discussed in view of the hormonal, metabolic and enzymatic changes in pre-eclampsia.

Copper↗

Pregnancy and delivery in Ehlers-Danlos syndrome. Role of copper and zinc.

Two pregnancies of a patient with the mitis type of the Ehlers-Danlos syndrome (EDS) were followed up. The first pregnancy ended at 26 weeks. The second one proceeded to term, but the infant had a low birth weight and the placenta showed dysmaturity. In view of these pregnancies, the authors consider the vaginal route as an alternative to caesarean section for delivery of patients with the mitis type of EDS. In connection with both deliveries, serum zinc and copper levels were determined with the method of particle-induced X-ray emission (PIXE); the concentrations of both trace elements were low. The ceruloplasmin levels, on the other hand, were within the normal range. The relevance of these findings is discussed.

Adult↗

Theory of long-range coherence in biological systems. I. The anomalous behaviour of human erythrocytes.

In this paper, an explicit expression of the interaction potential has been obtained, based on the Fröhlich model of long-range coherence in biological cells. These theoretical expressions are used to correlate with the experimental data obtained from the light scattering and the Brownian motion for the red blood cells (human erythrocytes). The necessary conditions are derived for the formation of rouleaux in human erythrocytes in the presence of long range interactions. The kinetics of rouleaux formation in terms of the properties of the diffusion coefficient has been investigated. It is concluded that both types of experimental data can be interpreted satisfactorily by this model.

Cell Movement↗

Variations in skin photosensitization during repeated oral 8-methoxypsoralen medication.

Nine adult volunteer dermatological patients were subjected to five repeated oral exposures of 0.6 mg/kg of 8-methoxypsoralen at near-fasting conditions. In the individual volunteer, the plasma 2-h drug level varied by a factor of 1.3 to 7.1, mean 3.5. The simultaneously measured skin minimal UVA sensitivity varied in the individual subjects by a factor of 1.3 to 3.8, mean 2.2. When all serum level and skin photosensitivity data of the study were tabulated, a negative correlation factor of 0.5758 was obtained, which is statistically highly significant (P less than 0.001). It is concluded that both serum drug levels and degree of skin photosensitivity may fluctuate considerably in a single subject during repeated exposures to a standard oral 8-methoxsalen dose. Attempts should be made to minimize such undesirable variation by improvements of drug formulations and better consideration of the influence of dietary factors on drug absorption.

Administration, Oral↗

Suppression of palmoplantar pustulosis symptoms with oral 8-methoxypsoralen and high-intensity UVA irradiation.

9 patients with long-standing palmoplantar pustulosis were treated with oral 8-methoxypsoralen and high-intensity UVA irradiation (PUVA, 46.2 mW/cm2). 20 irradiations with single doses of up to 14.8 J/cm2 resulted in good or excellent clearing in 4 out of 5 patients, while none of 4 patients receiving 5-6 irradiations of up to 5.2 J/cm2 improved significantly. Comparison with earlier investigations leads to the conclusion that systemic PUVA is more efficient than topical PUVA in the treatment of palmoplantar pustulosis. This may result from different skin distribution of psoralen or from a more rapid decline in the photosensitivity of topically medicated skin during prolonged irradiation as compared to skin sensitized by oral psoralen administration. The use of a high-irradiance UVA source diminishes the influence of this time factor and improves patient compliance.

Administration, Oral↗