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Biomedical subjects

G Thomas

Publications and source records attributed to G Thomas.

At least 703 records · Page 39Linked to original sources
PubMed1987

Controlled-release oral morphine sulfate in the treatment of cancer pain with pharmacokinetic correlation.

The bioavailability and clinical effects of an oral controlled-release morphine sulfate tablet, MS-contin (MSC; Purdue-Frederick, Norwalk, CT) in comparison to an immediate-release (IRMS) preparation were evaluated in normal subjects and cancer patients, respectively. The inherent slow-release character of MSC was confirmed by 2 1/2 X T1/2 absorption rate, one-half Cmax, and twice Tmax relative to IRMS. The T1/2 elimination of the two morphine preparations was similar, demonstrating insignificant risk of MSC accumulation. The difference in the mean number of side effects experienced by the control group per subject was significant (.70 for MSC and 1.26 for IRMS, P = .05) and was consistent with peak plasma morphine attenuation. The cancer patients were initially switched from their previous analgesic to four hourly IRMS and then to MSC at double the dose every eight hours. The majority had their MSC dosing interval lengthened to every 12 hours with a decrease in the total daily morphine requirement. While the mean duration on MSC was 20.5 days, many patients were followed poststudy for an extended period with no appreciable development of tolerance. Overall, MSC analgesia and side effects were perceived by the patients as superior compared with prestudy opioids. The advantage of less frequent dosing may lead to improvement of the quality of life of cancer patients.

Adult↗
PubMed1987

[Value of dapsone in the treatment of digestive manifestations of rheumatoid purpura in adults].

The authors report a case of adult rheumatoid purpura with severe gastrointestinal complications which responded extremely well to treatment with Dapsone. Although this drug has been reported to be effective in treating some forms of allergic vasculitis and the cutaneous manifestations of rheumatic purpura, there have not been any previous reports of its beneficial action in the treatment of the gastrointestinal complications of rheumatoid purpura. The mode of action is not fully understood. Dapsone could constitute a valuable therapeutic option together with steroids, parenteral nutrition and plasmapheresis in the treatment of the gastrointestinal complications of rheumatoid purpura.

Aged↗
PubMed1987

[Ploidy in colorectal cancer].

For several authors, DNA tumoral cell content represents an important prognostic factor in colorectal cancer. Samples obtained from 65 human colorectal cancers operated on between 1983 and 1986 were studied. Of 52 cases studied by flow cytometry 60 p. 100 were aneuploid tumors. The proliferative index was calculated in slightly over 50 p. 100 of the cases by DNA histogram analysis. During the same period 30 tumoral karyotypes were established by cytogenetic analysis. In 17 cases a comparison was possible between flow cytometry and cytogenetic results. In all cases a significant correlation was seen between the DNA histogram modal value and the mean number of chromosomes counted by cytogenic analysis. In this study, there was no statistical correlation between flow cytometry results and Dukes classification. Because of the short follow-up in our series, no prognostic value may be attributed to the DNA index.

Adult↗
PubMed1986

The influence of glutathione and other thiols on human platelet aggregation.

The platelet membrane contains sulfhydryl groups which are essential for normal platelet function. Reduced glutathione (GSH) and other thiols such as cysteine and 6-mercaptopurine were found to inhibit human platelet aggregation induced by adenosine diphosphate (ADP), collagen and arachidonic acid. The inhibition of ADP-induced aggregation by GSH (IC50 = 0.61 +/- 0.05 mM) was greater than that by cysteine (IC50 = 13 +/- 1 mM) or 6-mercaptopurine (IC50 = 5.4 +/- 0.2 mM). Two other thiols, dithiothreitol and beta-mercaptoethanol were found to cause platelet aggregation instead of inhibition. The interaction of GSH with the ADP receptor was noncompetitive in nature.

Adenosine Diphosphate↗
PubMed1986

Endothelium dependent vascular relaxation by arginine containing polypeptides.

The vascular endothelium appears obligatory for the expression of the vasodilating property of most polypeptides. A number of polypeptides were studied on the rat aortic ring preparation which was pre-contracted with phenylephrine and only basic polypeptides containing one or more arginine residues elicited relaxation which was endothelium dependent. These peptides included melittin and poly-L-Arg. The basic polypeptide poly-L-Lys also elicited endothelium dependent relaxation, but to a lesser extent than arginine containing polypeptides. Two basic polypeptides, apamin and mastoparan do not promote endothelium dependent relaxation. The former contains arginine between disulfide bonds and in the latter arginine is absent. Basic amino acids and dipeptides which contain arginine, and also polyamines did not elicit relaxation even at high concentrations (10(-3) M). The relaxation elicited by melittin, poly-L-Arg and poly-L-Lys was inhibited by ETYA, NDGA, p-bromophenacyl bromide and not by indomethacin. Methylene blue, an inhibitor of soluble guanylate cyclase, also abolished the relaxation. We suggest that arginine containing peptides may relax vascular smooth muscle by acting directly on the vascular smooth muscle (eg: atriopeptins) and/or or by eliciting release of a relaxing factor(s) from the endothelium.

Animals↗
PubMed1986

Induction of vascular relaxation by hydroperoxides.

Hydrogen peroxide, tert-butyl hydroperoxide, cumene hydroperoxide, and 3-chloroperoxybenzoic acid (CPB) and 15-HPETE relaxed, in a concentration dependent manner rat aortic rings contracted with PGF2 alpha (1 X 10(-5)). Relaxation is not inhibited by either indomethacin (2 X 10(-5) M), a cyclo-oxygenase inhibitor or eicosatetraynoic acid (1 X 10(-5) M), a dual cyclo-oxygenase and lipoxygenase inhibitor. Rings with intact endothelium relaxed to a greater degree on exposure to CPB and 15-HPETE. Methylene blue, a soluble guanylate cyclase inhibitor (1 X 10(-5) M) blocked the relaxation elicited by the five peroxides, whereas both superoxide dismutase (scavenger of superoxide anion) and mannitol (scavenger of hydroxyl radical) have no effect. We conclude that relaxation of vascular smooth muscle is a general property of peroxides and that the endothelium may in some instances facilitate this effect.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1986

Albumin does not inhibit endothelium-dependent relaxation.

Bovine serum albumin which is fatty acid free, enhances the endothelium-dependent vasodilating effect of various agonists like acetylcholine, carbachol, ATP, ADP and ionophore on rat aortic rings. The maximum effect was observed in buffers containing 5% albumin. Albumin has no effect on rings devoid of endothelium. On the other hand, both plasma and serum completely abolished the vasodilating effect of these agents.

Acetylcholine↗
PubMed1986

Expression and cell type--specific processing of human preproenkephalin with a vaccinia recombinant.

The posttranslational maturation of a complex precursor polyprotein, human proenkephalin, was assessed by infection of a wide spectrum of cell types with a recombinant vaccinia virus that expressed human proenkephalin. The infected cells rapidly produced both cellular and secreted Met-enkephalin immunoreactivity. Although each cell line could secrete intact proenkephalin, only a mouse pituitary line was capable of processing proenkephalin to mature enkephalin peptides. The quantity of intact proenkephalin secreted from BSC-40 cells (derived from African Green monkey kidney) was sufficient to establish the value of vaccinia virus as a mammalian cell expression vector.

Animals↗
PubMed1986

Activation of ribosomal protein S6 phosphorylation during meiotic maturation of Xenopus laevis oocytes: in vitro ordered appearance of S6 phosphopeptides.

During meiotic maturation of Xenopus laevis stage 6 oocytes into unfertilized eggs, 40S ribosomal protein S6 undergoes multiple phosphorylation. Extracts prepared from unfertilized eggs are up to 10-fold more efficient in phosphorylating S6 than those prepared from immature oocytes. When analyzed by DEAE chromatography the S6 kinase activity elutes as a single peak. If extracts from unfertilized eggs are prepared in the absence of beta-glycerol phosphate, a putative phosphatase inhibitor, there is a severe reduction in recovered S6 kinase activity. Under optimal conditions, incubation of unfertilized egg extracts with 40S ribosomes in the presence of ATP leads to the average incorporation of 3.5 mol of phosphate/mol of S6. Prior incubation of these extracts with the cAMP-dependent protein kinase inhibitor does not inhibit S6 phosphorylation indicating that another kinase is responsible. Analysis of the in vitro phosphorylated peptides demonstrates that they migrate to the equivalent position of those observed previously in vivo and in vitro. More strikingly, if each of the increasingly phosphorylated derivatives of S6 is analyzed independently, it is found that the phosphopeptides appear in a specific order.

Animals↗
PubMed1986

Behavior of intracellular glutathione during platelet thromboxane synthesis in diabetes.

The time-dependent relationship between the levels of the reduced form of glutathione (GSH) and thromboxane A2 (TXA2) synthesis, as measured by the accumulation of TXB2, in platelets from human diabetic and control subjects was investigated during aggregation. In platelets from control subjects, the GSH level decreased to 21% of the initial level within 30 sec in response to arachidonic acid (1.65 mM) and rapidly recovered to 91% by 1 min. In platelets from diabetic subjects, the GSH level decreased to 3% of the initial level within 30 sec and recovered to only 41% by 1 min. During collagen (20 ug/ml) aggregation, platelets from control subjects had a 15 sec lag phase which was followed by a decrease in the GSH level to 21% of the initial level within 1 min and a recovery to 74% by 2 min. Platelets from diabetic subjects in response to collagen showed no lag phase and decreased to 10% of the initial level within 1 min which was followed by a recovery to 34% by 2 min. In all aggregations, the initial GSH level was significantly (p less than .001) lower in platelets from diabetic subjects and remained significantly (p less than .01) lower than GSH in platelets from control subjects throughout the aggregation. The amount of TXB2 formed by platelets from control subjects reached a maximum in response to arachidonic acid and collagen by 1 min and 2 min, respectively, whereas, the TXB2 continued to increase up to 4 min when platelets from diabetic subjects were aggregated. These data indicate that TXA2 synthesis occurs during the decrease in GSH and ceases when the GSH level recovers. The continued synthesis of TXA2 by platelets from diabetic subjects coincides with the gradual recovery of the GSH level.

Arachidonic Acids↗
PubMed1986

Translational control of mRNA expression during the early mitogenic response in Swiss mouse 3T3 cells: identification of specific proteins.

Addition of serum or epidermal growth factor to quiescent Swiss mouse 3T3 cells in culture leads to a number of specific changes in the pattern of protein synthesis. Earlier experiments with actinomycin D suggested that the altered expression of these proteins was controlled at either the pretranslational or translational level. Here we have identified and further characterized the regulation of mRNA expression for ten of these proteins, including protein synthesis elongation factor eEF-1 alpha, poly A binding protein, vimentin, the multiple forms of the actin protein family, and alpha- and beta-tubulin. Using an in vitro translation system, we determined the change in the level of mRNA encoding for each of these proteins after serum stimulation. The results showed that the amount of mRNA coding for eEF-1 alpha, poly A binding protein, vimentin, and alpha- and beta-tubulin remains unchanged during this time, whereas that of the actin family increases. Thus, with the exception of the actin family, the results argue that the expression of all the proteins identified is regulated at the translational level. The importance of this latter group of proteins in cell growth and the abundance of their cognate mRNAs should prove them useful tools in elucidating the mechanisms involved in the activation of translationally repressed mRNA during the mitogenic response.

Actins↗
PubMed1986

Early inflammatory response to carrageenan in the pleural cavity and paw of rats with altered body temperature.

Polymorphonuclear leucocyte (PMNL) migration and oedema induced by carrageenan in the pleural cavity and paw, respectively, of rats made hyper- or hypothermic by physical and chemical means have been investigated. In rats placed in a warm environment to produce a rise in body temperature, carrageenan caused a moderate but significant increase in PMNL migration compared with the control animals. Opposite effects were obtained with hypothermic animals kept in a cold environment. While hyperthermia produced by amphetamine did not alter the PMNL migration, chlorpromazine-induced hypothermia caused a fall in the number of these cells present in the pleural cavity following carrageenan. Both hyper- and hypothermias, whether induced by physical or chemical means, inhibited the carrageenan paw oedema. The observed changes in the PMNL numbers in the pleural cavity did not reflect their numbers in the peripheral circulation. Results indicate that while a rise or a fall in body temperature may have opposite effects on PMNL migration, in carrageenan inflammation both conditions inhibit oedema formation.

Amphetamine↗
PubMed1986

Biological effects of estradiol-17 beta in postmenopausal women: oral versus percutaneous administration.

To determine whether the route of administration or the type of estrogen used in estrogen replacement therapy (ERT) is more important in avoiding effects on hepatic function, 24 postmenopausal women were studied before and at the end of 2 months of oral or percutaneous administration of the same estrogen, estradiol-17 beta (E2). The treatments studied were oral micronized E2, 2 mg/day (9 women); oral E2 valerate, 2 mg/day (5 women), and percutaneous E2, 3 mg/day (10 women). Specific plasma biological and biochemical markers of estrogenic action were evaluated, namely, E2, estrone (E1), LH, FSH, sex steroid binding protein (SBP), renin substrate, antithrombin activity, and lipoproteins (high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein triglycerides). Both oral and percutaneous administration of E2 increased plasma E2 levels up to midfollicular values and decreased LH and FSH levels into the same range. Oral administration of E2 led to substantial increases in plasma E1, SBP, renin substrate, and VLDL levels, whereas AT decreased significantly. Percutaneous administration of E2 led to a physiological plasma E1/E2 ratio and did not induce any change in hepatic proteins. These data suggest that the route of administration of E2 determines the biochemical response to ERT in postmenopausal women. SBP is the most sensitive marker of the liver action of estrogen, and triglycerides also are simple and useful markers for this effect. Percutaneous E2 therapy is an effective method of ERT, and has no measurable effects on hepatic markers of estrogen action.

Administration, Oral↗
PubMed1986

[Emphysematous pyelonephritis. Review of the literature apropos of 4 new cases].

Based on four new cases of emphysematous pyelonephritis, the authors review a total or 59 interpretable cases of this rare disease reported in the literature. The general features of this condition are as follows: diabetic women are most frequently affected, the clinical context is generally very serious, the diagnosis is based on X-ray findings, radiating or crescent-shaped radiolucent gas images are observed with a non-functioning kidney on intravenous pyelography. CT scan was performed in two cases and confirmed the presence of air in the renal parenchyma and provided a better evaluation of the extension into the perirenal space. The only effective treatment is nephrectomy which has been able to improve the prognosis of this very serious disease, especially as the characteristic necrosis observed on histology leaves no hope of functional recovery.

Adult↗