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Biomedical subjects

M Thompson

Publications and source records attributed to M Thompson.

At least 271 records · Page 15Linked to original sources
PubMed1989

A comparison of three nucleoside analogs with anti-retroviral activity on immune and hematopoietic functions in mice: in vitro toxicity to precursor cells and microstromal environment.

A number of 2'3'-dideoxynucleosides have been reported to markedly inhibit the in vitro growth of HIV, the causative agent of acquired immunodeficiency syndrome (AIDS). Clinical trials have shown that the continued therapeutic use of these nucleoside derivatives can be associated with adverse side effects. Since these side effects include myelotoxicity, as occurs in many patients treated with zidovudine (AZT; 3'-azido'3-deoxythymidine), and AIDS patients already represent an immunologically compromised population, we examined the immunological effects of three nucleoside inhibitors, including zidovudine, 2'3'-dideoxycytidine, and 2'3'-dideoxyadenosine (DDA) in a mouse model. Additional studies were conducted to further determine and characterize the potential toxic effects associated with these drugs on the hematopoietic system. Of the three dideoxynucleosides examined, only DDA altered immune functions following a 30-day subchronic exposure in mice. This was evidenced by a marked suppression of the antibody plaque-forming cell response and a slight alteration in macrophage function. None of the nucleoside derivatives affected bone marrow function following in vivo exposure, although AZT produced a mild macrocytic anemia in vivo and was myelotoxic when added in vitro to bone marrow cell cultures. In vitro studies indicated that AZT was capable of affecting both proliferating stem cells as well as the stromal cell microenvironment, both of which play a role in hematopoiesis. These data indicate that, although the mice may not develop the identical toxicities associated with nucleoside therapy in humans, certain adverse immunological and hematological effects were readily discerned which could have relevance to humans.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Molecular receptors and their potential for artificial transduction.

The thesis is presented that molecular receptor physical chemistry offers an interesting model for the design of biosensors with respect to chemical recognition and transduction. In order to appreciate the desirable features of this system and the inherent difficulties, the structures and binding state energetics of molecular receptors are considered via a direct comparison with enzyme chemistry. Detailed analyses of the candidate species nicotinic and beta-adrenergic receptors are provided to illustrate the complexity of molecular receptor binding properties. A revised ternary-complex model, which combines enzymatic and receptor energetics, is proposed to explain the free-energy changes which drive ligand-binding reactions of coupled systems. Throughout this discussion the relevance of the various arguments to applications in biosensor development is highlighted. Finally, a brief appraisal of attempts to produce devices ready for marriage to molecular receptor material is presented.

Animals↗
PubMed1989

The regulation of immunoglobulin production by B cells in patients with endometriosis.

Nineteen patients with endometriosis and 26 control infertile patients were included in the study. All patients were undergoing laparoscopy as part of their infertility evaluations. The study was conducted on sterile heparinized peripheral blood and peritoneal fluid. The age range was 20 to 37 years for both groups. Mononuclear cells were isolated on Ficoll-hypaque density gradients. T cells, B cells, and T cell subsets were identified by the specific immunobead rosette technique. Mononuclear cells 1 x 10(6) were cultured in Roswell Park Memorial Institute medium and stimulated in the presence or absence of pokeweed mitogen. Immunoglobulin production was measured by an enzyme-linked immunosorbent assay. Increased amounts of immunoglobulin (Ig) IgG and IgA were demonstrated in the peritoneal cell cultures (P less than 0.05), whereas peripheral blood cell cultures showed only an increase in IgG in patients with endometriosis (P less than 0.05). There was an increase in the number of T cells, B cells, and the ratio of CD4/CD8 lymphocytes in endometriosis compared with control patients (P less than 0.005) in both peritoneal fluid and peripheral blood. This study suggests that immunoglobulin production by the "activated" B cells may be regulated by the increased presence of T cells, specifically the helper cells (CD4) in endometriosis.

Adult↗
PubMed1989

A comparison of audiometric test methods for 2-year-old children.

Visual reinforcement audiometry (VRA), visual reinforcement operant conditioning audiometry (VROCA), and play audiometry were compared in terms of conditionability and number of responses obtained prior to habituation on normal 2-year-old (24-27 months) children. Results indicated that a higher percentage of children could be conditioned to VRA than to either VROCA or play audiometry. Results also indicated that for children who could be conditioned, the play audiometry group showed more responses prior to habituation than were obtained from the other two groups.

Age Factors↗
PubMed1989

Prospective, randomized, placebo-controlled trial of norfloxacin for the prophylaxis of recurrent urinary tract infection in women.

Thirty women were randomized in a double-blind, placebo-controlled study to receive either norfloxacin, 200 mg orally daily at bedtime, or placebo for the prevention of recurrent bladder infection. Subjects were followed monthly to monitor compliance and symptoms, for urine culture and periurethral and anal canal swabs to monitor colonization, and for blood specimens for hematologic and biochemical studies to monitor safety. During 1 year of follow-up, 10 of 15 placebo subjects and none of 15 norfloxacin subjects developed infection (P less than 0.001). Adverse effects occurred with equal frequencies in the two groups. For norfloxacin subjects, only 2 (1.6%) of 129 periurethral and 4 (3.1%) of 129 anal canal swabs showed colonization with aerobic gram-negative organisms, while 16 (22%) of 73 periurethral and 47 (64%) of 73 anal canal swabs from placebo subjects showed colonization. Daily therapy with norfloxacin at bedtime is effective in preventing recurrent cystitis. During 1 year of norfloxacin therapy, colonization was infrequent and superinfection with norfloxacin-resistant organisms did not occur.

Adult↗
PubMed1988

Purification and characterization of two forms of cyclic GMP-dependent protein kinase from bovine aorta.

Cyclic GMP-dependent protein kinase in extracts of bovine aortic tissue eluted from DEAE-cellulose ion-exchange resins as two distinct peaks of activity. This elution pattern was preserved when the peaks were combined, precipitated with ammonium sulfate, dialyzed, and rechromatographed. Proteolysis did not appear to account for the two forms of kinase because (i) aging of the extract did not cause interconversion of the two forms, and (ii) both forms retained cGMP sensitivity unlike the proteolytically formed monomer. In addition, treatment with saturating concentrations of cGMP (10 microM) did not cause interconversion of the two forms. The first peak of cGMP-dependent protein kinase eluting from DEAE-cellulose (form 1) had a slightly greater mobility on gradient sodium dodecyl sulfate-polyacrylamide gels than the second peak (form 2). On native, nondenaturing gradient polyacrylamide gels, however, form 2 displayed the greater electrophoretic mobility. Furthermore, form 1, when bound to cAMP-agarose, appeared to exchange more rapidly with cGMP than form 2 when subjected to affinity chromatography. Peptide maps generated from the two forms by protease treatment were very similar, although trypsin produced a unique peptide in form 1 and Streptomyces griseus protease gave rise to unique peptides in forms 1 and 2. Phosphorylation did not appear to account for the physical differences because both enzymes could be phosphorylated to similar extents and dephosphorylation using alkaline phosphatase did not result in the conversion of one form to the other. These results suggest that either differences in primary structure or post-translational modification, other than phosphorylation, are responsible for the presence of two forms of cGMP-dependent protein kinase in aortic tissue.

Animals↗
PubMed1988

Inhibition of the chemotactic peptide-induced elevation of intracellular calcium in differentiated human leukemic (HL-60) cells by the phorbol ester phorbol 12-myristate 13-acetate.

The chemotactic peptide formylmethionylleucylphenylalanine rapidly elevated the intracellular calcium concentration, in a concentration-dependent manner, of human leukemic (HL-60) cells which had been differentiated to polymorphonuclear leukocyte-like cells by pretreatment with dimethyl sulfoxide (1.3%). Preincubation of the cells with phorbol 12-myristate 13-acetate, a protein kinase C-activating phorbol ester, inhibited the formylmethionylleucylphenylalanine-induced rise in intracellular calcium in a time- and concentration-dependent manner. 4 alpha-Phorbol 12,13-didecanoate, which does not activate protein kinase C, was inactive in this capacity. The use of calcium-free medium suggested that the elevation of intracellular calcium by formylmethionylleucylphenylalanine consisted of rapid intracellular release followed by calcium influx. Phorbol 12-myristate 13-acetate (10(-7) M) inhibited both components of the elevation of intracellular calcium, whereas 10(-8) M phorbol 12-myristate 13-acetate inhibited only the calcium influx. The influx of calcium was not prevented by verapamil, which blocks the voltage-dependent calcium channels. These data suggest that, in differentiated HL-60 cells, 12-O-tetradecanoylphorbol-13-acetate rapidly inhibits both the intracellular release of calcium and calcium influx through non-voltage-dependent calcium channels in response to formylmethionylleucylphenylalanine.

Calcium↗
PubMed1988

Baseline metal-in-dust concentrations in Greater London.

Baseline concentrations of cadmium, copper, iron, lead and zinc have been measured in samples collected from surfaces remote from local sources of pollution across Greater London. The geometric means of concentrations of metals in dusts are 2.7 micrograms/g Cd, 79 micrograms/g Cu, 23,400 micrograms/g Fe, 370 micrograms/g Pb and 372 micrograms/g Zn. Concentrations of metals in dust have been shown to exhibit marked distributions across Greater London, and the survey has indicated the location of a number of areas of elevated metal-in-dust levels, for example the Lee Valley industrial area in north London, central London, and parts of east and west London. The concentrations found are compared with results reported in other studies, and the potential sources of metal contamination in the London area are discussed.

Cadmium↗
PubMed1988

Affinity purification of the mammalian beta-2-adrenergic receptor.

The efficiency of covalently linking alprenolol to Sepharose via a 14-atom spacer prepared from 1,4-butanediol diglycidyl ether has been increased. This in turn has aided in increasing the specific yield of beta-2-adrenergic receptor by a factor of 3 over earlier results. Further development of extraction and solubilization protocols are also described. The adsorption of the affinity-purified receptor to stainless steel was measured, and is cited as a potential problem in further purification by high-pressure liquid chromatography.

Adsorption↗
PubMed1988

A comparison of enprostil and ranitidine in treatment of duodenal ulcer.

Enprostil is a new synthetic prostaglandin E2 with antisecretory and mucosal-protective effects. We compared it with ranitidine in the healing of duodenal ulcer and also examined the subsequent relapse rate. Three hundred thirteen patients were recruited in 15 centers in Europe, of whom 158 were treated with enprostil (E) 35 micrograms twice daily and 155 with ranitidine (R) 150 mg twice daily for up to 6 weeks, using a double-blind method. Patients in both groups were of comparable demography. Healing was significantly quicker with ranitidine. Of patients randomized to treatment, healing (intention-to-treat analysis) at 4 weeks was E 47% and R 69%, and at 6 weeks it was E 66% and R 88%. In patients who met all protocol criteria and completed treatment, healing at 4 weeks was E 58% and R 80%, and at 6 weeks it was E 81% and R 92%. Early relief of pain, both during the day and at night, was significantly quicker with ranitidine. Nausea, diarrhea, vomiting, and abdominal pain occurred more often with enprostil. There were no clinically important abnormalities in hematology or biochemistry. Relapse rates were similar. In conclusion, enprostil is not as effective as ranitidine in healing duodenal ulcers.

Adolescent↗
PubMed1988

Impact of staff education on pressure sore development in elderly hospitalized patients.

To test the hypothesis that an educational program alone without the introduction of new technology could result in both higher quality care and cost savings, the incidence of development of pressure sores among patients over the age of 65 years was concurrently reviewed before and after an education program developed and disseminated by a skin care team composed of physicians and nurses. Before the education program, 18 (14.6%) of 123 patients with no pressure sores developed pressure sores during their hospital admission. After the education program, only six (5.4%) of 105 patients who entered the hospital with intact skin developed a pressure sore during their hospital stay. The data show that an educational program was effective in decreasing by 63% the development of pressure sores in an elderly hospitalized population. Furthermore, a cost savings of $74,372 in the use of special care beds was realized.

Aged↗
PubMed1988

Pulmonary embolism in outpatients with pleuritic chest pain.

Pleuritic chest pain is a frequent complaint in patients coming to the emergency room, but the proportion of such patients with pulmonary embolism is uncertain. In a prospective study, we evaluated the diagnostic outcomes in 173 consecutive patients who came to the emergency room with pleuritic chest pain. Pulmonary embolism, as demonstrated by angiography or autopsy, was present in 36 (21%). The need for objective testing is clearly indicated by our finding that the sensitivity (85%) and specificity (37%) of predetermined clinical variables for pulmonary embolism were insufficient to allow a definitive treatment decision. Optimal sensitivity and specificity are obtained by using pulmonary angiography in combination with lung scanning. The proportion of patients requiring angiography is substantially reduced, from 43% to 26%, without significant loss of accuracy, if ventilation imaging and impedance plethysmography are used together with perfusion scanning.

Adult↗
PubMed1987

High-performance liquid chromatographic quantitation of triacylglycerols containing fenoprofen from biological samples.

A normal-phase high-performance liquid chromatographic (HPLC) method has been developed for the quantitation of radiolabelled triacylglycerols containing fenoprofen, synthesized from [3H]glycerol by isolated hepatocytes and adipocytes. The assay consists of extracting the lipids into diethyl ether, separating triacylglycerols from polar endogenous lipids using silica Sep-Pak cartridges and quantitating endogenous triacylglycerols and triacylglycerols containing fenoprofen by HPLC resolution and scintillation counting. HPLC separation is achieved in less than 10 min. Using [14C]tripalmitin as internal standard the assay has a linear relationship between added triacylglycerol and measured endogenous triacylglycerols and triacylglycerols containing fenoprofen with regression coefficients of 0.997 and 0.998, respectively.

Animals↗