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Biomedical subjects

T M Smith

Publications and source records attributed to T M Smith.

At least 55 records · Page 3Linked to original sources
PubMed1995

A liquid perfluorochemical decreases the in vitro production of reactive oxygen species by alveolar macrophages.

OBJECTIVE: To determine whether reactive oxygen metabolite production by alveolar macrophages is affected by liquid perfluorochemical exposure. DESIGN: Controlled, animal laboratory investigation of alveolar macrophage function in vitro. SETTING: Animal research facility of a health sciences university. SUBJECTS: Six adult male New Zealand white rabbits and six young piglets. INTERVENTIONS: Alveolar macrophages were obtained after sacrifice from both species by total lung lavage. Macrophages were divided into control and experimental groups. Macrophages in the experimental groups were exposed to perfluorooctylbromide. To determine production of reactive oxygen metabolites, hydrogen peroxide production and chemiluminescence were measured in both experimental and control groups after chemical stimulation. MEASUREMENTS AND MAIN RESULTS: Perfluorooctylbromide-exposed alveolar macrophages produced significantly less hydrogen peroxide (1.4 +/- 1.5 vs. 2.4 +/- 1.6 nmol/10(6) cells; p = .002). Perfluorooctylbromide-exposed alveolar macrophages demonstrated significantly less chemiluminescence activity compared with nonexposed cells (0.70 +/- 0.2 vs. 1.5 +/- 0.2 mV of relative activity per 3.5 x 10(5) cells; p = .005). CONCLUSIONS: Exposure of alveolar macrophages to perfluorooctylbromide in vitro decreases the responsiveness of macrophages to potent stimuli. This finding may partially explain the decrease in pulmonary inflammation seen in animals treated with partial liquid ventilation during experimentally induced lung injury.

Animals↗
PubMed1995

Efficacy and safety of gentamicin and streptomycin in Optisol-GS, a preservation medium for donor corneas.

Increasing reports of gentamicin-resistant bacteria contaminating donor corneas and causing endophthalmitis have indicated that preservation of corneal storage media with 100 micrograms/ml of gentamicin alone needs reevaluation. We investigated the stability and possible cytotoxicity of streptomycin as a supplement to gentamicin in Optisol corneal storage medium. The combination of gentamicin and streptomycin in Optisol solution was stable at room temperature for at least 4 weeks and inhibited the growth of Staphylococcus aureus, S. epidermidis, alpha hemolytic streptococci, Streptococcus Group D, Propionibacterium acnes, Escherichia coli, and diphtheroids, but not Pseudomonas aeruginosa. The addition of vancomycin did not significantly improve the antibacterial effectiveness of the gentamicin and streptomycin combination when stored at 4 degrees C. The growth of 15 of 20 clinical ocular isolates of Ps. aeruginosa was suppressed by the gentamicin-streptomycin combination. Streptomycin in concentrations of up to 1,000 micrograms/ml did not decrease the mitotic activity of corneal endothelial cells as evaluated by the in vitro incorporation of tritiated thymidine or cause cytotoxicity. The addition of 200 micrograms/ml of streptomycin to Optisol corneal storage medium containing 100 micrograms/ml of gentamicin may significantly improve activity against gentamicin-sensitive and gentamicin-resistant contaminants.

Aged↗
PubMed1995

Smoking cessation: a clinical study of the transdermal nicotine patch.

Although cigarette smoking is a declining trend in the United States, the amount of cigarettes consumed by the American public is the same today as in 1964. The role of cigarette smoking in many disease processes is publicly well known, and smoking cessation has been proved to reduce risk for some diseases, but the various methods of cessation are often met with a high rate of treatment failure or relapse. In this study, the short-term efficacy of nicotine-replacement therapy by way of the transdermal patch system was evaluated in 110 patients in a family practice setting. Patches were tapered from 21 mg of nicotine to 14 mg to 7 mg, each for 30 days. Subjects wore one patch for every 24 hours and were instructed not to smoke. Telephone follow-up was used at 2 to 3 weeks to check smoking status and inquire for side effects, and further follow-up of those who had completed the 3-month program was initiated 6 months after the program began. Nineteen patients never filled the prescription, and six were lost to follow-up. Of the 85 who finished the program, 35% were still not smoking at 6 months after the study began. The other 65% had relapsed. Side effects were mild and were mainly related to skin irritation at the patch site and abnormal dreams. Combinations of this cessation method with physician counseling and other behavioral methods should improve the success rate of this encouraging treatment.

Administration, Cutaneous↗
PubMed1994

Advocacy training during pediatric residency.

Despite broad concerns about the welfare of children, most pediatric residents are not able to engage in child advocacy during their busy training years. Yet residency can provide an opportunity for young pediatricians to learn valuable advocacy skills by undertaking an independent project with an experienced mentor. We describe the University of Washington Pediatrics Residency Program's experience in training interested residents in child advocacy. Basic requirements are that advocacy projects must not interfere with clinical training, resident participation must be voluntary, and faculty with advocacy skills must be available to help guide the residents. Four resident projects are outlined and guidelines for instituting such programs are presented.

Child↗
PubMed1993

Body plasma membrane vesicles from Paramecium contain a vanadate-sensitive Ca(2+)-ATPase.

Paramecia are an excellent model system for studying the mechanisms involved in sensory transductions and intracellular Ca2+ regulation. These cells have two functionally distinct plasma membrane domains, body and cilia. The body plasma membrane is responsible for transduction of sensory stimuli into receptor potentials and the ciliary membrane is required for Ca2+ action potentials. Although ciliary membrane vesicles (cmv) have been purified and well characterized, body plasma membranes have not. We have generated body plasma membrane vesicles (bmv) by homogenization of deciliated cells and purified them from the microsome fraction by a two-phase aqueous polymer separation. The major criteria for purity of the bmv fraction are: (i) It is enriched 15-fold for a known plasma membrane marker (immobilization antigen) while the marker activities for other membranes were all decreased. The protein banding pattern of bmv is generally similar to cmv on SDS-PAGE. (ii) It contains a vanadate-sensitive Ca(2+)-ATPase activity that has been suggested to be a plasma membrane Ca2+ pump. The specific activity of this bmv Ca(2+)-ATPase is increased 4-fold over that of the homogenate. (iii) The phospholipid, fatty acid, and sterol composition of the bmv fraction are indicative of plasma membranes because they are qualitatively similar to cmv. The bmv also contains a membrane-bound NADPH-dependent cytochrome c reductase activity, suggesting that it may play a role in body plasma membrane function. This purified bmv preparation is useful for studying the role of the body plasma membrane in Ca2+ regulation, sensory transduction, protein and lipid trafficking, and plasma membrane fusion events.

Animals↗
PubMed1993

Combination antibiotic supplementation of corneal storage medium.

Gram-positive cocci frequently contaminate donor corneal tissue and represent the most common cause of postkeratoplasty endophthalmitis. Although gentamicin is currently added to corneal storage medium in an effort to decrease bacterial contamination of donor tissue, it has poor or variable in vitro activity against many strains of streptococci and staphylococci. To investigate whether the antibiotic supplementation of corneal storage media could be improved, we surveyed 11 antibiotics for antimicrobial efficacy under simulated storage conditions against gentamicin-resistant strains of Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae, and St. viridans. All antibiotics showed markedly reduced activity at 4 C as compared to their predicted activity at 37 C. Bactericidal activity of streptomycin and tobramycin was enhanced by preceding 4 C storage with a three-hour period at room temperature (23 C). Under these conditions, streptomycin showed the best antimicrobial activity of the 11 antibiotics tested. Addition of gentamicin to streptomycin resulted in further improvement of activity against S. aureus and S. epidermidis, whereas the addition of penicillin G to streptomycin enhanced the activity against St. viridans. Optimal antibiotic activity (99% or more killing) against all four isolates of gentamicin-resistant gram-positive cocci was best achieved with the combination of gentamicin, streptomycin, and penicillin G, coupled with a three-hour period at room temperature before 4 C storage.

Cornea↗
PubMed1993

Glucose regulation of transforming growth factor-alpha expression is mediated by products of the hexosamine biosynthesis pathway.

We have recently shown that glucose and glucosamine regulate the transcription of transforming growth factor-alpha (TGF alpha) in rat aortic smooth muscle (RASM) cells. Based on the increased potency of glucosamine compared to glucose, we hypothesized that stimulation of TGF alpha transcription by glucose is mediated through the hexosamine biosynthesis pathway. The yeast cDNA for the rate-limiting enzyme of this pathway, glutamine:fructose-6-phosphate amidotransferase (GFA), was therefore expressed in RASM cells. GFA-transfected cells showed an increase in GFA activity, exhibiting a 2.2-fold increase in the synthesis of glucosamine-6-phosphate, the first product of the hexosamine biosynthetic pathway. To test the effect of GFA overexpression on TGF alpha transcriptional activity, cells were transiently cotransfected with GFA along with a reporter plasmid containing the firefly luciferase gene under control of the TGF alpha promoter. GFA-transfected cells exhibited a glucose-dependent 2-fold increase in TGF alpha activity compared to control cells. Maximal stimulation of TGF alpha-luciferase activity by glucosamine, however, was equivalent in GFA-and control-transfected cells, confirming that the stimulation observed by both agents operated through the same pathway. This increase in TGF alpha activity was inhibited (85% at 0.5 mM glucose and 69% at 30 mM glucose) by the glutamine analog and inhibitor of GFA, 6-diazo-5-oxonorleucine (10 microM). Control studies confirmed that the increased TGF alpha-luciferase activity in the GFA-expressing cells was not an artifact of altered growth, survival, or transfection efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Regulation of insulin-stimulated glycogen synthase activity by overexpression of glutamine: fructose-6-phosphate amidotransferase in rat-1 fibroblasts.

High glucose concentrations such as are seen in diabetes mellitus are known to have deleterious effects on cells, but the pathways by which glucose induces these effects are unknown. One hypothesis is that metabolism of glucose to glucosamine might be involved. For example, it has been shown that glucosamine is more potent than glucose in inducing insulin resistance in cultured adipocytes and in regulating the transcription of the growth factor transforming growth factor alpha in smooth muscle cells. The rate-limiting step in glucosamine synthesis is the conversion of fructose-6-phosphate to glucosamine-6-phosphate by the enzyme glutamine:fructose-6-phosphate amidotransferase. To test the hypothesis that this hexosamine biosynthesis pathway is involved in the induction of insulin resistance, we have overexpressed the enzyme glutamine:fructose-6-phosphate amidotransferase in Rat-1 fibroblasts and investigated its effects on insulin action in those cells. We electroporated Rat-1 fibroblasts with expression plasmids that did and did not contain the gene for glutamine:fructose-6-phosphate amidotransferase and measured glycogen synthase activity at varying insulin concentrations. Insulin stimulation was blunted in the glutamine:fructose-6-phosphate amidotransferase-transfected cells, resulting in decreased insulin sensitivity reflected by a rightward shift in the dose-response curve for activation of synthase (ED50 = 7.5 nM vs. 3.4 nM insulin, in glutamine:fructose-6-phosphate amidotransferase and control cells, respectively). Rat-1 fibroblasts incubated with 5.- mM glucosamine for 3 days exhibited a similar shift in the dose-response curve. The rightward shift in the dose-response curve is seen as early as 2 days after poration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Perfluorocarbon-based antidiabetic agents.

In a preliminary communication (J. Med. Chem. 1989, 32, 11-13) a series of perfluoro-N-[4-(1H-tetrazol-5ylmethyl)phenyl]alkana mides (perfluoro anilides I), designed as novel analogues of ciglitazone, were reported to possess oral antidiabetic activity in two genetic animal models of non-insulin-dependent diabetes mellitus (NIDDM): obese (ob/ob) and diabetic (db/db) mice. In this report, the results from a structure-activity relationship (SAR) study of the series I are described. Comprehensive statistical analysis among the 86 analogues screened for blood glucose lowering in ob/ob mice was achieved by a new application of a general statistical procedure which made it possible to make meaningful comparisons between more than 140 separate experiments (N = 2966). Perfluoro anilides I lowered plasma glucose in the hyperglycemic ob/ob and db/db mice but not in euglycemic normal rats. In the hyperinsulinemic ob/ob mouse, decreases in plasma insulin levels paralleled the decline in plasma glucose. Potency and efficacy in the series was shown to be dependent on the length of the perfluorocarbon chain (RF) of I. Optimal activity occurred with the C7 and C8 RF chains. The more extensive SAR studies reported here, indicated that the lipophilic RF chain is the most important structural element of I since neither the phenyl nor tetrazole rings present in anilides I were necessary for antihyperglycemic activity while medium length (C7-C8) RF chains, especially the C7F15 chain, were shown to confer antihyperglycemic activity in ob/ob mice to a wide variety of structures.

Animals↗
PubMed1992

Analysis of individual CNS protein synthesis.

A procedure for labeling rat CNS proteins in vivo which is useful for behavioral and pharmacological studies has been developed. Intraventricular administration of 35S-methionine through bilateral indwelling cannulae provided reproducible and highly specific radiolabeling of proteins from frontal cortex (FC), parietal cortex (PC), occipital cortex (OC), striatum (ST), septal nuclei (SN), amygdala (AM), hippocampus (HIP), thalamus (TH), brain stem (BS) and cerebellum (CB). Relative rates of synthesis of over 200 individual proteins were subsequently analyzed by 2DGE. Regional analysis demonstrated increased labeling of a protein of MW 28 kD and pI 6.4 in the hippocampus that was barely detectable in striatum of control rats. In heat-shocked animals, there was increased relative synthesis of the 74 kD Heat Shock Protein in both the septal nuclei and hippocampus.

Amygdala↗
PubMed1992

Creating family-centered services in early intervention: perceptions of professionals in four states.

This article describes professional perceptions of the current status of family involvement in early intervention programs in four states. Significant discrepancies between current and ideal practices were found in four dimensions: parent involvement in decisions about child assessment, parent participation in assessment, parent participation in the team meeting and decision making, and the provision of family goals and services. In identifying barriers to ideal programs, professionals most frequently mentioned family barriers (35.8%) and system barriers (35.1%). Professional barriers, or those related to a lack of skill, accounted for only 14.8% of the barriers mentioned.

Attitude of Health Personnel↗
PubMed1991

Bacterial and mycoplasmal flora of the healthy camelid conjunctival sac.

Healthy conjunctival sacs of 88 animals of 3 species of captive camelids (Lama glama, Lama guanicoe, Lama pacos) and llama-guanaco hybrids were sampled for bacterial and mycoplasmal flora. Mycoplasmas were not isolated from any animal. Eleven genera of bacteria were isolated. The most frequent isolates were Staphylococcus epidermidis and Pseudomonas spp. Nine varieties of Pseudomonas were found, which represented at least 3 Pseudomonas species. Many of the bacterial isolates (especially the pseudomonads) are potential pathogens in the eyes of these camelids.

Animals↗
PubMed1990

Altered expression of self-reactive T cell receptor V beta regions in autoimmune mice.

Intrathymic tolerance results in elimination of T cells bearing self-reactive TCR V beta regions in mice expressing certain combinations of I-E and minor lymphocyte stimulatory (Mls) phenotypes. To determine if autoimmune strains of mice have a defect in intrathymic deletion of self-reactive TCR V beta regions, expression of V beta 3, V beta 6, V beta 8.1, and V beta 11 were examined in lpr/lpr and +/+ strains of mice; MRL/MpJ(H-2K, I-E+, Mlsb,), C57BL/6J(H-2b, I-E-, Mlsb,), C3H/HeJ(H-2k, I-E+, Mlsc), AKR/J(H-2k, I-E+, Mlsa); and in autoimmune NZB/N(H-2d, I-E+, Mlsa) and BXSB(H-2b, I-E-, Mlsb) mice. The results suggest that, during intrathymic development, self-reactive T cells are deleted in autoimmune strains of mice as found in normal control strains of mice. However, the TCR V beta repertoire is skewed in autoimmune strains compared to normal strains of mice. For example, MRL-lpr/lpr mice, but not other lpr/lpr strains, had increased expression of V beta 6 relative to expression in control MRL(-)+/+ mice, which is associated with collagen-induced arthritis. These data are consistent with a model of normal affinity for negative selection of self-reactive T cells in the thymus of autoimmune strains of mice followed by expansion of autoreactive T cell clones in the peripheral lymphoid organs. The peripheral lymphoid organs of lpr/lpr mice contain an expanded population of abnormal CD4-, CD8-, 6B2+ T cells. Elimination of self-reactive peripheral T cells suggests that these abnormal cells are derived from a CD4+ subpopulation in the thymus. Flow cytometry analysis of peripheral lymph node T cells from MRL-lpr/lpr mice reveal three populations of CD4+ T cells expressing low, intermediate and high intensity of B220 (6B2). This supports the hypothesis that in lpr/lpr mice, self-reactive CD4+ T cells are eliminated in the thymus, and that these cells lose expression of CD4 and acquire expression of 6B2 in the periphery.

Animals↗
PubMed1990

The use of logit models to investigate social and biological factors in infant mortality. V: A multilogit analysis of stillbirths, neonatal and post-neonatal mortality.

Infant mortality data for England and Wales, cross classified by mother's age, parity and social class were published for 1949/50 and 1975. Previous analyses of these data have been based on graphical, tabular and logit models of stillbirths, neonatal and post-neonatal deaths separately. This paper summarizes the overall changes in infant mortality using a multilogit model. The model selected is illustrated by appropriate graphical presentations.

Adolescent↗