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Biomedical subjects

D A Smith

Publications and source records attributed to D A Smith.

At least 73 records · Page 4Linked to original sources
PubMed2000

Evidence for charge domains on developing enamel crystal surfaces.

The control of hydroxyapatite crystal initiation and growth during enamel development is thought to be mediated via the proteins of the extracellular matrix. However, the precise nature of these matrix-mineral interactions remains obscure. The aim of the present study was to use a combination of atomic and chemical force microscopy to characterize developing enamel crystal surfaces and to determine their relationship with endogenous enamel matrix protein (amelogenin). The results show regular and discrete domains of various charges or charge densities on the surfaces of hydroxyapatite crystals derived from the maturation stage of enamel development. Binding of amelogenin to individual crystals at physiological pH was seen to be coincident with positively charged surface domains. These domains may therefore provide an instructional template for matrix-mineral interactions. Alternatively, the alternating array of charge on the crystal surfaces may reflect the original relationship with, and influence of, matrix interaction with the crystal surfaces during crystal growth.

Amelogenesis↗
PubMed2000

Sentence completion tests: a review of the literature and results of a survey of members of the Society for Personality Assessment.

Test usage surveys consistently find that sentence completion tests (SCTs) are among the most popular personality assessment instruments used by practitioners. What is not noted is which SCTs practitioners are using, why these tests are so popular, and whether practitioners are using formal scoring. We surveyed a random selection of 100 members of the Society for Personality Assessment. With a 60% return rate on a single mailing, we found that most psychologists who use incomplete sentence tests use the Rotter (1951) Incomplete Sentences Blank with children (18%), adolescents (32%), and adults (47%). Most practitioners said they do not read stems aloud and record answers themselves, and even fewer said they use formal scoring. The most common reasons for using an SCT are (a) to use it as part of an assessment battery (41 endorsements), (b) to determine personality structure (18 endorsements), and (c) to elicit quotable quotes (17 endorsements). Implications for practitioners and training suggestions for academicians who prepare future psychologists are noted.

Adolescent↗
PubMed2000

Early aneurysm recurrence after technically satisfactory Guglielmi detachable coil therapy: is early surveillance needed? Case report.

Guglielmi detachable coil (GDC) therapy was initially intended as a treatment for select patients harboring aneurysms deemed to be at high risk for clip ligation. As experience with the technique has grown, many centers are now offering GDC therapy as a primary treatment to patients who are also good surgical candidates. The authors report a case in which a ruptured anterior communicating artery aneurysm recurred within 2 weeks of a technically satisfactory GDC procedure. The patient subsequently underwent successful surgery for clip ligation of the lesion. This is the earliest reported recurrence of an aneurysm after angiographically confirmed successful GDC therapy and underscores the need for performing early control angiography in patients undergoing this procedure.

Aneurysm, Ruptured↗
PubMed2000

Pravastatin: an antithrombotic effect independent of the cholesterol-lowering effect.

Lipid-lowering with statins reduces blood thrombogenicity. However, it is unknown whether this is purely due to LDL-cholesterol reduction, or it is related to a statin or agent specific effect. We investigated the relationship between reduction in blood thrombogenicity and the magnitude of low-density lipoprotein cholesterol (LDL-C) during pravastatin therapy. We prospectively followed for 6 months 57 hyperlipidemic patients who initiated therapy with pravastatin, and 36 patients who were randomized into placebo plus diet. Pravastatin-treated patients were grouped according to the LDL-C reduction at 6 months; (i) "adequate LDL-C reduction": LDL-C reduction >30% from baseline or LDL-C<125 mg/dl (n = 38; LDL-C reduction 74 +/- 4 mg/dl; 6-month LDL-C 119 +/- 5 mg/dl); (ii) "inadequate LDL-C reduction": neither of the above criteria (n = 19; LDL-C reduction 31 +/- 5 mg/dl; 6-month LDL-C 158 +/- 6 mg/dl). Placebo patients were divided into those "with LDL-C reduction" (n = 17, mean reduction 21 +/- 5 mg/dl) and those "without LDL reduction" (n = 19). The following parameters were altered at 6 months in both patients with "adequate" and "inadequate" LDL-C reduction: (1) tissue plasminogen activator decreased by 1.4 +/- 0.4 and 1.5 +/- 0.5 ng/ml respectively (p = NS); (2) plasminogen activator inhibitor-1 decreased by 8.7 +/- 2.0 and 10.1 +/- 2.7 ng/ml respectively (p = NS); (3) thrombus formation under dynamic flow conditions decreased by 3.5 +/- 0.9 and 2.8 +/- 1.2 microm2 x 10(3) respectively (p = NS). In contrast, no significant changes from baseline were noted in placebo-treated patients, regardless of their LDL-C reduction category, and multivariate analysis eliminated LDL-C reduction as an independent predictor of reduction in thrombogenicity. Therefore, the reduction in thrombogenicity was not proportional to the magnitude of LDL-C reduction suggesting that a class or agent specific property is primarily responsible for the pro-fibrinolytic/antithrombotic effects observed.

Aged↗
PubMed1999

Gender differences in blood thrombogenicity in hyperlipidemic patients and response to pravastatin.

Thrombotic risk in hyperlipidemic women and its response to lipid therapy is unknown. We prospectively studied 28 men and 29 women with high low-density lipoprotein (LDL) cholesterol during 6 months of therapy with pravastatin. Women had significantly higher high-density lipoprotein (HDL) cholesterol (54.2 +/- 1.7 vs 39.5 +/- 2.2 mg/dl, p <0.01), lower prevalence of coronary artery disease (41% vs 67%, p = 0.04), and otherwise similar baseline characteristics compared with men. Both genders achieved a 33% reduction in LDL at 6 weeks (188 +/- 6 to 133 +/- 5 mg/dl) and maintained similar LDL levels throughout the study. Systemic hemostatic markers and thrombus formation under dynamic flow conditions were evaluated at baseline, and at 3 and 6 months of follow-up. Prothrombin fragment F1.2, a marker of thrombin generation, was higher in women versus men at baseline (2.4 +/- 0.2 vs 1.4 +/- 0.3 nmol/L, p = 0.02). The levels decreased in women to 2.0 +/- 0.3 nmol/L at 3 months and to 1.6 +/- 0.2 nmol/L at 6 months (p <0.045, analysis of variance), whereas it remained unchanged in men. Plasminogen activator inhibitor-I significantly decreased at 3 and 6 months of follow-up: by 12.6% and 18.7%, respectively, in women, and by 18.8% and 23.5%, respectively, in men. Similarly, tissue plasminogen activator decreased significantly by 7.4% in women and 11.8% in men at 6 months compared with baseline. Fibrinogen showed an increase in both genders at follow-up. Thrombus formation was similar at baseline between the 2 genders, and decreased at 3 and 6 months compared with baseline by 12.5% and 29.5% in women, and by 18.6% and 19.4% in men (p <0.04 at 6 months vs baseline in both men and women). Other markers, including C-reactive protein, fibrinopeptide A, D-dimer, and factor VIIa, did not differ between genders and did not change with therapy. Thus, despite higher HDL, and lower incidence of coronary disease, women with high LDL had a comparable thrombotic and/or fibrinolytic profile to men and even evidence of increased thrombin generation at baseline. Blood thrombogenicity was reduced with pravastatin in both genders; in addition, thrombin generation was gradually reduced in women to a level similar to that of men by 6 months of follow-up.

Aged↗
PubMed1999

Single-molecule biomechanics with optical methods.

Single-molecule observation and manipulation have come of age. With the advent of optical tweezers and other methods for probing and imaging single molecules, investigators have circumvented the model-dependent extrapolation from ensemble assays that has been the hallmark of classical biochemistry and biophysics. In recent years, there have been important advances in the understanding of how motor proteins work. The range of these technologies has also started to expand into areas such as DNA transcription and protein folding. Here, recent experiments with rotary motors, linear motors, RNA polymerase, and titin are described.

Biomechanical Phenomena↗
PubMed1999

Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the systemic hemostatic profile.

OBJECTIVES: The study sought to determine the effects of lipid-lowering with pravastatin on the systemic fibrinolytic profile and on thrombus formation under dynamic flow conditions. BACKGROUND: Lowering cholesterol (C) decreases clinical events in coronary artery disease (CAD) patients, but an analysis of the effects of lipid-lowering on the entire hemostatic and thrombotic profile has not been conducted. METHODS: We prospectively studied 93 stable patients with untreated low-density lipoprotein cholesterol (LDL-C) >145 mg/dl. The CAD patients received pravastatin, and non-CAD patients were randomized to pravastatin versus placebo (double-blind). Thrombus formation upon an injured vascular surface was assessed in a substudy of 40 patients with a previously validated ex vivo perfusion chamber system. Systemic hemostatic markers and thrombus formation were evaluated at baseline, three and six months. RESULTS: Placebo produced no changes in either the lipid profile, any of the hemostatic markers, or the ex vivo thrombus formation. Both pravastatin groups (CAD and non-CAD) showed decreased LDL-C by 30% within 6 weeks (188 to 126 mg/dl, p < 0.001 vs. baseline), and decreased plasminogen activator inhibitor-1 at 3- and 6-month follow-up compared to baseline (15% to 18% decrease at 3 months and 21% to 23% at 6 months). For the tissue plasminogen activator antigen, CAD and non-CAD groups showed significant decreases at 6 months compared to baseline (10% and 13%, respectively). No significant changes were observed with treatment in d-dimer, fibrinopeptide A, prothrombin fragment F1.2, factor VIIa, von Willebrand factor, or C-reactive protein. Fibrinogen levels were significantly increased at 6 months compared to baseline, though still below the upper normal limit. In the perfusion chamber substudy, there was a decrease in thrombus area in non-CAD patients treated with pravastatin at both 3 and 6 months compared to baseline (by 21% and 34%, respectively). The CAD patients showed decreases in thrombus formation by 13% at 3 months, and by 16% at 6 months. The change in LDL-C- correlated modestly with the change in thrombus formation (r = 0.49; p < 0.01). CONCLUSIONS: Pravastatin therapy significantly decreased thrombus formation and improved the fibrinolytic profile in patients with and without CAD. These early effects may, in part, explain the benefit rendered in primary and secondary prevention of CAD.

Aged↗
PubMed1999

Pharmacokinetics and metabolism in early drug discovery.

The need for high-throughput approaches in absorption, distribution, metabolism and excretion studies is driven by the impact of high-speed chemistry and pharmacological screening. Perhaps an even greater impact is that these studies will, in the future, provide large data sets that can be used to predict biological events related to absorption, bioavailability and metabolism of drugs. Through linking of in silico and in vitro methods, considerable progress has recently been made towards this future perspective. Despite this progress, these approaches do not yet replace in vivo methods.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Resting metabolic rate, body composition and aerobic fitness comparisons between active and sedentary 54-71 year old males.

OBJECTIVE: To test the hypothesis that 55-70 y old male longterm exercisers (LE) have higher resting metabolic rates (RMR) than longterm nonexercisers (LNE). DESIGN: A power analysis demonstrated that this cross-sectional study required 12 subjects per group to detect a 10% RMR difference (kJ x kg FFM(-1) x d(-1)) between the LE and LNE (power = 0.8;alpha = 0.05). SUBJECTS: Twelve LE (X +/- s.d.; 63.5+/-3.4 y; 1.75+/-0.06 m; 69.01+/-8.24 kg; 20.4+/-4.9 %BF) and 12 LNE (63.6+/-5.6 y; 1.72+/-0.07 m; 79.44 12.4 kg; 29.6 4.4 %BF) were recruited from advertisements placed in a newspaper and on university and community noticeboards. INTERVENTIONS: Measurements were conducted for: RMR using the Douglas bag technique; body composition via a four compartment model which is based on determination of body density, total body water and bone mineral mass; and aerobic fitness using a submaximal work test on a cycle ergometer. RESULTS: The LE (93.00+/-7.16 kJ x kg(-1) x d(-1)) registered a significantly greater (P = 0.04) RMR than the LNE (84.70+/-11.23 kJ x kg(-1) x d(-1)) when energy expenditure was expressed relative to body mass, but this difference disappeared (P = 0.55) when the data were corrected for the non-zero intercept of the graph of RMR (MJ/d) against body mass. ANCOVA with FFM as the covariate also indicated that the RMR (MJ/d) difference between the groups was not statistically significant (P = 0.28). The adjusted means for the LE and LNE were 6.39 and 6.62 MJ/d, respectively. CONCLUSIONS: There are no RMR (MJ/d) differences between LE and LNE 54-71 y old males when statistical control is exerted for the effect of FFM and the higher value of the former group for RMR normalised to body mass disappears when this ratio is corrected for statistical bias.

Aged↗
PubMed1999

Cytokine and chemokine responses following pulmonary challenge with Aspergillus fumigatus: obligatory role of TNF-alpha and GM-CSF in neutrophil recruitment.

Aspergillus fumigatus causes life-threatening invasive pulmonary aspergillosis in the immunocompromised patient. In this study we have used a murine model of intratracheal challenge with A. fumigatus to investigate the recruitment of inflammatory cells in the lung and the expression of proinflammatory cytokines and chemokines. Our results show that A. fumigatus causes an acute pulmonary inflammatory response which is dominated by neutrophils and to a lesser extent macrophages. During the peak of infection, proinflammatory cytokines (TNF-alpha, GM-CSF and IL-1beta) and chemokines (MIP-1alpha, MCP-1 and MIP-2), are induced within the lung. Furthermore, treatment of mice with neutralizing anti-TNF-alpha and anti-GM-CSF mAbs reduced the influx of neutrophils into the lung and delayed fungal clearance. Our observations show that Aspergillus conidia are effective inducers of host chemokine responses both in vitro and in vivo. Furthermore, TNF-alpha and GM-CSF play a central role in the recruitment of neutrophils into the lung in response to this clinically important pathogen.

Animals↗
PubMed1999

The use of microsatellite variation to infer population structure and demographic history in a natural model system.

To assess the reliability of genetic markers it is important to compare inferences that are based on them to a priori expectations. In this article we present an analysis of microsatellite variation within and among populations of island foxes (Urocyon littoralis) on California's Channel Islands. We first show that microsatellite variation at a moderate number of loci (19) can provide an essentially perfect description of the boundaries between populations and an accurate representation of their historical relationships. We also show that the pattern of variation across unlinked microsatellite loci can be used to test whether population size has been constant or increasing. Application of these approaches to the island fox system indicates that microsatellite variation may carry considerably more information about population history than is currently being used.

Animals↗
PubMed1999

Introduction to immunology and autoimmunity.

Autoimmune disease occurs when the immune system attacks self-molecules as a result of a breakdown of immunologic tolerance to autoreactive immune cells. Many autoimmune disorders have been strongly associated with genetic, infectious, and/or environmental predisposing factors. Comprising multiple disorders and symptoms ranging from organ-specific to systemic, autoimmune diseases include insulin-dependent diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, thyroiditis, and multiple sclerosis. There are also implications of autoimmune pathology in such common health problems as arteriosclerosis, inflammatory bowel disease, schizophrenia, and certain types of infertility. Largely of unknown etiology, autoimmune disorders affect approximately 3% of the North American and European populations, > 75% of those affected being women. This discussion provides a brief introduction to the immune system and tolerance maintenance, an overview of selected autoimmune diseases and possible mechanisms of immune autoreactivity, and a review of experimental autoimmune models.

Allergy and Immunology↗