Publications by authors named "Gladstone P"

Pyocyanin is produced by Ps. aeruginosa as a result of quorum sensing during wound colonisation increasing bacterial virulence and damaging host physiology, both of which contribute to an increased risk of infection. The use of carbon fibre tow as an electrochemical sensing matrix for assessing pyocyanin production is evaluated.

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A series of novel, multisubstrate, bicyclic pyrimidine nucleoside inhibitors of human thymidine phosphorylase (TP) is described. Thymidine phosphorylase has been implicated in angiogenesis and plays a significant role in tumor progression and metastasis. The presence and orientation of the phosphonate moiety (acting as a phosphate mimic) in these derivatives were critical for inhibitory activity.

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Post-streptococcal sequelae, especially acute rheumatic fever/rheumatic heart disease continue to occur in significant proportions in many parts of the world. Despite several attempts with various intervention strategies, little success has been achieved in the control of acute rheumatic fever/rheumatic heart disease in India. The success of the control programmes depends upon timely primary prophylaxis with benzathine penicillin for which a microbiological confirmation of group A streptococcal pharyngitis is essential.

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A series of oxamyl dipeptides were optimized for pan caspase inhibition, anti-apoptotic cellular activity and in vivo efficacy. This structure-activity relationship study focused on the P4 oxamides and warhead moieties. Primarily on the basis of in vitro data, inhibitors were selected for study in a murine model of alpha-Fas-induced liver injury.

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Resistance to carbapenems is commonly seen in nonfermenting gram negative bacilli (NFGNB). We document herein the prevalence of carbapenem resistance in NFGNB isolated from patients with respiratory tract infections in the intensive care units (ICUs). A total of 460 NFGNB were isolated from 606 endotracheal aspirate specimens during January through December 2003, of which 56 (12.

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Purpose: This is a retrospective analysis of the isolation rates of nontuberculous mycobacteria (NTM) from various clinical specimens and their antimicrobial susceptibility patterns.

Methods: All NTM isolated between 1999 and 2004 at Christian Medical College, Vellore, South India, were identified with various biochemical tests. Antimicrobial susceptibility test for all NTM was performed by standard methods.

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Group A streptococci (GAS) (n = 1313) isolated from patients with clinical symptoms of pharyngitis or tonsillitis attending a tertiary care hospital in southern India during 1986-2002 were tested for susceptibility to penicillin and erythromycin. The overall erythromycin resistance rate was 2.7% (n = 36).

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Dynamics of anti-M antibody response following intranasal infection with group A Streptococcus (GAS) M-18 were investigated in a Swiss albino mouse model. Mice arranged in three groups were inoculated intranasally with 2.0x10(7) c.

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The objective of this study was to consider the invasive properties of Streptococcus pyogenes in human pharyngeal epithelial cells, and to correlate these with their clinical significance. Clinical isolates of S. pyogenes obtained from blood cultures over a period of 10 years, and throat and skin isolates from a community-based study, were used in this investigation.

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A novel class of thymidine phosphorylase (TP) inhibitors has been designed based on analogy to the enzyme substrate as well as known inhibitors. Flexible docking studies, using a homology model of human TP, of the designed N-(2,4-dioxo-1,2,3,4-tetrahydro-thieno[3,2-d]pyrimidin-7-yl)-guanidines as well as their synthetic precursors provide insight into the observed experimental trends in binding affinity.

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Objective: To determine the effect of the Ischemic Heart Disease Shared Decision-Making Program (IHD SDP) an interactive videodisc designed to assist patients in the decision-making process involving treatment choices for ischemic heart disease, on patient decision-making.

Design: Randomized, controlled trial.

Setting: The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada.

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[reaction: see text] The syntheses of bis-trimethylstannanes 8, 10, 12-14, 16, 18, 21, and 22 are described. Treatment of these substances with approximately 5 equiv of CuCl in DMF at rt for 30-60 min effects, in each case, oxidative coupling between the two sp2 carbon centers bearing the Me3Sn function to produce good-to-excellent yields of tricyclic products 23-31, respectively.

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The primary objective of the Diabetes Atherosclerosis Intervention Study (DAIS) is to determine by quantitative coronary angiography whether long-term correction of the dyslipoproteinemia of diabetes with micronized fenofibrate results in evidence of decreased progression or regression of angiographically measured obstructive coronary atherosclerosis. The purpose of this communication is to describe the angiographic methodology for the DAIS project, and to present data documenting the reproducibility of measurements that will determine the primary outcome of DAIS. Four hundred eighteen subjects between the ages of 40 and 65 were entered from 11 centers in Canada, France, Finland, and Sweden, with 305 males and 113 females.

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Almost a century has passed since immunotherapy of cancer was first attempted using cancer immunogens (vaccines); however, its clinical impact remains modest. Although initial concerns about a lack of human tumor antigens have decreased, prevailing issues include inefficient procedures for immunization and downregulated expression of major histocompatibility complex (MHC) class I molecules in tumor cells. While immunization can be improved, deficient MHC class I expression remains a problem, because it hampers the ability of tumor cells to present antigens for killing by CD8+ T cells.

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Recent work from one laboratory has shown, in both nonobese diabetic mice and humans, an association between insulin-dependent diabetes mellitus (IDDM) and quantitative difference in MHC class I molecule expression. This reported decrease in MHC class I molecule expression is very controversial in the nonobese diabetic mouse model of IDDM, but to our knowledge, it has not been evaluated by another group in human IDDM. To evaluate this question, we studied 30 patients with IDDM and 30 age- and sex-matched normal controls.

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Background: Although smoking increases both the risk of developing coronary disease and the risk of coronary events in patients with known coronary atherosclerosis, the effect of smoking on the evolution of coronary atherosclerosis as assessed by serial angiography is poorly defined.

Methods And Results: Ninety smokers with coronary atherosclerosis shown on a recent angiogram and with fasting cholesterol levels between 220 and 300 mg/dL were enrolled in a randomized, double-blind, placebo-controlled trial of cholesterol-lowering therapy, along with 241 nonsmokers and exsmokers. Lovastatin at a mean dose of 36 mg/d lowered total and LDL cholesterol by 21 +/- 11% and 29 +/- 11%, respectively, but these levels changed by < 2% in placebo-treated patients.

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Following a successful immune response against invading microorganisms, the majority of activated T cells is eliminated, while a minor fraction survives as memory T cells. A decline in T lymphocyte growth factors such as interleukin-2 (IL-2) appears to play a role in the elimination of previously activated T cells. Thus, removal of IL-2 from proliferating T cells not only induces growth arrest, but triggers a massive cell death due to apoptosis.

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The synthesis of some novel bakkenolides and their epi-spiro analogues was achieved by a new approach. Photolysis of allyl 1-(phenylseleno)-2-oxocyclopentanecarboxylates 7-9 afforded the corresponding spiro lactones 10-12 by radical cyclization via group transfer of the phenylseleno group. Selenoxide elimination of 11 and 12 produced the corresponding beta-methylene lactones 14 and 15.

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Allograft vasculopathy (AV) causes intimal thickening with progressive luminal obstruction, endothelial dysfunction, and abnormal vasomotion. Subendocardial vacuolization indicating ongoing ischemia was observed at autopsy in transplanted hearts with severe AV. Whether myocyte vacuolization can be observed with lesser degrees of AV in cardia transplant patients has not been reported.

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The monocytic cell line I937 was derived from U937 by sorting for cells with high expression of MHC class II molecules. Further analysis of these class II molecules revealed the presence of the HLA-DR3 subtype suggesting that the cell line was a potential candidate for testing antigen presentation to T cells restricted by HLA-DR3. We found that the T cell clones CFTS4:2.

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A 43-year-old healthy man developed transmural myocardial infarction shortly after ingesting sumatriptan succinate 100 mg for migraine. Coronary arteriography revealed only minor irregularities in the left anterior descending artery. Oral sumatriptan should be used with caution in any patient with vascular risk factors and avoided in those with coronary artery disease or vasospasm.

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Background: Although coronary disease is the leading cause of death in women and its clinical features differ from those in men, very few women have been included in angiographic trials of cholesterol lowering.

Methods And Results: Sixty-two women with diffuse but not necessarily severe coronary atherosclerosis documented on a recent angiogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a double-blind, placebo-controlled trial. More than one half had a history of hypertension, approximately one quarter were diabetics, and one third were current smokers.

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