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Biomedical subjects

Thomas Weber

Publications and source records attributed to Thomas Weber.

80 records · Page 5Linked to original sources
PubMed2002

Structural basis for the cyclization of the lipopeptide antibiotic surfactin by the thioesterase domain SrfTE.

Many biologically active natural peptides are synthesized by nonribosomal peptide synthetases (NRPS). Product release is accomplished by dedicated thioesterase (TE) domains, some of which catalyze an intramolecular cyclization to form macrolactone or macrolactam cyclic peptides. The excised 28 kDa SrfTE domain, a member of the alpha/beta hydrolase enzyme family, exhibits a distinctive bowl-shaped hydrophobic cavity that hosts the acylpeptide substrate and tolerates its folding to form a cyclic structure. A substrate analog confirms the substrate binding site and suggests a mechanism for substrate acylation/deacylation. Docking of the peptidyl carrier protein domain immediately preceding SrfTE positions the 4'-phosphopantheinyl prosthetic group that transfers the nascent acyl-peptide chain to SrfTE. The structure provides a basis for understanding the mechanism of acyl-PCP substrate recognition and for the cyclization reaction that results in release of the macrolactone cyclic heptapeptide.

Amino Acid Sequence↗
PubMed2002

A putative link between exocytosis and tumor development.

Desmoplastic small round cell tumor (DSRCT) is characterized by a t(11;22)(p13;q12) translocation breakpoint. In this issue of Cancer Cell, now show that the resulting EWS-WT1 gene-fusion product leads to overexpression of BAIAP3, a protein implicated in regulated exocytosis.

Angiogenesis Inhibitors↗
PubMed2002

Lack of association between plasma lipoprotein(a) concentrations and the presence or absence of coronary atherosclerosis.

BACKGROUND: Findings from previous studies relating lipoprotein(a) [Lp(a)] as an independent risk factor for coronary atherosclerosis and the presence of angiographically detectable coronary atherosclerotic lesions are not consistent. This study was performed to determine whether the plasma concentration of Lp(a) is associated with coronary atherosclerosis asessed by coronary angiography. METHODS: We studied a total of 100 men and women (41 women, 59 men, age 63.7 +/- 11.0 years) who were referred for coronary angiography. Base-line data collection comprised conventional risk factors for coronary artery disease, lipids, fasting total homocysteine, and clinical characteristics. The relation between plasma Lp(a) levels and the presence or absence of coronary lesions was studied. The coronary angiograms were evaluated in a blinded manner. Any coronary stenosis was considered as coronary artery disease (CAD). RESULTS: From the 100 patients, 40 were found to have no CAD and 60 had CAD assessed by coronary angiography. Estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 0.87 (95 percent confidence interval, 0.66 to 1.34). After adjustment for age, sex, lipoproteins, and homocysteine levels, estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 1.06 (95 percent confidence interval, 0.81 to 1.39). The presence of angiographic CAD was associated with patient age (p=0.048), male sex (p<0.01), high LDL-cholesterol levels (p=0.02), low HDL-cholesterol levels (p=0.02), high plasma fibrinogen levels (p<0.01) and high fasting total homocysteine levels (p=0.04). CONCLUSION: These results suggest that the plasma concentration of Lp(a) is not associated with the presence of coronary artery disease in patients referred for coronary angiography.

Age Distribution↗
PubMed2002

Current and new drugs for the treatment of arrhythmias.

Sudden cardiac death is a leading cause of mortality in industrialized nations, accountingfor 50% of all cardiovascular deaths. Carefully performed randomized trials, technological advances and better understanding of arrhythmia mechanisms have resulted in improved approaches to rhythm disturbances. Risk assessment has to be individualized and can be approached through an analysis based upon all other clinical characteristics of the patient. The need for long-term therapy must be carefully individualized to each patient, since the severity and importance of symptoms are highly variable. This review will summarize the classification of antiarrhythmic drugs and main pharmacokinetic properties. Newer antiarrhythmic drugs either block a specific ionic current (eg, dofetilide-induced blockade of the rapidly activating component of the delayed rectifier potassium current) or block multiple ionic channels (eg, ibutilide and azimilide) in order to prolong atrial and ventricular action potentials without other specific pharmacological effects. Additionally, this manuscript reviews the newer class III agents' effectiveness in treating atrial and ventricular arrhythmias, and the development of novel antiarrhythmic drugs that act specifically to alter cell communication.

Animals↗
PubMedDate not supplied

Influenza A and B IgG seropositivity and coronary atherosclerosis assessed by angiography.

Infectious agents, in particular intracellular pathogens that can establish long-term, persistent seropositivity, may play an important role in atherogenesis. The possible association between influenza type A and B infection and angiographically proven coronary artery disease (CAD) and the effect of the aggregate pathogen burden on CAD was studied by testing blood from 218 patients undergoing coronary angiography for serum IgG antibodies to influenza A and B, and for antibodies to four other pathogens (hepatitis A, Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus). This analysis demonstrates that although influenza (A and B) seropositivity represents no predictor of risk for CAD, infectious burden is independently associated with coronary atherosclerosis.

Aged↗
PubMedDate not supplied

Risk factors of postoperative atrial fibrillation after cardiac surgery.

BACKGROUND: Postoperative atrial fibrillation (AF) occurs in up to 50% of cardiac surgery patients and represents the most common postoperative arrhythmic complication. The etiology of AF after open-heart surgery is incompletely understood and its prevention remains suboptimal. Identification of patients vulnerable for postoperative AF would allow targeting of those most likely to benefit from aggressive prophylactic intervention. The aim of the present study was to evaluate clinical predictors of postoperative AF. METHODS AND RESULTS: Patients undergoing elective cardiac surgery in the absence of significant left ventricular dysfunction (n = 253; average age 65 +/- 11 years) were recruited to the present prospective study. Ninety-nine patients (39.1%) of the total study population developed AF during the postoperative period. The median age for patients with postoperative AF was 69 years compared with 64 years for patients without (p < 0.001). In addition to advanced age, AF patients were more likely to have surgery for valvular heart disease and less likely to have preoperative beta-adrenergic blockers than patients without AF. Multivariate logistic regression analysis (odds ratio, +/-95% CI, p value) was used to identify the following independent clinical predictors of postoperative AF: increasing age (above vs. below median [OR = 2.6; CI, 1.2 to 3.9; p < 0.01]), and surgery for valvular heart disease (vs. coronary artery bypass grafting [OR 2.8; CI, 1.1 to 3.5; p < 0.01)]). Additionally, postoperative complications (stroke, infections, unstable hemodynamics [OR = 1.9; CI, 1.0 to 7.5; p < 0.05]), and preoperative nonuse of beta-adrenergic blockers (OR = 1.7; CI, 1.1 to 4.9; p < 0.05) were associated with increased risk for postoperative AF. Both, patients with and without AF had similar body mass index, preoperative heart rate, preoperative blood pressure, and duration of surgery. Male sex did not identify patients at high risk for development of AF after cardiac surgery. CONCLUSIONS: Postoperative AF remains the most common complication after cardiac surgery. A combination of advanced age and type of surgery identifies patients at high risk for development of AF after cardiac surgery.

Adult↗