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1.
Eur J Prev Cardiol ; 19(1): 15-22, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21450615

ABSTRACT

BACKGROUND: Patients with pathological glucometabolism are at increased risk of recurrent cardiovascular events after acute coronary syndrome (ACS). The goal of this study was to investigate the association of glucometabolism and the one-year outcome of cardiac rehabilitation patients. DESIGN: Prospective multicentre registry from four German rehabilitation clinics. METHODS: During 2005-2006, 1614 consecutive patients (85.9% male, mean age 55 ± 10.3 years) were included after the first ACS (mean 18.9 days) and classified into group 1 (apparent diabetes mellitus, n = 268), group 2 (no diabetes, impaired oral glucose tolerance [OGT], n = 185), and group 3 (normal fasting glucose and normal OGT, n = 1161). The mean follow-up was 13.4 months and the follow-up events were analysed by multivariate logistic regression models with backward elimination. RESULTS: The overall mortality was 1.3% (group 1: 1.2%; group 2: 1.8%; group 3: 1.5%; p(Trend) = NS). The target blood pressure values at discharge (<140/90 mmHg) were achieved by 88.7%, 89.1% and 90.8% of patients in groups 1, 2 and 3, respectively (p(Trend) = NS). The target value for LDL cholesterol (<100 mg/dl) was attained by 87.0%, 80.8% and 81.5% of the patients in groups 1, 2 and 3, respectively (p(Trend) = NS). There was a trend of a lower proportion of patients reaching the target values for HDL-C of 46.1%, 51.4% and 60.8% (p(Trend) < 0.001) and triglycerides of 65.1%, 79.9% and 74.6% (p(Trend) = 0.004) for groups 1, 2 and 3, respectively. The strongest multivariate predictors for overall mortality were patients experiencing a previous stroke (OR, 6.29 [95% CI: 1.06-37.19]; p = 0.042) and, with a trend, peripheral arterial disease (OR, 3.60 [95% CI: 0.95-13.68]; p = 0.061). In the multivariate analysis, the diabetic state had no association with poor outcomes (i.e. death or rehospitalization). CONCLUSION: The short-term prognosis for both diabetic and non-diabetic patients was good and was determined by end organ damage rather than by glucometabolic status. Diabetic patients received comparable (and not more aggressive) pharmacotherapy and therefore achieved target values for cardiovascular risk factors to a lesser extent than the non-diabetic and pre-diabetic patients.


Subject(s)
Acute Coronary Syndrome/rehabilitation , Diabetes Mellitus, Type 2/complications , Glucose Intolerance/complications , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/mortality , Aged , Biomarkers/blood , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/mortality , Female , Germany/epidemiology , Glucose Intolerance/blood , Glucose Intolerance/mortality , Glucose Tolerance Test , Glycated Hemoglobin/metabolism , Humans , Lipids/blood , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Patient Discharge , Patient Readmission , Prospective Studies , Registries , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
2.
Bioorg Med Chem Lett ; 8(5): 499-504, 1998 Mar 03.
Article in English | MEDLINE | ID: mdl-9871606

ABSTRACT

HIV-1 reverse transcriptase (RT) incorporates 2'-deoxyisoguanosine triphosphate (d-isoGTP) opposite thymidine (T) in a DNA template and opposite uracil (U) in an RNA template about 10 times more efficiently than the eukaryotic DNA polymerase alpha, both in the absence and presence of dATP.


Subject(s)
DNA-Directed DNA Polymerase/metabolism , Guanosine/metabolism , HIV Reverse Transcriptase/metabolism , Adenosine , Base Sequence , DNA , Guanosine/chemistry , Substrate Specificity , Templates, Genetic
3.
Bioorg Med Chem Lett ; 8(10): 1149-52, 1998 May 19.
Article in English | MEDLINE | ID: mdl-9871725

ABSTRACT

Examination of several commercially available thermostable DNA polymerases identifies 9 degrees N DNA polymerase as single enzyme that could incorporate two components of an expanded genetic alphabet, 2,4-diaminopyrimidine and xanthosine as deoxynucleoside triphosphate opposite their cognate base in a DNA template.


Subject(s)
Base Pairing , DNA-Directed DNA Polymerase/chemistry , DNA-Directed DNA Polymerase/metabolism , Deoxyribonucleotides/chemical synthesis , Base Sequence , DNA Primers , Deoxyribonucleotides/metabolism , Enzyme Stability , Hydrogen Bonding , Pyrimidines , Pyrococcus/enzymology , Ribonucleosides , Substrate Specificity , Templates, Genetic , Thermodynamics , Thermus/enzymology , Xanthines
4.
Pure Appl Chem ; 70(2): 263-6, 1998 Feb.
Article in English | MEDLINE | ID: mdl-11542721

ABSTRACT

A research program has applied the tools of synthetic organic chemistry to systematically modify the structure of DNA and RNA oligonucleotides to learn more about the chemical principles underlying their ability to store and transmit genetic information. Oligonucleotides (as opposed to nucleosides) have long been overlooked by synthetic organic chemists as targets for structural modification. Synthetic chemistry has now yielded oligonucleotides with 12 replicatable letters, modified backbones, and new insight into why Nature chose the oligonucleotide structures that she did.


Subject(s)
DNA/chemistry , Molecular Biology/trends , Nucleic Acids/chemistry , Oligonucleotides/chemical synthesis , Catalysis , Codon , Molecular Structure , Nucleic Acids/chemical synthesis , Oligonucleotides/chemistry , Phosphates/chemistry , Sulfones/chemistry
5.
Proc Natl Acad Sci U S A ; 92(14): 6329-33, 1995 Jul 03.
Article in English | MEDLINE | ID: mdl-7541538

ABSTRACT

The ability of DNA polymerases (pols) to catalyze the template-directed synthesis of duplex oligonucleotides containing a nonstandard Watson-Crick base pair between a nucleotide bearing a 5-(2,4-diaminopyrimidine) heterocycle (d kappa) and a nucleotide bearing either deoxyxanthosine (dX) or N1-methyloxoformycin B (pi) has been investigated. The kappa-X and kappa-pi base pairs are jointed by a hydrogen bonding pattern different from and exclusive of those joining the AT and GC base pairs. Reverse transcriptase from human immunodeficiency virus type 1 (HIV-1) incorporates dXTP into an oligonucleotide opposite d kappa in a template with good fidelity. With lower efficiency and fidelity, HIV-1 reverse transcriptase also incorporates d kappa TP opposite dX in the template. With d pi in the template, no incorporation of d kappa TP was observed with HIV reverse transcriptase. The Klenow fragment of DNA pol I from Escherichia coli does not incorporate d kappa TP opposite dX in a template but does incorporate dXTP opposite d kappa. Bovine DNA pols alpha, beta, and epsilon accept neither dXTP opposite d kappa nor d kappa TP opposite d pi. DNA pols alpha and epsilon (but not beta) incorporate d kappa TP opposite dX in a template but discontinue elongation after incorporating a single additional base. These results are discussed in light of the crystal structure for pol beta and general considerations of how polymerases must interact with an incoming base pair to faithfully copy genetic information.


Subject(s)
DNA-Directed DNA Polymerase/metabolism , Deoxyribonucleosides , Formycins , Oligodeoxyribonucleotides/chemistry , Oligodeoxyribonucleotides/metabolism , Pyrimidine Nucleosides , RNA-Directed DNA Polymerase/metabolism , Base Composition , Base Sequence , DNA Polymerase I/metabolism , DNA Polymerase II/metabolism , Escherichia coli/enzymology , HIV Reverse Transcriptase , HIV-1/enzymology , Hydrogen Bonding , Molecular Sequence Data , Recombinant Proteins/metabolism , Structure-Activity Relationship , Templates, Genetic , Thymus Gland/enzymology
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