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Biomedical subjects

T Kurth

Publications and source records attributed to T Kurth.

At least 19 recordsLinked to original sources
PubMed2006

Characteristics and antecedents of progressive multifocal leukoencephalopathy in an insured population.

Based on health insurance claims from a large U.S. health insurer, the authors identified 44 progressive multifocal leukoencephalopathy (PML) cases from 2002 through 2004 and described their characteristics, including antecedent diagnoses and treatments as well as survival. Immunosuppressive conditions such as HIV/AIDS, rather than potentially immunosuppressive treatments, were the main antecedents of PML. A lower mortality was observed among PML patients whose antecedent diagnosis was HIV/AIDS, the majority of whom received highly active antiretroviral therapy.

Adolescent↗
PubMed2006

Blood pressure measures and risk of total, ischemic, and hemorrhagic stroke in men.

OBJECTIVE: To evaluate which blood pressure measure is the best predictor of risk of total, ischemic, and hemorrhagic stroke. METHODS: The authors used a prospective cohort study among 11,466 men followed for incident stroke during a median of 19.4 years in the Physicians' Health Study. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were self-reported. They calculated relative risks (RRs) and 95% CIs for total, ischemic, and hemorrhagic stroke using Cox proportional hazards models. Model fit was compared using the chi(2) test statistic from likelihood ratio tests. RESULTS: During follow-up, 508 strokes occurred (411 ischemic, 89 hemorrhagic, and eight of unknown etiology). For each 10-mm Hg increase in SBP, the multivariable RRs were 1.31 (95% CI: 1.20 to 1.42) for total stroke, 1.28 (95% CI: 1.16 to 1.40) for ischemic stroke, and 1.38 (95% CI: 1.13 to 1.68) for hemorrhagic stroke. Although DBP, pulse pressure, and mean arterial pressure were all significant predictors of stroke risk, none was a significantly better predictor than SBP alone. Adding DBP did not significantly improve the model fit of SBP alone for any stroke type. CONCLUSION: In this large cohort of initially healthy men, systolic blood pressure was a consistent and significant predictor of total, ischemic, and hemorrhagic stroke. Systolic blood pressure alone was the only measure necessary to predict risk of total stroke or its major subtypes.

Adult↗
PubMed2006

Cluster headache is associated with the G1246A polymorphism in the hypocretin receptor 2 gene.

The G1246A polymorphism in the gene of the hypocretin receptor 2 (HCRTR2) has been linked to the risk for cluster headache (CH). The authors examined this association in a large sample of 226 patients with CH and 266 controls from Germany. The genotype and allele distribution varied significantly between patients and controls. Homozygous carriers of the G-allele had a twofold increase in risk for CH (OR 1.97; 95% CI 1.32 to 2.92; p = 0.0007).

Adult↗
PubMed2006

Prevalence of unexplained upper abdominal symptoms in patients with migraine.

Patients with functional gastrointestinal disorders frequently report migraine. We aimed to determine the prevalence of idiopathic upper abdominal symptoms in patients with migraine and compare it with a control population of healthy blood donors. We assessed abdominal symptoms using the Bowel Disease Questionnaire in a series of 488 consecutive blood donors without migraine and 99 patients with migraine. Upper abdominal symptoms were reported by 38%[95% confidence interval (CI) 32, 44] of blood donors compared with 81% (67, 91, P<0.001) of migraine patients. Of the blood donors, 23% (18, 28) reported frequent dyspepsia compared with 60% (44, 74, P<0.001) of the migraine patients. Migraine was associated with frequent upper abdominal symptoms (odds ratio 2.7, 95% CI 1.2, 6.1) after adjusting for age, gender, smoking and consumption of analgesics and alcohol. Upper abdominal symptoms are significantly more frequent in patients with migraine compared with healthy controls. The association between migraine and idiopathic upper abdominal symptoms may suggest common pathophysiological mechanisms.

Adult↗
PubMed2006

Predictors of hazardous alcohol consumption among patients with cluster headache.

The purpose of this study was to identify predictors of hazardous alcohol consumption in patients with cluster headache (CH). We investigated 246 German CH patients with the Alcohol Use Disorders Identification Test (AUDIT). The average daily alcohol consumption was 6.5 g. Predictors for hazardous drinking (AUDIT>or=5 points; 21.5% of patients) were male gender [odds ratio (OR) 4.15, 95% confidence interval (CI) 1.35, 12.71], episodic as opposed to chronic CH (OR 4.8, 95% CI 1.38, 16.67) and a low demanding job as opposed to a high demanding job (OR 2.28, 95% CI 1.15, 4.51). Our data indicate that CH patients drink less alcohol compared with the German population and that CH seems to protect against hazardous alcohol consumption. Moreover, predictors for hazardous alcohol consumption in CH patients are not different from the general population.

Adult↗
PubMed2006

Polymorphisms of prostaglandin-endoperoxide synthase 2 gene, and prostaglandin-E receptor 2 gene, C-reactive protein concentrations and risk of atherothrombosis: a nested case-control approach.

OBJECTIVE: Recent data have shown an association between polymorphisms of prostaglandin-endoperoxide synthase-2 gene (PTGS2; alias COX-2), and prostaglandin-E receptor-2 gene (PTGER2) and risk of atherothrombotic disorders. METHODS: We evaluated two PTGS2 (rs20417, rs689470), and three PTGER2 (rs708494/uS5, rs708495/uS7, and chr14: 50 764 013/uS10) gene polymorphisms among 600 Caucasian male participants of the Physicians' Health Study with incident myocardial infarction (MI) or ischemic stroke and 600 age- and smoking-matched controls who remained free of all reported cardiovascular disease. RESULTS: Genotype distributions were in Hardy-Weinberg equilibrium in the control groups. Genotype and allele distribution were similar between cases and controls. The polymorphisms tested were in linkage disequilibrium. Results from the adjusted haplotype-based conditional logistic regression analysis showed a modest association of the PTGER2 2-1-1 haplotype with reduced risk of MI (odds ratio = 0.50, 95% CI; CI = 0.26-0.97, P = 0.04), and the 2-2-1 haplotype with reduced risk of ischemic stroke (odds ratio = 0.68, 95% CI = 0.47-0.99, P = 0.048). In contrast to prior data, we found no evidence for an association of the PTGS2 polymorphisms/haplotypes tested with risk of incident MI nor with ischemic stroke. However, we found suggestive evidence for an association of specific PTGER2 haplotypes with reduced risk of these outcomes. CONCLUSION: Although these prospective data implicate the potential involvement of prostaglandin-E receptor-2 gene variation in atherothrombosis, external validation of our findings is needed.

Adult↗
PubMed2005

Migraine, headache, and the risk of stroke in women: a prospective study.

BACKGROUND: Migraine and headache in general have been associated with subsequent risk of stroke, primarily in retrospective case-control studies. Prospective data evaluating the association between specific headache forms and stroke are sparse. METHODS: A prospective cohort study was conducted among 39,754 US health professionals age 45 and older participating in the Women's Health Study with an average follow-up of 9 years. Incident stroke was self-reported and confirmed by medical record review. RESULTS: A total of 385 strokes (309 ischemic, 72 hemorrhagic, and 4 undefined) occurred. Compared with nonmigraineurs, participants who reported migraine overall or migraine without aura had no increased risk of any stroke type. Participants who reported migraine with aura had increased adjusted hazards ratios (HRs) of 1.53 (95% CI 1.02 to 2.31) for total stroke and 1.71 (95% CI 1.11 to 2.66) for ischemic stroke but no increased risk for hemorrhagic stroke. Participants with migraine with aura who were <55 years old had a greater increase in risk of total (HR 1.75; 95% CI 1.02 to 3.00) and ischemic (HR 2.25; 95% CI 1.30 to 3.91) stroke. Compared with participants without headache, headache in general and nonmigraine headache were not associated with total, ischemic, or hemorrhagic stroke. CONCLUSIONS: In these prospective data, migraine was not associated with total, ischemic, or hemorrhagic stroke. In subgroup analyses, we found increased risks of total and ischemic stroke for migraineurs with aura. The absolute risk increase was, however, low, with 3.8 additional cases per year per 10,000 women.

Brain↗
PubMed2005

[The reliability of the german version of the barthel-index and the development of a postal and telephone version for the application on stroke patients].

BACKGROUND AND PURPOSES: Aim of the study was to translate the original version of the Barthel-Index (BI) into German and to investigate the reliability of the German version. In addition, a German version of the BI for postal and telephone use was developed. METHODS: Data were collected in four neurological hospitals in Germany. The translation of the BI followed the protocol of the Medical Outcomes Trust. The interrater reliability of the German version of the BI was investigated in 72 patients after acute stroke. The reliability of the postal and telephone version of the BI was compared with face-to-face interview in 147 patients three months after stroke. Reliability was assessed using simple weighted kappa-statistics. RESULTS: The interrater reliability of the German version of the BI was excellent (mean kappa 0.93). The mean kappa coefficient was 0.79 for the postal version of the BI and 0.80 for the telephone version. Thus, the agreement between the postal and the telephone administration of the BI compared to the face-to-face interview was substantial to excellent. CONCLUSIONS: Our study published the first German version of the BI which was investigated for interrater reliability in a standardized way. The development of a postal and a telephone version allows the widespread use of the German BI for the follow up of stroke patients in different access paths.

Acute Disease↗
PubMed2004

Incidence and predictors for chronicity of headache in patients with episodic migraine.

The authors followed 532 consecutive patients with episodic migraine (<15 days/month) for 1 year. Sixty-four patients (14%) developed chronic headache (>/=15 days/month). The odds ratios for developing CH were 20.1 (95% CI 5.7 to 71.5) comparing patients with a "critical" (10 to 14 days/month) vs "low" (0 to 4 days/month) and 6.2 (95% CI 1.7 to 26.6) in patients with an "intermediate" (6 to 9 days/month) vs "low" headache frequency and 19.4 (95% CI 8.7 to 43.2) comparing patients with and without medication overuse.

Adult↗
PubMed2000

Tight junction biogenesis in the early Xenopus embryo.

Tight junctions (TJs) perform a critical role in the transport functions and morphogenetic activity of the primary epithelium formed during Xenopus cleavage. Biogenesis of these junctions was studied by immunolocalization of TJ-associated proteins (cingulin, ZO-1 and occludin) and by an in vivo biotin diffusion assay. Using fertilized eggs synchronized during the first division cycle, we found that membrane assembly of the TJ initiated at the animal pole towards the end of zygote cytokinesis and involved sequential incorporation of components in the order cingulin, ZO-1 and occludin. The three constituents appeared to be recruited from maternal stores and were targeted to the nascent TJ site by different pathways. TJ protein assembly was focused precisely to the border between the oolemma-derived apical membrane and newly-inserted basolateral membrane generated during cytokinesis and culminated in the formation of functional TJs in the two-cell embryo, which maintained a diffusion barrier. New membrane formation and the generation of cell surface polarity therefore precede initiation of TJ formation. Moreover, assembly of TJ marker protein precisely at the apical-basolateral membrane boundary was preserved in the complete absence of intercellular contacts and adhesion. Thus, the mechanism of TJ biogenesis in the Xenopus early embryo relies on intrinsic cues of a cell autonomous mechanism. These data reveal a distinction between Xenopus and mammalian early embryos in the origin and mechanisms of epithelial cell polarization and TJ formation during cleavage of the egg.

Animals↗
PubMed2000

Bottle cell formation in relation to mesodermal patterning in the Xenopus embryo.

The appearance of bottle cells at the dorsal vegetal/marginal boundary of Xenopus embryos marks the onset of blastopore formation. The conditions leading to this epithelial activity were investigated by inducing bottle cells ectopically in the animal region with VegT or different members of the transforming growth factor (TGF)-beta family. Morphological studies on the ectopic bottle cells indicate their close similarity to the endogenous bottle cells at the dorsal blastopore lip. The subepithelial cells of the induced animal region express mesodermal genes in a pattern reminiscent to that observed on the dorsal lip. Relating this expression pattern to the position of the ectopic bottle cells leads to the conclusion that bottle cells form in regions of high TGF-beta signalling. The specific inhibitory effects of cerberus on ectopically induced bottle cells revealed that nodal related growth factors are the intrinsic signals that elicit bottle cell formation in the normal embryo. In addition, fibroblast growth factor signalling is an essential precondition for this epithelial response as it is for mesoderm formation. We conclude that bottle cell formation in the epithelial layer of the gastrula is closely linked to mesodermal patterning in the subepithelial tissues.

Activins↗
PubMed2000

Tubulointerstitial injury and loss of nitric oxide synthases parallel the development of hypertension in the Dahl-SS rat.

OBJECTIVE: Alterations in renal nitric oxide (NO) are involved in the hypertension of the Dahl salt-sensitive (Dahl-SS) rat We sought to identify the kinetics and sites of expression of the major NO synthase (NOS) isoforms. DESIGN: The renal expression of the major NOS were examined in Dahl-SS and salt-resistant rats (Dahl-SR) while on a low salt (0.1% NaCl) diet at 3 and 9 weeks of age. METHODS: Renal biopsies from Dahl-SS and Dahl-SR rats were compared for evidence of renal injury and for alterations in expression of the NOS enzymes by quantitative immunohistochemistry. RESULTS: At 3 weeks of age Dahl-SS and Dahl-SR rats have normal renal histology and similar immunohistochemical expression of NOS1, -2, and -3. At 9 weeks Dahl-SS rats had significantly higher blood pressure than Dahl-SR rats (P< 0.005 ), and lower macula densa NOS1 (P< 0.05) and cortical and medullary NOS3 (P< 0.05). NOS2 was reduced in cortical tubules in biopsies showing severe tubulointerstitial damage, but was not significantly different between Dahl-SS and Dahl-SR groups as a whole. Dahl-SS rats also manifested glomerular and tubulointerstitial injury. Tubular expression of osteopontin (OPN), which is an inhibitor of NOS2, correlated with the systolic BP in individual Dahl-SS rats (r2 = 0.80, P < 0.0001 ). CONCLUSION: Tubulointerstitial injury and the loss of NOS occur after birth and parallel the development of hypertension. We suggest that the structural and functional changes that occur with renal injury in the Dahl-SS rat may contribute to the development of hypertension.

Animals↗
PubMed1999

S' subsite mapping of serine proteases based on fluorescence resonance energy transfer.

A microassay based on fluorescence resonance energy transfer has been developed to determine the S' specificity of serine proteases. The protease-catalyzed acyl transfer from a fluorescing acyl donor ester to a P'1/P'2 variable hexapeptide library of nucleophiles labeled with a fluorescence quencher leads to an internally quenched peptide product and a fluorescent hydrolysis product. The amount of fluorescence quenching allows one to draw conclusions about the interaction of the nucleophile at the S' sites of the protease. o-Aminobenzoic acid and 3-nitrotyrosine were used as an efficient donor-acceptor pair for the resonance energy transfer. The P'1/P'2 variable hexapeptide library with the general structure H-Xaa-Ala-Ala-Ala-Tyr(NO2)-Gly-OH and H-Ala-Xaa-Ala-Ala-Tyr(NO2)-Gly-OH, where Xaa represents Arg, Lys, Met, Phe, Ala, Gly, Ser, Gln and Glu, was prepared by solid-phase synthesis. Investigations of the S' specificity of trypsin, chymotrypsin and trypsin variants show that this assay is a fast and sensitive screening method for S' subsite mapping of serine proteases and is suitable for a high throughput screening. The assay might be useful for the development of restriction proteases and the estimation of yields in enzymatic peptide synthesis.

Binding Sites↗
PubMed1999

Domains of axin involved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization.

Axin was identified as a regulator of embryonic axis induction in vertebrates that inhibits the Wnt signal transduction pathway. Epistasis experiments in frog embryos indicated that Axin functioned downstream of glycogen synthase kinase 3beta (GSK3beta) and upstream of beta-catenin, and subsequent studies showed that Axin is part of a complex including these two proteins and adenomatous polyposis coli (APC). Here, we examine the role of different Axin domains in the effects on axis formation and beta-catenin levels. We find that the regulators of G-protein signaling domain (major APC-binding site) and GSK3beta-binding site are required, whereas the COOH-terminal sequences, including a protein phosphatase 2A binding site and the DIX domain, are not essential. Some forms of Axin lacking the beta-catenin binding site can still interact indirectly with beta-catenin and regulate beta-catenin levels and axis formation. Thus in normal embryonic cells, interaction with APC and GSK3beta is critical for the ability of Axin to regulate signaling via beta-catenin. Myc-tagged Axin is localized in a characteristic pattern of intracellular spots as well as at the plasma membrane. NH2-terminal sequences were required for targeting to either of these sites, whereas COOH-terminal sequences increased localization at the spots. Coexpression of hemagglutinin-tagged Dishevelled (Dsh) revealed strong colocalization with Axin, suggesting that Dsh can interact with the Axin/APC/GSK3/beta-catenin complex, and may thus modulate its activity.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Immunocytochemical studies of the interactions of cadherins and catenins in the early Xenopus embryo.

Linkage of cadherins to the cytoskeleton is crucial for their adhesive function. Since alpha- and beta-catenin play a key role in this linkage, these proteins are possible targets for processes that control cell-cell adhesion. To achieve a better understanding of the regulation of cell-cell adhesion in embryonic morphogenesis, we used immunohistology to investigate how in Xenopus blastomeres catenins respond to disturbances in the expression of maternal cadherins. Overexpression of myc-tagged maternal cadherin leads to a proportionate increase of the level of beta-catenin. The two proteins colocalize in the endoplasmic reticulum, in cytoplasmic vesicles, and along the cell membrane, indicating that the beta-catenin binds to overexpressed cadherin early in its passage to the plasma membrane. Expression of cadherin is essential for the stable presence of beta-catenin, as depletion from maternal cadherin mRNA leads to a complete loss of beta-catenin from the blastomeres. alpha-Catenin behaves differently. Overexpression of cadherin leaves the amount and localization of alpha-catenin largely unaffected, and additional cadherin inserts itself into the membrane without a proportionate rise in the level of membrane-bound alpha-catenin. However, cadherin mRNA depletion leads to a redistribution of alpha-catenin from the membrane to the cytoplasm. Thus, cadherin is required to localize alpha-catenin to the membrane, but the amount of alpha-catenin along the membrane seems to be restricted to a certain level which cannot be exceeded. The relevance of these observations for the regulation of cadherin-mediated cell adhesion in the Xenopus embryo is discussed. Additionally, we demonstrate that plakoglobin, like beta-catenin an armadillo repeat protein, shows neither accumulation after overexpression nor colocalization with the overexpressed cadherin.

Animals↗
PubMed1999

[Secondary prevention of ischemic infarct].

Secondary prevention of transient or permanent cerebral ischemia is performed with antiplatelet drugs, e.g. aspirin, ticlopidine, clopidogrel or dipyridamole. The four substances have different indications and different side effect profiles. Patients with proven or suspected cardiac source of embolism are treated with anticoagulants. Patients with > 70% stenosis of the internal carotid artery and TIA or minor stroke receive carotid endarterectomy in combination with aspirin. Stroke risk is reduced between 20 and 65% by these measures.

Anticoagulants↗
PubMed1998

Engineering the S1' subsite of trypsin: design of a protease which cleaves between dibasic residues.

The serine protease trypsin was converted into a site-specific protease which hydrolyzes peptides between dibasic residues. Trypsin exhibits a high S1 specificity for Arg and Lys residues. However, the S1' specificity of trypsin is very broad, with only a slight preference for hydrophobic residues in P1'. We replaced Lys60 with Glu and Asp to introduce a high specificity for basic residues into the S1' site of trypsin. Both mutations cause a dramatic increase in the S1' specificity for Arg and Lys as measured by acyl transfer reactions. In K60E, the preference for Arg increases 70-fold while the preference for P1'-Lys increases 12-fold. In contrast, the preferences for other P1' residues either decrease slightly or remain the same. Thus, K60E prefers P1'-Arg over most other P1' residues by 2 orders of magnitude. Similar results are obtained when P1' specificity is measured in peptide cleavage assays. K60D exhibits an S1' specificity profile very similar to that of K60E, although the P1'-Arg preference is reduced by a factor of 2.5. Molecular modeling studies suggest that the high S1' specificity for Arg in K60E may be due to the formation of a salt bridge between Glu60 and the P1'-Arg of the substrate.

Amino Acids, Diamino↗