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Biomedical subjects

N von Ahsen

Publications and source records attributed to N von Ahsen.

At least 19 recordsLinked to original sources
PubMed2006

Homocysteine levels in aqueous humor and plasma of patients with primary open-angle glaucoma.

We determined homocysteine (Hcy) levels in aqueous humor (AH) and plasma and their association with B-vitamin levels in patients with primary open-angle glaucoma (POAG) and controls. Both AH Hcy and plasma Hcy levels were significantly increased in POAG, and elevation of AH Hcy and plasma Hcy was a significant risk factor for POAG. In contrast to controls, neither plasma nor AH Hcy of POAG patients demonstrated a significant association with important non-genetic determinants of elevated Hcy such as low B-vitamin levels, increasing age and caffeine consumption. Considering that Hcy is a neurotoxin that induces apoptotic retinal ganglion cell death via stimulation of the N-methyl-D-asparate (NMDA) receptor, increased Hcy concentrations in AH and plasma might contribute to the optic nerve damage in POAG.

Aged↗
PubMed2004

Serum S100beta increases in marathon runners reflect extracranial release rather than glial damage.

The contribution of extracranial tissue damage to serum S100beta increases was examined in 18 marathon runners without clinical or laboratory signs of brain damage. Postrace serum S100beta and creatine kinase (CK) concentrations increased (p < 0.001), and areas under the curve were highly correlated (p = 0.001). To conclude, serum S100beta increases after running originate from extracranial sources. CK determination may improve specificity of S100beta as a marker of brain tissue damage in acute trauma.

Adult↗
PubMed2004

CPAP-therapy effectively lowers serum homocysteine in obstructive sleep apnea syndrome.

Assessment of serum total homocysteine (tHcy) in patients with obstructive sleep apnea (OSA) syndrome is highly relevant since both are strongly associated with stroke and cognitive dysfunction. Seven of 16 untreated OSA patients showed tHcy levels exceeding 11.7 micromol/l. The circadian pattern of serum tHcy in untreated and treated patients (p < 0.001) implied a diagnostic impact of blood sampling time. Treatment with continuous positive airway pressure (CPAP) effectively lowered tHcy levels in patients by about 30% (p < 0.005) and thus probably the (hyper)homocysteinemia-related cognitive dysfunction and the risk for cardio-/cerebrovascular diseases.

Chromatography, High Pressure Liquid↗
PubMed2004

Erythropoietin: a candidate compound for neuroprotection in schizophrenia.

Erythropoietin (EPO) is a candidate compound for neuroprotection in human brain disease capable of combating a spectrum of pathophysiological processes operational during the progression of schizophrenic psychosis. The purpose of the present study was to prepare the ground for its application in a first neuroprotective add-on strategy in schizophrenia, aiming at improvement of cognitive brain function as well as prevention/slowing of degenerative processes. Using rodent studies, primary hippocampal neurons in culture, immunohistochemical analysis of human post-mortem brain tissue and nuclear imaging technology in man, we demonstrate that: (1) peripherally applied recombinant human (rh) EPO penetrates into the brain efficiently both in rat and humans, (2) rhEPO is enriched intracranially in healthy men and more distinctly in schizophrenic patients, (3) EPO receptors are densely expressed in hippocampus and cortex of schizophrenic subjects but distinctly less in controls, (4) rhEPO attenuates the haloperidol-induced neuronal death in vitro, and (4) peripherally administered rhEPO enhances cognitive functioning in mice in the context of an aversion task involving cortical and subcortical pathways presumably affected in schizophrenia. These observations, together with the known safety of rhEPO, render it an interesting compound for neuroprotective add-on strategies in schizophrenia and other human diseases characterized by a progressive decline in cognitive performance.

Adult↗
PubMed2004

MDR1 haplotypes modify BEN disease risk: a study in Bulgarian patients with Balkan endemic nephropathy compared to healthy controls.

BACKGROUND: Balkan endemic nephropathy (BEN) is a slow progressive nephropathy with frequent occurrence of uroepithelial tumors in the upper urinary tract. Genetic factors involved in xenobiotic detoxification mechanisms may cause genetic predisposition to BEN and influence the risk for this disease. Polymorphic MDR1 variants with decreased P-glycoprotein (P-gp) activity modulate the risk for renal neoplasm. We have therefore investigated the impact of MDR1 polymorphisms on BEN manifestation. METHODS: The constitutional genotype frequencies of two SNPs (C3435T and G2677T) in the MDR1 gene in 112 healthy control subjects were investigated and compared with those of 96 patients with BEN. Identification of the SNPs was done with rapid cycle real-time PCR and melting curve analysis with allele-specific probes. RESULTS: The frequency of mutant alleles was comparable in both groups. Significant differences were revealed when the MDR1 haplotypes were analyzed. Individuals with a predicted haplotype 12 (2677G/3435T) were less frequent in BEN cases (frequency 7.3%) than in controls (16.1%, p = 0.006). We found that carriers of the haplotype 12 had a decreased risk for BEN (OR = 0.411; 0.21-0.78). CONCLUSIONS: The data suggest that haplotype 12 is protective against BEN. There is no clear molecular explanation of the MDR1 haplotype effects on the protein activity, which can explain the modified effect of the haplotype 12 on BEN risk.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Homocysteine and risk of open-angle glaucoma.

Homocysteine levels and the frequency of heterozygous methylenetetrahydrofolate reductase (MTHFR) C677T mutation are increased in open-angle glaucoma. Since homocysteine can induce vascular injury, alterations in extracellular matrix remodelling, and neuronal cell death, these findings may have important implications for understanding glaucomatous optic neuropathy.

Adult↗
PubMed2002

Analysis of two common alpha 1-antitrypsin deficiency alleles (PI*Z and PI*S) in subjects with periodontitis.

BACKGROUND: pi alpha 1-Antitrypsin deficiency is a genetically determined condition resulting in predisposition to certain inflammatory diseases due to a protease: antiprotease imbalance that is exacerbated by tobacco smoking. Limited evidence suggests that there may be a significant enrichment of mild alpha 1-antitrypsin deficiency phenotypes in subjects with chronic inflammatory periodontal disease. OBJECTIVE: To examine the prevalence of two common alpha1-antitrypsin deficiency alleles (PI*Z and PI*S) in a UK population of subjects with periodontitis. SUBJECTS AND METHODS: The prevalence of PI*M, PI*S and PI*Z allele combinations was determined in 31 subjects with periodontitis and compared with 31 healthy control subjects matched for smoking status, ethnicity, age and gender. alpha 1-Antitrypsin genotyping was performed by multiplex real-time fluorescence polymerase chain reaction (PCR) using DNA extracted from whole blood. RESULTS: There was no difference in the proportion of any alpha 1-antitrypsin genotype found in the diseased and control populations. CONCLUSIONS: We did not find evidence to support an association between mutant PI* alleles and periodontitis in a small, controlled study. Larger studies will be required to clarify the relationship between alpha1-antitrypsin genotype and susceptibility to inflammatory periodontal disease.

Adult↗
PubMed2001

Role of the astrocytic ET(B) receptor in the regulation of extracellular endothelin-1 during hypoxia.

Astrocytes are known to possess an effective endothelin (ET) eliminatory system which involves astrocytic ET(A) and ET(B) receptors and may become particularly relevant under pathophysiological conditions. The present study has therefore been designed to explore the effect of standardized hypoxia on extracellular concentrations of endothelin-1 (ET-1) and on endothelin-converting enzyme (ECE) activity in primary rat astrocytes genetically (sl/sl) or experimentally (dexamethasone) deficient in ET(B) receptors. The results revealed (1) a hypoxia-mediated decrease of extracellular ET-1 in wildtype astrocytes (+/+) that was not observed in ET(B)-deficient (sl/sl) cultures; (2) an ET receptor antagonist-induced increase in ET-1 in the media of both genotypes with further elevation upon hypoxia in +/+ cultures only; (3) augmentation of the dexamethasone-induced increase in extracellular ET-1 by hypoxia in +/+, but not in sl/sl cultures; (4) synergistic reduction of ET(B) gene transcription by hypoxia and dexamethasone; and (5) significant increases in endothelin-converting enzyme activity in the presence of hypoxia. To conclude, hypoxia stimulates astrocytic release of mature ET-1. This stimulation is (over)compensated for by increased ET-1 binding to functional ET(B) receptors. ET(B) deficiency, whether genetic or experimentally induced, impairs elimination of extracellular ET-1.

Animals↗
PubMed2001

No influence of the MDR-1 C3435T polymorphism or a CYP3A4 promoter polymorphism (CYP3A4-V allele) on dose-adjusted cyclosporin A trough concentrations or rejection incidence in stable renal transplant recipients.

BACKGROUND: A substantial proportion of the variability in the absorption and clearance of cyclosporin A (CsA) after oral administration has been attributed to variability in liver cytochrome P-450 3A4 (CYP3A4) activity and intestinal P-glycoprotein (P-gp) concentration. A polymorphism in the CYP3A4 promoter region, termed "variant" allele CYP3A4-V, was postulated to be associated with altered CYP3A4 enzyme activity. A polymorphism in exon 26 (C3435T) of the multidrug resistance-1 (MDR-1) gene was correlated with intestinal expression and in vivo activity of P-gp. METHODS: We investigated the occurrence of both polymorphisms in 124 stable Caucasian renal transplant recipients (>6 months after transplantation) on CsA as the primary immunosuppressant. Real-time, rapid-cycle PCR methods were developed and used for genotyping. RESULTS: The estimated allele frequencies for the MDR-1 C3435T allele (54%) and the CYP3A4-V allele (4.8%) were similar to those reported for Caucasian populations. No significant differences were found for the CsA doses needed to maintain similar CsA trough concentrations in patients with and without the CYP3A4-V allele or in patients with different MDR-1 C3435T genotypes. Furthermore, neither of the polymorphisms investigated was associated with renal function as assessed by creatinine plasma concentration or, in a retrospective analysis, the incidence of acute rejection. CONCLUSIONS: These findings suggest that the MDR-1 C3435T mutation and the CYP3A4-V variant are not major determinants of CsA efficacy in renal transplant recipients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Oligonucleotide melting temperatures under PCR conditions: nearest-neighbor corrections for Mg(2+), deoxynucleotide triphosphate, and dimethyl sulfoxide concentrations with comparison to alternative empirical formulas.

BACKGROUND: Many techniques in molecular biology depend on the oligonucleotide melting temperature (T(m)), and several formulas have been developed to estimate T(m). Nearest-neighbor (N-N) models provide the highest accuracy for T(m) prediction, but it is not clear how to adjust these models for the effects of reagents commonly used in PCR, such as Mg(2+), deoxynucleotide triphosphates (dNTPs), and dimethyl sulfoxide (DMSO). METHODS: The experimental T(m)s of 475 matched or mismatched target/probe duplexes were obtained in our laboratories or were compiled from the literature based on studies using the same real-time PCR platform. This data set was used to evaluate the contributions of [Mg(2+)], [dNTPs], and [DMSO] in N-N calculations. In addition, best-fit coefficients for common empirical formulas based on GC content, length, and the equivalent sodium ion concentration of cations [Na(+)(eq)] were obtained by multiple regression. RESULTS: When we used [Na(+)(eq)] = [Monovalent cations] + 120(square root of ([Mg2+]-[dNTPs])) (the concentrations in this formula are mmol/L) to correct DeltaS(0) and a DMSO term of 0.75 degrees C (%DMSO), the SE of the N-N T(m) estimate was 1.76 degrees C for perfectly matched duplexes (n = 217). Alternatively, the empirical formula T(m) ( degrees C) = 77.1 degrees C + 11.7 x log[Na(+)(eq)] + 0.41(%GC) - 528/bp - 0.75 degrees C(%DMSO) gave a slightly higher SE of 1.87 degrees C. When all duplexes (matched and mismatched; n = 475) were included in N-N calculations, the SE was 2.06 degrees C. CONCLUSIONS: This robust model, accounting for the effects of Mg(2+), DMSO, and dNTPs on oligonucleotide T(m) in PCR, gives reliable T(m) predictions using thermodynamic N-N calculations or empirical formulas.

Cations, Divalent↗
PubMed2000

Prothrombin activity and concentration in healthy subjects with and without the prothrombin G20210A mutation.

A common mutation in the prothrombin gene (G20210A) is associated with elevated prothrombin levels and thrombosis. The pathomechanism related to the G20210A mutation is currently not understood and the interdependence of prothrombin activity and prothrombin concentration in plasma is still poorly defined. Six of 191 blood donors examined in the present study carried the prothrombin allele G20210A. Despite the small number of cases, plasma samples from these individuals had significantly higher prothrombin activities than wild type carriers, whereas their prothrombin concentrations-although elevated-did not differ significantly from wild type. In subjects with the G20210A mutation there was also no significant correlation between prothrombin activity and concentration. Analyzing data from healthy blood donors without the prothrombin G20210A mutation, we found only weak correlations between prothrombin activity and concentration of immunoreactive prothrombin. Samples with a relatively high prothrombin concentration but low activity were observed as well as samples with a relatively high activity for a given concentration (hyperactive prothrombin). F1+2 concentrations as indicators of activated coagulation were only elevated in 13 of 125 investigated samples and could not explain any of these findings. Dysfunctional variants of prothrombin, a well known phenomenon, may be responsible for the former, and we speculate that posttranscriptionally modified prothrombin species may explain the observed functional diversity of this factor including hyperactivity. The genotype-phenotype association of the non-coding G20210A mutation is not clear cut. Therefore, further studies are needed to determine which factors apart from the known G20210A polymorphism regulate prothrombin concentration and/or activity and may trigger the manifestation of thrombosis.

Adult↗
PubMed2000

Plasma homocysteine is a predictor of alcohol withdrawal seizures.

An adaptive consequence of prolonged ethanol consumption is a compensatory up-regulation of NMDA receptors in certain brain areas. Taking into account that homocysteine and its breakdown products (i.e. homocysteic acid) are putative neurotransmitters and agonists at the NMDA receptor, the aim of this study was to assess the influence of levels of homocysteine on alcohol withdrawal seizures. Six patients with chronic alcoholism who suffered from withdrawal seizures had significantly higher levels of homocysteine on admission (84.7 +/- 29.8 micromol/l) than patients (n = 26) who did not develop seizures (30.2 +/- 23.2 micromol/l; U = 8.0, p = 0.0007). Furthermore, seizure patients had significantly lower levels of folate and significantly higher blood alcohol concentrations. Using a logistic regression analysis, withdrawal seizures were best predicted by a high homocysteine level on admission (p < 0.01; odds ratio = 1.05). Homocysteine levels on admission may be a useful screening method to identify patients at risk for withdrawal seizures.

Adult↗
PubMed2000

A method for homogeneous color-compensated genotyping of factor V (G1691A) and methylenetetrahydrofolate reductase (C677T) mutations using real-time multiplex fluorescence PCR.

OBJECTIVES: To set up an optimized multiplex polymerase chain reaction for real-time genotyping of the prothrombotic risk factors methylenetetrahydrofolate reductase C677T and factor V Leiden on the LightCycler. DESIGN AND METHODS: Novel primer and probe sets were designed on the basis of thermodynamic double-strand DNA stability calculations. Detection probes were labeled with LC-Red640 or Cy5.5 dye. RESULTS: The polymerase chain reaction efficiency was reduced in multiplex polymerase chain reaction but this could be overcome by the design of novel amplification primers. The selection of detection probes with a lower melting temperature (T(m)) and high Delta T(m) improved the discrimination of heterozygous samples. Color compensation was not compromised by either the use of the Cy5.5 dye or different fluorescein linker chemistries. CONCLUSIONS: Probes with a Delta T(m) of 5 degrees C or more between the matched and mismatched state are desirably for genotyping. Such probes can be selected by using a priori calculations based on the thermodynamic nearest neighbor model.

DNA Mutational Analysis↗
PubMed2000

Use of two reporter dyes without interference in a single-tube rapid-cycle PCR: alpha(1)-antitrypsin genotyping by multiplex real-time fluorescence PCR with the LightCycler.

BACKGROUND: alpha(1)-Antitrypsin is the major plasma serine protease inhibitor. Its deficiency is mainly associated with the alleles PI*S and PI*Z and can lead to obstructive lung disease in adults and to liver cirrhosis during childhood. METHODS: A multiplex PCR method has been established that uses two sets of primers to amplify the gene regions covering the PI*S or PI*Z mutations sites. Mutation detection was performed on the LightCycler by melting curve analysis of detection probes labeled with two different fluorescent dyes, LC-Red640 and LC-Red705. RESULTS: Unequivocal genotyping results were obtained for all investigated samples in an assay time of approximately 30 min. The color compensation procedure greatly improved the readability of the resulting diagnostic melting curves. CONCLUSIONS: To our knowledge, this is the first report of simultaneous detection of two mutations in a single tube by PCR of genomic DNA and the use of two different reporter dyes with the LightCycler color compensation feature. This approach is a rapid, convenient, and economic alternative to other methods described to date for the detection of alpha(1)-antitrypsin deficiency alleles.

DNA↗