Search PubMed⌕ Search

Biomedical subjects

C Singer

Publications and source records attributed to C Singer.

At least 19 recordsLinked to original sources
PubMed2006

Herbicide exposure modifies GSTP1 haplotype association to Parkinson onset age: the GenePD Study.

BACKGROUND: Polymorphisms in the glutathione S-transferase pi gene (GSTP1), encoding GSTP1-1, a detoxification enzyme, may increase the risk of Parkinson disease (PD) with exposure to pesticides. Using the GenePD Study sample of familial PD cases, we explored whether GSTP1 polymorphisms were associated with the age at onset of PD symptoms and whether that relation was modified by exposure to herbicides. METHODS: Seven single-nucleotide polymorphisms (SNPs) were genotyped and tested for association with PD onset age in men in three strata: no exposure to herbicides, residential exposure to herbicides, and occupational exposure to herbicides. Haplotypes were similarly evaluated in stratified analyses. RESULTS: Three SNPs were associated with PD onset age in the group of men occupationally exposed to herbicides. Three additional SNPs had significant trends for the association of PD onset age across the herbicide exposure groups. Haplotype results also provided evidence that the relation between GSTP1 and onset age is modified by herbicide exposure. One haplotype was associated with an approximately 8-years-earlier onset in the occupationally exposed group and a 2.8-years-later onset in the nonexposed group. CONCLUSIONS: Herbicide exposure may be an effect modifier of the relation between glutathione S-transferase pi gene polymorphisms and onset age in familial PD.

Disease Susceptibility↗
PubMed2006

Clinico-immunologic aspects of botulinum toxin type B treatment of cervical dystonia.

In this multicenter study of 100 patients with cervical dystonia, we examined the immunogenicity of botulinum toxin type B (BTX-B) and correlated the clinical response with the presence of blocking antibodies (Abs) using a novel mouse protection assay. One-third of the patients who were negative for BTX-B Abs at baseline became positive for BTX-B Abs at last visit. Thus, the high antigenicity of BTX-B limits its long-term efficacy.

Botulinum Toxins↗
PubMed2006

[Guideline conformance for outpatient management of COPD in Germany].

BACKGROUND AND OBJECTIVE: Primary care physicians (PCPs) are the ones mainly responsible for the initial diagnosis and outpatient care of patients with COPD. The aim of the present survey was to investigate their initial management of COPD in Germany based on current guidelines and to identify any deviations. METHODS: A prospective cross-sectional survey was conducted as a multiple-choice questionnaire sent out to 1836 PCPs in seven Federal States of Germany (one large town and surrounding country in each). The product-neutral questions focused on the key aspects of current national and international (GLOBAL) COPD guidelines. RESULTS: 486 physicians participated in the study (response rate 26.5%). 66.5% of the physicians used the German COPD guidelines, 20.8% used GOLD guidelines, and only 11.7% observed no guidelines. The physicians were aware of the epidemiological and public health significance of COPD. 76.5% saw spirometry as the diagnostic standard: it was available in 90.1% of the practices. However, only 60-65% were able to cite the correct spirometric criteria for classifying severity of the disease. Educational measures to help patients quit smoking and the teaching and monitoring of patients' inhalation technique were inadequately implemented. The two most important therapeutic goals cited were to improve quality of life (69.1%) and prevent exacerbations (53.1%). Except for the criteria for the use of steroids and the implementation of pulmonary rehabilitation measures, treatment of COPD based on severity class was largely in compliance with the guidelines. However, a significant percentage of the physicians incorrectly assessed the evidence-based clinical benefits of various therapeutic measures. CONCLUSION: The study shows that, despite the high regard in which COPD guidelines are held, deficiencies exist with regard to the diagnosis and treatment of COPD and the practical implementation of educational measures.

Adult↗
PubMed2006

Botulinum toxin A during pregnancy: a survey of treating physicians.

Botulinum toxin A (btxA) is widely used for cosmetic purposes, headaches, dystonia, spasticity, pain and other on and off label uses. Despite the widespread use of btxA in women of childbearing potential, there are few data on the effects of this drug on pregnant women and the fetus. The goal of this study was to survey physicians who use btxA, to determine their experience with pregnant women. We surveyed 900 physicians who used commercially available btxA. The questionnaire asked treating physicians if they had knowingly or unknowingly injected pregnant women and what was the outcome of each pregnancy. In total, 396 physicians (44%) returned questionnaires, of whom only 12 physicians reported injecting pregnant women with btxA. Sixteen pregnant women were injected, mostly in the first trimester, and only one patient, who had prior spontaneous abortions, suffered a miscarriage. Another woman had a therapeutic abortion. All other pregnancies went to term and there were no fetal malformations. Based on this limited survey of treating physicians in the USA, btxA appears to be relatively safe for both expectant mother and fetus. We need further data, however, and we would recommend that physicians and patients carefully consider the risks and benefits before using btxA in pregnant women.

Beauty↗
PubMed2005

BDNF genetic variants are associated with onset age of familial Parkinson disease: GenePD Study.

Brain-derived neurotrophic factor (BDNF) stimulates neuronal growth and protects nigral dopamine neurons in animal models of Parkinson disease (PD). Therefore, BDNF is a candidate gene for PD. The authors investigated five single-nucleotide polymorphisms in 597 cases of familial PD. Homozygosity for the rare allele of the functional BDNF G196A (Val66Met) variant was associated with a 5.3-year older onset age (p = 0.0001). These findings suggest that BDNF may influence PD onset age.

Age of Onset↗
PubMed2004

Chorea and contraceptives: case report with pet study and review of the literature.

Chorea is a well-recognized but rare complication of oral contraceptive use. A 27-year-old woman developed right hemichorea while taking an oral contraceptive (OC). No other causes of chorea were found. A positron emission tomography (PET) study with (18)F-fluorodeoxyglucose demonstrated a dense focus of increased glucose metabolism involving the body of the left caudate nucleus. To our knowledge, this is the first report of a PET study in a patient with OC-induced chorea in the absence of systemic lupus erythematosus or antiphospholipid antibodies.

Adult↗
PubMed2004

Genomic profiling of interpopulation diversity guides prioritization of candidate-genes for autoimmunity.

Autoimmune diseases seem to have strong genetic attributes, and are affected to some extent by shared susceptibility loci. The latter potentially amount to hundreds of candidate genes (CG), creating the need for a prioritization strategy in genetic association studies. To form such a strategy, 26 autoimmune-related CG were genotyped for a total of 72 single nucleotide polymorphisms (SNPs) in three distinct Israeli ethnic populations: Ashkenazi Jews, Sephardic Jews and Arabs. Four quantitative criteria reflecting population stratification were analyzed: allele frequencies, haplotype frequencies, the Fst statistic for homozygotes distribution and linkage disequilibrium extents. According to the consequent interpopulation genomic diversity profiles, the genes were classified into conserved, intermediate and diversified gene groups. Our results demonstrate a correlation between the biological role of autoimmune-related CG and their interpopulation diversity profiles as classified by the different analyses. Annotation analysis suggests that genes more readily influenced by environmental conditions, such as immunological mediators, are 'population specific'. Conversely, genes showing genetic conservation across all populations are characterized by apoptotic and cleaving functions. We suggest a research strategy by which CG association studies should focus first on likely conserved gene categories, to increase the likelihood of attaining significant results and promote the development of gene-based therapies.

Adult↗
PubMed2003

A haplotype at the PARK3 locus influences onset age for Parkinson's disease: the GenePD study.

OBJECTIVE: To identify a haplotype influencing onset age for Parkinson's disease (PD) in the PARK3 region on chromosome 2p13. METHODS: Single nucleotide polymorphisms (SNP) spanning 2.2 Mb and located in or near potential candidate genes were used to fine map the PARK3 region in 527 patients with familial PD, from 264 families. RESULTS: TT homozygotes for rs1876487 (G/T) had a 7.4-year younger mean age at onset (p = 0.005) compared to patients with GT and GG genotypes. Furthermore, SNP flanking the sepiapterin reductase (7,8-dihydrobiopterin: NADP+ oxidoreductase) (SPR) gene, rs1876487 (p = 0.02) and rs1150500 (p = 0.04), were associated with younger onset age among persons who did not carry the 174 allele of D2S1394. The SPR gene is implicated in dopamine synthesis. Haplotype analysis of three SNP-rs2421095, rs1876487, rs1561244-revealed an association with onset age (p = 0.023) and a haplotype of A-T-G alleles was associated with younger onset for PD (p = 0.005). CONCLUSIONS: A haplotype at the PARK3 locus, harboring the SPR gene, is associated with onset age of PD. This may suggest a role for the SPR gene in modifying the age at onset of PD.

Adolescent↗
PubMed2002

Epidemiologic study of 203 sibling pairs with Parkinson's disease: the GenePD study.

OBJECTIVE: To examine patterns of familial aggregation and factors influencing onset age in a sample of siblings with PD. METHODS: Sibling pairs (n = 203) with PD were collected as part of the GenePD study. Standardized family history, medical history, and risk factor data were collected and analyzed. RESULTS: The mean age at onset was 61.4 years and did not differ according to sex, exposure to coffee, alcohol, or pesticides. Head trauma was associated with younger onset (p = 0.03) and multivitamin use with later onset (p = 0.007). Age at onset correlation between sibling pairs was significant (r = 0.56, p = 0.001) and was larger than the correlation in year of onset (r = 0.29). The mean difference in onset age between siblings was 8.7 years (range, 0 to 30 years). Female sex was associated with increased frequency of relatives with PD. The frequency of affected parents (7.0%) and siblings (5.1%) was increased when compared with frequency in spouses (2.0%). CONCLUSIONS: The greater similarity for age at onset than for year of onset in sibling pairs with PD, together with increased risk for biological relatives over spouses of cases, supports a genetic component for PD. Risk to siblings in this series is increased over that seen in random series of PD cases; however, patients in this sample have similar ages at onset and sex distribution as seen for PD generally. These analyses suggest that factors influencing penetrance are critical to the understanding of this disease.

Age of Onset↗
PubMed2002

Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is an autosomal recessive neurological disorder whose characteristic features include hyperkinetic movements and abnormal red blood cell morphology. Mutations in the CHAC gene on 9q21 were recently found to cause chorea-acanthocytosis. CHAC encodes a large, novel protein with a yeast homologue implicated in protein sorting. In this study, all 73 exons plus flanking intronic sequence in CHAC were screened for mutations by denaturing high-performance liquid chromatography in 43 probands with ChAc. We identified 57 different mutations, 54 of which have not previously been reported, in 39 probands. The novel mutations comprise 15 nonsense, 22 insertion/deletion, 15 splice-site and two missense mutations and are distributed throughout the CHAC gene. Three mutations were found in multiple families within this or our previous study. The preponderance of mutations that are predicted to cause absence of gene product is consistent with the recessive inheritance of this disease. The high proportion of splice-site mutations found is probably a reflection of the large number of exons that comprise the CHAC gene. The CHAC protein product, chorein, appears to have a certain tolerance to amino-acid substitutions since only two out of nine substitutions described here appear to be pathogenic.

Chorea↗
PubMed2002

Endometrial nuclear receptor co-factors SRC-1 and N-CoR are increased in human endometrium during menstruation.

Steroid hormone receptor co-factors are abundantly expressed in the uterus in order to modify steroid hormone receptor action, either leading to activation or repression of transcription in the endometrium. However, the role of co-factors in remodelling of the human endometrium has not been established. We therefore endeavoured to evaluate the presence of the co-activator SRC (steroid receptor co-activator)-1 and the co-repressors N-CoR (nuclear receptor co-repressor) and steroid co-repressor SMRT (silencing mediator of retinod and thyroid) receptors in the human endometrium during the different phases of the menstrual cycle. By using a real-time RT-PCR assay, we showed that SRC-1, N-CoR and SMRT mRNA are expressed in human endometrium during all phases of the menstrual cycle, as well as in inactive endometrium. Moreover, endometrial expression of SRC-1 and N-CoR mRNA increased during menstruation when compared with the other phases of the menstrual cycle (P < 0.001). Immunohistochemistry demonstrated that SRC-1 and N-CoR stain positive in the glandular epithelium and stroma in menstrual phase endometrium. The staining was weak in proliferative and secretory endometrium and absent in inactive endometrium. Our results suggest that differential expression of endometrial steroid receptor co-factors probably play a role in the regulation of human endometrium remodelling.

DNA-Binding Proteins↗
PubMed2001

Genome-wide scan for Parkinson's disease: the GenePD Study.

A genome-wide scan for idiopathic PD in a sample of 113 PD-affected sibling pairs is reported. Suggestive evidence for linkage was found for chromosomes 1 (214 cM, lod = 1.20), 9 (136 cM, lod = 1.30), 10 (88 cM, lod = 1.07), and 16 (114 cM, lod = 0.93). The chromosome 9 region overlaps the genes for dopamine beta-hydroxylase and torsion dystonia. Although no strong evidence for linkage was found for any locus, these results may be of value in comparison with similar studies by others.

Aged↗
PubMed2001

Late-onset erythropoietic porphyria caused by a chromosome 18q deletion in erythroid cells.

The erythropoietic porphyrias, erythropoietic protoporphyria and congenital erythropoietic porphyria, result from germline mutations in the ferrochelatase gene and uroporphyrinogen III synthase gene, respectively. Both conditions normally present in childhood but rare cases with onset past the age of 40 y have been reported. Here we show that late-onset erythropoietic protoporphyria can be caused by deletion of the ferrochelatase gene in hematopoietic cells with clonal expansion as part of the myelodysplastic process. This is the first direct demonstration of porphyria produced by an acquired molecular defect restricted to one tissue. Some other cases of late-onset erythropoietic porphyria may be explained by a similar mechanism.

Age of Onset↗
PubMed2001

Diagnostics of neisseriaceae and moraxellaceae by ribosomal DNA sequencing: ribosomal differentiation of medical microorganisms.

Fast and reliable identification of microbial isolates is a fundamental goal of clinical microbiology. However, in the case of some fastidious gram-negative bacterial species, classical phenotype identification based on either metabolic, enzymatic, or serological methods is difficult, time-consuming, and/or inadequate. 16S or 23S ribosomal DNA (rDNA) bacterial sequencing will most often result in accurate speciation of isolates. Therefore, the objective of this study was to find a hypervariable rDNA stretch, flanked by strongly conserved regions, which is suitable for molecular species identification of members of the Neisseriaceae and Moraxellaceae. The inter- and intrageneric relationships were investigated using comparative sequence analysis of PCR-amplified partial 16S and 23S rDNAs from a total of 94 strains. When compared to the type species of the genera Acinetobacter, Moraxella, and Neisseria, an average of 30 polymorphic positions was observed within the partial 16S rDNA investigated (corresponding to Escherichia coli positions 54 to 510) for each species and an average of 11 polymorphic positions was observed within the 202 nucleotides of the 23S rDNA gene (positions 1400 to 1600). Neisseria macacae and Neisseria mucosa subsp. mucosa (ATCC 19696) had identical 16S and 23S rDNA sequences. Species clusters were heterogeneous in both genes in the case of Acinetobacter lwoffii, Moraxella lacunata, and N. mucosa. Neisseria meningitidis isolates failed to cluster only in the 23S rDNA subset. Our data showed that the 16S rDNA region is more suitable than the partial 23S rDNA for the molecular diagnosis of Neisseriaceae and Moraxellaceae and that a reference database should include more than one strain of each species. All sequence chromatograms and taxonomic and disease-related information are available as part of our ribosomal differentiation of medical microorganisms (RIDOM) web-based service (http://www.ridom.hygiene.uni-wuerzburg.de/). Users can submit a sequence and conduct a similarity search against the RIDOM reference database for microbial identification purposes.

DNA, Ribosomal↗