PubMed Health⌕ Search

Biomedical subjects

Andreas Ziegler

Publications and source records attributed to Andreas Ziegler.

At least 19 recordsLinked to original sources
PubMed2003

Midterm results of the Ross procedure preserving the patient's aortic root.

BACKGROUND: Since the early 1990s, the pulmonary autograft is predominantly implanted as a freestanding root for less aortic valve regurgitation is reported. However, there is a certain risk of dilatation of the root over time potentially impairing valve function. We favor since 8 years the original subcoronary or inclusion technique to preserve the root of the patient as a restrain to dilatation. METHODS AND RESULTS: Between June 1994 and May 2002 the subcoronary (n=228) and inclusion technique (n=17) were performed in 245 patients (191 male, 54 female), mean age 45.7+/-13.4 (15-70) years. The underlying aortic valve disease was an aortic insufficiency in n=83, stenosis in n=48, a combined aortic valve disease in n=111 and an acute endocarditis in n=19 patients. Previous aortic valve surgery was performed in n=23. Last follow-up investigations (within last year) including echocardiography was performed at a mean follow-up of 29.4+/-24.7 months (553.7 patient years). Hospital mortality was n=2, late mortality n=4 (all noncardiac). Two patients were lost to follow-up (99% complete clinical follow-up). Reoperations were necessary in n=7 valves (autograft: endocarditis n=1, malpositioning n=1, leaflet prolapse n=1; homograft: stenosis n=2, insufficiency n=2). Autograft insufficiency (AI) was AI 0 in n=154, AI I n=66, AI II n=8. The maximum/mean pressure gradient across the autograft was 6.6+/-3.4 (2.1 to 25.9)/3.6+/-1.8 (1.2 to 13.2) mm Hg, respectively. Homograft insufficiency was 0 in n=167, I in n=54, II in n=9, and III in n=1. Maximum and mean transhomograft pressure gradients were 11.7+/-6.8 (2.2 to 42.6)/6.2+/-3.8 (1.2 to 24.5) mm Hg. Most patients were NYHA class I (n=214), class II (n=19), class III (n=2). Significant aortic root dilatation was not observed. CONCLUSIONS: Aortic valve replacement with a pulmonary autograft in the subcoronary or inclusion technique provides excellent hemodynamics with no root dilatation at least in a mid term postoperative period. Transhomograft pressure gradients are slightly increased. Longer term results with special emphasis on the pulmonary homograft are necessary.

Adolescent↗
PubMed2003

Analysis of pregnancy and other factors on detection of human papilloma virus (HPV) infection using weighted estimating equations for follow-up data.

Generalized estimating equations have been well established to draw inference for the marginal mean from follow-up data. Many studies suffer from missing data that may result in biased parameter estimates if the data are not missing completely at random. Robins and co-workers proposed using weighted estimating equations (WEE) in estimating the mean structure if drop-out occurs missing at random. We illustrate the differences between the WEE and the commonly applied available case analysis in a simulation study. We apply the WEE and reanalyse data of a longitudinal study of pregnancy and human papilloma virus (HPV) infection. We estimate the response probabilities and demonstrate that the data are not missing completely at random. Upon use of the WEE, we are able to show that pregnant women have an increased odds for an HPV infection compared with non-pregnant women after delivery (p=0.027). We conclude that the WEE are useful for dealing with monotone missing data due to drop-outs in follow-up data.

Cohort Studies↗
PubMed2003

HLA-DRB genotyping in Gilles de la Tourette patients and their parents.

Gilles de la Tourette syndrome (GTS) is a common neuropsychiatric disorder of unknown cause. There is, however, growing evidence that both autoimmune and genetic factors are involved in the pathogenesis of GTS. In classical autoimmune disorders such as diabetes mellitus or multiple sclerosis, genetic susceptibility is at least in part conferred by human leucocyte antigen (HLA-) subtypes, in particular by distinct HLA-DRB alleles. We undertook modern, PCR-based HLA-DRB typing in 83 trios (affected index child and both parents) to investigate whether GTS may be associated with a particular HLA-DRB allele. The extended transmission/disequilibrium test (ETDT) was applied to analyze transmission disequilibrium for any of the 13 alleles detected. The ETDT failed to detect transmission disequilibrium for any allele at the DRB1 locus (overall allele-wise chi(2) (12) = 12.741, Monte Carlo P = 0.4998). Our results imply that the HLA-DRB locus does not confer genetic susceptibility to GTS.

Family Health↗
PubMed2003

Complex transcription and splicing of odorant receptor genes.

Human major histocompatibility (human leucocyte antigen (HLA)) complex-linked odorant receptor (OR) genes are among the best characterized OR genes in the human genome. In addition to their functions as odorant receptors in olfactory epithelium, they have been suggested to play a role in the fertilization process. Here, we report the first in-depth analysis of their expression and regulation within testicular tissue. Sixteen HLA-linked OR and three non-HLA-linked OR were analyzed. One OR gene (hs6M1-16, in positive transcriptional orientation) exhibited six different transcriptional start sites combined with extensive alternative splicing within the 5'-untranslated region, the coding exon, and the 3'-untranslated region. Long distance splicing, exon sharing, and premature polyadenylation were features of another three OR loci (hs6M1-18, -21, and -27, all upstream of hs6M1-16, but in negative transcriptional orientation). Determination of the transcriptional start sites of these OR genes identified a region of 81 bp with potential bi-directional transcriptional activity. The results demonstrate that HLA-linked OR genes are subject to unusually complex transcriptional regulatory mechanisms.

Base Sequence↗
PubMed2003

BRCA2 germline mutations in familial pancreatic carcinoma.

BACKGROUND: Although as many as 10% of pancreatic cancer cases may have an inherited component, familial pancreatic cancer has not been linked to defects in any specific gene. Some studies have shown that families with germline mutations in the breast cancer susceptibility gene BRCA2 have an increased risk of breast and ovarian cancers, as well as a modestly increased risk of pancreatic cancer. To study these relationships in more detail, we examined whether BRCA2 germline mutations are associated with familial pancreatic cancer. METHODS: We identified 26 European families in which at least two first-degree relatives had a histologically confirmed diagnosis of pancreatic ductal adenocarcinoma. We sequenced genomic DNA isolated from peripheral blood lymphocytes obtained from participating family members to identify germline mutations in BRCA2. RESULTS: Three (12%, exact 95% confidence interval [CI] = 2% to 30%) families carried germline frameshift mutations in the BRCA2 gene that are predicted to result in a truncated BRCA2 protein. Two additional families harbored mutations previously designated as unclassified variants of BRCA2. Thus, 19% (exact 95% CI = 7% to 39%) of the families in our study had either a frameshift mutation or an unclassified variant of BRCA2. None of the families in our study met the criteria for familial breast or ovarian cancer. CONCLUSIONS: Our data support an important role for BRCA2 germline mutations in a subpopulation of families with familial pancreatic cancer. BRCA2 mutation analysis should be included in molecular genetic testing and counseling strategies in families with at least two first-degree relatives affected with ductal adenocarcinoma of the pancreas.

Adult↗
PubMed2003

Secular trends in body mass index measurements in preschool children from the City of Aachen, Germany.

UNLABELLED: On account of the recent increases in prevalence of childhood obesity in Western countries, the present study tried to verify a secular trend for increasing body mass index (BMI; kg/m(2)) in preschool children in Aachen, Germany. The total sample was based on weight and height data for all 99,500 children of German nationality before enrollment in school in the City of Aachen from 1968-1999. For each year, 10% of the boys and girls respectively, were randomly selected for the analyses. Quantile regression was used to examine the pattern and extent of change in BMI percentiles over this 31-year period. Anthropometric data of a total of 5081 boys and 4863 girls were subjected to quantile regression. While significant increases occurred for any given BMI percentile, the annual increase for both sexes was most prominent in the upper range. No change in body height was observed during the study period. CONCLUSION: preschool children have gained a higher body mass index during the last 30 years. The mechanisms underlying the secular trend towards increasing body mass index seemingly affect children in the upper weight range more than those in the lower range.

Body Height↗
PubMed2003

Novel intronic polymorphisms in the RET proto-oncogene and their association with Hirschsprung disease.

Germline mutations of the RET proto-oncogene have been found in familial and sporadic forms of Hirschsprung disease (HSCR), but also in the autosomal dominantly inherited multiple endocrine neoplasia type 2 (MEN2) syndromes, which comprise the medullary thyroid carcinoma (MTC) as an obligatory feature. Besides mutations various polymorphisms of the RET proto-oncogene are associated with the HSCR. In this study, we have characterized seven intronic RET polymorphisms (IVS2+9G>A, IVS4+48A>G, IVS12+47C>T, IVS14-24G>A, IVS19+47T>C, IVS20+96C>T, 3'UTR+124A>G) and investigated these variants by DNA sequencing in populations of 76 HSCR patients and 40 sporadic MTC patients as well as in a control population. Variants of four of these seven polymorphisms have a strong association with the HSCR phenotype. In contrast, none of the investigated polymorphisms show a significant difference in the genotype distribution and the allele frequencies in patients with sporadic MTC when compared to controls. These findings support the hypothesis that specific RET haplotypes cause or modify the HSCR phenotype.

Female↗
PubMed2003

Analysis of CaCO3 deposit formation and degradation during the molt cycle of the terrestrial isopod Porcellio scaber (Crustacea, Isopoda).

Terrestrial isopods store cuticular calcium in large sternal deposits composed of an amorphous CaCO(3) compound. A large part of the deposits consists of numerous small spherules that increase the exposed surface to facilitate resorption of CaCO(3) during cuticle mineralization. It is not known how these spherules are formed and how they are dissolved. This paper presents for the first time an analysis of ultrastructural changes occurring in the sternal CaCO(3) deposits of a terrestrial isopod during their formation and degradation. Our results indicate that formation of the spherules takes place in a specialized aggregation zone, in which 10- to 30-nm-thick granules form agglomerations that then increase in size to form spherules that reveal a concentric growth pattern. Degradation of the deposits occurs in a manner that exposes a maximum of surface area on all levels of their structural organization.

Animals↗
PubMed2003

Ankylosing spondylitis: a beta2m-deposition disease?

To explain the strong association between HLA-B27 and ankylosing spondylitis, we suggest that the release of beta(2)-microglobulin (beta(2)m) from a subpopulation of cell surface-expressed HLA-B27 molecules leads to beta(2)m-deposition within synovia and to the initiation of an inflammatory process, which culminates in destructive spondyloarthropathy.

Antiporters↗
PubMed2003

Cytokine gene polymorphisms in allergic contact dermatitis.

Susceptibility to contact allergy may be influenced by genetically determined alterations in the production of pro- and anti-inflammatory cytokines. This report focuses on functional polymorphisms in the genes encoding for several cytokines involved in the pathogenesis of contact allergic responses, including tumour necrosis factor (TNF)-alpha (G-238 A, G-308 A), interleukin (IL)-1beta (C-511G, T+ 3953C), its natural antagonist, the IL-1 receptor antagonist (VNTR intron 2), and IL-6 (G-174C). Polymorphisms were investigated by PCR techniques among polysensitized individuals, defined as individuals with confirmed contact sensitization to para-substituted aryl compounds and at least one other structurally unrelated allergen (n = 86), and healthy control individuals without a history of eczema (n = 310). The distribution of TNFA-308 genotypes was significantly different in these groups (Padjusted= 0.0378). Compared with carriers of 2 wild-type alleles (TNFA-308*1/1 (*G/G)), carriers of the TNFA-308*1/2 (*G/A) and TNFA-308*2/2 (*A/A) genotypes tended to be more common among polysensitized individuals [OR = 1.54, 95% CI (0.92-2.55) and OR = 2.36 (0.84-6.51), respectively]. No significantly different distribution of genotypes was detected at any other polymorphic loci among control individuals without eczema and polysensitized subjects. These findings suggest a possible relationship between the TNFA-308 polymorphism and contact allergy. The results need to be confirmed in future studies.

Adult↗
PubMed2003

Polymorphisms of the NADPH oxidase P22PHOX gene in a Caucasian population with intracranial aneurysms.

BACKGROUND: Vascular remodeling generated by reactive oxygen species contributes to aneurysm formation. The NADPH oxidase system is a major source of superoxide anion not only in phagocytes, but also in endothelial and vascular smooth muscle cells. Polymorphisms of p22phox, an essential component of the NADPH oxidase system, are found to be associated with atherosclerosis, while a recent study found a significant association between the 214C>T polymorphism and the occurrence of ischemic cerebrovascular disease. We conducted a case-control study to investigate the relationship of five polymorphisms of the P22PHOX gene and the occurrence of cerebral aneurysms. METHODS: The study population consisted of 113 patients with intracranial aneurysms and 53 control subjects. The 214C>T polymorphism was investigated by restriction fragment length polymorphism analysis, while polymorphisms 381T>C, 480G>A, 521C>T, and *24A>G were analyzed by direct sequencing of exon 6 and adjacent intronic sequences. RESULTS: The analysis of a primary study sample comprising 35 cases and 28 controls failed to show a significant association between any of the five polymorphisms and the occurrence of intracranial aneurysms using both allele frequencies and genotypes (all nominal p > 0.05). Although there was a deviation from Hardy-Weinberg equilibrium in cases at the 521C>T locus (nominal p < 0.05), this could not be confirmed in a second study sample of 78 patients. Haplotypes were constructed regarding three frequent polymorphisms (214C>T, 521C>T, and *24A>G); haplotype frequencies in cases and controls were not significantly different. CONCLUSION: Although polymorphisms of the P22PHOX gene located in the coding region and the 3'-untranslated region were reported to be associated with atherosclerosis and cerebrovascular disease, our data provide evidence that there is no association between these polymorphisms and the occurrence of cerebral aneurysms in Caucasians.

Adult↗
PubMed2003

A statistical model for the evaluation of sensory tests in glaucoma, depending on optic disc damage.

PURPOSE: To analyze the sensitivity of various sensory tests adjusted for glaucomatous optic disc damage. METHODS: In a cross-sectional study, the results of testing of 196 control subjects (age range, 18-69 years) and 308 patients with chronic open-angle glaucoma (age range, 18-70 years) were included. The perimetric mean defect (MD), a temporal contrast sensitivity test (TCS), a spatiotemporal contrast sensitivity test (STCS), the peak time of a blue-on-yellow visual evoked potential (BYVEP), and the amplitude of a pattern-reversal electroretinogram (PERG) were evaluated by a specific logistic regression model. This model included glaucomatous damage, quantified by neuroretinal rim area corrected for disc size, as a covariate of sensitivity. RESULTS: Sensitivity of diagnostic tests increased for all procedures with increasing loss of neuroretinal rim area. With progressing optic disc damage, MD and STCS showed higher sensitivity than did TCS. BYVEP showed a higher sensitivity than PERG in all disease stages. In general, the psychophysical tests were more sensitive than the electrophysiological ones. CONCLUSIONS: The specific model used in this study was an appropriate tool to analyze the sensitivity of several sensory glaucoma tests in relation to disease stage. Moreover, tests that were more sensitive in early disease stages (TCS) and others that were more sensitive in more advanced stages (MD, STCS) were identified.

Adolescent↗
PubMed2003

Molecular characterisation of the smooth endoplasmic reticulum Ca(2+)-ATPase of Porcellio scaber and its expression in sternal epithelia during the moult cycle.

The anterior sternal epithelial cells of the terrestrial isopod Porcellio scaber transport large amounts of calcium during the formation and resorption of intermittent calcium carbonate deposits. Recent investigations on epithelia involved in mineralisation processes suggest a role of the smooth endoplasmic reticulum Ca(2+)-ATPase (SERCA) in transcellular calcium transport. We present the first molecular characterisation of a SERCA within a crustacean mineralising epithelium. We cloned the SERCA from a cDNA library of the anterior sternal epithelium and used in situ hybridisation to compare the expression of the SERCA mRNA between three different moulting stages. The full-length SERCA cDNA has an open reading frame of 3006 nucleotides. The deduced 1002 amino-acid polypeptide has a predicted molecular mass of 109.7 kDa and 87% identity to the SERCA of Procambarus clarkii axial muscle isoform. In situ hybridisation confirmed expression within the anterior sternal epithelium and revealed an increase in SERCA mRNA abundance from the non-transporting, early premoult stage to the calcium transporting, late premoult and intramoult stage. The results support previous indications of a contribution by the smooth endoplasmic reticulum to transcellular calcium transport and suggest a transcriptional regulation of SERCA activity.

Amino Acid Sequence↗
PubMed2003

Genome scan for childhood and adolescent obesity in German families.

OBJECTIVE: Several genome scans have been performed for adult obesity. Because single formal genetic studies suggest a higher heritability of body weight in adolescence and because genes that influence body weight in adulthood might not be the same as those that are relevant in childhood and adolescence, we performed a whole genome scan. METHODS: The genome scan was based on 89 families with 2 or more obese children (sample 1). The mean age of the index patients was 13.63 +/- 2.75 years. A total of 369 individuals were initially genotyped for 437 microsatellite markers. A second sample of 76 families was genotyped using microsatellite markers that localize to regions for which maximum likelihood binomial logarithm of the odd (MLB LOD) scores on use of the concordant sibling pair approach exceeded 0.7 in sample 1. RESULTS: The regions with MLB LOD scores >0.7 were on chromosomes 1p32.3-p33, 2q37.1-q37.3, 4q21, 8p22, 9p21.3, 10p11.23, 11q11-q13.1, 14q24-ter, and 19p13-q12 in sample 1; MLB LOD scores on chromosomes 8p and 19q exceeded 1.5. In sample 2, MLB LOD scores of 0.68 and 0.71 were observed for chromosomes 10p11.23 and 11q13, respectively. CONCLUSION: We consider that several of the peaks identified in other scans also gave a signal in this scan as promising for ongoing pursuits to identify relevant genes. The genetic basis of childhood and adolescent obesity might not differ that much from adult obesity.

Adolescent↗
PubMed2002

HLA-B27 subtypes differentially associated with disease exhibit subtle structural alterations.

The reasons for the association of the human major histocompatibility complex protein HLA-B27 with spondyloarthropathies are unknown. To uncover the underlying molecular causes, we determined the crystal structures of the disease-associated B*2705 and the nonassociated B*2709 subtypes complexed with the same nonapeptide (GRFAAAIAK). Both differ in only one residue (Asp(116) and His(116), respectively) in the F-pocket that accommodates the peptide C terminus. Several different effects of the Asp(116) --> His replacement are observed. The bulkier His(116) induces a movement of peptide C-terminal pLys(9), allowing the formation of a novel salt bridge to Asp(77), whereas the salt bridge between pLys(9) and Asp(116) is converted into a hydrogen bond with His(116). His(116) but not Asp(116) adopts two alternative conformations, one of which leads to breakage of hydrogen bonds. Water molecules near residue 116 differ with regard to number, position, and contacts made. Furthermore, F-pocket atoms exhibit higher B-factors in B*2709 than in B*2705, indicating an increased flexibility of the entire region in the former subtype. These changes induce subtle peptide conformational alterations that may be responsible for the immunobiological differences between these HLA-B27 subtypes.

Aspartic Acid↗
PubMed2002

A novel mutation in PTPRC interferes with splicing and alters the structure of the human CD45 molecule.

CD45, encoded by the protein tyrosine phosphatase receptor type C ( PTPRC) gene, is essentially involved in maturation, activation, and migration of immune cells. Lack of CD45 results in severe immunodeficiency, and alterations of the receptor may result in autoimmunity. Here, we describe a novel mutation in PTPRCas a cause of variant CD45 expression in humans. Several members of a multiple sclerosis multiplex family showed expression of CD45RA on memory T cells and monocytes. The variant expression pattern was linked to the PTPRCgene by DNA microsatellite studies. DNA analysis identified a novel point mutation in exon 4 (position 59 C-->A) in all family members with variant CD45 expression, but not in donors with normal CD45 expression. The mutation interferes with alternative splicing and alters amino acid sequence (H-->Q), interfering with antibody binding to the CD45RA domain. Overall, we describe the first mutation in PTPRCthat interferes with splicing and results in surface expression of a structurally altered CD45 molecule in humans.

Alternative Splicing↗
PubMed2002

HLA-B27 misfolding is associated with aberrant intermolecular disulfide bond formation (dimerization) in the endoplasmic reticulum.

The class I protein HLA-B27 confers susceptibility to inflammatory arthritis in humans and when overexpressed in rodents for reasons that remain unclear. We demonstrated previously that HLA-B27 heavy chains (HC) undergo endoplasmic reticulum (ER)-associated degradation. We report here that HLA-B27 HC also forms two types of aberrant disulfide-linked complexes (dimers) during the folding and assembly process that can be distinguished by conformation-sensitive antibodies W6/32 and HC10. HC10-reactive dimers form immediately after HC synthesis in the ER and constitute at least 25% of the HC pool, whereas W6/32-reactive dimers appear several hours later and represent less than 10% of the folded HC. HC10-reactive dimers accumulate in the absence of tapasin or beta(2)-microglobulin, whereas W6/32-reactive dimers are not detected. Efficient formation of W6/32-reactive dimers appears to depend on the transporter associated with antigen processing, tapasin, and beta(2)-microglobulin. The unpaired Cys(67) and residues at the base of the B pocket that dramatically impair HLA-B27 HC folding are critical for the formation of HC10-reactive ER dimers. Although certain other alleles also form dimers late in the assembly pathway, ER dimerization of HLA-B27 may be unique. These results demonstrate that residues comprising the HLA-B27 B pocket result in aberrant HC folding and disulfide bond formation, and thus confer unusual properties on this molecule that are unrelated to peptide selection per se, yet may be important in disease pathogenesis.

Antiporters↗