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J T Epplen

Publications and source records attributed to J T Epplen.

At least 91 records · Page 5Linked to original sources
PubMed2000

High telomerase activity and high HTRT mRNA expression differentiate pure myxoid and myxoid/round-cell liposarcomas.

Molecular markers characterizing the transition of a myxoid to a more round-cell liposarcoma have not been described. To examine whether telomerase activity, hTRT and hTR mRNA expression were associated with tumor progression in myxoid liposarcoma, we investigated a total of 28 myxoid liposarcomas (13 pure myxoid tumors, 14 mixed-type tumors, and 1 pure round-cell variant) from 19 patients. Telomerase activity was detected by using the fluorescent PCR-based TRAP-assay. Expression of hTRT and hTR mRNAs was determined by the semi-quantitative RT-PCR. On the basis of only one tumor sample per patient, telomerase activity was found in 9 of 9 myxoid/round-cell liposarcomas and in 3 of 10 pure myxoid tumors. Elevated hTRT expression was found in 13 of 17 liposarcomas. All telomerase-positive tumors showed hTRT expression, whereas there were 3 cases showing hTRT expression without telomerase activity. HTR mRNA expression was elevated in all 19 liposarcomas. Thus, only the levels of telomerase activity and of hTRT mRNA expression differentiated pure myxoid liposarcoma and myxoid/round-cell liposarcoma (p < 0.003 and p = 0.029, respectively). We believe that high levels of telomerase activity and of hTRT expression are associated with tumor progression from low-grade pure myxoid to higher-grade malignant round-cell liposarcoma, and may consequently represent a useful prognostic marker for this histological sub-type of soft-tissue tumors.

Biomarkers↗
PubMed2000

Low probe concentration can cause problems in multilocus DNA fingerprinting (cautionary notes III).

The power of multilocus DNA fingerprinting depends on the reliability with which the uniqueness of an individual's profile can be demonstrated. This cautionary note stresses the importance of the probe concentration in this procedure. In case of a probe shortage, DNA fragments rich in tandem repeats have the potential to impede hybridization in other parts of the gel, and thus interfere with bands that are part of a DNA fingerprinting profile.

Animals↗
PubMed2000

The IL-10 gene is not involved in the predisposition to inflammatory bowel disease.

Although genetic predisposition for inflammatory bowel disease (IBD) is well established, little is known about the accountable genes. The pathogenesis of IBD is characterized by an imbalanced activation of Th1- and Th2-lymphocytes. IL-10 represents an anti-inflammatory cytokine which downregulates the production of Th1-derived cytokines. To evaluate the role of the IL-10 gene in IBD, two polymorphisms in the promoter region (G/A at position -1082 and C/A at position -592) were genotyped in 142 patients with Crohn's disease (CD), 104 patients with ulcerative colitis (UC), and 400 healthy controls. Significant differences were not apparent, neither in the allele frequencies of either polymorphism, nor in the haplotype frequencies. Screening of the coding region of the IL-10 gene by polymerase chain reaction--single strand conformation polymorphism (PCR-SSCP) analysis revealed a rare sequence variation in exon 1 leading to an amino acid exchange (G-->A; G15R) in two patients with CD and five healthy controls. Therefore, polymorphisms of the IL-10 gene are not demonstrably involved in the predisposition of IBD in our cohorts of patients.

Colitis, Ulcerative↗
PubMed2000

The association of CD18 alleles with anti-myeloperoxidase subtypes of ANCA-associated systemic vasculitides.

Wegener granulomatosis (WG), microscopic polyangiitis (MP), and Churg Strauss syndrome (CSS) are rare systemic autoimmune disorders. Common features are anti-neutrophil cytoplasmic antibodies (ANCA) in patient sera. Whereas WG patients show mainly anti-proteinase 3 ANCA, MP and CSS patients typically present anti-myeloperoxidase (MPO) ANCA. ANCA play an important role in the pathogenesis in the vessel wall by activating polymorphonuclear cells (PMN) and increased adhesivity between PMN and endothelial cells via adhesion molecules. Here we investigated major adhesion molecules as predisposition factors via common polymorphisms in or in the vicinity of the candidate genes ICAM-1, e-selectin, PLAUR, CD11b, and CD18. A restriction fragment-length polymorphism in exon 11 of the CD18 gene was associated with MPO-ANCA(+) systemic vasculitis. Our data indicate that a common variant of the CD18 gene confers increased risk for CSS and MP, supporting that genetic factors are involved in the etiology and pathogenesis of ANCA-associated systemic vasculitides.

Alleles↗
PubMed2000

Genetic background of apparently idiopathic sporadic cerebellar ataxia.

Disease-causing mutations have been identified in various entities of autosomal dominant ataxia and in Friedreich's ataxia. However, no molecular pathogenic factor is known to cause idiopathic cerebellar ataxias. We investigated the CAG/CTG trinucleotide repeats causing spinocerebellar ataxia types 1, 2, 3, 6, 7, 8 and 12, and the GAA repeat of the frataxin gene in 124 patients apparently suffering from idiopathic sporadic ataxia, including 20 patients with the clinical diagnosis of multiple system atrophy. Patients with a positive family history, a typical Friedreich phenotype, or symptomatic ataxia were excluded. Genetic analyses uncovered the most common Friedreich mutation in 10 patients with an age at onset between 13 and 36 years. The SCA6 mutation was present in nine patients with disease onset between 47 and 68 years of age. The CTG repeat associated with SCA8 was expanded in three patients. One patient had SCA2 attributable to a de novo mutation from a paternally transmitted, intermediate allele. We did not identify the SCA1, SCA3, SCA7 or SCA12 mutation in idiopathic sporadic ataxia patients. No trinucleotide repeat expansion was detected in the MSA subgroup. This study has revealed the genetic basis in 19% of apparently idiopathic ataxia patients. SCA6 is the most frequent mutation in late onset cerebellar ataxia. The frataxin trinucleotide expansion should be investigated in all sporadic ataxia patients with onset before age 40, even when the phenotype is atypical for Friedreich's ataxia.

Age of Onset↗
PubMed2000

Genetic analysis of immunomodulating factors in sporadic Parkinson's disease.

Immunomodulating factors have been shown to play a role in the pathogenesis of Parkinson's disease (PD) by biochemical methods. In order to investigate functionally important genes of the tumor necrosis factor alpha (TNFalpha) pathway we studied the frequency of DNA polymorphisms in the interleukin 6 (IL6), the TNFalpha, and the TNFalpha receptor 1 (TNFR1) genes in 264 sporadic German PD patients and in 183 age and sex matched German healthy controls. Analyzing the TNFalpha-308 polymorphism we found heterozygous individuals carrying alleles 1 and 2 more frequently in patients with a relative risk of 1.56 (p = 0.046, p(c) = 0.13, chi2 = 3.98). In contrast, the frequency of the B/2 haplotype described by the TNFR1-609 and TNFRI+36 polymorphisms was significantly decreased in our PD patients group (p = 0.0097, p(c) = 0.048, chi2 = 6.69) with a relative risk reduced to 0.52. Our results suggest an involvement of immunomodulating factors in the pathogenesis of sporadic PD as revealed by a molecular genetic approach.

Adjuvants, Immunologic↗
PubMed2000

Mitochondrial impairment of human muscle in Friedreich ataxia in vivo.

Friedreich ataxia occurs due to mutations in the gene encoding the mitochondrial protein frataxin. This (31)P magnetic resonance spectroscopy study on the calf muscle of Friedreich ataxia patients provides in vivo evidence of a severe impairment of mitochondrial function. Mitochondrial adenosine triphosphate resynthesis was studied by means of the post-exercise recovery of phosphocreatine. After ischemic exercise in calf muscles of all patients, phosphocreatine recovery was dramatically delayed. Time constants of recovery correlated with mutations of the frataxin gene, the age of the patients, and disease duration. (31)P magnetic resonance spectroscopy represents the first expedient tool for monitoring therapeutic trials in Friedreich ataxia non-invasively.

Adenosine Triphosphate↗
PubMed2000

Lack of association between the interferon regulatory factor-1 (IRF1) locus at 5q31.1 and multiple sclerosis in Germany, northern Italy, Sardinia and Sweden.

Interferon regulatory factor-1 (IRF-1) is a transcriptional inducer of the interferon-beta (IFN-beta) gene and other interferon-stimulated genes. A GT repeat polymorphism in the 7th intron of the IRF-1 gene was used as a marker to test for association with multiple sclerosis (MS) in a case-control study including individuals from Germany, Northern Italy and Sweden. In none of these populations, did we find any significant allelic association with disease. This lack of association was confirmed by testing transmission disequilibrium of individual IRF1 alleles in a representative sample of Sardinian simplex MS families. No deviation of the expected 50% transmission rates was seen. Therefore, our work does not provide evidence in favor of IRF1 being a candidate for conferring genetic susceptibility to, or protection against, MS in Europe.

Adolescent↗
PubMed2000

Exclusion of the PDE6A gene for generalised progressive retinal atrophy in 11 breeds of dog.

The cyclic guanosine monophosphate specific phosphodiesterase (cGMP-specific PDE) is a key enzyme in the phototransduction cascade of the vertebrate retina. This enzyme consists of two catalytic alpha and beta subunits, two identical inhibitory gamma subunits as well as a delta subunit. Mutations in PDE6A and the PDE6B genes lead to autosomal recessive (ar) forms of retinitis pigmentosa (RP) in human and to the homologous disease in dogs, designated generalised progressive retinal atrophy (gPRA). We investigated the PDE6A gene in 13 gPRA-affected dog breeds including healthy animals, obligate gPRA carriers and gPRA-affected dogs. In the coding region of PDE6A only a rare sequence variation (G103A; Asp35Asn) was found in exon 1 of two healthy Tibet Terriers and one affected Cocker Spaniel. Using single-stranded conformation polymorphism (SSCP) analyses we detected several sequence variations in eight of the PDE6A introns in different investigated breeds. Most informative for excluding the PDE6A gene as a cause for gPRA was a polymorphic microsatellite ((GT)10CG(GT)2CG(GT)12) in intron 14 and four sequence variations in intron 18 for almost all breeds investigated. The sequence variations of PDE6A did not segregate together with gPRA in 11 breeds. Since diseased animals were heterozygous for the polymorphisms, the PDE6A gene is unlikely to harbour the critical mutation causing gPRA in the following breeds: Chesapeake Bay Retriever. Entlebucher Sennenhund, Labrador Retriever. Tibet Mastiff, Dachshund (long- and wire-haired), Tibetan Terrier, Miniature Poodle. Australian Cattle Dog, Cocker Spaniel, Saarloos/Wolfshound, Sloughi.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

Evaluation of RDS/Peripherin and ROM1 as candidate genes in generalised progressive retinal atrophy and exclusion of digenic inheritance.

Generalised progressive retinal atrophy (gPRA) is a heterogeneous group of hereditary diseases causing degeneration of the retina in dogs and cats. As a combination of mutations in the RDS/Peripherin and the ROM1 genes leads to the phenotype of retinitis pigmentosa in man we first performed mutation analysis to screen these genes for disease causing mutations followed by the investigation of a digenic inheritance in dogs. We cloned the RDS/Peripherin gene and investigated the RDS/Peripherin and ROM1 genes for disease causing mutations in 13 gPRA-affected dog breeds including healthy animals, obligate gPRA carriers and gPRA-affected dogs. We screened for mutations using single strand conformation polymorphism (SSCP) analysis. Sequence analysis revealed several sequence variations. In the coding region of the RDS/Peripherin gene three nucleotide exchanges were identified (A277C; C316T; G1255A), one of which leads to an amino acid substitution (Ala339Thr). Various silent sequence variations were found in the coding region of the ROM1 gene (A536G, G1006A, T1018C, T1111C, C1150T, C1195T), as well as an amino acid substitution (G252T; Ala54Ser). By excluding the respective gene as a cause for gPRA several sequence variations in the intronic regions were investigated. None of these sequence variations cosegregated with autosomal recessively (ar) transmitted gPRA in 11 breeds. The candidate gene RDS/Peripherin obviously does not harbour the critical mutation causing the autosomal recessive form of gPRA because diseased individuals show heterozygous genotypes for sequence variations in the Miniature Poodle, Dachshund, Australian Cattle Dog, Cocker Spaniel, Chesapeake Bay Retriever, Entlebucher Sennenhund, Sloughi, Yorkshire Terrier, Tibet Mastiff, Tibet Terrier and Labrador Retriever breeds. In the following breeds the ROM1 gene was also excluded indirectly for gPRA: Miniature Poodle, Dachshund, Australian Cattle Dog, Sloughi, Collie, Tibet Terrier, Labrador Retriever and Saarloos/Wolfhound. Digenic inheritance for gPRA is practically excluded for both these genes in four breeds: Miniature Poodle, Dachshund, Labrador Retriever and Saarloos/Wolfhound.

Amino Acid Substitution↗
PubMed2000

Association of polycystic ovary syndrome with an interstitial deletion of the long arm of chromosome 11.

Several pathways have been implicated in the etiology of the polycystic ovary syndrome (PCOS). The observation of familial aggregation of PCOS is consistent with a genetic component of this disorder. We report on a 21-year-old woman with menstrual irregularity, hirsutism, elevated serum androgen levels and polycystic ovarian morphology on ultrasonography, meeting the diagnostic criteria of PCOS. A cytogenetic investigation was performed because of a congenital heart defect, craniofacial anomalies in infancy (quadricephaly with protruding forehead, flat nasal bridge, low set ears with attached earlobes, small mouth, high arched palate with submucous palatal cleft, retrognathia), broad neck, motor and speech developmental delay. Chromosomal analysis revealed an unbalanced interstitial deletion of one of the chromosomes 11 [del (11) (q21q23.1)]. Interstitial deletions of the long arm of chromosome 11 have been reported in at least 18 patients. Candidate genes for PCOS have not been suspected at this chromosomal location so far. Follistatin and CYP11A, the genes with the strongest evidence for linkage with PCOS, are located on chromosomes 5 and 15. In the chromosomal region deleted in our patient a progesterone receptor gene is located in band q22. Lowered progesterone receptor concentration is associated with retardation of endometrial development. A disturbance of the hypothalamic-pituitary gonadal axis, due to a reduction of hypothalamic and pituitary progesterone receptors might be a component in the etiology of PCOS.

Adult↗
PubMed2000

The nonfunctional allele TCRBV6S1B is strongly associated with Helicobacter pylori infection.

To determine genetic susceptibility factors for Helicobacter pylori infection, polymorphic T-cell receptor gene elements were investigated in 203 H. pylori-infected individuals and 180 uninfected individuals (controls). H. pylori infection is highly associated with individuals homozygous for the nonfunctional TCRBV6S1B element (odds ratio = 5.9; chi(2) = 13; P = 0.00032; P value corrected for multiple comparisons [Bonferroni correction] = 0. 00063).

Alleles↗