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C Seidl

Publications and source records attributed to C Seidl.

At least 37 records · Page 2Linked to original sources
PubMed2000

Characterisation of patients with primary biliary cirrhosis responding to long term ursodeoxycholic acid treatment.

BACKGROUND: In some patients with primary biliary cirrhosis, ursodeoxycholic acid causes full biochemical normalisation of laboratory data; in others, indexes improve but do not become normal. AIMS: To characterise complete and incomplete responders. METHODS: Seventy patients with primary biliary cirrhosis were treated with ursodeoxycholic acid 10-15 mg/kg/day and followed up for 6-13 years. RESULTS: In 23 patients (33%) with mainly stage I or II disease, cholestasis indexes and aminotransferases normalised within 1-5 years, except for antimitochondrial antibodies. Histological findings improved. Indexes were not normalised in 47 patients (67%) although the improvement of their biochemical functions parallelled the trend in the first group. In these incomplete responders histological findings improved to a lesser extent. The only difference between the two groups before treatment was higher levels of alkaline phosphatase and gamma glutamyl transpeptidase in the incomplete responders. At onset of treatment the discriminant value separating responders from incomplete responders was 660 U/l for alkaline phosphatase and 131 U/l for gamma glutamyl transpeptidase. One year later it was 239 and 27 U/l (overall predictive value for responders 92%, for incomplete responders 81%). There were no differences between the two groups concerning immune status, antimitochondrial antibody subtypes, liver histology, or any other data. HLA-B39, DRB1*08, DQB1*04 dominated in both groups. CONCLUSIONS: In patients with mainly early stages of primary biliary cirrhosis, higher values of alkaline phosphatase and gamma glutamyl transpeptidase are the only biochemical indexes which allow discrimination between patients who will completely or incompletely respond to ursodeoxycholic acid treatment.

Adult↗
PubMed1999

Sequence analysis and population data of short tandem repeat polymorphisms at loci D8S639 and D11S488.

Short tandem repeat loci are ideal markers for forensic and paternity case work. A high degree of polymorphism, as determined by gross length measurement, is very often due to complex underlying sequence variation. In the present study, we have studied the sequence structure and population genetics of two short tandem repeat polymorphisms at loci D8S639 and D11S488 in German Caucasians from the region of Hesse. Sequence data revealed a considerable polymorphism at both loci. Locus D8S639 is characterized by a tetranucleotide (AGAT)n repeat pattern with (GAT) and (AGGT) repeats dispersed throughout several alleles. These microvariations lead to alleles differing by one base pair or alleles of identical size. At locus D8S639 we observed 17 allelic lengths comprising 25 different alleles. Alleles at locus D11S488 possess a compound repeat region consisting of (AAAG)n and (GAAG)n repeats. At locus D11S488 we observed 15 allelic lengths with a total of 24 alleles. Allelic lengths increased in size by 4bp increments corresponding to the addition of one tetranucleotide repeat unit. Population data of loci D8S639 and D11S488 revealed a high polymorphism with heterozygosity rates of 0.85 (D8S639) and 0.91 (D11S488).

Alleles↗
PubMed1999

An endogenous retroviral long terminal repeat at the HLA-DQB1 gene locus confers susceptibility to rheumatoid arthritis.

Human endogenous retrovirus (HERV) long terminal repeat (LTR) elements contain regulatory sequences that can influence the expression of adjacent cellular genes, which may contribute to breakdowns of the immune function leading to autoimmune disease. Rheumatoid arthritis (RA) is associated with particular HLA-DR/DQ haplotypes that modulate the pathogenesis of this autoimmune disease. We have therefore studied a solitary LTR element (DQ-LTR3) of the HERV-K family at the HLA-DQB1 locus for a possible disease association among 228 RA patients and 311 unrelated blood donors. The DQ-LTR3 was significantly more frequent among patients (76% vs 33%, OR = 5.07,p < 0.0001), with the majority of patients being heterozygous for the DQ-LTR3 (61% vs 22%, p < 0.0001). HLA-DRB1*04 positive patients did still differ for the presence of the DQ-LTR3 (88% vs 70%, OR = 3.03, p < 0.001), with an increase of both DQ-LTR3 homozygous and heterozygous patients, when compared to DRB1*04 positive controls (p = 0.0015). HLA-DR/DQ genotype analysis among HLA-DRB1*04 positive individuals revealed significantly more DQ-LTR3 homozygotes among HLA-DRB1*04-DQBI*03 homozygous patients (72% vs 27%, P = 0.015), and the number of DQ-LTR3 homozygous (23% vs 19%) and heterozygous (66% vs 53%) individuals was also increased among HLA-DRB1*04 heterozygous patients (p = 0.034). The presence of the DQ-LTR3 element increased both the relative risk and the positive predictive value for either DRB1*04-DQB1*03 positive/negative individuals when compared to the presence of HLA-DRB1*04-DQB1*03 alone. In conclusion, these data suggest that this DQ-LTR3 enhances susceptibility to RA.

Arthritis, Rheumatoid↗
PubMed1999

A second unrelated bone marrow transplant: successful quantitative monitoring of mixed chimerism using a highly discriminative PCR-STR system.

A second bone marrow transplant (BMT) might be considered as an option in patients with leukaemia with graft failure after BMT. We report the successful treatment of a patient with graft failure by a second stem cell transplant from another unrelated donor. We evaluated the usefulness of an unrelated donor as the source of the second BMT in this clinical setting. In addition to this, a penta PCR-STR system was tested and shown to be sensitive for monitoring of marrow engraftment. The conditioning regimen for the first transplantation consisted of busulfan and cyclophosphamide while anti-thymocyte globulin and CY were used for the second BMT. The patient successfully engrafted at day +11 after second BMT.

Adult↗
PubMed1999

HLA-DR/DQ interaction in patients with erosive rheumatoid arthritis presenting articular and extraarticular disease manifestations.

In the present study we have analysed the effect of HLA-DRB1 and -DQB1 alleles on disease progression and genetic predisposition among 201 RA patients. We clearly confirm the association of RA with HLA class II alleles sharing the (Q)R/KRAA amino acid (AA) cassette in the third hypervariable region (HVR3) of the DR beta-chain. The HVR3 (Q)R/KRAA motif was significantly overrepresented among RA patients (79% vs. 40%, P < 0.001), with one third of the patients homozygous (28% vs. 6.7%, P < 10(-9)) and the number of rheumatoid factor positive (RF+) patients was significantly increased among HVR3 (Q)R/KRAA homozygous in comparison to HVR3 (Q)R/KRAA negative individuals. Erosive disease defined by the Larsen Score and personal disability determined using the Health Assessment Questionnaire (HAQ) was significantly increased among patients positive for the HVR3 motif with the worst outcome among HVR3 (Q)R/KRAA homozygous patients. In contrast, there was no association of the shared HVR3 AA cassette and disease severity in the majority of patients presenting systemic (extraarticular) disease. Homozygosity for the shared HVR3 motif was only marginally increased among patients presenting 'severe' extraarticular disease in comparison to patients with articular disease (33% vs. 43%, P = ns). Similarly, patients with nodular disease were not more often homozygous for the HVR3 (Q)R/KRAA motif. Furthermore, we observed no HLA-DR independent association of DQB1 alleles among HVR3 (Q)R/KRAA positive patients and controls. Our analysis supports the predominant role of HLA-DR for genetic susceptibility to RA. In the clinical setting, however, HLA-DR typing may be limited to assess the individual risk of patients for disease progression.

Adult↗
PubMed1999

Association of (Q)R/KRAA positive HLA-DRB1 alleles with disease progression in early active and severe rheumatoid arthritis.

OBJECTIVE: We have shown that HLA-DRB1 alleles influence inflammatory activity in patients with early active and severe rheumatoid arthritis (RA). Therefore, we analyzed the effect of HLA-DRB1 alleles on disease progression in patients with early RA during a clinical followup period of 18 months. METHODS: Disease progression was defined by the Larsen Score, the Ritchie Index (RI), and the Health Assessment Questionnaire (HAQ) score. RESULTS: Patients carrying arthritogenic HLA-DRB1 alleles on one or both haplotypes are characterized by increased radiological joint destruction (Larsen Score). Further, (Q)R/KRAA homozygous patients were characterized by worse overall disease course (higher RI and HAQ). However, analysis of changes in joint effects (delta-RI) and personal disability (delta-HAQ) did not reveal significant differences between patients with or without disease associated HLA-DRB1 alleles. CONCLUSION: The predisposing genetic pattern with disease associated HLA-DRB1 alleles did not profoundly influence the therapeutic outcome. Our data support the role of the HLA-DRB1 gene locus in disease modulation of RA. The genetic predisposition due to HLA-DRB1, however, may have only a limited influence on the therapeutic outcome in clinically severe cases of RA.

Adult↗
PubMed1998

Rhnull disease: the amorph type results from a novel double mutation in RhCe gene on D-negative background.

Rhnull disease, which includes the amorph and regulator types, is a rare genetic disorder characterized by stomatocytosis and chronic hemolytic anemia. We studied here a German family transmitting a putative amorph Rhnull disease gene and identified a rare mutation causing the loss-of-function phenotype. We analyzed the genomic and transcript structure of RH30, RH50, and CD47, the three loci thought to be most critical for expression of the Rh complex in the red blood cell membrane. We showed that in this family the Rh50 and CD47 transcripts were normal in primary sequence. However, the RH30 locus contained an unusual double mutation in exon 7 of the RhCe gene, in addition to a deletion of the RhD gene. The mutation targeted two adjacent codons in multiple arrangements probably via the mechanism of microgene conversion. One scheme entails a noncontiguous deletion of two nucleotides, [ATT(Ile322)-->AT] and [CAC(His323)-->CC], whereas the other involves a T-->C transition [ATT(Ile322)--> ATC] and a dinucleotide deletion [CAC(His323)-->C]. They caused the same shift in open reading frame predicted to encode a shortened protein with 398 amino acids. The loss of two transmembrane domains and gain of a new C-terminal sequence are likely to alter the protein conformation and impair the Rh complex assembly. Our findings establish the molecular identity of an amorph Rhnull disease gene, showing that Rh30 and Rh50 are both essential for the functioning of the Rh structures as a multisubunit complex in the plasma membrane.

Amino Acid Sequence↗
PubMed1998

A novel UV-damaged DNA binding protein emerges during the chromatin-eliminating cleavage period in Ascaris suum.

During the early cleavage period of Ascaris suum , chromatin diminution takes place in the somatic founder cells. In the process of chromatin diminution numerous heterochromatic blocks, consisting predominantly of highly repeated DNA, are discarded during mitotic anaphase and are later on digested in the cytoplasm. Very little is known about proteins that are involved in chromatin diminution. We have detected a nuclear protein and purified it to near homogeneity by its preferential binding to UV-damaged DNA. We termed this protein chromatin diminution associated factor 1 (CDAF1), because maximum binding activity per nucleus was observed to develop in 4-8-cell stages, when chromatin diminution occurs for the first time. CDAF1 recognizes cyclobutane pyrimidine dimers in UV-damaged double-stranded DNA. Its binding properties identify CDAF1 as a novel kind of damaged-DNA binding protein. CDAF1 activity is almost not detectable in 1-celled embryos. It increases dramatically during formation of somatic founder cells and persists up to the first larval stage. However, CDAF1 is absent in tissues of adults. These findings led us to suggest that CDAF1 plays a dual role: during the early segregative cleavage period it might be involved in chromatin diminution as a transfactor and act in nucleotide excision repair as an accessory factor throughout embryogenesis.

Animals↗
PubMed1998

A New Test of Image Theory.

This paper investigates two hypotheses of the screening phases of two-staged multiattribute choice procedures: the editing phase in which dominated choice alternatives are eliminated and the compatibility test of image theory. As the importance weights and rejection thresholds of the compatibility test are recalcitrant to elicitation, we develop a new method to examine the compatibility phase treating importance weights and rejection thresholds as latent parameters. Our method allows a checkup of the application of a compatibility test without any knowledge of subjects' importance weights and rejection thresholds. Our experimental findings show that the compatibility test enjoys consistency rates of some 70% as compared to consistency rates of about 15% for the editing hypothesis of the elimination of dominated choice alternatives. This result is supported by applying Selten's measure of predictive success. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

[Leiomyosarcoma of the spermatic cord with paraneoplastic beta-hCG production].

Leiomyosarcomas of the spermatic cord are very rare tumours, which, in contrast to the rhabdomyosarcoms of childhood, occur almost exclusively in adults. We report the case of a 51-year-old male patient with a metastasizing, pleomorphic leiomyosarcoma of the spermatic cord. The tumour showed paraneoplastic secretion of beta-chain human chorionic gonadotropin (beta-hCG), as was demonstrated by the elevated levels of beta-hCG in serum samples and by immunohistochemistry. Histologically, the tumour was a high-grade leiomyosarcoma which showed an aggressive course with pulmonary metastases appearing 4 months after primary surgery. A concomitant rise in the serum levels of beta-hCG was also noted at this time. A wide spectrum of tumours with a choriocarcinomatous component or paraneoplastic production of beta-hCG has been described, the vast majority being carcinomas. Only two leiomyosarcomas producing beta-hCG have so far been reported. The paraneoplastic production of beta-hCG should prevent confusion with germ-cell tumours, especially teratomas.

Adult↗
PubMed1998

CTLA4 codon 17 dimorphism in patients with rheumatoid arthritis.

The genetic susceptibility to rheumatoid arthritis is conferred by genes in the human leukocyte antigen (HLA) region on chromosome 6, but additional genes may be involved to determine disease susceptibility. We have studied the distribution of the CTLA4 exon 1 polymorphism (49 A/G) in rheumatoid arthritis. This dimorphism at codon 17 results in an amino acid exchange (Thr/Ala) in the leader peptide of the expressed protein and was analyzed by PCR, SSCP and RFLP in 258 Caucasian rheumatoid arthritis patients and 456 controls. Rheumatoid arthritis patients were characterized by a decreased frequency of homozygotes for the Thr-17 substitution (32% versus 39%) and an overrepresentation of patients heterozygous for the Thr/Ala substitution (54% versus 46%). Gene frequencies for the Ala/Thr substitution differed only marginally from controls. In contrast, analyses of the CTLA4 exon 1 polymorphism with respect to HLA-DRB1*04 revealed significantly more patients with Ala in the homozygous (19% versus 15% controls) or heterozygous state (54% versus 39% controls) and less homozygous for Thr (27% versus 46% controls), with a particular increase of Ala/Ala genotypes among rheumatoid arthritis patients carrying the HLA-DRB1*0401 subtype. Among HLA-DRB1*04 negative rheumatoid arthritis patients, we observed no difference between the allele frequencies of the Ala-17 or Thr-17 substitution.

Abatacept↗
PubMed1998

HFE codon 63/282 (H63D/C282Y) dimorphism in German patients with genetic hemochromatosis.

Genetic hemochromatosis (GH) is closely associated with genes of the major histocompatibility complex (MHC) on chromosome 6. Recently, a candidate gene for GH, with structural similarities to MHC class I genes, designated HLA-H and presently named HFE, has been cloned. The HFE gene is localized telomeric to the MHC and several reports have indicated that the HFE gene is mutated in GH patients. In the present study we have analyzed the relationship of HFE gene variants and disease manifestation in GH patients and family members. Fifty-seven patients with GH, 73 family members and 153 healthy blood donors were studied for the amino acid dimorphism at codon 63 (His63Asp=H63D) and codon 282 (Cys282Tyr= C282Y) of the HFE gene. The codon 63 and 282 dimorphism were defined by PCR amplification of genomic DNA samples and restriction enzyme digestion using RsaI/SnaBI for C282Y and BclI/MboI for H63D. Ferritin, transferrin serum levels and total iron-binding capacity were determined prior to therapeutic intervention. The Tyr-282 substitution occurred in 53 (93%) of patients compared with 8 (5.2%) of controls (OR=169, P<0.0001). Fifty-one (90%) patients were Tyr-282 homozygous. In contrast, the Asp-63 substitution was present in 5 (8.8%) of the patients compared with 34 (22%) of controls (OR=0.39, P=NS) with none of the patients being homozygous. In Tyr-282 homozygous GH patients serum ferritin levels, transferrin saturation, liver iron and liver iron index were elevated significantly compared to Tyr-282-negative patients, whereas no difference was observed between Tyr/Cys-282 heterozygous and Tyr-282-negative patients.

Aspartic Acid↗
PubMed1998

Soluble HLA class I and class II antigens in patients with multiple sclerosis.

Soluble HLA class I (sHLA-I) and soluble HLA class II (sHLA-II) antigen levels during different stages of disease were investigated in paired serum and cerebrospinal fluid (CSF) samples from 37 patients with multiple sclerosis (MS) using ELISA and Western blot analysis. Soluble HLA-II antigens in the serum of untreated patients with the relapsing-remitting type of MS (RRMS) were found to be significantly elevated in acute relapse as compared to values obtained from patients under steroid treatment, in remission or healthy controls. No significant differences in circulating sHLA-I levels could be detected. In contrast, a trend towards increased intrathecal production of sHLA-I molecules in the CSF was observed in untreated RRMS patients in acute relapse, whereas the levels of soluble HLA-II antigens in the CSF were below the detection limit of the ELISA method. Our observations underline the presence of systemic immune activation in MS patients, as reflected in elevated serum sHLA-II antigen levels, and reveal a dichotomy between sHLA class I and II antigen production in the peripheral blood versus CSF in acute MS. Serial measurements of sHLA-II antigen levels might represent a non-invasive method to assess disease activity in MS patients.

Enzyme-Linked Immunosorbent Assay↗
PubMed1998

Clinical trial on the effect of regular tea drinking on iron accumulation in genetic haemochromatosis.

BACKGROUND: Black tea is known to be a potent inhibitor of intestinal absorption of non-haem iron at least in healthy subjects. AIMS: To investigate this effect in patients with genetic haemochromatosis, and, more importantly, the effect of regular tea drinking on the accumulation of storage iron in these patients over one year. PATIENTS: Investigations were carried out on 18 patients with clinically proven genetic haemochromatosis. For the study of storage iron accumulation, they were separated into a group instructed to drink a particularly tannin rich tea regularly with meals and a control group. METHODS: Intestinal iron absorption from a test meal was measured using whole body counting. Body iron stores were evaluated quantitatively by exhaustive phlebotomy, using haemoglobin, saturation of serum iron binding capacity, and serum ferritin for the assessment of body iron status. RESULTS: A significant reduction in iron absorption was observed when the test meal was accompanied by drinks of tea instead of water. In the tea drinking group, the increase in storage iron was reduced by about one third compared with that of the control group. CONCLUSIONS: Regular tea drinking with meals reduces the frequency of phlebotomies required in the management of patients with haemochromatosis.

Adult↗