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Biomedical subjects

H Traupe

Publications and source records attributed to H Traupe.

At least 37 records · Page 2Linked to original sources
PubMed2002

Cell surface bound and soluble adhesion molecules in CSF and blood in multiple sclerosis: correlation with MRI-measures of subclinical disease severity and activity.

BACKGROUND: The expression of soluble cell adhesion molecules (AM) in cerebrospinal fluid (CSF) and blood and their significance as measures of disease activity has been extensively studied in patients with multiple sclerosis (MS). In previous studies, we found that cell surface bound AM on mononuclear cells (MNC) in CSF and blood might be useful markers of clinical disease activity in MS patients. OBJECTIVE: To analyze the correlation of cell surface bound and soluble AM in CSF and blood with magnetic resonance imaging (MRI) markers of subclinical disease severity and activity in patients with MS. METHODS: Expression levels of cell surface bound AM on peripheral blood and CSF MNC were determined by flow cytometry analysis in 77 (CSF: 33) MS patients. Concentration levels of the soluble forms of AM were measured by enzyme-linked immunosorbent assay (ELISA). In corresponding cerebral gadolinium (Gd)-enhanced MRI scans, we determined both measures of subclinical disease severity and subclinical disease activity. RESULTS: The expression levels of cell surface bound AM in peripheral blood correlated inversely with parameters for subclinical disease severity and activity on cerebral MRI scans as well as with the disease duration. Furthermore, we found significant correlations between serum levels of soluble AM and patient age but not with disease duration. CONCLUSIONS: Our results suggest that subclinical disease progression may be associated with a decrease of the expression of cell surface bound AM on peripheral blood MNC. This might be a result of activated MNC migration into the CNS.

Adult↗
PubMed2002

Serum cytokine levels do not correlate with disease activity and severity assessed by brain MRI in multiple sclerosis.

OBJECTIVE: Chronic and acute dysregulation of the cytokine network has been described in multiple sclerosis (MS). Inflammatory lesions in the central nervous system of MS patients can be assessed by brain magnetic resonance imaging (MRI). This study has been performed to investigate whether changes of cytokines correlate with morphological changes as determined by MRI. MATERIALS AND METHODS: We included 46 patients with relapsing-remitting MS in the study. The serum concentrations of tumor necrosis factor-beta (TNF-beta), TNF receptor-1 (TNFR-1; 55 kDa) and TNFR-2 (75 kDa), interleukin-4 (IL-4), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) were measured by enzyme linked immunosorbent assay in all patients. Each parameter was correlated with clinical findings and brain MRI parameters. We measured both the number (lesion load) and cumulated area (disease burden) of all lesions on brain MRI. In addition, the number and cumulated area of those lesions showing signs of activity [Gadolinium (Gd)-enhancement, perifocal edema] were determined. RESULTS: A non-significant trend (P < 0.05) was found only for the correlation of serum IFN-gamma levels and the number of active MRI lesions showing both Gd-enhancement and perifocal edema in the subgroup of patients (n=21) with active lesions. When corrected for multiple comparisons, this correlation was not significant anymore, as it was above the corrected P-value of 0.001. We could not observe any further correlation of cytokine levels and MRI parameters. However, TNF-beta serum levels were significantly (P < 0.05) elevated in the patient subgroups with higher number of lesions and disease burden, respectively. CONCLUSION: Our data show that the determination of serum levels of the investigated cytokines and cytokine receptors is not useful as a tool to determine subclinical disease activity and severity as assessed by brain MRI.

Adult↗
PubMed2002

Sonographic harmonic grey scale imaging of brain perfusion: scope of a new method demonstrated in selected cases.

AIM: Transient response harmonic transcranial sonography is a new bed-side technique which provides information on brain tissue perfusion. This paper demonstrates the scope of perfusion transcranial sonography (p-TCS). METHODS: P-TCS was performed in an axial insonation plane through the thalamus and third ventricle in a case with Moyamoya disease and a patient with bilateral thalamic oedema due to thrombosis of the internal cerebral veins, and compared to results in 10 healthy controls. Signal increase induced by a bolus of an echo-contrast agent (Optison trade mark ) was quantified in regions of interest (ROI) in the thalamus (TH), lentiform nucleus (LN) and the cerebral white matter (WM). RESULTS: In Moyamoya disease p-TCS could demonstrate a decreased perfusion in the WM and LN as a result of bilateral, high-grade stenoses of the intracranial part of the internal carotid artery. Peak intensity was increased in the TH due to collateral cross-over flow from the vertebrobasilar system. TH perfusion was decreased in thrombosis of the internal cerebral vein thrombosis with normal LN perfusion. The extention of the thalamic oedema into the white matter could also be demonstrated by decreased perfusion in the adjacent WM. ROI ratios of different tissues proved helpful in quantifying the perfusion results. CONCLUSION: P-TCS is a new, promising technique that can supply information on pathological brain tissue perfusion at the patient's bed-side.

Adult↗
PubMed2001

Assignment of PGL3 to chromosome 1 (q21-q23) in a family with autosomal dominant non-chromaffin paraganglioma.

We performed a whole genome scan in a family with maternally transmitted paraganglioma (PGL3). The family included five patients with histologically proven paraganglioma and one patient with imaging findings consistent with a paraganglioma. In addition, there were 33 clinically unaffected family members. Of these eight could be examined by magnetic resonance imaging. Our investigations indicate that PGL3 is located in 1q21-q23 for several reasons: 1) two-point linkage analysis yielded the highest LOD score of 2.25 at 1q21-q23 (marker D1S2675); 2) haplotype analysis was most consistent for 1q21-q23 markers; and 3) the locus was excluded from more than 97% of the genome using a total of 381 highly polymorphic markers.

Chromosomes, Human, Pair 1↗
PubMed2001

Comparative association analysis reveals that corneodesmosin is more closely associated with psoriasis than HLA-Cw*0602-B*5701 in German families.

HLA antigens are associated with psoriasis vulgaris across populations with different ethnic background. We have previously shown that in Caucasians this association is primarily based on the class I alleles of the extended HLA haplotype 57.1 (EH57.1/I), HLA-Cw6-HLA-B57. However, it remained unclear whether HLA-Cw6 itself or a closely linked locus predisposes to the disease. An interesting candidate for this presumed locus is corneodesmosin, which is exclusively synthesized in keratinocytes. The corneodesmosin gene locus (CDSN) is only 160 kb telomeric to HLA-C and tightly associated with psoriasis. In order to find out whether EH57.1/I or a corneodesmosin variant are the susceptibility determinants on 6p, HLA class I alleles and single-nucleotide polymorphisms (SNPs) of corneodesmosin were investigated at the sequence level and analyzed by comparative association tests. Transmission disequilibrium tests (TDT) were performed in 52 nuclear families, of which 36 were fully informative for a joint comparison of HLA and CDSN with regard to association to psoriasis. The extended TDT according to Wilson was employed to test for locus interaction. Using the HLA haplotype EH57.1/I and the CDSN haplotype formed by three intragenic variant sites at nt=619 (T), 1236 (T), and 1243 (C), we obtained the best resolution of parental transmission to index cases in the trio families. On direct comparison of the contributions of the HLA and the CDSN haplotypes, there was a markedly stronger association of the corneodesmosin TTC haplotype, which is not apparent in single locus analysis. We show furthermore that there is no higher order interaction between psoriasis, HLA, and CDSN. This lack of three-locus interaction is suggestive of two independent genetic contributions to psoriasis within the major histocompatibility complex (MHC).

Alleles↗
PubMed2001

Induction of sTNF-R1 and sTNF-R2 by interferon beta-1b in correlation with clinical and MRI activity.

OBJECTIVES: To investigate the influence of interferon (IFN) beta-1b on the serum levels of sTNF-R1, sTNF-R2 and TNF-beta in patients with multiple sclerosis (MS) in correlation with clinical and MRI activity. MATERIALS AND METHODS: Serum samples were obtained every 3 months from 24 patients treated with 8 x 10(6) U of IFN beta-lb every other day (treatment group) and from 21 patients without any immunomodulatory therapy (control group) over a 15-month observation period. The cytokine levels were measured by ELISA. Cranial MRI was performed every 6 months to determine the burden of disease of every patient. RESULTS: In the treatment group we found an obvious increase of sTNFR1 and sTNF-R2 (P < 0.001) and relatively stable serum levels of TNFbeta with no statistical significance (P = 0.56). In the control group, sTNF-R1 showed a significant decrease (P < 0.001) during the same observation period of 15 months. During the 15-month observation period, the MRI-responders group had significant larger mean AUC (area under the concentration-time curve) values of sTNF-R1 (P = 0.04) and sTNF-R2 (P = 0.01) when compared to the group of MRInonresponders. CONCLUSION: The present data suggest that IFN beta-1b induces the expression and shedding of TNF-R1 and TNF-R2. The magnitude of an increase of sTNF-Rs may be a marker for the effectiveness of treatment with IFN beta-1b.

Adjuvants, Immunologic↗
PubMed2001

Prognostic value of soluble tumor necrosis factor receptors 1 and 2 in multiple sclerosis patients treated with interferon beta-1b.

The objective of this study was to investigate the effect of interferon (IFN) beta-1b on the serum levels of soluble tumor necrosis factor receptor 1 (sTNF-R1) and sTNF-R2 in patients with multiple sclerosis (MS) in correlation with clinical and magnetic resonance image (MRI) activity. Serum samples were obtained every 3 months from 24 patients treated with 8 x 10(6) U of IFN beta-1b every other day (treatment group) and from 21 patients without any immunomodulatory therapy (control group) over a 15-month observation period. The cytokine receptor levels were assessed by ELISA. Cranial MRI was performed every 6 months to determine the burden of disease. In the treatment group, the MRI responders had significantly larger mean values for the area under the concentration-time curve of sTNF-R1 (p = 0.04) and sTNF-R2 (p = 0.01) when compared to the MRI nonresponders during the 15-month observation period. With regard to an increase in sTNF-R1 and -2 of more than 20% during the first 3 months of treatment, we observed a sensitivity of 33 and 58%, respectively, a specificity of 90 and 60%, respectively, and a positive predictive value of 80 and 64%, respectively, for MRI response during the 15-month observation period. A decrease in sTNF-R1 and -2 of more than 20% during the first 3 months of treatment had a sensitivity of 40 and 20%, respectively, a specificity of 100 and 100%, respectively, and a positive predictive value of 100 and 100%, respectively, for further MRI nonresponse (during the 15-month observation period). The present data suggest that assessment of sTNF-Rs may contribute to the identification of subgroups of patients who are likely to respond better than others to treatment with IFN beta-1b. This could help to establish a cost-effective prescription pattern for this expensive treatment, which is of importance for the future management of patients with MS.

Adult↗
PubMed2000

Genomewide scan in german families reveals evidence for a novel psoriasis-susceptibility locus on chromosome 19p13.

Psoriasis is a common chronic inflammatory skin disease with a strong genetic component. Few psoriasis-susceptibility loci have been reported, and only two have been confirmed in independent data sets. This article reports results of a genomewide scan that was performed, using 370 microsatellite markers, for psoriasis-susceptibility loci in 32 German extended families, comprising 162 affected and 195 unaffected individuals. Nonparametric linkage analysis of all families provided strong evidence for a novel psoriasis-susceptibility locus on chromosome 19p (Zlr=3.50; P=.0002). Parametric analysis revealed a heterogeneity LOD score of 4.06, corresponding to a genomewide significance level of.037, under the assumption of a recessive model with high disease-allele frequency and 66% as the proportion of linked families. This study confirms linkage of psoriasis to the HLA region on chromosome 6p and suggests additional regions on chromosomes 8q and 21q for further investigations.

Adult↗
PubMed2000

The Conradi-Hünermann-Happle syndrome (CDPX2) and emopamil binding protein: novel mutations, and somatic and gonadal mosaicism.

The Conradi-Hünermann-Happle (CHH) syndrome (X-chromosomal dominant chondrodysplasia punctata type II; MIM 302960) is an X-linked dominant disorder that is characterized by ichthyosis, chondrodysplasia punctata, cataracts and short stature. The disease occurs almost exclusively in females and shows increased disease expression in successive generations (anticipation). Recently, causative mutations in the emopamil binding protein (EBP) have been identified. To better appreciate the genetics of this syndrome we analyzed the EBP gene in seven independent families using PCR, conformation-sensitive gel electrophoresis, direct sequencing and restriction enzyme analysis. We found five novel mutations: three nonsense mutations in exon 2 and exon 3 and two frameshift mutations, one deletion in exon 4 and an insertion in exon 5. In two families, known mutations affecting exon 2 were identified. Surprisingly, we failed to detect the mutation in a grandmother exhibiting minor disease symptoms such as sectorial cataract and attribute this to gonadal and somatic mosaicism. Gonadal mosaicism appeared also to be involved in the case of healthy parents having two affected girls, one of whom died due to the disease. We conclude that gonadal mosaicism has to be considered when dealing with seemingly sporadic cases.

Adolescent↗
PubMed2000

Hereditary angioedema with normal C1-inhibitor activity in women.

BACKGROUND: Hereditary angioedema (HAE) is a well defined autosomal dominant disease (Mendelian Inheritance in Man #106100) that results from an inherited deficiency of C1 (the activated first component of complement) inhibitor function. We report an unusual variant of HAE with normal biochemical C1-inhibitor function, occurring only in women. METHODS: We screened 574 patients with recurrent angioedema of the skin for presence of HAE. 283 patients were selected, in whom angioedema was associated with abdominal pain attacks or recurrent life-threatening episodes of upper-airway obstruction, or both, rather than with urticaria. We measured C1-inhibitor concentration and functional activity as well as complement C4 concentration and took pedigrees to characterise patients. FINDINGS: 94 HAE cases with C1-inhibitor deficiency, positive family history, or both were identified. Biochemical testing showed that 84 patients from 49 families had a functional C1-inhibitor deficiency. 11 of these patients had no affected family members (probably representing de-novo mutations). Ten women with HAE, from ten families, had normal C1-inhibitor protein concentrations and function, and normal C4 concentration. A more detailed study of these families identified another 26 affected members, who were also all women. Of those women, 14 could be studied and also had normal C1-inhibitor concentration and function. The disease was seen in successive generations, and in offspring of affected mothers, the sex ratio (M/F) was shifted to 1/1.5. INTERPRETATION: HAE with normal C1-inhibitor concentration and function represents a unique genetic disease arising only in women. The formal genetics of this entity are suggestive of an X-linked dominant mode of inheritance. For this disorder we propose the term hereditary angioedema type 3 (HAE III).

Abdominal Pain↗
PubMed2000

CD45RA+ ICAM-3+ lymphocytes in cerebrospinal fluid and blood as markers of disease activity in patients with multiple sclerosis.

OBJECTIVES: Autoreactive T cells targeted against antigens of the myelin sheath are suggested to play an important role in the pathogenesis of multiple sclerosis (MS). Naive (CD45RA+) T cells and intercellular adhesion molecule-3 (ICAM-3) are markers for un-activated lymphocytes. This study was performed to investigate, whether the expression levels of these antigens both on cerebrospinal fluid (CSF) and peripheral blood lymphocytes can be used as activity markers in MS. MATERIALS AND METHODS: Corresponding blood and CSF samples were obtained from 31 patients with relapsing-remitting MS. Of the 31 MS patients 23 were suffering from acute relapses at the time of examination and all of them were treated with high-dose methylprednisolone (MP). Blood was collected again on the 10th day of therapy and after 3 months. The control group consisted of 12 healthy persons. Two-color flow cytometry was performed to evaluate the percentage of both CD45RA+ and ICAM-3+ cells within the lymphocyte population. RESULTS: The percentage of CD45RA+ ICAM-3+ cells in the CSF of MS patients with relapses was significantly increased compared to patients in remission (P<0.05). In blood, a significantly lower percentage of CD45RA+ ICAM-3+ lymphocytes was found in both patient groups compared to healthy controls (Relapse: P<0.05, Remission: P<0.10). Additionally, we found a significant increase (P < 0.01) in the percentage of CD45RA+ ICAM-3+ lymphocytes in blood of MS patients suffering from acute relapse on the 10th day of high-dose MP treatment. CONCLUSION: Our data suggest that the percentage of CD45RA+ ICAM-3+ lymphocytes in CSF can be used as marker of disease activity in MS patients.

Acute Disease↗
PubMed2000

The Conradi-Hünermann-Happle syndrome is caused by mutations in the gene that encodes a 8- 7 sterol isomerase and is biochemically related to the CHILD syndrome.

We here review the clinical and genetic features of the Conradi-Hünermann-Happle syndrome. The disease is characterized by chondrodysplasia punctata, linear ichthyosis, cataract, and short stature. The X-linked dominant mode of inheritance was first recognized by Rudolf Happle in the years 1977 to 1981, who also fully delineated the clinical spectrum of this clinico-genetic entity. In the past, linkage studies had firmly excluded the gene for this syndrome from the Xq28 region, but unfortunately had also failed to clearly map the gene elsewhere on the X-chromosome. Very recently, causative mutations were identified in a large number of patients in the gene for emopamil binding protein. This gene is located on the short arm of Xp11.22-23 and also acts as a D8-D7 sterol isomerase. This enzymatic function plays a crucial role in cholesterol biosynthesis. It is of note that very recent investigations by the Marburg group have disclosed that the CHILD syndrome is likewise caused by a similar metabolic defect, namely a deficiency of a 3b-hydroxysteroid dehydrogenase (NSDHL). In the pathway of cholesterol biosynthesis this enzyme functions "upstream" of D8-D7 sterol isomerase and was shown to underlie the mouse mutant bare patches. Molecular studies in these syndromes now allow us to determine which family members carry the mutation and have already provided evidence in the Conradi-Hünermann-Happle syndrome for both gonadal and somatic mosaicism. As gonadal mosaicism seems to be frequent in this disease, a recurrence risk for further pregnancies has to be considered when dealing with a seemingly sporadic case.

3-Hydroxysteroid Dehydrogenases↗
PubMed1999

Functional X-chromosomal mosaicism of the skin: Rudolf Happle and the lines of Alfred Blaschko.

In this article, the contribution of Rudolf Happle to the understanding of X-linked skin diseases is reviewed. In 1977 he proposed functional X-chromosomal mosaicism as the genetic mechanism underlying cutaneous anomalies that were seen in a number of X-linked skin diseases such as incontinentia pigmenti or focal dermal hypoplasia. Moreover, he recognized that these cutaneous anomalies followed the lines of Blaschko and thus he could tie in the development of the lines of Blaschko with a datable embryonic event. Convincing proof for the concept of functional X-chromosomal mosaicism was later provided by his group from functional sweat studies in female carriers of the X-linked gene defect hypohidrotic ectodermal dysplasia showing again on the back of the patient a gross, fountain-like mosaic typical of the lines of Blaschko. Moreover, in the years 1977 to 1981 he recognized the mosaic pattern in a syndrome of chondrodysplasia punctata, linear ichthyosis, patchy cicatricial alopecia, unilateral cataracts, and short stature again as a functional X-chromosomal mosaic becoming manifest exclusively in women and proposed that this syndrome, which is today named after him, is because of an X-linked dominant gene defect. Finally, the puzzling molecular genetics of the Happle syndrome are reviewed. Most likely, the Happle syndrome gene is not lethal for hemizygously affected males but rather similar to the example of epilepsy with mental retardation limited to females, the gene actually spares male gene carriers.

Alopecia↗
PubMed1999

Identification of novel mutations in basic hair keratins hHb1 and hHb6 in monilethrix: implications for protein structure and clinical phenotype.

Monilethrix is an hereditary hair dystrophy recently shown to be due to mutations in the helix termination motif of two type II (basic) human hair keratin genes, hHb1 and hHb6. It has been suggested that mutation in hHb1 produces a less severe phenotype. We have studied hair keratin genes and clinical features in 18 unrelated pedigrees of monilethrix from Germany, Scotland, Northern Ireland, and Portugal, in 13 of which mutations have not previously been identified. By examining the rod domains of hHb1, hHb3 and hHb6, we have identified mutations in nine of the new pedigrees. We again found the glutamine-lysine substitution (E413K) in the helix termination motif of hHb6 in two families, and in another, the corresponding E413K substitution in the hHb1 gene. In four families a similar substitution E402K was present in a nearby residue. In addition two novel mutations within the helix initiation motif of hHb6 were found in Scottish and Portuguese cases, in whom the same highly conserved asparagine residue N114 was mutated to histidine (N114H) or aspartic acid (N114D) residues, respectively. In four other monilethrix pedigrees mutations in these domains of hHb1, hHb3, and hHb6 were not found. The mutations identified predict a variety of possible structural consequences for the keratin molecule. A comparison of clinical features and severity between cases with hHb1 and hHb6 mutations does not suggest distinct effects on phenotype, with the possible exception of nail dystrophy, commoner with hHb1 defects. Other factors are required to explain the marked variation in clinical severity within and between cases.

Amino Acid Sequence↗