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Biomedical subjects

C Schneider

Publications and source records attributed to C Schneider.

At least 91 records · Page 5Linked to original sources
PubMed2001

Proximal myotonic myopathy and proximal myotonic dystrophy: two different entities? The phenotypic variability of proximal myotonic syndromes.

Multisystemic myotonic myopathies are characterised by a variable pattern of symptoms and signs and a variable degree of disease severity. Proximal myotonic dystrophy has been described as an entity distinct from proximal myotonic myopathy because of severe proximal muscle weakness and dystrophic changes on magnetic reasonace imaging and on muscle histopathology. We describe two siblings, one of them presenting with a proximal myotonic myopathy phenotype, the other with a proximal myotonic dystrophy-like phenotype. The variability of disease expression in these two siblings suggests that a proximal myotonic dystrophy-like variant may occur in proximal myotonic myopathy.

Biopsy↗
PubMed2001

Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder.

Autistic disorder (MIM 209850) is currently viewed as a neurodevelopmental disease. Reelin plays a pivotal role in the development of laminar structures including the cerebral cortex, hippocampus, cerebellum and of several brainstem nuclei. Neuroanatomical evidence is consistent with Reelin involvement in autistic disorder. In this study, we describe several polymorphisms identified using RNA-SSCP and DNA sequencing. Association and linkage were assessed comparing 95 Italian patients to 186 ethnically-matched controls, and using the transmission/disequilibrium test and haplotype-based haplotype relative risk in 172 complete trios from 165 families collected in Italy and in the USA. Both case-control and family-based analyses yield a significant association between autistic disorder and a polymorphic GGC repeat located immediately 5' of the reelin gene (RELN) ATG initiator codon, as well as with specific haplotypes formed by this polymorphism with two single-base substitutions located in a splice junction in exon 6 and within exon 50. Triplet repeats located in 5' untranslated regions (5'UTRs) are indicative of strong transcriptional regulation. Our findings suggest that longer triplet repeats in the 5'UTR of the RELN gene confer vulnerability to autistic disorder.

Adult↗
PubMed2001

Exercise-associated hyponatremia: a review.

This paper reviews the extensive literature on hyponatremia, a common and potentially serious complication of ultra-distance exercise. Fluid overload is the likely aetiology. Fluid intakes are typically high in athletes who develop hyponatremia, although hyponatremia can occur with relatively modest fluid intakes. The development of fluid overload and hyponatremia in the presence of a modest fluid intake raises the possibility that athletes with this condition may have an impaired renal capacity to excrete a fluid load. The bulk of evidence favours fluid retention in the extracellular space (dilutional hyponatremia) rather than fluid remaining unabsorbed in the intestine. Female gender is an important risk factor for the development of hyponatremia. Management and prevention of exercise-associated hyponatremia are discussed.

Adolescent↗
PubMed2001

[Factoral structure and psychometric properties of the German version of the Toronto Alexithymia Scale (TAS-20) in psychosomatic patients].

The present paper describes the attempt to cross-validate the three-factorial structure of the German Version of the 20-Item Toronto Alexithymia Scale in a population of 419 patients, suffering of psychogenic disorders. However, results neither revealed good internal consistencies nor was it possible to obtain an acceptable adaptation of the empirical data on the postulated model. Therefore an explorative factor analysis was performed in order to get a more consistent factor model. The hereby resulting four-factorial structure was congruent with reference to theoretical and empirical data of Alexithymia. However, additional cross-validation in other populations has to be investigated.

Adult↗
PubMed2001

[MR angiography of pelvic and leg vessels with automatic table movement technique ("Mobi-Trak")--clinical experience with 450 studies].

PURPOSE: By a retrospective clinical evaluation of 450 MR angiograms of the lower extremity arteries the question was posed of whether MR angiography can replace i.a. DSA. MATERIAL AND METHODS: Image quality of 450 MR angiograms was graded by 4 radiologists; in 102 patients who underwent radiological intervention a comparison between MR angiogram and i.a. DSA was done. Additionally, MR angiography was compared with the results of surgical intervention in 106 cases. RESULTS: 6% of 450 examinations showed a significant limitation of diagnostic information. 5 examinations (1%) had to be redone by i.a. DSA. In all cases the diagnosis from MRA was proven by the results of the following i.a. DSA or surgical procedure. CONCLUSION: The retrospective clinical evaluation of 450 examinations demonstrated that MR angiography of the lower extremity arteries can replace i.a. DSA in routine use.

Adult↗
PubMed2001

Expression of specific matrix metalloproteinases in inflammatory myopathies.

The family of matrix metalloproteinases (MMPs) comprises endopeptidases that are capable of degrading all extracellular matrix components. Given these actions, it is conceivable that MMPs may play a pathogenic role in inflammatory myopathies. These immune-mediated disorders are characterized by the invasion of mononuclear phagocytes and T lymphocytes and the loss of muscle fibres. We examined whether specific MMPs and their natural inhibitors (tissue inhibitors of metalloproteinases; TIMPs) are expressed in muscle during acute inflammatory attacks by studying muscle biopsies obtained from patients diagnosed as having polymyositis, dermatomyositis, sporadic inclusion body myositis and, for comparison, from cases of various muscular dystrophies. Quantitative polymerase chain reaction analysis revealed significantly elevated mRNA expression of interstitial collagenase (MMP-1) and gelatinase B (MMP-9) in polymyositis and dermatomyositis and to a lesser extent in inclusion body myositis, whereas the level of expression of TIMPs remained unchanged in comparison with controls. Increased mRNA levels were associated with enhanced enzyme expression, as determined by immunoblotting, gelatin zymography and in situ zymography. Immunohistochemically, MMP-1 could be localized around the sarcolemma of diseased muscle fibres and to cells resembling fibroblasts, whereas MMP-9 seemed to be expressed primarily by invading T lymphocytes. Raised levels of MMPs could not be detected in the sera of affected patients, emphasizing the crucial action of MMPs in the inflamed muscle. Our results imply a pathogenic role for specific MMPs in the genesis of inflammatory myopathies, and open new strategies for therapeutic intervention.

Adult↗
PubMed2001

No association between the 4g/5G polymorphism of the plasminogen activator inhibitor-1 gene promoter and autistic disorder.

Plasmin, a serine protease, is involved in many physiologically relevant processes, including haemostasis, cellular recruitment during immune response, tumour growth, and also neuronal migration and synaptic remodelling. Both tissue-type and urokinase-type plasminogen activators can be efficiently inhibited by plasminogen activator inhibitor-1 (PAI-1), a protease inhibitor of the serpin family. The human PAI-1 gene is located on chromosome 7q, within or close to a region that has been linked to autism in several linkage studies. Autism seems to be characterized by altered neuronal cytoarchitecture, synaptogenesis and possibly also cellular immune responses. We began addressing the potential involvement of the PAI-1 gene in autistic disorder with this linkage/association study, assessing transmission patterns of the 4G/5G polymorphism in the PAI-1 gene promoter that was previously shown to significantly affect PAI-1 plasma levels. No linkage/association was found in 167 trios with autistic probands, recruited in Italy and in the USA. We thus found no evidence that this polymorphism, or putative functionally relevant gene variants in linkage disequilibrium with it, confer vulnerability to autistic disorder.

Adolescent↗
PubMed2001

Helicobacter pylori eradication treatment does not benefit patients with nonulcer dyspepsia.

OBJECTIVES: The aim of this study was to assess the still controversial role of treatment of Helicobacter pylori (H. pylori) infection in patients with nonulcer dyspepsia. METHODS: We conducted a double-blind, randomized, placebo-controlled, multicenter trial comparing the efficacy of 7 days of eradication treatment (lansoprazole 15 mg b.i.d., amoxicillin I g b.i.d., and clarithromycin 500 mg b.i.d.) with a control treatment (lansoprazole 15 mg b.i.d. and placebo) in H. pylori-infected patients with nonulcer dyspepsia. 13C breath tests were performed at baseline and during follow-up. We assessed patient symptoms, health status (based on the SF-12 questionnaire), patient satisfaction, drug consumption, health care consultation behavior, and absenteeism related to dyspepsia over a 1-yr period. RESULTS: A total of 74 patients randomized to eradication treatment and 70 patients randomized to placebo were compared. The rate of eradication of H. pylori infection was 75% in the active treatment group and 4% in the placebo group (p < 0.005). The symptom score improved to a similar extent in the group receiving active treatment (-4.0; 95% CI = -5.0 to -3.0) and placebo (-3.6; 95% CI = -4.5 to -2.7). Treatment response was not related to the severity or duration of initial symptoms or to the severity of gastritis on histology. Quality of life scores were comparable at 12 months. There was no significant difference in dyspepsia-related absenteeism or satisfaction with management of NUD. Patients receiving active treatment were more likely not to have had to use any dyspepsia treatment over the 12 months (60.8% vs 44.3%; p = 0.047). CONCLUSIONS: This study did not demonstrate any substantial benefit of curing H. pylori infection in patients with nonulcer dyspepsia. The study adds further evidence that H. pylori is not the main pathogenetic or therapeutic target in these patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Gas6 induces growth, beta-catenin stabilization, and T-cell factor transcriptional activation in contact-inhibited C57 mammary cells.

Gas6 is a growth factor related to protein S that was identified as the ligand for the Axl receptor tyrosine kinase (RTK) family. In this study, we show that Gas6 induces a growth response in a cultured mammalian mammary cell line, C57MG. The presence of Gas6 in the medium induces growth after confluence and similarly causes cell cycle reentry of density-inhibited C57MG cells. We show that Axl RTK but not Rse is efficiently activated by Gas6 in density-inhibited C57MG cells. We have analyzed the signaling required for the Gas6 proliferative effect and found a requirement for PI3K-, S6K-, and Ras-activated pathways. We also demonstrate that Gas6 activates Akt and concomitantly inhibits GSK3 activity in a wortmannin-dependent manner. Interestingly, Gas6 induces up-regulation of cytosolic beta-catenin, while membrane-associated beta-catenin remains unaffected. Stabilization of beta-catenin in C57MG cells is correlated with activation of a T-cell factor (TCF)-responsive transcriptional element. We thus provide evidence that Gas6 is mitogenic and induces beta-catenin proto-oncogene stabilization and subsequent TCF/Lef transcriptional activation in a mammary system. These results suggest that Gas6-Axl interaction, through stabilization of beta-catenin, may have a role in mammary development and/or be involved in the progression of mammary tumors.

3T3 Cells↗
PubMed2001

Mycophenolate mofetil in the therapy of severe myasthenia gravis.

Mycophenolate mofetil is a novel immunosuppressive drug already established in transplantation medicine. Recently, results of three open clinical trials on mycophenolate mofetil in myasthenia gravis have been reported. Mycophenolate mofetil in a dose of 1.0-2.0 g/day was given in 2 patients with severe refractory myasthenia gravis and in 1 patient with myasthenia gravis-polymyositis syndrome. Apart from dose-dependent reversible hemolytic anemia in 1 patient, no severe side effects occurred. Considerable improvement of myasthenic symptoms was seen in all patients within 3-6 months after the initiation of this therapy. Mycophenolate mofetil may be considered as a useful alternative in the treatment of severe myasthenia gravis when standard therapeutic regimens fail. It is usually well tolerated and its application is simple.

Aged↗
PubMed2001

Laparoscopic anterior resection for rectal carcinoma. Results of a registry.

At the present time, laparoscopic anterior resection of the rectum cannot be recommended for routine use. Such operations should be performed for curative intent only within scientifically valid studies. Furthermore, only interventions involving the upper part of the rectum or the rectosigmoidal junction can, on the basis of the morbidity rate, be justified. Procedures done on the low rectum necessitating a total mesorectal excision technically are difficult and, in the present study, are associated with a significant increase in morbidity, in particular anastomotic leakage. Therefore, tumors in the lower two thirds of the rectum that may be eligible for restorative proctectomy should not be treated for curative intent by the laparoscopic approach. General reservations also persist with regard to compliance with the principles of oncologic radicality.

Adult↗
PubMed2000

Malignant potential and cytogenetic characteristics of occult disseminated tumor cells in esophageal cancer.

Although micrometastatic cancer cells in lymph nodes can be detected by monoclonal antibodies against epithelial or tumor-associated antigens, it remains unclear whether these cells are precursors of overt metastases or shedded tumor cells with a limited life span. Here we used esophageal cancer as a model to evaluate the prognostic significance and biological characteristics of such micrometastases. In lymph nodes classified as tumor free by conventional histopathological staging, tumor cells were identified with monoclonal antibody Ber-EP4 in 89 of 126 patients (71%) with completely resected (R0) esophageal carcinomas. Multivariate survival analysis underlined the strong and independent prognostic significance of Ber-EP4-positive cells in "node-negative" (pN0) patients. To assess the biology of Ber-EP4-positive cells, we established tumor cell lines from an immunohistochemically positive lymph node and the autologous primary tumor. p53 mutational analysis and multiplex-fluorescence in situ hybridization revealed common aberrations shared between both cell lines, whereas an insertion of chromosome 13 material in the short arm of chromosome 1 was only observed in micrometastatic cells. The tumorigenicity and metastatic potential of both cell lines were demonstrated in severe combined immunodeficient mice. In conclusion, our data provide first direct evidence for the malignant potential of micrometastatic cancer cells.

Adenocarcinoma↗
PubMed2000

Adenosine deaminase alleles and autistic disorder: case-control and family-based association studies.

Adenosine deaminase (ADA) plays a relevant role in purine metabolism, immune responses, and peptidase activity, which may be altered in some autistic patients. Codominant ADA1 and ADA2 alleles code for ADA1 and ADA2 allozymes, the most frequent protein isoforms in the general population. Individuals carrying one copy of the ADA2 allele display 15 to 20% lower catalytic activity compared to ADA1 homozygotes. Recent preliminary data suggest that ADA2 alleles may be more frequent among autistic patients than healthy controls. The present study was undertaken to replicate these findings in a new case-control study, to test for linkage/association using a family-based design, and to characterize ADA2-carrying patients by serotonin blood levels, peptiduria, and head circumference. ADA2 alleles were significantly more frequent in 91 Caucasian autistic patients of Italian descent than in 152 unaffected controls (17.6% vs. 7.9%, P = 0.018), as well as among their fathers. Family-based tests involving these 91 singleton families, as well as 44 additional Caucasian-American trios, did not support significant linkage/association. However, the observed preferential maternal transmission of ADA2 alleles, if replicated, may point toward linkage disequilibrium between the ADA2 polymorphism and an imprinted gene variant located in its vicinity. Racial and ethnic differences in ADA allelic distributions, together with the low frequency of the ADA2 allele, may pose methodological problems to future linkage/association studies. Direct assessments of ADA catalytic activity in autistic individuals and unaffected siblings carrying ADA1/ADA1 vs ADA1/ADA2 genotypes may provide stronger evidence of ADA2 contributions to autistic disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:784-790, 2000.

Adenosine Deaminase↗
PubMed2000

Regulation of p53 activity in nuclear bodies by a specific PML isoform.

Covalent modification of the promyelocytic leukaemia protein (PML) by SUMO-1 is a prerequisite for the assembly of nuclear bodies (NBs), subnuclear structures disrupted in various human diseases and linked to transcriptional and growth control. Here we demonstrate that p53 is recruited into NBs by a specific PML isoform (PML3) or by coexpression of SUMO-1 and hUbc9. NB targeting depends on the direct association of p53, through its core domain, with a C-terminal region of PML3. The relocalization of p53 into NBs enhances p53 transactivation in a promoter-specific manner and affects cell survival. Our results indicate the existence of a cross-talk between PML- and p53-dependent growth suppression pathways, implying an important role for NBs and their resident proteins as modulators of p53 functions.

Biological Transport, Active↗
PubMed2000

[Cardiac manifestations of peripheral primitive neuroectodermal tumor (pPNET): a rare case].

HISTORY: A 44-year-old man presented to his general practitioner with increasing exertional dyspnoea. After a syncope he was admitted to hospital. INVESTIGATIONS: Echocardiography on admission demonstrated a large pericardial effusion (45 mm over the right and 57 mm over the left ventricle) which, in view of its haemodynamic relevance, had to be removed by pericardiocentesis. Cytological examination of the fluid showed various blood constituents but no atypical cells. Computed tomography (CT) of the thorax revealed a homogeneous hyperdense structure in the area of the left atrium. After several more pericardiocenteses echocardiography showed a pericardial tumour between the left atrium and ventricle. Gastroscopy, coloscopy, abdominal CT, an octreotide scan and positron-emission tomography did not indicate an extracardiac tumour. Coronary angiography and video-assisted thoracoscopy were performed. They confirmed an epicardial tumour at the level of the left atrium. TREATMENT AND COURSE: The entire round and solid tumour of about 3 cm in diameter, at the tip of the left atrial appendage was removed under extracorporeal circulation. No adjuvant treatment was given. Histological and immunohistological tests of the resected specimen (CD-99 and NSE-positive) provided the diagnosis of malignant peripheral primitive neuroectodermal tumour (pPNET). CONCLUSION: There are at present no adequate data on optimal treatment of pPNET in the heart. This case demonstrates that even with a large such tumour long remission is possible after complete removal without any adjuvant treatment.

Adolescent↗
PubMed2000

An entirely humanized CD3 zeta-chain signaling receptor that directs peripheral blood t cells to specific lysis of carcinoembryonic antigen-positive tumor cells.

Recombinant T-cell receptors with antibody-like specificity for tumor-associated antigens are successfully used to direct the cytolytic activity of T cells toward tumor cells. Clinical application, however, needs to comply with the low immunogenicity of the recombinant receptor, efficient gene transfer into peripheral blood T cells, and enrichment of receptor-grafted cells. Here, we address these issues and describe an entirely humanized immune receptor for use in adoptive immunotherapy of colorectal carcinoma. The receptor consists of a single-chain antibody (scFv) binding domain specific for carcinoembryonic antigen (CEA), the IgG hinge and CH2/CH3 (Fc) joining region, and the transmembrane and intracellular CD3 zeta signaling chain. To express the receptor in peripheral blood T cells, both GALV envelope and MuLV 4070A pseudotyped retrovirus turned out to be equally efficient, with transduction efficiencies of about 5% to 40%, depending on the lymphocyte donor. Furthermore, receptor-grafted T cells could be 2- to 6-fold enriched by magnetic activated cell sorting, utilizing an antibody directed to the extracellular IgG domain of the receptor. Upon co-culture with CEA(+) tumor cells, receptor-grafted T cells are specifically and efficiently activated to cytolysis and IFN-gamma secretion, demonstrating their feasibility for the adoptive immunotherapy of CEA(+) carcinomas.

Antibody Specificity↗