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S Schauer

Publications and source records attributed to S Schauer.

11 recordsLinked to original sources
PubMed2005

mRNA expression patterns indicate CD30 mediated activation of different apoptosis pathways in anaplastic large cell lymphoma but not in Hodgkin's lymphoma.

One of the main functions of the tumor necrosis factor receptor (TNFR) family is induction of apoptosis. CD30, a member of the TNFR superfamily is overexpressed in highly proliferating tumors such as anaplastic large cell lymphoma (ALCL) and Hodgkin's lymphoma (HL). CD30 stimulation leads to apoptosis and growth arrest in cultured ALCL, but not in Hodgkin-Reed-Sternberg cells. To identify changes in the transcriptional program responsible for these opposing effects, we performed gene expression analysis in CD30-stimulated ALCL (Karpas 299) and HL (KM-H2) cell lines using cDNA microarrays. Selected genes were validated by real-time PCR. Hierarchical clustering was applied to the whole dataset and separated the cell lines clearly with respect to their origin. In HL, there were only minor CD30-specific alterations, whereas ALCL unequivocally showed a pronounced CD30-specific transcriptional response. Ninety-three genes (6.6% of total) were deregulated by more than a factor of two after CD30 stimulation in ALCL cells. The majority of genes identified are involved in cell cycle regulation and apoptosis. mRNA expression patterns further indicate that in contrast to HL, CD30 stimulation in ALCL induces cell death via the CD95-CD95 ligand (CD95L) pathway and the TNF-R1/TNF-R2 crosstalk. These data provide a detailed view on the transcriptional changes upon CD30 stimulation and may explain the observed functional differences of HL and ALCL.

Apoptosis↗
PubMed2000

cDNA cloning and analysis of tissue-specific expression of mouse peroxisomal straight-chain acyl-CoA oxidase.

Straight-chain acyl-CoA oxidase is the first and rate limiting enzyme in the peroxisomal beta-oxidation pathway catalysing the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs, thereby producing H2O2. To study peroxisomal beta-oxidation we cloned and characterized the cDNA of mouse peroxisomal acyl-CoA oxidase. It consists of 3778 bp, including a 1983-bp ORF encoding a polypeptide of 661 amino-acid residues. Like the rat and human homologue the C-terminus contains an SKL motif, an import signal present in several peroxisomal matrix proteins. Sequence analysis revealed high amino-acid homology with rat (96%) and human (87%) acyl-CoA oxidase in addition to minor homology ( approximately 40%) with other related proteins, such as rabbit trihydroxy-cholestanoyl-CoA oxidase, human branched chain acyl-CoA oxidase and rat trihydroxycoprostanoyl-CoA oxidase. Acyl-CoA oxidase mRNA and protein expression were most abundant in liver followed by kidney, brain and adipose tissue. During mouse brain development acyl-CoA oxidase mRNA expression was highest during the suckling period indicating that peroxisomal beta-oxidation is most critical during this developmental stage. Comparing tissue mRNA levels of peroxisome proliferator-activated receptor alpha and acyl-CoA oxidase, we noticed a constant relationship in all tissues investigated, except heart and adipose tissue in which much more, and respectively, much less, peroxisome proliferator-activated receptor alpha mRNA in proportion to acyl-CoA oxidase mRNA was found. Our data show that acyl-CoA oxidase is an evolutionary highly conserved enzyme with a distinct pattern of expression and indicate an important role in lipid metabolism.

Acyl-CoA Oxidase↗
PubMed1997

[Point mutations of the thyrotropin receptor gene in autonomously functioning thyroid gland nodules: correlation with clinical findings and morphology].

Seventeen autonomously functioning thyroid nodules (AFTN) were analyzed for the most frequent mutations of the thyrotropin (TSH) receptor gene at codons 619, 631, 632 and 633. DNA was extracted from formalin-fixed, paraffin-embedded samples from both nodules and surrounding tissue after micro- or macrodissection. A fragment of the TSH receptor gene (bp 1762-1976) encoding the third cytoplasmic loop and the sixth transmembranous domain was amplified by PCR. Screening for mutations at codons 619, 631, 632 and 633 was performed by restriction enzyme analysis using Asp 718, Hph I, Taq I and EcoR I, respectively. For verification, cases with a mutated restriction site were cloned and sequenced. Mutations were found in 3 AFTNs (18%): in 2 cases at codon 632 and in 1 case at codon 631. The 2 cases with a mutation at codon 632 harbored additional mutations at codon 599 and 640, respectively, detected by sequencing. Normal thyroid tissue outside the AFTNs did not harbor mutant TSH-receptor. Mutations occurred in patients with clinical and subclinical hyperthyroidism. Mutations were associated both with total (2 cases) and partial (1 case) suppression of the surrounding thyroid tissue as noted on the scinti scan. AFTNs with TSH-receptor mutation occurred as single nodules. All 3 nodules with mutations were classified histologically as nodular hyperplasia according to the criteria of the WHO. Although the number of cases is small, our data suggest that AFTNs are clinically and morphologically heterogenous. Since the most common TSH-receptor mutations occur only in a small subset of AFTNs other molecular genetic alterations may be involved in the development of AFTNs.

Adenoma↗
PubMed1996

[CASUS model trial. A computer-assisted author system for problem-oriented learning in medicine].

The CASUS-project, a three year publicly funded effort to improve the quality of continuing medical education in Germany, has one major goal: The development and evaluation of an easy-to-handle author-system for problem-oriented learning in medicine. On the theoretical basis of the cognitive apprenticeship-approach, the concept of a teaching and learning database as a hypermedia system was built. The student should learn to manage authentical problems in the form of authentical clinical cases. The step-by-step learning process is expert-guided by the clinical authors of each case. The creation of various differential diagnoses by the learner is strongly supported in the process. The structure of the program can also be used for case-based examinations. In parallel to the technical development, a case-selection process for medical students students in internal medicine was initiated. About 120 relevant diseases were identified to be represented in the CASUS-case library. Prevalence, transferability of knowledge, treatability, urgence of treatment and preventive aspects were used as selection criteria. The system will be evaluated during the implementation of test cases and will then be available to be used by authors and students on a routine basis in 1997.

Authorship↗
PubMed1993

Human ERCC5 cDNA-cosmid complementation for excision repair and bipartite amino acid domains conserved with RAD proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe.

Several human genes related to DNA excision repair (ER) have been isolated via ER cross-species complementation (ERCC) of UV-sensitive CHO cells. We have now isolated and characterized cDNAs for the human ERCC5 gene that complement CHO UV135 cells. The ERCC5 mRNA size is about 4.6 kb. Our available cDNA clones are partial length, and no single clone was active for UV135 complementation. When cDNAs were mixed pairwise with a cosmid clone containing an overlapping 5'-end segment of the ERCC5 gene, DNA transfer produced UV-resistant colonies with 60 to 95% correction of UV resistance relative to either a genomic ERCC5 DNA transformant or the CHO AA8 progenitor cells. cDNA-cosmid transformants regained intermediate levels (20 to 45%) of ER-dependent reactivation of a UV-damaged pSVCATgpt reporter plasmid. Our evidence strongly implicates an in situ recombination mechanism in cDNA-cosmid complementation for ER. The complete deduced amino acid sequence of ERCC5 was reconstructed from several cDNA clones encoding a predicted protein of 1,186 amino acids. The ERCC5 protein has extensive sequence similarities, in bipartite domains A and B, to products of RAD repair genes of two yeasts, Saccharomyces cerevisiae RAD2 and Schizosaccharomyces pombe rad13. Sequence, structural, and functional data taken together indicate that ERCC5 and its relatives are probable functional homologs. A second locus represented by S. cerevisiae YKL510 and S. pombe rad2 genes is structurally distinct from the ERCC5 locus but retains vestigial A and B domain similarities. Our analyses suggest that ERCC5 is a nuclear-localized protein with one or more highly conserved helix-loop-helix segments within domains A and B.

Amino Acid Sequence↗
PubMed1991

Phagocytosis activity of polymorphonuclear cells of normal persons and dialysis patients is influenced by different dialysis membranes.

Leukocyte (PMN) functional capacity has been investigated through evaluation of phagocytosis of opsonised yeast cells in a radiometric test system. The PMN of dialysis patients (DP) had a slightly lower ability to ingest opsonised yeast cells in comparison with normal persons (NP), suggesting that an intrinsic cellular defect may exist. Under the influence of six membranes (cellulose acetate, regenerated cellulose, modified cellulose, cuprophane, polysulphone, and polymethylmethacrylate) the phagocytosis index decreased significantly between 10 and 17% in NP and between 13 and 23% in DP. There is a clear correlation with the membrane surface area. These results are not explained by the number of dead leukocytes (4-6.5% in DP and also in NP independently of membrane contact). The direct membrane effect could be responsible for the diminished phagocytic activity of leukocytes in NP and DP. Aqueous extracts of membranes alone resulted in no change of the phagocytic ability of PMN. Extracellular or 'uraemic factors' were excluded by the test procedure. The killing rate of yeast cells by PMN in NP and DP was not influenced in any of the membranes tested.

Adult↗
PubMed1990

Influence of membranes on generation of beta 2 M and release of leukocyte lysosomal enzymes.

Normal leukocyte functional capacity was investigated by evaluation of phagocytosis of opsonised yeast cells in a radiometric test system. After incubation with dialysis membranes (different cellulosic membranes, polysulfon membrane (PS), polymethylmetacrylate membrane (PMMN), the phagocytosis index, expressed as percent decrease with respect to initial values without membrane, decreased by 10%-25%. The most pronounced effect was observed with PS, cuprophane, modified cellulose and PMMA. The results are not related to differences in the viability of PMN during the test procedure; dead PMN amounted to about 4-6.5%. A significant increase in beta-NAG and beta-Gluc activities was released in the supernatants of the phagocytosis suspensions. This increase activity can be explained by the phagocytosis of PMN but it was not influenced by membrane contact. There was no influence of membrane contact or phagocytosis activity of PMN on the beta 2 M concentration in the supernatant demonstrating that no in vitro generation during incubation with either membrane exists.

Acetylglucosaminidase↗
PubMed1988

New one-step enzyme immunoassay for free thyroxin.

This enzyme immunoassay for free thyroxin (FT4) involves simultaneous incubation of sample and thyroxin conjugated to horseradish peroxidase (EC 1.11.1.7) in antibody-coated tubes at room temperature. The test can be performed in 90 min. It is not influenced by variations in concentrations of thyroxin-binding globulin (TBG), thyroxin-binding prealbumin, or albumin. With increased concentrations of non-esterified fatty acids, the measured FT4 equivalent concentrations increase immediately, indicating displacement of endogenous thyroxin from its binding sites. FT4 values obtained with this assay for 110 samples, including sera with low albumin and high TBG as well as sera of patients treated with heparin, agreed well with those measured by a two-step radioimmunoassay and with the T4/TBG ratio. The measurable range of FT4 with our assay is 2.5 to 65 ng/L. Intra-assay CVs range from 3.4% to 2.2%, interassay CVs from 6.6% to 2.6% at concentrations of 9 to 45 ng of FT4 equivalent per liter.

Fatty Acids, Nonesterified↗
PubMed1979

Effect of pili on susceptibility of Escherichia coli to phagocytosis.

The degree of piliation of 20 clinical isolates of Escherichia coli was correlated with their susceptibility to phagocytosis by human polymorphonuclear leukocytes. Piliation was quantitated by negative staining, and phagocytosis was quantitated by a monolayer technique. Ingestion was confirmed by electron microscopy. In the absence of source of opsonins, there was a positive correlation between the degree of piliation and susceptibility to phagocytosis (y = 0.83x + 19.58; correlation coefficient = 0.65; P < 0.01). Heavily piliated strains were no longer phagocytized after their pili were removed by ultraviolet irradiation. Phagocytosis was reduced 75% in the presence of 0.1 M d-mannose, an agent which competitively inhibits binding of pili to cell surfaces. l-Mannose, d-glucose, and d-galactose were much less inhibitory. The viability of piliated organisms was reduced by 1 log after 1 h of incubation with polymorphonuclear leukocytes. Addition of 10% fresh human serum increased both the rate and completeness of killing. These observations suggest that polymorphonuclear leukocytes may interact with the pili of E. coli to promote phagocytosis. This phenomenon may have clinical relevance in situations where normal opsonic activity is poor, such as the renal medulla.

Binding Sites↗
PubMedDate not supplied

Muscle-specific overexpression of human lipoprotein lipase in mice causes increased intracellular free fatty acids and induction of peroxisomal enzymes.

A transgenic mouse model for peroxisomal and mitochondrial induction caused by increased uptake of fatty acids in muscle was established. Transgenic mouse lines were generated using a human lipoprotein lipase (LPL) mini gene (3-20 copies) driven by the promoter of the muscle creatine kinase gene. Expression of human LPL was only observed in skeletal and cardiac muscle. In proportion to the level of LPL overexpression increased LPL activity in skeletal (up to 24-fold) and cardiac (up to three-fold) muscle, decreased plasma triglyceride levels, elevated free fatty acid (FFA) uptake by muscle tissue, weight loss (due to a reduction in muscle mass as well as adipose tissue mass) and premature death were observed. A remarkable increase in the number of mitochondria and peroxisomes was detected using oxide-electron microscopy. Proliferation of mitochondria and peroxisomes was confirmed by a dose-dependent increase of marker enzyme activity (succinate-dehydrogenase and catalase). In addition, peroxisomal acyl-CoAse enzyme protein was markedly elevated whereas mRNA was increased only up to two-fold. No changes in peroxisomal proliferator activated receptor alpha mRNA was found. This degree of proliferation and enzyme activity of mitochondria and peroxisomes suggests that FFA play an important role in the induction of these organelles. In addition, myopathy characterized by excessive glycogen storage, muscle fiber degeneration, and fiber atrophy with centralization of nuclei, mimicking several forms of human myopathies was noted. Our results imply that improper regulation of muscle LPL leading to increased fatty acid levels in muscle can cause severe pathological changes. This effect may be important in the pathogenesis of human myopathies. We conclude that these transgenic mouse lines could serve as a useful animal model for the investigation of myopathies and the effects of fatty acids on the induction of mitochondria and peroxisomes.

Animals↗