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S Schmid

Publications and source records attributed to S Schmid.

At least 37 records · Page 2Linked to original sources
PubMed2004

Intercomparison experiments of systems for the measurement of xenon radionuclides in the atmosphere.

Radioactive xenon monitoring is one of the main technologies used for the detection of underground nuclear explosions. Precise and reliable measurements of (131m)Xe, (133g)Xe, (133m)Xe, and (135g)Xe are required as part of the International Monitoring System for compliance with the Comprehensive Nuclear-Test-Ban Treaty (CTBT). For the first time, simultaneous testing of four highly sensitive and automated fieldable radioxenon measurement systems has been performed and compared to established laboratory techniques. In addition to an intercomparison of radioxenon monitoring equipment of different design, this paper also presents a set of more than 2000 measurements of activity concentrations of radioactive xenon made in the city of Freiburg, Germany in 2000. The intercomparison experiment showed, that the results from the newly developed systems agree with each other and the equipment fulfills the fundamental requirements for their use in the verification regime of the CTBT. For 24-h measurements, concentrations as low as 0.1 mBqm(-3) were measured for atmospheric samples ranging in size from 10 to 80 m(3). The (133)Xe activity concentrations detected in the ambient air ranged from below 1 mBqm(-3) to above 100 mBqm(-3).

Air Pollutants, Radioactive↗
PubMed2004

Cytotoxic mechanisms in different forms of T-cell-mediated drug allergies.

BACKGROUND: Cytotoxic mechanisms are involved in different forms of drug induced exanthems. METHODS: Here we compare the killing pathways of CD4+, CD8+ and CD4/CD8+ T-cell lines (TCL) and clones derived from patients suffering from maculopapular, bullous and pustular drug eruptions. In vitro, perforin and Fas-mediated killing was analysed in cytotoxicity assays against autologous Epstein-Barr virus (EBV)-transformed B-cell lines, Fas-transfected mouse lymphoblasts and natural killer (NK)-target cells. In addition, affected skin lesions and the TCL and clones were stained for perforin and FasL-expression. RESULTS: We detected perforin and some FasL-mediated killing in all three types of exanthems. Some of the drug-specific T-cell clones analysed exerted mainly perforin-, other more FasL-mediated killing showing no strict relationship between their perforin- and Fas-mediated cytotoxic capacity. Using a cell culture method focusing on the generation of cytotoxic T cells, we detected drug-specific CD8+, TCRalphabeta+ T cells, which failed to proliferate to drug presentation by antigen presenting cells but killed in a drug dependent way. Interestingly, these cells had substantial natural killer-like T cell(s) like features as they were CD56+ and CD94+ and had the ability to kill the NK-sensitive cell line K562. CONCLUSION: Our data underline the important role of cytotoxic mechanisms in different forms of drug induced exanthems and suggest that even some T cells with NK-like characteristics may be involved in drug hypersensitivity.

Cell Line↗
PubMed2004

Controlled prospective evaluation of the diagnostic yield of a laryngopharyngeal screening examination during upper gastrointestinal endoscopy.

BACKGROUND AND AIMS: Examination of the laryngopharyngeal area is not always performed during routine upper gastrointestinal (UGI) endoscopies although older studies reported pathological findings in 0.9-3.5% of cases. The aim of our study was to prospectively evaluate the positive and negative predictive value of screening the laryngopharyngeal area during routine UGI endoscopy. METHODS: All patients undergoing elective UGI endoscopy between July 2000 and July 2001 were prospectively enrolled into the study. These patients underwent a careful structured examination of the laryngopharyngeal area, which was videotaped for later blinded review. If a pathological finding was suspected, patients were referred to the study otorhinolaryngologist for further evaluation. In all other cases the videotapes were reviewed by the otorhinolaryngologist, who was blinded to the endoscopic findings. RESULTS: During the study period, 1311 endoscopies were performed in 1209 patients; 1191 were fully evaluated. In 62 endoscopies a pathology in the laryngopharyngeal area was suspected. Forty two were examined by the study otorhinolaryngologist whereas in the remaining 19 only a review of the videotape was possible. In 26 patients pathology was confirmed, corresponding to a positive predictive value of 43% and a negative predictive value of 100%. In one patient (0.08%), an early cancer of the pharyngeal region was detected whereas all other findings were benign lesions. CONCLUSIONS: A screening examination of the laryngopharyngeal area should be part of every UGI endoscopy. A serious pathology such as an early cancer may be detected in approximately 1 in 1000 endoscopies.

Adolescent↗
PubMed2004

BRAF and endocrine tumors: mutations are frequent in papillary thyroid carcinomas, rare in endocrine tumors of the gastrointestinal tract and not detected in other endocrine tumors.

The tumorigenesis of sporadic endocrine tumors is still not fully understood. Activating point mutations of the serine/threonine kinase gene BRAF located on 7q34 are found in a wide range of malignancies, with the highest frequency (66%) occurring in malignant melanomas. Melanomas are tumors of neural-crest-derived cells as are medullary thyroid carcinomas, pheochromocytomas and paragangliomas. BRAF has not been examined in endocrine tumors of the diffuse neuroendocrine system or of neural-crest-derived cells. We examined 130 endocrine tumors of the pancreas, parathyroid gland, adrenal medulla, paraganglia, lung and gastrointestinal tract as well as follicular and c-cell-derived thyroid tumors. We found a high rate of V559E mutations in papillary thyroid carcinomas (47%), one V599E mutation in a well-differentiated gastric endocrine carcinoma (malignant carcinoid), but no activating BRAF mutations in all other endocrine tumors examined. These results point towards different pathways in tumorigenesis of endocrine tumors of various localizations and only rare involvement of the MAP kinase (MAPK) pathway in a subset of malignant neuroendocrine tumors.

Carcinoma, Papillary, Follicular↗
PubMed2002

Reduced IL-4 associated antibody responses to vaccine in early pre-diabetes.

AIMS/HYPOTHESIS: The aim of this study was to determine whether beta-cell autoimmunity is associated with immune response bias to exogenous antigens. METHODS: IgG subclass responses against tetanus toxoid and rubella were measured after vaccination in children with (n=36) and without (n=73) islet autoantibodies participating in the BABYDIAB prospective study of offspring of parents with Type I (insulin-dependent) diabetes mellitus. All children had been vaccinated against tetanus toxoid antigen before 6 months of age and at 18 months of age, and against live attenuated rubella virus at 18 months of age and again before 5 years of age. Tetanus toxoid specific IgG subclasses and cytokine responses were compared in a second cohort of subjects. RESULTS: Responses to tetanus toxoid in islet-autoantibody-negative children were characterized by early IgG1 antibodies at 9 months of age followed by the appearance of IgG4 and lesser IgG2 antibodies at 2 years of age. Children who had developed islet autoimmunity before one year of age (n=15) did not have the shift to IgG4 and IgG2 anti-TT after booster vaccination (p<0.01), and had undetectable or IgG1 restricted responses. This defect was independent of HLA class II genotype, was restricted to children who had islet autoimmunity before 1 year of age, and was most evident in children who already had multiple islet autoantibodies by 9 months of age. IgG4 and IgG2 anti-TT correlated with IL-4 (p<0.005), but not IFNgamma responses. Antibody responses to the IFNgamma-inducing rubella vaccination were strongly IgG1 dominated and no differences were observed between islet autoantibody positive and negative children. CONCLUSIONS/INTERPRETATION: These data are consistent with a reduced capacity to make IL-4 promoted antibody responses to exogenous antigen in early pre-diabetes.

Aging↗
PubMed2001

Analysis of the activity-deprived zebrafish mutant macho reveals an essential requirement of neuronal activity for the development of a fine-grained visuotopic map.

The formation of a retinotopic map is thought to involve an activity-independent molecular phase for early steps of both axon pathfinding and projection and a later phase in which cross talk between retinal ganglion cells (RGCs) and tectal neurons modifies and refines the neuronal connections. We report that the maturation of the retinotopic map in the zebrafish tectum involves activity-dependent processes. Zebrafish larvae mutant for the gene macho (mao) lack neuronal activity in RGCs and also display an enlarged retinotectal projection field but no significant increase in single axon length. This morphological defect can be phenocopied by raising larvae under TTX-induced neural impulse blockade. The effect of activity deprivation is dependent on the developmental stage. The projection phenotype in mao as well as in the TTX-treated larvae develops between 4 and 6 d post-fertilization (dpf), after complete tectal coverage is first achieved. Electrophysiological recordings of RGCs in wild-type and mao zebrafish larvae reveal a temporally regulated reduction of sodium current in the mutant between 5 and 6 dpf. This coincides with the time of the axonal projection shifting on the tectum to compensate for the disparate growth patterns of the retina and the tectum. Our genetic and physiological analyses suggest a model in which neuronal activity in RGCs is needed for the establishment of morphological plasticity.

Animals↗
PubMed2001

Activation of NF-kappa B via the Ikappa B kinase complex is both essential and sufficient for proinflammatory gene expression in primary endothelial cells.

Activation of the transcription factor NF-kappaB is necessary for full expression of tumor necrosis factor alpha (TNF-alpha)-inducible endothelial chemokines and adhesion molecules. However, a detailed analysis regarding contribution of the different NF-kappaB upstream components to endothelial activation has not been performed yet. We employed a retroviral infection approach to stably express transdominant (TD) mutants of IkappaBalpha, IkappaBbeta, or IkappaBepsilon and dominant negative (dn) versions of IkappaB kinases (IKK) 1 or 2 as well as a constitutively active version of IKK2 in human endothelial cells. TD IkappaBalpha, IkappaBbeta, and IkappaBepsilon were not degraded upon TNF-alpha exposure, and each prevented NF-kappaB activation. These TD IkappaB mutants almost completely inhibited the induction of monocyte chemoattractant protein-1, interleukin-8, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression by TNF-alpha, whereas interferon-gamma-mediated up-regulation of intercellular adhesion molecule-1 and HLA-DR was not affected. Expression of dn IKK2 completely blocked TNF-alpha-induced up-regulation, whereas dn IKK1 showed a partial inhibition of expression of these molecules. Importantly, expression of constitutively active IKK2 was sufficient to drive full expression of all chemokines and adhesion molecules in the absence of cytokine. We conclude that the IKK/IkappaB/NF-kappaB pathway is crucial and sufficient for proinflammatory activation of endothelium.

Blotting, Western↗
PubMed2001

Expression of AMPA receptor subunit flip/flop splice variants in the rat auditory brainstem and inferior colliculus.

The expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit mRNAs and their flip/flop splice variants was evaluated in the rat auditory brainstem and inferior colliculus employing in situ hybridization with radiolabeled oligonucleotide probes. A differential expression of AMPA receptor subunits in auditory nuclei was observed. In general, neurons in all nuclei of the auditory brainstem express high levels of GluR-C flop and GluR-D flop mRNA, but low to very low levels of GluR-A and GluR-B mRNA. The strongest GluR-C and -D flop expression is found in the ventral and medial part of the anteroventral cochlear nucleus, the posteroventral cochlear nucleus, and the medial and the lateral superior olive. These nuclei are part of the binaural auditory pathway which is important for sound localization in space. In contrast, neurons in the central nucleus of the inferior colliculus express high levels of GluR-B flip but only low levels of the other AMPA receptor subunits. From our data, we conclude that neurons of nuclei involved in binaural processing exhibit a specific "auditory AMPA receptor" which consists primarily of GluR-C flop and -D flop and often lacks GluR-B subunits; this indicates fast kinetics and high Ca(2+) permeability of AMPA receptor currents. In contrast, neurons in the central nucleus of the inferior colliculus contain large amounts of GluR-B flip subunits resulting in Ca(2+) impermeable AMPA receptors with slow kinetics.

Animals↗
PubMed2001

Surgical treatment of early oral carcinoma-results of a prospective controlled multicenter study.

PURPOSE OF THE STUDY: To assess whether early stage (pT1-2,pN0-1) oral cavity carcinoma is adequately treated by radical surgical resection alone. MATERIAL AND METHODS: Prospective multicenter study. Of 105 patients with cT1-2 cN0-1 oral carcinoma treated in conformity with the study design, 12 had to be excluded because of tumor-positive margins or pN stage > N1. The remaining 93 patients were monitored for at least 2 years. RESULTS: Seventeen patients had local or regional recurrence develop. In 12 of the 17 patients locoregional control was achieved by second treatment. Overall, the 4-year disease-specific survival probability was 94%. Patients treated initially without selective neck dissection had significantly higher recurrence rates than those with neck dissection, although the survival probability was not adversely affected. CONCLUSIONS: Early (pT1-2, pN0-1) squamous cell carcinoma of the oral cavity is adequately treated by surgery alone, provided the resection margins are tumor free. On the basis of the presented data, we would also advocate routine selective neck dissection.

Adult↗
PubMed2001

Quality of life after treatment for early laryngeal carcinoma.

Radiotherapy and surgery for early laryngeal cancer achieve comparably good results in patient survival, and the choice of treatment between them is being influenced increasingly by the expected voice quality and quality of life (QoL). The superiority of vocal function after radiotherapy has been shown in previous objective voice assessment studies. This study compared the QoL of long-term survivors after endoscopic laser surgery or radiotherapy for early laryngeal carcinoma. QoL was evaluated with two validated questionnaires: the global EORTC QLQ-C30 and the head- and neck-specific EORTC QLQ-H&N35. A total of 62 patients were included. Among 56 patients completing the questionnaires (90% completion rate) 40 were treated by endoscopic CO2 laser surgery and 16 with radiation therapy. All 56 patients showed a good global QoL with no significant difference between the two treatment modalities. The head- and neck-specific evaluation revealed significantly better scores for surgically treated patients in questions about swallowing of solid food, xerostomia, and tooth problems, but no difference in questions about voice quality. Both treatment modalities achieve good QoL after treatment of early laryngeal tumors. Irradiated patients mainly complain about xerostomia related problems. In contrast to objective measurements long-term survivors after surgery do not rate their voice poorer than irradiated patients. The EORTC questionnaires are validated and useful tools in assessing QoL and should further be used in prospective trials.

Carcinoma, Squamous Cell↗
PubMed2001

A comparative study of the expression of cytotoxic proteins in allergic contact dermatitis and psoriasis: spongiotic skin lesions in allergic contact dermatitis are highly infiltrated by T cells expressing perforin and granzyme B.

Recent reports indicate that cytotoxic T cells are critically involved in contact hypersensitivity reactions in animals. In this study we sought to investigate the in vivo expression of cytotoxic granule proteins in the elicitation phase of allergic contact dermatitis in humans. Skin biopsy specimens were obtained from patients with allergic contact dermatitis (n = 8) and psoriasis (n = 6) and from controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by in situ hybridization and immunohistochemistry. In contrast to normal skin and psoriasis, a significant enhancement of perforin and granzyme B gene expression and immunoreactivity was observed in the mononuclear cell infiltrate of allergic contact dermatitis. Immunoreactivity for perforin and granzyme B was mainly found in the cytoplasm of lymphocytic cells, which were located in the dense perivascular infiltrate as well as at sites of marked spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and CD8+ T cells are capable of expressing perforin and granzyme B. In conclusion, our data suggest that T-cell-mediated mechanisms involving cytotoxic granule proteins may elicit epidermal cell injury in vivo and thereby strongly contribute to the development of allergic contact dermatitis in humans.

Adult↗
PubMed2001

Putative tumor suppressor loci at 6q22 and 6q23-q24 are involved in the malignant progression of sporadic endocrine pancreatic tumors.

Our previous comparative genomic hybridization study on sporadic endocrine pancreatic tumors (EPTs) revealed frequent losses on chromosomes 11q, 3p, and 6q. The aim of this study was to evaluate the importance of 6q losses in the oncogenesis of sporadic EPTs and to narrow down the smallest regions of allelic deletion. A multimodal approach combining polymerase chain reaction-based allelotyping, double-target fluorescence in situ hybridization, and comparative genomic hybridization was used in a collection of 109 sporadic EPTs from 93 patients. Nine polymorphic microsatellite markers (6q13 to 6q25-q27) were investigated, demonstrating a loss of heterozygosity (LOH) in 62.2% of the patients. A LOH was significantly more common in tumors >2 cm in diameter than below this threshold as well as in malignant than in benign tumors. We were able to narrow down the smallest regions of allelic deletion at 6q22.1 (D6S262) and 6q23-q24 (D6S310-UTRN) with LOH-frequencies of 50.0% and 41.2 to 56.3%, respectively. Several promising tumor suppressor candidates are located in these regions. Additional fluorescence in situ hybridization analysis on 46 EPTs using three locus-specific probes (6q21, 6q22, and 6q27) as well as a centromere 6-specific probe revealed complete loss of chromosome 6 especially in metastatic disease. We conclude that the two hot spots found on 6q may harbor putative tumor suppressor genes involved not only in the oncogenesis but maybe also in the malignant and metastatic progression of sporadic EPTs.

Adenoma, Islet Cell↗
PubMed2001

Perforin and granzyme B may contribute to skin inflammation in atopic dermatitis and psoriasis.

BACKGROUND: Infiltration of the skin by pathogenic T cells is regarded as a key factor in the development of inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. OBJECTIVES: To investigate whether T cells containing cytotoxic proteins may contribute to the generation of skin inflammation in these skin diseases. METHODS: Skin biopsy specimens were obtained from non-lesional and lesional skin of patients with chronic AD (n = 8) and psoriasis (n = 6), and from non-atopic controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by immunohistochemistry. RESULTS: A significant enhancement of perforin and granzyme B expression was observed in lesional AD skin as compared with normal skin, non-lesional AD skin and psoriasis. Expression of these cytotoxic proteins was also increased in psoriasis as compared with normal skin and non-lesional psoriatic skin. Immunoreactivity for perforin and granzyme B was mainly found in the cytoplasm of lymphocytic cells located in the perivascular infiltrate. In AD increased numbers of positive cells were also observed focally at sites of spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and CD8+ T cells are capable of expressing perforin and granzyme B. CONCLUSIONS: Our data suggest that cytotoxic CD4+ and CD8+ T cells containing perforin and granzyme B may play an integral part in eliciting cutaneous inflammation in AD.

Adolescent↗
PubMed2001

Role of routine panendoscopy in cancer of the upper aerodigestive tract.

Patients with squamous cell carcinoma of the aerodigestive tract routinely undergo panendoscopy to detect possible synchronous second primary tumors. The aim of our study was to assess the incidence of synchronous and metachronous second primary tumors and to refine the role of panendoscopy. The charts of 358 patients evaluated by means of panendoscopy during work-up of a first primary squamous cell carcinoma of the upper aerodigestive tract were reviewed. The incidence of a second primary tumor was 16.2%, with 6.4% being synchronous and 9.8% being metachronous. In only 3.1% of all patients, a synchronous tumor was clinically silent and only revealed by means of the panendoscopy. The synchronous tumors were mainly in the oral cavity, pharynx, or larynx (61%), whereas the metachronous tumors were most likely in the lung (57%). Despite the low incidence of synchronous second primary tumors, we still recommend panendoscopy for assessment of the primary tumor and as a training field for residents.

Adult↗