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Biomedical subjects

Mathias Wagner

Publications and source records attributed to Mathias Wagner.

17 recordsLinked to original sources
PubMed2007

Validation of 8-[123I]iodo-L-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid as an imaging agent for prostate cancer in experimental models of human prostate cancer.

INTRODUCTION: Very few tracers are currently available for the detection and staging of prostate cancer with positron emission tomography and single-photon emission computed tomography. This study evaluates the potential of 8-[123I]iodo-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid [ITIC(OH)] as an imaging agent for prostate cancer in experimental models of human prostate cancer. METHODS: ITIC(OH) was prepared by the IODO-GEN method, with 82+/-7% radiochemical yield and >99% radiochemical purity after high-performance liquid chromatography. Thereafter, ITIC(OH) was examined in CD-1 nu/nu mice engrafted with human PC-3 and DU-145 prostate cancer in the flank or orthotopically in the prostate. Bioevaluation involved examination of the in vivo stability and uptake characteristics of ITIC(OH) into tumors and different organs by dynamic in vivo analysis and gamma counting of organs of interest after dissection. RESULTS: ITIC(OH) showed good in vivo stability for biological investigations and was primary cleared through urine. In vivo, ITIC(OH) accumulated highly and specifically in tumors, reaching 13.6+/-2.1% to 16.2+/-2.5% injected dose per gram (ID/g) in heterotopic tumors compared with 14.8+/-2.6% and 17.6+/-3.4% ID/g in orthotopic tumor engrafts at 60 and 240 min postinjection, respectively. In contrast, radioactivity uptake in the blood, spleen, liver and gastrointestinal tract was moderate and decreased with time, resulting in marked tumor-to-background and excellent visualization of tumors. CONCLUSION: These results suggest that ITIC(OH) is a promising candidate as radiotracer for detecting prostate cancer and warrants further studies in patients to ascertain its potential as an imaging agent for clinical use.

Animals↗
PubMed2006

Chemokine expression in hepatocellular carcinoma versus colorectal liver metastases.

AIM: To evaluate and compare the expression profiles of CXCL12 (SDF-1), CCL19 (MIP-3beta), CCL20 (MIP-3alpha) and CCL21 (6Ckine, Exodus2) and their receptors on RNA and protein levels in hepatocellular carcinoma (HCC) versus colorectal liver metastases (CRLM) and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases. METHODS: Chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent non-tumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RT-PCR and Western blot analysis in the same cases of HCC and CRLM. RESULTS: Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20 demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly up-regulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues. CONCLUSION: Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked up-regulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.

Adult↗
PubMed2006

Low prevalence of transfusion transmitted virus (TTV)-like DNA sequences in cystadenolymphoma and pleomorphic adenoma of the salivary glands.

Titers of transfusion transmitted virus (TTV)-like DNA in saliva samples have been reported 100-1,000 times higher than those of the corresponding sera, suggesting viral transmission by saliva droplets. The present study was conducted to determine whether TTV-like DNA sequence elements play a role in the pathogenesis of cystadenolymphoma or pleomorphic adenoma and if the parotid or the submandibular gland is a major source of TTV persistence. Sixty-two archival salivary gland samples (16 cystadenolymphomas, 13 pleomorphic adenomas, and 33 controls) and 23 corresponding saliva samples were examined using a polymerase chain reaction (PCR) for TTV DNA. All PCR products that displayed DNA bands were sequenced. Leder's stain and immunohistochemistry (anti-CD8, anti-CD20, anti-CD45R0, anti-CD68, and anti-Ki67/MiB1) were applied to detect possible changes associated with findings of TTV-like DNA sequences. Tissue displayed TTV-like DNA sequences in 8.1% (5/62; saliva: 47.8%, 11/23). Tissue that contained TTV-like DNA sequences was histologically indistinguishable from samples lacking such DNA. TTV appears to be only a bystander in cystadenolymphoma, pleomorphic adenoma, and other salivary gland affections. Neither of the glands seems to be a major source of TTV persistence.

Adenolymphoma↗
PubMed2006

Naturally occurring T-cell response against mutated p21 ras oncoprotein in pancreatic cancer.

Mutated p21 ras proteins (muRas) are present in approximately 90% of pancreatic adenocarcinomas and express mutants which can function as cancer-specific antigens. To evaluate the frequency and magnitude of the natural T-cell response against muRas in 19 HLA-A2-positive patients with muRas-positive pancreatic carcinomas, antigen-experienced T lymphocytes in fresh peripheral blood mononuclear cells were shown by IFN-gamma enzyme-linked immunospot using muRas peptides (5-21) that encompass both HLA class I (HLA-A2)- and class II-restricted (HLA-DRB1) epitopes. Six of 19 patients (32%) were found to have a specific T-cell response against individual mutation-specific ras(5-21) but not against other ras mutations or wild-type ras. In contrast, none of 19 healthy subjects had T cells specifically secreting IFN-gamma (P = 0.004). The T-cell response consisted of both CD8(+) and CD4(+) T cells but was dominated by CD8 T cells in three of four patients. MuRas(5-14) and muRas(6-14) were shown to specifically induce CD8(+) T-cell mediated cytotoxicity against HLA-A2-positive, muRas-bearing pancreatic carcinoma cells. The T-cell response was not correlated with prognostic or clinical variables such as tumor-node-metastasis status, stage, or survival. In conclusion, a natural T-cell response against muRas proteins that could be exploited for immunostimulatory therapeutic approaches has been shown in a significant proportion of patients with pancreatic cancer.

Adenocarcinoma↗
PubMed2006

Evaluation of two 3D virtual computer reconstructions for comparison of cleft lip and palate to normal fetal microanatomy.

Cleft lip and palate reconstructive surgery requires thorough knowledge of normal and pathological labial, palatal, and velopharyngeal anatomy. This study compared two software algorithms and their 3D virtual anatomical reconstruction because exact 3D micromorphological reconstruction may improve learning, reveal spatial relationships, and provide data for mathematical modeling. Transverse and frontal serial sections of the midface of 18 fetal specimens (11th to 32nd gestational week) were used for two manual segmentation approaches. The first manual segmentation approach used bitmap images and either Windows-based or Mac-based SURFdriver commercial software that allowed manual contour matching, surface generation with average slice thickness, 3D triangulation, and real-time interactive virtual 3D reconstruction viewing. The second manual segmentation approach used tagged image format and platform-independent prototypical SeViSe software developed by one of the authors (F.W.). Distended or compressed structures were dynamically transformed. Registration was automatic but allowed manual correction, such as individual section thickness, surface generation, and interactive virtual 3D real-time viewing. SURFdriver permitted intuitive segmentation, easy manual offset correction, and the reconstruction showed complex spatial relationships in real time. However, frequent software crashes and erroneous landmarks appearing "out of the blue," requiring manual correction, were tedious. Individual section thickness, defined smoothing, and unlimited structure number could not be integrated. The reconstruction remained underdimensioned and not sufficiently accurate for this study's reconstruction problem. SeViSe permitted unlimited structure number, late addition of extra sections, and quantified smoothing and individual slice thickness; however, SeViSe required more elaborate work-up compared to SURFdriver, yet detailed and exact 3D reconstructions were created.

Cleft Lip↗
PubMed2006

Involvement of chemokine receptor CCR6 in colorectal cancer metastasis.

Various chemokine receptors, namely CXCR4, CCR6 and CCR7, have recently been shown to be involved in the regulation of metastasis in malignant tumors. However, little is known about the role of these receptors in promoting tumor metastasis of colorectal cancer (CRC) to the primary site of CRC metastasis in the liver. To investigate this issue, we analyzed the expression of the chemokine receptors CXCR4, CCR6 and CCR7 in colorectal tumors and colorectal liver metastases. In the present study, 30 human cancer samples from colorectal tissue, 30 human samples from colorectal liver metastases and the adjacent nontumorous liver tissues were screened using quantitative real-time PCR, Western blot analysis, histochemistry, microdissection and the enzyme-linked immunosorbent assay (ELISA). While an overexpression of all the chemokine receptors was found in CRC, in colorectal liver metastases only the chemokine receptors CXCR4 and CCR6 were significantly upregulated. Consequently, we investigated the expression of the corresponding ligands CXCL12/SDF1alpha, CCL20/MIP3alpha, CCL19/MIP3beta and CCL21/6Ckine in various organs, such as the stomach, esophagus, pancreas, colon and rectum, in comparison with their expression in the liver as the primary site of metastatic spread in CRC. We found that only CCL20 exhibits peak levels of expression in the liver, thus indicating that an increased production of CCL20 may contribute to the selective recruitment of CCR6-expressing cancer cells in CRC. Furthermore, we could demonstrate that CRC patients who developed liver metastases express significantly more CCL20 and CCL21 in the liver in comparison with an unaffected control group. Therefore, our findings strongly suggest an association between CCL20/CCR6 expression in human CRC and the promotion of colorectal liver metastasis.

Blotting, Western↗
PubMed2005

A computer-based approach to assess the perception of composite odour intensity: a step towards automated olfactometry calibration.

The 2004 Nobel Prize in Physiology or Medicine laureates, Richard Axel and Linda Buck, have made smell a less enigmatic sense to study. In clinical routine, olfactory function is assessed using defined concentrations of a single defined substance, a setting which is uncommon in daily life. The present study was therefore conducted to evaluate the applicability of composite odours. Air was contaminated with different quantities of cyclohexanol, cyclohexanone and cyclohexane to generate 73 gas mixtures (one component: n = 21, two components: n = 40, three components: n = 12). The intensity of perception was estimated for each mixture by an average of 60.3 healthy individuals (4,403 assessments). An artificial neural network (ANN) was trained and validated using the contaminants' concentrations with the corresponding estimated intensities. The inter-rater variability was low, as 75.7% of the assessments did not exceed a difference beyond 0.5 from the corresponding median (considered correct predictions). The ANN correctly estimated 78.1% of the gas mixtures, and in terms of the regression task the ANN demonstrated a sufficient prediction performance (Pearson's correlation coefficient r = 0.883; R(2) = 0.757) and outperformed linear regression (r = 0.770; R(2) = 0.667). Evaluating extra ANNs for gas mixtures comprising one, two or three components, the predictive power did not decrease when complexity increased. The aforementioned results reflect nonlinearity in human perception. ANN technology helps simulate human perception of composite odour intensity which may be applicable to olfactometry calibration and systems biological mathematical modelling. The use of composite odours may represent real-life problems more adequately than single substances.

Adult↗
PubMed2005

The human eye (retina): a site of persistent HCMV infection?

BACKGROUND: Human cytomegalovirus (HCMV) retinitis frequently occurs in severely naturally and iatrogenically immunocompromised patients. It has been shown that the immune-privileged retina is a major site of HCMV infection in AIDS patients. It is conceivable either that during the immunosuppression HCMV infection reactivates in various other organs viremically affecting the retina or that HCMV persisting in the retina may locally reactivate and result in HCMV retinitis. METHODS: As there is still controversy about the sites of HCMV latency and persistence we investigated 75 eyes of HIV-seronegative patients undergoing enucleation due to a variety of malignant and non-viral benign ophthalmic disorders for the retinal presence of HCMV antigen and DNA. RESULTS: None of the analyzed patients had symptoms of HCMV retinitis. Immunohistologic staining as well as Taq Man DNA PCR analysis showed all samples to be free of HCMV. CONCLUSIONS: Our data suggest that the human eye is rather unlikely to be a site of productive or latent HCMV persistence.

Adult↗
PubMed2005

Tissue-plastinated vs. celloidin-embedded large serial sections in video, analog and digital photographic on-screen reproduction: a preliminary step to exact virtual 3D modelling, exemplified in the normal midface and cleft-lip and palate.

This study analyses tissue-plastinated vs. celloidin-embedded large serial sections, their inherent artefacts and aptitude with common video, analog or digital photographic on-screen reproduction. Subsequent virtual 3D microanatomical reconstruction will increase our knowledge of normal and pathological microanatomy for cleft-lip-palate (clp) reconstructive surgery. Of 18 fetal (six clp, 12 control) specimens, six randomized specimens (two clp) were BiodurE12-plastinated, sawn, burnished 90 microm thick transversely (five) or frontally (one), stained with azureII/methylene blue, and counterstained with basic-fuchsin (TP-AMF). Twelve remaining specimens (four clp) were celloidin-embedded, microtome-sectioned 75 microm thick transversely (ten) or frontally (two), and stained with haematoxylin-eosin (CE-HE). Computed-planimetry gauged artefacts, structure differentiation was compared with light microscopy on video, analog and digital photography. Total artefact was 0.9% (TP-AMF) and 2.1% (CE-HE); TP-AMF showed higher colour contrast, gamut and luminance, and CE-HE more red contrast, saturation and hue (P < 0.4). All (100%) structures of interest were light microscopically discerned, 83% on video, 76% on analog photography and 98% in digital photography. Computed image analysis assessed the greatest colour contrast, gamut, luminance and saturation on video; the most detailed, colour-balanced and sharpest images were obtained with digital photography (P < 0.02). TP-AMF retained spatial oversight, covered the entire area of interest and should be combined in different specimens with CE-HE which enables more refined muscle fibre reproduction. Digital photography is preferred for on-screen analysis.

Artifacts↗
PubMed2004

A comparative ultrastructural and molecular biological study on Chlamydia psittaci infection in alpha-1 antitrypsin deficiency and non-alpha-1 antitrypsin deficiency emphysema versus lung tissue of patients with hamartochondroma.

BACKGROUND: Chlamydiales are familiar causes of acute and chronic infections in humans and animals. Human pulmonary emphysema is a component of chronic obstructive pulmonary disease (COPD) and a condition in which chronic inflammation manifested as bronchiolitis and intra-alveolar accumulation of macrophages is common. It is generally presumed to be of infectious origin. Previous investigations based on serology and immunohistochemistry indicated Chlamydophila pneumoniae infection in cases of COPD. Furthermore, immunofluorescence with genus-specific antibodies and electron microscopy suggested involvement of chlamydial infection in most cases of pulmonary emphysema, but these findings could not be verified by PCR. Therefore, we examined the possibility of other chlamydial species being present in these patients. METHODS: Tissue samples from patients having undergone lung volume reduction surgery for advanced alpha-1 antitrypsin deficiency (AATD, n = 6) or non-alpha-1 antitrypsin deficiency emphysema (n = 34) or wedge resection for hamartochondroma (n = 14) were examined by transmission electron microscopy and PCR. RESULTS: In all cases of AATD and 79.4% of non-AATD, persistent chlamydial infection was detected by ultrastructural examination. Intra-alveolar accumulation of macrophages and acute as well as chronic bronchiolitis were seen in all positive cases. The presence of Chlamydia psittaci was demonstrated by PCR in lung tissue of 66.7% AATD vs. 29.0% non-AATD emphysema patients. Partial DNA sequencing of four positive samples confirmed the identity of the agent as Chlamydophila psittaci. In contrast, Chlamydophila pneumoniae was detected only in one AATD patient. Lung tissue of the control group of non-smokers with hamartochondroma was completely negative for chlamydial bodies by TEM or chlamydial DNA by PCR. CONCLUSIONS: These data indicate a role of Chlamydophila psittaci in pulmonary emphysema by linking this chronic inflammatory process to a chronic infectious condition. This raises interesting questions on pathogenesis and source of infection.

Base Sequence↗
PubMed2004

The 'subsequent artificial neural network' (SANN) approach might bring more classificatory power to ANN-based DNA microarray analyses.

MOTIVATION: Human decisions often proceed in two steps. Initially those most preferred are chosen followed by a subsequent choice of these preferences. Applying one artificial neural network (ANN), a classification is limited to the preselection process. The final categorization is only possible by a subsequent ANN that distinguishes the pre-chosen classes. Existing strategies using coupled ANNs are discussed and a new approach particularly suited for multiclass classification problems is introduced ('Subsequent ANN', SANN). RESULTS: Evaluating a simulated data base comprising 3 classes, classification results of SANN were obviously superior to those achieved by ANN. To evaluate a real-world data base the microarray benchmark GCM (14 classes) was chosen. The ANN results reached 72%, comparable to previous results. Using SANN, up to 81% of the tumors were correctly classified. AVAILABILITY: Programs used in this work and numerical results are available upon request.

Algorithms↗
PubMed2004

Nutrition of very low birth weight infants fed human milk with or without supplemental trace elements: a randomized controlled trial.

BACKGROUND: Very low birth weight infants (<1500 g) have high nutritional needs. Deficiencies of minerals, trace elements (especially zinc) may develop as a result of rapid growth, low body stores and low content of these substances in human milk We hypothesized that fortification of human milk might prevent deficiencies. METHODS: Prospective, randomized trial to evaluate mineral, trace element, thyroid status and growth of infants fed human milk fortified with different amounts of calcium, phosphorus and protein, with (BMF) or without (FM 85) trace elements. Sixty-two infants, 1000 to 1499 g birth weight, were randomized. Minerals and trace elements in serum, red blood cells and human milk and alkaline phosphatase activity, TSH, T4 and FT4 in serum were measured once until the fifth day and at 3 and 6 weeks of life. Clinical course and anthropometric measurements were recorded. RESULTS: Intake of zinc, copper, manganese, calcium, phosphorus and magnesium was higher in the BMF group (P < 0.001). Serum zinc concentrations <0.49 mg/L occurred in 12% of the FM 85 group and 7% of the BMF group at 6 weeks (not significant). Median alkaline phosphatase activity was 436/379 IU/L in the FM 85/BMF group at 6 weeks (P < 0.01). The FM 85 group showed a higher weight gain (P < 0.05), possibly because of higher caloric (P < 0.01) and protein intake (P < 0.05) at 3 weeks. CONCLUSIONS: Zinc deficiency was rare. Elevated intake of calcium, phosphorus and zinc was associated with lower serum alkaline phosphatase activity but did not influence serum zinc concentration.

Alkaline Phosphatase↗
PubMed2003

Etiopathogenesis of cholesteatoma.

Cholesteatoma is a destructive lesion of the temporal bone that gradually expands and causes complications by erosion of the adjacent bony structures. Bone resorption can result in destruction of the ossicular chain and otic capsule with consecutive hearing loss, vestibular dysfunction, facial paralysis and intracranial complications. Surgery is the only treatment of choice. The etiopathogenesis of cholesteatoma, however, is still controversial. This review was designed to understand the reasons for these disparities and to reduce or eliminate them. Future studies focused on developmental, epidemiological, hormonal and genetic factors as well as on treatment are likely to contribute to further understanding of cholesteatoma pathogenesis.

Antigens, Differentiation↗
PubMed2003

Detection of HHV-8 sequences and antigens in a MALT lymphoma associated with Sjögren's syndrome.

We describe the case of a bilateral parotid mucosa-associated lymphoid tissue (MALT) lymphoma associated with 2 years history of Sjögren's syndrome (SS), which was linked to human herpes virus 8 (HHV-8) infection. Using polymerase chain reaction (PCR) assay HHV-8 sequences were detectable in the lymphoma tissue of both sides. Serologic testing of the patient revealed HHV-8 antibodies in enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA). Immunohistologic staining with two antibodies against open reading frame (ORF) 26 and v-cyclin homologues of HHV-8 revealed positive staining of the salivary acinic cells whereas the lymphoma cells were negative. The potential influence of HHV-8 infection for MALT lymphoma development in this case and possible parallels to gastric MALT lymphoma are discussed.

Antigens, Viral↗
PubMed2002

DeltaF508-CFTR causes constitutive NF-kappaB activation through an ER-overload response in cystic fibrosis lungs.

The clinical course of Cystic Fibrosis is characterized by recurrent pulmonary infections which ultimately lead to death by respiratory failure. The most common CF causing mutation, deltaF508-CFTR, produces an incorrectly folded protein, which accumulates within the endoplasmic reticulum. However, the molecular mechanism by which the deltaF508-CFTR protein facilitates pulmonary infection and inflammation remains unclear. Here we show that the expression of deltaF508-CFTR causes a constitutive activation of the pro-inflammatory transcription factor NF-kappaB by eliciting an ER stress reaction, the ER-overload response. This endogenous NF-kappaB activation stimulates the transcription of pro-inflammatory cytokines thereby commencing an inflammatory cascade within the CF lung.

Animals↗
PubMedDate not supplied

Simulating soft data to make soft data applicable to simulation.

BACKGROUND: Biomedical processes are often influenced by measures considered "non-crisp", "soft" or "subjective". Despite the growing awareness of the importance of such measures, they are rarely considered in biomedical simulation. This study introduces an input generator for soft data (input generator SD) that makes soft data applicable to simulation. MATERIALS AND METHODS: Machine learning approaches and standard regression techniques were applied to simulate odour intensity ratings. RESULTS: The performance of all the applied methods was satisfactory and the results can be used to modify systems biological mathematical models. CONCLUSION: Soft data should no longer be discounted in systems biological simulations. Exemplarily, it can be demonstrated that the input generator SD produces results that are similar to those that the simulated system can generate. Machine learning and/or appropriate conventional mathematical approaches may be applied to simulate noncrisp processes that can be used to modify mathematical models of any granularity.

Adult↗