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Biomedical subjects

C Schmidt

Publications and source records attributed to C Schmidt.

At least 127 records · Page 7Linked to original sources
PubMed2001

CD44 in normal human pancreas and pancreatic carcinoma cell lines.

CD44 is an integral cell-surface glycoprotein. Overexpression of the CD44 standard (CD44st) and its variants (CD44v) has been implicated in transformation and progression of many cancer types. Here, we investigated expression of CD44st, CD44v3-7, CD44v7/8, and v10 in five human pancreatic tumor cell lines and normal human pancreatic duct cells transfected with the SV40 large T antigen. CD44st and its variant proteins were quantified using immunocytochemistry and flow cytometry. CD44v7 was expressed at low levels, whereas CD44st, CD44v3, CD44 v4, CD44v, and CD44v6 were expressed at moderate levels in all pancreatic tumor cell lines. In contrast, CD44v7/8 and CD44v10 were expressed at very low levels in two out of the five pancreatic tumor cell lines. Overall, staining of CD44st and CD44 variants was significantly weaker compared to another surface molecule, ICAM-1, reported to be overexpressed in pancreatic cancer cells. Furthermore, the SV40 large T transfected duct cells showed only a weak staining for CD44st, CD44v5, and CD44v6. To determine a possible mechanism for the regulation of surface expression of CD44st, v5 and v6, we incubated Panc-1 cells with bFGF, TGF-beta1, EGF, TNFalpha, and IFNgamma. Only IFNgamma affected the CD44 expression by down-regulation of CD44v6. The constitutive expression of CD44 variants seems to be associated with the malignant state of invasive carcinoma.

Adenocarcinoma↗
PubMed2001

Impact of febrile infections on the long-term function of kidney allografts.

PURPOSE: We prospectively determined the impact of febrile infectious disease on long-term renal graft function compared with a matched control group. MATERIALS AND METHODS: Included in our study were 39 patients who presented with episodes of febrile infection with body temperature greater than 38C on 2 consecutive occasions, necessitating hospitalization. In addition, 39 controls without febrile infection requiring hospitalization within 2 months were chosen from the complete data pool of all renal transplant recipients followed at our transplant clinic using the matched pair technique. Renal function was estimated by serum creatinine and calculated creatinine clearance. RESULTS: Of the 39 patients with infection 15 had urinary tract infection and 24 had other, mostly bacterial infection, including pneumonia/severe bronchitis in 12, oral/dental infection in 2, gastroenteritis in 2, shunt sepsis in 1, herpes zoster in 1, cytomegalovirus in 1 and other in 5. Mean estimated creatinine clearance plus or minus standard deviation was similar in the infection and control groups at the beginning of the study (51 +/- 22 and 51 +/- 23 ml. per minute, respectively). During the infectious episode mean creatinine clearance significantly decreased to 38 +/- 17 ml. per minute in the infection group. After infection resolved creatinine clearance returned to an almost baseline mean value of 50 +/- 23 ml. per minute. However, after 2 years of followup there was a significant difference in mean creatinine clearance in the infection group versus controls (45 +/- 25 versus 52 +/- 25 ml. per minute, p = 0.022). CONCLUSIONS: To our knowledge we have shown for the first time in a prospective controlled study that febrile infectious episodes correlate with poor long-term renal graft function.

Adult↗
PubMed2001

[Gene therapy--therapeutic option in treatment of chronic wounds?].

Chronic wounds seem to be a severe problem in terms of socioeconomical meanings due to the fact, that the average age of patients suffering from these wounds rises steadily. Therapy of chronic wounds is complicated and oftenly not satisfying. Even application of local growth factors according to the latest findings in terms of cell and molecular regulatory mechanisms during wound healing does not lead to success because of the immediate inactivation of these growth factors in the wound fluid of chronical wounds. Knowing these facts one has to ask if new developments like genetical modification of cells participating in wound healing may lead to sufficient results in the therapy of chronical wounds.

Chronic Disease↗
PubMed2001

[Gene therapy--therapeutic option in treatment of chronic wounds?].

Chronic wounds seem to be a severe problem in terms of its socioeconomical meaning due to the fact that the average age of patients suffering from these wounds is rising steadily. Therapy of chronic wounds is complicated and often not satisfying. Even application of local growth factors according to the latest findings in terms of cell and molecular regulatory mechanisms during wound healing does not lead to success because of the immediate inactivation of these growth factors in the wound fluid of chronic wounds. Knowing these facts one has to ask if new developments such as genetic modification of cells participating in wound healing may lead to sufficient results in the therapy of chronic wounds.

Chronic Disease↗
PubMed2001

[Molecular biology of cystinuria].

Cystine stones belong to the kidney stones diseases which are difficult to manage due to the high rate of recidivation and the necessary surgical procedures. Cystinuria is an autosomal recessive defect of the transport of cystine and the dibasic amino acids in the proximal kidney tube. Recently, two subunits of a renal cystine transporter have been identified. Mutations in these genes have been shown to lead to the cystinuria phenotype. Genetic and functional analyses have helped to modify the classification of cystinuria which had previously been exclusively based on biochemical data. Furthermore, first steps towards a molecular genetic testing have been carried out replacing the so far diagnostic procedure which are stressing for the patients. The results of these testings make an individual therapy possible.

Cystinuria↗
PubMed2000

Compartmentalization of the somite and myogenesis in chick embryos are influenced by wnt expression.

Muscles of the body and bones of the axial skeleton derive from specialized regions of somites. Somite development is influenced by adjacent structures. In particular, the dorsal neural tube and the overlying ectoderm have been shown to be necessary for the induction of myogenic precursor cells in the dermomyotome. Members of the Wnt family of signaling molecules, which are expressed in the dorsal neural tube and the ectoderm, are postulated to be responsible for this process. It is shown here that ectopically implanted Wnt-1-, -3a-, and -4-expressing cells alter the process of somite compartmentalization in vivo. An enlarged dorsal compartment results from the implantation of Wnt-expressing cells ventrally between the neural tube/notochord and epithelial somites, at the expense of the ventral compartment, the sclerotome. Thus, ectopic Wnt expression is able to override the influence of ventralizing signals arising from notochord and floor plate. This shift of the border between the two compartments was identified by an increase in the domain of Pax-3 expression and a complete loss of Pax-1 expression in somites close to the ectopic Wnt signal. The expanded expression of MyoD and desmin provides evidence that it is the myotome which increases as a result of Wnt signaling. Paraxis expression is also drastically amplified after implantation of Wnt-expressing cells indicating that Wnts are involved in the formation and maintenance of somite epithelium and suggesting that Paraxis is activated through Wnt signaling pathways. Taken together these results suggest that ectopic Wnts disturb the normal balance of signaling molecules within the somite, resulting in an enhanced recruitment of somitic cells into the myogenic lineage.

Animals↗
PubMed2000

Cryptorchidism: fowler-stephens procedure or autotransplantation-a new experimental model.

OBJECTIVES: To investigate the effect of different operative procedures on testicular development in cryptorchidism. METHODS: One hundred ten postpubertal Wistar-WU rats were divided into four groups. Group 1 (35 rats) underwent microsurgical autotransplantation of the right testis with end-to-end anastomosis of the testicular vessels. Group 2 (35 rats) underwent the Fowler-Stephens maneuver with intra-abdominal fixation of the testis. To determine the influence of temperature on testicular development, group 3 (35 rats) underwent the Fowler-Stephens maneuver with scrotal replacement of the testis. Group 4 (5 rats) was a control group without operative treatment. To assess the early and late changes of testicular ischemia and reperfusion, groups 1 to 3 were divided into seven subgroups (5 rats each) with defined postoperative intervals (0.5 hour, 2 hours, 4 hours, 8 hours, 16 hours, 14 days, and 60 days). Testicular development, sperm density, pH value, tissue lactate concentration, and tubular diameter were the parameters used to determine success or failure. RESULTS: After autotransplantation, testicular development exhibited an atrophy rate of less than 50% and a significant decrease in groups 2 and 3 after 60 days. The sperm density was significantly different between groups 2 and 4 (control). The pH value was significantly different after 2 hours in groups 2 and 3. The tissue lactate concentration revealed no significant differences. The tubular diameters were significantly diminished in group 2 after 60 days. CONCLUSIONS: The smaller atrophy rate of the testes suggests that we successfully established a model in the rat to compare the operative outcome after autotransplantation and the Fowler-Stephens procedure in cryptorchidism. The significant difference in the tubular diameters for the intra-abdominally placed testes might be caused by the exposure of the testis to a higher temperature.

Anastomosis, Surgical↗
PubMed2000

Effects of fluoroquinolones on HERG currents.

We have investigated the effects of four fluoroquinolones on the human ether-à-go-go-related gene (HERG) mediated K(+) currents to evaluate their potential to induce QT-prolongation. HERG currents were measured from stably transfected Chinese hamster ovary (CHO) cells by means of the patch-clamp technique. Bath application of sparfloxacin, moxifloxacin and grepafloxacin produced an inhibition of HERG outward currents at -40 mV with EC(50) of 13.5+/-0.8, 41. 2+/-2.0 and 37.5+/-3.3 microg/ml, respectively. Current inhibitions were reversible after washout of the compounds. By contrast, ciprofloxacin at concentrations of up to 100 microg/ml did not effect HERG outward currents.

Animals↗
PubMed2000

A Chip-Based Biosensor for the Functional Analysis of Single Ion Channels We thank E. Ermanntraut, L. Giovangrandi, T. Wohland, A. Brecht, M. Köhler, C. Bieri, D. Stamou, and R. Hovius for advice. This work was supported by the Swiss National Science Foundation (Priority Program for Biotechnology) and by an interdepartmental grant of the Swiss Federal Institute of Technology Lausanne (EPFL, Project Microtechnique 96).

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Journal Article↗
PubMed2000

Incorporation of N-propanoylneuraminic acid leads to calcium oscillations in oligodendrocytes upon the application of GABA.

Sialylation of glycoproteins and glycolipids plays an important role during development, regeneration and pathogenesis. It has been shown that unnatural sialylation within glial cell cultures can have distinct effects on their proliferation and antigenic profiles. These cultures metabolize N-propanoylmannosamine (N-propanoylneuraminic acid precursor=P-NAP), a synthetic non-physiological precursor of neuraminic acid, resulting in the expression of N-propanoylneuraminic acid in glycoconjugates of their cell membranes [Schmidt, C., Stehling, P., Schnitzer, J., Reutter, W. and Horstkorte, R. (1998) J. Biol. Chem. 273, 19146-19152]. To determine whether these biochemically engineered sialic acids influence calcium concentrations in cells of the oligodendrocyte lineage, mixed glial cultures of oligodendrocytes growing on top of an astrocyte monolayer were exposed to glutamate, histamine, adrenaline, gamma-aminobutyric acid (GABA), high potassium (high K(+)) and ATP. Calcium responses in P-NAP-treated oligodendrocytes were determined by confocal microscopy with the calcium indicator fluo-3 AM, and compared with control cultures. We showed that P-NAP differentially modulated the calcium responses of individual oligodendrocytes when GABA was applied. GABA induced calcium oscillations with up to four spikes per min in 60% of oligodendrocytes when treated with P-NAP.

Adenosine Triphosphate↗
PubMed2000

Early evolution of cytochrome bc complexes.

Primary structures, functional characteristics and phylogenetic relationships of subunits of cytochrome bc complexes from phylogenetically diverse bacterial and archaeal species were analysed. A single case of lateral gene transfer, i.e. the import of an epsilon-proteobacterial cytochrome bc(1) complex into Aquificales, was identified. For the enzyme in the remainder of the species studied, the obtained phylogenies were globally in line with small subunit rRNA trees. The distribution of a few key phylogenetic markers, such as contiguousness of cytochrome b, nature of the c-type subunit or spacing between b-heme ligands, are discussed. A localised modification of previous tree topologies is proposed on the basis of the obtained data. The comparison of extant enzymes furthermore allowed us to define the minimal functional and evolutionary core of the enzyme. The data furthermore suggest that the ancestral enzyme was put together from subunits that previously had played a role in other electron transfer chains.

Amino Acid Sequence↗
PubMed2000

Risk of Pseudomonas aeruginosa cross-colonisation in patients with cystic fibrosis within a holiday camp--a molecular-epidemiological study.

OBJECTIVE: A study on the molecular epidemiology of Pseudomonas aeruginosa in patients with cystic fibrosis (CF) from Germany (N = 18) and Israel (N = 12) is presented. The aim is to provide an answer to the question as to whether or not social contact outside the hospital environment involves a potential risk for person-to-person spread of this pathogen. METHODS: Sputa from German and Israeli patients were obtained while these were attending a holiday camp in Israel. The sputum samples were analysed with regard to Pseudomonas aeruginosa. Strains dissimilar in macroscopic appearance and/or antibiotic resistance patterns were genotyped using pulsed-field gel electrophoresis after digestion of genomic DNA with restriction endonuclease Spel. The genetic polymorphism of DNA fragment patterns of all strains (N = 146) was studied for their overall relatedness using a fingerprint software system. RESULTS: Most of the German patients (77.7%) were colonised persistently by a unique clonal type during the four-week screening period. Isolates obtained from Israeli patients displayed a very close clonal relationship and a higher antibiotic resistance as a result of preceding epidemic spread of certain clones before the camp. Additionally, isolates showing identical PFGE patterns were demonstrated once in a single male Israeli patient and in one female German patient, suggesting previous cross-colonisation. CONCLUSION: The occurrence of person-to-person spread through social contact in patients with CF is supported by our findings, but remains a rare event outside the hospital environment, provided appropriate hygienic measures are applied.

Adult↗
PubMed2000

Significance of accelerated idioventricular rhythm in idiopathic dilated cardiomyopathy.

Holter monitoring was performed in 202 patients with idiopathic dilated cardiomyopathy, which revealed accelerated idioventricular rhythm in 16 patients (8%) and nonsustained ventricular tachycardia in 70 patients (35%). During 32 +/- 15-month prospective follow-up, no significant difference was observed for major arrhythmic events and transplant-free survival between patients with and without accelerated idioventricular rhythm, whereas patients with nonsustained ventricular tachycardia had a significantly higher incidence of major arrhythmic events and a lower transplant-free survival rate.

Accelerated Idioventricular Rhythm↗
PubMed2000

Identification of genes differentially over-expressed in lung squamous cell carcinoma using combination of cDNA subtraction and microarray analysis.

In order to develop effective vaccine products against human cancer, we are interested in identifying genes over-expressed in tumor cells. Through a combination of cDNA library subtraction and microarray technology, we identified seventeen genes preferentially expressed in lung squamous cell carcinoma, including four novel genes. To date, expression profiles of these genes were confirmed by Northern and/or real-time analysis, and several genes were also found to be expressed in head and neck squamous tumors. Thus, these combined methods represent a high throughput approach for identifying tumor specific genes. Furthermore, the report of characterization on these genes will allow them to be exploited for their diagnostic, prognostic, and therapeutic potentials including immunotherapy and antibody based anticancer therapy.

Antigens, Neoplasm↗
PubMed2000

RNA double cleavage by a hairpin-derived twin ribozyme.

The hairpin ribozyme is a small catalytic RNA that catalyses reversible sequence-specific RNA hydrolysis in trans. It consists of two domains, which interact with each other by docking in an antiparallel fashion. There is a region between the two domains acting as a flexible hinge for interdomain interactions to occur. Hairpin ribozymes with reverse-joined domains have been constructed by dissecting the domains at the hinge and rejoining them in reverse order. We have used both the conventional and reverse-joined hairpin ribozymes for the design of a hairpin-derived twin ribozyme. We show that this twin ribozyme cleaves a suitable RNA substrate at two specific sites while maintaining the target specificity of the individual monoribozymes. For characterisation of the studied ribozymes we have evaluated a quantitative assay of sequence-specific ribozyme activity using fluorescently labelled RNA substrates in conjunction with an automated DNA sequencer. This assay was found to be applicable with hairpin and hairpin-derived ribozymes. The results demonstrate the potential of hairpin ribozymes for multi-target strategies of RNA cleavage and suggest the possibility for employing hairpin-derived twin ribozymes as powerful tools for RNA manipulation in vitro and in vivo.

Base Sequence↗
PubMed2000

Machinability of IPS Empress 2 framework ceramic.

Using ceramic materials for an automatic production of ceramic dentures by CAD/CAM is a challenge, because many technological, medical, and optical demands must be considered. The IPS Empress 2 framework ceramic meets most of them. This study shows the possibilities for machining this ceramic with economical parameters. The long life-time requirement for ceramic dentures requires a ductile machined surface to avoid the well-known subsurface damages of brittle materials caused by machining. Slow and rapid damage propagation begins at break outs and cracks, and limits life-time significantly. Therefore, ductile machined surfaces are an important demand for machine dental ceramics. The machining tests were performed with various parameters such as tool grain size and feed speed. Denture ceramics were machined by jig grinding on a 5-axis CNC milling machine (Maho HGF 500) with a high-speed spindle up to 120,000 rpm. The results of the wear test indicate low tool wear. With one tool, you can machine eight occlusal surfaces including roughing and finishing. One occlusal surface takes about 60 min machining time. Recommended parameters for roughing are middle diamond grain size (D107), cutting speed v(c) = 4.7 m/s, feed speed v(ft) = 1000 mm/min, depth of cut a(e) = 0.06 mm, width of contact a(p) = 0.8 mm, and for finishing ultra fine diamond grain size (D46), cutting speed v(c) = 4.7 m/s, feed speed v(ft) = 100 mm/min, depth of cut a(e) = 0.02 mm, width of contact a(p) = 0.8 mm. The results of the machining tests give a reference for using IPS Empress(R) 2 framework ceramic in CAD/CAM systems.

Aluminum Silicates↗
PubMed2000

Effect of pre-existing cytotoxic T lymphocytes on therapeutic vaccines.

Therapeutic vaccines which aim to induce CD8(+) cytotoxic T lymphocyte (CTL) responses will often be required to perform in the presence of pre-existing CTL which recognize epitopes within the vaccine. Here we explore the ability of a viral vaccine vector presenting several co-dominant CTL epitopes to prime CTL responses in animals that have a pre-existing CTL response to one of the epitopes in the vaccine. The vaccine was usually capable of inducing multiple new responses, suggesting that immunodomination effects of pre-existing CTL may generally be minimal following vaccination. However, when large numbers of pre-existing CTL were present, a novel type of immune modulation was observed whereby (1) the vaccine failed to prime efficiently new CTL responses that were restricted by the same MHC gene as the pre-existing responses, and (2) vaccine-induced CTL responses restricted by other MHC genes were enhanced. These results may have implications for therapeutic multi-epitope vaccines for diseases like HIV and melanoma, which aim to broaden CTL responses.

Adoptive Transfer↗