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Biomedical subjects

P Schweizer

Publications and source records attributed to P Schweizer.

At least 19 recordsLinked to original sources
PubMed2005

Tracheal surgery in children.

BACKGROUND: The aim of this study is to show that five distinct types of tracheal anomalies should be differentiated with respect to therapy and prognosis. METHODS: The records of 12 infants and children seen over a period of 20 years for different tracheal anomalies such as laryngotracheal stenosis (n = 3), long or short-segment stenosis of the upper (n = 2), middle (n = 6), and lower (n = 1) trachea were reviewed. In addition to these 12 patients with congenital stenosis, 3 other patients needed tracheal resections because of oncologic or traumatic disease: in 2, the trachea was infiltrated by a papillary carcinoma of the thyroid gland and in one, the upper part of the trachea was injured by an oral explosion accident. 25 patients presenting during the same period for other tracheal pathologies including esophagotracheal cleft syndrome (n = 7), tracheomalacia (n = 4), total tracheal agenesis (n = 3), or for placement of a tracheostomy (n = 11) due to other diseases were excluded from this study. RESULTS: There was 1 early death after repair of a laryngotracheal stenosis by cricoid-split and cricoid-splint due to both cerebral hemorrhage and cardiac insufficiency secondary to Fallot's tetralogy. Another child died four weeks after slide tracheoplasty as a result of hypoxic cerebral lesions induced by severe central catheter-related septicemia. One child with therapy-resistant obstructing granulation tissue which developed after a slide tracheoplasty required a tracheostomy. The patient with the tracheal injury died after another accident one year after discharge. All other patients (n = 11) are doing well. CONCLUSIONS: With respect to therapy of congenital and post-intubation tracheal stenosis, four types should be distinguished. Each of these types requires an adequate surgical procedure. The most important postoperative problem in tracheal surgery is the development of granulation tissue. However, the pathogenesis of granulation is still unknown.

Bronchoscopy↗
PubMed2005

Pathogenesis of extrahepatic bile duct atresia (EHBA): comprehension from a surgical point of view.

INTRODUCTION: The aim of the study is to establish a complete comprehension of the pathogenesis of Biliary Atresia, and to explain both the variable and redundant pathomorphological, as well as, histological findings. MATERIALS AND METHODS: The pathomorphological and histological findings in 223 patients with histologically evident EHBA were recorded retrospectively (72 patients) or prospectively (151 patients), according to a projected ascending study. These findings were compared with histological findings in human and rat embryos. RESULTS: 1) The pathomorphological findings recorded in patients with EHBA were also found in stages of normal embryogenesis of the bile duct system in human and rat embryos. 2) Each histological finding in Biliary Atresia corresponds to a finding in an interrupted stage of the normal development in human and rat embryos. 3) The findings in patients and embryos can be explained completely by a disturbed intrinsic epithelium/mesoderm interaction. 4) Some findings in Biliary Atresia cannot be explained easily by the assumption of an extrinsic factor. CONCLUSION: There is no finding in Biliary Atresia which cannot be completely explained as the result of an intrinsic developmental error, probably due to disturbances or interruption of epithelium/mesoderm interaction during embryogenesis.

Animals↗
PubMed2005

A high-throughput gene-silencing system for the functional assessment of defense-related genes in barley epidermal cells.

Large-scale gene silencing by RNA interference (RNAi) offers the possibility to address gene function in eukaryotic organisms at a depth unprecedented until recently. Although genome-wide RNAi approaches are being carried out in organisms like Caenorhabditis elegans, Drosophila spp. or human after the corresponding tools had been developed, knock-down of only single or a few genes by RNAi has been reported in plants thus far. Here, we present a method for high-throughput, transient-induced gene silencing (TIGS) by RNAi in barley epidermal cells that is based on biolistic transgene delivery. This method will be useful to address gene function of shoot epidermis resulting in cell-autonomous phenotypes such as resistance or susceptibility to the powdery-mildew fungus Blumeria graminis f. sp. hordei. Gene function in epidermal cell elongation, stomata regulation, or UV resistance might be addressed as well. Libraries of RNAi constructs can be built up by a new, cost-efficient method that combines highly efficient ligation and recombination by the Gateway cloning system. This method allows cloning of any blunt-ended DNA fragment without the need of adaptor sequences. The final RNAi destination vector was found to direct highly efficient RNAi, as reflected by complete knock-down of a cotransformed green fluorescent protein reporter gene as well as by complete phenolcopy of the recessive loss-of-function mlo resistance gene. By using this method, a role of the t-SNARE protein HvSNAP34 in three types of durable, race-nonspecific resistance was observed.

Gene Expression Profiling↗
PubMed2005

A pattern recognition tool for quantitative analysis of in planta hyphal growth of powdery mildew fungi.

The development of fungal pathogens can be quantified easily at the level of spore germination or penetration. However, the exact quantification of hyphal growth rates after initial, successful host invasion is much more difficult. Here, we report on the development of a new pattern recognition software (HyphArea) for automated quantitative analysis of hyphal growth rates of powdery mildew fungi on plant surfaces that usually represent highly irregular and noisy image backgrounds. By using HyphArea, we measured growth rates of colonies of the barley powdery mildew, Blumeria graminis f. sp. hordei, on susceptible and induced-resistant host plants. Hyphal growth was not influenced by the resistance state of the plants up to 48 h postinoculation. At later time points, growth rate increased on susceptible plants, whereas it remained restricted on induced-resistant plants. This difference in hyphal growth rate was accompanied by lack of secondary haustoria formation on induced-resistant plants, suggesting that induced resistance in barley against Blumeria graminis is caused mainly by reduced penetration rates of primary as well as secondary appressoria leading, finally, to fewer and less-developed fungal colonies. No evidence was found for reduced nutrient-uptake efficiency of the primary haustoria in induced-resistant leaves, which would be expected to have resulted in reduced hyphal growth rates during the first 48 h of the interaction.

Ascomycota↗
PubMed2004

Intrathoracic and intraabdominal locations of a cystic benign tumor: congenital etiology due to embryological diaphragm development?

A rare case of a benign cystic two-cavity tumor with intrathoracic and intraabdominal localisation is presented. The tumor's embryological etiology, embryological development of the diaphragm and the occurrence of embryonic tumors in general, are discussed. To our knowledge this is the first documented case of a benign two-cavity tumor in childhood and infancy.

Abdominal Neoplasms↗
PubMed2003

Immunohistochemical and molecular biological investigations regarding the pathogenesis of extrahepatic biliary atresia. (Part 1: immunohistochemical studies).

INTRODUCTION: The pathogenetic model for biliary atresia presently most favored is that EHBA is the result of a peri- or postnatal bile duct lesion. Several authors demonstrated inflammatory infiltrations in the mesenchymal areas of the liver and thus concluded an infectious genesis. An association of rota-, reo- (and CMV) virus infection with EHBA was suspected, but the presence of these viruses in EHBA could not be reproduced. In view of this controversial debate we found it to be indicated to investigate tissue blocks from the porta hepatis and liver biopsies in children with EHBA by histo- and immunohistochemistry for the quality and quantity of leukocyte infiltrations. METHODS: 31 tissue excidates of the porta hepatis were gained on the occasion of hepatoportoenterostomy, fixed in 4 % buffered formalin and embedded in paraffin. The presence of leukocyte infiltrations and their subpopulations was demonstrated by histochemical reactions and immunohistochemical staining methods using specific antibodies against surface markers. The number of leukocytes and their subpopulations was counted in three different regions of the porta hepatis, the obliterated extrahepatic bile duct, the fibrous mass of the porta hepatis and the transition zone between the fibrous mass and liver parenchyma. A statistical analysis was done. RESULTS: In EHBA, leukocyte infiltrations consist mainly of macrophages. Antigen-presenting cells and lymphatic cells play a minor role. Lymphatic cells could only be detected in 6 out of 31 tissue preparations. Antigen-presenting cells could only be detected via anti-F13a antibody which shows cross-reactivities, i.e. against macrophages and embryonal tissue. Evaluating the density of leukocyte infiltrations with regard to the different anatomical regions of the porta hepatis we could demonstrate that leukocyte infiltrations are scarce around the rudiment of the bile duct whereas the highest leukocyte density could be found in the fibrous mass of the porta hepatis and the intrahepatic fibrous septs interconnecting the fibrous mass of the porta hepatis with liver parenchyma. Liver parenchyma was mainly free of leukocyte infiltrations with the exception of neutrophilic granulocytes. Regardless of the subpopulations, leukocytes were mainly arranged around the bile ducts of the fibrotic septa. CONCLUSIONS: Most tissue preparations from children operated on during the 4th-8th week of life show only small leukocyte infiltrations and in the majority of cases no immunocompetent lymphocytes. This leads to the conclusion that a virus infection as an underlying cause for EHBA is very unlikely. Most probably, the observed leukocyte infiltrations are due to an unspecific phagocytotic activity. Comparing our results to reports from Hadchouel et al (9) and Landing et al (12) led us to believe that a pathologic immunoreaction with a possible defective antigen elimination could also be considered as a reason for EHBA.

Antigens, CD↗
PubMed2001

Tolerance of human MSH2+/- lymphoblastoid cells to the methylating agent temozolomide.

Members of hereditary nonpolyposis colon cancer (HNPCC) families harboring heterozygous germline mutations in the DNA mismatch repair genes hMSH2 or hMLH1 present with tumors generally two to three decades earlier than individuals with nonfamilial sporadic colon cancer. We searched for phenotypic features that might predispose heterozygous cells from HNPCC kindreds to malignant transformation. hMSH2(+/-) lymphoblastoid cell lines were found to be on average about 4-fold more tolerant than wild-type cells to killing by the methylating agent temozolomide, a phenotype that is invariably linked with impairment of the mismatch repair system. This finding was associated with an average 2-fold decrease of the steady-state level of hMSH2 protein in hMSH2(+/-) cell lines. In contrast, hMLH1(+/-) heterozygous cells were indistinguishable from normal controls in these assays. Thus, despite the fact that HNPCC families harboring mutations in hMSH2 or hMLH1 cannot be distinguished clinically, the early stages of the carcinogenic process in hMSH2 and hMLH1 mutation carriers may be different. Should hMSH2(+/-) colonocytes and lymphoblasts harbor a similar phenotype, the increased tolerance of the former to DNA-damaging agents present in the human colon may play a key role in the initiation of the carcinogenic process.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Lack of MSH2 and MSH6 characterizes endometrial but not colon carcinomas in hereditary nonpolyposis colorectal cancer.

Hereditary nonpolyposis colorectal cancer syndrome is associated with an inherited predisposition to primarily colorectal cancer (CRC) and endometrial cancer (EC); however, the biological basis of the organ involvement remains unknown. As an attempt to explore whether the expression levels of MLH1, MSH2, and MSH6 may play a role, we used immunohistochemistry to study 42 ECs and 35 CRCs from patients carrying the same predisposing mutations. Among MSH2 mutation carriers, MLH1 was expressed in both tumor types, whereas MSH2 and, in many cases, also MSH6, were absent. Remarkably, among MLH1 mutation carriers, 54% of ECs (21 of 39), but none of the CRCs (0 of 32), lacked the MSH2 and/or MSH6 protein in addition to lacking MLH1 protein expression. These results demonstrate a marked difference between hereditary nonpolyposis colorectal cancer-related CRCs and ECs and suggest that the development of the latter tumors is selectively associated with the MSH2/MSH6 protein complex deficiency.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Laser resection of posterior urethral valves.

Laser resection (LR) of posterior urethral valves during infancy as early as possible after diagnosis appears to represent a safe and reliable method. In contrast to other procedures, LR allows valve ablation with thin cystoscopes and carries little risk, even in premature and newborn infants. Its application in seven children in the course of 2 years principally confirmed its suitability for use: it could be applied in all cases without any problems and led to extensive resection of the valve tissue and removal of the obstruction in all patients. The encouraging clinical findings were confirmed by control cystoscopies and micturating cystourethrograms. Complications arising from the method were not observed.

Cystoscopy↗
PubMed2001

Semicircular papillotomy: a new surgical technique for removal of bile stones lodged in the ampulla of Vater.

Bile stones lodged in the ampulla of Vater present a rare but often difficult problem. Considering the disadvantages of conventional papillotomy and papillectomy, we developed a technique in which both the anatomic structures and their function are preserved. Histologic studies of the ampulla provided the basis for the technique, in which the muscular layers of the ampulla are not cut through as in conventional papillotomy but are bluntly separated, preserving this important anatomic component of the ampulla saved. The postoperative and long-term outcome of seven patients with bile stones lodged in the ampulla are reported. We found semicircular lateral papillotomy a safe procedure that preserves the muscular structures and function of the ampulla.

Adolescent↗
PubMed2001

Anatomy of the porta hepatis as a basis for extended hepatoporto-enterostomy for extrahepatic biliary atresia--a new surgical technique.

UNLABELLED: Reports on long-term survival rates after Kasai's HPE reveal that 23% of patients are healthy ten and more years after surgery. Therefore we studied again the anatomy and histology of the porta hepatis and the portal tracts in order to improve this surgical procedure. METHODS: Autopsied livers of 6 children with and 6 without EHBA were investigated with regard to the topographical and histological anatomy of the major intra- and extrahepatic bile ducts. RESULTS: On the basis of anatomical findings we have modified the conventional Kasai's HPE and developed an extended exploration of the porta hepatis. The procedure and surgical technique is described in this paper.

Bile Ducts, Extrahepatic↗
PubMed2001

Neuroblastoma: inhibition of progression (Part II). Basic science in pediatric surgery.

In neuroblastoma, amplification of the protooncogene N-myc is the most important molecular characteristic predicting a bad outcome for the patients. Despite the importance of the N-myc gene, little is known about the mechanisms regulating its expression. We found evidence that insulin-like growth factor II stimulates the growth of neuroblastoma in a paracrine fashion. Two neuroblastoma cell lines predominantly expressed IGF-II whereas two other cell lines expressed the IGF-receptor. In a receptor-positive cell line, N-myc expression was enhanced by stimulation with IGF-II. As the growth-stimulating signals of the IGF receptor are transmitted via Ras proteins, inactivation of Ras is one promising tool to prevent the induction of N-myc expression by IGF-II. Treatment of neuroblastoma cells with an inhibitor of the farnesyl-protein-transferase (FPTase) inactivated H-ras protein completely and N-ras protein by more than 50 %. Cell growth of neuroblastoma cells in serum containing medium was clearly diminished by inhibition of FPTase. The growth-promoting effect of IGF-II was reduced to exactly half the amount observed in non-inhibited cells.

Alkyl and Aryl Transferases↗
PubMed2001

Induction of bile ducts in embryonic liver by mesenchyme: a new perspective for the treatment of biliary atresia?

Presently only those forms of Extrahepatic Biliary Atresia (EHBA) with minimal or no intrahepatic manifestations can be treated successfully by extensive hepatoportoenterostomy. Intraoperative macro- and microscopic observations show that the typical pathogenetic manifestations in EHBA are most prominent at the porta hepatis. We therefore postulate that EHBA is the result of a defective embryonic development of the porta hepatis. In rat embryos hepatic bile duct formation is initiated at the porta hepatis and in this context mesenchyme from the periportal region seems to play a major inductive role. In order to demonstrate the role of invading periportal mesenchyme for the process of bile duct rudiment formation we established an organ culture model of the embryonic porta hepatis by recombining periportal mesenchyme with peripheral liver fragments from 15 days old rat embryos (Carnegie Stage 21). The degree of mesenchyme invasion as well as the formation of mesenchyme-surrounded liver cell clusters, rosettes or vesicles (bile duct rudiments) were assessed. Mesenchyme from the porta hepatis invaded the peripheral liver fragments and induced the formation of mesenchyme-surrounded liver cell clusters and rosettes with the beginning of lumen formation. Kidney mesenchyme recombined with liver fragments as a mesenchymal alternative showed almost the same effect, lung mesenchyme showed only a very weak inductive effect. To assess the effect of a diffusible factor versus direct cell contact, a millipore filter with and without paraffin coating was interposed between mesenchyme containing tissue and peripheral liver tissue fragments. Without direct cell contact to mesenchyme no hepatoblast cluster or rosette formation could be observed. Comparing this result to the normal development of the liver in rats our investigations suggest that the embryogenesis of the porta hepatis is probably defined by the following two developmental steps: First, differentiation of the intrahepatic bile duct system which is induced by invading mesenchyme originating from the extrahepatic periportal region and realized by epithelium mesenchyme interaction. Second, fusion of extra- and intrahepatic bile duct systems at the level of the later porta hepatis. Disturbances of this complex process can possibly lead to biliary atresia. Further investigations regarding details of the role of the mesenchyme, its inductive factors and the kidney mesenchyme's inductive potential in liver development may provide a new perspective for future treatment of biliary atresia.

Animals↗
PubMed2001

Syringolin reprograms wheat to undergo hypersensitive cell death in a compatible interaction with powdery mildew.

We had previously isolated and characterized syringolin A, one of the molecular determinants secreted by Pseudomonas syringae pv syringae that is perceived by nonhost plant species such as rice. Here, we show that syringolin A is recognized by wheat and that it induces the accumulation of gene transcripts and increases protection against powdery mildew when applied before inoculation. Moreover, syringolin A essentially eradicates powdery mildew from infected wheat if applied after inoculation. This curative effect is accompanied by the induction of cell death and the reactivation of pathogenesis-related genes whose transcript levels initially accumulate after powdery mildew inoculation but then decline during the later course of infection. Because syringolin A has no fungicidal activity against a variety of fungi and its action on wheat cannot be mimicked by the fungicide cyprodinil, syringolin A is hypothesized to counteract the suppression of host defense reactions imposed by the pathogen on the colonized cells.

Cell Death↗
PubMed2000

Prognosis of extrahepatic bile-duct atresia after hepatoportoenterostomy.

Clinical and histologic findings from 206 patients operated upon for extrahepatic biliary atresia (EHBA) are analyzed in order to define the prognosis of patients with EHBA. The prospective study took into consideration both initial fibrosis of the liver and the morphology of the porta hepatis (PH) at surgery. Kaplan-Meier survival estimates and statistical calculations demonstrated a relationship between long-term survival and histologic findings in the liver and porta hepatis. The efficacy of HPE is significantly influenced by the morphology of the PH and to a lesser extent by the initial liver fibrosis. Surgery should thus achieve pattern 1 morphology of the PH, but this is problematic because of the close relationship of the vascular and biliary structures in its two lateral zones.

Biliary Atresia↗
PubMed2000

Peritonitis in childhood: aspects of pathogenesis and therapy.

The pathogenesis of peritonitis due to hollow-viscus perforation is currently accepted as being mainly based on the local and systemic release of pro- and anti-inflammatory mediators triggered by the presence of bacteria and bacterial products in the abdominal cavity. Therefore, treatment consists in focal restoration, intraoperative debridement and lavage, and postoperative measures such as drainage, continuous peritoneal lavage, or scheduled reoperation aiming at the removal of infectious agents from the peritoneal cavity to prevent persisting peritonitis and sepsis. In order to evaluate the pathophysiologic relevance of the bacterial and endotoxin load of the peritoneal exudate, we examined the peritoneal fluid of 20 children with perforated appendicitis for qualitative and quantitative analysis of bacteria, antibiotic concentrations, and endotoxin content. The time period ranged in 12-h intervals from intraoperatively to day 5. Eighteen of 20 fluid specimens (90%) showed endotoxin levels above 1.5 endotoxin units EU/ml (standard <0.1 EU/ml). The most common bacterial species isolated was Escherichia coli, mostly in high concentrations. Despite persisting high endotoxin concentrations and bacterial loads in the peritoneal cavity during the 5 postoperative days, the children recovered uneventfully and the systemic signs of infection disappeared rapidly. In conclusion, neither the bacterial nor the endotoxin load of the peritoneal cavity proved to be associated with the clinical course. Therefore, we hypothesize that during peritonitis compartmentalization of the focus of infection prevents further systemic reactions and ultimately leads to removal of the infectious agents by endogenous mechanisms. At least in peritonitis due to perforated appendicitis in children, adjuvant surgical measures in addition to appendectomy and intraoperative debridement are not necessary.

Anti-Bacterial Agents↗
PubMed2000

Ceramide induces apoptosis in neuroblastoma cell cultures resistant to CD95 (Fas/APO-1)-mediated apoptosis.

BACKGROUND/PURPOSE: Spontaneous tumor regression is a well-known characteristic in neuroblastomas. Because preliminary reports have shown that regression may be caused by apoptosis (a lethal cascade mediated by the CD95 (APO-1/Fas)-receptor), we analyzed the expression of CD95-receptors in 5 human neuroblastoma cell lines. Ceramides (known stimuli of apoptosis downstream from the CD95-receptor complex) also were used to test whether apoptosis would be induced in neuroblastoma cell cultures resistant to CD95-mediated programmed cell death. METHODS: The expression of the CD95-receptor was assessed by flow cytometry after incubation with either fluorisothiocyanate-conjugated (FITC) anti-CD95-antibody (UB2) or CD95-ligand for 16 hours. Apoptotic cell death was detected via microscopy, cell viability testing (MTT, 3-[4,5 dimehylthiazole-2-yl]-2,5 diphenyltetrazoliumbromide), and flow cytometric analysis after propidium iodide staining of the DNA. RESULTS: CD95-receptor expression was found on all neuroblastoma cell lines. Stimulation of the CD95-receptor of the malignant glioblastoma cell line LN229 (positive control) with either anti-CD95-antibody or CD95-ligand induced apoptosis. Apoptosis was not seen, however, in any of the neuroblastoma cell lines when the CD95-receptor was stimulated with anti-CD95-antibody or the CD95-ligand. Significant apoptosis was detected in all neuroblastoma cell lines after the addition of 25 micromol/L C2- and C6-ceramide. CONCLUSIONS: CD95-receptors are present on neuroblastoma cell lines, and these cells are resistant to apoptosis stimulated by anti-CD95-antibody or CD95-ligand. Apoptosis is induced, however, when these cells are treated with ceramide. A signal blockage downstream from the CD95-receptor complex and upstream of ceramide may account for this finding, and the "cellular FLICE inhibitory protein" (cFLIP) may be primarily responsible.

Apoptosis↗