Biomedical subjects

M Schweizer

Publications and source records attributed to M Schweizer.

At least 19 recordsLinked to original sources

PubMed2006

[Analgesia in colon surgery. Can the use of NSAIDs reduce the opioid consumption following conventional and laparoscopic interventions?].

BACKGROUND: The goal of our study was to evaluate the morphine-sparing effect of nonsteroidal anti-inflammatory drugs (NSAIDs) following both conventional and laparoscopic colon surgery. MATERIALS AND METHODS: In this prospective, randomized clinical trial, 180 patients were assigned to three groups. Two groups received either paracetamol or parecoxib/valdecoxib in addition to piritramid via patient-controlled or nurse-controlled analgesia pump. Patients in the control group received piritramid only. The total piritramid consumption during hospital stay was recorded. RESULTS: Total opioid consumption was significantly lower in the two groups who received NSAIDs. Comparing conventional and laparoscopic surgery, the latter group had much lower opioid consumption. CONCLUSION: The use of NSAIDs following colon surgery significantly reduces postoperative opioid consumption.

Acetaminophen↗

PubMed2006

[How the bovine viral diarrhea virus outwits the immune system].

The interaction of bovine viral diarrhea virus (BVD virus) with its host has several unique features, most notably the capacity to infect its host either transiently or persistently. The transient infection stimulates an antiviral immune reaction similar to that seen in other transient viral infections. In contrast, being associated with immunotolerance specific for the infecting BVD viral strain, the persistent infection differs fundamentally from other persistent infections like those caused by lentiviruses. Whereas the latter are characterized by complex viral evasion of the host's adaptive immune response by mechanisms such as antigenic drift and interference with presentation of T cell epitopes, BVD virus avoids the immune response altogether by inducing both humoral and cellular immune tolerance. This is made possible by invasion of the fetus at an early stage of development. In addition to adaptive immunity, BVD virus also manipulates key elements of the host's innate immune response. The non-cytopathic biotype of BVD virus, which is capable of persistently infecting its host, fails to induce type I interferon. In addition, persistently infected cells are resistant to the induction of apoptosis by double-stranded RNA and do not produce interferon when treated with this pathogen-associated molecular pattern (PAMP) that signals viral infection. Moreover, when treated with interferon, cells persistently infected with non-cytopathic BVD virus do not clear the virus. Surprisingly, however, despite this lack of effect on persistent infection, interferon readily induces an antiviral state in these cells, as shown by the protection against infection by unrelated viruses. Overall, BVD virus manipulates the host's interferon defense in a manner that optimises its chances of maintaining the persistent infection as well as decreasing the risks that heterologous viral infections may carry for the host. Thus, since not all potential host cells are infected in animals persistently infected with BVD virus, heterologous viruses replicating in cells uninfected with BVD virus will still trigger production of interferon. Interferon produced by such cells will curtail the replication of heterologous viruses only, be that in cells already infected with BVD virus, or in cells in which the heterologous virus may replicate alone. From an evolutionary viewpoint, this strategy clearly enhances the chances of transmission of BVD virus to new hosts, as it attenuates the negative effects that a global immunosuppression would have on the survival of persistently infected animals.

Animals↗

PubMed2005

Ramifications of impaired PRPP synthesis in Saccharomyces cerevisiae.

The model eukaryote Saccharomyces cerevisiae is well suited to investigate the causes of metabolic disturbance. PRPP [5-phospho-D-ribosyl-1(alpha)-pyrophosphate] may be regarded as a junction of carbon and nitrogen metabolism. As a result of this central position, perturbations in its synthesis can give rise to many unexpected cellular events, such as impaired cell integrity. We have taken advantage of S. cerevisiae's genetic tractability to investigate the metabolic links responsible for connecting the biochemical intermediate PRPP to apparently unrelated cellular functions. This approach provides insight into the co-ordination of different biological processes.

Molecular Structure↗

PubMed2005

In Saccharomyces cerevisiae, impaired PRPP synthesis is accompanied by valproate and Li+ sensitivity.

The biosynthetic intermediate PRPP (phosphoribosylpyrophosphate) has a central role in cellular biochemistry since it links carbon and nitrogen metabolism. Its importance may be reflected in the fact that, in the Saccharomyces cerevisiae (yeast) genome, there are five unlinked genes, PRS1-PRS5, each of which is theoretically capable of encoding the enzyme synthesizing PRPP. Interference with the complement of PRS genes in S. cerevisiae has far-reaching consequences for yeast physiology and has uncovered unexpected metabolic links including cell wall integrity and phospholipid metabolism.

Binding Sites↗

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

Association between early postoperative coagulation activation and peri-operative myocardial ischaemia in patients undergoing vascular surgery.

We investigated the association of peri-operative myocardial ischaemia with activation of coagulation and endogenous fibrinolysis in patients undergoing vascular surgery. In 50 patients, continuous Holter monitoring was performed to assess peri-operative myocardial ischaemia and 12-lead electrocardiography was recorded preoperatively and 72 h postoperatively to assess myocardial infarction. Serial blood samples were drawn peri-operatively to determine the concentrations of fibrin monomers (for activation of coagulation), D-dimer (for endogenous fibrinolysis) and cardiac troponin T and I. Patients with myocardial ischaemia showed higher concentrations of fibrin monomers at 48 h, and higher concentrations of d-dimer preoperatively and at 24 and 48 h postoperatively. In patients with peri-operative myocardial ischaemia, strong positive correlations were observed between fibrin monomer and D-dimer concentrations at 15 min and 4 h postoperatively, and cardiac troponins at 15 min and at 4, 24, 48 and 72 h postoperatively. Early postoperative activation of coagulation and fibrinolysis is associated with peri-operative myocardial cell damage among patients who are at risk for, or have a history of, coronary artery disease plus peri-operative myocardial ischaemia.

Aged↗

PubMed2004

Postoperative 12-lead ECG predicts peri-operative myocardial ischaemia associated with myocardial cell damage.

Peri-operative myocardial ischaemia is the single most important risk factor for an adverse cardiac outcome after non-cardiac surgery. The present study examines whether intermittent 12-lead ECG recordings can be used as an early warning tool to identify patients suffering from peri-operative myocardial ischaemia and subsequent myocardial cell damage. Fifty-five vascular surgery patients at risk for or with a history of coronary artery disease were monitored for peri-operative myocardial ischaemia using intermittent 12-lead ECG recordings taken pre-operatively and at 15 min, 20 h, 48 h, 72 h and 84 h postoperatively. The effectiveness of the 12-lead ECG was gauged by examining concordance with continuous 3-channel Holter monitoring and capturing peri-operative myocardial ischaemia by serial analyses of creatine kinase myocardial band isoenzyme and cardiac troponin T and I. The incidence of peri-operative myocardial ischaemia detected by 12-lead ECG was 44% and was identifiable in most patients (88%) 15 min after surgery. The incidence of peri-operative myocardial ischaemia detected by continuous monitoring was 53%, with the most severe episodes occurring intra-operatively and during emergence from anaesthesia. The concordance of the 12-lead method with continuous monitoring was 72%. The concordance of creatine kinase myocardial band isoenzyme activity with the 12-lead method was 71% and with Holter monitoring 57%. The concordance of mass concentration of creatine kinase myocardial band with 12-lead ECG recordings was 75%, and the corresponding value for Holter monitoring was 68%. The concordance of cardiac troponin T and I levels with the 12-lead method was 85% and 87%, respectively, and concordance with Holter monitoring was 72% and 66%, respectively. The postoperative 12-lead ECG identified peri-operative myocardial ischaemia associated with subsequent myocardial cell damage in most patients undergoing vascular surgery.

Aged↗

PubMed2003

Replication of primate foamy viruses in natural and experimental hosts.

Foamy viruses (FVs) are common apathogenic retroviruses readily spread by horizontal transmission in nonhuman primate and some other mammalian host populations. Primate FV infections have been known for half a century, i.e., 15 years before the definition of retroviruses and another 15 years before the detection of primate immune deficiency viruses. The emerging interest in human retroviruses included primate FV, and although the role of human hosts for FV was greatly overestimated temporarily, enthusiastic researchers compiled invaluable data on molecular biology and classic as well as molecular epidemiology of these viruses. It has been shown that lytic FV infection in a wide range of cell cultures is in great contrast to the silent state of the infection in animals. Once transmitted by saliva via biting, FVs reside in all tissues as DNA copies, but their replication is untraceable except in oral submucosal cells, which are thought to supply the virus for transmission. FVs have not definitely been associated with any disease, regardless of viral phylogenetic differences. Various primate and nonprimate species have been used for studies on the natural carrier state and primary infection. Experimental infections have mostly proven to be inefficient in primates as well as lower laboratory animals. However, investigation of the immune response in FV-infected animals has only partly explained the control of FV replication in the animal host. Thus, the biological role of FV remains an enigma to be resolved in the future.

Animals↗

PubMed2003

Human infection with foamy viruses.

Virtually all nonhuman primate species investigated thus far including prosimians, New World and Old World monkeys and apes all harbor distinct and species-specific clades of simian foamy virus (SFV). However, evidence supporting the existence of a human-specific foamy virus (FV) is not yet available. Early reports describing widespread infection of healthy and sick humans with FV could not be confirmed. In contrast, all FV infections documented in humans are of zoonotic origin and are identified in persons occupationally exposed to nonhuman primates. The introduction of SFV into humans raises several public health questions regarding disease outcomes and potential for human-to-human transmissibility. The available data from a very limited number of SFV-infected humans suggest that these infections are nonpathogenic and are not easily transmissible. Additional studies are needed to better define the prevalence and natural history of SFV in humans.

Animals↗

PubMed2002

Peroxovanadate inhibits Ca2+ release from mitochondria.

Mitochondria contain a specific Ca2+ release pathway which operates when oxidized mitochondrial pyridine nucleotides are hydrolyzed. NAD+ hydrolysis and therefore Ca2+ release is possible when some vicinal thiols are cross-linked. Here we report that the thiol oxidant peroxovanadate inhibits the specific Ca2+ release pathway. In mitochondria, peroxovanadate causes a complete loss of reduced glutathione, which is not accompanied by formation of glutathione disulfide, and a partial loss of protein thiols. In model reactions, peroxovanadate oxidizes reduced glutathione predominantly to the sulfonate derivative, but does not react with glutathione disulfide. When the vicinal thiols relevant for Ca2+ release are cross-linked, Ca2+ release is no longer inhibited by peroxovanadate. Conversely, pretreatment of mitochondria with peroxovanadate makes them insensitive to compounds promoting the disulfide state. These results suggest that peroxovanadate inhibits the prooxidant-induced Ca2+ release from mitochondria by (i) depleting mitochondria of reduced glutathione and (ii) oxidizing the vicinal thiols relevant for Ca2+ release to a state higher than disulfide, presumably the sulfonate state. The findings provide further insight into the regulation of Ca2+ release from intact mitochondria, and may be relevant for a better understanding of the action of peroxovanadate in cells, where the compound can be insulin mimetic.

Animals↗

PubMed2002

Transcription factors acting on the promoter of the rat fatty acid synthase gene.

Fatty acid synthase (FAS), one of the main lipogenic enzymes, converts dietary calories into a storage form of energy. The transcription factors, stimulatory proteins 1 and 3 (Sp1 and Sp3), nuclear factor Y (NF-Y), upstream stimulatory factor (USF) and sterol regulatory element binding protein-1 (SREBP-1) have cognate binding sites on the promoter of the FAS gene. It was shown that Sp1 and NF-Y interact co-operatively at the diet-induced DNase I-hypersensitive site at position -500. Adjacent binding sites for NF-Y and Sp1 have also been found between -71 and -52, and -91 and -83. cAMP regulation is mediated via the inverted CAAT element (ICE) at -99 to -92, which binds NF-Y. The FAS insulin-responsive element 3 (FIRE3)-binding site at -71 to -52 is capable of binding NF-Y, USF and SREBP-1, and is required for the sterol response in conjunction with the co-activator NF-Y around -100. Surprisingly, both FIRE3 and ICE are also necessary for the response to retinoic acid that plays a role in development and is an essential component of the diet.

Animals↗

PubMed2001

A novel lentivirus vector derived from apathogenic simian immunodeficiency virus.

The improvement of gene transfer efficiency in growth-arrested cells using human immunodeficiency virus type 1 (HIV-1)-derived vectors led to the development of vectors derived from other members of the lentivirus family. Here we report the generation of a lentiviral vector derived from the apathogenic molecular virus clone SIVagm3mc of the simian immunodeficiency virus from African green monkeys (Cercocebus pygerythrus). Upon pseudotyping with the G-protein of vesicular stomatitis virus (VSV-G), the SIVagm-derived vector was shown to transduce proliferating and growth-arrested mammalian cell lines, including human cells. After in vivo inoculation into the striatum of the adult rat brain, the vector was shown to transduce terminally differentiated neurons and oligodendrocytes as well as quiescent and reactive astrocytes. Moreover, SIVagm transfer vector mRNA was efficiently packaged by HIV-1 vector particles. Homologous [SIV(SIV)] vectors generated by using the SIVagm-derived envelope glycoproteins allowed selective gene transfer into human CD4(+)/CCR5(+) cells. Thus, the SIVagm3mc-derived vector is a useful alternative to HIV-1-derived lentiviral vectors in somatic gene therapy.

Animals↗

PubMed2001

Toward an understanding of the furoxan-dinitrosoethylene equilibrium.

The tautomerism of furoxan (1,2,5-oxadiazole-2-oxide) has been investigated by different computational methods comprising modern density functionals as well as single-reference and multi-reference ab initio methods. The ring-opening process to 1,2-dinitrosoethylene is the most critical step of the reaction and cannot be treated reliably by low-level computations. The existence of cis-cis-trans-1,2-dinitrosoethylene as a stable intermediate is advocated by perturbational methods, but high-level coupled-cluster calculations identify this as an artifact. In contrast to the analogous reaction in benzofuroxans, cis-cis-cis-1,2-dinitrosoethylene was found to be a transition state rather than a local minimum. Model potentials were used to explain the occurrence and the disappearing of transition states and local minima relative to the reaction of benzofuroxan. Low-lying triplet states that can be accessed due to spin-orbit coupling were investigated as taking part in alternative routes to a proposed singlet pathway. Barriers for rotations of the nitroso groups on the S(0) and T(1) surfaces are reported.

Journal Article↗

PubMed2001

Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man.

Chloride channels play important roles in the plasma membrane and in intracellular organelles. Mice deficient for the ubiquitously expressed ClC-7 Cl(-) channel show severe osteopetrosis and retinal degeneration. Although osteoclasts are present in normal numbers, they fail to resorb bone because they cannot acidify the extracellular resorption lacuna. ClC-7 resides in late endosomal and lysosomal compartments. In osteoclasts, it is highly expressed in the ruffled membrane, formed by the fusion of H(+)-ATPase-containing vesicles, that secretes protons into the lacuna. We also identified CLCN7 mutations in a patient with human infantile malignant osteopetrosis. We conclude that ClC-7 provides the chloride conductance required for an efficient proton pumping by the H(+)-ATPase of the osteoclast ruffled membrane.

Adenosine Triphosphatases↗

PubMed2001

Role of Sp1 and Sp3 in the transcriptional regulation of the fatty acid synthase gene.

Inspection of the 5' region of the sequence of the rat fatty acid synthase (FAS) gene revealed a high GC content between -900 and +500, implying several binding sites for members of the Sp1 family of transcription factors. Using SL2 and H4IIE cells in conjunction with FAS promoter/luciferase constructs either successively deleted or containing defined deletions we characterized six GC boxes--GC-I to GC-VI--located between -557 and -83 and discovered a seventh, GC-VII, in the first intron. In vitro DNAse I-footprinting, electrophoretic mobility shift assays, and the yeast one-hybrid system indicated that Sp1 as well as Sp3 interacts with GC-I to GC-VII. Each of the GC boxes conferred Sp1-dependent transcription on the FAS-Mini promoter and in the case of GC-I, Sp1, and Sp3 exert an additive effect on FAS promoter activity.

Animals↗

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

Disruption of ClC-3, a chloride channel expressed on synaptic vesicles, leads to a loss of the hippocampus.

Several plasma membrane chloride channels are well characterized, but much less is known about the molecular identity and function of intracellular Cl- channels. ClC-3 is thought to mediate swelling-activated plasma membrane currents, but we now show that this broadly expressed chloride channel is present in endosomal compartments and synaptic vesicles of neurons. While swelling-activated currents are unchanged in mice with disrupted ClC-3, acidification of synaptic vesicles is impaired and there is severe postnatal degeneration of the retina and the hippocampus. Electrophysiological analysis of juvenile hippocampal slices revealed no major functional abnormalities despite slightly increased amplitudes of miniature excitatory postsynaptic currents. Mice almost lacking the hippocampus survive and show several behavioral abnormalities but are still able to acquire motor skills.

Acids↗