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Biomedical subjects

C Meyer

Publications and source records attributed to C Meyer.

At least 289 records · Page 16Linked to original sources
PubMed1996

Xenograft rejection: molecular mechanisms and therapeutic prospects.

The use of animal organs for transplantation in humans is seen as a potential solution to the short supply of human donor organs available for clinical transplantation. However, while several attempts at clinical xenografting have been made over the last ninety years, xenotransplantation has not matched the success of allotransplantation, because of a vigorous rejection response. Xenograft rejection is mediated by mechanisms that differ from those involved in alloreactivity and which are inadequately controlled by conventional immunosuppressive agents. Xenotransplantation therefore requires the development of specific strategies to overcome rejection, through modification of the host immunity or production of genetically engineered pig organs. This article reviews the cellular and molecular events underlying xenograft rejection and the potential strategies of prevention and gives a brief history of the main attempts at clinical xenotransplantation since the beginning of the century.

Animals↗
PubMed1996

Magnesium in the prophylaxis of migraine--a double-blind placebo-controlled study.

The migraine prophylactic effect of 10 mmol magnesium twice-daily has been evaluated in a multicentre, prospective, randomized, double-blind, placebo-controlled study. Patients with two to six migraine attacks per month without aura, and history of migraine of at least 2 years, were included. A 4-week baseline period without medication was followed by 12 weeks of treatment with magnesium or placebo. The primary efficacy end-point was a reduction of at least 50% in intensity or duration of migraine attacks in hours at the end of the 12 weeks of treatment compared to baseline. With a calculated total sample size of 150 patients, an interim analysis was planned after completing treatment of at least 60 patients, which in fact was performed with 69 patients (64F, 5M), aged 18-64 years. Of these, 35 had received magnesium and 34 placebo. The number of responders was 10 in each group (28.6% under magnesium and 29.4% under placebo). As determined in the study protocol, this was a major reason to discontinue the trial. With regard to the number of migraine days or migraine attacks there was no benefit with magnesium compared to placebo. There were no centre-specific differences, and the final assessments of treatment efficacy by the doctor and patient were largely equivocal. With respect to tolerability and safety, 45.7% of patients in the magnesium group reported primarily mild adverse events like soft stool and diarrhoea in contrast to 23.5% in the placebo group.

Adolescent↗
PubMed1996

[Form deprivation myopia caused by keratitis scrophulosa].

Zrenner and Schaeffel reported that translucent occluders may induce axial eye elongation in animals. This axial growth is also called form deprivation myopia (FDM). Searching for a clinical correlate we examined in a retrospective study 115 patients with keratitis scrophulosa peracta, mainly corneal transplant patients. These patients had an average refraction of -4.27 dpt. In epidemiologic studies Stenström found +0.5 dpt as the mean refraction in the general population. When the onset of the corneal disease was before the age of 5 years, the myopia was found to be higher than in patients with later age of onset. In 43 patients we determined axial length by ultrasound biometry and found an average axial length of 26.89 mm, whereas the general average is 24.00 mm. In conclusion, these results confirm that not only in animal experiments but also in clinical cases FDM is responsible for the axial growth of eyes.

Adolescent↗
PubMed1996

[Immediate resection-anastomosis after intra-operative colonic irrigation in cancer of the left colon with obstruction].

In a consecutive series of 38 patients over 5 years, who required emergency surgery for obstructing left colonic carcinoma, 24 had primary bowel resection with immediate anastomosis, after intraoperative anterograde colonic irrigation. Complete colonic obstruction was present in all cases. There were 7 Dukes B tumors, 11 Dukes C tumors and 6 Dukes D tumors. The operative mortality was 8.3% (2 patients, with one from anastomotic leakage), anastomotic leakage rate was 4%. Superficial wound infection occurred in 4% of patients. The median postoperative hospital stay was 19.5 days. The Kaplan-Meier survival curve showed a 41% survival rate after 5 years. This technique was found to be safe and effective to perform a primary anastomosis, without requiring temporary colostomies, after emergency resection of selected left colonic carcinoma obstruction.

Aged↗
PubMed1996

[Value of an antiparasitic treatment against Strongyloidea and Coccidia in Djallonke ewes at lambing].

Three groups of 14 Djallonke ewes each have been compared: group E received one antiparasitic treatment with Ivermectin, or Valbazen and Amprol at lambing, group T2 received three classical antiparasitic treatments with the same drugs according to the seasons (at the beginning and at the end of the long rainy season, and at the end of the short rainy season) group T1 remained untreated. The onset of sexual activity occurred 71.5 +/- 5.4 days (lot E), 74.5 +/- 6.3 (lot T2) and 104.3 +/- 10.3 (lot T1) after lambing. So, intervals between lambings were 255.7 +/- 11.8 (lot E), 245.9 +/- 13.5 (lot T2) and 298.2 +/- 24 (lot T1). Lambing other characteristics were almost the same in the three groups: prolificacy 127-137%, weight at birth 1.2-1.4 kg, daily weight gains (0-90 days) 99-114 g and mortality 39-48%. It seems economically more profitable to treat against internal parasites once at lambing rather than three times a year according to the seasons.

Animals↗
PubMed1996

[Tonometric monitoring of the viability of free transplants of the jejunum and the stomach after total circulary pharyngolaryngectomy].

A prospective study concerning the tonometric viability supervision of 9 digestive free autografts after total pharyngolaryngectomy was conducted. This technic is based on the Henderson and Hasselbalch's equation which calculates the intramucosal pH (pHi) in the graft using a tonometric catheter. When the pHi is under 7.10, there is a graft ischemia. This invasive technique seems to be sensitive and specific provided that minimally rigorous measurement procedures are used. Late graft necrosis is the major limitation of the technique.

Adult↗
PubMed1995

Characterization of an fdxN mutant of Rhodobacter capsulatus indicates that ferredoxin I serves as electron donor to nitrogenase.

A mutant of Rhodobacter capsulatus, carrying an insertion into the fdxN gene encoding ferredoxin I (FdI), has been studied by biochemical analysis and genetic complementation experiments. When compared to the wild-type strain, the fdxN mutant exhibited altered nitrogen fixing ability and 20-fold lower levels of nitrogenase activity as assayed in vivo. When assayed in vitro with an artificial reductant, nitrogenase activity was only 3- to 4-fold lower than in the wild type. These results suggested that the FdI-deleted mutant had impaired electron transport to nitrogenase. Immunochemical assay of both nitrogenase components showed that the fdxN mutant contained about 4-fold less enzyme than wild-type cells. Results of pulse-chase labeling experiments using [35S]methionine indicated that nitrogenase was significantly less stable in the FdI-deleted mutant. When a copy of fdxN was introduced in the mutant in trans, the resulting strain appeared to be fully complemented with respect to both diazotrophic growth and nitrogenase activity. Depending on whether fdxN expression was driven by a nif promoter or a fructose-inducible promoter, FdI was synthesized either at wild-type level or in 10-fold lower amounts. The strain producing 10-fold less FdI did, however, display normal N2-fixing ability. Analysis of cytosolic proteins by bidimensional electrophoresis revealed that the fdxN mutant produced a 14 kDa polypeptide in amounts about 3-fold greater than wild-type cells. This protein was identified by N-terminal microsequencing as a recently purified [2Fe-2S] ferredoxin, called FdV, which cannot reduce nitrogenase. It is concluded that FdI serves as the main electron donor to nitrogenase in R. capsulatus and that an ancillary electron carrier, distinct of FdV, is responsible for the residual nitrogenase activity observed in the FdI-deleted mutant.

Base Sequence↗
PubMed1995

Nucleotide sequence of the lantibiotic Pep5 biosynthetic gene cluster and functional analysis of PepP and PepC. Evidence for a role of PepC in thioether formation.

The biosynthesis of Pep5, a lanthionine-containing antimicrobial peptide, is directed by the 20-kbp plasmid pED503. We identified a 7.9-kbp DNA-fragment within this plasmid which covers the information for Pep5 synthesis in the homologous host Staphylococcus epidermidis 5 which has been cured of pED503. This fragment contained, in addition to the previously described structural gene pepA and the immunity gene pepI [Reis, M., Eschbach-Bludau, M., Iglesias-Wind, M. I., Kupke, T. & Sahl, H.-G. (1994) Appl. Env. Microbiol. 60, 2876-2883], a gene pepT coding for a translocator of the ABC transporter family, a gene pepP coding for a serine protease and two genes pepB and pepC coding for putative modification enzymes; the gene arrangement is pepTIAPBC. We analyzed the biosynthetic genes with respect to their function in Pep5 biosynthesis. Deletion of PepT reduced Pep5 production to about 10%, indicating that it can be partially replaced by other host-encoded translocators. Inactivation of PepP by site-directed mutagenesis of the active-site His residue resulted in production of incorrectly processed Pep5 fragments with strongly reduced antimicrobial activity. Deletion of pepB and pepC leads to accumulation of Pep5 prepeptide in the cells without excretion of processed peptide. A pepC-deletion clone did not excrete correctly matured Pep5 but it did produce fragments from which serine and threonine were absent. Only one of these fragments contained a single lanthionine residue out of three expected while the remaining, unmodified cysteine residues could be detected by reaction with Ellman's reagent. These results demonstrate that PepC is a thioether-forming protein and strongly suggest that PepB is responsible for dehydration of serine and threonine.

ATP-Binding Cassette Transporters↗
PubMed1995

Identification by mutational analysis of four critical residues in the molybdenum cofactor domain of eukaryotic nitrate reductase.

The nucleotide sequence of the nitrate reductase (NR) molybdenum cofactor (MoCo) domain was determined in four Nicotiana plumbaginifolia mutants affected in the NR apoenzyme gene. In each case, missense mutations were found in the MoCo domain which affected amino acids that were conserved not only among eukaryotic NRs but also in animal sulfite oxidase sequences. Moreover an abnormal NR molecular mass was observed in three mutants, suggesting that the integrity of the MoCo domain is essential for a proper assembly of holo-NR. These data allowed to pinpoint critical residues in the NR MoCo domain necessary for the enzyme activity but also important for its quaternary structure.

Amino Acid Sequence↗
PubMed1995

Rapid aldosterone signaling in vascular smooth muscle cells: involvement of phospholipase C, diacylglycerol and protein kinase C alpha.

Rapid in vitro effects of aldosterone (ALDO) on intracellular sodium, potassium and calcium, cell volume and the sodium-proton-antiport have been described in human mononuclear leukocytes and rat vascular smooth muscle cells (VSMC). These nongenomic effects are signaled through membrane receptors with a high affinity for aldosterone, but not for hydrocortisone. Effects of ALDO on the production of diacylglycerol (DAG) and protein kinase C alpha (PKC) were measured in VSCM by enzymatic assay and immunoblotting. DAG production was stimulated twofold by ALDO (> or = 1 nM) within 30 sec while hydrocortisone was inactive at concentrations of up to 1 microM. The inhibitors of phospholipase C, neomycin and U-73122 completely blocked this effect. PKC translocation from cytosol to membranes by ALDO occurred within 5 min, the extent of this effect was comparable to that of angiotensin II. These data demonstrate rapid intracellular signaling for ALDO in VSMC through phospholipase C, DAG and PKC in addition to calcium and inositol-1,4,5-trisphosphate as determined earlier.

Aldosterone↗