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K Robert

Publications and source records attributed to K Robert.

10 recordsLinked to original sources
PubMed2005

Regulation of extracellular signal-regulated kinase by homocysteine in hippocampus.

In several neurological disorders including hyperhomocysteinemia, homocysteine (Hcy) accumulates in the brain, and acts as a potent neurotoxin. However, the molecular mechanisms induced by increased levels of Hcy in brain are not well understood. Here we show an activation of the extracellular signal-regulated kinases (ERK1 and ERK2) and the downstream nuclear targets Elk-1 and calcium/cAMP response element binding protein, in the hippocampus of cystathionine beta synthase deficient mice, a murine model of hyperhomocysteinemia. An ex vivo model of hippocampal slices allowed us to reproduce Hcy -induced ERK activation and to unravel the mechanisms responsible of this activation. Of interest, N-methyl-d-aspartate (NMDA), non-NMDA and metabotropic glutamate receptor antagonists all blocked Hcy -induced ERK activation. Moreover, the ERK activation was blocked in the presence of Na+-channel blocker tetrodotoxin, indicating the existence of a trans-synaptic activity in ERK activation by Hcy in hippocampal slices. The effects of Hcy on ERK cascade activation were also dependent on calcium influx, CaMK-II, PKC as well as PKA activation. Thus, altogether these data support a role of Hcy on ERK activation, via complex mechanisms, starting with a control of glutamate release, which in turn activates ionotropic and metabotropic receptor subtypes and produces increases in intracellular calcium levels.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2005

A HIPS-mimic.

Explore the source record for details and available documents.

AIDS-Related Opportunistic Infections↗
PubMed2004

Protective effect of a low K+ cardioplegic solution on myocardial Na,K-ATPase activity.

Long duration ischemia in hypothermic conditions followed by reperfusion alters membrane transport function and in particular Na,K-ATPase. We compared the protective effect of two well-described cardioplegic solutions on cardiac Na,K-ATPase activity during reperfusion after hypothermic ischemia. Isolated perfused rat hearts (n = 10) were arrested with CRMBM or UW cardioplegic solutions and submitted to 12 hr of ischemia at 4 degrees C in the same solution followed by 60 min of reperfusion. Functional recovery and Na,K-ATPase activity were measured at the end of reperfusion and compared with control hearts and hearts submitted to severe ischemia (30 min at 37 degrees C) followed by reflow. Na,K-ATPase activity was not altered after 12 hr of ischemia and 1 hr reflow when the CRMBM solution was used for preservation (55 +/- 2 micromolPi/mg prot/hr) compared to control (53 +/- 2 micromol Pi/mg prot/hr) while it was significantly altered with UW solution (44 +/- 2 micromol Pi/mg prot/hr, p < 0.05 vs control and CRMBM). Better preservation of Na,K-ATPase activity with the CRMBM solution was associated with higher functional recovery compared to UW as represented by the recovery of RPP, 52 +/- 12% vs 8 +/- 5%, p < 0.05 and coronary flow (70 +/- 2% vs 50 +/- 8%, p < 0.05). The enhanced protection provided by CRMBM compared to UW may be related to its lower K+ content.

Adenosine↗
PubMed2003

Pleiotrophic cellular deficiencies conferred by the blm5-1 mutation of Saccharomyces cerevisiae.

Mutational alteration of the BLM5 gene of the model eukaryote, Saccharomyces cerevisiae, confers extreme hypersensitivities to lethal effects of ionizing radiation, anticancer bleomycins and structurally-related phleomycins. Additional properties conferred by the blm5-1 mutation in haploid and diploid strains were investigated for the current report. Only one copy of blm5-1 together with the normal BLM5 allele was sufficient to produce mitotic and meiotic defects in diploids, and greatly increase killing by bleomycin beyond wild type levels. Mitotic growth rates of blm5-1/blm5-1 homozygous mutant strains were slower than wild type or BLM5/blm5-1 heterozygous strains at 30 degrees C, and growth was nearly completely inhibited at 37 degrees C. Meiosis was inhibited at 30 degrees C and 37 degrees C in mutant homozygotes, and at 37 degrees C in BLM5/blm5-1 heterozygotes, while meiosis occurred at equivalent frequencies in wild type strains at both temperatures. Surprisingly, mutant strains were found to associate extremely low quantities of [S-methyl-3H]bleomycin A2, in contrast to normal strains that associated quite high amounts. However, the fractions of the total associated radioactivities that were released from normal and blm5-1 cells were equivalent. These results suggested that the extremely high killing suffered by blm5-1 mutant strains in response to bleomycin treatments results from something other than increased intracellular drug concentrations.

Alleles↗
PubMed2001

Quantitation of immunosuppression by tacrolimus using flow cytometric analysis of interleukin-2 and interferon-gamma inhibition in CD8(-) and CD8(+) peripheral blood T cells.

The authors have determined the frequency of intracellular interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) synthesis by T-cell subsets in whole blood (WB) and isolated lymphocytes in 16 transplant recipients treated with tacrolimus and 10 control patients who were not transplant recipients. The authors also determined the impact of varying amounts of red blood cells (RBC) on immunosuppression by tacrolimus. Samples were analyzed by two-color flow cytometry, and the results were expressed as a ratio of whole blood to isolated lymphocytes. In healthy subjects who were not transplant recipients, the frequency of IL-2--producing CD8(-) and CD8(+) cells was higher in WB than in isolated lymphocytes (mean +/- SD of whole blood to lymphocytes ratio: 1.24 +/- 0.5 and 1.67 +/- 0.62, respectively). Adding varying amounts of RBC had no significant impact on IL-2 production by CD8(-) and CD8(+) T cells. Adding tacrolimus (10 ng/mL) to lymphocyte cultures inhibited (90%) IL-2 production in isolated T cells but not in the whole-blood assay. The dose of tacrolimus required for a 50% inhibition of IL-2 release in T cells was 10-fold higher in cultures with RBC than without. Peripheral blood mononuclear cells (PBMC) isolated from tacrolimus-treated whole blood (WB) showed less IL-2 inhibition than did lymphocytes in the WB. The authors also tested cytokine production in WB and PBMCs in 16 transplant recipients and observed various patterns of reactivity. The frequency of IL-2--producing CD8(-) and CD8(+) cells was similar using two different methods in 10 of 16 patients tested. By contrast, in the remaining six patients the authors observed a significant inhibition of IL-2 production in both CD8(-) and CD8(+) T-cell subsets in the whole-blood assay but not in the isolated lymphocytes. The frequency of CD8(-) IFN-gamma--producing cells was significantly lower in 9 of 16 patients, but the same individuals showed no inhibition of their CD8(+) IFN-gamma T cells. The trough levels of tacrolimus did not predict the level of cytokine inhibition in the whole-blood assay in these patients. The authors' results show that the whole-blood assay for cytokine production can be used for monitoring the in vivo effect of tacrolimus in transplant recipients.

Adult↗
PubMed2001

[Long-term results after resection arthroplasty according to Girdlestone for treatment of persisting infections of the hip joint].

INTRODUCTION: Persisting infections of the hip joint are regarded as one of the most feared complications following total hip arthroplasty or failed osteosynthetic treatment of fractures of the proximal femoral part. In these cases resection arthroplasty according to Girdlestone often is the ultimate treatment. METHODS: Twenty-seven patients (11 men and 16 women) who had undergone resection arthroplasty according to Girdlestone could be included in this study. In all cases Girdlestone operations had been performed because of persisting infections of the hip joint. The mean follow-up was 7.1 years. RESULTS: In 22 out of 27 cases (81.5%) eradication of the infection was finally achieved. At the time of re-evaluation 6 patients had no pain, 12 sometimes suffered from moderate pain, 7 from pain during physical activities and 2 patients experienced pain even at rest. At the time of follow-up, 11 patients used a cane, 14 patients needed two canes or crutches and in 2 cases a wheelchair was necessary. The mean shortening of the leg was 5.2 cm (range 3-15 cm). Clinical evaluation using the score according to Merle d'Aubigné and Postel to assess the functional results showed a mean of 6.7 points (range 2-10 points). Of our patients, 59.3 % were satisfied with the functional results obtained. CONCLUSION: In the long run the Girdlestone procedure still seems to be a reasonable salvage operation for persisting deep infections following hip surgery.

Activities of Daily Living↗
PubMed1990

The Convatec Wound Manager: a new stoma appliance.

Very occasionally, the surgeon must deal with a complicated abdominal wound which drains large volumes of fluid. One such situation arises when a postoperative enteric fistula occurs in association with a partial or complete dehiscence of a laparotomy wound. Another example occurs when the abdominal cavity is left open in the management of severe intra-abdominal sepsis. Both result in large abdominal wounds that are not satisfactorily contained by conventional dressings. Frequent changes of dressing are required and considerable skin excoriation and damage may occur. In addition, quantification of fluid output from a fistula may be grossly inaccurate. We wish to report the use of a new stoma appliance, the Convatec Wound Manager (Squibb Surgicare) which facilitates the management of these wounds. The case described illustrates many of the advantages of the appliance.

Aged↗
PubMedDate not supplied

Restrictive dermopathy: a case report and a critical review of all hypotheses of its origin.

Restrictive dermopathy (RD) is a rare, fatal, autosomal recessive genodermatosis in which tautness of a translucent thin skin is the major clinical observation. This causes an intrauterine fetal akinesia deformation sequence (FADS) resulting in polyhydramnios, reduced fetal movements at around 31 weeks gestation, dysmorphic facies, arthrogryposis, and early neonatal death because of respiratory insufficiency. The characteristic histologic abnormalities of the skin are located in a thin dermis, consisting of compactly arranged collagen fibers, scant elastic fibers, and poorly developed skin appendages. The epidermal rete ridges are flattened and the dermal-hypodermal border is remarkably straight. The etiology of these changes remains unclear. We tested several existing hypotheses and could not confirm them. These included fibroblast dysfunction, abnormal keratin composition, desmosomal changes, and increased proinflammatory cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL)-6]. We conclude that RD is a relatively easy clinical and pathologic diagnosis, but that the pathogenesis of the disease is not clarified.

Abnormalities, Multiple↗
PubMedDate not supplied

Canine cardiac digitalis receptors are preserved in congestive heart failure induced by rapid ventricular pacing.

In dogs, it has been reported that acute ischemia or severe and terminal heart failure results in a selective reduction of myocardial alpha 3 isoform of Na, K-ATPase activity. The aim of this study was to evaluate if a similar change in the two canine digitalis receptor isoforms occurs following 4 weeks of rapid ventricular pacing-induced heart failure without profound necrosis. Heart failure was induced in dogs by rapid ventricular pacing (240 beats x min-1). Digitalis receptors were quantitated by [3H]-ouabain binding with isolated microsomal membranes from sham-operated (n = 3) and heart failure dogs (n = 4) and by Western blot analysis using specific alpha 1 and alpha 3 polyclonal antibodies. In kinetic studies, similar dissociation rates of 19 to 22 x 10(-4) s-1 and 1.3 to 2.4 x 10(-4) s-1 corresponding to high and low affinity sites respectively, were found in sham-operated and CHF dogs. Immunoblotting showed similar abundance of alpha 1 isoform in the two groups; however, levels of alpha 3 were increased by at least 50% in pacing-induced heart failure animals. In conclusion, heart failure selectively modulates the expression of cardiac alpha 3 isoform in dogs.

Animals↗