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M Weber

Publications and source records attributed to M Weber.

At least 1,009 records · Page 56Linked to original sources
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Basophil and eosinophil activation by CC chemokines.

Recent studies have shown that CC chemokines act on monocytes, lymphocytes, eosinophils and basophils, but not neutrophils, with distinct target cell selectivities, possibly explaining the selective attraction and activation of these cell types in different types of chronic inflammation and allergic disease. Functional and desensitization studies on basophils and eosinophils indicate the expression of at least three distinct G-protein-coupled CC chemokine receptors (three on basophils and two on eosinophils), which exert partially selective and partially overlapping ligand specificities and also appear to mediate distinct functions despite similar signal transduction pathways. Functional studies with all known six human CC chemokines show that each cytokine has a distinct spectrum of bioactivities and target cell profile. Interestingly, overall sequence homologies between the chemokines are not predictive for the cell function or cell type that a particular chemokine will preferentially activate, and thus discrete sequence motifs may be important for activating the different CC chemokine receptors. Using different chemokine mutants and hybrids between chemokines, the functional importance of selected individual amino acids and short motifs are now being analysed. These structure-function studies could also lead to antagonists that have more disease-selective anti-inflammatory properties than currently available drugs.

Basophils↗
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Reduced NO production improves early canine islet xenograft function: a role for nitric oxide in islet xenograft primary nonfunction.

Isolated canine islets transplanted to hyperglycemic rats fail to restore euglycemia in almost all cases, although the grafted islet tissue appears to be morphologically intact for up to 48 h following transplantation. Cytokines typically produced in the xenograft environment (e.g., IL-1 and TNF) inhibit insulin biosynthesis and secretion from isolated pancreatic islets, and are associated with the production of nitric oxide (NO). To further define the relationship between NO production and islet xenotransplantation, the inhibition of NO in a splenocyte/islet coculture system, and the in vivo effect of this inhibition on canine islet xenotransplantation, was investigated. Splenocytes (SPLC) from Lewis rats were cocultured with canine islets (freshly isolated or cultured 7 days), supernatant removed, and NO concentration (NO2) determined by optical density (Griess reaction, 550 nm, expressed as nmol nitrite/10(6) cells/18 h). Lipopolysaccharide (LPS) was used as a positive control of SPLC production of NO. Stimulation by LPS resulted in maximal NO production (2.20 +/- 0.16 nmol/10(6) cells/18 h, p < 0.001 compared to baseline values of 0.73 +/- 0.04 nmol/10(6) cells/18 h). In the presence of NO inhibitors (NMA, polymyxin B, hydrocortisone, aminoguanidine, DMSO), nitrite levels did not significantly rise above unstimulated values. Freshly isolated canine islets did stimulate NO production (1.26 +/- 0.12 nmol/10(6) cells/18 h, p < 0.001). In contrast, cultured canine islets did not stimulate NO production (0.84 +/- 0.09 nmol/10(6) cells/18 h). Transplantation of freshly isolated canine islets to STZ-diabetic recipient Lewis rats resulted in amelioration of hyperglycemia in only 50% (n = 6) of recipients 12 h posttransplant, with a return to hyperglycemia at all subsequent time points. Transplantation of 7-day cultured canine islets resulted in amelioration of hyperglycemia in 88% of recipients 12 h posttransplant and 63% of recipients 24 h posttransplant [p = 0.028, mean survival time (MST) = 1.0 days, n = 8]. Transplantation of canine islet xenografts with aminoguanidine therapy (BID, n = 11) resulted in amelioration of hyperglycemia in 100% of recipients at 12 h posttransplant, decreasing to 82% by 24 h following transplantation (p = 0.002, MST = 0.9 days). These results demonstrate that freshly isolated canine islets are potent stimulators of NO production by rat SPLC in vitro, and that culture of canine islets, or addition of NO inhibitors, abrogates stimulated NO production. These results also demonstrate a statistically significant improvement (p < 0.001) in early function of canine islet xenografts following 7 days of islet culture prior to transplant, and following recipient treatment with aminoguanidine. These studies suggest that the production of NO in the microenvironment of the graft site may adversely affect engraftment and function of canine islets, and suggest that the abrogation of islet-stimulated NO production may improve engraftment following islet xenotransplantation.

Animals↗
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Deflazacort increases laminin expression and myogenic repair, and induces early persistent functional gain in mdx mouse muscular dystrophy.

Deflazacort slows the progress of Duchenne muscular dystrophy (DMD) with fewer side effects than prednisone. In mdx mice, deflazacort treatment augments repair and growth of new muscle fibers. We tested the hypothesis that deflazacort improves muscle function and promotes repair by increasing myogenic cell proliferation and fiber differentiation. mdx mice (3.5 weeks old) were treated with deflazacort (1.2 mg/kg) or vehicle for 4 weeks. Forelimb grip strength was measured. After 4 weeks, the right tibialis anterior muscle (TA) was crush injured to induce synchronous regeneration. DNA was labeled using different markers 24 and 2 h before collecting tissues 4 days after injury. The expression of creatine kinase (CK) isoforms, laminin-2 (merosin) mRNA and protein, and proliferation by myogenic cells were measured and satellite cells were identified by immunolocalization of c-met receptor. Peak grip strength increased 15% within 10 days of treatment, and was maintained up to 6 weeks after the end of treatment in a second experiment. Expression of CK MM in the regenerating TA rose from 46% to 55% of total CK activity after deflazacort treatment. Satellite cells were more numerous and appeared earlier on new fibers, in concert with a threefold increase in proliferation by myogenin+ (but not MyoD+) myoblasts. alpha2-Laminin mRNA expression and protein increased 1.3-5.5-fold relative to MM CK in regenerating and dystrophic TA, respectively. These studies support the hypothesis that deflazacort promotes functional gains, myogenic differentiation, myoblast fusion, and laminin expression in regenerating dystrophic muscle. The potential to augment precursor specification, strength, and possible membrane stability may be useful in directing long-term benefits for DMD patients and short-term amplification of precursors prior to myoblast transfer.

Animals↗
PubMedDate not supplied

[Ethical approach to informed consent for participation in clinical studies in acute cerebral infarct].

OBJECTIVE: We sought to evaluate the application of the French law for the protection of persons participating in research studies in biology and medicine. Specifically, we examined comprehension and consequences of informed consent procedures in the field of stroke, characterized by an emergency setting, cognitive impairment and poor prognosis. PATIENTS AND METHODS: Patients (or proxies) included in recent years in clinical studies conducted in our Neurology Department for evaluating treatment of acute phase cerebral ischemia were interviewed to determine their knowledge of the disease, its treatment, the study protocol and the legal regulations, and the affective and psychological consequences of the informed consent procedure. RESULTS: Among 72 patients included in 7 studies ([fibrinolytic agent: 3 (n = 43), anticoagulant agent: 1 (n = 4), neuroprotective drugs (n = 25)], [7 randomized studies, 6 double-blind versus placebo, 5 with a 6-hour inclusion time interval]), 15 died during the acute phase, 5 were lost to follow-up, 4 refused to participate and 7 gave very partial answers. Consent was signed by the patient in 15% of cases, the spouse in 50%, a descendant in 23%. These persons were aware of the spontaneous risk of death (85%) or definitive functional impairment (95%). Half of them thought a specific treatment existed, 11% had some idea of the mechanism of action of the proposed treatment while 67% learned about this mechanism from the information provided. Although they had received information, only 25% of the patients had knowledge of placebo and 7% of therapeutic risk. 37% expected complete recovery from the treatment, 44% partial recovery, and 13% were very disappointed by the outcome. 81% felt they were free to make their own decision. Although 86% did not know there was a law protecting them, 82% were in agreement with the requirement for their consent while 17% would have preferred to delay consent. Most wished to be given the opportunity to discuss the study again, after the acute phase, and to receive the results of the study. CONCLUSION: This study shows that most French stroke victims and their closest relatives are unaware of the law protecting persons in biomedical research and have poor knowledge of medical data after being given appropriate information. Even so, the quality of information increases the quality of the patient-physician relationship. Patients want to be free to make their own decision to consent to biomedical research, but their desire was more for good information than for the power to make their decision alone. Being asked to give informed consent in order to participate in a clinical study accentuates the affective and psychological consequences of stroke, a factor which should be taken into consideration during follow-up.

Acute Disease↗
PubMedDate not supplied

[Mycobacterium xenopi: epidemiological and bacteriological features].

Mycobacterium xenopi is a scotochromogenic slow-growing atypical mycobacteria, with a thermostable catalase, no production of niacin and whose cell wall contains types I and VI long-chain fatty acids. Cosmopolitan, it is mainly recovered in tap-warm water. The contamination occurs through aerosol inhalation, water ingestion or use of contaminated medical or surgical equipment. M. xenopi is an opportunistic pathogen; the infection is facilitated by the incidental introduction of the bacteria in the body, pre-existing pulmonary lesions and an immunodepression. M. xenopi is mainly involved in infections of lungs, bones and joints. The treatment consists in the combination of three or four antibiotics, among rifampicin, rifabutin, ethambutol, macrolides, amikacin and fluoroquinolones.

Anti-Bacterial Agents↗
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[Acute diltiazem (DTZ) poisoning. Survey of french poison control centers].

UNLABELLED: The end-points of this study upon 134 cases reports by the french Poison Centers from 1979 to 1988 (10 years) were to specify the acute toxicity of diltiazem (DTZ). There were 83 self-poisonings in adults, with diltiazem alone (36 cases) or associated with other non cardiotoxic drugs (47), the doses of DTZ ranging from 300 to 5400 mg, and 51 acute accidental overdose in children, the doses of DTZ ranging from 60 to 420 mg. One case of hypotension was observed in a child, without rhythmic disorder, occurring twelve hours post-ingestion of 180 mg of DTZ. In adults, the clinical effects were observed following 360 mg of dose DTZ, occurring 1 1/2 hour post-ingestion. There were discomfort, brady-cardia in 16% of the cases, hypotension in 23% of the cases, cardiogenic shock in 4% of the cases and cardiac arrest in 2.4% of the cases. The rhythmic disorders occurred 2 to 15 hours post-ingestion. There were conduction defects like atrio-ventricular heart bloc I degree in 9% of the cases, II degree in 2.4% of the cases and III degree in 9% of the cases. Less frequently, sinusal bradycardia in 11% of the cases or sino-auricular heart block in 4% of the cases with sometimes auriculo ventricular heart block. These cardiac disorders occurred with 600 mg of DTZ. A cardiac arrest happened in a young healthy man who had absorbed 5400 mg of DTZ. The cardiogenic shocks occurred in patients with an history of coronary on heart disease. The poison removal is likely to prevent the occurrence of clinical or EKG effects when performed within 2 hours post-ingestion, whatever toxic the dose is. The inotropic drugs have been used in 18% of the cases; a percutaneous ventricular pacing was always effective in patients with II or III degree atrio-ventricular block or/and cardiogenir shock. These data confirm the data in thirteen patients of the literature. IN CONCLUSION: The acute diltiazem poisoning can occur after 600 mg of DTZ and can induce severe cardiac disorders which can be prevented with poison removal or treated with supportive care.

Acute Disease↗
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[Restitutio ad integrum of femur head necrosis due to early detection using nuclear magnetic resonance tomography].

Avascular necrosis of the hip was diagnosed early with magnetic resonance (MR) imaging in a 50-year-old man with pain and slightly diminished function of his right hip. Conservative treatment (non-weight bearing) of the hip led to complete recovery at one year follow-up. This case emphasizes the importance of MR imaging as first evaluation for avascular necrosis of the hip.

Femur Head↗
PubMedDate not supplied

Determination of fat in raw milk: comparison of mojonnier (ether extraction) and Gerber method.

Results are compared for the approved Gerber method that specifies a TC 11.07 mL pipet and 2 modifications that specify a TC 10.77 mL pipet or a weighed 11.125 g sample of milk rather than a pipetted sample. All results were also compared with results obtained with the Mojonnier method for determining the fat content of raw milk. The standard deviation is somewhat lower for the Mojonnier method than for any of the Gerber methods; among the Gerber methods, the standard deviations were lower for the TC 10.77 mL and 11.125 g modifications. It is recommended that one of these modifications replace the current specified TC 11.07 mL pipet method.

Animals↗
PubMedDate not supplied

[Argyria].

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Acute Disease↗