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Biomedical subjects

M Arnaud

Publications and source records attributed to M Arnaud.

At least 37 records · Page 2Linked to original sources

Fluoroquinolone induced tendinopathy: report of 6 cases.

We describe 6 cases of fluoroquinolone induced Achilles tendinitis in 4 women and 2 men, mean age 68.6 years. Patients presented with pain and swelling of sudden onset, which was most often bilateral. Tendon rupture was frequent, accompanied by nodules and ecchymoses. The diagnosis was clinical, occasionally ultrasonography was helpful; the role of magnetic resonance imaging has yet to be defined. Certain risk factors were found, particularly association with longterm steroid therapy, and close surveillance of high risk subjects is mandatory. Although proper dosage and duration of treatment were respected, the principal fluoroquinolones were clearly incriminated. We found no correlation between treatment duration and the degree of involvement. Nevertheless, immediate discontinuation of the antibiotic and placement of both Achilles tendons at rest is essential. Early and appropriate management did not prevent prolonged recovery times and there was always a risk of functional sequelae. This side effect is class related and rare. Its physiopathologic mechanism is poorly understood.

Adult↗

Association of the amino-terminal half of c-Src with focal adhesions alters their properties and is regulated by phosphorylation of tyrosine 527.

We have characterized the mechanism by which the subcellular distribution of c-Src is controlled by the phosphorylation of tyrosine 527. Mutation of this tyrosine dramatically redistributes c-Src from endosomal membranes to focal adhesions. Redistribution to focal adhesions occurs independently of kinase activity and cellular transformation. In cells lacking the regulatory kinase (CSK) that phosphorylates tyrosine 527, c-Src is also found predominantly in focal adhesions, confirming that phosphorylation of tyrosine 527 affects the location of c-Src inside the cell. The first 251 amino acids of c-Src are sufficient to allow association with focal adhesions, indicating that at least one signal for positioning c-Src in focal adhesions resides in the amino-terminal half. Point mutations and deletions in the first 251 amino acids of c-Src reveal that association with focal adhesions requires the myristylation site needed for membrane attachment, as well as the SH3 domain. Expression of the amino-terminal region alters both the structural and biochemical properties of focal adhesions. Focal adhesions containing this non-catalytic portion of c-Src are larger and exhibit increased levels of phosphotyrosine staining. Our results suggest that c-Src may regulate focal adhesions and cellular adhesion by a kinase-independent mechanism.

Amino Acid Sequence↗

Crystal structure of transcription factor E47: E-box recognition by a basic region helix-loop-helix dimer.

A large group of transcription factors regulating cell growth and differentiation share a dimeric alpha-helical DNA-binding domain termed the basic region helix-loop-helix (bHLH). bHLH proteins associate as homodimers and heterodimers having distinctive DNA-binding activities and transcriptional activities that are central to the regulated differentiation of a number of tissues. Some of the bHLH residues specifying these activities have been identified, but a full understanding of their function has awaited further structural information. We report here the crystal structure of the transcription factor E47 bHLH domain bound to DNA. The bHLH of E47 is a parallel, four-helix bundle with structural features that distinguish it from the bHLH-zipper protein Max. The E47 dimer makes nonequivalent contacts to each half of the -CACCTG- binding site. Sequence discrimination at the center of the E box may result from interaction with both the DNA bases and the phosphodiester backbone.

Amino Acid Sequence↗

[The risk/benefit ratio of low-dose cyclosporin in the treatment of severe rheumatoid arthritis].

Although the efficacy of cyclosporine therapy in rheumatoid arthritis has been established, there have been no long term studies of the risk/benefit ratio of cyclosporine A in severe rheumatoid arthritis. A prospective, open-label one-year study included 106 patients (83 women and 23 men; mean age 53 years; mean disease duration, 11 years) with rheumatoid arthritis. Mean number of previous second-line treatments was four and 69% of patients had failed methotrexate therapy. The initial dosage of cyclosporine was 3 mg/kg/d and was increased if needed up to 5 mg/kg/d. The dosage was reduced in the event of serum creatinine elevation (by more than 30% versus baseline) or diastolic blood pressure elevation (above 95 mmHg). The statistical analysis was performed on an intention-to-treat basis. In the 45 patients who completed the one-year study period, the mean dosage was 3.6 +/- 1 mg after six months and 3.3 +/- 1 mg/kg/d after one year. Significant improvements were seen in all the clinical efficacy parameters. The mean reduction in corticosteroid dosage was 0.5 mg/d. The study drug was discontinued prematurely in 61 patients (36 because of adverse events and 21 because of inefficacy). Twelve of the 56 patients with serum creatinine level elevation on at least one occasion and seven of the 35 patients with diastolic blood pressure elevation were taken off the study drug.

Adult↗

Idiopathic retroperitoneal fibrosis with systemic manifestations.

We describe a previously unreported association of idiopathic retroperitoneal fibrosis with mesenteric, pulmonary and perhaps periarticular fibrotic involvement, and panniculitis resembling Weber-Christian panniculitis. The onset of the disease was uncommon with arthritis. Then, several episodes of migratory panniculitis appeared; biopsy showed septal panniculitis without necrosis of adipose tissue. Considering the patient's anamnesis, it is tempting to speculate that these manifestations all originate from the same mechanism.

Adult↗

Maternal caffeine consumption and fetal behavior in normal third-trimester pregnancy.

OBJECTIVE: Our aim was to perform a longitudinal cohort study of 20 normal third-trimester pregnancies to observe whether the level of long-term maternal caffeine ingestion influenced fetal behavior. STUDY DESIGN: By dietary history 10 normal pregnant women were categorized as "high" caffeine consumers (> 500 mg/day, group H) and 10 as "low" caffeine consumers (> 200 mg/day, group L). Between 30 and 40 weeks biweekly 2-hour continuous ultrasonographic observations of fetal heart rate; breathing activity; and eye, trunk, and extremity movements were conducted. Maternal caffeine levels were determined at each session, and fetal states were identified and their duration quantified. Data were compared by analysis of variance by means of repeated measures or t tests. RESULTS: When compared with group L fetuses, group H fetuses spent similar mean time in state 1F (quiet sleep), less mean time in state 2F (active sleep), and much greater mean time in state 4F (arousal). The mean time spent in no state decreased significantly in group L, was unchanged in group H, and was similar for both groups at term. Both groups had similar mean numbers of state changes at all gestational ages studied. Mean maternal serum caffeine levels in group H were always significantly higher than those in group L. CONCLUSION: Evolving fetal behavior may be influenced by the level of maternal caffeine consumption during the last trimester.

Adult↗

Bacillus subtilis genome project: cloning and sequencing of the 97 kb region from 325 degrees to 333 degrees.

In the framework of the European project aimed at the sequencing of the Bacillus subtilis genome the DNA region located between gerB (314 degrees) and sacXY (333 degrees) was assigned to the Institut Pasteur. In this paper we describe the cloning and sequencing of a segment of 97 kb of contiguous DNA. Ninety-two open reading frames were predicted to encode putative proteins among which only forty-two were found to display significant similarities to known proteins present in databanks, e.g. amino acid permeases, proteins involved in cell wall or antibiotic biosynthesis, various regulatory proteins, proteins of several dehydrogenase families and enzymes II of the phosphotransferase system involved in sugar transport. Additional experiments led to the identification of the products of new B. subtilis genes, e.g. galactokinase and an operon involved in thiamine biosynthesis.

Amino Acid Sequence↗

Breast cancer with systemic manifestations mimicking Still's disease.

We describe a case whose clinical features strongly suggested Still's disease, which led to the discovery of breast cancer. Our patient's symptoms consisting of fever, joint inflammation, pleuritis, and pericarditis, were initially resistant to high doses of steroids, and disappeared only after the cancer was removed, despite rapid tapering and cessation of steroid therapy. A paraneoplastic phenomenon seems probable.

Breast Neoplasms↗

Adolescent osteoporosis disclosing familial osteopenia.

The observations of familial juvenile osteoporosis, presumably of genetic origin are exceptional. The authors report the observation of a 16-year old adolescent suffering from osteoporosis, confirmed by histomorphometry and decrease in bone density (lumbar vertebrae 0.79 g/cm2 and femoral neck 0.88 g/cm2: LUNAR DPX). We prescribed fluorine and calcium therapy. Lumbar bone density increases by 11% and bone density of the thighbone neck by 7.6%. We cannot rule out growth as a factor in the changes observed, given that the propositus is only 16. A densitometric investigation performed in 4 of his 12 brothers shows a decrease in the lumbar bone mineral content (from 61 to 94% expressed as Z score). A genotypic origin seems to be conceivable, especially since no other cause could be considered (endocrinal, alimentary...). On the other hand, there is no argument in favour of osteogenesis imperfecta disease. The bone densitometry is a useful diagnostic means to detect familial forms of osteoporosis.

Adolescent↗

Regulation of the sacPA operon of Bacillus subtilis: identification of phosphotransferase system components involved in SacT activity.

The sacT gene which controls the sacPA operon of Bacillus subtilis encodes a polypeptide homologous to the B. subtilis SacY and the Escherichia coli BglG antiterminators. Expression of the sacT gene is shown to be constitutive. The DNA sequence upstream from sacP contains a palindromic sequence which functions as a transcriptional terminator. We have previously proposed that SacT acts as a transcriptional antiterminator, allowing transcription of the sacPA operon. In strains containing mutations inactivating ptsH or ptsI, the expression of sacPA and sacB is constitutive. In this work, we show that this constitutivity is due to a fully active SacY antiterminator. In the wild-type sacT+ strain or in the sacT30 mutant, SacT requires both enzyme I and HPr of the phosphotransferase system (PTS) for antitermination. It appears that the PTS exerts different effects on the sacB gene and the sacPA operon. The general proteins of the PTS are not required for the activity of SacY while they are necessary for SacT activity.

Bacillus subtilis↗