[Treatment of chronic left ventricular insufficiency]. / Traitement de l'insuffisance ventriculaire gauche chronique.

Left ventricular failure results from many myocardial diseases: the symptoms of left ventricular failure are the consequence of adaptations which the left ventricle and circulatory system activate to counteract the initial myocardial disease. The aims of treatment of cardiac failure are diverse depending on whether treatment is directed to correct the initial myocardial disease, its myocardial consequences, its circulatory consequences or, more simply, the patient's symptoms. The ideal treatment of cardiac failure would include a drug acting on the cause, a drug restoring left ventricular contraction and relaxation adapted to the conditions of cardiac load, a drug correcting regional blood flow disturbances and a drug relieving symptoms related to salt retention. An ideal drug for chronic left ventricular failure does not exist, and so treatment is a composite effort. Should it be in first intention? This is the current trend.

[The treatment of chronic left ventricular insufficiency]. / Traitement de l'insuffisance ventriculaire gauche chronique.

Left ventricular failure is caused by a variety of myocardial diseases and its symptoms results from adjustments attempted by the left ventricle and the circulatory system to cope with the initial myocardial pathology. Treatment of heart failure has various objectives, depending on whether one tries to correct the initial myocardial disease, or its consequences on the myocardium, or its repercussions on blood circulation, or, more simply, to alleviate the symptoms experienced by the patient. The ideal treatment of heart failure would include a drug acting on its cause, another drug to restore a degree of contraction and relaxation adjusted to the amount of load, a third drug bringing back to normal a perturbed peripheral circulation and a fourth drug to relieve the symptoms due to sodium retention. Such a treatment does not exist, and the management of chronic left ventricular failure can only be composite. Should it be prescribed from the start? This, increasingly, is the current trend.

Calmodulin content and distribution in six human melanoma cell lines.

Calmodulin content and distribution between soluble and particulate fractions were determined by radioimmunoassay in six human melanoma cell lines exhibiting differences in tumor origin (primary or metastatic), degree of tumorigenicity and of pigmentation (amelanotic or melanotic). The results indicate that a) total, soluble and particulate calmodulin levels expressed as ng/10(6) cells or ng/micrograms of proteins remained constant for five out of six cell lines when cells grew from subconfluency to confluency. For IGR 37 line, derived from metastatic melanoma, the calmodulin content decreases from 2.39 to 1.27 ng/micrograms protein for total calmodulin, from 2.17 to 1.52 ng/micrograms protein for soluble calmodulin and from 2.61 to 1.02 ng/micrograms protein for particulate calmodulin, b) total, soluble and particulate calmodulin levels expressed as ng/microgram proteins were twofold (at confluency) to fourfold (at subconfluency) higher in the two cell lines from metastatic origin, IGR 37 and IPC 167. As for example, for total calmodulin, values in IGR 37 and IPC 167 cell lines, were, respectively at subconfluency, 2.39 and 2.31 ng/micrograms protein as compared with the four other cell lines: 0.76 to 0.96 ng/micrograms protein and at confluency: 1.27 and 1.98 ng/micrograms protein as compared with the four other cell lines: 0.76 to 0.90 ng/micrograms protein, c) ratio of calmodulin between soluble and particulate fractions was about 1 for the two autologous cell lines IGR 37 and IGR 39 and varies from 2 to 3 for the four other cell lines.

[Platelet antiaggregants and coronary pathology]. / Antiagrégants plaquettaires et pathologie coronaire.

Platelet inhibitors have widely been studied in various clinical situations resulting from atherosclerosis of the coronary arteries. At present, aspirin is virtually the only drug that has proved to be effective in all cases where the risk of coronary thrombosis was very high. Administered in daily doses of 160 to 1,500 mg, acetylsalicylic acid reduces the frequency of coronary thrombosis and its consequence, myocardial infarction, in the following clinical situations: year following myocardial infarction, acute phase of myocardial infarction, unstable angina, year following aorto-coronary bypass, days following dilatation of the coronary arteries. Acetylsalicylic acid has been compared with heparin and anti-vitamin K agents in four trial: whatever the model studied, no difference was found in the effectiveness of the two treatments tested. Aspirin ha recently been reported as preventing myocardial infarction in healthy subjects. The practical value of this finding is questionable. The various effects of aspirin have been ascribed to the fact that it interrupts a cascade of events ranging from rupture of atherosclerosis plaques to arterial thrombosis.

Bactericidal effect of ofloxacin alone and combined with fosfomycin or vancomycin against Staphylococcus aureus in vitro and in sera from volunteers.

The bactericidal activity of ofloxacin alone and in combination was evaluated against strains of Staphylococcus aureus by measuring MBCs, FBC indexes and by the killing curve technique. Bactericidal titres were determined in sera from volunteers given ofloxacin alone or in combination with fosfomycin or vancomycin. FBC indices less than 0.75 were observed with fosfomycin, showing moderate synergy. FBC indices of 1 were seen with vancomycin. Killing kinetic experiments indicated that ofloxacin (1 and 4 mg/l) exerted a rapid bactericidal effect (99.9% killing in 4 h); the combination of ofloxacin and fosfomycin was synergistic for one of three strains, while killing kinetics of ofloxacin were unaltered by fosfomycin for two of three strains or by vancomycin for the three strains. Sera collected two hours after ofloxacin or fosfomycin had been administered had bactericidal titres less than 1/2. Bactericidal titres were significantly greater in sera from volunteers given the combination of these two drugs. Similar bactericidal titres were obtained in sera after the administration of vancomycin alone or in combination with ofloxacin. A loading dose of 400 mg ofloxacin with subsequent doses of 200 mg had no significantly prolonged effect on bactericidal titres.

Thyroid peroxidase is the organ-specific 'microsomal' autoantigen involved in thyroid autoimmunity.

Autoantibodies (aAb) in serum of patients with autoimmune thyroid diseases (AITD) are directed to an antigen associated with thyroid microsomes. Although it has been investigated over almost three decades, the nature of this autoantigen remained unknown. Taking advantage of monoclonal antibodies (mAb) produced in our laboratory, we have demonstrated that thyroid peroxidase (TPO) is the 'microsomal' antigen. Sera of patients with AITD strongly inhibited the binding of only one of 19 mAb raised against human thyroid plasma membranes. This mAb did not react with thyroglobulin but achieved significant binding to preparations of human, bovine and porcine TPO, bovine lactoperoxidase and human myeloperoxidase without altering the enzyme activity. The mAb has been used to immunopurify the human TPO from solubilized thyroid microsomes. The procedure allowed high purification (approximately 3500-fold) of the native enzyme with a reasonable yield (approximately 10 mg TPO/kg thyroid tissue). Human TPO exhibited a specific activity of 350-400 guaiacol U/mg, a peak in the Soret region and a ratio of A411 nm to A280 nm of 0.20-0.25. Upon SDS-polyacrylamide gel electrophoresis, the purified enzyme gave two contiguous bands in the 100 kDa region. Performed in non-reducing conditions, electrophoresis of TPO showed one band in the same 100 kDa region. Sera with aAb to the microsomal antigen immunoprecipitated purified TPO to an extent ranging from 80 to 100% of the initial enzyme amount while sera from normal subjects or from patients with undectable level of anti-microsomal aAb elicit a decrease of less than 30% of the total TPO activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Radioiodination of tyrosine residue(s) of ox testis and of wheat germ calmodulins.

Radioiodination of the two tyrosine residues (Tyr-99 and Tyr-138) of ox testis calmodulin was performed using several methods, and studied through the specific activity, and the [125I]iodoamino acid analysis of the radiolabeled calmodulins. Hydrolysis by thrombin of 125I-calmodulin labeled by the lactoperoxidase method and subsequent isolation of peptides TM1 and TM2 by gel electrophoresis showed preferential labeling by 125I of Tyr-99 (TM1) over Tyr-138 (TM2). Analysis of [125I]iodoamino acids of radiolabeled TM1, TM2 and calmodulin demonstrated that [125I]monoiodotyrosine was predominant, the remainder being [125I]diiodotyrosine. Radioiodination of wheat germ calmodulin, which contains a single tyrosine residue (Tyr-139), showed that only TM2 was labeled by 125I on the Tyr-139 residue and also on the His-108 residue (radiolabeled monoiodotyrosine, diiodotyrosine and monoiodohistidine being present).

[Demonstration of calmodulin in cultured human malignant melanocytes by indirect immunofluorescence]. / Mise en évidence de la calmoduline dans des mélanocytes malins humains en culture par immunofluorescence indirecte.

Using calmodulin antibody, evidence for the presence of calmodulin, a calcium-binding protein modulator of numerous enzymes was shown by indirect immunofluorescence in 9 cell lines of cultured human malignant melanocytes. Calmodulin was localized in cytoplasm and in higher concentration in the perinuclear region. These observations agree with the distribution of calmodulin-binding proteins in cytoplasm and membranes.