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Biomedical subjects

J Constans

Publications and source records attributed to J Constans.

At least 19 recordsLinked to original sources

[Measurement of arterial distensibility by the QKd method a new vascular marker].

INTRODUCTION: Distensibility is the ability of large elastic arteries to increase in diameter from diastole to systole. Pulse wave velocity (PWV) is one of the ways to measure this parameter. Several techniques, including QKd, are able to measure PWV. PURPOSE: QKd is the time interval between the Q wave on EKG and auscultation of the second Korotkoff's sound at the brachial artery. QKd is measured by a specific apparatus that registers ambulatory blood pressure as well as EKG (normal > 200 ms). Arterial distensibility seems to be able to predict cardiovascular morbidity and QKd has been demonstrated to predict such morbidity in a sample of elderly hypertensives. Currently the relationship between QKd and prognosis is under investigation in systemic sclerosis (ERAMS study). CONCLUSION: QKd is a noninvasive ambulatory method that measures arterial distensibility as well as blood pressure.

Age Factors↗

Some hints concerning the shape of T-cell receptor structures.

Several models are proposed for T-cell antigen receptor (TCR) assembly and structure. However, there is little experimental data favouring directly either one or the other(s). The minimal complex appears to be composed of a TCRalphabeta/CD3deltaepsilon,gammaepsilon/zeta2 structure but at the cell membrane, multimers of this minimal structure may be formed. Quantitative cytofluometry has suggested three CD3epsilon chains for two TCRbeta (or TCRdelta) chains/complex. Such data should be repeated with monoclonal antibodies (MoAb) against extracellular (EC) parts of CD3delta or CD3gamma chains. In the present review, we have compared the TCR/CD3 assembly of pre-TCR, TCRgammadelta and TCRalphabeta containing complexes, and analysed the reactivity of antibodies (Abs) against the EC part of CD3delta chains. Our data suggest an alternative assembly pathway and structure of TCR/CD3 complexes.

Animals↗

Plasma vascular endothelial growth factor and its receptor Flt-1 in patients with hyperlipidemia and atherosclerosis and the effects of fluvastatin or fenofibrate.

Increased vascular endothelial cell growth factor (VEGF) may be important in cardiovascular pathophysiology (perhaps relating to angiogenesis and collateral vessel development) and binds target endothelium via receptors such as Flt-1. We hypothesized that there would be increased levels of plasma VEGF and Flt-1 in patients with atherosclerosis and others with hyperlipidemia compared with controls, and a reduction in these factors with 3 months of lipid-lowering therapy. Twenty patients with uncomplicated hyperlipidemia but no atherosclerosis, 20 patients with hyperlipidemia plus clear atherosclerosis, and 40 matched controls were studied. Plasma VEGF was higher in patient groups than in healthy controls (p <0.01), but Flt-1 was not significantly altered. After lipid-lowering therapy, patients with uncomplicated hyperlipidemia had significantly reduced total cholesterol and VEGF (all p <0.05) but no significant change in Flt-1. Lack of a significant correlation between the von Willebrand factor and VEGF suggests the latter is unrelated to endothelial damage. Plasma VEGF that increases in patients with uncomplicated hyperlipidemia free of major underlying atherosclerosis and in patients with hyperlipidemia plus established atherosclerosis is reduced by successful lipid-lowering treatment. These findings may have implications for the pathophysiology and treatment of hyperlipidemia and atherosclerosis, and suggest an alternative mechanism (i.e., modulation of angiogenesis) by which lipid-lowering therapy may reduce cardiovascular events beyond lipid reduction alone.

Anticholesteremic Agents↗

Molecular modelling and endoplasmic reticulum retention of mutated TCR/CD3 complexes.

T cell receptor (TCR)/CD3 complex assembly takes place in the endoplasmic reticulum (ER). Normal TCR/CD3 complexes egress from the ER to the cis-Golgi, where the interaction with zeta2 homodimers occurs. This interaction leads to further uncontrolled transport of TCR/CD3/zeta molecules to the cell surface. The purpose of the present experiments was to determine firstly the basis for the impact of the Phe195/216 --> Val mutations on TCR/CD3 expression in Jurkat cells, and secondly why mutated J79-cell TCRalphabeta/CD3 hexamers are prevented from interacting with zeta2 homodimers. We found that Phe --> Val mutations cause serious perturbations in a so far undefined hydrophobic area formed by the two Phe195/216 on beta-strand F and aromatic/large hydrophobic amino acids on neighboring beta-strands B and A in Calpha and Cbeta domains, respectively. In addition, TCR/CD3 hexamers and zeta2 homodimers colocalize in normal Jurkat T cells, in revertant J79r58 cells, and in J79 cells transfected with wild-type TCRalpha cDNA but not in J79 mutant cells (confocal microscopy). Furthermore, mutated TCR/CD3 complexes seem to be actively retained in the ER in J79 cells but not in revertant J79r58 cells by a nondominant mechanism. We propose that a hitherto undefined ER-retention molecule controls both the protein structure and egress of TCR/CD3 complexes from the ER of alphabeta and gammadelta T cells.

Brefeldin A↗

Cannabis arteritis revisited--ten new case reports.

The purpose of this paper was to revisit the old concept of cannabis arteritis first described in the 1960s and report 10 new cases. Ten male patients, with a median age of 23.7 years developed subacute distal ischemia of lower or upper limbs, leading to necrosis in the toes and/or fingers and sometimes to distal limb gangrene. Two of the patients also presented with venous thrombosis and three patients were suffering from a recent Raynaud's phenomenon. Biological test results did not show evidence of the classical vascular risk factors for thrombosis. Arteriographic evaluation in all cases revealed distal abnormalities in the arteries of feet, legs, forearms, and hands resembling those of Buerger's disease. A collateral circulation sometimes with opacification of the vasa nervorum was noted. In some cases, arterial proximal atherosclerotic lesions and venous thrombosis were observed. All patients were moderate tobacco smokers and regular cannabis users. Despite treatment with ilomedine and heparin in all cases, five amputations were necessary in four patients. The vasoconstrictor effect of cannabis on the vascular system has been known for a long time. It has been shown that delta-8- and delta-9-tetrahydrocanabinols may induce peripheral vasoconstrictor activity. Cannabis arteritis resembles Buerger's disease, but patients were moderate tobacco smokers and regular cannabis users. These cases show that prolonged use of cannabis could be an additive risk factor for juvenile and young adult arteritis. Cannabis arteritis is a forgotten and severe occlusive vascular disease occurring in young adults. Search for cannabis use may be an important tool for a better knowledge of arteritis in young smokers.

Adolescent↗

Clinical prediction of lower limb deep vein thrombosis in symptomatic hospitalized patients.

We evaluated two clinical scores for the prediction of deep venous thrombosis (DVT) in hospitalized patients (Wells' and Kahn's). We included 273 patients referred to the vascular exploration unit for the suspicion of DVT. A clinical questionnaire was tilled in by the practitioner and the scores were calculated from this form. 66 of the 273 patients had a DVT. When Wells' score was 3, a DVT was found by duplex echography in 51% patients; when the score was 0, a DVT was found in 9%. Kahn's score was not adapted to this population. We then developed a new simple score (cancer, palsy or plaster immobilization, warmth, superficial venous dilation, unilateral pitting edema, other diagnosis). A DVT was found in 76% patients with a score of 3 and in 11% in those with a score of 0. We therefore propose a 6-item score whose main advantages are simplicity and usefulness in routine practice.

Female↗

[Homocysteinemia: role in vascular disease].

HEREDITARY DISEASE: Hereditary anomalies of homocysteine metabolism are quite uncommon and manifest by very high homocysteine levels (> 100 mumol/l) and associated homocysteinuria. The risk of premature cardiovascular disease is high. Clinical, biological and epidemiological data accumulated since the 70 s have demonstrated that a moderately elevated serum homocysteine level favors the development of atherothrombosis. PROVEN RISK: The risk of coronary or cerebral events is 1.5 to 3-fold higher for fasting homocysteine levels above 15 mumol/l. These data show that moderately elevated homocysteine level is a powerful cardiovascular risk factor. Further information is however needed to ascertain its frequency in the population and determine whether it is a truly independent risk factor. THERAPEUTIC OPTIONS: Most cases of moderately elevated homocysteine can probably be explained by gene-environment interactions. Homocysteine levels can be lowered by oral administration of vitamin cofactors implicated in homocystein metabolisms: folic acid, vitamin B6, vitamin B12.

Cerebral Infarction↗

Proton magnetic resonance spectroscopy (1H-MRS) of the thalamus in schizophrenia.

This study applied (1)H-MRS in the thalamus of schizophrenic patients and healthy subjects. There were no differences in the metabolite ratios (NAA/Cr, Cho/Cr or mI/Cr) between the two groups. Relationships were noted between NAA/Cr and age in patients with a trend toward this correlation in controls, suggesting an effect of age on the metabolism of the thalamus.

Adult↗