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Biomedical subjects

J Bonnet

Publications and source records attributed to J Bonnet.

At least 109 records · Page 6Linked to original sources

Monocyte adherence to endothelial cells in patients with atherosclerosis: relationships with risk factors.

Monocyte adhesion to endothelium appearing determinant in atherosclerosis, the possibility that circulating monocytes have an increase of their adherence on endothelial cells were investigated in patients with atherosclerosis. The adherence of circulating monocytes on endothelial cell monolayers was determined in 26 patients with atherosclerosis (age 59 +/- 4), and 25 healthy individuals (age 55 +/- 4). No difference of monocyte adherence was observed between the two groups (18.8 +/- 13.8% vs 19.2 +/- 13.4%), or following atherosclerosis severity. However, monocyte adherence appeared positively correlated to smoking habits (r = 0.34, P < 0.02) and fibrinogen level (r = 0.31, P < 0.03), and negatively to the degree of plasmatic LDL oxidation (r = -0.28, P < 0.05). These results suggest that the adherence of monocytes to endothelial cells is not increased in atherosclerosis, but enhanced by risk factors. A weak plasmatic LDL oxidation could inhibit monocyte adhesion.

Arteriosclerosis↗

Tumor necrosis factor-alpha stimulates ICAM-1 expression in human vascular smooth muscle cells.

Human atherosclerotic plaques contain numerous smooth muscle cells (SMCs) that express intercellular adhesion molecule-1 (ICAM-1). Expression of ICAM-1 in different cells is known to be regulated by tumor necrosis factor-alpha (TNF-alpha), which has recently been found to be present in the intimal thickening of human arteries. Therefore, we studied the effect of TNF-alpha on ICAM-1 mRNA content and surface expression in cultured human aortic SMCs by using the methods of Northern blotting and immunofluorescence flow cytometry. Under basal conditions of cultivation, ICAM-1 mRNA was not revealed in SMCs. However, treatment of the cells with recombinant human TNF-alpha induced substantial levels of ICAM-1 mRNA. The content of ICAM-1 on the surface of SMCs also increased in a dose- and time-dependent manner after incubation with TNF-alpha. Twenty-four hours of treatment with 10 ng/mL TNF-alpha led to an approximately 10-fold increase in ICAM-1 surface expression in the SMCs. Under the same conditions, pretreatment of SMCs with TNF-alpha resulted in a twofold increase of their adhesiveness for monocytes. In the presence of anti-ICAM-1 monoclonal antibody 10F3, monocyte adhesion to TNF-alpha-pretreated SMCs was significantly inhibited, suggesting that the observed monocyte-SMC interaction involved the ICAM-1 expressed on SMC surfaces as a result of TNF-alpha stimulation. These results led us to propose that TNF-alpha may act a regulator of functional ICAM-1 expression on the SMC surface and thus can increase the possibility of interactions between mononuclear cells and SMCs in atherosclerotic plaques.

Antibodies, Monoclonal↗

[Occlusive spasm of a coronary artery not treated during angioplasty. Apropos of a case].

The authors report the case of a patient who, during percutaneous transluminal angioplasty of the circumflex artery, developed sudden occlusion of the anterior interventricular artery without stenosis and not touched by the operator. The fact that this occlusion was completely reversible after an intra-coronary injection of nitroglycerin suggests that this was due to spasm. This case suggests the possibility of consequences of angioplasty at a point distant from the dilated site. The authors use this case and a review of the literature to discuss the pathophysiological mechanisms which could be responsible for such consequences.

Angioplasty, Balloon, Coronary↗

Preparation and microscopic visualization of multicolor luminescent immunophosphors.

The preparation of charge-stabilized suspensions of small phosphor particles (0.1-0.3 micron) and their coupling with antibodies to immunoreactive conjugates is described. Phosphor particles consisting of yttriumoxisulfide activated with europium served as a model system in the evaluation of the stabilizing properties of several polycarboxylic acids. The optimal reagents were then applied to other phosphors which differ in spectral characteristics as well as in luminescence lifetime. These phosphors were ground to a size of 0.1-0.3 micron and proteins or other macromolecules were adsorbed to the phosphor particles to prepare conjugates of different physico-chemical properties. A time-resolved microscope, suitable for real time visualization of the time-delayed luminescence of the immunophosphors by the human eye, is described in detail. Since most phosphors require excitation with far UV light, a special fluorescence microscope allowing far UV excitation was developed for conventional visualization of the luminescence emitted by the phosphor. The possibility of multiple color labeling using various phosphor conjugates was demonstrated in a model system consisting of haptenized latex beads.

Adsorption↗

Biological risk factors for sudden death in patients with coronary artery disease and without heart failure.

In a study of biological risk factors for sudden death in patients with coronary artery disease, 320 patients were, prospectively, recruited and followed-up over two years. None of the patients had heart failure or recent myocardial infarction. The following variables were recorded: previous acute myocardial infarction, hypertension, smoking habits, ventricular arrhythmia; the angiographic variables included: left ventricular ejection fraction, Jenkins' and mean atherosclerotic scores; lipid profile: cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoproteins Al and B; hemostatic profile: fibrinogen, fibrinopeptide A, antithrombin III, factor VIII antigen, factor VIII coagulant, protein C, plasminogen, alpha 2-antiplasmin, euglobulin clot lysis time and tissue plasminogen activator before and after venous occlusion, tissue plasminogen activator inhibitor, platelet factor 4, beta-thromboglobulin. During the follow-up period, 12 of the patients died suddenly. In these patients, ejection fraction was lower: 49 +/- 16% versus 61 +/- 14% for the other patients (P less than 0.02), fibrinogen higher: 3.9 +/- 0.8 g/l versus 3.5 +/- 0.8 for the living patients (P less than 0.05) and protein C lower: 89 +/- 39% versus 111 +/- 39% (P = 0.06) for the other patients. In multivariate analysis: lower ejection fraction (P less than 0.008), older age (P less than 0.03) and lower protein C (P less than 0.01) were correlated with sudden death. Among the patients with coronary artery disease, the raised fibrinogen and the decreased protein C appeared to be risk factors for sudden cardiac death. These alterations reflected a prothrombotic state which might increase the ischemic risk, due to an acute thrombosis, leading to the fatal ventricular arrhythmia. Determination of these hemostatic variables might be a useful adjunct for assessment of the vital prognosis of patients with coronary artery disease, especially the risk of sudden death in addition to other known clinical, electrocardiographic, hemodynamic risk factors. This would also guide both the instigation of complementary investigations and appropriate therapy in such high risk group of patients.

Aged↗

Iridium-192 interstitial therapy for squamous cell carcinoma of the penis.

From February 1971 through February 1989, 51 patients with biopsy proven epidermoid carcinoma of the penis were treated with interstitial therapy (Iridium 192). The breakdown according to the stage was T1s = 3, T1 = 14, T2 = 28, T3 = 6, N0 = 43, N1 = 7, N2 = 1. The dose ranged from 50 to 65 Gy (mean: 60 Gy). Patients without clinical nodal involvement received no treatment to the nodes. Stage N1 and N2 patients had surgery and external irradiation to the inguinal and iliac nodes. Six of fifty-one (12%) patients developed nodal and/or metastatic disease following therapy. Five of six presented initially with clinical nodal involvement. Seven of fifty-one (14%) developed local recurrence only, requiring surgery (four partial penectomies, three total penectomies). Six of these seven patients are alive and free of disease with a mean follow-up of 5.5 years. Nine of thirty eight (23%) patients with local control developed local necrosis. The treatment consisted of local excision (one patient), partial amputation (six patients) or total amputation (two patients). Partial urethral stenosis was noted in 17/38 (45%) of the patients. Foreskin sclerosis occurred in 3/38 (8%) uncircumcised patients. Interstitial irradiation for penile carcinoma provided effective local control rates, especially for T1-T2 patients (91%). Local failures could be treated successfully with surgery. Complications could be treated conservatively in most patients. Local control with penile conservation was achieved in 67% of all patients and 75% of patients with T1-T2 disease.

Adult↗

P0 protein in normal, trembler heterozygous/homozygous mice during active PNS myelination.

The quantification of P0 protein has been currently used to measure the myelination of the peripheral nervous system (PNS). Using immunological techniques, we show that, as early as postnatal day 8, the P0 content of mice homozygous and heterozygous for the Trembler mutation, represent respectively one tenth and half of the normal values. Thus, although the Trembler mutation is dominant, the myelination defect observed in heterozygous Trembler mice is more pronounced in the homozygous Trembler mice. This gene dosage effect should be taken into account when a molecular model of the Trembler mutation will be proposed.

Animals↗

Expression of the PMP-22 gene in Trembler mutant mice: comparison with the other myelin protein genes.

The Trembler mouse suffers from a dominantly inherited autosomal mutation affecting the Schwann cell activities, which results in an abnormal myelination of the peripheral nervous system. Very recently, it has been shown that the mutation is in the PMP-22 gene. However, the level of expression of the mutated gene in trembler mice has not been studied. Therefore, we measured the steady-state levels of mRNA encoding PMP-22 in the sciatic nerve of normal and trembler mice, and we compared these results with the steady-state levels of mRNAs encoding the major peripheral nervous system myelin proteins. Our results show that all the myelin protein genes studied are affected by the trembler mutation but to a different extent, and that the PMP-22 gene is expressed at very low levels in the trembler nerve. This suggests that regulation of the expression of the PMP-22 gene is altered in the Trembler mutant.

Animals↗

Evaluation of plasmatic leucocyte elastase levels in coronary artery disease.

Leucocyte elastase may be involved in the structural modification observed in the atherosclerotic process. Therefore, we tested the usefulness of leucocyte elastase plasma level determination as a marker for atherosclerosis. Plasma levels of elastase were determined by ELISA in 100 consecutive patients (mean age 56 +/- 9.8 years) admitted to hospital for coronary angiographic investigation of chest pain. Eighty-seven patients had evidence of atherosclerosis, and 13 patients had normal coronary vessels. No significant difference in leucocyte elastase was found between the 2 groups, nor was there any relationship between elastase levels and the severity of atherosclerosis. However, relationships between plasma leucocyte elastase levels and various lipid fractions (Apo AI, LDL) and daily tobacco consumption were found. Leucocyte elastase may thus play a role not only by direct modification of the vessel wall, but also indirectly via risk factors such as dyslipoproteinemia and leucocyte toxicity.

Coronary Angiography↗

[The anticoagulant properties of the endothelium studied by the standard venous occlusion test].

Venous occlusion (VO) during which thrombin (Th) is postulated to be generated is routinely used for evaluation of fibrinolytic potential of endothelium (E). This study was performed to find out whether VO can also be used for assessment of anticoagulant function of E. VO was performed in 98 male patients (pts) with ischemic heart disease. Levels of protein C (PrC) which is related to Th binding by thrombomodulin and fibrinopeptide A (FpA)--a marker of presence of free Th--were determined together with some other factors of coagulation and fibrinolysis. Differences between pre- and postVO PrC levels fluctuated from -54.8% to +57.3%. According to reaction of PrC to VO pts were divided into 2 groups: 13 pts with increase or no change and 17 pts with decrease (consumption) of PrC. In pts without PrC consumption there was a significant increase in FpA. In pts with PrC consumption FpA was unchanged. In pts with PrC consumption exceeding its median value for this group (14%) PAI-1 antigen level fell significantly (-8.4 + 4%) during VO. Thus PrC consumption after VO indicates that TH is effectively removed from blood stream by endothelial factors. Absence of consumption of PrC is a sign of ineffective anticoagulant function of E. Increase in PrC level during VO in some pts may be due to its escape from tissue depot.

Adult↗

[Cardiac lesions in Takayasu's disease. A case with initial pericarditis and tamponade].

The authors report the case of 21-year old female patient with a particular form of Takayasu's disease remarkable for its initial presentation and its cardiac and coronary lesions. The disease began with miscarriage at the 5th months of pregnancy, followed by acute pericarditis with tamponade. Subsequently, lesions of the aortic and mitral valves developed, while the myocardium became involved with left ventricular dilatation and hypokinesia confirmed by echocardiography and cineangiography. Coronary arteriography revealed large coronary aneurysms which are exceptional in this disease. This case prompted the authors to discuss the various cardiac lesions and the relationship of Takayasu's disease with pregnancy.

Adult↗

Fractionated radiotherapy of small inoperable lesions of the brain using a non-invasive stereotactic frame.

Arteriovenous malformations (AVMs) and benign or low grade, small malignant tumors can be treated by stereotactic radiotherapy in a single fraction. This report describes a technique for stereotactic treatment of small lesions using conventional, fractionated, photon beam irradiation. The Laitinen's stereoadapter, non-invasive head frame was used. This device was tested for accuracy by serial mountings and found to be accurate within 1 mm. The accuracy of the dose delivered was within 2%. Adaptation of this device to the linear accelerator required the design of secondary circular collimators which decreased the penumbra from 3-4 mm to 2-3 mm. The dose fall off outside the target volume is steep enough when using two non-coplanar arcs (90 to 10% within 1 cm). Thermoluminescent dosimetry (TLD) in a humanoid phantom showed good correlation with the calculated dose. This system permits delivery of fractionated radiation therapy to small volumes, easily and accurately, under stereotactic conditions.

Adolescent↗

A case of the Budd Chiari syndrome attributed to a deficit in protein C.

We report a case of Budd Chiari syndrome associated with a deficit in protein C, in a young women admitted to hospital for investigation of thromboembolic disease and ascites. This coagulation defect was thought to be an aetiological factor in the suprahepatic vein thrombosis. The diagnosis and treatment of this rare form of the syndrome are discussed.

Budd-Chiari Syndrome↗

Typing of Chlamydia trachomatis by restriction endonuclease analysis of the amplified major outer membrane protein gene.

A procedure was developed for characterization of Chlamydia trachomatis strains by using restriction endonuclease analysis of amplified genes of the major outer membrane protein (MOMP). Reference strains of the 15 serovars (A through K and L1 through L3) and clinical isolates were tested. The nucleotide sequences of the MOMP genes of each of the 15 serovars were arbitrarily constructed by using the sequences of the four variable domains known for each serovar and the constant domains of serovar L1. Computer analysis of these sequences indicated that two restriction digestions performed in parallel, one with AluI and the other with IIpaII, followed by HinfI and EcoRI, would allow the theoretical differentiation of 13 serovars. Serovars Ba and L1 presented the same theoretical restriction profile. Our typing method consisted of polymerase chain reaction amplification of a fragment of about 1,200 bp of the MOMP gene, followed by restriction endonuclease digestion with the aforementioned enzymes. From the 15 serovars, we obtained 14 different patterns; 13 profiles were serovar specific, while serovars B and Ba presented the same pattern. Application of this typing method to C. trachomatis strains isolated from clinical material gave the same results as the immunotyping method for 14 of 17 strains. Furthermore, restriction endonuclease analysis detected differences within a serovar. This method seems to be promising for epidemiological studies.

Bacterial Outer Membrane Proteins↗

Different expression of the two dopaminergic D2 receptors, D2415 and D2444, in two types of lactotroph each characterised by their response to dopamine, and modification of expression by sex steroids.

Dopamine inhibits prolactin liberation acting via the D2 type receptor. Two different electrophysiological responses to dopamine have been shown to characterise two types of lactotroph isolated from the lactating female rat. It is now known that differential splicing of the pre-messenger RNA coding for the D2 receptor leads to the production of two D2 subtypes, D2(415) and D2(444). These subtypes differ in the region which is believed to be responsible for the binding of G proteins, and could thus lead to the activation of different intracellular second messenger systems. Here we show that the pre-messenger RNA for the D2 receptor is differentially spliced in such a way that the ratio D2(415)/D2(444) is significantly different (2.91 +/- 0.6 vs 1.29 +/- 0.14) between two populations of lactotrophs, each enriched in cells showing one type of response to DA. We further show that the ratio D2(415)/D2(444) can be changed by treatment of prolactin cells in primary culture with progesterone or testosterone. Estrogen did not change the ratio, but diminished the total amount of D2 cDNA. Regulation of differential splicing by sex steroids could provide a mechanism for modifying lactotroph responsiveness to DA in different physiological situations.

Animals↗