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Biomedical subjects

P Benoit

Publications and source records attributed to P Benoit.

At least 37 records · Page 2Linked to original sources
PubMed1995

Relationship between interatrial conduction times and left atrial dimension in patients undergoing atrioventricular stimulation.

Interatrial conduction time (IACT) and left atrial dimension (LAD) were determined in 75 patients (41 males, 34 females, mean age 78.2 +/- 7.9 years) undergoing atrioventricular (AV) stimulation. The LAD was measured by M mode echocardiography as the distance between the posterior aortic wall and the posterior left atrial wall. The IACT was determined during a transvenous dual chamber pacemaker implant done under local anesthesia (lidocaine). The spontaneous interatrial conduction time (SIACT) was measured from the intrinsic deflection (ID) of the right atrium recorded in a unipolar mode (unipolar J-shaped lead positioned in the right appendage) to the ID of the left atrium (bipolar esophageal lead, left atrial positive deflection equal to the negative one) during sinus rhythm. The right atrium then was paced at a rate slightly greater than the spontaneous one. The paced interatrial conduction time (PIACT) was measured from the stimulus artifact to the left atrial ID. The PIACT was also measured during incremental right atrial pacing (10 beats/min step increase to 180 beats/min) and, from these measurements, the maximum increase of PIACT (MIPIACT) was deduced. The LAD was measured at 39.5 +/- 8.7 mm, SIACT at 70.3 +/- 24.8 msec, PIACT at 118.8 +/- 27.9 msec, and MIPIACT at 16.5 +/- 16.4 msec. We found highly significant relationships between SIACT and LAD (P = 0.0006, r = 0.39), PIACT and LAD (P = 0.0001, r = 0.45), and MIPIACT and LAD (P = 0.0006, r = 0.38). We also noted that the LAD was greater in patients in whom MIPIACT was > 10 msec than in patients in whom the MIPIACT was negligible (P < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Voltage dependencies of the effects of chlorpromazine on the nicotinic receptor channel from mouse muscle cell line So18.

The effects of chlorpromazine (CPZ) on nicotinic acetylcholine receptor (nAChR) were re-investigated by patch-clamp recordings on a mouse muscle cell line: (1) CPZ decreased the channel-opening frequency and, thus, acted as a closed-channel blocker. This effect was independent of the membrane potential and was consistent with an enhanced desensitization of the nAChR. (2) In addition, CPZ decreased the mean channel open time of the nAChR in a concentration- and voltage-dependent manner and, thus, behaved as an open-channel blocker. The latter effect supports the notion that CPZ binds to a site within the nAChR ionic channel.

Animals↗
PubMed1993

A monoclonal antibody to recombinant human IFN-alpha receptor inhibits biologic activity of several species of human IFN-alpha, IFN-beta, and IFN-omega. Detection of heterogeneity of the cellular type I IFN receptor.

A cDNA encoding a 63-kDa human IFN-alpha R (hIFN-alpha R) has recently been cloned. Mouse cells transfected with this cDNA failed to show any signal transmission for IFN-beta, suggesting the involvement of additional chains in the receptor complex. We have expressed in Escherichia coli and COS 7 cells a soluble recombinant protein (sIFN-alpha R) comprising the extracellular domain of the hIFN-alpha R fused at the carboxyl terminus to a sequence of five histidine residues. The sIFN-alpha R was affinity purified and used to generate mAb. One mAb, 64G12, which recognized the cellular receptor as well as the recombinant proteins was found to neutralize the biologic activity of IFN-alpha, -beta, and -omega and natural type I IFN, but not IFN-gamma. To our knowledge, this is the first report of a neutralizing mAb against the human IFN-alpha R. Interestingly, we found that the affinity of this antibody for the cellular receptor depended on the cell line used. These results provide strong evidence that the cloned hIFN-alpha R chain is required for binding and signal transmission of all subspecies of type I IFN and suggest a structural heterogeneity of the receptor at the cell surface.

Animals↗
PubMed1993

Organization of the human CD9 gene.

The CD9 antigen was originally described as a 24-kDa molecule present on B-lineage-derived acute lymphoblastic leukemia cells and developing B lymphocytes. Platelets also express a large amount of CD9 antigen and can be activated by CD9 antibodies. We report here the structure of the CD9 gene, which is composed of 8 exons spanning more than 20 kb. There is no TATA or CAAT box in the 5'-flanking domain of the CD9 gene, but a 120-bp region extremely rich in C and G (88%) contains several Sp 1 binding sites and a consensus site for the binding of zinc-finger proteins of the Krox/EGR family. The CD9 antigen belongs to a new cell surface protein family. The organization of its gene closely resembles the organization of the genes for two other members of this protein family, TAPA1 and CD63, which share with CD9 respectively 45 and 25% identity at the amino acid level.

Amino Acid Sequence↗
PubMed1993

Length-tension relationship of the posterior deltoid to triceps transfer in C6 tetraplegic patients.

We assessed the length-tension relationship of the posterior deltoid to triceps transfer in 8 tetraplegics (n = 11 transfers) and compared the results to the length-tension relationship of the normal triceps measured in a check sample composed of 9 able bodied, right handed women. We designed a device to lock the arm and forearm and used a force transducer to assess the torque output isometrically. The muscle was tested at 6 different lengths (130, 110, 90, 70, 45 and 0 degree of elbow flexion) with the shoulder abducted at 90 degrees. As expected, the transfer behaved differently from the normal triceps. The mean maximum torque recorded was 7.8 Nm in patients while it was 27 Nm in the check sample. When compared, the absolute values (ie values expressed with a dimension of torque) were significantly different between groups (0.00001 < p < 0.002). The expression of this relation (ie the relative values expressed as percentage of maximum values) revealed significant statistical differences (p < 0.002) at 90 and 70 degrees of elbow flexion; the peak torque was recorded at 130 degrees in patients while it was recorded at 110 degrees in the check sample, with a plateau between 110 degrees and 70 degrees. On the other hand, if the length-tension relationship was fairly similar among subjects of the check sample, it exhibited tremendous differences among patients; it seemed that initial tension given by the surgeon represented a variable difficult to control without a device dedicated to that task.

Adult↗
PubMed1993

The IL-2 receptor present on human embryonic fibroblasts is functional in the absence of P64/IL-2R gamma chain.

In this study, we have investigated the IL-2R gamma gene expression in several human embryonic fibroblasts which express other components of the IL-2 receptor (IL-2R). Polymerase chain reaction did not allow us to detect IL-2R gamma transcripts in these cells but the functionality of the IL-2R alpha beta was not affected. Indeed, in the human IL-2R alpha+beta+gamma- embryonic lung fibroblasts ICIG-7, IL-2 induced identical phenomena to those previously reported in lymphoid cells: rapid internalization of the IL-2R alpha beta-IL-2 complex, specific phosphorylation of cellular proteins (56 and 38 kDa) and up-regulation of ICAM-1 expression. IL-2 induction of ICAM-1 was only observed in sparse cultures and for IL-2 concentrations over 180 pM. We have also observed, in these fibroblastic cells, the up-regulation of ICAM-2 expression by IL-2, both in sparse and dense cultures. These data show that p64/IL-2R gamma expression in human embryonic fibroblasts does not correlate with the ability of the IL-2R to deliver a biological signal.

Amino Acid Sequence↗
PubMed1993

Comparison of the damping effect of different shoeing by the measurement of hoof acceleration.

The purpose of this study was to compare the damping effect of 16 types of shoeing by measuring hoof acceleration parameters on two trotting horses. At impact, maximal deceleration had extreme values such as 188 m/s2 (+/- 55) for the most damping combination (p < 0.01) and 746 m/s2 (+/- 14) for the steel shoe (mean = 551 m/s2 +/- 125). After the shock, the hoof was exposed to a mean vibrating acceleration at 418 Hz (+/- 84) which was progressively damped in 37.3 ms (+/- 10.5). According to these results, the damping ability of different farriery products significantly reduces (p < 0.05) shocks and vibrations at hoof impact in the athletic horse caused by runs on asphalt or similar surfaces. In practice, the use of the most efficient shoeing should help to reduce the incidence of the over-used joint diseases in the athletic horse caused by runs on hard surfaces.

Acceleration↗
PubMed1991

Molecular cloning of the CD9 antigen. A new family of cell surface proteins.

The CD9 antigen was described originally as a 24-kDa surface protein of non-T acute lymphoblastic leukemia cells and developing B-lymphocytes. It is also strongly expressed on platelets, among other cells, where it shows the property of mediating platelet activation and aggregation upon binding with mAbs. The primary structure has been elucidated by cloning the cDNA from a lambda gt11 expression vector library constructed with megakaryocytic mRNA. Monoclonal antibodies were used as probes with an APAAP amplification of the signal. The 5' region was further cloned in a lambda gt10 randomly primed cDNA library. The initiation codon was immediately followed by a sequence coding for the tetrapeptide corresponding to the NH2-terminal sequence identified in a microsequencing procedure. Only one species of mRNA was found with an estimated size of 1.4 kilobase. CD9 antigen appears to be a 227-amino acid molecule with four hydrophobic domains and one N-glycosylation site. Sequence and structural comparisons showed extensive similarity of the CD9 antigen with a 237-amino acid molecule described previously as the human melanoma-associated antigen ME491 and a Schistosoma mansoni membrane protein of 218 amino acids. These three proteins identify a new family of cell-surface proteins.

Amino Acid Sequence↗
PubMed1991

Functional adult acetylcholine receptor develops independently of motor innervation in Sol 8 mouse muscle cell line.

We have defined culture conditions, using a feeder layer of cells from the embryonic mesenchymal cell line, 10T1/2 and a serum-free medium, which allow cells from the mouse myogenic cell line Sol 8 to form contracting myotubes for two weeks. Under these culture conditions, Sol 8 myotubes undergo a maturation process characterized by a sequential expression of two phenotypes. An early phenotype is typified by the expression of the nicotinic acetylcholine receptor (AChR) gamma-subunit transcripts and the presence of low conductance ACh-activated channels, typical of embryonic AChR. A late phenotype is characterized by the expression of AChR epsilon-subunit transcripts, the decreased accumulation of gamma-subunit transcripts and the appearance of high conductance ACh-activated channels, typical of adult AChR. These results indicate that the expression of functional adult type AChR does not require the presence of the motor nerve and therefore represents an intrinsic feature of the Sol 8 muscle cells. Chronic exposure of the cells to the voltage-sensitive Na+ channel blocking agent tetrodotoxin does not affect the appearance of the AChR epsilon-subunit transcripts but prevents the reduction of the steady-state level of the AChR gamma-subunit transcripts and yields a reduced proportion of the adult type channels. Thus, activity seems to facilitate the switch from the embryonic to the adult phenotype of the AChR protein. The Sol 8 cell system might be useful to analyse further the genetic and epigenetic regulation of muscle fibre maturation in mammals.

Animals↗
PubMed1991

Existence of different subtypes of nicotinic acetylcholine receptors in the rat habenulo-interpeduncular system.

Neuronal nicotinic ACh receptors (nAChRs) are present in the rat medial habenula (MHB) and interpeduncular nucleus (IPN), two brain regions connected through the fasciculus retroflexus (FR). The goal of the present study was to compare the electrophysiological and pharmacological characteristics of nAChRs located at pre- and postsynaptic sites within the MHB-IPN system. nAChRs located on the soma of IPN neurons were studied using patch-clamp techniques and a preparation of acutely isolated neurons. Whole-cell currents evoked by Ach and nicotine showed an intense rectification at positive membrane potentials. nAChR channels were relatively nonselective for cations, had a unitary conductance of 35 pS, and were activated by several nicotinic agonists with the following rank order: cytisine greater than ACh greater than nicotine greater than dimethylphenylpiperazinium (DMPP). They were blocked by mecamylamine, hexamethonium, curare, and dihydro-beta-erythroidine (DHBE), but were insensitive to alpha-bungarotoxin and neuronal bungarotoxin. In contrast, nAChRs recorded on the soma of MHB neurons under equivalent experimental conditions exhibited different characteristics for single-channel conductance and agonist and antagonist sensitivity. The pharmacological properties of presynaptic nAChRs in the IPN were analyzed in a rat brain slice preparation. Stimulation of the FR produced a presynaptic afferent volley recorded in the rostral subnucleus of the IPN. Nicotinic agonists decreased the amplitude of the afferent volley with different efficacies: nicotine greater than cytisine greater than ACh greater than DMPP. The action of nicotine was insensitive to alpha-bungarotoxin and to neuronal bungarotoxin, but was blocked by mecamylamine, hexamethonium, curare, and DHBE, with IC50 values different from those reported for IPN postsynaptic nAChRs. This study thus demonstrates the functional diversity of nAChRs in the rat CNS.

Animals↗
PubMed1991

[Additional contribution of high amplification electrocardiography in the follow-up of children with muscular dystrophy].

Fifteen children and adolescents with muscular dystrophy underwent investigation by Doppler echocardiography and high amplification electrocardiography to evaluate the quality of left ventricular function. High amplification ECG showed minor intra-atrial conduction defects in 3 cases and abnormal late micro potentials without arrhythmogenic late potentials in 3 other cases. Significant abnormalities were observed in 40% of children examined. Doppler echocardiography showed relative conservation of systolic left ventricular function but a decrease in indices of contractility was observed in 46% of cases, especially in patients with Duchenne muscular dystrophy. Abnormalities of left ventricular distensibility were observed earlier and were more common (53% of cases). A significant decrease in cardiac output was found in 50% of patients, especially among the older and more severely affected children irrespective of the type of muscular dystrophy. These two investigations provide complementary information for the evaluation of left ventricular function of children with muscular dystrophy and they are proposed routinely for the follow-up of these patients.

Adolescent↗
PubMed1990

Extent of multiple innervation of cerebellar Purkinje cells by climbing fibers in adult X-irradiated rats. Comparison of different schedules of irradiation during the first postnatal week.

The multiple innervation of cerebellar Purkinje cells (PCs) by climbing fibers (CFs) that is transient in normal developing rats can be experimentally maintained in cerebella which have been degranulated by repetitive postnatal X-irradiation restricted to the first postnatal week. Since the involution of redundant CFs occurs essentially between postnatal days 5 and 10, and given that postirradiation effects last 2-3 days, the question arose to know whether it is possible to further delimit a 'critical period' of irradiation within the first week. An estimate of the extent of multiple innervation of PCs by CFs was made in adult rats that had been irradiated according to 5 different schedules: in two groups, rats received X-rays applied repetitively during the first postnatal week (PN0-7 groups); in the 3 other groups, X-rays were delivered either during the first part of the week (early group PN1-3) or during the last part of the week (late groups PN4-7). In addition, two daily doses were tested (150 and 200 r). The CF pathway was electrically stimulated in anesthetized rats at the level of the inferior olive or in the cerebellar white matter. Intracellular recordings of spontaneous and evoked CF responses in PCs allowed to estimate the number of afferent CFs and to calculate the mean value (m) per PC for each group. The majority of recorded cells was located in lobules VII and VIII and similar results were obtained in these two lobules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Oncogene amplification correlates with dense lymphocyte infiltration in human breast cancers: a role for hematopoietic growth factor release by tumor cells?

One hundred six primary breast cancer samples were analysed for c-erbB2, int-2, and c-myc gene amplification. Surgically confirmed nodal involvement was observed in 42%. Level of gene amplification was studied by Southern and/or slot blot techniques. Amplified c-erbB2 gene sequences were present in 21.5% of all samples. Int-2 was amplified in 13.1% and c-myc was amplified in 10.3%. In a non-parametric test (Kruskal-Wallis) a strong negative association was found between high levels of c-erbB2 amplification and absence of estrogen receptor (ER) (P = .0009) or progesterone receptor (PR) (P = .011) expression. No correlations were found between all or high levels of amplification of each oncogene separately or combined with T, N, grade, multifocality of tumor, or associated carcinoma in situ. There was a trend approaching statistical significance for patients with c-erbB2 amplifications to have positive lymph nodes at surgery (P = 0.09). A somewhat surprising finding however was a very strong association between oncogene amplification and dense lymphocyte infiltration of the tumor (P = .05). This correlation is even stronger when only high levels of amplification are considered, either for each oncogene separately (P = .0048) or in combination (P = .0007). We propose that malignant cell cytokine production may help explain this observation.

Breast Neoplasms↗
PubMed1990

Manipulation of the immune response by monoclonal antibodies in auto-immune pathology.

Murine monoclonal antibodies have proven to be invaluable tools in medical research and diagnosis. However, their use as therapeutic agents remains limited since these proteins can act as foreign antigens in the human host. An immune response subsequent to administration of monoclonal antibodies may result in unpredictable in vivo distribution and insufficient interaction with cellular or molecular targets of the immune system. Also, the patient may produce anti-antibodies that can neutralize the effects of the therapeutically administered monoclonal antibodies. Treatment of auto-immune disease is an important potential therapeutic application of monoclonal antibodies, provided that these difficulties can be overcome.

Animals↗