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Biomedical subjects

P Benoit

Publications and source records attributed to P Benoit.

At least 19 recordsLinked to original sources
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↗
PubMed1990

[Progression from hypertrophic obstructive cardiomyopathy to dilated cardiomyopathy. Apropos of 4 cases].

Four cases of hypertrophic obstructive cardiomyopathy diagnosed on clinical, phonomechanographic, echocardiographic and haemodynamic criteria progressing to dilated cardiomyopathy are reported. This evolution was observed over a number of years (up to 20 years) and was accompanied by a clinical aggravation in all cases with 2 deaths and atrial fibrillation in 3 of the 4 cases. The signs of intraventricular obstruction [systolic murmur, bulge on the carotid pulse tracing, systolic anterior motion of the mitral valve (SAM) and intraventricular pressure gradient] disappeared as the left heart chambers dilated with a reduction in ventricular wall motion and parietal thinning but no change in myocardial mass.

Adult↗
PubMed1989

Calcium rise in human platelets elicited by anti-CD9 and -CD41 murine monoclonal antibodies.

Three murine monoclonal antibodies (anti-CD9: ALB6, anti-CD41: VI-PL3 and PL2-49/GPIIb - final concentration: 7.5 micrograms/mL) are shown to elicit after a lag time aggregation of washed platelets and a calcium signal (as detected by light emitted by loaded aequorin), which is only partially inhibited by aspirin. By comparison the rise induced by thrombin is greater and almost instantaneous. In the presence of EGTA a calcium mobilization from internal stores can be detected with thrombin and with ALB6, but neither with PL2-49 nor with VI-PL3, whereas platelets still change their shape and release ATP. It is tempting to speculate that although all the antibodies induce a calcium change, they activate platelets by different pathways: calcium may be not primarily involved in the activation induced by the anti-CD41 antibodies.

Adenosine Triphosphate↗
PubMed1988

Calcitonin gene-related peptide enhances the rate of desensitization of the nicotinic acetylcholine receptor in cultured mouse muscle cells.

Calcitonin gene-related peptide (CGRP) is a neuropeptide that coexists with acetylcholine in spinal cord motoneurons. The effects of CGRP on the functional properties of the nicotinic acetylcholine receptor (AcChoR) were examined by electrophysiological methods. Using the whole-cell patch-clamp technique and a mouse cell line derived from soleus muscle, we found that CGRP produces a progressive and reversible enhancement of the rapid-decay phase of AcChoR desensitization. Single-channel data further show that CGRP decreases acetylcholine-activated channel opening frequency. This decrease occurs when CGRP and acetylcholine are applied on different cell-surface areas and thus is likely mediated by a second-messenger system. CGRP is also shown to increase cAMP accumulation in this cell line. The effects of CGRP on macroscopic acetylcholine-activated currents are mimicked by external application of forskolin (10 microM) or by internal perfusion of the cell with cAMP (1 microM). In both these cases, further application of CGRP produces no additional enhancement of AcChoR desensitization. These results suggest that, on mouse muscle cells, CGRP regulates AcChoR desensitization by a mechanism that involves, at least in part, cAMP-dependent phosphorylation of the AcChoR.

Animals↗
PubMed1988

[Hemodynamic effects on intravenous propafenone in hypertrophic myocardiopathy].

None of the medical treatments of hypertrophic cardiomyopathy is perfect. In the present study conducted on 11 patients with hypertrophic cardiomyopathy in whom the usual treatments were either ineffective or badly tolerated, the haemodynamic effects of propafenone administered intravenously were investigated. The drug was injected centrally in doses of 2 mg/kg over 10 minutes, then by continuous intravenous infusion of 1.5 mg/min during 30 minutes. Various parameters were recorded before and after propafenone treatment by right and left cardiac catheterization. This anti-arrhythmic drug, which has beta-blocking and amiodarone-like properties, reduced left intraventricular obstruction but had no beneficial effect on diastolic function. The baseline and induced left intraventricular gradients were reduced from 30.4 to 17.7 mmHg and from 74 to 43 mmHg respectively. Diastolic function values showed a fall in dp/dt min from 1470 to 1307 mm/sec and an increase in T value from 0.066 to 0.084. The use of propafenone in hypertrophic cardiomyopathy must be accurately determined by long-term oral studies.

Adolescent↗
PubMed1987

[Borrelian meningoencephalomyelitis. A case].

A 22-year old man had spastic paraparesis and cerebellar syndrome of 5 months duration. CSF showed lymphocytosis, elevated protein content, hypoglycorachia, hypochlorurachia and oligoclonal banding. CT scan and MRI were normal. Extensive laboratory procedures disclosed no bacterial, viral, fungic, parasitic or inflammatory disease. Anti-Borrelia burgdorferi antibodies were present in blood (1/4000) and in CSF (1/1024). With antibiotics (penicillin G 20 millions units per day for 10 days, followed by latamoxef 1.5 g per day for 3 months) and prednisone (50 mg per day for 2 months), the cerebellar signs disappeared, the paraparesis improved and the CSF abnormalities disappeared; blood and CSF anti-Borrelia antibody levels decreased. This case is an example of a severe form of CNS impairment by Borrelia burgdorferi. In Europe, most reports show progressive para- or tetraparesis with, sometimes, intellectual, cerebellar or cranial nerve impairment. In some cases, the signs are less diffuse or more acute. Lymphocytic meningitis is present with hyperalbuminorachia and oligoclonal banding; hypoglycorachia is mentioned in only one other report. Diagnosis is made by high blood and CSF antibody titers and demonstration of local synthesis. As in syphilis, borrelian meningoencephalomyelitis could be the third stage of the disease. Its treatment, often disappointing, consists of antibiotics (penicillin G or latamoxef) and in some cases corticosteroids.

Adult↗