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Biomedical subjects

C Baudoin

Publications and source records attributed to C Baudoin.

At least 55 records · Page 3Linked to original sources

A novel beta 1 integrin isoform produced by alternative splicing: unique expression in cardiac and skeletal muscle.

The mRNA's of several integrin subunits are alternatively spliced in the region encoding cytoplasmic domains, that may potentially provide alternative integrin-cytoskeleton interactions and transmembrane signaling pathways. We identified a novel cytoplasmic tail variant of the human beta 1 subunit by reverse transcriptase polymerase chain reaction. This fourth beta 1 variant, named beta 1D, is specific for skeletal and cardiac muscle. The determined genomic organization of the 3'-region of the human beta 1 gene reveals that beta 1D is produced by alternative splicing of mRNA. In addition, we show that the expression of beta 1D is developmentally regulated during murine myoblast differentiation, suggesting a role for beta 1D in myogenesis.

Alternative Splicing↗

[Present and future epidemiology of osteoporosis].

Osteoporotic patients are exposed to fractures at all bones sites, mainly the upper extremity of the femur, the vertebral bodies, and the distal forearm. According to an overview of 6 French surveys, it is estimated that there has been, in 1990, 45,000 to 50,000 new fractures of the upper extremity of the femur, in patients aged 20 years and above. Owing population aging, more than 145,000 fractures are expected to occur in 2050. The frequency of osteoporosis, its spontaneous tendency to increasing prevalence, its functional consequences and its cost make it a major public health issue with a requirement for a specific preventive strategy.

Adolescent↗

Social isolation partially restores reproduction of male staggerer mutant mice.

Social isolation is generally known to promote sexual performances in male mice. We employ here other indices to investigate the positive effects of social isolation on sexual behavior. Mutant staggerer male mice generally do not mate. However some of their reproductive traits can be restored by environmental modifications. We demonstrate that a postpubertal period of social isolation can significantly enhance mutant male sexual behavior. After a period of partial social isolation of one or 2 mo a significantly larger number of mutant males were observed to attempt mounting receptive non mutant C57BL/6 females during a 30 min test encounter. When reproductive success is considered, a larger number of males who were isolated for a period of 2 mo and then allowed to remain with non mutant females were found to sire pups than control (non-isolated) males. The results show that staggerer males isolated for 2 mo can partially overcome the reproductive deficit usually associated with the mutation.

Animals↗

A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in lethal (Herlitz) junctional epidermolysis bullosa.

The inherited mechanobullous disorder, junctional epidermolysis bullosa (JEB), is characterized by extensive blistering and erosions of the skin and mucous membranes. The diagnostic hallmarks of JEB include ultrastructural abnormalities in the hemidesmosomes of the cutaneous basement membrane zone, as well as an absence of staining with antibodies against the anchoring filament protein, laminin 5. Therefore, the three genes encoding alpha 3, beta 3 and gamma 2 chains of laminin 5, known as LAMA3, LAMB3 and LAMC2, are candidate genes for JEB. We have previously demonstrated mutations in the LAMB3 and LAMC2 genes in several families with JEB. We initiated mutation analysis from an affected child by PCR amplification of individual LAMA3 exons, followed by heteroduplex analysis. Nucleotide sequencing of heteroduplexes identified a homozygous nonsense mutation within domain I/II of the alpha 3 chain. These findings provide the first evidence that nonsense mutations within the LAMA3 gene are also involved in the pathogenesis of JEB, and indicate that mutations of all three genes of laminin 5 can result in the JEB phenotype.

Base Sequence↗

[Modifications of the olfactory bulb electrocorticogram and trans-glomerular evoked potentials in staggerer mutant mice].

Electrophysiological observations have been made on normal C57-BL/6J and staggerer mutant mice. Morphological observations have given evidence it existed various neurones modifications which affected the olfactory bulb in the mutant mice. Olfactory bulb electrocorticograms (ECoG) of mutant have shown rare bursts of potentials of longer time duration than in normal mice. These bursts were less affected by odor stimulations (ammonia and urine of opposite sexes) than in the normal mice and never varied under urine odor influence in female mutant. Evoked potential induced by the odors had long latency and long duration (up to 50 ms vs 30 ms). In a large amount of them, the late phases and the late oscillatory potentials, which generally followed the evoked potential, were absent. All these results improved the idea that staggerer mutation, which mainly affected the N-CAM gene, not only induced cerebellar diseases, but also functionally affects the olfactory bulb.

Animals↗

Opposite effects of cholinergic agents and benzodiazepine receptor ligands in a passive avoidance task in rats.

Benzodiazepine (Bzd) agonist, diazepam (Dzp) and inverse agonist methyl beta-carboline-3-carboxylate (beta-CCM); acetylcholinesterase inhibitor, physostigmine (Physo) and muscarinic antagonist, scopolamine (Scopo), were investigated for their mnesic effect in a passive avoidance (PA) task in rats. Impairments were observed after Dzp- and/or Scopo-pretraining treatments. Physo was without effect but antagonized the Dzp-induced impairments. beta-CCM enhanced acquisition and antagonized the Scopo-induced impairing effect. All these drugs had no effect in posttraining administration.

Animals↗

The 100-kDa chain of nicein/kalinin is a laminin B2 chain variant.

We have isolated the basement membrane component nicein and performed rotary-shadow analyses using electron microscopy that showed the presence of two forms (I and II) of the protein. Molecular cloning of the cDNA that codes for the 100-kDa chain of the protein revealed that the sequence matches those independently identified for the 105-155-kDa subunit of kalinin, a recently identified basement membrane component. These data demonstrate that nicein and kalinin contain an identical chain. The length of the open reading frame in the cDNA (approximately 5200 nucleotides) and amino acid sequence obtained from the N-terminus of the 105-kDa kalinin chain showed the occurrence of a precursor polypeptide. This immature polypeptide is probably related to form I, observed by rotary shadowing, while the mature form is related to form II. It is noteworthy that nicein/kalinin subunits share discrete sequence similarities with the B2 chain of human laminin, but with a cleavage occurring within domain III that eliminates domains IV and V from the final product. The sequence of this subunit is nearly identical to that of B2t, a recently described polypeptide supposed to be related to a new laminin variant. Since nicein/kalinin expression is specifically impaired in the severe genodermatosis Herlitz junctional epidermolysis bullosa, the role and structure of this tissue-restricted laminin variant is crucial for the understanding of epidermal-dermal adhesion.

Amino Acid Sequence↗

Herlitz junctional epidermolysis bullosa keratinocytes display heterogeneous defects of nicein/kalinin gene expression.

Previous studies have correlated the Herlitz junctional epidermolysis bullosa (H-JEB) to an altered expression of the basement membrane component nicein/kalinin. This heterotrimeric glycoprotein appears to be present in H-JEB tissues in an abnormal form, because a number of antibodies specific to the protein either do not react with or weakly stain the epidermal basement membranes of most of the patients. With cDNA probes encoding each subunit of nicein and polyclonal antibodies raised against bacterial fusion polypeptides corresponding to the individual chains of the protein, we have molecularly analyzed the expression of nicein in H-JEB tissues and cultured keratinocytes. By immunohistochemistry, Northern blot, and protein analysis, we show a defective synthesis of one of the nicein subunits in six cases of H-JEB from five different consanguineous families. In two patients, the disease correlates with an impaired synthesis of the nicein B2 (nic B2) chain, in three others with that of the B1 (nic B1) chain, and in a sixth patient with that of the heavy A (nic A) chain. In this report, we thus demonstrate that H-JEB is a genetically heterogeneous disease and we provide strong evidence that the genes of nicein are the candidates for this genodermatosis.

Blotting, Northern↗

Developmental expression of nicein adhesion protein (laminin-5) subunits suggests multiple morphogenic roles.

Nicein/kalinin (laminin-5) is a heterotrimeric laminin-like adhesion protein, which is secreted at the basement membrane of subsets of epithelia and is involved in the etiology of junctional epidermolysis bullosa, a severe human blistering disease characterized by disadhesion of epidermis from dermis. cDNA clones encoding the three chains of mouse nicein and antibodies specific to each polypeptide were used to examine the expression of the protein in the developing mouse embryo from 10.5 day post coitum to 7 days after birth. At various stages of development, co-expression of the three chains of nicein was observed in amnion, skin, and in epithelia of respiratory, urinary and digestive systems. High level expression of nicein was seen in enamel-secreting ameloblasts in developing teeth. Cell-specific distribution of nicein was also detected in other specialized tissues representative of the three primary embryonic germ layers with prominent secretory or protective functions. Differential and focal expression of nicein subunits was observed in the choroid plexus and the floor plate of the neural tube. Messenger for the heavy chain of nicein was detected in the floor plate, where mouse s-laminin messengers were also found. This suggests that nicein genes may play a role in the migration and polarization of motor neurons in the developing spinal cord.

Amino Acid Sequence↗

Peripherin, a neuronal intermediate protein, is stably expressed by neuroendocrine carcinomas of the skin, their xenograft on nude mice, and the corresponding primary cultures.

The histogenesis of neuroendocrine carcinomas of the skin is still controversial. To determine the degree of neural differentiation of these neoplasias, we studied the expression of intermediate filament proteins in tumoral tissues. Expressions of peripherin, the neurofilament protein NF-L, vimentin, and cytokeratin 8 were analyzed by immunohistochemical methods on 12 human primary tumors and 3 tumor xenografts on nude mice. Peripherin was detected in 10 primary tumors by immunofluorescence. The protein and the corresponding messenger RNA were identified by two-dimensional gel electrophoresis and Northern analysis in extracts of an immunofluorescence-negative tumor. Peripherin, NF-L, and cytokeratin 8 were detected in tumoral cells, whereas vimentin was found exclusively in the stroma. The histological and ultrastructural properties of the original cells of neuroendocrine carcinomas of the skin, as well as coexpression of peripherin, cytokeratin 8, and neurofilament polypeptides, were preserved in tumor xenografts and their primary cultures in vitro. These results bring new elements to the knowledge of the biology of neuroendocrine carcinomas of the skin and indicate that peripherin constitutes a marker for tumor identification.

Animals↗

Pharmacokinetic study and effects on growth hormone secretion in healthy volunteers of the new somatostatin analogue BIM 23014.

We have studied the pharmacokinetics and the effects of BIM 23,014 (BIM), a new, long-acting octapeptide somatostatin analogue, on basal and stimulated GH secretion in normal men. BIM 250 micrograms sc significantly reduced a GHRH-induced increase in plasma GH. The continuous sc administration of BIM for 24 h dramatically blunted spontaneous GH secretion; 2000 and 3000 micrograms daily reduced GH secretion to a greater extent than 1000 micrograms daily. During these experiments a significant negative correlation (r - 0.66) was found between plasma GH and BIM levels. Acute sc administration of 1000 micrograms BIM significantly reduced the rise in plasma GH observed in the second part of the oral glucose tolerance test. Plasma BIM levels peaked around 30 min, and the elimination half life was 90 min. Plasma BIM levels were below 1 ng/ml 6 h after the injection of 1000 micrograms BIM, and at that time GH started to rise again. We conclude that BIM 23,014 250 to 1000 micrograms sc is able to reduce the plasma GH response to GHRH or to the fall in glucose following an oral glucose tolerance test; a constant infusion of BIM, in doses 1000 micrograms daily, dramatically suppresses spontaneous GH secretion; 2000 micrograms/day by chronic subcutaneous infusion was the most effective dose of BIM in the suppression of GH secretion, and was associated only with minor adverse effects.

Adult↗

Fractures of the proximal femur in Picardy, France, in 1987.

Between 1 January and 31 December 1987, 1178 hip fractures were recorded in the 28 clinical centres, public and private, of the Picardy region (19443 km2, 1.8 million inhabitants). Patients under 20 years and those with metastatic cancer and myelomatous fractures were excluded. Women sustained 853 fractures (age mean +/- SD: 80.2 +/- 10.4 years) and men 325 (age 69.7 +/- 16.0 years). The crude incidence rate per 10,000 person years was 13.4 for women and 5.4 for men (female/male ratio 2.6). These incidences are among the lowest recorded in Northern Europe. Women with trochanteric fractures were older than those with cervical ones, but no difference was observed for men. After adjusting for age and sex, the incidence of hip fracture was greater in urban (10.5 per 10,000 person years) and semi-rural areas (8.2) than in rural areas (5.3). The mean bed-days per patient (+/- SD) was 21.6 +/- 16.0 (quartiles: 13-17-26 days); no difference was observed between sex or age classes. The in-hospital mortality rate was 8.7%, it increased with age and was higher in men, whatever their age. We review the data in different countries, mostly European, to compare with the Picardy region.

Adult↗

Sexual experience and preferences for odors of estrous females in staggerer mutant male mice.

Staggerer mutant male mice generally do not mate and olfactory disabilities may be involved. Choice tests were used to determine the preference of C57BL/6 male mice with the staggerer mutation for urine and vaginal secretions from receptive and unreceptive females. The staggerer mutation does not prevent the olfactory discrimination between vaginal secretions of estrous and anestrous females. Male preferences for odors of receptive females are related to the presence of sexual experience.

Animals↗

Effect of sex and age on the ratio of cervical to trochanteric hip fracture. A meta-analysis of 16 reports on 36,451 cases.

We analyzed 15 published reports and our own data. In women, the ratio of cervical to trochanteric fractures (C/T) evolved in 3 periods. 1) Before the age of 50 years, the annual incidence of cervical fracture is close to that of trochanteric fracture. 2) Between 50 and 60 years, cervical fracture increases markedly, and the C/T ratio is well above unity at an age when the fracture incidence is still very low. 3) This imbalance progressively diminishes to reach unity in the very old, as the result of a progressive increase in trochanteric fractures. In men, cervical fractures are progressively more common with increasing age, and the C/T ratio exceeds unity after 70 years of age. In both genders, the incidence of cervical fracture is thus greater than that of trochanteric fracture during a limited period of time, in the perimenopausal period for women and in elderly men. Several hypotheses on the mechanics of falls and bone strength have been advanced, without any satisfactory explanation for the C/T sex and age changes.

Age Factors↗

[Analysis of the behavior of rats in the Morris water-basin: new methodology and pharmacological application].

The Morris water-maze has been designed to test spatial orientation ability, learning and memory processes. In order to improve the analyse of the organization of the trajectory of rats, during the training phase, a computer program was elaborated. The study of the effect of a benzodiazepine, diazepam, was chosen to illustrate and validate this methodological approach. Results showed that rats pre-treated with diazepam (2 mg/kg) presented an impairment of spatial learning associated with the occurrence of a stereotyped circular swimming behaviour.

Animals↗

[Reduced influence of penile disability on the mating capacity of male staggerer mice].

Most staggerer mutant mice do not mate spontaneously. This deficiency may be attributed to a penile disability (during erection, the penis in extension is directed backward). The main characteristics of this phenomenon and its involvement in the reproduction of the staggerer mutant have been considered in our study. Seventy-four percent (n = 66) of staggerer males presented this temporary abnormality at least once. It appeared when the males were 84 +/- 37-d old (M +/- SD). In most animals the penile abnormality was labile and did not exceed 1 wk duration in 48% (n = 32) of the males. Three males mated in spite of presenting this abnormal erection. Moreover, 25% of males (n = 23) did not present this disability; nevertheless, most of them (91%) still did not reproduce. Other mechanisms are certainly responsible for the inefficient mating. In any case, the influence of penile disability on this deficiency appears to be weak.

Aging↗

Does increased platelet aggregation have a prognostic value in the deterioration of background diabetic retinopathy? The Damad Study Group.

Many case-control studies have suggested that increased platelet aggregation (PA) could be involved in the pathogenesis of diabetic microangiopathy. However, longitudinal data are needed to support this hypothesis. We consider here such an approach in the placebo group (93 diabetic patients) of a controlled clinical trial on the effect of PA inhibitors in the treatment of diabetic retinopathy (Damad program). We have measured spontaneous PA and PA induced by ADP, collagen and arachidonic acid before treatment and yearly during a 3-year period. The assessment of retinopathy was based on the changes in the number of microaneurysms present in the macular field as seen on fluorescein angiograms during follow-up. PA was estimated by maximal decrease in optical density. The lowest ADP concentration still able to induce irreversible aggregation was also determined. No significant correlations between any baseline PA measurements and end point criterion were found (all correlation coefficients lower than 0.20). No significant changes in mean PA were observed during follow-up. Within-subject variation of PA was markedly large accounting for 61% to 98% of the total variance of various measurements. Allowances for the main characteristics of diabetes made no substantial difference to the results. These negative findings can be partly attributed to the lack of reliability of PA tests. In our study, we conclude that PA tests are not useful measures for the prediction of evolution of background diabetic retinopathy.

Adenosine Diphosphate↗