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Biomedical subjects

S Richard

Publications and source records attributed to S Richard.

At least 181 records · Page 10Linked to original sources

Allelic loss on chromosome 22 correlates with histopathological predictors of recurrence of meningiomas.

Meningiomas are common tumors of the nervous system. Although usually benign, they may exhibit variable degrees of aggressiveness. Their probability of recurrence after subtotal resection has been correlated with several histological parameters. Independently, a loss of chromosome 22, as evidenced either by cytogenetics or by somatic loss of alleles, has been observed in about half of the cases studied. In 34 meningiomas we have examined the relationship between loss of chromosome 22 alleles and 6 histological predictors of recurrence. Significant correlations were found for 3 of these, i.e. prominent nucleoli (p less than 0.002), microscope count of mitoses (p less than 0.05) and nuclear pleomorphism (p less than 0.02). Correlation with the other 3, i.e. sheeting of cells, vascularity and micronecrosis, did not reach significance. Total tumor score, defined by the sum of the individual scores for these 6 parameters, was strongly correlated to allelic loss (p less than 0.0001). Thus, the loss of chromosome 22 alleles, which possibly contribute to the inactivation of tumor-suppressor gene(s), might be a potent genetic marker of the aggressiveness of meningiomas.

Aneuploidy↗

Enterocytozoon bieneusi infection in acquired immunodeficiency syndrome-related sclerosing cholangitis.

Acalculous cholecystitis and sclerosing cholangitis due to Cryptosporidium sp, and cytomegalovirus have been described in patients with the acquired immunodeficiency syndrome (AIDS). However, in about 40% of cases of AIDS-related biliary disease, no opportunistic pathogen is identified. The current case report describes the first case, to the best of the authors' knowledge, of AIDS-related sclerosing cholangitis associated with microsporidiosis. Enterocytozoon bieneusi was detected in the duodenum and bile by means of light microscopy and confirmed by electron microscopy. Microsporidian infection should be suspected in patients with AIDS-related sclerosing cholangitis as well as in cases of diarrhea in which none of the usual pathogens are found.

Acquired Immunodeficiency Syndrome↗

[Pheochromocytoma, first manifestation of Von Hippel-Lindau disease: a possibility to be considered].

Von Hippel-Lindau (VHL) disorder is an autosomal dominant disease characterized by the almost constant development of hemangioblastomas in the central nervous system (cerebellum, spinal cord and retina). In addition, various types of tumors including renal cell carcinomas, pancreatic cysts and pheochromocytomas are frequently observed in VHL gene carriers. Linkage of the VHL locus to the RAF-1 oncogene on the short arm of chromosome 3 (3p25-26) has been recently reported. Pheochromocytoma is of particular interest because of the risk of inaugural malignant hypertensive crisis but especially because of a great degree of interfamily variability (from 0 to 92% of affected members in previously reported large kindreds). We have studied a French series of 25 pheochromocytoma (11 males, 14 females) in VHL affected patients. Twenty pheochromocytoma (80%) occurred in a familial context, whereas 5 (20%) were consistent with "apparent sporadic cases". The mean age at pheochromocytoma diagnosis was 27 years (5-55 years). Bilateral tumours have been documented in 13 cases (52%). The prevalence of pheochromocytoma revealing VHL was 14 out 25 (56%). In these cases, VHL diagnosis was considered up to 25 years later. In 6 cases (2 deceased) pheochromocytoma was the only manifestation of VHL. Thus, search for VHL must be systematic in the presence of pheochromocytoma, in the interest of the patients themselves and of potential at-risk family members (prevention of hypertensive crisis linked to latent tumours). Basic check-up (neurological and somatic examination, ophthalmoscopy, familial inquiry) may be completed with cerebral CT scan or MRI and abdominal ultrasonography followed, if positive or doubtful, by abdominal MRI or selective angiography.

Adolescent↗

Identification of a retinoic acid response element in the human oxytocin promoter.

Retinoids are known to have profound effects on cellular differentiation and embryo pattern formation. In the adult organism, retinoid acid (RA) receptors are present in a large variety of tissues, including brain. However, little is known of the precise roles of RA at these different sites. In the present study we have identified a novel potential target of RA action by identifying an RA response element (RARE) in the human oxytocin (OT) gene promoter. We have used DNA-mediated gene transfer techniques to introduce various portions of the OT 5'-flanking sequences next to the chloramphenicol acetyltransferase (CAT) gene in neuroblastoma cells. RA elicited a marked stimulation of the transcriptional activity of the OT promoter in cells cotransfected with either the human RA receptor alpha, beta, or gamma. In cells cotransfected with the RA receptor alpha, the ED50 of this response was 5 x 10(-10) M. The RA response could also be conferred to a heterologous promoter independent of orientation. 5'-Deletions as well as site-directed mutations demonstrated that four TGACC motifs, located at -162, -156, -103, and -83 in the OT promoter, are necessary for optimal RA induction. Mutation or deletion of any of these elements reduces significantly the RA response. Interestingly, the first two TGACC motifs overlap with the estrogen response element that we have previously characterized in this gene. Furthermore, the TGACC motif located at -83 overlaps with the CCAAT box. We further demonstrate that in neuroblastoma cells transfected with an RAR alpha expression vector expression of the endogenous OT gene is stimulated greater than 4-fold in response to RA. Our studies constitute the first report of a RARE in a neuropeptide gene and define a mechanism by which OT gene expression can be modulated by retinoic acid.

Animals↗

Inhibition of T-type calcium currents by dihydropyridines in mouse embryonic dorsal root ganglion neurons.

The effects of dihydropyridines (DHPs) normally considered to be specific for L-type calcium channels were studied on the T-type Ca channel current of acutely isolated dorsal root ganglion (DRG) neurons taken from 13-day-old (E13) mouse embryos. Potent but reversible inhibitory effects of the DHP nicardipine were found in the micromolar range. For example, 5 microM nicardipine suppressed 93 +/- 5% of T-type currents. In comparison, other classical DHPs such as nifedipine, PN 200-110 and nitrendipine had only weak effects (less than 20% inhibition) at the same concentration. The inhibition by nicardipine was found slightly to be voltage dependent and the drug induced a leftward shift in the steady-state inactivation. The DHP agonist (-)-Bay K 8644, which dramatically increased the L-type current, weakly decreased T-type Ca currents (17 +/- 8% at 5 microM). In conclusion, neuronal T-type Ca channels may be potential targets for some dihydropyridines. This property is not only a feature of the central nervous system (J. Physiol., 412 (1989) 181-195) and can be extended to peripheral neurons.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Voltage-dependent regulation of L-type cardiac Ca channels by isoproterenol.

The beta-adrenergic cascade is important for the regulation of voltage-dependent Ca channels by phosphorylation. Here we report that isoproterenol (ISO) profoundly alters the voltage-dependent properties of L-type Ca channels studied in rat ventricular cells. ISO (1 microM) shifted both threshold and maximal activation of Ba current (IBa) towards more negative potentials (approx. 10 mV). An equivalent shift was observed in the steady-state voltage-dependent inactivation curve. As a consequence, the potentiation induced by ISO on IBa was greater for weak depolarizations and from negative holding potentials (Vh). We have excluded that the contribution of minor uncompensated series resistances, the activation of Cl currents or changes in junction potential during the experiments account for these effects. In addition, ISO had a dual effect on IBa decay depending on the voltage step (acceleration below, slowing above -10 mV). In conclusion, it is postulated that the voltage dependence of the potentiating effects of ISO on Ca channels activity may ensure a selective regulation among heart tissues with different membrane resting potentials.

Animals↗

Dihydropyridines interact with calcium-independent potassium currents in embryonic mammalian sensory neurons.

Early embryonic sensory neurons have two K currents resembling delayed rectifier and transient K currents of mature neurons. However, in contrast to those of adult neurons, the embryonic currents can hardly be separated either by electrophysiological or pharmacological methods, limiting their characterisation at these developmental stages. Using the whole-cell recording technique, we found that dihydropyridines (DHPs) inhibit the noninactivating component of the Ca-independent K currents of 13-day mouse embryo dorsal-root ganglion (DRG) cells. The inhibitory effect of nicardipine began around 0.5 microM and was nearly complete at 5 microM while Na currents were not altered. This effect was reversible and voltage-dependent. The same results were obtained using another DHP Ca antagonist, nimodipine, whereas Bay K 8644, a DHP Ca agonist, had no effect. Kinetic properties of the DHP-insensitive K current have been described and compared with those of transient K currents found in differentiated neurons. These results suggest that both Ca and K channels have DHP sites, possibly homologous, at this developmental stage. The DHP inhibition of Ca-independent K channels provides a new tool with which to study K channels both at a molecular level and during DRG development.

Animals↗

Properties and Modulation of Ca channels in adult human atrial cells.

Ca-channel currents have been investigated in single cells isolated from adult human atrium using the whole-cell patch clamp technique. Ca-channel currents are activated at voltage positive to -40 mV, peak between -10 and 0 mV and inactivate with a slow decay when Ba2+ ions (5 mM) are used as charges carrier. These properties correspond to those of the high voltage activated, DHP-sensitive, (L-type) Ca channel. No low voltage activated (T-type) currents have been evidenced. The present work also provides the first report about the modulation of Ca channels in adult human atrial cells by beta-adrenergic agonists and dihydropyridines (agonists and antagonists). Electrophysiological and pharmacological properties of these Ca channels are qualitatively similar to those of the L-type Ca currents recorded from cardiac animal cells. However, at a physiological calcium concentration (2 mM), basal Ca currents are often very small or even absent but are revealed following the addition of the dihydropyridine (DHP) agonist Bay K 8644. Whether the decrease of the basal Ca current amplitude may be related to the chronic pretreatment of the patients by Ca channel blockers or to the pathology is discussed.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Modulation of Ca currents in isolated frog atrial cells studied with photosensitive probes. Regulation by cAMP and Ca2+: a common pathway?

We have studied the regulation of cardiac Ca current by intracellular cyclic AMP (cAMP) and Ca2+, using photosensitive, caged compounds and the whole-cell, patch-clamp technique in isolated frog atrial cells. Although both low voltage activated (LVA) and high voltage activated (HVA) Ca channels were found to be present in these cells, only the HVA Ca currents were sensitive to modulation by isoproterenol or dihydropyridines (DHPs). The application of extracellular isoproterenol, as well as the photorelease of intracellular cAMP or Ca2+ at micromolar and submicromolar concentrations, respectively, had no effect on LVA Ca currents. In contrast, these agents: (i) increased the amplitude of currents through HVA channels, carried by either Ca2+ or Ba2+ with a similar time-course, (ii) slowed the decay of the current when Ba2+ was the permeating ion, and (iii) modulated the agonist effect of the DHP Bay-K 8644. The strong similarities between the effects of cAMP and Ca2+ suggest that both of these intracellular messengers might eventually lead to the phosphorylation of HVA Ca channels. It is possible that Ca-dependent phosphorylation of the channels may account for the potentiation of Ca current induced by repetitive stimulation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Lingual localization of an inclusion body fibromatosis (Reye's tumor).

This report illustrates a lingual localization of an inclusion body fibromatosis, the so-called Reye tumor or infantile digital fibromatosis (IDF). The light microscopic features were identical to those found in IDF, showing eosinophilic perinuclear inclusions located in spindle-shaped cells arranged in interlacing fascicles. The immunocytochemical and ultrastructural findings suggested a fibroblastic and/or myofibroblastic nature of the proliferative cells. However, the inclusions in our case were strongly stained with vimentin and their ultrastructural appearance was in keeping with intermediate filaments. These findings have never been described in other reports of fibromatosis. Whereas most reviews state that IDF occurs exclusively on the digits, this unique case describes its possible occurrence in the tongue.

Fibroma↗

In vivo proton relaxation times analysis of the skin layers by magnetic resonance imaging.

If in vivo magnetic resonance imaging is nowadays a powerful non-invasive method in medical diagnosis, its application in order to study the skin in vivo is not yet in common use because skin imaging requires a high resolution, at least in the direction perpendicular to the skin surface. We have therefore designed a specific imaging module, which, connected to a standard whole-body imager at 1.5 Tesla, allows us to obtain in vivo magnetic resonance images of skin on most parts of the body. With a depth resolution of about 70 microns, we are able to differentiate the skin layers: epidermis, dermis, subcutaneous fat, and even a thickened stratum corneum on palm as well as on heel. This paper reports the T1 and T2 water proton relaxation times of the different skin layers, in vivo, which are magnetic resonance parameters extracted from the images. Results show that skin layers are characterized by shorter T2 relaxation times than other biologic soft tissues. On the contrary, the measured T1 values are in the same range as in other tissues. These short T2 values may be assigned to the fibrous protein content of the skin and particularly of the dermis. This study on normal skin is the precursor of further works such as the influence of aging. As regards skin pathologies, it will be a powerful tool to follow the evolution of skin diseases under treatment.

Adult↗

Several groups among human herpesvirus 6 strains can be distinguished by Southern blotting and polymerase chain reaction.

Eight human herpesvirus 6 (HHV-6) strains were studied by Southern blot and polymerase chain reaction. DNA from infected cells was digested by a panel of restriction enzymes and hybridized with cloned BamHI fragments corresponding to about 30% of the HHV-6 strain SIE genome. In parallel, this DNA was amplified by polymerase chain reaction using pairs of primers derived from the strain SIE nucleotide sequence. Subsequently, amplification products were analyzed by hybridization, digestion with restriction endonucleases, and partial nucleotide sequencing. Overall results indicated that all strains were closely related to one another. However, concordant differences in restriction patterns allowed at least two groups to be distinguished, typified by strains SIE and HST, respectively. Differences between the two groups were found to reflect a limited number of punctual changes in nucleotide sequences. These results strengthen the idea of a unique HHV-6 species with genetic polymorphism. In addition, this study provides useful markers for the diagnosis and molecular epidemiology of HHV-6 infections.

Base Sequence↗

Responses of subcultured rat aortic smooth muscle myocytes to vasoactive agents and KCl-induced depolarization.

We have developed a culture system in which a single-mass primary culture can be used for as long as 6 wk as a source of subcultured smooth muscle myocytes for the study of the changes of their shape upon addition of vasoactive agents (angiotensin, vasopressin, norepinephrine, and serotonin) and KCl depolarization. Responses of subcultivated myocytes were shown to be reproducible with time in primary culture before subculture and consistent with responses of thoracic aorta to the same agents. Effect of KCl depolarization could be blocked with calcium antagonist PN 200-110. Consistently, the presence of calcium L-channels was shown using whole cell patch-clamp recordings. A comparative study of the responses of myocytes derived from two different segments of the thoracic aorta showed that these cells displayed responses with different maximal amplitudes and the same potencies according to their topological origin in the vessel.

Angiotensin II↗

Tissue-specific effects of aldose reductase inhibition on fluorescence and cross-linking of extracellular matrix in chronic galactosemia. Relationship to pentosidine cross-links.

Chronic experimental hyperglycemia mediated by galactose has been shown to induce browning and cross-linking of rat tail tendon collagen that could be duplicated in vitro by nonenzymatic galactosylation. To investigate the nature of these changes, Sprague-Dawley rats were placed on a 33% galactose diet without and with sorbinil for 6 and 12 mo. Collagen-linked fluorescence and pentosidine cross-links increased with age and galactosemia in tail tendons (P less than 0.001) and skin but were essentially unresponsive to aldose reductase inhibition (ARI). In contrast, tendon breaking time in urea, a likely parameter of cross-linking, was markedly improved (P less than 0.001) by ARI. Fluorescence that was inhibited by sorbinil treatment was increased in pepsin and proteinase K digest of aortic tissue from galactosemic rats (P less than 0.001), but impaired enzymatic digestibility was not observed. Systolic blood pressure as potential consequence of aortic stiffening was not increased in galactosemia. These data suggest that fluorescence in skin and tendon might be in part due to advanced glycosylation and pentosidine formation because these were not decreased by ARI. However, they also suggest that nonfluorescent cross-links may also be forming because, in contrast to fluorescence, tail tendon breaking time was partly corrected by ARI. Thus, it appears that extracellular matrix changes in chronic galactosemia are complex, being partly attributable to advanced glycosylation and partly to polyol-pathway activation.

Aldehyde Reductase↗

[Chondromyxoid fibroma of the cervical spine. Apropos of a case treated by partial vertebrectomy].

A case of chondromyxoid fibroma revelated by cervicalgias and involving the right part of the 5th cervical vertebra is reported. This uncommon cartilaginous tumor is usually described in the metaphysis of long bones and appears very rare in the spine. If radiological aspects have been reported, the majors series do not describe a typical appearance of vertebral lesions; our patient is one of the first to have been evaluated by CT scan. Chondromyxoid fibromas are benign tumors, but recurrence is possible especially when treated by curettage alone. In our case, operated on two stages, the resection seemed sufficiently large and CT control on the 10th month did not show evidence of recurrence. Clinical and radiologic findings, and surgical management of these vertebral tumors are discussed.

Adult↗

[Pathological anatomy of the heart in myopathies and infantile muscular atrophies].

In progressive muscular dystrophy, the heart is always affected and presents characteristic histological lesions: irregular, diffuse and intense rearrangements predominantly in the left ventricle, the septum and conductive tissue, consisting of wide, poorly vascularized fibrous bands, that are destructive but without an inflammatory aspect. The remaining myocardium is dystrophic with degeneration of the fibers (hyalin, atrophic or hypertrophic) with irregular nuclei. Plaques of adipose tissue are found under the epicardium within the heart wall. Sometimes, a fibrous thickening of the intracoronary arteries is observed without modification of the intima, but vascular lesions are not systematically seen. In congenital muscular dystrophy, cardiomyopathy certainly exists, but there is no histological description. Half of the patients suffering from myopathy with intracytoplasmic inclusions also have dystrophic and fibrotic cardiac involvement. Congenital myopathies may have their own specific cardiomyopathy, as in central core myopathy, nemaline (rod) myopathy and especially myotubular myopathy, where involvement is common. Werdnig-Hoffmann disease types I and II do not affect the heart. In contrast, several cases of fibrotic lesions have been described in KugelbergWelander disease.

Adolescent↗