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Biomedical subjects

S Richard

Publications and source records attributed to S Richard.

At least 163 records · Page 9Linked to original sources
PubMed1994

The role of individual Fc gamma receptors in aggregated IgG-stimulated protein tyrosine phosphorylation in the human neutrophil.

Having previously shown that heat-aggregated IgG stimulates a significant increase in tyrosine phosphorylation in the human neutrophil, we next sought to determine the role of individual Fc gamma receptors in this response. Specific cross-linking of Fc gamma RII reproduced the phosphorylation observed with heat-aggregated IgG treatment and monoclonal antibodies recognizing the ligand binding domain of Fc gamma RII efficiently blocked the heat-aggregated IgG induced response. Thus engagement of Fc gamma RII alone appears sufficient to mimic the heat-aggregated IgG stimulation. Similar experiments carried out with antibodies specific for Fc gamma RIII suggested that Fc gamma RII and Fc gamma RIII may cooperate in the phosphorylation response. The activation of a tyrosine kinase by Fc gamma R engagement was demonstrated by the specific immunoprecipitation of several tyrosine phosphorylated proteins from lysates of neutrophils following treatment with aggregated IgG.

Antibodies, Monoclonal↗
PubMed1994

C5a as a model for chemotactic factor-stimulated tyrosine phosphorylation in the human neutrophil.

Human neutrophils were exposed to the chemotactic factors C5a, FMLP, IL-8, leukotriene B4, and PAF, for 30 s, and subsequently analyzed for protein tyrosine phosphorylation by immunoblotting whole cell lysates with a polyclonal antiphosphotyrosine Ab. All chemotactic factors caused the rapid de novo tyrosine phosphorylation of a broad band of approximately 120 kDa and increased the phosphotyrosine content of several other proteins, including two with molecular masses of 60 and 56 kDa that were present in the unstimulated neutrophil. Tyrosine phosphorylation was evident as early as 10 s after stimulation and was maintained for 1 to 3 min before dephosphorylation occurred. The extent of tyrosine phosphorylation was dependent on the concentration of chemotactic factor, with stimulation observed at concentrations as low as 10 to 100 nM. To investigate the pathway used by chemotactic factors to transduce this signal, neutrophils were treated with PMA. PMA also stimulated tyrosine phosphorylation in the neutrophil but with a slower response time and a different pattern of affected proteins. Additional experiments suggested that tyrosine phosphorylation is involved in the regulation of the neutrophil respiratory burst because the tyrosine kinase inhibitor, herbimycin A, inhibited C5a-induced protein tyrosine phosphorylation and also prevented C5a- and FMLP-induced superoxide anion production. Herbimycin A also inhibited PMA-induced tyrosine phosphorylation and superoxide anion production. To confirm that the ability to stimulate tyrosine phosphorylation was intrinsic to the C5a receptor, tyrosine phosphorylation was examined in both undifferentiated U937 cells (C5a receptor negative) and cAMP differentiated U937 cells (C5a receptor positive). C5a induced tyrosine phosphorylation only in differentiated U937 cells. Analysis of the C5a receptor mRNA using the PCR confirmed its presence in differentiated and its absence in undifferentiated U937 cells. Therefore, C5a stimulates tyrosine phosphorylation via a receptor-mediated mechanism and U937 cells provide a system in which G-coupled receptor-mediated tyrosine phosphorylation can be investigated.

Benzoquinones↗
PubMed1994

In vivo hydration profile in skin layers by high-resolution magnetic resonance imaging.

In recent years magnetic resonance imaging has become a very efficient tool for in vivo quantification of water content and water behavior in living tissues. We have applied this technique to the study of the in vivo hydration profile in heel skin layers by quantification of the mobile water proton density versus depth. Effects of a bath, a moisturizer and repeated soaping are present. Hydration profiles by magnetic resonance imaging delineate two different structures in stratum corneum: an outer layer where hydration can be modified by external mechanisms and an inner layer where hydration is not altered. The main interest of this method lies in the fact that the physical signal is exactly located, as spatial encoding is the basis of in vivo imaging. This method differs from other noninvasive methods which acquire an averaged signal from a nondelimited volume of interest.

Administration, Topical↗
PubMed1994

[Does hemangioblastoma exist outside von Hippel-Lindau disease?].

Hemangioblastoma may arise in isolation ("sporadic" cases) or as a major manifestation of von Hippel-Lindau (VHL) disease, an autosomal dominant disorder with a prevalence of at least 1/36,000. In addition of central nervous system hemangioblastomas (cerebellum, spinal cord and retina), affected patients may develop renal cysts or carcinomas, pheochromocytomas and pancreatic cysts. A multidisciplinary group including neurosurgeons, geneticists, pathologists and clinicians from all involved specialities has been organized to develop a national registration of all hemangioblastoma and VHL patients. The findings of a preliminary 10-year study (1983-1993) conducted in France are presented. Two hundred thirteen cases of hemangioblastoma were reviewed for their location and genetic features. The majority (77%) of the tumors were located in the cerebellum whereas 23% were located inside the spinal canal. By thorough clinical examination of the patients and systematic genetic inquiry of their family background, it was found that 34.3% of the total (58.7% before age 30) were afflicted with VHL disease. Spinal hemangioblastomas were more often related to VHL disease than infra-tentorial locations (50% versus 36.6%). In addition, mean age at diagnosis in VHL disease was significantly younger than in sporadic cases (33.5 +/- 10 versus 43.6 +/- 15 years). Recent progress in VHL molecular genetics led to the identification of the mutated gene to the distal part of the short arm of chromosome 3 (3p25-3p26), paving the way to presymptomatic diagnosis and, hopefully, to elucidation of pathogenesis, which may offer a further glimpse into tumorigenesis in general. Because of the usually early adulthood onset, accurate presymptomatic diagnosis of affected members would be of great benefit to VHL families. However, the fact that very few mutations in the VHL gene are identified precludes molecular diagnosis of "sporadic" hemangioblastomas. In summary, this study reveals that VHL-related hemangioblastoma is a more common clinical problem that it was previously reported. Thus, all patients with an apparently isolated central nervous system hemangioblastoma should be investigated for evidence of VHL disease.

Adolescent↗
PubMed1994

[Intraspinal hemangioblastoma. Apropos of a recent series of 20 cases].

This report deals with a series of 20 patients admitted for a spinal hemangioblastoma between 1970 and 1993, 18 of whom between 1978 and 1993. There are 8 men and 12 women and the onset of spinal symptoms is before the age of 50 years for 76% of the patients. Nineteen patients have an intra-dural tumor (extramedullary 15.5%, intramedullary 75% with 62.5% close to the dorsal surface, 37.5% partly out, none totally enclosed with spinal cord) and only one patient has an extra-dural tumor. Cysts are present in 70% of our cases. Two cases have been revealed by an hemorrhagic syndrome. Ten cases belong to a von Hippel-Lindau (vHL) disease. Nineteen patients were operated on, one patient died. Total resection of the tumor was performed in 17. Symptoms improved postoperatively in 8 patients, were inchanged in 6, and worsened temporary in 4. MRI with gadolinium is the best procedure for both the diagnosis and the follow-up. After surgery, the prognosis is very good for sporadic cases with a single spinal lesion whereas it is very poor in case of vHl disease. For these patients (50% of our cases), half of them died because of the evolution of multifocal lesions even if they were operated on several times. Thus, each patient should have a precise check-up (SNC and visceral lesions). The gene causing vHL disease located on the short arm of the chromosome 3 has just been characterized. This will help to elaborate a presymptomatic diagnosis and a better screening of the patients with the hope of a specific treatment.

Adolescent↗
PubMed1994

Noninvasive measurement of the effect of lifetime exposure to the sun on the aged skin.

The cumulative and comparative effects of chronological and actinic changes to the skin were studied in an elderly population. Two adjacent sites with different degrees of exposure to the sun were examined to distinguish the contribution of each factor, by means of noninvasive measurements. The following parameters were measured on the skin of the low neck (an exposed site), as well as on the adjacent clothes-protected skin of 30 elderly women: electrical conductance, color, microrelief, biomechanical properties and the thickness of both the full skin and the subepidermal nonechogenic band (SENEB), using ultrasound measurements. Persistent exposure to the sun accentuated most of the age-induced modifications. The following changes were significantly more marked in exposed skin: SENEB thickening, full-skin thinning, loss of extensibility and elasticity, and color heterogeneity. The cumulative effects of sun exposure and chronological aging lead to atrophy in elderly people. These results suggest that, if there is an autoprotective skin reaction, such as thickening in young adults, it is eliminated in old people.

Aged↗
PubMed1994

Pheochromocytoma as the first manifestation of von Hippel-Lindau disease.

BACKGROUND: von Hippel-Lindau disease is an autosomal dominant disorder characterized by the development of hemangioblastomas in the cerebellum, spinal cord, and retina, renal cell carcinoma and cysts, pancreatic cysts, and pheochromocytoma. METHODS: We have studied a series of 36 French patients affected with von Hippel-Lindau disease pheochromocytoma. Thirty (83%) of them were diagnosed as having von Hippel-Lindau disease because the disease occurred in a familial von Hippel-Lindau disease setting; six (17%) were diagnosed as having von Hippel-Lindau disease because they displayed another characteristic manifestation of that disease. RESULTS: The mean age at pheochromocytoma diagnosis was 29 +/- 14 years (5 to 62 years). Bilateral tumors were documented in 15 (42%) cases, paraganglioma was associated with adrenal pheochromocytoma in four cases, and malignant pheochromocytoma occurred in three cases. Prevalence of pheochromocytoma revealing von Hippel-Lindau disease was 20 (53%) out of 36. In six cases pheochromocytoma was the only manifestation of the disease. CONCLUSIONS: In the interest of the patients themselves and of family members who are at risk, search for von Hippel-Lindau disease must be systematic in the presence of pheochromocytoma. Basic checkup may be completed with familial inquiry, ophthalmoscopy, cerebral magnetic resonance imaging, abdominal ultrasonography, and computed tomography-scan for detection of latent lesions. In the future, after characterization of von Hippel-Lindau disease gene mutations, molecular diagnosis is going to be possible in individual patients.

Adolescent↗
PubMed1994

Comparative analysis of cellular and tissular expression of c-fos in human keratinocytes: evidence of its role in cell differentiation.

Recent studies on normal and pathological skin have suggested a role of the c-fos proto-oncogene in keratinocyte differentiation. To further elucidate this question we have used keratinocyte and skin culture models to study in vitro regulation of c-fos expression and attempted to correlate it with the keratinocyte maturation process. Our results show that c-fos expression is prolonged in keratinocyte monolayers both at the mRNA and protein level. Extracellular calcium which stimulate keratinocyte differentiation is able to induce c-fos expression in the presence of growth factors. However this c-fos expression cannot be maintained by these factors as seen in normal human skin in vivo. Conversely, spontaneous expression of c-fos can be seen in reconstituted skin when the neo-epidermis has completed its differentiation. All these data strongly support a role of c-fos as a switch between the early and late phases of keratinocyte differentiation allowing them to be definitively committed to their elimination process. Additionally, a differential regulation of c-fos seems to exist between keratinocyte culture and reconstituted epidermis, suggesting that tissular and serum factors are involved in the prolonged c-fos expression observed in human epidermis.

Animals↗
PubMed1993

Microsporidia infection in patients with the human immunodeficiency virus and unexplained cholangitis.

BACKGROUND: Cholangitis in patients with the acquired immunodeficiency syndrome (AIDS) is usually associated with opportunistic infections by cryptosporidium species or cytomegalovirus, but in about a third of cases no opportunistic agent is identified. We suspected some of these cases of biliary disease might be explained by infection with the microsporidia species Enterocytozoon bieneusi, an obligate intracellular protozoan that causes chronic diarrhea in patients infected with the human immunodeficiency virus (HIV). METHODS: We studied eight HIV-infected homosexual men (in either group IV of the classification of the Centers for Disease Control and Prevention or group II, with a CD4 cell count of < or = 10 per cubic millimeter) who were referred because of cholangitis for which no causative agent had been found by standard tests. All the patients underwent abdominal ultrasonography and endoscopic ultrasonography or endoscopic retrograde cholangiopancreatography with collection of bile from the common bile duct. One patient had transhepatic biliary catheterization, and two others had cholecystectomy. Bile samples, duodenal- and liver-biopsy specimens, and gallbladder tissue were studied by light and electron microscopy. RESULTS: All eight patients with unexplained AIDS-related cholangitis had biliary microsporidosis. Intraepithelial E. bieneusi spores (1 to 2 microns) and supranuclear plasmodia (3 to 8 microns) were identified in the six duodenal-biopsy specimens. May-Grünwald-Giemsa staining of bile samples revealed free forms of microsporidia in all eight patients, and the presence of E. bieneusi was confirmed by electron microscopy. E. bieneusi was also identified in ductal biliary cells on a liver biopsy, in one common-bile-duct smear, and in gallbladder epithelium (in two patients). Four patients were found to have associated but previously undetected biliary or duodenal cryptosporidiosis, whereas another had biliary infection associated with cytomegalovirus. CONCLUSIONS: Infection of the biliary tract with E. bieneusi is associated with and may be a cause of AIDS-related cholangitis.

AIDS-Related Opportunistic Infections↗
PubMed1993

Two high-voltage-activated, dihydropyridine-sensitive Ca2+ channel currents with distinct electrophysiological and pharmacological properties in cultured rat aortic myocytes.

In smooth muscle cells, essentially two distinct types of voltage-gated Ca2+ channels have been shown, on the basis of their distinct electrophysiological and pharmacological properties, to coexist. Here we report that, in addition to a dihydropyridine (DHP)-sensitive, low-voltage-activated Ba2+ current (IBa,LVA), two types of high-voltage-activated Ba2+ currents with distinct waveforms were recorded in whole-cell clamped aortic myocytes; these were referred to as IBa,HVA1 and IBa,HVA2. They were investigated in cells where no IBa,LVA was detectable. IBa,HVA1 had a slow, monoexponential decay. In contrast, the decay of IBa,HVA2 was much faster and biexponential. In addition, IBa,HVA2 had more negative ranges of activation and steady-state inactivation than IBa,HVA1 and was more sensitive to the DHP antagonist nicardipine (concentrations for half maximum inhibition 0.2 microM and 2 microM, respectively). When using the physiological ion Ca2+ as the charge carrier, the decay of HVA1 currents was not altered, whereas both time constants of HVA2 current decay were accelerated five-fold. Moreover, permeability ratios (ICa/IBa) were also significantly different (0.2 and 0.6 for HVA1 and HVA2 respectively). IBa,HVA1 and IBa,HVA2 are consistent either with the existence and activation of two functionally distinct subtypes of the so-called "DHP-sensitive L-type" Ca2+ channel or with different gating behaviours of a single type of channel. Potentially, they may serve distinct biological functions and constitute distinct targets for neurotransmitters and drugs.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Primary infection of kids with Teladorsagia circumcincta: susceptibility and blood constituents.

Fourteen male cross-bred Alpine x Saanen kids were infected with Teladorsagia circumcincta and four were used as controls. Three different levels of susceptibility to infection were apparent: resistant to infection and resilient to its adverse effects; intermediate (poorly resistant and poorly resilient); susceptible and relatively resilient. In the susceptible kids the establishment rate of infective larvae was twice as large and the nematode egg output five times greater during Weeks 4-8 after infection than in resistant kids. Susceptible kids harboured larger females with higher numbers of eggs in utero; the proportion of Teladorsagia trifurcata was higher in susceptible than in resistant kids. The blood constituents were significantly modified in infected compared with control animals: a lower number of leucocytes (particularly lymphocytes and basophils) and a higher complement activity were recorded in the latter. Compared with resistant kids, susceptible kids had higher counts of leucocytes, basophils and lower lymphocyte levels, less depleted complement pathway activity, higher pepsinogen values and lower levels of albumin and glucose.

Analysis of Variance↗
PubMed1993

Characterization of the skin in vivo by high resolution magnetic resonance imaging: water behavior and age-related effects.

The age-related modifications of magnetic resonance imaging parameters in the skin have been studied in vivo. Modification of these parameters should provide important information about alterations in water structure and content in aged skin. Relaxation times, T1 and T2, and relative proton density, which corresponds to the mobile water proton fraction of tissues, have been measured on people under age 40 and over 70 on a sun-protected area. Results have confirmed in vivo skin layer differentiation through relaxation times performed in a previous study. Moreover, relative proton density quantification has shown that epidermal mobile water is at least twice as abundant as dermal mobile water. No significant age-related T1 and T2 modification could be established, basically because of a large dispersion of values. The main result concerns the upper part of dermis (about 200 microns in thickness) which contains significantly more mobile water protons in chronologic aged skin than in young adult skin. This increase has been related both to an increase of total water content in dermis with age and to an apparent decrease of collagen and proteoglycan content. Associated with alterations of their structure, this decrease reduces macromolecular-water interaction sites. This finding has to be compared with ultrasound evaluation of aged skin, which is characterized by modifications of the echogenicity, related to collagen bundles size and density, in the outer part of dermis, too. Both of the imaging techniques tend to consider the outer part of dermis as one of the privileged sites of skin aging.

Adult↗
PubMed1993

Interconversion between distinct gating pathways of the high threshold calcium channel in rat ventricular myocytes.

1. High-voltage-activated Ca2+ current (ICa) waveforms in adult rat ventricular myocytes comprise two components, referred to here as ICa(fc) and ICa(sc) to denote the fast and slow components, respectively, of ICa decay. At all test potentials, the two time constants of ICa decay, tau fc and tau sc, differ by approximately an order of magnitude. Neither tau fc nor tau sc varies appreciably with test potential, however, suggesting that current inactivation is not markedly voltage dependent. 2. Current activation at all test potentials follows a sigmoidal time course and is best described by a power function with n = 4. Deactivation of the currents, examined following variable length depolarizations to various test potentials, however, follows a single exponential time course. In addition, the kinetics of activation and deactivation of ICa(fc) and ICa(sc) are indistinguishable. 3. Although both begin to activate at approximately -30 mV, the voltage dependences of ICa(fc) and ICa(sc) are distinct: ICa(fc) peaks at -10 mV and ICa(sc) peaks at +10 mV. 4. The relative amplitudes of ICa(fc) and ICa(sc) vary with the holding potential from which the currents are evoked and with the frequency of current activation: hyperpolarized holding potentials and low stimulation frequencies reveal preferential activation of ICa(fc), whereas depolarized holding potentials and high stimulation frequencies potentiate ICa(sc). In addition, the observed voltage- and frequency-dependent changes in ICa(fc) and ICa(sc) amplitudes are reciprocal. 5. The apparent voltage dependences of steady-state inactivation of ICa(fc) and ICa(sc) are also distinct. ICa(fc) is reduced to approximately 50% of its maximal amplitude at -45 mV, whereas ICa(sc) is approximately 50% inactivated at -30 mV. 6. Recovery of ICa(peak) from steady-state inactivation follows a complex time course. Following inactivation at -10 mV, ICa(peak) recovers at -90 mV to its maximal value over a biexponential time course; ICa(peak) then decreases over the next several seconds to a steady-state level. 7. The time course of recovery from steady-state inactivation of ICa(fc) at -90 mV is best described by the sum of two exponentials; the two time constants of recovery differ by approximately a factor of 25. ICa(sc), in contrast, recovers rapidly and over a single exponential time course to its maximal value. When the recovery time at -90 mV is increased, however, ICa(sc) amplitude decreases slowly and over a single exponential time course to a steady-state level.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Repriming of L-type calcium currents revealed during early whole-cell patch-clamp recordings in rat ventricular cells.

1. The establishment of the whole-cell patch-clamp recording configuration (WCR) revealed a type of inhibition to which L-type Ca2+ channels were subject in static rat ventricular myocytes before obtaining the WCR. 2. Immediately after membrane disruption (< 10 s), the Ca2+ current (ICa) was absent but gradually increased in amplitude to reach its final waveform (amplitude and kinetics) 2-3 min after the WCR was reached. 3. Three distinct phases (P) were identified. First, no inward but an outward current, blocked (1-2 min) by Cs+ dialysing from the patch pipette (P1), was recorded. Second, overlapping with (P1), ICa increased dramatically to reach a maximum peak amplitude within 2-3 min (P2). Concomitantly, its rate of decay, initially monoexponential and slow, became biexponential owing to the appearance of a fast component of inactivation (P3). Complete interconversion between slow and fast components sometimes occurred. 4. Changes in current waveform were not related to voltage loss or series resistance variation, and suppression of an outward current (P1) was unlikely to account for P2 and P3. 5. The run-up of ICa was independent of the nature of the permeating ions, the membrane holding potential, depolarization, rate of stimulation, the intracellular Ca2+, ATP, Mg2+, Cs+ and the pH of the pipette solution. Since large Ca2+ currents were recorded using the perforated patch technique, the run-up of ICa is not explained by the wash-out of an inhibitory endogenous macromolecule during cell-pipette exchanges. 6. Pharmacological manipulations, including the use of Ca(2+)-Ba(2+)-EGTA and exposure of the cells to isoprenaline and/or Bay K 8644 prior to recording, did not alter the mechanism primarily responsible for build-up. Unrepriming of channel activity was required before these modulations could be effective. 7. Currents could however be instantly augmented when cells were extracellularly superfused during the run-up step. The wash-out of an inhibitory agent originating in the cell itself (such as H+, NH4+ and lactate) and accumulating in the extracellular microenvironment of the cells seems unlikely. Rather, we suggest that pressure-induced mechanostimulation may be involved in the restoration of Ca2+ channel activity.

Animals↗
PubMed1992

[Meningeal melanocytoma or multiple pigmented meningioma of the spinal canal. Report of a case. Review of the literature].

In a 64-year-old male with pain and weakness of the right lower limb, investigations disclosed a cervical tumor, several dorsal tumors, and tumoral infiltration of the lumbosacral area. Histological and, above all, immunohistochemical and ultrastructural features were suggestive of meningeal melanocytoma. Before the use of immunohistochemical and electron microscopy techniques, meningeal melanocytoma was designated by the term pigmented meningioma because its histological features bear some resemblance to those of meningioma. However, only a few cases of meningeal melanocytoma have been documented by immunohistochemistry and electron microscopy. Previously reported patients with meningeal melanocytoma had solitary tumors. In contrast, a review of the literature showed that multiple intraspinal or intraspinal and intracranial meningiomas are not exceptional, although meningiomatous infiltration is considerably less frequent. Treatment of such cases rests on surgery, radiotherapy, and chemoimmunotherapy.

Combined Modality Therapy↗
PubMed1992

Differential expression of voltage-gated Ca(2+)-currents in cultivated aortic myocytes.

The expression of different types of Ca(2+)-channels was studied using the whole-cell patch-clamp technique in cultured rat aortic smooth-muscle myocytes. Ca(2+)-currents were identified as either low- or high voltage-activated (ICa,LVA or ICa,HVA, respectively) based on their distinct voltage-dependences of activation and inactivation, decay kinetics using Ba2+ as the charge carrier and sensitivity to dihydropyridines. The heterogeneity in the functional expression of the two types of Ca(2+)-channels in the cultured myocytes delineated four distinct phenotypes; (i), cells exhibiting only LVA currents; (ii), cells exhibiting only HVA currents; (iii), cells exhibiting both LVA and HVA currents and (iv), cells exhibiting no current. The myocytes exclusively expressed HVA currents both during the first five days in primary culture and after the cells had reached confluence (> 15 days). In contrast, LVA currents were expressed transiently between 5 and 15 days, during which time the cells were proliferating and had transient loss of contractility. Thus, both LVA and HVA Ca(2+)-current types contribute to Ca(2+)-signalling in cultured rat aortic myocytes. However, the differential expression of the two Ca2+ current types associated with differences in contractile and proliferative phenotypes suggest that they serve distinct cellular functions. Our results are consistent with the idea that LVA current expression is important for cell proliferation.

Animals↗