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S Peyrol

Publications and source records attributed to S Peyrol.

At least 19 recordsLinked to original sources

[Use of talc and sarcoidosis - pathogenic role of cutaneous talc exposure in sarcoidosis].

INTRODUCTION: We report on two patients with sarcoidosis with disseminated nodes, who used talc on irritated cutaneous areas. CASE REPORT: A histologic examination with intense polarised light showed up cristalline bi-refringent particles within vessels in contact with granulomatous areas. Microdissection followed by an electronic microscopy study and microanalysis was realised. In situ microanalysis allowed us to identify bi-refringent particles with a size of roughly 0.25microm as silica or silicate coming possibly from talc. We consequently studied a brand name talc. The diffraction spectrum showed that this product not only contained talc but also chlorite and quartz. Electron microscopy examination showed particles of all sizes even smaller than 0.25microm. These infra-microscopic particles, visible in a vessel only when agglomerated, could be invisible under optic microscopy (resolution: roughly 0.5microm) inside the granuloma even though they are responsible for it. Moreover, at this level of size of particles, they may escape mineralogic analyses which use methods involving the destruction of organic material, the mineral residue collecting on cellulose filter with a diameter generally of 0.45microm. CONCLUSION: Two recent epidemiologic studies confirm the possible role of mineral exposure in sarcoidosis. Some sarcoidosis could be caused by mineral overload on genetically predisposed patients. Some cases could be related to mineral powder application. Among different types of mineral exposure, applications of cosmetic products may induce disseminated granulomatous reaction on genetically predisposed patients. Such applications have to be considered in epidemiologic studies.

Adult↗

Effect of a combination of clevudine and emtricitabine with adenovirus-mediated delivery of gamma interferon in the woodchuck model of hepatitis B virus infection.

Our aim was to evaluate the antiviral effect of a combination of two nucleoside reverse transcriptase inhibitors, emtricitabine (FTC) and clevudine (L-FMAU), with the addition of an adenovirus-driven delivery of recombinant gamma interferon (IFN-gamma) in the woodchuck model of hepatitis B virus infection. Six woodchuck hepatitis virus (WHV)-infected woodchucks received L-FMAU (10 mg/kg) plus FTC (30 mg/kg) intraperitoneally for 8 weeks; six other animals received in addition an intravenous injection of a recombinant adenovirus vector expressing woodchuck IFN-gamma (Ad-IFN) at weeks 4 and 8. In the control group, two animals received Ad-IFN alone, two received adenovirus vector expressing the green fluorescent protein reporter gene, and one remained untreated. In less than 2 weeks, all woodchucks that received L-FMAU plus FTC showed a rapid and marked inhibition of viral replication, with a 4-log(10) drop in serum WHV DNA. In two animals, viremia remained suppressed for several months after the end of treatment. Similarly, a dramatic decrease in intrahepatic replicative intermediates of viral DNA was observed in the L-FMAU/FTC-treated groups. The additional administration of Ad-IFN led to increased inflammation in the liver but did not enhance the antiviral effect of the L-FMAU/FTC combination. In conclusion, therapies combining L-FMAU and FTC in WHV-infected woodchucks resulted in a potent and sustained antihepadnaviral effect both in the liver and in the blood circulation. However, no extra benefit of adding IFN-gamma gene transduction to the L-FMAU/FTC combination could be detected.

Adenoviridae↗

In vitro expression of fas and CD40 and induction of apoptosis in human cystic fibrosis airway epithelial cells.

Cystic fibrosis is characterized by a damaged airway epithelium with inflammation and chronic infection. The aim of this study was to investigate the process of apoptosis in this disease. To evaluate the effects of interferon gamma and the Fas apoptotic pathway on cystic fibrosis airway epithelial cells, we used immortalized cystic fibrosis (CFT-1 and CFT-2) and normal (NT-1) human tracheal epithelial cell lines. Cell death was determined usingannexin-V/propidium iodide labelling and electron microscopy. In vitro expression of Fas and CD40 surface antigens was analysed by immunofluorescence staining and flow cytometry. Normal and cystic fibrosis cells constitutively express these antigens. CD40, but not Fas expression, was upregulated by interferon gamma. Treatment of interferon gamma-stimulated cells with anti-Fas resulted in apoptosis for about 80% of CFT-2 (homozygous for delta F508 deletion) cells and for 35-40% of CFT-1 (heterozygous) or normal cells. Our results suggest that Fas may mediate apoptosis in cystic fibrosis airway epithelium.

Antibodies, Monoclonal↗

Constrictive bronchiolitis obliterans. Characterisation of fibrogenesis and lysyl oxidase expression patterns.

The process leading to irreversible fibrotic constriction of the bronchioles was studied in two cases of bronchiolitis obliterans (BO) after bone marrow transplantation. Because lysyl oxidase (LOX) is the main collagen cross-linking enzyme that might account for irreversible fibrosis, its expression was studied together with expression of extracellular matrix (ECM) proteins. Characteristic types of lesions could be distinguished on the basis of histological and immunohistological criteria. An inflammatory stage was characterised by infiltration restricted to the bronchioles by lymphocytes and dendritic cells. A fibro-inflammatory stage was characterised by the coexistence of a persistent immune cellular lesion pattern with further focal modelling of a sub-epithelial neo-synthesised connective matrix. LOX expression was observed at the tips of intra-luminal fibrotic protrusions, together with tenascin and cellular fibronectin. A fibrotic stage was characterised by dense ECM deposits spreading throughout the peri-bronchiolar connective tissue, resulting in bronchiole obliteration and final disappearance. In contrast to reversible cases of fibrosis, persistence of long-term LOX expression reflecting continuing fibrosing activity might account for the irreversible status of BO. Our two cases illustrated that, at inflammatory and fibro-inflammatory stages, BO may be stabilised by immunosuppressive treatment, while the persistence of LOX expression in the fibrotic stage might correspond to a disease that becomes irreversible and fatal.

Adult↗

Antiviral activity of beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine in woodchucks chronically infected with woodchuck hepatitis virus.

The L-nucleoside analog beta-L-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine (beta-L-Fd4C) was first shown to exhibit potent activity against hepatitis B virus (HBV) in tissue culture and then to significantly inhibit viral spread during acute infection in the duck HBV model (F. Le Guerhier et al., Antimicrob. Agents Chemother. 44:111-122, 2000). We have therefore examined its antiviral activity in a mammalian model of chronic HBV infection, the woodchuck chronically infected with woodchuck hepatitis virus (WHV). Side-by-side comparison of beta-L-Fd4C and lamivudine administered intraperitoneally during short-term and long-term protocols demonstrated a more profound inhibition of viremia in beta-L-Fd4C-treated groups. Moreover, beta-L-Fd4C induced a marked inhibition of intrahepatic viral DNA synthesis compared with that induced by lamivudine. Nevertheless, covalently closed circular (CCC) DNA persistence explained the lack of clearance of infected hepatocytes expressing viral antigens and the relapse of WHV replication after drug withdrawal. Liver histology showed a decrease in the inflammatory activity of chronic hepatitis in woodchucks receiving beta-L-Fd4C. An electron microscopy study showed the absence of ultrastructural changes of hepatic mitochondria, biliary canaliculi, and bile ducts. However, a loss of weight was observed in all animals, whatever the treatment, as was a transient skin pigmentation in all woodchucks during beta-L-Fd4C treatment. There was no evidence that lamivudine or beta-L-Fd4C could prevent the development of hepatocellular carcinoma with the protocols used. These results indicate that beta-L-Fd4C exhibits a more potent antiviral effect than lamivudine in the WHV model but was not able to eradicate CCC DNA and infected cells from the liver at the dosage and with the protocol used.

Animals↗

Early activation of hepatic stellate cells and perisinusoidal extracellular matrix changes during ex vivo pig liver perfusion.

In previous works, we observed during liver transplantation procedure, the early activation of hepatic stellate cells (HSC) which acquire alpha-smooth muscle (SM) actin expression. In this study, we evaluated changes in HSC and in perisinusoidal extracellular matrix during ex vivo pig liver perfusion. Under general anesthesia, pig livers were flushed and removed, and then perfused ex vivo for 6 h with homologous blood. Liver biopsies were taken before and after washout, at 5 min perfusion, and then hourly. Tissues were processed for immunohistochemistry, immunofluorescence, confocal microscopy, in situ hybridization and electron microscopy. Before and after liver washout, alpha-SM actin was present in vessel walls but in very few lobular HSC. After 1 h perfusion, a strong reactivity for alpha-SM actin was present in HSC, particularly along dilated sinusoids. At the ultrastructural level, numerous microfilament bundles appeared in HSC cytoplasmic processes. During perfusion, type I and type IV collagens, type III procollagen, and fibronectin acquired a looser organisation in relation with the enlargement of perisinusoidal spaces; laminin appeared in perisinusoidal spaces around portal areas and fibrillin deposits increased. In situ hybridization studies showed an increase of the type I procollagen mRNA expression mainly in portal tracts and septa. Ex vivo liver perfusion induces: 1) an early activation of HSC which acquire the expression of alpha-SM actin, and 2) significant changes in the perisinusoidal extracellular matrix. These results are compatible with the view that HSC function as liver specific pericytes participating in the regulation of sinusoidal blood pressure.

Actin Cytoskeleton↗

Keratinocytes influence the maturation and organization of the elastin network in a skin equivalent.

Elastic fibers form a complex network that contributes to the elasticity of connective tissues. Alterations in the elastic fiber network are involved in several disease affecting organs in which compliance of the connective tissue is essential: skin, main vasculature, lung, joints, muscle, and ligament. The aim of our work was to study the deposition, maturation, and organization of elastic fiber components in a dermal equivalent model consisting of collagen-GAG-chitosan seeded with fibroblasts. The influence of keratinocytes was studied in parallel, thus constituting a skin equivalent model. These models were examined by transmission electron microscopy (TEM) and by immunohistochemistry to determine the staining patterns of fibrillin-1 and elastin proteins representative of the microfibrillar framework and of the elastic fibers, respectively. After 2 mo of fibroblast culture in the dermal equivalent, elastin was undetectable, whereas fibrillin-1 staining was weak and microfibrils were infrequently observed by TEM. In the skin equivalent, fibrillin-1 and elastin were detected by immunostaining 15 d after epidermization and TEM revealed the typical structure and organization of the elastic network in the dermis, with elastin deposition on the microfibrillar scaffold. This in vitro skin equivalent model is to our knowledge the first in which elastic fibers have been detected, thus demonstrating the influence of keratinocytes on the maturation and organization of the elastic network.

Antibodies↗

Gastric helicobacters in cats.

The types of helicobacter which are found in the stomachs of carnivorous pets, especially cats, have been traditionally referred to as 'gastric helicobacter-like organisms' (GHLOs). These are microaerophilic, Gram-negative, spiral bacteria with multiple terminal flagellae and are endowed with high-level urease activity which allows them to survive in an acidic environment. Certain species have one or more periplasmic fibrils. The two GHLOs most commonly found in cats are Helicobacter felis and a species related to H heilmannii which was recently cultured from dogs. All phenotypic and genotypic (16S RNA gene sequences) evidence suggests that both of these bacteria belong in the genus Helicobacter. Whether or not helicobacters can be transmitted to humans from carnivorous pets is controversial but the recent discovery of H pylori -infected cats may be evidence of an animal reservoir for this pathogen. Although the role of H pylori in inducing antral gastritis and perpetuating pyloric ulcers in humans is well established, whether or not Helicobacter spp are causally involved in any feline gastric inflammatory conditions is unknown.

Animals↗

Selective expression of lysyl oxidase (LOX) in the stromal reactions of broncho-pulmonary carcinomas.

Lysyl oxidase (LOX) is the extracellular enzyme that initiates the main pathway of collagen and elastin cross-linking. LOX has also been correlated with the ras recision gene, a putative tumour suppressor isolated from revertants of ras-transformed fibroblasts. The present study investigates the potential correlation of LOX-dependent matrix protein cross-linking in the stromal reaction of lung carcinomas, with reference to the architecture of the main stromal reactions accompanying the neoplastic breast tissues. A strong LOX expression was associated with the hypertrophic scar-like stromal reaction found at the front of tumour progression in squamous carcinomas, adenocarcinomas, large cell carcinomas, or at sites of initial extense in bronchiolo-alveolar carcinomas. In contrast, little or no LOX expression was found within the stromal reaction of invasive carcinomas, small cell carcinomas, and neuro-endocrine carcinomas. The significance of LOX expression and of the stromal reaction are discussed, in light of data that associate LOX expression with tumours displaying a rather good prognosis.

Adenocarcinoma↗

Coexpression of the lysyl oxidase-like gene (LOXL) and the gene encoding type III procollagen in induced liver fibrosis.

We have isolated a mouse lysyl oxidase-like (LOXL) cDNA from a mouse embryo cDNA library and used this cDNA to measure changes in steady state levels of LOXL mRNA during the development of carbon tetrachloride-induced liver fibrosis in adult mice. These results revealed the coincident appearance of increased steady state levels of LOXL mRNA and type III procollagen mRNA early in the development of liver fibrosis. In contrast, steady state levels of lysyl oxidase mRNA increased throughout the onset of hepatic fibrosis and appeared in parallel with the increased steady state levels of pro-alphaI (I) collagen mRNA. These findings suggest that the LOXL protein (possibly an isoform of lysyl oxidase) is involved in the development of lysine-derived cross-links in collagenous substrates. Moreover, the substrate specificity of the LOXL protein may be different to that of lysyl oxidase and this difference may be collagen-type specific.

Animals↗

Mechanical forces induce scar remodeling. Study in non-pressure-treated versus pressure-treated hypertrophic scars.

Reparative process of second and third degree burns usually results in hypertrophic scar formation that can be treated by pressure. Although this method is efficient, its mechanisms of action are not known. In this work, we have studied the histological organization of hypertrophic scars submitted to pressure. Skin biopsies were performed 2 to 7 months after the onset of treatment in two adjacent regions of the scar, non-pressure- or pressure-treated and analyzed by immunohistochemistry and transmission electron microscopy for extracellular matrix organization and cellular morphology. In non-pressure-treated regions, fibrillin deposits did not present the classical candelabra-like pattern under epidermis and were reduced in dermis; in pressure-treated regions the amount was increased compared to non-pressure-treated regions but the organization was still disturbed. In non-pressure-treated regions, elastin was present in patch deposits; in pressure-treated regions elastin formed fibers, smaller than in normal dermis. Tenascin was present in the whole dermis in non-pressure-treated regions, whereas in pressure-treated regions it was observed only under epidermis and around vessels, as in normal skin. alpha-Smooth muscle actin-expressing myofibroblasts were absent in normal skin, present in large amounts in non-pressure-treated regions, and almost absent in pressure-treated regions. The disturbed ultrastructural organization of dermal-epidermal junction observed in non-pressure-treated regions disappeared after pressure therapy; typical features of apoptosis in fibroblastic cells and morphological aspects of collagen degradation were observed in pressure-treated regions. Our results show that, in hypertrophic scars, pressure therapy restores in part the extracellular matrix organization observed in normal scar and induces the disappearance of alpha-smooth muscle actin-expressing myofibroblasts, probably by apoptosis. We suggest that the pressure acts by accelerating the remission phase of the postburn reparative process.

Adolescent↗

CD40 expression by human bronchial epithelial cells.

CD40 is a 50-kDa protein expressed on B cells, dendritic cells, monocytes and epithelial cells, but the distribution of CD40 expression in humans is not completely known. It binds to a ligand (CD40L) which is expressed essentially on activated T cells. The interaction between CD40 and CD40L plays important roles in immune responses. CD40 expression was investigated on bronchial tissues and human bronchial cell lines using immunohistochemistry, immunofluorescence staining and analysis with a cytometer, respectively. Constitutive CD40 expression, but not that of CD40L, was slightly detectable on normal human bronchial epithelial cells (HBEC) in situ and on an adult lung adenocarcinoma (SKLU1) cell line, while another cell line, a bronchial transformed SV40 cell line (WI26VA4), was negative for CD40. Among the various cytokines tested, only interferon (IFN)-gamma was found to induce CD40 expression on WI26VA4. Tumour necrosis factor (TNF)-alpha was the best cytokine able to up-regulate CD40 in SKLU1 cells. A combination of IFN-gamma and TNF-alpha was slightly more effective than the cytokine alone at up-regulating CD40 expression on both cell lines. We further investigated the functional consequences of CD40 ligation on both cell lines. These bronchial cells expressed CD40, HLADR and CD54 under basal conditions or when stimulated by cytokines. Stimulation through CD40 did not affect cell-surface-antigen expression on either cell line. The production of cytokines such as interleukin (IL)-6 and granulocyte macrophage-colony stimulating factor (GM-CSF) by HBEC has been described. SKLU1 and WI26VA4 cells released IL-6 and GM-CSF spontaneously. Whatever the case, CD40 engagement did not modulate spontaneous or TNF-alpha-induced production of these two cytokines. These data indicate for the first time that normal HBEC express CD40 in situ. Further investigations are required in order to determine the role of CD40 on normal HBEC.

Bronchi↗

The Saccharomyces cerevisiae Cdc14 phosphatase is implicated in the structural organization of the nucleolus.

Cdc14, a dual-specificity protein phosphatase, has been previously implicated in triggering exit from mitosis in the yeast Saccharomyces cerevisiae. Using immunofluorescence microscopy and immunogold labeling, we demonstrate that a functional HA-tagged version of the phosphatase Cdc14 localizes to the nucleolus. Moreover, Cdc14-HA co-localized with the nucleolar NOP2 and GAR1 proteins. By immunofluorescence, Cdc14-HA was found in the nucleolus during most of the mitotic cell cycle, except during anaphase-telophase when it redistributed along the mitotic spindle. While this work was in progress, the same pattern of Cdc14 localization was described by others (Visintin et al, Nature 398 (1999) 818). Constitutive overexpression of CDC14 was toxic and led to cell cycle arrest of cells, mainly in G1. This correlated with the appearance of abnormal nuclear structures. A genetic search for suppressors of the lethality associated with CDC14 overexpression identified YJL076W. Because overproduction of Yj1076w buffered the toxic effect of Cdc14 overproduction, this suggested that it might be a substrate of Cdc14. This has indeed been found to be the case by others who recently described Yj1076w/Netl as a nucleolar protein that physically associates with Cdc14 (Shou et al, Cell 97 (1999) 233). The present data confirm several recently uncovered aspects of the regulation of Cdc14 localization and activity and suggest that the level of expression of CDC14 influences the structural organization of the nucleolus.

Cell Cycle↗

Subepithelial fibrosis and degradation of the bronchial extracellular matrix in cystic fibrosis.

Cystic fibrosis is a genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator gene. Chronic inflammation and proteolysis lead to progressive damage of the bronchial wall. Extracellular matrix determines the structural organization and the mechanical properties of lung airways. It was thus examined in nine patients with cystic fibrosis (six bronchial biopsies and three lobectomies) in order to assess its level of alteration. The submucosal changes in matrix protein distribution were analyzed by immunochemistry and electron microscopy: the subepithelial basal lamina was thinned; an acellular collagen fiber layer composed of interstitial collagens (types I and III) subtended by tenascin and devoid of elastin-associated microfibrils was deposited beneath the basal lamina; this dense fibrous deposit generally formed a thick layer and could extend into the bronchial wall; the bronchial elastic framework lost arborescent distribution and appeared slender, packed, or lacunar; ultrastructural observation gave evidence for elastic and collagenic fiber lysis. Proteolytic activity is probably the major cause of matrix degradation. Fibrosis appears as a repair process rather than as an active fibrogenesis. The reversibility of extracellular matrix alterations is an important challenge and various interventions such as anti-inflammatory treatments can be targeted to halt or reverse this degradation process.

Adolescent↗

Lysyl oxidase-like protein localizes to sites of de novo fibrinogenesis in fibrosis and in the early stromal reaction of ductal breast carcinomas.

Lysyl oxidase (LO) initiates the first step in the crosslinking of collagens and elastin and has also been shown to function as a tumor suppressor. The purpose of the present work was to determine whether the products of a newly described LO-like gene (LOXL) that encodes a close homolog of LO, the LO-like (LOL) protein, is associated with extracellular matrix remodeling during fibrotic disorders. Specific antibody against LOL identified proteins of approximately 30, 42, 52 and 68 kd in various cells and in bovine aorta. These proteins were immunochemically distinct from the recombinant LO expressed by fibroblasts and from the bovine aorta LO. The LO gene (LOX) and LOXL were transiently up-regulated at early stages of liver granuloma development in Schistosoma mansoni-infected mice, although the peak of LOL mRNA synthesis preceded that of LO. LOL protein and LO were colocalized at sites of fibrogenesis in human lung fibrosis and in the stromal reaction of bronchiolo-alveolar carcinomas and of in situ ductal breast tumors. In conclusion, the LOL protein was identified as a secreted protein and localized in the extracellular matrix in active fibrotic diseases and in the early stromal reaction of breast cancer.

Adenocarcinoma, Bronchiolo-Alveolar↗

Differential pathogenic effect of two Helicobacter-like organisms in dog gastric mucosa.

Two forms of Helicobacter were detected in the gastric mucosa of twelve healthy beagle dogs. According to ultrastructural criteria they could be classified as Helicobacter bizzozeronii-like and Helicobacter felis-like species. In five animals, the light fundic load of Helicobacter bizzozeronii-like did not affect the integrity of the glandular epithelium. In three animals, the heavy bacterial load extended in the lumens of antral glands and coincided with increased intraepithelial lymphoid infiltrate. The heavy bacterial load observed in 4 animals was mixed (Helicobacter bizzozeronii-like and Helicobacter felis-like), fundic and antral, luminal and intracellular. Adherence of Helicobacter felis-like to epithelial cells and intracellular penetration were responsible for focal necrosis, and glandular atrophy might be observed. Helicobacter bizzozeronii-like thus appeared non pathogenic in beagle dogs, even when the heavy bacterial load extended to the antrum. By contrast, Helicobacter felis-like showed a constant pathogenic effect linked to its properties of adhesion and penetration into epithelial cells. A wider comparative study in humans and domestic carnivorous will determine if the latter may play a role of reservoir-host for pathogenic bacteria.

Animals↗

[Helicobacter infections of man and of domestic carnivores: comparative data].

The role of Helicobacter pylori in generating of the chronic gastritis and in the maintaining of the gastroduodenal ulcerous disease, has been a major medical discovery of these past years in human gastroenterology. More recently in Man, studies have showed that the gastric tumours (adenocarcinoma, lymphoma) are epidemiologically associated with the H. pylori infection. Although the H. pylori infection is the one of the most frequent in the word, the epidemiologic and ecologic aspects of this infections are still not very well known. Thanks to phylogenic studies using the new molecular biology techniques and to fundamental experimental studies, we know more about helicobacteria in domestic carnivores as well as their morphologic characteristic, their taxonomia and more importantly details concerning their ecological niche. Few clinical studies have been made to this day, but the ones that have been undertaken are interesting in confirming the extensive prevalence of Helicobacter infections in domestic carnivores and in underlining their role in the genesis of the inflammatory gastropathies observed in these species. Recent observations have demonstrated the ubiquitous character of these helicobacteria by showing their presence in the stomach of man, dogs and cats. This ubiquitous character has led some scientists to consider the potential zoonotic risk of the human infection by Helicobacter heilmannii, felis or pylori. Finally, the Helicobacter infection of animals seems to be an interesting model not only in the study of the affections caused by these bacteria, but also in the elaboration of a future vaccine against the H. pylori infection in man.

Animals↗