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Biomedical subjects

N Roche

Publications and source records attributed to N Roche.

At least 55 records · Page 3Linked to original sources
PubMed2001

Helicobacter pylori-binding gangliosides of human gastric adenocarcinoma.

Acidic and neutral glycosphingolipids were isolated from a human gastric adenocarcinoma, and binding of Helicobacter pylori to the isolated glycosphingolipids was assessed using the chromatogram binding assay. The isolated glycosphingolipids were characterized using fast atom bombardment mass spectrometry and by binding of antibodies and lectins. The predominating neutral glycosphingolipids were found to migrate in the di- to tetraglycosylceramide regions as revealed by anisaldehyde staining and detection with lectins. No binding of H. pylori to these compounds was obtained. The most abundant acidic glycosphingolipids, migrating as the GM3 ganglioside and sialyl-neolactotetraosylceramide, were not recognized by the bacteria. Instead, H. pylori selectively interacted with slow-migrating, low abundant gangliosides not detected by anisaldehyde staining. Binding-active gangliosides were isolated and characterized by mass spectrometry, proton nuclear magnetic resonance, and lectin binding as sialyl-neolactohexaosylceramide (NeuAcalpha3Galbeta4GlcNAcbeta3Galbeta4GlcNAcbeta3Galbeta4Glcbeta1Cer) and sialyl-neolactooctaosylceramide (NeuAcalpha3Galbeta4GlcNAcbeta3Galbeta4GlcNAcbeta3Galbeta4GlcNAcbeta3Galbeta4Glcbeta1Cer).

Adenocarcinoma↗
PubMed2001

Glycosphingolipid binding specificities of rotavirus: identification of a sialic acid-binding epitope.

The glycosphingolipid binding specificities of neuraminidase-sensitive (simian SA11 and bovine NCDV) and neuraminidase-insensitive (bovine UK) rotavirus strains were investigated using the thin-layer chromatogram binding assay. Both triple-layered and double-layered viral particles of SA11, NCDV, and UK bound to nonacid glycosphingolipids, including gangliotetraosylceramide (GA1; also called asialo-GM1) and gangliotriaosylceramide (GA2; also called asialo-GM2). Binding to gangliosides was observed with triple-layered particles but not with double-layered particles. The neuraminidase-sensitive and neuraminidase-insensitive rotavirus strains showed distinct ganglioside binding specificities. All three strains bound to sialylneolactotetraosylceramide and GM2 and GD1a gangliosides. However, NeuAc-GM3 and the GM1 ganglioside were recognized by rotavirus strain UK but not by strains SA11 and NCDV. Conversely, NeuGc-GM3 was bound by rotaviruses SA11 and NCDV but not by rotavirus UK. Thus, neuraminidase-sensitive strains bind to external sialic acid residues in gangliosides, while neuraminidase-insensitive strains recognize gangliosides with internal sialic acids, which are resistant to neuraminidase treatment. By testing a panel of gangliosides with triple-layered particles of SA11 and NCDV, the terminal sequence sialyl-galactose (NeuGc/NeuAcalpha3-Galbeta) was identified as the minimal structural element required for the binding of these strains. The binding of triple-layered particles of SA11 and NCDV to NeuGc-GM3, but not to NeuAc-GM3, suggested that the sequence NeuGcalpha3Galbeta is preferred to NeuAcalpha3Galbeta. Further dissection of this binding epitope showed that the carboxyl group and glycerol side chain of sialic acid played an important role in the binding of such triple-layered particles.

Animals↗
PubMed2001

Guidelines versus clinical practice in the treatment of chronic obstructive pulmonary disease.

The main purpose of this study was to assess whether pharmacological treatments prescribed by respiratory physicians to patients with chronic obstructive pulmonary disease (COPD) were consistent with the guidelines. The treatments prescribed by respiratory physicians to 631 consecutive patients with COPD, compared to 879 asthmatics were prospectively recorded. All subjects underwent peak expiratory flow rate measurement, spirometry and assessment of recent evolution and dyspnoea (visual analogue and Medical Research Council scales). Patients with COPD received more treatments than asthmatics (mean+/-SD: 2.6+/-0.5 versus 2.2+/-0.4, p<0.0001). Treatments administered to patients with COPD were beta2-agonists in 78% (versus 94% in asthmatics), anticholinergic agents (AC) in 56% (versus 16% in asthma), methylxanthines in 31% (versus 15% in asthma) and inhaled corticosteroids in 76% (versus 85% in asthma). Intensity of treatment was influenced by disease severity for all treatments except AC. In conclusion, pharmacological treatment of chronic obstructive pulmonary disease by respiratory physicians is only partially consistent with current guidelines, with a high proportion of inhaled corticosteroid prescriptions and a relative under-use of anticholinergic agents; this most likely reflects the persistent uncertainties of physicians, and emphasizes that more efforts are required to improve implementation of chronic obstructive pulmonary disease guidelines and assess the efficacy and cost-effectiveness of recommended strategies.

Adult↗
PubMed2001

Automated monitoring of activated sludge in a pilot plant using image analysis.

An automated procedure for the characterisation by image analysis of the morphology of activated sludge has been used to monitor the biomass in a pilot wastewater treatment plant, in complement to the usual settleability (sludge volume index, settling velocity) and size distribution (by laser granulometry) measurements.

Automation↗
PubMed2000

Dermatophagoides pteronyssinus and bioelectric properties of airway epithelium: role of cysteine proteases.

Several epidemiological studies suggest that exposure to house dust mite allergens plays a role in the pathogenesis of asthma. Since many of these allergens exhibit enzymatic properties, they may damage the airway epithelium. To characterize the effects of low doses of Dermatophagoides pteronyssinus on the airway epithelium, the effect of D. pteronyssinus on the epithelial bioelectric properties of tracheal fragments of non-sensitized Lewis rats was studied, using Ussing-type chamber technique. The addition of a crude D. pteronyssinus extract containing 20 microg mL(-1) of Der pI allergen in the presence of 1.5 mM dithiothreitol (DTT, an activator of cysteine proteases), induced a progressive increase in bioelectrical conductance (+12.0+/-1.5%, n=12, p<0.005), an index of epithelial permeability, without affecting the short circuit current (which reflects active ion transports). The D. pteronyssinus-induced increase in epithelial conductance was related to the cysteine-protease activity of the allergen since it was not observed in the absence of DTT (n=12), and was completely suppressed in the presence of 10 nM E-64, a specific inhibitor of cysteine proteases (n=12). D. pteronyssinus-induced increase in epithelial conductance could be entirely attributed to an increase in the paracellular conductance (+11.2+/-1.2%, n=8, p<0.01). There was no electrophysiological evidence of rupture in epithelial continuity, and no cell detachment was observed on microscopic examination. In conclusion, the cysteine protease activity of crude Dermatophagoides pteronyssinus extract is able to increase the epithelial paracellular conductance of rat tracheal tissues, even at relatively low doses that do not induce cell detachment or cell death.

Animals↗
PubMed2000

Rationale for the choice of an aerosol delivery system.

The choice of an aerosol delivery system depends on numerous factors such as the drug itself, the characteristics of the aerosol generator, the patient and his or her disease, the physician, and the clinical setting, notably an emergency situation or not. Some rules always apply: an ultrasonic nebulizer should not be used to aerosolize a drug suspension; whenever possible, the same type of aerosol generator should be used for all inhaled medications received by a given patient; for outpatients, education is a major factor to ensure treatment efficacy. When the deposition of the aerosolized drug is aimed at the terminal respiratory units, nebulizers that generate micronic aerosols should be chosen. When the deposition of the aerosolized drug is aimed at the conducting airways, the metered dose inhaler (MDI) is the first choice. However, the MDI is often ill-used, notably in children and elderly people. Therefore, other inhalation devices have been developed: spacers, dry-powder inhalers, breath-actuated MDIs and, more recently, piezo-electric devices. They have been shown to increase lung deposition of drugs in poor coordinators but they all have limitations, which may affect their clinical efficacy. These limitations include the cumbersome dimensions of spacers, the dependency of lung deposition of dry powders on the inspiratory flow rate, the need for reformulation of breath-actuated or not MDIs with CFC-free gases. Nebulization of drugs should be considered only when no portable device is available for the considered drug, or in case of failure of other forms of aerosol administration.

Aerosols↗
PubMed2000

Balance of matrix metalloprotease-9 and tissue inhibitor of metalloprotease-1 from alveolar macrophages in cigarette smokers. Regulation by interleukin-10.

An imbalance between proteases and antiproteases may play a role in emphysema, which is characterized by increased degradation of extracellular matrix, and in airway remodeling in chronic bronchitis and asthma, in which there is increased collagen deposition. We assessed the effect of smoking on release of matrix metalloprotease-9 (MMP-9) and of its inhibitor, tissue inhibitor of metalloprotease-1 (TIMP-1), from alveolar macrophages, and determined the effects of proinflammatory (interleukin [IL]-1beta and lipopolysaccharide [LPS]) and antiinflammatory (IL-10) stimuli on the release of MMP-9 and TIMP-1. We performed bronchoalveolar lavage in 11 smokers and 11 nonsmokers, and cultured airway macrophages in the presence of control medium, IL-1beta, and LPS. Airway macrophages from smokers released greater amounts of MMP-9 and TIMP-1 at baseline and in response to IL-1beta and LPS than did those of nonsmokers. Airway macrophages from smokers produced more TNF-alpha and IL-10. IL-10 increased TIMP-1 release without modifying that of MMP-9, leading to a decrease in the MMP-9 to TIMP-1 ratio. Anti-IL-10 antibody had no effect on MMP-9 production induced by LPS. We conclude that the release of proteases and antiproteases by airway macrophages is increased in cigarette smokers, and can be regulated by exogenous IL-10.

Adult↗
PubMed1999

Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression.

Transgenic mice which express the simian virus 40 large T-antigen (Tag) under the regulatory control of the hormone responsive rat C3(1) gene develop unusual lesions of heterotopic bone growth associated with mixed tumor formation arising from eccrine sweat glands found only in the foot pads of mice, ischiocavernosus muscle adjacent to bulbourethral glands and occasionally the salivary and mammary glands. These lesions are very similar to mixed tumors arising in several types of human cancers. Based upon electron microscopic examination and immunocytochemical analyses of cellular differentiation markers, the mixed proliferative lesions in this transgenic mouse model begin with the Tag-induced proliferation of epithelial and myoepithelial cells. The proliferation of these two types of cells results in hyperplasia and adenomatous transformation of the epithelial component, whereas the proliferating myoepithelial cells undergo metaplasia to form chondrocytes which deposit extracellular matrix, including collagen fibers. Cartilage develops focally between areas of epithelial proliferation and subsequently ossifies through a process of endochondrial bone formation. The metaplasia of myoepithelial cells to chondrocytes appears to require the inductive interaction of factors produced by the closely associated proliferating epithelial cells, including members of the TGF-beta superfamily. We demonstrate that TGF-beta1 protein accumulates in the extracellular matrix of the lesions, whereas RNA in situ hybridization reveals that BMP-2, another strong inducer of heterotopic bone formation, is overexpressed by the proliferating epithelial cells during the development of ectopic bone. The formation of sarcomatous tumors within the mixed tumors appears to be androgen-dependent and more frequent in mice lacking a normal allele of p53. This process of cartilage and bone induction may mimic epithelial-mesenchymal interactions which occur during embryonic bone formation. These transgenic mice may provide new insights into the processes of ectopic endochondrial bone formation associated with mixed tumor formation and serve as a useful model for human heterotopic bone disease.

Actins↗
PubMed1999

Value of clinical, functional, and oximetric data for the prediction of obstructive sleep apnea in obese patients.

OBJECTIVE: To evaluate the diagnostic value of clinical features, pulmonary function testing, blood gas tensions, and oximetric data for case finding of obstructive sleep apnea (OSA) before polysomnography (PSG) in a series of consecutive overweight patients. METHODS: We studied a population of 102 consecutive patients referred by an obesity clinic for suspected OSA, in whom body mass index was > or = 25 kg/m(2). The following tests were performed: clinical score (CS), pulmonary function tests (PFTs), measurement of arterial blood gas tensions, nocturnal oximetry, and full-night PSG. RESULTS: Six of 34 women and 34 of 68 men had OSA, defined by an apnea-hypopnea index > or = 15. CS and the cumulative time spent below 80% arterial oxygen saturation (SaO(2)) were higher, and PaO(2), minimal SaO(2), and mean nocturnal SaO(2) (mSaO(2)) were lower in OSA patients than in non-OSA patients. Logistic regression showed that sex, CS, and the ratio of FEV(1) over forced expiratory volume in 0.5 s (an index of upper airway obstruction on flow-volume curves) and mSaO(2), expressed as categorical variables, were independent predictors of OSA. None of these individual variables had a satisfactory diagnostic value for the diagnosis of OSA. A logistic regression model including sex and all continuous variables would have allowed us to predict the presence or absence of OSA confidently in 72.5% of the population, in whom the positive predictive value of the model was 94% and the negative predictive value was 90%. CONCLUSION: In obese patients referred to a respiratory sleep laboratory and evaluated by CS, PFTs, arterial blood gases, and oximetry, no individual sign or symptom may accurately predict the presence or absence of OSA. Provided that it is validated in prospective studies, a logistic regression model using these variables may be useful for the prediction of OSA.

Adult↗
PubMed1998

Altered expression of transforming growth factor betas during urethral and bulbourethral gland tumor progression in transgenic mice carrying the androgen-responsive C3(1) 5' flanking region fused to SV40 large T antigen.

We demonstrate that targeted expression of SV40 large T antigen (TAg) to the urethral (periurethral) and bulbourethral gland epithelium leads to adenocarcinoma formation in these tissues after 7 months of age, which are extremely rare sites for spontaneous tumor formation in humans. The development of proliferative lesions in the urethral gland predictably follows a temporal course of progression with approximately one third of male animals developing urethral tumors by 1 year of age. Tumor progression in these organs correlates to the level of TAg and p53 expression. Immunoprecipitation confirmed that SV40 TAg protein was bound to p53 and Rb p110 in vivo. Expression of transforming growth factor beta (TGFbetas) was evaluated during tumor progression of urethral gland carcinomas. Elevations of intracellular and extracellular TGFbeta1 and extracellular TGFbeta3 were found in preneoplastic and neoplastic lesions, suggesting that increased TGFbetas may augment tumor growth. c-Met expression showed a tendency for increased expression in the urethral gland carcinomas. We speculate that the directed expression of SV40 TAg by the hormone responsive C3(1) gene and subsequent tumor formation in these organs is influenced by androgens, since these tissues and carcinomas express androgen receptor (AR) and arise only in male transgenic mice. Several cell lines established from the urethral carcinomas were also shown to express AR, but are not androgen dependent in culture. To our knowledge, this is the first transgenic animal model for urethral and bulbourethral carcinomas. This transgenic mouse model and the cell lines derived from it may provide a unique opportunity for dissecting molecular mechanisms involved in the tumorigenesis of these organs which otherwise rarely develop cancer.

Aging↗
PubMed1998

Metered-dose inhaler to deliver methacholine in bronchial provocation testing: a pilot study.

BACKGROUND: Nonspecific bronchial provocation tests may be simplified by the use of hand-held devices to deliver methacholine. OBJECTIVE: To study the feasibility of using a metered-dose inhaler (MDI) to administer methacholine in bronchial provocation tests, and the ability of such a device to diagnose bronchial hyperresponsiveness (BHR) accurately. METHODS: In an open randomized crossover pilot study, we compared the provocative dose that induces a 20% fall in FEV1 (PD20 FEV1) obtained with the methacholine MDI with that obtained using a conventional nebulizer in 20 hyperresponsive and 20 nonhyperresponsive subjects. The MDI delivers 400 doses of 100 microg of methacholine, and was used via a spacer. Bronchial hyperresponsiveness (BHR) was defined as a PD20 FEV1 <2,000 microg with the conventional test using the nebulizer. The tests were performed in each subject in a randomized order, 1 to 7 days apart. RESULTS: Of the subjects who had a nebulizer PD20 FEV1 <2,000 microg, all but one had an MDI PD20 FEV1 <800 microg. When 800 microg was taken as the threshold for the diagnosis of BHR with the MDI test, the accuracy of this test to diagnose BHR was 97.5%, and the two tests were highly concordant for the diagnosis of BHR (Pearson chi2, 36.19; p<0.0001). CONCLUSION: A hand-held device may be suitable for delivery of methacholine during bronchial provocation tests, if these results are confirmed in large samples.

Adult↗