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Biomedical subjects

C Schweitzer

Publications and source records attributed to C Schweitzer.

At least 19 recordsLinked to original sources
PubMed2006

[Alteration of bronchomotor tone after deep inhalation. Mechanisms and pediatric data].

There is significant alteration of airway calibre after deep inhalation (DI). An increase of airway calibre has been evidenced in children in case of mild asthmatic obstruction and after a positive response to methacholine or exercise challenge. Such an increase is blunted in the presence of a moderate to severe asthmatic airway obstruction and no bronchodilatory effect of DI has been found in infants. Bronchial hyperreactivity and airway inflammation strongly influence post-DI alterations of bronchomotor tone. Airways and lung parenchyma are interdependent but both exhibit imperfect elasticity. Hysterisis characterizes imperfect elasticity of pressure-volume relationship. The mechanical theory of relative hysteresis between airway and lung parenchyma is the main mechanism implicated in the induced changes of airway calibre. DI may influence results of lung function testing in children. The technique may be of interest to increase sensibility of routine lung function testing in children.

Asthma↗
PubMed2006

Estimation of the bronchodilatory effect of deep inhalation after a free run in children.

The bronchomotor effects of a deep inhalation (DI) may provide relevant information about the mechanisms of exercise-induced airway obstruction in children and may be assessed by respiratory conductance (Grs) measured using the forced oscillation technique. The aims of the present study were to assess the effect of DI on Grs after exercise in relationship to the lung function response to exercise. Grs at 12 Hz using a head generator and spirometric data were measured in 62 children suspected of asthma before and 5 min after a 6-min free run. After exercise, Grs was significantly increased by DI in 38 subjects, who also showed larger Grs and forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) responses to exercise than the 24 nonresponders. Stepwise regression indicated significant correlation between the response of Grs to DI and both Grs and FEV1/FVC responses to exercise. The data are consistent with exercise-induced bronchoconstriction being reversed by deep inhalation.

Adolescent↗
PubMed2004

Evaluation of the mercury exposure of dental amalgam patients by the Mercury Triple Test.

AIMS: To establish and analyse reference data for the mercury burden of patients with and without amalgam fillings. METHODS: Atomic absorption spectroscopy was used to quantify Hg concentrations in the scalp hair and urine (before and after application of dimercaptopropane sulphonate), and Hg release from dental amalgams (using a newly developed, amalgam specific chew test), in 2223 subjects. RESULTS: 50th centiles were 1.3 microg Hg/g creatinine in basal urine, 32 microg Hg/g creatinine after DMPS application, 454 ng Hg/g in hair, and 27 microg Hg per g of chewing gum, which corresponds to about 1 micro g Hg released per minute of chewing. Total Hg intake (from ambient air, drinking water, food, and amalgams) of most patients is well below the provisioned tolerable weekly intake (PTWI) defined by the WHO, unless extremely Hg rich food is consumed on a regular basis. However, for patients exceeding the 75th centile in chew tests, total Hg intake exceeds the PTWI by about 50%, even at the low limit of intake from food. In the absence of occupational exposure, significant Hg release from dental amalgams is a necessary but insufficient condition to obtain a high long term body burden. After removal of dental amalgams, chew tests no longer exhibit oral Hg exposure, while basal urine Hg content and DMPS induced excretion display a exponential decrease (half life about 2 months in both cases). CONCLUSIONS: A standardised procedure for evaluation of the magnitude and origin of the Hg burden of individuals has been developed, which, by comparison with the database presented here for the first time, can serve as a diagnostic tool.

Body Burden↗
PubMed2002

Respiratory impedance response to a deep inhalation in asthmatic children with spontaneous airway obstruction.

The aim of the study was to determine whether the bronchomotor effect of a deep inhalation (DI) may be detected during tidal breathing in asthmatic children with spontaneous airway obstruction (AO). Two groups of children aged 5-15 yrs were studied. AO was mild in group 1 (n=12, forced expiratory volume in one second (FEV1) > or = 75% predicted) and moderate-to-severe in group 2 (n=9, FEV1 > or = 70% pred). The forced oscillation technique at 12 Hz using a head generator allowed the determination of respiratory resistance in inspiration (Rrsi) and expiration (Rrse) before and after DI, at baseline and after salbutamol. At baseline, Rrsi but not Rrse was found to decrease significantly after DI in group 1 but not in group 2. The change induced by DI was significantly different in group 1 (-1.5+/-0.5 hPa x s x L(-1)) compared to group 2 (0.5+/-0.5 hPa x s x L(-1)) and exhibited significant negative correlation to FEV1 % pred. After salbutamol, DI had no effect. In conclusion, asthmatic children show a bronchomotor response to deep inhalation that depends on the degree of airway obstruction. The effect is more readily demonstrated in inspiration than in expiration.

Adolescent↗
PubMed2002

[Domiciliary assisted ventilation in children].

The concept of assisted ventilation in the home setting has greatly progressed as a routine practice. This technique was used from 1990 to 2000 in 16 children cared for at our center. Ten children had neuromuscular disease (infantile spinal amyotrophy 6, Duchenne myopathy 3, and mitochondrial myopathy 1) or other conditions including central hypoventilation (n = 2), traumatic tetraplegia (n = 2), encephalopathy with chronic bronchitis (n = 1) and bronchopulmonary dysplasia (n = 1). Only 5 children had a tracheotomy, the others were treated successfully with non-invasive ventilatory assistance. Initialization of non-invasive ventilatory assistance had been planned before development of respiratory failure in 4 of the 11 children, but generally was indicated after an episode of acute respiratory distress. Home ventilation, particularly with non-invasive assistance is a reliable method for long-term treatment of chronic alveolar hypoventilation in children. The appropriate time for initiating this therapy should be better defined.

Adolescent↗
PubMed2001

Semliki Forest virus vectors: efficient vehicles for in vitro and in vivo gene delivery.

Rapidly generated high-titer Semliki Forest virus (SFV) vectors can infect numerous mammalian cell lines and primary cell cultures, and result in high levels of transgene expression. SFV-based expression of transmembrane receptors has been characterized by specific ligand-binding activity and functional responses. Adaptation of the SFV technology for mammalian suspension cultures has allowed the production of hundreds of milligrams of recombinant receptor for purification and structural studies. The same SFV stock solutions used for the infection of mammalian cells in culture have also been successfully applied for efficient transgene expression in organotypic hippocampal slices, as well as in vivo in rodent brain.

Animals↗
PubMed2001

Quantum yield of singlet oxygen production by monomeric and aggregated forms of hematoporphyrin derivative.

Hematoporphyrin derivative (HpD) is a complex mixture of monoporphyrinic compounds, including hematoporphyrin, and oligomers containing up to eight porphyrin units. In methanol a sensitizer concentration-independent quantum yield of 0.64 is measured for the HpD-induced production of singlet molecular oxygen O2 (1Delta(g)). This finding is consistent with the dye components remaining unassociated in this solvent. In water pH 7.4 HpD consists of a complex mixture of non-aggregated and self- and cross-aggregated monoporphyrinic and oligomeric species, and the quantum yield of O2 (1Delta(g)) formation decreases significantly with increasing HpD concentration due to the lower quantum yield of aggregates. These variations can be quantitatively described in terms of a monomer-dimer equilibrium, with quantum yields of 0.64 and 0.11, respectively, for monomers and dimers. The yields of unassociated species are identical in methanol and water.

Dimerization↗
PubMed2001

Feedback regulation of the MBF transcription factor by cyclin Cig2.

The Mlu1-binding factor (MBF) from the fission yeast Schizosaccharomyces pombe contains the proteins Res1p and Res2p and binds to the Mlu1 cell-cycle box (MCB) element in DNA, activating the transcription of genes required for S phase. We report here that the cell-cycle-regulated expression of the cyclin cig2 gene is dependent on MBF. Deletion of MCB elements in the cig2 promoter perturbed the expression not only of cig2 but also of other MBF-dependent genes, indicating that Cig2p could regulate MBF activity. Cig2p can bind to Res2p, promote the phosphorylation of Res1p and inhibit MBF-dependent gene transcription. Cig2p thus forms an autoregulating feedback-inhibition loop with MBF which is important for normal regulation of the cell cycle.

Base Sequence↗
PubMed2001

Improved Semliki Forest virus vectors for receptor research and gene therapy.

We have modified Semliki Forest virus (SFV) vectors to broaden their application range. Here we describe a series of site-directed mutagenesis experiments on the SFV subgenomic 26S promoter to down-regulate the heterologous gene expression. Several mutants showed a dramatic effect on transgene expression levels in BHK cells. The luciferase activity was reduced to approximately 30%, 3%, and 1% compared to the wild type promoter. Similarly, a decrease in beta-galactosidase activity was observed in BHK cells and after injection into the striatum of male Wistar rats. Novel non-cytopathogenic and temperature-sensitive SFV vectors have recently been developed by introduction of point mutations in the viral nonstructural genes nsP2 and nsP4. These vectors do not show the typical shut down of host cell protein synthesis after SFV infections and therefore allow for a substantially prolonged survival of host cells. Both the mutant vectors demonstrating lower and more physiological expression levels and the non-cytopathogenic vectors should be valuable tools for various applications within receptor research. Furthermore, recent studies suggest that SFV vectors can be efficient gene delivery vehicles for gene therapy applications.

Amino Acid Sequence↗
PubMed2000

Characterization of [(3)H]-LY354740 binding to rat mGlu2 and mGlu3 receptors expressed in CHO cells using semliki forest virus vectors.

The binding properties of [(3)H]-LY354740 were characterized on rat metabotropic glutamate receptors mGlu2 and mGlu3 expressed in Chinese hamster ovary (CHO) cells using Semliki Forest virus vectors. The saturation isotherm gave K(D) values of 20+/-5 and 53+/-8 nM and B(max) values of 474+/-161 and 667+/-89 fmol/mg protein for mGlu2 and mGlu3 receptors, respectively. NMDA, CaCl(2), DHPG and kainate were inactive up to 1 mM, whereas LY341495, DCG IV and ibotenate inhibited [(3)H]-LY354740 binding with similar potencies on both receptors. L-CCG I, L-AP4, L-AP5, LY354740 and 1S,3R-ACPD were 2- to 4-fold more potent inhibitors of [(3)H]-LY354740 binding to mGlu2 than mGlu3 receptors. However, MPPG and L-AP3 had a 6-fold and DTT a 28-fold preference for mGlu2 over mGlu3. ZnCl(2), at 10 mM, inhibited more than 70% of [(3)H]-LY354740 binding to mGlu2 receptors. At the same concentration it did not affect significantly [(3)H]-LY354740 binding to mGlu3 receptors. On the contrary, glutamate, quisqualate, EGLU and NAAG showed a 3-, 5-, 7- and 12-fold preference for mGlu3 over mGlu2. Finally, GTPgammaS, which partially inhibited the binding on mGlu2 receptors, was inactive to inhibit [(3)H]-LY354740 binding on mGlu3 receptors.

Amino Acids↗
PubMed2000

Comparison of antibiotic drops placed in the conjunctival cul-de-sac to antibiotic ointment applied to the lid margin in reduction of bacterial colonization on the lid margin.

PURPOSE: To compare the efficacy of antibiotic drops placed in the conjunctival cul-de-sac to antibiotic ointment applied to the lid margin in reduction of bacterial colonization on the lid margin. METHODS: A randomized, prospective, single-masked study was conducted on 19 patients with culture-proven colonization of bacteria on the lid margins. Ophthalmic eligibility criteria included the presence of > or =50 colony-forming units/mL (CFU/mL) of bacteria on both right and left lids. Each patient received one drop of ofloxacin in one eye every night for one week, followed by one drop once a week for one month. In the same manner, each patient received bacitracin ointment (erythromycin or gentamicin ointment if lid margin bacteria were resistant to bacitracin) to the lid margin of the fellow eye. Quantitative lid cultures were taken at initial visit, one week, one month, and two months. Fifteen volunteers (30 lids) served as controls. Lid cultures were taken at initial visit, one week, and one month. RESULTS: Both antibiotic drop and ointment reduced average bacterial CFU/mL at one week and one month. Average bacterial CFU/mL reestablished to baseline values at two months. There was no statistically significant difference between antibiotic drop and ointment in reducing bacterial colonization on the lid margin. CONCLUSION: Antibiotic drops placed in the conjunctival cul-de-sac appear to be as effective as ointment applied to the lid margins in reducing bacterial colonization in patients with > or =50 CFU/mL of bacteria on the lid margins.

Adult↗
PubMed2000

Mechanistic and kinetic aspects of photosensitization in the presence of oxygen.

Determining whether the first step of photooxygenation is Type I or Type II is a necessary prerequisite in order to establish the mechanism of photodynamic action. But this distinction is not sufficient, because other processes, both consecutive and competitive, commonly participate in the overall mechanism. Thus, in both Type I and Type II reactions, the initial products are often peroxides that can break down and induce free radical reactions. These aspects of photosensitization are discussed and illustrated by sensitizer/substrate systems involving (1) only radical reactions (decatungstate/alkane) and (2) reactions of singlet oxygen occurring in competitive and consecutive processes and possibly followed by radical reactions (methylene blue/2'-deoxyguanosine). Two other previously investigated systems involving, respectively, a Type II interaction followed by radical processes (methylene blue/alkene) and Type II reactions, some of which being competitive or consecutive (rose bengal/alkene), are briefly reconsidered.

Free Radicals↗
PubMed2000

Recombinant Semliki forest virus infects and kills human prostate cancer cell lines and prostatic duct epithelial cells ex vivo.

Semliki Forest Virus (SFV) is a broad host range RNA virus capable of high-level recombinant protein expression and apoptosis induction in many cell types. We have successfully used a recombinant, replication deficient SFV vector to express the LacZ marker gene product in seven human prostate cell lines, as well as in human prostate tissue explants. Flow cytometry revealed that 40-60% of PPC-1 prostate cancer cells died 24-72 h after infection with SFV-LacZ virus. Most human prostate cancer cell lines expressed high levels of recombinant protein. Infection of human prostate tissue ex vivo led to similarly high expression levels but the recombinant beta-galactosidase was confined to duct epithelial cells. Infection of cell and tissue cultures resulted in detachment of adherent cells from the culture surface and detachment of epithelial cells from the basement membrane of tissue. Our results indicate that SFV may be useful in targeting recombinant protein expression and apoptosis to prostatic duct epithelial cells.

Apoptosis↗
PubMed2000

[Several aspects of respiratory function testing in children].

Some practical aspects of respiratory function testing (RFT) are reviewed with special interest on applications in preschool children. RFT may be used for diagnostic, management and follow up purposes. Children may benefit from RFT in a variety of pathological situations. Asthma and other obstructive airways diseases certainly represent the most frequent conditions. Vital Capacity and Forced Expiratory Volume in one second (FEV1) may usually be obtained from age 7 on. In smaller children, the forced expiratory manoeuvre is much less successful. Non invasive measurements such as respiratory resistance (Rrs) or specific airway resistance (sRaw) may be used. Rrs is usually measured by the interrupter technique or the forced oscillation technique and sRaw by body plethysmography, not requiring the estimation of thoracic gas volume. Because much variability is introduced by the upper airways, these parameters are less suited than FEV1 to establish the degree of baseline airway obstruction. On the other hand, Rrs and sRaw may quantify reversibility of airway obstruction and/or bronchial hyperresponsiveness. Lung hyperinflation may be identified by the assessment of Functional Residual Capacity (FRC) with a dilution method. More generally lung growth may be followed up in longitudinal studies of FRC even in small children. More work is needed to standardize RFT techniques and indications in the preschool child.

Age Factors↗
PubMed1999

Recombinant Semliki Forest virus and Sindbis virus efficiently infect neurons in hippocampal slice cultures.

Gene transfer into nervous tissue is a powerful tool for the analysis of gene function. By using a rat hippocampal slice culture preparation, we show here that Semliki Forest virus (SFV) and Sindbis virus (SIN) vectors are useful for the effective infection of neurons. The stratum pyramidale and/or the granular cell layer were injected with recombinant virus encoding beta-galactosidase (LacZ) or green fluorescent protein (GFP). By using low concentrations of injected SFV-LacZ or SIN-LacZ, we detected LacZ staining of pyramidal cells, interneurons, and granule cells. About 60% of the infected cells showed clear neuronal morphology; thus, relatively few glial cells expressed the transgene. Expression of GFP from SFV and SIN vectors gave similar results, with an even higher percentage (>90%) of the GFP-positive cells identified as neurons. Infected pyramidal cells were readily recognized in living slices, displaying GFP fluorescence in dendrites of up to fourth order and in dendritic spines. They appeared morphologically normal and viable at 1-5 days postinfection. We conclude that both SFV and SIN vectors efficiently transfer genes into neurons in hippocampal slice cultures. In combination with the GFP reporter, SFV and SIN vectors will allow the physiological examination of identified neurons that have been modified by overexpression or suppression of a specific gene product.

Alphavirus Infections↗
PubMed1999

Effect of the umami peptides on the ligand binding and function of rat mGlu4a receptor might implicate this receptor in the monosodium glutamate taste transduction.

1. The effect of several metabotropic ligands and di- or tripeptides were tested on the binding of [3H]-L(+)-2-amino-4-phosphonobutyric acid ([3H]-L-AP4) on rat mGlu4 receptor. For selected compounds, the functional activity was determined on this receptor using the guanosine-5'[gamma-35S]-thiotriphosphate [gamma-35S]-GTP binding assay. 2. Using the scintillation proximity assay, [3H]-L-AP4 saturation analysis gave binding parameters K(D) and Bmax values of 150 nM and 9.3 pmoles mg-1 protein, respectively. The specific binding was inhibited concentration-dependently by several mGlu receptor ligands, and their rank order of affinity was established. 3. Several peptides inhibited the [3H]-L-AP4 binding with the following rank order of potency: glutamate-glutamate>glutamate-glutamate-leucine=aspartate - glutamate>>glutamate - glutamate-aspartate>lactoyl-glutamate>>aspartate-aspartate. Aspartate-phenylalanine-methyl ester (aspartame) was inactive up to 1 mM and guanosine-5'-monophosphate and inosine-5'-monophosphate were inactive up to 100 micronM. 4. The [gamma-35S]-GTP binding functional assay was used to determine the agonist activities of the different compounds. For the rat mGlu4 agonists, L-AP4 and L-glutamate, the correlation between their occupancy and activation of the receptor was close to one. The peptides, Glu-Glu, Asp-Glu and Glu-Glu-Asp failed to stimulate the [gamma-35S]-GTP binding at receptor occupancy greater than 80% and Glu-Glu-Leu appeared to be a weak partial agonist. These peptides did not elicit a clear dose-dependent umami perception. However, Glu-lac showed a good correlation between its potency to stimulate the [gamma-35S]-GTP binding and its affinity for displacement of [3H]-L-AP4 binding. These data are in agreement with the peptide taste assessment in human subjects, which showed that the acid derivatives of glutamate had characteristics similar to umami.

Adult↗
PubMed1998

Hypericum perforatum inhibits the binding of mu- and kappa-opioid receptor expressed with the Semliki Forest virus system.

The effects of Hypericum perforatum extracts on in vitro [3H]naloxone binding to the human mu- and rat kappa-opioid receptors were studied in chinese hamster ovary (CHO) cells using the Semliki Forest virus (SFV) expression system. Binding of [3H]naloxone to the mu- and kappa-opioid receptor was inhibited in the presence of Hypericum extracts showing IC50 values of approximately 25 and 90 micrograms/ml, respectively. In contrast, extracts of Valeriana officinalis did not inhibit binding to the mu-opioid receptor. Also, single constituents of H. perforatum like the flavonoids quercetin and kaempferol and the glycosilated flavonoid quercitrin did not inhibit [3H]naloxone binding to the mu-opioid receptor up to a concentration of 10 microM. The present in vitro data may suggest a new possible mechanism for the anti-depressant effect of H. perforatum.

Animals↗