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Biomedical subjects

S Richard

Publications and source records attributed to S Richard.

212 records · Page 12Linked to original sources
PubMed1986

Association with HeLa cells of Campylobacter jejuni and Campylobacter coli isolated from human feces.

We developed a rapid in vitro test for determining the association of Campylobacter jejuni and C. coli with HeLa cells. Association was expressed as a weighted mean of the number of bacteria associated with one cell in an association index (AI). The reproducibility of the AI was checked by repeating the test six times, using four strains chosen at random. Means and standard deviations of the means were 7.3 +/- 1.2, 6.8 +/- 0.9, 1.8 +/- 1.2, and 0.1 +/- 0.2. The experimental conditions for which the results are reliable have been standardized. Among 42 strains from human feces, two groups appeared: for 22 nonassociative strains (52%), AI values ranged from 0.0 to 2.1 (mean +/- SD, 0.5 +/- 0.6); for 20 associative strains (48%), AI values ranged from 3.5 to 8.3 (mean +/- SD, 6.2 +/- 1.4). Of these 42 strains, 17 were clinically documented. Diarrhea occurred more frequently in patients infected with associative strains than in those infected with noninvasive strains (7/7 versus 3/10, P = 0.01). Fever also occurred more frequently in patients infected with associative strains (6/7 versus 2/10, P = 0.03). Transmission electron microscopy and viable counts made after killing of extracellular bacteria by gentamicin support the fact that associated Campylobacter spp. are adherent to the cell membrane and are internalized into cytoplasmic vacuoles. The described test seems to be a convenient and rapid method for estimating the pathogenicity of a given strain.

Bacterial Adhesion↗
PubMed1986

[Filamentary granules in human bronchi].

Mucous cells of human bronchial glands contain secretory granules with 5,5-7 nm parallel filaments. In contrast with the glycoproteic-rich mucous granules, filamentary granules exhibit weak reactivity with tannic acid, indicative of proteins. Exocytosis or discharge in glandular lumen are sometimes observed. These original granules may probably represent an additional component of fibrillar matrix in mucus.

Bronchi↗
PubMed1985

Photochemically produced intracellular concentration jumps of cAMP mimic the effects of catecholamines on excitation-contraction coupling in frog atrial fibers.

Previously, we reported that concentration jumps of cAMP produced by light flashes in the presence of a photosensitive analogue of cAMP increase the amplitude of the slow inward current (Isi) in isolated bullfrog atrial trabeculae (Nargeot et al. 1983). Here, using newly designed photolabile cyclic nucleotides (Nerbonne et al. 1984a), we have examined the effects of intracellular concentration jumps of cAMP and cGMP on excitation-contraction coupling in frog heart. Concentration jumps of cAMP increase the amplitude and the duration of action potentials, increase Isi and twitch tension. Following single flashes, maximum responses are observed in 10-30 s and recovery times are 30-120 s. The time courses of the cAMP-induced increases in Isi and phasic tension amplitudes are parallel, implying a direct correlation between Ca2+ influx through the slow channels and the development of phasic tension. Although the amplitudes are increased severalfold, cAMP jumps do not measurably alter the kinetics or voltage dependences of the current or tension. cAMP concentration jumps increase the delayed K+ current (IK) and decrease tonic tension; relaxation of contraction is not, however, influenced by cAMP jumps. Concentration jumps of cGMP, on the other hand, have no measurable effects on the action potential, Isi, IK or tension in this preparation.

Action Potentials↗
PubMed1985

Mucoid impaction of bronchi. A scanning electron microscopic study.

An example of mucoid impaction in the culminal bronchus in a potentially asthmatic child is related. Histological sections of the plug showed the characteristic pattern with clusters of eosinophils and other cells within the impacted mucus, which consisted of mainly sulfated glycoproteins. Scanning electron microscopy revealed new data on the three-dimensional structure of the plug. Ten to fifteen micron thick fascicles of partially rolled-up mucous fibres surrounded wide meshes filled with eosinophils and other components. As far as can be determined, this is the first reported ultrastructural description of this particular lesion.

Bronchial Diseases↗
PubMed1985

Calcium channels are 'unblocked' within a few milliseconds after photoremoval of nifedipine.

The organic Ca2+ antagonists are potent inhibitors of Ca2+ influx in cardiac and smooth muscle and are widely used clinically in the treatment of various cardiovascular disorders. It appears that Ca2+ antagonist binding prevents the normal movement of ions through Ca2+ channels, perhaps via an open-channel blockade mechanism. Although this concept is generally accepted, questions do remain about the detailed relationship between binding and blockade in the case of the structurally diverse organic Ca2+ channel blockers; e.g., (1) do they bind preferentially to open, closed and/or inactivated channels; (2) are there multiple binding sites; (3) do they act at extracellular and/or intracellular sites; and (4) does blocking or unblocking depend on membrane potential or its history? The dihydropyridine Ca2+ antagonist, nifedipine, contains an o-nitrobenzyl moiety and is photolabile; irradiation yields a molecule devoid of channel blocking activity and the photoconversion reactions are complete within 100 microseconds. Taking advantage of these properties to study the mechanistic details of nifedipine blockade of Ca2+ channels, we examined the waveform of the slow inward Ca2+ current (Isi) in atrial fibers before and following flash-induced removal of nifedipine. After flashes, we find that nifedipine blockade is reversed within at most a few milliseconds and that the rate of Isi reactivation parallels the normal, voltage-dependent activation rate. Our results imply that nifedipine binds to and stabilizes resting, closed Ca2+ channels and are not in agreement with the recent conclusions of Morad and coworkers that photoconversion of nifedipine must be followed by membrane repolarization in order to effect recovery of Isi and tension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Determination of organ volume by single-photon emission tomography.

A method for estimation of organ volume is proposed, based on analysis of individual slices obtained from SPET images. In a phantom simulating clinical circumstances, the data show that the level a threshold at 46% of the maximum activity predicts most closely the true volume over a wide range above one liter. The level at 45% predicted better volumes of less than one liter. For phantoms of 839 ml or less, the error was 6.3 ml (one standard error of estimation). This level seems to be independent of the plane or position of the phantom and also independent of the amount of scattering material around it. Nonradioactive voids ("holes") within a phantom may be included or excluded at will when their edges are not tangent to the edge of the phantom. In such cases, their edges are not distinguishable from the edge of the phantom and their volumes are excluded. Knowledge of organ volumes has both diagnostic and therapeutic importance and could lead to a more precisely quantitated total of the radioactivity contained in an organ or space.

Models, Structural↗
PubMedDate not supplied

Pharmacokinetics of ketoprofen in rabbit after a single topical application.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used by topical application in management of joint pain and inflammation. Little is known, however, about their pharmacokinetics, especially in the synovial compartment versus the plasma compartment, following topical administration. Ketoprofen, a NSAID, was delivered by a single topical application (KETUM 2.5% gel) on the rabbit knee-joint region of one hind limb. Concentrations of ketoprofen were measured in plasma, synovial fluid, joint capsule and synovial fat tissue at 2, 4, 6 and 12 hours after application. Whatever the time period after application, ketoprofen concentrations in synovial fluid were much higher than in plasma. The time-course of the decrease in ketoprofen plasma concentrations was more rapid than that in synovial fluid. Similarly, concentrations in joint capsule were higher than those found in synovial fat tissue. Finally, while ketoprofen concentrations decreased rapidly in plasma and in synovial fat tissue, concentrations in joint capsule and particularly in synovial fluid were more sustained. The increase in residence time of ketoprofen in synovial fluid could be in favour of its efficiency in the management of joint pain and inflammation.

Administration, Topical↗
PubMedDate not supplied

New photoactivatable cyclic nucleotides produce intracellular jumps in cyclic AMP and cyclic GMP concentrations.

The cyclic nucleotides cyclic AMP and cyclic GMP are important intracellular messengers mediating the responses to neurotransmitters and neurohormones and regulating cellular function over a wide range of time scales. Despite the widespread acceptance of this second messenger mechanism in many systems, much remains unknown about their mechanism of action, except that such events are associated with increases or decreases in intracellular cyclic nucleotides. Quantitative descriptions of cyclic nucleotide-dependent processes are hampered by the absence of a means by which intracellular cyclic nucleotide concentrations can be accurately controlled. We have now designed, synthesized and characterized new, substituted photolabile cyclic nucleotide analogues, the 4,5-dimethoxy-2-nitrobenzyl esters of cyclic AMP and cyclic GMP (Fig. 1), which are physiologically inert before irradiation and which liberate free cyclic AMP or cyclic GMP on absorption of a photon. The thermal properties and photolysis rates and efficiencies of light-induced release of cyclic nucleotides from these analogues are more favourable than for the simple o-nitrobenzyl derivatives used previously. These molecules should permit intracellular "concentration jumps' of cyclic AMP or cyclic GMP to be produced in cells under physiological investigation with spatial and temporal resolution unmatched by conventional techniques.

Chemical Phenomena↗
PubMedDate not supplied

14-3-3 protein, neuron-specific enolase, and S-100 protein in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

We explored simultaneously 14-3-3 protein, neuron-specific enolase (NSE), and one astroglial protein, S-100, recently proposed as Creutzfeld-Jakob disease (CJD) markers, in the cerebrospinal fluid (CSF) of 129 patients with suspected CJD. Cutoff values for NSE and S-100 were established at 25 and 2.5 ng/ml, respectively. The highest sensitivity was observed for S-100 (94.2%) followed by 14-3-3 (89.8%) and NSE (79.7%), while the highest specificity in CJD diagnosis was obtained with 14-3-3 protein (100%) as compared with NSE (91.5%) and S-100 (85.4%). No influence of sex, genotype at codon 129 of the prion protein gene, time between sampling, and death or disease duration has been found. Based on 90 cases initially referred as 'probable' or 'possible' CJD, with 14-3-3, NSE, or S-100 we could correctly discriminate between 'CJD' or 'non-CJD' categories in 94.4, 86.5, and 90% of the cases, respectively. When limited to 'possible CJD' cases, diagnosis based on one of the three CSF proteins was accurate in 98, 90.7 and 87.3%, respectively. In view of the fact that the CSF 14-3-3 protein test alone has the highest specificity and good sensitivity, it appears that there is no additional advantage at the moment to include NSE and/or S-100 protein in the exploration of clinically suspected CJD cases.

14-3-3 Proteins↗
PubMedDate not supplied

Congenital soft tissue dysplasias: a morphological and biochemical study.

The term congenital soft tissue dysplasias (CSTDs) regroups some localized malformations of covering soft tissues in children, presenting as various clinical entities, either recognized as particular syndromes (e.g., Parkes-Weber, Klippel-Trenaunay, Proteus) or, most often, appearing less stereotyped (e.g., segmental hypertrophy or gigantism, lymphedema, angiodysplasia, phakomatosis), with a common histopathological lesion, the hamartoma. The aim of this paper is to report a morphological and biochemical study of the extracellular matrix of skin and subcutaneous tissue in children with CSTD. For every patient, pathological tissues were compared with contralateral, symmetrical tissues, taken as controls. In all CSTDs, pathological samples were characterized by an increase in water and total glycosaminoglycan (GAG) content with a decrease in collagen content. Other results lead the authors to distinguish two main entities, segmental dysplasia (SeD) and neuroectodermal dysplasia (NeD). Elastic fiber content was increased in SeD and decreased in NeD. Hyaluronic acid (HA) and dermatan sulfate (DS) were increased in NeD, whereas in SeD, HA was decreased with an increase in the DS/HA ratio. Cultured fibroblasts from dysplastic skin had slower proliferation in vitro than fibroblasts from control skin, whereas their biosynthetic activity concerning collagen and GAGs was greater. The difference in the composition of extracellular matrix supports the clinical classification of CSTDs in two main groups: segmental dysplasia with or without gigantism and neuroectodermal dysplasia (in von Recklinghausen's disease and nevi).

Abnormalities, Multiple↗
PubMedDate not supplied

The preclinical assessment of the risk for QT interval prolongation.

Some drugs have been reported to induce severe ventricular arrhythmias, including torsades de pointes, and have been responsible in some cases for sudden death of patients. Although the mechanisms of these arrhythmias are not well understood, they are often, but not always, associated with QT interval prolongation. Regulatory authorities (CPMP in Europe) have recently pointed out the necessity to assess most carefully the potential, especially of non-cardiovascular drugs, for QT interval prolongation. Different methodological approaches are presented in this paper and experimental protocols are suggested; limitations and advantages of the presently available in vitro and in vivo models are discussed. It appears that both in vitro and in vivo approaches are complementary. In particular it is pointed out that only the in vitro models using isolated cardiac tissues (Purkinje fibres or papillary muscles) enable assessment of the drug properties under low cardiac rhythm conditions. This model allows us to mimic pathological situations of long QT interval (such as acquired or congenital long QT syndrome) in which most of the major clinical problems are encountered. Finally, a strategy for the preclinical assessment of the potential of a molecule for QT interval prolongation is presented.

Animals↗
PubMedDate not supplied

[Presence of filamentary secretory granules in the mucous cells of human bronchial glands].

Secretory granules containing 6-8 nm fine filaments are described in mucous cells of human bronchial glands. In contrast with the strongly marked classical mucous granules, filamentary granules exhibit weak positivity with Thiéry's method providing an easy characterization. Exocytosis in glandular lumen are often observed. These undescribed filaments may probably represent an usual component of fibrillar matrix in bronchial mucus.

Adult↗