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Biomedical subjects

J Pierre

Publications and source records attributed to J Pierre.

At least 73 records · Page 4Linked to original sources

Fine structure of the optic fiber termination layer in the tectum of the teleost Rutilus: a stereological and morphometric study.

The stratum fibrosum et griseum superficiale (SFGS) of the Rutilus optic tectum, which receives a massive fiber projection from the contralateral retina, was studied by electron microscopy. The qualitative and quantitative analysis of the laterodorsal (LD) portion of the stratum involved both a stereological examination of the different elements and a morphometric study of the various profiles containing synaptic vesicles (PCSVs). The relative volume of each element in the LD SFGS was as follows: myelinated and unmyelinated axons, 6.6%; PCSVs, 38%; dendrites without vesicles, spines, and cell bodies, 41.7%; glia, 10.5%. With the fixation employed, 35% of PCSVs showed spheroidal synaptic vesicles. These profiles could be subdivided into three types: (1) S1 (23.5%) represented optic terminals, since they degenerated after retinal ablation or were labeled after intraocular injection of HRP or [3H] proline. Three subgroups of S1 were identified: S1m--profiles containing clear mitochondria;S1c--profiles that were contiguous with S1m and lacked mitochondria;S1i--isolated profiles without mitochondria. (2) S2 (9.3%) were characterized mainly by their dark mitochondria. (3) S3 (2.2%) corresponded to small nonvisual terminals that were isolated and lacked mitochondria. The PCSVs with pleiomorphic synaptic vesicles (65%) were subdivided into three groups: P1 (38%), P2 (19%), and P3 (8%). P1 and P2 were axonal in nature; P2 could be distinguished from P1 by a greater density of synaptic vesicles. P3 was of dendritic origin. Analysis of synaptic patterns revealed a small number of serial synapses. The presynaptic elements were optic boutons, whereas the intermediate profiles were dendrites with synaptic vesicles (P3). Results are compared with ultrastructural data obtained in the superficial tectal layers of other teleosts and other vertebrate groups.

Animals↗

The anatomical organization of retinal projections in the shark Scyliorhinus canicula with special reference to the evolution of the selachian primary visual system.

The retinal projections of the shark Scyliorhinus canicula were investigated using both the degeneration technique after eye removal and the radioautographic method following the intraocular injection of various tritiated tracers (proline, leucine, fucose, adenosine). The results showed contralateral projection via different optic tract components (TOM, AOT, TOm, TOl, ROVm, RODm) to various areas and nuclei of the hypothalamus (NSC), thalamus (NODLAT, NODMAT, NTTOM, NOVT, NODPT), pretectum (NOPC, NOCPd, NOCPv), tectum (SFGS, SGI) and mesencephalic tegmentum (AOTMd, NOTMv). Ipsilateral retinal projections were found to arborize within 7 distinct zones at the hypothalamic (NSC), thalamo-pretectal (NODLAT, NTTOM, NOVT, NOPC, NOCpd) and tectal (SFGS) levels. A comparison of the data with those previously obtained in different species of elasmobranchs and batoids indicate the existence of a common and consistent pattern of organization of the primary visual system in all selachians. Many of the discrepancies reported in studies on the organization of selachian retinal projection may be listed to methodological differences and/or interspecies variations in the cytoarchitecture of the different visual centers. Moreover, a comparison of the primary visual system of more primitive squalomorph sharks with that of the more advanced galeomorph sharks and batoids suggests that this system evolved through an increase in the neuronal density of the target structures and transformations in the dendritic configurations of the postsynaptic neurons rather than through an increase in the total number of projection zones.

Animals↗

Cloning of Micrococcus luteus 3-methyladenine-DNA glycosylase genes in Escherichia coli.

The 3-methyladenine-DNA glycosylase (m3ADG) excises 3-methyladenine (m3A) residues formed in DNA after treatment with alkylating agents. In Escherichia coli, the repair of this type of damage depends on the products of the genes tagA and/or alkA, which code for m3ADG I (20 kDa) and II (30 kDa), respectively. The tagA- and alkA--single mutants are sensitive to alkylating agents, the double mutant much more so. We have cloned two genes of Micrococcus luteus that can partly substitute the function of the E. coli tagA- and alkA- genes. An M. luteus genome bank was made by shotgun cloning of EcoRI + BamHI-digested DNA into pBR322. Two hybrid plasmids were identified that confer methylmethane sulfonate (MMS) resistance to the tagA- ada+ mutant and a capacity to reactivate MMS-treated bacteriophage lambda. Each hybrid plasmid directed the synthesis of 21-kDa m3ADG in E. coli tagA- ada-, which were not inhibited by 4 mM m3A. However, the restriction maps of the two cloned genes were different, and they showed no sequence homology as judged by the lack of cross hybridization.

Cloning, Molecular↗

Use of granulated sugar in treatment of open mediastinitis after cardiac surgery.

19 critically ill adults with acute mediastinitis after cardiac surgery were treated with granulated sugar, either directly (11 patients) or after failure of continuous irrigation (8 patients). Mediastinal tissue cultures were positive in 18 patients. Packing the mediastinal cavity with granulated sugar every 3 or 4 h resulted in near-complete debridement of the wound and rapid formation of granulation tissue in all patients and sterilisation of the wound after an average of 7.6 days. Dressings were easy and painless to change. 5/19 (26%) patients died before discharge, but none because of wound complications. The rest were discharged on average 54.2 days (range 29-120) after initial debridement of the wound; 11 underwent secondary surgical closure of the wound and in 3 the wound healed by granulation tissue formation alone. No recurrence of sternal infection has occurred after a mean follow-up of 8.2 months (range 3 to 17).

Adult↗

The penetration of macrolides into bronchial secretions.

Macrolides have shown efficacy in the treatment of a large range of respiratory infections. These antibiotics are well tolerated, have a narrow antibacterial spectrum, and excellent diffusion properties. We have studied the penetration into bronchial secretions of three macrolides, erythromycin, josamycin and oleandomycin. The bronchial concentrations of erythromycin reached an average of 1 mg/l 2 h after oral administration of 1 g; they were lower for josamycin (0.52 mg/l) but the ratio between bronchial and simultaneous serum concentrations was similar for both drugs. Bronchial levels of oleandomycin were rapidly higher than the serum levels, reaching 3 to 4 mg/l, a ratio of more than 100%. Other studies on tissue concentrations of erythromycin and josamycin showed local levels of 4 to 6 mg/l, whereas in bronchial secretions the concentrations were identical to those measured in our study. On the whole, the good diffusion of macrolides into respiratory tissues and secretions as well as in-vitro antibacterial activity against most species responsible for respiratory infections confirm their indication in the treatment of these infections.

Adult↗

Pharmacokinetics of apalcillin in intensive-care patients: study of penetration into the respiratory tract.

A pharmacokinetic study of apalcillin was performed in 12 patients in an intensive-care unit. All received a single dose of 30 mg/kg in a 30 min infusion followed by 90 mg/kg/day for four days; six patients (group A) were treated by intermittent administration for two days (30 mg/kg in 30 min infusion, three times daily), followed by continuous infusion for the next two days; six other patients (group B) first received continuous infusion followed by intermittent infusion. Serial serum specimens were collected after the first infusion and on the third and fifth days of treatment. Bronchial secretions were taken simultaneously via an endotracheal tube or the tracheostomy cannula, in order to study the penetration of the drug into the respiratory tract. Assays were performed by a microbiological method. A mean serum peak value of 87.1 +/- 6.13 mg/l 5 min after the end of the first injection was followed by a slow decrease in serum levels and a residual value of 6.29 +/- 3.21 mg/l (8h). Intermittent administration resulted in a mean serum peak of 79.56 +/- 12.35 mg/l whereas after continuous infusion, a steady state of about 30 mg/l was obtained. No significant difference was found between pharmacokinetic parameters for the two groups. In bronchial secretions, a mean peak value of 5.8 mg/l was attained by the second hour. Decreased levels in bronchial secretions measured after three or five days treatment were possibly related to a decrease in inflammation.

Ampicillin↗

Prospective evaluation of the protected specimen brush for the diagnosis of pulmonary infections in ventilated patients.

To determine the relative cultural accuracy of the bronchoscopic protected specimen brush (PSB) in ventilated patients, we compared this method in the same area of the lung with histologic and bacteriologic examinations of pulmonary specimens. The procedures were concluded just after death when the ventilator was still functioning. Samples via the PSB were taken from a branch of the anterior basal bronchus of the left lower lobe, and immediate left thoracotomy was performed to obtain peripheral specimens from the corresponding segment for quantitative cultures. Twenty-six patients were studied; 6 had histologically proved pneumonia. Using quantitative cultures, a correlation was evidenced between PSB and lung cultures, especially in the subgroup of patients who received no antibiotic during the week preceding their death. No pneumonia was observed when PSB cultures isolated no organisms in concentrations greater than 10(3) colony-forming units (cfu) per ml. The PSB cultures at a level of 10(3) cfu/ml identified every patient with histologically proved pneumonia and every microorganism present in concentrations of 10(4) cfu/g or greater in the lungs. Moreover, in the subgroup of patients receiving no antibiotic, only 4 microorganisms were isolated by the PSB in concentrations greater than 10(3) cfu/ml and not found in the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[New findings on the organization of retinal projections in the Scyliorhinus canicula shark. Radioautographic study].

The retinal projections of the shark Scyliorhinus canicula were re-examined using the radioautographic method following the intraocular injection of tritiated tracers. New primary visual centers were identified. Overall 12 distinct sites of termination of contralateral optic endings were found distributed within five levels of the brain (hypothalamus, thalamus, pretectum, tectum and mesencephalic tegmentum). Furthermore the presence of a small ipsilateral retinal projection was demonstrated attaining the hypothalamic thalamo:pretectal and tectal levels. These new data broaden our understanding of the organization of the primary visual system in Scyliorhinus as defined previously using the degeneration technique.

Animals↗

[Bronchial diffusion of new anti-pseudomonal beta-lactams. Clinical significance].

In treating severe respiratory infections due to Pseudomonas aeruginosa and in patients with cystic fibrosis, new anti-pseudomonal beta-lactams constitute a good alternative to the traditional aminoglycoside antibiotic therapy. Among several criteria for the choice of an antibiotic, estimation of intrabronchial levels is to be taken into account. The authors report the results of the study of a new semi-synthetic penicillin, apalcillin, and two cephalosporins (cefsulodin, ceftazidime), active in vitro against Pseudomonas; their penetration into respiratory secretions was evaluated in 48 patients, intubated, tracheostomized, or undergoing fiberoptic bronchoscopy. Antibiotic concentrations were measured by the microbiological procedure. Bronchial penetration of apalcillin was early and noticeable, reaching a bronchial peak representing 20% of the simultaneous seric concentration. The local levels of cefsulodin and of ceftazidime did not differ from those achieved with cephalosporins studied previously; the bronchial peak reached 5,6 micrograms/ml for both drugs 2 hours after administration; this bronchial level corresponded to 15 to 20% of the serum concentration. The clinical response could not be evaluated due to the severe underlying pathology which compromised the outcome of the disease in the patients of this study. However, at least for apalcillin, a significant correlation was noted between bronchial levels, susceptibility of bacteria isolated in patients, and eradication of susceptible organisms.

Anti-Bacterial Agents↗

[Effect of a secretolytic agent (bromhexine) on the penetration of erythromycin into bronchial secretions].

The authors report the results of a double blind study in 22 patients on the penetration of erythromycin into bronchial secretion. The antibiotic erythromycin was administered in combination with bromhexine, which is known to disrupt mucopolysaccharide fibers in respiratory secretions. The objective of the study was to demonstrate the possible increase of the rate of penetration of erythromycin when combined with bromhexine. The study was carried out in a double blind experiment; bronchial secretions were obtained from patients with bronchial hypersecretion by means of fiberoptic bronchoscopy. The assessment of erythromycin concentrations in all samples was performed by means of microbiological agar diffusion method. The results of the investigation show a significant increase of the ratios between bronchial levels and simultaneous serum concentrations of erythromycin when administered in combination with bromhexine. The results of this preliminary study suggest the continuation of similar investigations with other antibiotics usually administered for the treatment of respiratory infections.

Bromhexine↗

[Pharmacokinetics of mezlocillin in bronchial secretions (author's transl)].

This study was designed to measure the penetration of mezlocillin into respiratory secretions taken from tracheostomized patients admitted to an intensive care unit. In these patients admitted to an intensive care unit. In these patients, samples can be taken at set intervals. Eighteen patients were divided into two groups, one group received a single i.v. dose of 5 g. mezlocillin and the other a one day treatment with eight-hourly infusions of 5 g mezlocillin, samples being taken after the fourth infusion. Antibiotic concentrations were measured in simultaneous samples of serum and bronchial secretions by an agar diffusion method. The results showed considerable penetration of mezlocillin into bronchial secretions. Two hours after the end of the infusion, the peak of bronchial mezlocillin concentrations varied from 10 to more than 20 micrograms/ml. The kinetics of bronchial levels exhibited slow elimination, with still measurable levels at the sixth hour (1.5 to 3 micrograms/ml). Important individual variations were seen in patients with different clinical conditions (respiratory insufficiency, acute intoxication in forced diuresis). There was no difference between the two groups of patients, which showed that no cumulation took place. It is concluded that the passage of mezlocillin in the human respiratory tract results in high bronchial concentrations which are bactericidal to most species of Enterobacteriaceae.

Adult↗

One-electron photoreduction of bacterial cytochrome P-450 by ultraviolet light. I. Steady-state irradiations.

Bacterial ferric cytochrome P-450 can be photoreduced by ultraviolet light in presence of camphor as shown by the formation of the ferrous cytochrome P-450--CO complex absorbing at 446 nm in CO-saturated solutions. This photoreduction can only be performed with wavelengths (lambda less than 315 nm) corresponding to the absorption of light by aromatic residues and in particular, tryptophan. The primary process leading to the photoreduction is thus the photoionization of tryptophan residue(s) near the active site of the protein as deduced from competitive electron scavenging with N2O. In agreement with results obtained with chemical reduction, the quantum yield of photoreduction is proportional to the content of the high-spin state of the ferric cytochrome P-450 solution. It is also shown that the camphor concentration affects the CO binding.

Camphor↗

[Penetration of cefotaxime into bronchial secretions].

The objective of this study was to evaluate the penetration into bronchial secretions, of cefotaxime, a new highly-active cephalosporin. The study was performed in 45 patients with respiratory infections. The doses and the route of administration of the drug were different in 3 groups of patients: 10 patients received 0.750 g and 20 received 1 g intramuscularly; 10 patients received a 30 min IV Infusion of 2 g of cefotaxime. Bronchial samples were taken by means of fiberoptic bronchoscopy, after a single dose in all patients, and, respectively, after 3 and 7 days treatment in 30 and 15 patients. Simultaneous serum samples were collected in order to determine relationship between bronchial and corresponding serum levels. Assays were performed by means of the microbiological agar diffusion technique. In 30 cases bacteriological analysis was performed in order to determine the MICs for cefotaxime of the bacteria isolated in sputum. The results of the study showed a mean bronchial peak reaching about 2 microgram/ml at the 3d h. Individual concentrations were varying according to doses, route of administration and underlying pathology; the ratios between bronchial and corresponding serum levels were about 15 to 23 p. cent as usual for other cephalosporins. This study indicates that cefotaxime realizes significant bronchial amounts superior to MICs of microorganisms responsible for respiratory infections.

Bronchi↗

One-electron photoreduction of bacterial cytochrome P-450 by ultraviolet light. II. A study using laser flash photolysis of the dynamics of the reduction of bacterial cytochrome P-450 in the presence of carbon monoxide. The role of the protein conformation.

The intramolecular photoreduction of the bacterial cytochrome P-450 demonstrated by the formation of the complex of reduced cytochrome m with camphor and CO has been studied by photolysis with a laser flash at 265 nm. This photoreduction of the heme follows the photoionization of a proximal aromatic amino acid residue and especially tryptophan in the nanosecond time scale as evidenced by the N2O effect on the reduction yield. However most of the hydrated electrons released in the solution do not react with the ferric porphyrin. In agreement with steady state studies, the quantum yield for formation of the complex of reduced cytochrome m with camphor and CO is proportional to the concentration of the high-spin species. The low-spin ferric porphyrin is thus not reducible by photoejected electrons. It is also shown that the growth kinetics of the transient absorbance at 446 nm characterizing the complex of reduced cytochrome m with camphor and CO correspond to a structural change affecting the protein and not to the formation of the complex of CO with the camphor-bound reduced cytochrome in which occurs on a shorter time scale in the present experimental conditions.

Carbon Monoxide↗

Specific nicking of DNA at apurinic sites by peptides containing aromatic residues.

Tripeptides containing aromatic residues between basic ones, such as Lys-Trp-Lys and Lys-Tyr-Lys can nick supercoiled or relaxed DNAs containing apurinic/apyrimidinic sites (AP-sites). The nicking, which is ionic strength-dependent, occurs at AP-sites, since native PM2 DNA is not hydrolyzed. The nicking activity of the tripeptides at AP-sites occurs in total darkness. An activation energy of 21 +/- 2 kcal . mol-1 has been calculated for the incision of PM2 DNA by Lys-Trp-Lys. Tripeptides without aromatic residues, such as Lys-Ala-Lys-O-Methyl and Lys-Lys-Lys, can nick apurinic DNA, although with a much lower efficiency. Relaxed depurinated PM2 DNA is a poor substrate for the tripeptide, indicating that single-stranded regions are better recognition sites. The nicking of the DNA backbone probably occurs by beta elimination, since reduced AP-sites do not act as substrate. The termini generated are 3'-hydroxyl and 5'-phosphoryl.

Apurinic Acid↗