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Biomedical subjects

N Meslier

Publications and source records attributed to N Meslier.

32 records · Page 2Linked to original sources
PubMed1989

Leukotriene A4 hydrolase activity of human airway epithelial cells.

Human tracheal epithelial cells were incubated with LTA4 and metabolic products were identified in extracted supernatants by high pressure liquid chromatography, ultraviolet spectroscopy, and gas chromatography-mass spectrometry. In the presence of epithelial cells, LTA4 was converted to LTB4, but not to LTC4 or LTD4. Maximum LTB4 was released at an LTA4 concentration of 3 microM and had occurred by 30 min. LTB4 release was increased in the presence of albumin, but was not affected by extracellular calcium or A23187. This LTA4 hydrolase activity had a slower time course and could not be clearly inactivated by repeated exposure to substrate as is the case for previously described LTA4 hydrolase enzymes. This hydrolase appears to have novel biochemical characteristics.

Chromatography, High Pressure Liquid↗
PubMed1989

Biosynthesis of paf-acether. Paf-acether but not leukotriene C4 production is impaired in cultured macrophages.

After adherence for 24 or 48 h mouse peritoneal macrophages, upon a zymosan challenge, synthesized 114 +/- 55 and 82 +/- 31 pmol of paf-acether (paf)/mg of protein respectively, as compared with 513 +/- 195 pmol of paf/mg of protein in 2 h-adherent macrophages (means +/- S.D., n = 10). By contrast, 24 h- and 48 h-adherent macrophages exposed to zymosan produced more leukotriene C4 (2.7 +/- 1.1 and 1.4 +/- 0.2 nmol/mg of protein respectively, n = 5) than did 2 h-adherent macrophages (0.5 +/- 0.2 nmol/mg of protein, n = 5). Paf production was not altered when 2 h- and 24 h-adherent cells were cultured and/or stimulated in the presence of 5 microM-indomethacin, 10 microM-nordihydroguaiaretic acid or 100 microM-BW755C as compared with untreated cells. These results indirectly exclude the regulation of paf production by arachidonic acid metabolites. We investigated the efficiency of the enzymic steps which govern paf synthesis. We showed that the anabolic process was not impaired since (1) the amounts of alkylacylglycerophosphocholine and lyso-paf were similar in 2 h-, 24 h- and 48 h-adherent macrophages; (2) adding synthetic lyso-paf or acetyl-CoA to intact cells did not increase paf production in zymosan-stimulated 24 h- and 48 h-adherent macrophages; (3) the basal level of acetyltransferase was comparable in 2 h-, 24 h- and 48 h-adherent macrophages and in all cases was increased by 2-3 times upon zymosan challenge. We also showed that impaired paf production in 24 h- and 48 h-cultured macrophages was not due to the nature of the stimulus used to induce its synthesis.

Acetyltransferases↗
PubMed1989

Transcellular lipoxygenase metabolism between monocytes and platelets.

We have examined the effects of co-culture and in vitro co-stimulation on lipoxygenase metabolism in monocytes and platelets. Monocytes were obtained from the peripheral blood of normal volunteers by discontinuous gradient centrifugation and adherence to tissue culture plastic. Platelets were obtained from the platelet-rich plasma of the same donor. When 10(9) platelets and 2.5 x 10(6) monocytes were co-stimulated with 1 microM A23187, these preparations released greater quantities of 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid, 5(S),12-(S)dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acid, and leukotriene C4, 5(S)-hydroxy-6(R)-S-glutathionyl-7,9-trans-11,14-cis-eicosatetraenoic (LTC4) when compared with monocytes alone. Release of arachidonic acid, 5-HETE, delta 6-trans-LTB4, and delta 6-trans-12-epi-LTB4 from monocytes was decreased in the presence of platelets. A dose-response curve was constructed and revealed that the above changes became evident when the platelet number exceeded 10(7). Dual radiolabeling experiments with 3H- and 14C-arachidonic acid revealed that monocytes provided arachidonic acid, 5-HETE, and LTA4 for further metabolism by the platelet. Monocytes did not metabolize platelet intermediates detectably. In addition, as much as 1.2 microM 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid and 12(S)-hydroperoxy-10-trans-5,8,14-cis-eicosatetraenoic acid had no effect on monocyte lipoxygenase metabolism. Platelets were capable of converting LTA4 to LTC4, but conversion of LTA4 to LTB4 was not detected. We conclude that the monocyte and platelet lipoxygenase pathways undergo a transcellular lipoxygenase interaction that differs from the interaction of the neutrophil and platelet lipoxygenase pathways. In this interaction monocytes provide intermediate substrates for further metabolic conversion by platelets in an unidirectional manner.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1989

Diagnostic value of reversibility of chronic airway obstruction to separate asthma from chronic bronchitis: a statistical approach.

Our aim was to assess the usefulness of tests of reversibility of airways obstruction (AO) in the differential diagnosis of asthma (A) and chronic bronchitis (CB). We selected on strict clinical criteria 20 CB and 32 A patients with stable AO and measured maximal forced expiratory flows before and after increasing doses of inhaled salbutamol. The highest sensitivity (Se), specificity (Sp) and likelihood ratio (L) were obtained when the improvement in forced expiratory volume in one second (FEV1) was expressed as a percentage of predicted FEV1. Se, Sp and L were 0.97, 0.95 and 19.3 (highest possible L: 20) for an increase of 10% of predicted FEV1 on 0.2 mg of salbutamol, and 1.0, 1.0 and 20, respectively, for an increase of 15% on 1 mg of salbutamol. Conversely, L was only 2.8 when the widely used increase in FEV1 of 20% over baseline was tested. In a second group of 42 unselected patients, who were referred to the laboratory for routine lung function testing with a presenting diagnosis of A or CB, L was only 5.5 when the 10% increase in predicted FEV1 was used and even lower for the classical 20% increase over baseline FEV1. We submit that routine tests of reversibility of AO have little diagnostic usefulness in unselected patients with AO and that the commonly used criteria of 15 or 20% increase in FEV1 over baseline are of no value in separating A from CB.

Albuterol↗
PubMed1988

Local cellular and humoral responses to antigenic and distilled water challenge in subjects with allergic rhinitis.

We studied nasal responses to allergen, saline, and distilled water aerosol in 7 subjects with allergic rhinitis to determine whether they caused a similar release of mediators and influx of inflammatory cells into the nasal lumen. The subjects were challenged first with allergen and then with aerosols of distilled water and of normal saline in random order on separate days. We measured nasal airway resistance (Rn) by posterior rhinomanometry, measured the concentrations of protein, histamine, leukotrienes (LT) B4, C4, and D4, and platelet-activating factor (PAF-acether) and performed total and differential cell counts in nasal lavage fluid obtained before and after each challenge. Allergen challenge provoked a 2-fold or greater increase in nasal airway resistance in all subjects (mean increase = 12.2-fold). This response was associated with significant increases in protein, histamine, LTB4, and sulfidopeptide leukotrienes. 2-lyso-PAF-acether increased significantly, indicating activation of phospholipase A2, but PAF-acether was detected in only one subject. The total cell count increased from 55 +/- 44 x 10(3)/ml to 200 +/- 168 x 10(3)/ml; polymorphonuclear neutrophils increased from 11 +/- 22 x 10(3)/ml to 108 +/- 96 x 10(3)/ml, and eosinophils increased from 1.3 +/- 1.8 x 10(3)/ml to 10.6 +/- 15.3 x 10(3)/ml (p less than 0.05). Saline insufflation provoked insignificant changes in mean Rn, in the levels of protein and all inflammatory mediators, and in the number and types of cells in nasal lavage fluid. Distilled water insufflation also provoked an insignificant increase in mean Rn, but there was a 14-fold increase in one subject.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Frequency and severity of hypoxemia during sleep in COPD. Clinical and therapeutic impact].

The occurrence of episodes of desaturation during sleep in patients suffering from chronic airflow obstruction is well known. The severity of nocturnal hypoxaemia depends, in part, on the level of the diurnal PaO2. Hypoventilation linked to sleep is the principle mechanism responsible for the decrease in PaO2 and the desaturation which results and depends on the level of oxyhaemoglobin saturation (SaO2) during wakefulness. However, it is not possible to predict the severity of nocturnal desaturation solely on the basis of diurnal oxyhaemoglobin saturation. Numerous factors may contribute to a worsening of nocturnal desaturation. In some patients it may be associated with hypoventilation and a worsening of the ventilation perfusion inequalities. A fall in the ventilatory response to hypoxaemia and hypercapnea contributes equally to the severity of desaturation. The awake response to hypoxia is variable according to the stage of their respiratory failure but may play a role in worsening nocturnal hypoxia. Snoring and obstructive apnoea are responsible for severe desaturation in chronic airflow obstruction presenting as hypoxaemia which may be moderated during the day. At present the value of systematic nocturnal polygraphic recordings in the "work-up" of chronic airflow obstruction has not been demonstrated. Its principle practical interest is in research into the associated sleep apnoea syndrome. It should be recognised in a patient with chronic airflow obstruction who snores and is somnolent with hypoxaemia and/or poorly explained hypercapnea. The therapeutic approach in respiratory failure should take account of nocturnal desaturation and the oxygen flow at night should be superior to the one to two litres which are required to correct the diurnal hypoxaemia.

Humans↗
PubMed1987

Forced expirations in normal subjects. Is the shape of the flow rate curve related to existence of a wheeze?

The flow rate curve takes different shapes during forced expirations performed by normal subjects. In some cases a wheeze may exist. In this study, we examine the conditions for appearance of a wheeze, before and after the peak flow, and the relationship between the wheeze and the shape of the flow rate curve. We analyzed ten parameters in 83 forced expirations produced by 32 normal subjects (16 men and 16 women) using multidimensional scaling techniques. Among these expirations, 53 presented a wheeze. The first two axes of the analysis define a plane on which forced expirations are divided into four quadrants. Two opposite quadrants (upper right and bottom left) contain the wheezing expirations, while the two others only have the ones with no wheezing. This distribution corresponds to specific shapes of the flow rate curve. We found that wheezes are associated with two main shapes. One of them consists of a short onset until a sharp peak, followed by a fast exponential decay. The other is about triangular, with a late appearance of the wheeze, and is only produced by women.

Adult↗
PubMed1987

The effect of long-term almitrine therapy on sleep hypoxaemia in patients with chronic airways obstruction.

Sleep hypoxaemia was investigated in 11 patients. The patients were randomly assorted to receive almitrine bismesylate therapy or identical placebo tablets. Almitrine therapy was associated with an increase of daytime PaO2, mean SaO2 awake and during sleep, and less time when SaO2 fell below 90% during sleep. The number of desaturation episodes and lowest SaO2 were unaffected.

Administration, Oral↗
PubMed1986

[Treatment of the sleep apnea syndrome by continuous positive pressure].

Six patients with severe sleep apnoea syndrome (SAS) were treated for one night by continuous positive pressure by the nasal route (PPC). The six patients tolerated the treatment well. During the course of the night, while receiving PPC, we noticed that in five patients there was a normalisation of the indices of apnoea, a disappearance of the episodes of desaturation and a re-organisation of sleep pattern. In one patient PPC was effective on obstructive apnoea, but did not make all mixed and central apnoea disappear. After a 4 or 5 day trial in hospital, 4 patients have now been treated at home for at least 6 months. PPC remains effective and well tolerated in the long term. As it is well tolerated and effective, PPC may be used to treat patients with SAS at an earlier stage than that at which tracheotomy is proposed.

Aged↗