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Biomedical subjects

A Pelletier

Publications and source records attributed to A Pelletier.

At least 37 records · Page 2Linked to original sources

Immunoscintigraphy of human lung squamous cell carcinoma using an iodine-131 labelled monoclonal antibody (Po66).

Monoclonal antibody (McAb) Po66 has been obtained by immunisation of mice against a human lung squamous cell carcinoma. The in vitro reactivity of the antibody with cancer cells and its ability to localise in human lung cancer xenografts growing in nude mice have been reported earlier. Presented here is the first clinical evaluation of the antibody for scintigraphic detection of tumours. Thirty-three patients with histologically confirmed primary non-small cell lung carcinoma were investigated. Twenty-seven of them were explored at the preoperative stage and six at 6 months after surgery. Biodistribution results were obtained from seven operated patients by combining injections of 131I-radiolabelled Po66 and of 125I-labelled unrelated immunoglobulin. The localisation index was three times higher for this specific antibody. Immunoscintigraphy detected 78% of primary tumours and 100% of recurrences. In this short series of patients, immunoscintigraphy proved helpful in the assessment of tumour spread in four patients by visualising localisations in the mediastinum or the contralateral lung which the CT scan had failed to demonstrate. Immunoscintigraphy was also more efficient than plain chest X-ray for the detection of local tumour recurrences.

Adult↗

Molecular species of choline and ethanolamine phospholipids in rat cerebellum during development.

The molecular species composition of rat cerebellar phospholipid subclasses has been studied by HPLC after phospholipase C treatment and dinitrophenyl derivatization. During rat cerebellum development (3-90 days postpartum), cholinephosphoglycerides and ethanolamine phosphoglycerides represented approximately 80% of all phospholipids, with their relative amount changing after 1 month. Among ethanolamine phosphoglycerides, the molar ratio of diacylglycerophosphoethanolamine (diacylGPE) to alkenylacylGPE decreased from approximately 1.4 at 3 days to approximately 0.5 after 10 days. The phospholipids investigated contained up to 12 different molecular species. The rate of accumulation of the various molecular species of diacylglycerophosphocholine (diacylGPC), diacylGPE, and alkenylacylGPE during cerebellar development allowed a classification into three main groups. The overall increase of the molecular species of the first group (6-diacylGPC, 5-diacylGPE, and 4-alkenylacylGPE) was approximately 18-fold between 3 and 90 days, with a faster rate of accumulation between 3 and 30 days. Those of the second group (3-diacylGPC, 5-diacylGPE, and 5-akenylacylGPE) increased by approximately 45-fold during the same developmental period, at a slow rate before day 15 and a faster one thereafter. The molecular species of the third group (3-alkenylacylGPE) increased by greater than 250-fold between 3 and 90 days, at a very slow rate before day 21 and more quickly thereafter. The different rates of accumulation of the components of the three groups during cerebellar development suggest a preferential location of the first group in membranes of neuronal perikaryons, glial cells, and synaptosomal structures. Those of the second group appear to be located in both synaptosomal membranes and myelin sheets, and those of the third group can be considered as myelin markers.

Animals↗

Purification and Characterization of Three Chitosanase Activities from Bacillus megaterium P1.

Bacillus megaterium P1, a bacterial strain capable of hydrolyzing chitosan, was isolated from soil samples. Chitosan-degrading activity was induced by chitosan but not by its constituent d-glucosamine. Extracellular secretion of chitosanase reached levels corresponding to 1 U/ml under optimal conditions. Three chitosan-degrading proteins (chitosanases A, B, and C) were purified to homogeneity. Chitosanase A (43 kilodaltons) was highly specific for chitosan and represented the major chitosan-hydrolyzing species. Chitosanases B (39.5 kilodaltons) and C (22 kilodaltons) corresponded to minor activities and possessed comparable specific activities toward chitosan, chitin, and cellulose. Chitosanase A was active from pH 4.5 to 6.5 and was stable on the basis of activity up to 45 degrees C. The optimum temperature for enzymatic chitosan hydrolysis was 50 degrees C. Kinetic studies on chitosanase A suggest that the enzyme is substrate inhibited. The apparent K(m) and V(max) determined at 22 degrees C and pH 5.6 were 0.8 mg/ml and 280 U/mg, respectively. End products of chitosan hydrolysis by each of the three chitosanases were identified as glucosamine oligomers, similar to those obtained for previously reported chitosanase digestions.

Journal Article↗

The antielastase screen of the lower respiratory tract of alpha 1-proteinase inhibitor-sufficient patients with emphysema or pneumothorax.

The present study was aimed at testing whether alpha 1-proteinase inhibitor-sufficient patients with lung emphysema or idiopathic spontaneous pneumothorax have an impaired antielastase protection at the lung alveolar level. We have collected bronchoalveolar lavage fluids (BALF) from 20 PIMM emphysematous patients (44 +/- 12 yr), 24 patients with pneumothorax but no radiologic evidence of emphysema (30 +/- 11 yr), 32 healthy subjects (27 +/- 6 yr), and 56 patients with sarcoidosis (30 +/- 11 yr). The BALF were assayed for immunoreactive albumin, alpha 1-proteinase inhibitor (alpha 1PI), leukocyte elastase-alpha 1PI complex (LE-alpha 1PI), and mucus proteinase inhibitor (MPI) as well as for porcine pancreatic elastase inhibitory capacity, a measure of active alpha 1PI. The healthy subjects and the patients with emphysema or pneumothorax had comparable levels of total and active alpha 1PI and total MPI. In contrast, the levels of LE-alpha 1PI complex were elevenfold higher in patients with emphysema than in normal subjects (p = 0.021) and tended to increase with the severity of the disease because they were negatively correlated with FEV1/FVC% (r = -0.55; 0.05 less than p less than 0.1). They did not vary with age in a population of patients with sarcoidosis (r = 0.03), suggesting that their eleven-fold increase in emphysematous patients is not related to the age of these subjects. Patients with pneumothorax had levels of LE-alpha 1PI complex that did not significantly differ from those of normal subjects (p = 0.24).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Changes in economic well-being of families with children in Canada and Quebec over the last 15 years].

"This study analyses changes in the average real income of families with children [in Canada] over the 1971-1987 period. It presents the factual basis with which to evaluate changes in incomes at a variety of positions along the income distribution, focusing on poverty and income inequality. The study presents the sources of family income changes by emphasizing: the contributions of wives' earnings which affect total family income, the incidence of poverty as well as time available for leisure and child care; the role of government's cash transfers and personal income taxes." (SUMMARY IN ENG AND SPA)

Americas↗

On the evolution of Tn21-like multiresistance transposons: sequence analysis of the gene (aacC1) for gentamicin acetyltransferase-3-I(AAC(3)-I), another member of the Tn21-based expression cassette.

The aminoglycoside-3-O-acetyltransferase-I gene (aacC1) from R plasmids of two incompatibility groups (R1033 [Tn1696], and R135) was cloned and sequenced. In the case of R1033, it was shown that the aacC gene is coded by a precise insertion of 833 bp between the aadA promoter and its structural gene in a Tn21 related transposon (Tn1696). This insertion occurs at the same target sequence as that of the OXA-1 beta-lactamase gene insertion in Tn2603. Upstream of the aacC gene, we found an open reading frame (ORF) which is probably implicated in the site-specific recombinational events involved in the evolution of this family of genetic elements. These results provide additional confirmation of the role of Tn21 elements as naturally occurring interspecific transposition and expression cassettes.

Acetyltransferases↗

Nonchromogenic hydrolysis of elastase and cathepsin G p-nitroanilide substrates by Pseudomonas aeruginosa elastase.

Pseudomonas aeruginosa, which may cause severe lung infections, secretes a metalloelastase that may interfere with the assay of neutrophil elastase and cathepsin G in lung secretions. Using nuclear magnetic resonance spectroscopy, we have shown that P. aeruginosa elastase (PsE) cleaves succinyl-Ala3-p-nitroanilide between the first and the second alanine residue, rendering this substrate inefficient for the assay of neutrophil elastase. The cleavage occurs with a kcat/Km of 2.4 X 10(3) M-1 s-1, a value eightfold higher than the kcat/Km for the chromogenic cleavage of succinyl-Ala3-p-nitroanilide by neutrophil elastase. P. aeruginosa elastase also cleaves the elastase substrate succinyl-Ala3-Val-p-nitroanilide between the second and the third alanine residue and the cathepsin G substrate succinyl-Ala2-Pro-Phe-p-nitroanilide at the Pro-Phe linkage. By contrast, methoxysuccinyl-Ala2-Pro-Val-p-nitroanilide, another elastase substrate, is not hydrolyzed by the bacterial enzyme. Our data indicate that synthetic substrates should be used with caution to assay elastase and cathepsin G in lung secretions or other biologic fluids in which metalloproteinases may be present.

Amino Acid Sequence↗

[Multiple elemental organic components of the broncho-alveolar lavage fluid in normal subjects and in various lung pathologies (excluding silica and asbestos fibers)].

Owing to a technical analysis enabling the detection of mineral elements present in trace amounts in small volumes, an analysis of the liquid obtained in 148 broncho-alveolar lavages could be studied. The elements consistently recovered were as follows: iron, copper, zinc, nickel, lead and titanium. Normal values were established. In the absence of exposure, there was no significant difference distinguishing the different pulmonary diseases studied. In occupational disease, the presence of iron in large quantities, tungsten, nickel and rare earths could be shown objectively, as well as the persistence of gold or iodine after medical absorption. However, this preliminary work does not allow one to establish a formal correlation between the alveolar concentrations obtained and the pulmonary disease observed.

Adolescent↗

Transfusions enriched for W3/25+ helper/inducer T lymphocytes prevent spontaneous diabetes in the BB/W rat.

Transfusions of spleen cells are known to prevent spontaneous autoimmune diabetes in susceptible BB/W rats, while T cell-depleted transfusions are ineffective. To characterize further the protective cell(s), we transfused young diabetes prone rats with splenocytes from diabetes resistant BB/W rats that were treated in vitro to enrich them in either OX8+ (suppressor/cytotoxic) T cells or W3/25+ (helper/inducer) T cells. Diabetes subsequently occurred in 19 of 29 (66%) recipients of OX8-enriched, W3/25-depleted cells and 20 of 37 (54%) controls, but in only 7 of 30 (23%) recipients of W3/25-enriched, OX8-depleted cells (p less than 0.005). Transfusion of spleen cells from diabetes resistant donor rats pretreated in vivo to deplete OX8+ cells also prevented diabetes in susceptible BB/W recipients. We conclude that transfusions of W3/25+ helper/inducer splenic T lymphocytes obtained from diabetes resistant animals prevent spontaneous diabetes in the BB/W rat.

Animals↗

The elastase inhibitory capacity and the alpha 1-proteinase inhibitor and bronchial inhibitor content of bronchoalveolar lavage fluids from healthy subjects.

Pulmonary emphysema is currently thought to be due to an elastase-antielastase imbalance with resultant destruction of alveolar structures. The present study was aimed at testing whether alpha 1-proteinase inhibitor (alpha 1 PI) is the major component of the antielastase screen of the lower respiratory tract of healthy subjects. Bronchoalveolar lavage was performed in 8 nonsmokers (27.8 +/- 3.8 years) and 9 smokers (25 +/- 0.96 years). The lavage fluids were tested for leukocyte and pancreatic elastase inhibitory capacity (LEIC and PEIC) and immunoreactive alpha 1 PI and bronchial inhibitor (brI) content. The mean +/- s.e.m. levels of LEIC, PEIC, alpha 1 PI and brI were 0.16 +/- 0.039, 0.042 +/- 0.006, 0.09 +/- 0.007 and 0.013 +/- 0.002 mol/mol albumin, respectively. Thus, on the average, the molar concentration of brI was about 14% that of alpha 1 PI. The difference between LEIC and alpha 1 PI did not reach statistical significance (P = 0.0503). The PEIC was however significantly lower than the alpha 1 PI levels (P less than 0.05), indicating that the lavage fluids contained both active and inactive alpha 1 PI. Nonsmokers and smokers did not differ in their LEIC, PEIC, alpha 1 PI and brI levels. When the data were examined on an individual basis, the subjects could be divided into 2 groups: group I (n = 9; 3 nonsmokers, 6 smokers) whose LEIC/alpha 1 PI molar ratios were higher than unity and group II (n = 8; 5 nonsmokers, 3 smokers) whose LEIC/alpha 1 PI molar ratios were equal or lower than unity. Group I subjects had significantly higher LEIC values (0.26 +/- 0.05 mol elastase inhibited/mol albumin) than group II individuals (0.055 +/- 0.006; P less than 0.001) but the two groups had similar levels of immunoreactive alpha 1 PI (0.09 and 0.08 mol alpha 1 PI/mol albumin for group I and II, respectively), functionally active alpha 1 PI (percentage of active alpha 1 PI: 53% and 37% for group I and II, respectively) and immunoreactive brI (0.016 and 0.010 mol brI/mol albumin for group I and II, respectively). These results suggested that the lavage fluids from group I contained significant amounts of undefined leukocyte elastase inhibitor(s). Gel filtration of a lavage fluid from group I showed that the undefined elastase inhibitor(s) co-eluted with brI. Most of the lavage fluids were still able to inhibit leukocyte elastase following removal of alpha 1 PI by perchloric acid precipitation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Prevention of postoperative anaerobic bacterial infections in abdominal surgery with metronidazole suppositories].

Metronidazole is widely used for the prevention and treatment of post-operative anaerobic infections. In this study, the prophylactic effectiveness of metronidazole suppositories was tested in patients undergoing abdominal surgery. The suppositories had previously been tested in healthy subjects for drug absorption and tolerance. Patients were divided into three treatment groups: one group received the drug intravenously, another as suppositories and the third one by both routes. Clinical effectiveness was evaluated and plasma metronidazole levels were measured. On the basis of the results obtained, we suggest that a 1 g suppository should be administered 8-hourly over the 20 hours preceding surgery, then 12-hourly if preparation of the digestive tract can be inserted between two administrations. In emergency surgery, 1 suppository must be given at least 1 hour before induction, the 12-hourly, and a 500 mg intravenous infusion at the time of induction.

Abdomen↗

Abnormalities of in vitro responses to polyclonal activation of peripheral blood lymphocytes in patients with active sarcoidosis.

A variety of immunological abnormalities have been described in patients with sarcoïdosis. At the blood level, both hypo and hyper immune responsiveness seem to coexist and were related to abnormal T cell and macrophage functions by using allogenic cocultures and/or lymphocyte fractionation. We tested several components of cell mediated responses with two in vitro models: (a) the pokeweed mitogen activation of B cells which is T cells and macrophage dependent; (b) the Epstein-Barr virus (EBV) activation of B cells which is T cell- and macrophage-independent. We confirm previous data showing that PWM induced Ig Production of peripheral blood lymphocytes (PBL) of patients with sarcoïdosis is significantly reduced compared with normal PBL. However, this is associated with an increase of IgG, IgM synthesis of EBV-infected PBL in these sixteen patients. Thus, there is no evidence for a complete B cell defect in sarcoïd PBL. Furthermore, by using limiting dilution analysis of antibody secreting cells, there is an increase of precursor B cells EBV infectable in PBL of sarcoïd patients but T cells are effective in reducing EBV-induced B cell proliferation. Finally, these abnormalities are concomitant to the disease, disappear with it, and are apparently not correlated with the stage or the activity of sarcoïdosis.

Adult↗

Long-term oxygen therapy can reverse the progression of pulmonary hypertension in patients with chronic obstructive pulmonary disease.

Sixteen patients with severe chronic obstructive pulmonary disease (COPD) (average values at the onset of O2 therapy: FEV1, 891 +/- 284 ml; PaO2, 50.2 +/- 6.6 mmHg; PaCO2, 51.0 +/- 6.4 mmHg) underwent 3 consecutive right heart catheterizations. The first was performed 47 +/- 28 months (T0) before the onset of long-term O2 therapy (LTO2). The second was performed just before the onset of LTO2 (T1). The third was performed after 31 +/- 19 months of LTO2 (T2). Oxygen therapy (15 to 18 h/day) was prescribed on the basis of usual criteria. From T0 to T1, PaO2 decreased from 59.3 +/- 9.4 to 50.2 +/- 6.6 mmHg, and mean pulmonary arterial pressure (Ppa) worsened from 23.3 +/- 6.8 to 28.0 +/- 7.4 mmHg (p less than 0.005). From T1 to T2, PaO2 was stable, whereas Ppa decreased from 28.0 +/- 7.4 to 23.9 +/- 6.6 mmHg (p less than 0.05). Pulmonary hypertension improved in 12 of the 16 patients. Before the onset of LTO2 (from T0 to T1), there was a yearly increase in Ppa of 1.47 +/- 2.3 mmHg, whereas during LTO2 a yearly decrease of 2.15 +/- 4.4 mmHg was observed, and the difference between these 2 values was highly significant. The changes in Ppa either from T0 to T1 or from T1 to T2 were not associated with concomitant changes in cardiac output or pulmonary capillary wedge pressure but were related to changes in pulmonary vascular resistance. These results suggest that LTO2 for 15 to 18 h/day can reverse the progression of pulmonary hypertension in a high percentage of patients with severe COPD, but that normalization of Ppa is rarely observed.

Aged↗

The concentration of leukocyte elastase-alpha 1-proteinase inhibitor complex in bronchoalveolar lavage fluids from healthy human subjects.

Although alpha 1-proteinase inhibitor (alpha 1-antitrypsin) is widely thought to protect lung elastin against the elastolytic action of leukocyte elastase, there is only circumstantial evidence for such a protective role. We have demonstrated and quantified elastase-alpha 1-proteinase inhibitor complex in bronchoalveolar lavage fluids from healthy smokers and nonsmokers using a new enzyme-linked immunosorbent assay. The relative concentration of complex is 0.36 +/- 0.48 mmol/mol albumin in nonsmokers and 0.33 +/- 0.29 mmol/mol albumin in smokers. Less than 1% of lavage fluid alpha 1-proteinase inhibitor is complexed with elastase (0.31% in nonsmokers and 0.34% in smokers). This proportion is, however, much higher than in normal plasma where only approximately 0.006% of inhibitor is bound to elastase. Our data confirm that alpha 1-proteinase inhibitor efficiently acts as an antielastase barrier in the lower respiratory tract.

Bronchi↗

A study of the criteria used for clinical evaluation of prophylactic treatment in bronchial asthma.

In an attempt to find better criteria for the evaluation of prophylactic treatment of asthma, we have studied the significance and the correlations of the 3 parameters usually measured: symptoms, bronchodilator requirements, changes in Peak Expiratory Flow (PEF). We have collected these data daily over a 16 week period in 13 adult asthmatics allergic to Dermatophagoides pteronyssinus. For each patient, the 3 scores were compared graphically. Linear regression was used to analyze the individual relationship between 2 daily scores. Incomplete cards mostly revealed unexpected behaviour (e.g. normal lung function but many symptoms recorded) and cannot of course be taken into account in a trial protocol. We found a good correlation between PEF and symptom scores in 10 out of 13 patients and we could point out the poor correlation between medication score and the other scores. To our knowledge, it is the first time such an objective result has been shown in asthmatic adults. Our analysis provides data which should improve the studies of prophylactic treatment efficacy in asthma.

Adult↗

Simultaneous determination of trace elements in lavage fluids from human bronchial alveoli by energy dispersive x-ray fluorescence. 1: Technique and determination of the normal reference interval.

We have applied energy dispersive x-ray fluorescence to the analysis of broncho-alveolar lavage fluids, to determine the concentration of several elements simultaneously with manipulation of the sample minimized. A 20-microL sample of a homogenized lavage fluid, to which two internal standards (containing Y and V) have been added, is deposited on a polypropylene film, 4 microns in thickness, and analyzed by x-ray fluorescence. We report the analytical procedure, the detection limits, and the reproducibility. The normal concentration range for trace elements is reported for a selected population. The simplicity and rapidity of the method, and the possibility of automating measurements, make this procedure suitable for screening large numbers of lavage specimens and to establish the diagnosis of some pneumoconioses.

Blood↗

Transbronchial needle aspiration in the diagnosis of sarcoidosis.

A total of 258 patients with suspected sarcoidosis underwent transbronchial needle aspiration lymph node biopsies and forceps bronchial biopsies during rigid bronchoscopy. Transbronchial needle aspiration biopsies revealed noncaseating granulomas in 66.3 percent of patients. When transbronchial needle aspiration biopsies were combined with forceps bronchial biopsies, the positive rate increased to 77.7 percent. No major complication occurred when using transbronchial needle aspiration. Rigid bronchoscopy with transbronchial needle aspiration biopsies appears to offer a sensitive and specific alternative to more invasive techniques used in the diagnosis of sarcoidosis.

Adolescent↗