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P Masson

Publications and source records attributed to P Masson.

At least 19 recordsLinked to original sources
PubMed1992

Soman inhibition of butyrylcholinesterase in the presence of substrate: pressure and temperature perturbations.

Irreversible inhibition of butyrylcholinesterase by soman was studied in the presence of the substrate (o-nitrophenyl butyrate). Inhibition was found of the competitive complexing type. Study at different temperatures and pressures showed that the behavior of the enzyme differs from that of the inhibitor-free enzyme. In the absence of inhibitor, enzyme kinetics displayed a non-linear temperature dependence with a break at 21 degrees C. In the presence of a non-inhibitor structural analog of soman (pinacolyl dimethylphosphinate and methyl dimethylphosphinate), the Arrhenius plot break is slightly shifted (18 degrees C). On the other hand, in the presence of soman this break is abolished. The pressure-dependence of the substrate hydrolysis revealed also differences between the native enzyme and the enzyme in the presence of soman: the sign and magnitude of the apparent activation volume (delta V not equal to) were different for the two reactions. Beyond 300 bar, in the presence of soman, a plateau (delta V not equal to approx. 0) was observed over a large pressure range depending on temperature. Such a behavior with respect to temperature and pressure can reflect a soman-induced enzyme conformational state. Thus, temperature and pressure perturbations of the kinetics allow to complete the inhibition scheme of butyrylcholinesterase by soman. Our data suggest that upon soman binding, the enzyme undergoes a long-lived soman-induced-fit conformational change preceding the phosphonylation step. However, an alternative hypothesis according to which the enzyme processes a secondary soman-binding site cannot be ruled out.

Binding Sites↗
PubMed1992

Development of a novel series of styrylquinoline compounds as high-affinity leukotriene D4 receptor antagonists: synthetic and structure-activity studies leading to the discovery of (+-)-3-[[[3-[2-(7-chloro-2-quinolinyl)-(E)-ethenyl]phenyl][[3- (dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid.

Based on LTD4 receptor antagonist activity of 3-(2-quinolinyl-(E)-ethenyl)pyridine (2) found in broad screening, structure-activity studies were carried out which led to the identification of 3-[[[3-[2-(7-chloro-2-quinolinyl)-(E)-ethenyl]phenyl][[3- (dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid (1, MK-571) as a potent and orally active LTD4 receptor antagonist. These studies demonstrated that a phenyl ring could replace the pyridine in 2 without loss of activity, that 7-halogen substitution in the quinoline group was optimal for binding, that the (E)-ethenyl linkage was optimal, that binding was enhanced by incorporation of a polar acidic group or groups in the 3-position of the aryl ring, and that two acidic groups could be incorporated via a dithioacetal formed from thiopropionic acid and the corresponding styrylquinoline 3-aldehyde to yield compounds such as 20 (IC50 = 3 nM vs [3H]LTD4 binding to the guinea pig lung membrane). It was found that one of the acidic groups could be transformed into a variety of the amides without loss of potency and that the dimethylamide 1 embodied the optimal properties of intrinsic potency (IC50 = 0.8 nM on guinea pig lung LTD4 receptor) and oral in vivo potency in the guinea pig, hyperreactive rat, and squirrel monkey. The evolution of 2 to 1 involves the increase of > 6000-fold in competition for [3H]LTD4 binding to guinea pig lung membrane and a > 40-fold increase in oral activity as measured by inhibition of antigen-induced dyspnea in hyperreactive rats.

Animals↗
PubMed1992

Crude isolation of DNA from unselected human pancreatic tissue and amplification by the polymerase chain reaction of Ki-ras oncogene to detect point mutations in pancreatic cancer.

Human pancreatic tissue obtained during surgery was divided into two samples, one stored in formalin for histology and the other frozen directly for DNA studies. A small bit of the frozen tissue was excised without prior differentiation of malignant from non-malignant tissue and crude DNA prepared. The DNA was used to amplify the Ki-ras oncogenes with the polymerase chain reaction (PCR) using primers for codons 12, 13 and 61. The PCR products were hybridized with oligonucleotides to detect mutations in these codons. No mutations were seen in patients histologically free from pancreatic cancer, having cancer of the papilla of Vater or endocrine pancreatic cancer. In the 9 cases of pancreatic cancer, point mutations were detected in codon 12 in 7 cases and in codon 13 in one patient. Thus, the PCR technique can be used to detect point mutations in Ki-ras oncogenes even in crude DNA without selection of malignant from non-malignant tissue.

Codon↗
PubMed1992

[Intervention framework of the Quebec Healthy Heart Demonstration Project].

Cardiovascular diseases are Canada's primary cause of death and hospitalisation, and are the second major cause of restricted physical activity. Quebec province, with a mortality rate of 399/100,000, has figures even higher than the national average of 323/100,000, and 7 out of every 10 Quebecois present at least one of the major cardio-vascular risk factors. Following an exploratory task force on this question, the Canadian government initiated a partnership programme with the provinces wherein the federal government and provincial governments would each contribute one million Canadian dollars over a five year period for heart disease prevention programmes. Quebec province selected three different projects in which multifactorial, multisectorial community-based programmes were to be implemented. The sites chosen for the projects were: a rural region situated on the banks of the St. Laurence River, a Montreal suburban district, and a multi-ethnic, socio-economic disadvantaged community in downtown Montreal. Despite a common public health approach and the ultimate goal of improving heart health through the lowering of risk factors, each project had its own specific major intervention strategy and primary target population. The projects were linked by a study design to evaluate community and family mechanisms which favour the adoption of low risk behaviours. A coordinating committee was formed to supervise the overall project which included strategic planning, consultancy services to project staff, methodology, development and implementation, and evaluation. Each specific project team was free, however, to choose its particular orientations.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular Diseases↗
PubMed1991

Use of the polymerase chain reaction for homology probing of butyrylcholinesterase from several vertebrates.

Genomic blots from man, monkey, cow, sheep, pig, rabbit, dog, rat, mouse, guinea pig, and chicken DNA were hybridized with probes derived from the four exons of the human butyrylcholinesterase gene (BCHE) (Arpagaus, M., Kott, M., Vatsis, K. P., Bartels, C. F., La Du, B. N., and Lockridge, O. (1990) Biochemistry 29, 124-131). Results showed that the BCHE gene was present in a single copy in the genome of all these vertebrates. The polymerase chain reaction was used to amplify genomic DNA from these animals with oligonucleotides derived from the human BCHE coding sequence. The amplified segment contained 423 bp of BCHE sequence including the active site serine of the enzyme (amino acid 198) and a component of the anionic site, aspartate 70. Amplification was successful for monkey, pig, cow, dog, sheep, and rabbit DNA, but unsuccessful for rat, guinea pig, mouse, and chicken DNA. Amplified segments were cloned in M13 and sequenced. The mouse sequence was obtained by sequencing a genomic clone. The highest identity of the human amino acid sequence was found with monkey (100%) and the lowest with mouse (91.5%). The sequence around the active site serine 198, Phe-Gly-Glu-Ser-Ala-Gly-Ala, was conserved in all eight animals as was the anionic site component, aspartate 70. A phylogenetic tree of mammalian butyrylcholinesterases was constructed using the partial BCHE sequences.

Amino Acid Sequence↗
PubMed1991

Structural and functional investigations of cholinesterases by means of affinity electrophoresis.

1. After a brief survey of the basic affinity electrophoresis concepts, the usual ways for preparing affinity electrophoresis ligands are examined. 2. Then results obtained on cholinesterases are reviewed. This section includes (a) structural and functional investigations on anionic sites, i.e., study of ligand-induced conformational change, organophosphate-induced "aging," genetic variants, and active-site topology; and (b) characterization of cholinesterase conjugates (hybrid proteins) and glycoinositol phospholipid-anchored cholinesterases. 3. The future prospects of affinity electrophoresis, e.g., investigations on the esteratic site and exploration of the carbohydrate moiety, are emphasized in the concluding section.

Affinity Labels↗
PubMed1991

Evaluation of CEA, CA 19-9, CA-50, CA-195, and TATI with special reference to pancreatic disorders.

The tumor markers CEA, CA 19-9, CA-50, CA-195, and TATI were analyzed in patients with pancreatic diseases as well as disorders in the upper quadrant of the abdomen. Two different methods for CA-50, namely CA-50 IRMA and CA-50 DELFIA, which are based on the same monoclonal antibody, were used. The sensitivities, specificities, and predictive values of positive and negative results were calculated at one, three, and ten multiples of the upper reference value ("cutoff") for each method. All the tumor markers except TATI had sensitivities exceeding 90% at one cutoff level, but CEA had low specificity. Poor sensitivities were observed for CEA and TATI at three cutoff levels, whereas CA 19-9, CA-50, and CA-195 had sensitivities and specificities greater than 80%. The sensitivities of these tumor markers decreased at 10 cutoff levels, although the specificities exceeded 95%. The predictive values of positive and negative results were also evaluated at these three cutoff levels. High scores were observed at three cutoff levels. Examined together with the sensitivity and specificity, the evaluation at three cutoff levels indicated that CA 19-9, CA-50, and CA-195 can be used in the diagnostic arsenal for the detection of cancer of the exocrine pancreas in symptomatic patients, and in the differential diagnosis between pancreatic cancer and chronic pancreatitis. Although CA-50 IRMA and CA-50 DELFIA are based on the same monoclonal antibody, there were substantial differences in the levels of CA-50 in a lot of the patients when samples were analyzed by the two methods. These differences were shown to be methodological, and they affected the test evaluations to some extent.

Antibodies, Monoclonal↗
PubMed1991

Plasma concentrations of CA-50 in relation to tumour burden in exocrine pancreatic cancer.

The tumour-associated antigen CA-50 was analysed in plasma from 90 patients with cytologically verified exocrine carcinoma of the pancreas, and related to the size of the primary carcinoma, the largest metastasis of the liver and the degree of tumour-transformed liver parenchyme at 143 examinations. The median concentration of CA-50 in the patients with metastases of the liver was significantly higher than in the group lacking metastases. Spearman rank correlation test at three different levels of CA-50 (all values, exceeding 100 U/ml and exceeding 200 U/ml), showed a correlation between CA-50 and diameter of the primary pancreatic carcinoma in patients with liver metastases, but not in the group lacking liver metastases. No correlations were seen between CA-50 levels and size of liver metastasis or degree of tumour-transformed liver parenchyme. Hence, high plasma concentrations of CA-50 in patients with diagnosed or suspected exocrine pancreatic carcinoma could strongly indicate metastatic processes.

Adult↗
PubMed1991

Structure and function of the maize Spm transposable element.

The Spm's primary transcript is alternatively spliced to give at least 4 different transcripts which code for proteins with extensive overlapping domains. Two of these proteins, the tnpA and tnpD gene products, are necessary and sufficient to promote dSpm transposition in tobacco. Moreover, the tnpA gene product is also sufficient to suppress the basal level of expression observed in some dSpm-disrupted genes, and probably to activate the expression of inactive elements and of other dSpm-disrupted genes. The functions of the tnpB and tnpC gene products remain unknown. However, their structure suggests that they act as negative regulators of the Spm transposase function.

DNA Transposable Elements↗
PubMed1991

A comparative Raman spectroscopic study of cholinesterases.

We report Raman spectra of various cholinesterases: lytic tetrameric forms (G4) obtained by tryptic digestion of asymmetric acetylcholinesterase (AChE) from Torpedo californica and Electrophorus electricus, a PI-PLC-treated dimeric form (G2) of AChE from T marmorata, and the soluble tetrameric form (G4) of butyrylcholinesterase (BuChE) from human plasma. The contribution of different types of secondary structure was estimated by analyzing the amide I band, using the method of Williams. The spectra of cholinesterases in 10 mM Tris-HCl (pH 7.0) indicate the presence of both alpha-helices (about 50%) and beta-sheets (about 25%), together with 15% turns and 10% undefined structures. In 20 mM phosphate buffer (pH 7.0), the spectra indicated a smaller contribution of alpha-helical structure (about 35%) and an increased beta-sheet content (from 25 to 35%). This shows that the ionic milieu profoundly affects either the conformation of the protein (AChE activity is known to be sensitive to ionic strength), or the evaluation of secondary structure, or both. In addition, we analyzed vibrations corresponding to the side chains of aromatic and aliphatic amino acids. In particular, the analyses of the tyrosine doublet (830-850 cm-1) and of the tryptophan vibration at 880 cm-1 indicated that these residues are predominantly 'exposed' on the surface of the molecules.

Acetylcholinesterase↗
PubMed1991

The tnpA and tnpD gene products of the Spm element are required for transposition in tobacco.

The maize Suppressor-mutator (Spm) element encodes four alternatively spliced transcripts designated tnpA, tnpB, tnpC, and tnpD. tnpA and tnpB are monocistronic, whereas tnpC and tnpD are dicistronic, and the protein-coding sequences of each transcript overlap extensively with those of one or more of the other transcripts. We have analyzed the role of the Spm-encoded gene products in element transposition by using cDNAs with a single open reading frame to (1) complement Spm elements with frameshift mutations and (2) complement each other in a tobacco transposition assay. We report that whereas the tnpA and tnpD gene products are essential for transposition, the tnpB and tnpC gene products are not. We have analyzed the structure of empty donor sites, new insertion sites, and potential transposition intermediates. We discuss the implications of our findings for the mechanism of Spm transposition.

Base Sequence↗
PubMed1991

Pharmacology of the leukotriene antagonist verlukast: the (R)-enantiomer of MK-571.

Verlukast (MK-679) (3-[(3-(2-(7-chloro-2-quinolinyl)-(E)-ethenyl)phenyl)[3-(dimethylamino)- 3- oxopropyl)thio)methyl)-thio)propionic acid) is a potent and selective inhibitor of [3H]leukotriene D4 binding in guinea-pig (IC50 = 3.1 +/- 0.5 nM) and human (IC50 = 8.0 +/- 3.0 nM) lung homogenates and dimethyl sulfoxide differentiated U937 cell membrane preparations (IC50 = 10.7 +/- 1.6 nM) but is essentially inactive versus [3H]leukotriene C4 binding in guinea-pig lung homogenates (IC50 values of 19 and 33 microM). Functionally, when tested at 60 nM, it antagonized contractions of guinea-pig trachea (GPT) induced by leukotriene C4, leukotriene D4, and leukotriene E4 (respective-log KB values of 8.6, 8.8, and 8.9) and contractions of human trachea (HT) induced by leukotriene D4 (-log KB value 8.3 +/- 0.2). In contrast, verlukast (20-200 nM) failed to antagonize contractions of GPT induced by leukotriene C4 in the presence of 45 mM L-serine borate. Intravenous (i.v.) and aerosol verlukast antagonized bronchoconstriction (BC) induced in anaesthetized guinea pigs by i.v. leukotriene D4 but did not block BC to arachidonic acid or histamine. Intraduodenal verlukast (0.25 mg/kg) antagonized leukotriene D4 (0.2 micrograms/kg) induced BC in guinea pigs. Oral and aerosol administration blocked leukotriene D4-induced BC in conscious squirrel monkeys. Orally administered compound also blocked ovalbumin-induced BC in conscious sensitized rats treated with methysergide (3 micrograms/kg). The pharmacological profile for verlukast is similar to that of the racemic compound, MK-571. Verlukast is currently in clinical development for the treatment of asthma and related diseases.

Animals↗
PubMed1991

[Parental knowledge about their asthmatic children].

A questionnaire was administered to parents of 171 asthmatic children, and their knowledge of asthma was evaluated using a quantitative score. The mean age of children was 5 yr and the mean duration of their asthma was 3 yr. Each sign of the classical triad "noisy breathing, cough, indrawing" was mentioned by two-thirds of parents. Inhaled agents perceived as triggers of asthma were: animal hair (73.7%), dust (69.6%), pollen (60.2%), tobacco (44.4%), molds (14.6%). Other triggering agents mentioned were: stress (51.5%), infections (38%), exercise (13.5%). Mothers with college or university education knew more clinical signs of an attack (P less than 0.01) and more triggering factors (P less than 0.005). Parents satisfied with previous teaching knew more threatening signs of an attack (P less than 0.01). About 80% of those that used theophylline and 49.4% of those that used inhaled beta-2-agonists knew the correct mode of administration. Parents satisfied with previous teaching had better knowledge of the side-effects of theophylline (P less than 0.005) and beta-2-agonists (P less than 0.02). 58.5% of those that used cromolyn sodium did not know the mean duration of a therapeutic trial and 15% did not use it as prophylaxis. 57.1% of those that used oral corticosteroids did not know any side-effects of the drug. About half of the parents indicated that they would like to receive more information about the causes and the appropriate treatment of asthma. It was concluded that parental teaching should focus more on environmental and therapeutic issues.

Asthma↗
PubMed1991

Neonatal Noonan syndrome with a molluscoid cutaneous excess over the scalp.

The Noonan syndrome is a multiple congenital anomalies syndrome with variable expressivity and autosomal dominant inheritance. We report an observation of a newborn with Noonan syndrome and an unusual molluscoid cutaneous excess over the scalp that might represent a new skin manifestation in Noonan Syndrome rather than a consequence of lymphatic dysplasia.

Chromosome Aberrations↗
PubMed1991

Television and the 3- to 10-year-old child.

A questionnaire on the use of television was administered to the parents of 387 children aged between 3 and 10 years. All families owned at least one television set and 57.6% of families owned two or more sets, with one in the child's bedroom in 10.6% of cases. Television was turned on all day in 16% of cases, mostly in families with low level of parental education (P less than .01). Television was on at mealtime in 54.5% of cases; 45.2% of children were watching television for between 7 to 16 hours per week, and the heavy viewers belonged to families with low levels of maternal education (P less than .05). About one third of children watched television without any interdiction set by their parents. According to age, from 28% to 40% of children watched violence on television. Parents believed that television facilitates learning (65.3%) but were concerned about violence (22.7%) and commercials (7.4%). Finally, 63.3% of parents reported that they would like to obtain more information about television use. According to this survey, many children are watching television without any limits being set by their parents and are witnessing violent scenes at an impressionable and vulnerable age. The pediatrician should include at routine office visits parental guidance on the mediation of television effects through coviewing, content discussion with children, and program selection.

Analysis of Variance↗