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J M Robert

Publications and source records attributed to J M Robert.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cholinesterase inhibition by derivatives of 2-amino-4,6-dimethylpyridine.

Derivatives of 2-amino-4,6-dimethylpyridine, aryl(alkyl)carboxamides, thiocarbamides and amidrazones, already known for their anti-inflammatory properties, were found to be moderately active inhibitors of acetyl and butyrylcholinesterase. Quantitative structure-activity relationships showed that the binding affinity was enhanced by the following structural modifications: (1) increase in molecular volume, (2) decrease in the energy of the lowest unoccupied molecular orbital, (3) insertion of a methylene group between the amide carbonyl and the aromatic ring, (4) replacement of the amide oxygen by sulfur. The affinity remained, however, weaker than that of the specific inhibitor 9-amino-1,2,3,4-tetrahydroacridine (tacrine). The association of anti-inflammatory and cholinesterase inhibiting activities within the same compound may prove useful for the treatment of Alzheimer's disease.

Acetylcholinesterase↗
PubMed1997

Synthesis and anti-inflammatory activity of polyazaheterocyclic derivatives of 6-amino-2,4-lutidine and their precursors.

Derivatives of N-(4,6-pyridin-2-yl)arylcarboxamides resulting from the integration of the amidic function into 4H-1,2,4-triazole, triazol-3(2H)-one and 1H-tetrazole rings were evaluated as potential anti-inflammatory compounds. The level of activity decreased as compared to carboxamides, nevertheless their precursors and notably the corresponding amidrazones exhibited potent activity; amidrazone 21, whose ID50 was 34.4 mg.kg-1 in the rat paw edema test, was selected for further investigation. These heteroarylcarboxamide derivatives could represent an interesting alternative to classical non-steroidal anti-inflammatories in so far as they partly act by inhibition of tumor necrosis factor-alpha production.

Animals↗
PubMed1995

Multinuclear magnetic resonance studies of the interaction of inorganic cations with heparin.

The interaction of Na+, Ca2+, Mg2+, Zn2+ and La3+ with heparin, a highly negatively charged glycosaminoglycan, was studied by 1H and 23Na nuclear magnetic resonance spectroscopy. 1H chemical shift and nuclear Overhauser effect (NOE) data indicate that the counter ions Na+, Ca2+ and Mg2+ interact with the low pH, carboxylic acid form of heparin by delocalized, long-range electrostatic interactions. At higher pH, 1H chemical shift and NOE data indicate that Na+ and Mg2+ continue to interact with heparin in the same manner, even upon deprotonation of the carboxylic acid group; however, there is a site-specific contribution to the binding of Ca2+, Zn2+ and La3+ under these conditions. Acid dissociation constants for heparin carboxylic acid groups and heparin-metal binding constants were determined from the pH dependence of 1H chemical shifts and 23Na spin-lattice (T1) relaxation times. Equilibrium constants for exchange of M2+ for heparin-bound Na+ were obtained from 23Na T1 data. The acid dissociation constants show a strong dependence on Na+ concentration due to the polyelectrolyte character of heparin.

Animals↗
PubMed1995

Binding of the growth factor glycyl-L-histidyl-L-lysine by heparin.

Evidence is presented that the growth factor glycyl-histidyl-lysine (GHK) binds to heparin, and the interaction has been characterized by [1H]NMR spectroscopy. 1H chemical shifts indicate that GHK interacts with both the carboxylic acid and the carboxylate forms of heparin. The chemical shift data are consistent with a weak delocalized binding of the triprotonated (ImH+, GlyNH3+, LysNH3+) form of GHK by the carboxylic acid form of heparin. As the pD is increased and the carboxylic acid groups are titrated, chemical shift data indicate that ammonium groups of GHK are hydrogen bonded to heparin carboxylate groups, while the histidyl imidazolium ring occupies the imidazolium-binding site of heparin. Evidence for site-specific binding includes displacement of chemical shift titration curves for heparin to lower pD, increased shielding of specific heparin protons by the imidazolium ring current and displacement of chemical shift titration curves for GHK to higher pD. Specific binding constants were determined for binding of the (ImH+, GlyNH3+), LysNH3+) forms of GHK by the carboxylate form of heparin from chemical shift vs. pD titration data.

Amino Acid Sequence↗
PubMed1995

New antiinflammatory compounds that inhibit tumor necrosis factor production: probable interaction with protein kinase C activation.

We have previously described a family of benzamide derivatives that showed antiinflammatory activity in vivo on carragenin-induced paw edema and experimental cerebral edema. Those compounds inhibited eicosanoids production from activated macrophages (M phi) without inhibiting cyclooxygenase. To further investigate their antiinflammatory activity and compare it to that of classical cyclooxygenase inhibitors, we analyzed their effect on the production of a major proinflammatory cytokine, tumor necrosis factor (TNF-alpha), by in vitro-activated peritoneal macrophages. We show that, in marked contrast with ibuprofen, flurbiprofen and indomethacin which all significantly enhanced TNF production, the two benzamide derivatives tested, JM34 and JM42, significantly inhibited TNF-alpha production by zymosan or lipopolysaccharide-activated M phi. Those compounds did not interfere with the calcium-dependent pathway because they did not affect TNF production of either mice peritoneal M phi or human T cell clones induced by the calcium ionophore A23187 alone. More likely, these benzamide derivatives acted mainly at the level of the protein kinase C (PKC) pathway because: 1) After treatment of M phi with PKC inhibitors which significantly inhibited TNF production, our compounds showed no additional inhibition. 2) Our compounds significantly inhibited TNF production of M phi stimulated with the phorbol ester phorbol di-butyrate alone or in combination with A23187. 3) After depletion of PKC by prolonged phorbol di-butyrate treatment of M phi, inhibition of TNF production by our compounds was markedly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Diffusion of a particular 4.1(-) hereditary elliptocytosis allele in the French Northern Alps.

Heterozygous 4.1(-) hereditary elliptocytosis results from the absence of one haploid set of protein 4.1, a major component of the red cell skeleton. Two successive epidemiological investigations revealed fifteen probands in the French Northern Alps. The frequency of this disease seems to be very high in four small villages isolated in the Aravis mountains. The genealogical study shows that eleven probands share common ancestors who lived eight or ten generations ago in these villages. Thus there was probably a founder effect from one pair of ancestors, strengthened by endogamy. In contrast, four probands originate from another area and are not genealogically related. Recent results in molecular genetics support the present data.

Adult↗
PubMed1992

[Epidemiology of cleft palate and cleft lip inthe Rhône-Alpes/Auvergne/Jura region. Apropos of 903 cases registered 1978-1987].

Data from the Rhône-Alpes/Auvergne birth defects registry have been used to realise an epidemiological analysis of facial clefts (cleft palate and total cleft lip). Between 1978 and 1987, 903 cases have been ascertained giving an incidence of 0.67 per 1,000 for cleft lips with/without cleft palate (CLP) and 0.44 per 1,000 for cleft palates (CP). Several epidemiological characteristics have been studied: CLP are more frequent in males, and CP are more frequent in females. There is no detectable time trend, and birthweights are significantly lower in affected children than in the general population. There are more twins, more maternal epilepsy and more stimulations of ovulation in the studied sample than in the general population. The ranks of birth are higher in CP and CLP than in general population. The incidence of facial clefts in first degree relatives is 50 to 60 times the one in the general population, which is comparable to the literature findings.

Cleft Lip↗
PubMed1991

Indirect detection of mercury-199 nuclear magnetic resonance spectra of methylmercury complexes.

Measurement of 199Hg NMR spectra of methylmercury species by the heteronuclear multiple quantum coherence (HMQC) indirect proton detection method and its application to the study of the solution chemistry of CH3HgII-thiol ligand complexes are described. A sensitivity enhancement factor of 16 is obtained for measurement of the 199Hg NMR spectrum of a 4 mM solution of the CH3HgII-glutathione complex by the indirect detection method, as compared to a theoretical enhancement of 74. The less-than-theoretical enhancement is attributed to loss of signal by relaxation during the HMQC pulse sequence. Longitudinal relaxation of the 199Hg in CH3HgII-thiolate complexes is fast at the field strength used in this research (11.7 T) due to efficient relaxation by the chemical shift anisotropy mechanism. This in turn causes the transverse relaxation rate for the 199Hg spin-coupled methyl protons to be fast due to efficient relaxation by another mechanism, scalar relaxation of the second kind. Depending on the rate of exchange of CH3HgII among its complexed forms, the 199Hg line width can also include a large contribution from exchange broadening. In such cases, it is shown that extremely broad 199Hg resonances, which would be difficult to detect by direction observation, can be observed by the indirect detection method. For example, 199Hg resonances with exchange-broadened line widths up to 8000 Hz are observed by the indirect detection method for CH3HgII in mixtures of CH3HgOD and the CH3HgII-mercaptoethanol or CH3HgII-glutathione complex. The chemical shift of 199Hg in CH3HgII-thiolate ligand complexes is found to be extremely sensitive to the nature of the thiolate ligand.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic Resonance Spectroscopy↗
PubMed1991

Molecular analysis of hereditary elliptocytosis with reduced protein 4.1 in the French Northern Alps.

4.1(-) hereditary elliptocytosis (HE) is a variety of elliptocytosis resulting from the reduction (heterozygosity) or the absence (homozygosity) of protein 4.1. It is nearly always encountered in its heterozygous form. It has been found among Caucasians and North Africans in a sporadic fashion. We report the study on nine family cases of 4.1(-) HE. They were recruited independently (to the exclusion of any other variety of HE) in a limited area around the city of Annecy (French Northern Alps). The mode of genetic transmission, as well as the clinical, morphologic, and protein phenotypes fully conformed to the classical description. Western blots ruled out the existence of any protein 4.1 species of abnormal size. No obvious DNA rearrangement was detectable in any of the nine families with three 4.1 cDNA probes covering the entire coding sequence and part of the flanking 5' and 3' untranslated sequences. On the basis of five polymorphic sites (Bgl II, 2; Pvu II, 3), we found five different haplotypes in normal members of the 4.1(-) families. 4.1(-) HE was associated with the most common haplotype in all the propositi. 4.1 mRNA was studied in four families. Dot-blot hybridization experiments and Northern blots failed to show any detectable change in three families. On the other hand, they showed a 2-kb deletion in the 4.1(-) messenger RNA 5'-moiety in one family. These findings emphasize the heterogeneity of 4.1(-) HE at the molecular level.

Blotting, Southern↗
PubMed1991

Relationships between bone and skin atrophies during aging.

Bone mineral density (BMD) was measured in 133 female subjects (age: 61.7 +/- 16.3 years) by dual energy X-ray absorptiometry (DEXA). Vertebral bone mineral density (BMD; L1-L4) and BMD of the whole upper femoral extremity were taken into account. In addition, skinfold thickness was measured with a callipers on the dorsum of the nondominant hand. A significant negative correlation was found between skinfold thickness and age (r = -0.623, p less than 0.0001). Both vertebral and femoral BMD decreased with age and the slopes were similar to those observed by other authors. Skinfold thickness was significantly correlated with vertebral (r = 0.364, p less than 0.0001) and femoral BMD (r = 0.486, p less than 0.0001). Skin and bone are connective tissues whose extracellular matrix mainly contains type I collagen. It is postulated that age-related skin atrophy and bone atrophy have a common genetic mechanism. Skinfold thickness measurement may help in defining the women at risk for osteoporotic bone fractures who should be referred for a DEXA examination.

Absorptiometry, Photon↗
PubMed1991

[Genetics of neurofibromatosis: recent progress and prospects].

Two forms of neurofibromatosis are currently described. Von Reckinghausen Neurofibromatosis (NF 1) is the classic and common form, recently localised to chromosome 17. Neurofibromatosis type 2 (NF 2) or bilateral acoustic Neurofibromatosis, formerly the "central form" of von Reckinghausen disease, is characterized by multiple brain tumors, most often bilateral acoustic neuromas. The NF 2 mutation lies on the long arm of chromosome 22. The two forms predispose to benign or malignant familial tumors, derived from neural crest germ lines, such as Schwann cells. Rapid progress in the understanding of mechanisms underlying neurological tumor formation is expected in these inherited diseases. Molecular biology will allow the precise identification of genes responsible for the neurofibromatose syndromes. Practical applications, such as screening of individuals at risk for the disease will soon be available. Medical follow-up and genetic counselling should improve as a result of these advances.

Genes, Neurofibromatosis 1↗
PubMed1990

[Oculopharyngeal muscular dystrophy. A census of French families and genealogic study].

The first results of a collaborative study aimed at collecting all French families affected by oculopharyngeal muscular dystrophy (OPMD) and their genealogy are presented. The study was carried out in 28 families in whom the diagnosis of OPMD in the propositus was confirmed by the presence of typical intranuclear tubulo-filamentous inclusions in the muscle biopsy. Results suggest that the prevalence of OPMD in France is at least of 1/200,000. The disease has been observed in many countries but to our knowledge no epidemiological studies have been reported so far. However, it is known to be particularly frequent in the French-Canadian community living in Canada and USA. In the present study genealogical researches were carried out in 18 families. Three families were of Italian and two of Armenian origin. Amongst the 13 families of French ascent, 3 familial relationships were found: one from a couple married in 1783. In the other 10 French families, no interlineage was discovered in a genealogical enquiry pursued back to the 18th century. Further studies are needed to find out whether there was only one mutation responsible for all French cases or whether several mutations occurred in France, as suggested by the present study. It would be also interesting to ascertain whether there is a parental link between the French and the French-Canadian OPMD patients, the latter considered to be descendants of a couple who emigrated to Quebec in 1634.

Blepharoptosis↗
PubMed1989

Age-related clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population.

We report the results of a comprehensive and systematic clinical study of 324 patients with hereditary hemorrhagic telangiectasia, selected from a total of 1,270 cases recruited by epidemiological survey. In 94% of the cases, familial occurrence suggested autosomal dominant inheritance; maximum penetrance for at least one manifestation was 97%. Epistaxis was reported by 96% of the patients and, in more than 50%, developed before age 20. Heavy and frequent bleeding occurred mainly in middle-aged patients. Telangiectasia was documented in 74% of cases, half of whom were younger than 30 years. The frequency of involvement of the hands and wrists was 41%, and for the face, 33%. Visceral involvement was present in 25% of patients, with affected lungs and CNS in the young and gastrointestinal tract and liver in older patients. Symptomatic urinary tract involvement was seen in only two/324 patients. Involvement of other internal sites was not observed.

Adolescent↗
PubMed1989

[Results of pregnancies characterized by a decrease in the level of alpha-fetoprotein in the maternal blood].

Pregnancy outcome was followed in 123 women showing maternal serum alpha-fetoprotein, less than or equal to 0.50 MOM. In 28 cases AFP was secondarily considered as normal either after ultrasonography and correction of gestation age or after a second sample normal result. In 95 cases AFP level was confirmed lowered; perinatal outcome was normal in 70 cases and abnormal in 25. Among these 25 cases, 3 autosomal trisomies occurred, 2 trisomies 18 and 1 trisomy 21; in the 22 other cases, we observed antepartum risk factors (10 cases with impending premature labor or premature labor, 9 cases with chronic hypertension, 2 cases with Ag HBs hepatitis and 1 case with diabetes).

Female↗