Biomedical subjects
Publications and source records attributed to A Nicolas.
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In order to enhance the detection sensitivity of various glucuronic acid conjugates (phenol, menthol borneol, estrone and testosterone) in high-performance liquid chromatography (HPLC), the compounds were esterified with 4-bromomethyl-7-methoxycoumarin in the presence of potassium carbonate and 18-crown-6 in acetone. The resulting esters were chromatographed on either a normal-phase (NP) column (LiChrospher DIOL) with hexane-ethanol mixtures as eluents or a reversed-phase column (LiChrospher CH-18) with methanol-water mixtures. They were detected by UV spectrophotometry at 328 nm. The structure of the derivatives was confirmed by mass spectrometry by direct introduction and chemical ionization. Prior to this step, their isolation on a semi-preparative scale was performed by NP-HPLC. The extraction of the studied glucuronides from microsomal solutions was tested by ion-suppression and ion-pair liquid-liquid partition and liquid-solid chromatography (on octadecylsilica cartridges). Extraction and chromatographic data are discussed with regard to the determination of glucuronyltransferase activity towards the aglycones cited above.
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A method to test the uniformity of Belladonna powder in multicomponent pharmaceutical dosage forms, by the determination of atropine, is described. The procedure involves a liquid-liquid extraction, followed by liquid chromatographic separation of atropine, apoatropine and scopolamine and quantification of atropine with either ultraviolet or electrochemical detection. The method is shown to be selective, sensitive and offers good reproducibility. A detailed study of the electrochemical properties of atropine also is undertaken.
A cell line designated SRT was established from a sheep sinus tumor. Following primary culture, the cells were serially passaged 40 times. SRT cells maintained an epithelioid fibroblast-like appearance and had a population doubling time of approximately 18 hr. Karyotype analysis of 14th passage cells showed the modal 2n chromosome number to be between 46 to 60, due to a large variation in acrocentric chromosome number. The electrophoretic mobilities of enzymes extracted from SRT cells were identical with those from normal sheep sinus cells. It propagated a number of ovine, bovine and canine viruses. Some virus-like particles (80-120 nm) were observed under the electron microscope. The tumor origin, good growth and wide range of virus susceptibility make SRT a highly suitable cell line for in vitro cancer research and for comparative virology studies.
Penicillamine exists as 2 stereoisomers, but only the D-isomer is used therapeutically. Its chemical reactivity derives from its functional groups, of which the thiol group seems the most important. It is difficult to determine penicillamine in biological fluids because of its instability, the presence of endogenous compounds with a thiol function, and the various chemical forms in which it occurs, namely reduced free penicillamine, penicillamine bound to proteins, and internal (P-S-S-P) and mixed (P-S-S-C) disulphides. The earliest assay methods (colourimetry, isotopic methods, gas-phase chromatography) were neither sensitive nor specific. High performance liquid chromatography with electrochemical detection has led to a more specific assay for D-penicillamine, with detection based on either derivatisation reactions or on electro-oxidisation of the thiol function. With dual-electrode detectors (Au/Hg) disulphides can be assayed directly. D-penicillamine is absorbed rapidly but incompletely (40 to 70%) in the intestine, with wide interindividual variations. Food, antacids and, in particular, iron reduce absorption of the drug. Its bioavailability is also dramatically decreased in patients with malabsorption states. The peak plasma concentration occurs at 1 to 3 hours after ingestion, regardless of dose, and is of the order of 1 to 2 mg/L after an oral dose of 250 mg; some investigators have reported a double peak in plasma, which is probably not due to an enterohepatic cycle. The concentration in plasma then decreases rapidly, generally following a biphasic curve. When long term treatment is discontinued, there is a slow elimination phase lasting 4 to 6 days, which suggests that there is a 'deep compartment' or 'slow pool of the drug reversibly bound to tissues', particularly the skin. This may explain the persistence of its therapeutic effect and the occurrence of undesirable side effects after treatment has been stopped. During long term treatment plasma concentrations are highly variable between individuals. They do not seem to be correlated with the activity or the toxicity of D-penicillamine in patients with rheumatoid arthritis. More than 80% of plasma D-penicillamine is bound to proteins, particularly albumin. The rest is mainly in the free reduced form or as disulphides. Only a small portion of the dose is metabolised in the liver to S-methyl-D-penicillamine. The route of elimination is mainly renal; disulphides represent the main compounds found in the urine. Faecal excretion corresponds mainly to the non-absorbed fraction of the drug.
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A 5.1-kb DNA fragment from Saccharomyces cerevisiae, which complements a yeast met2 mutant strain, has been cloned. This fragment contains the wild-type MET2 gene which codes for the homoserine O-transacetylase, one of the methionine biosynthetic enzymes. The presence of the MET2 gene has been shown by integrative transformation experiments and genetic analyses of the resulting transformants. The complete nucleotide sequence of a 2826-bp DNA fragment carrying the MET2 gene has been determined. The sequence contains one major open reading frame of 438 codons, giving a calculated Mr of 48,370 for the encoded protein. We have identified the transcriptional product of the MET2 gene and estimated its size at 1650 nucleotides.
G234 is a large silent deletion located in the middle of gene b2, which controls spore pigmentation in Ascobolus immersus. Its gene conversion directionality was studied in asci, which show evidence of heteroduplex DNA at flanking markers, and was compared to the behavior of closely linked single-base-pair insertions or deletions. We found that with the G234 deletion, the genotype of the donor strand in the heteroduplex is preferentially recovered, irrespective of its G234 or wild-type nature, whereas with single-base-pair insertions or deletions, the direction of conversion favors one genotype, whether it was the donor or the recipient strand. We conclude that there exists two mechanisms for directional gene conversion, the "donor-directed" conversion mechanism being epistatic to the "genotype-directed" one. We discuss these data with regard to models for mismatch repair.
One hundred and sixty-six children aged 3-30/12 were enrolled in this study. Initially all children were given a single injection containing live measles vaccine, diphtheria and tetanus toxoids, inactivated polio vaccine and meningococcal, A & C polysaccharide, plus an intradermal injection of BCG. In a second visit 6 months later each child was tuberculin tested and given a second dose of all the above vaccines with the exception of BCG. Blood samples were obtained before and 1 month after each vaccination. Following the second dose there was satisfactory seroconversion for all the vaccines. Tuberculin positivity rose from 5.4% before BCG vaccination to 94.4% 6 months after its administration. It is concluded that it is safe and effective to give these antigens simultaneously and that this particular schedule lends itself for use with nomadic and other unaccessible groups of population.
The authors report an eleven year old girl who manifested predominantly an acute cerebellar syndrome secondary to infection by Epstein Barr Virus. This complication is unusual and males are predominantly affected. The diagnostic and common physiopathological hypothesis are discussed.
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To assay various secondary amino drugs (sympatomimetic, beta-blocking, antiarrhythmic agents), they were converted to metal (copper or nickel) dithiocarbamate complexes by means of a pre-column derivatization method. The electrochemical properties of the complexes were studied. They were chromatographed on a reversed-phase column (LiChrosorb RP-18) with mixtures of acetate buffer (pH 5.8) and organic solvents (methanol, acetonitrile, ethanol or dichloromethane) as mobile phases. The complexes were detected by amperometry (applied potential of +0.7 V vs. SCE) or by UV spectrophotometry. The procedure has great sensitivity (10(-12) mole for each injected compound) and good selectivity for the more substituted amino drugs.
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The effects of heterozygosity on meiotic gene conversion characteristics have been studied in the fungus Ascobolus immersus. The non-Mendelian segregation patterns of seven white ascospore mutants of the b2 gene were established in the presence or the absence of additional neighbouring allelic mutations. These correspond to nine different double mutants with wild-type or pseudo-wild-type phenotypes, constituted by two +1, -1 frameshift mutations of complementary phases. When heterozygous, these double point mutations decrease, by an average of one third, the gene conversion frequencies of the mutants located on their right, toward the low conversion end of the gene. The decrease corresponds either to a reduction in all classes of non-Mendelian segregation (6:2, 5:3 and aberrant 4:4 asci) or to a reduction restricted to the single class of aberrant 4:4 asci. These modifications are explained by changes in hybrid DNA parameter values: frequencies of formation and modalities of distribution (asymmetric versus symmetric ratio). Besides the nature of the non-homology, point mutation versus deletion, which leads to quantitative differential effects, the region where the non-homology is located within the gene also appears to play an important role.