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Biomedical subjects

G Paul

Publications and source records attributed to G Paul.

At least 109 records · Page 6Linked to original sources
PubMed1988

[Plasmid resistance to 3d generation cephalosporins].

Beta-lactamases still play an important part in medical bacteriology, as shown by the emergence, since 1983, of plasmid-mediated beta-lactamases with an enlarged spectrum (SHV-2, CTX-1, etc.). Such enzymes are only produced by enterobacteria and, more specifically, by Klebsiella pneumoniae. This phenomenon, described in Europe and in Africa, is certainly more widespread than it would appear, as some strains are now known to be less sensitive to third generation cephalosporins (MIC 1 to 4 mg/l). Despite differences in behaviour (cefotaximase and ceftazidimase phenotypes), resistance to amino-, carboxy- and ureido-penicillins is associated with reduced sensitivity or resistance to oxyimino beta-lactams (cefotaxime, ceftriaxone, ceftazidime, aztreonam), but cefamycins and imipenem are untouched. Being sensitive to enzyme inhibitors (e.g. clavulanic acid), these beta-lactamases can easily be detected and some infections (notably urinary tract infections) can probably be treated using these inhibitors. These enzymes show modified kinetic constants (better affinity and quicker hydrolysis) against penicillins, third generation aminothiazolimino-cephalosporins and aztreonam. The producing strains are mutants, with aminoacid 1 to 2 substitutions, of those which produce the usual plasmid-borne and transposable beta-lactamases (TEM or SHV). Because these beta-lactamases are plasmid-mediated, enzyme production mechanisms are spreading among enterobacteria species in relation to other resistance markers (tobramycin, netilmicin, amikacin). Strains which produce these new enzymes are mainly isolated from patients treated in intensive care units.

Cell Membrane Permeability↗
PubMed1988

Dissemination in five French hospitals of Klebsiella pneumoniae serotype K25 harbouring a new transferable enzymatic resistance to third generation cephalosporins and aztreonam.

A strain of Klebsiella pneumoniae K25 resistant to newer beta-lactam drugs was isolated in clusters in five hospitals in the Paris area. The MICs of ceftazidime and aztreonam (greater than or equal to 128 mg/l) were higher than that of cefotaxime (16 mg/l) for the strain but, when measured in the presence of clavulanic acid, they were less than or equal to 1 mg/l. The donor strains and derivatives produced a beta-lactamase with a pI of 7.75-7.8 and hydrolysing activity against a wide spectrum of beta-lactams similar to that of SHV-2 and SHV-3, but with significant hydrolysis of ceftazidime. This new enzyme could be designated SHV-4.

Aztreonam↗
PubMed1988

Peptide histidine methionine (PHM) increases ileostomy output.

The human vasoactive intestinal peptide (VIP) gene also encodes peptides histidine methionine (PHM) which has substantial sequence homology with VIP. Both are present in nerve fibers in the human ileum and circulate in greatly increased concentrations in patients with the watery diarrhoea syndrome. We have infused PHM (23 pmol/kg/min) into 5 patients with ileostomies to determine the effect of PHM on human ileal output. Plasma PHM levels rose from 22 +/- 6 to 6013 +/- 874 pM (mean +/- S.E.M.) during PHM infusions and ileal output rose from 16 +/- 3 to 177 +/- 27 g/30 min (P less than 0.0001). PHM infusions also produced a significant fall in the percentage of solid material and a rise in the concentration of chloride in the ileal effluent. Mean plasma PHM concentrations during PHM infusions were equal to the highest levels seen in patients with the watery diarrhoea syndrome, so PHM may contribute to diarrhoea in this condition. Neuronal PHM may exert physiological control over ileal transport of water and electrolytes.

Chlorides↗
PubMed1988

[Titration curves (ph gradient electrophoresis) of SHV-1 and SHV-2 beta-lactamases and a new type].

The molecular structures of the SHV-1 (p 453) and SHV-2 (pBP 60-1) beta-lactamases and of a new enzyme, a SHV-2 like extended broad-spectrum beta-lactamase (86-4), were compared by analysis of their titration curves (pH gradient electrophoresis). The titration curves of SHV-1 and SHV-2, which have the same isoelectric points (pI = 7.7). were completely superimposable for the whole of the pH gradient (pH 3.5-10), indicating a close homology between the two proteins, with perhaps the substitution of several amino acids by ones having the same charge. The curves of SHV-1 (pI = 7.7) and the new SHV-2-like enzyme (pI = 6.98) indicated that a basic residue in SHV-1 has been replaced by an acidic residue in the new SHV-2-like enzyme. These results show that, like SHV-2, the new beta-lactamase is a variant of SHV-1, and that the structural differences are probably limited to a very small number of amino acid residues. Nevertheless, this new beta-lactamase (SHV-3) may have arisen directly from SHV-1, indirectly via SHV-2, or even from another beta-lactamase.

Electrophoresis, Polyacrylamide Gel↗
PubMed1988

[Electrophoretic behavior of beta-lactamases in gram-negative bacteria].

The ongoing discoveries of new beta-lactamases, mainly penicillinases, in Gram-negative bacteria has emphasized the problem of their precise identification, and thus their phylogeny. Crude extracts, prepared by sonication, of 14 plasmid beta-lactamases, types TEM, carbenicillinases (CARB or PSE) and oxacillinases (OXA) were analysed by a simple, rapid (3.5 to 4 hours) method of electrophoresis on polyacrylamide (7%) agarose (1.4%) gels, using Tris-glycine buffer at pH 8.7. Preliminary serial dilutions were made to determine enzymic activity levels. Enzymes were then characterized by their relative electrophoretic mobilities. These mobilities had coefficients of variability between 2% and 10%, ranged from 5 to 61, and were correlated with their isoelectric points (pI). Thus, the lower the pI is, the greater the mobility is. Despite the high resolving power of the polyacrylamide-agarose gel system, enzymes with similar pI's and of similar types (PSE-1 and CARB-3, or OXA-1 and OXA-4) or different types (SHV-1 and OXA-6) could not be distinguished on the basis of their mobilities. However, this technique provides for rapid and easy identification of the major penicillinases in Gram-negative bacteria. A combination of polyacrylamide-agarose gel electrophoresis and pH gradient electrophoresis (titration curve) could provide a powerful approach to the study of the molecular structure of these enzymes.

Electrophoresis, Agar Gel↗
PubMed1987

[Human Pasteurella multocida infections. Value of serological diagnosis].

In five human cases of Pasteurella multocida infection, high titres of specific antibodies were found by indirect haemagglutination (capsular antigens) and agglutination (somatic antigens). The specificity of the antibodies fitted with the serotypes of the isolated strains (three A 3 and two A 7). Subsequent changes in antibody titres in human beings were similar to those observed in animals. The risk of this animal-acquired infection being probably underestimated in medical practice, the usefulness of these tests in human beings is discussed.

Adult↗
PubMed1987

Sequence of the halobacterial glycosaminoglycan.

The cell-surface glycoprotein of halobacterium contains a sulfated repeating unit saccharide chain, similar to the mammalian glycosaminoglycans. The composition of a presumptive repeating pentasaccharide unit of this glycosaminoglycan is 1 GlcNAc, 1 GalNAc, 1 Gal, 1 GalA (where GalA represents galacturonic acid), 1 3-O-methyl-GalA, and 2 SO42-. Linkage to protein of this glycoconjugate involves the hitherto unique unit Asn-GalNAc, with the N-linked asparagine residue being the second NH2-terminal amino acid and part of the common N-linked glycosyl acceptor sequence Asn-X-Thr(Ser). Transfer of the completed, sulfated glycosaminoglycan from its lipid precursor to the protein occurs at the cell surface, and the presence of this sulfated saccharide chain in the cell-surface glycoprotein seems to be required to maintain the structural integrity of the rod-shaped halobacteria. In this paper, we report the complete saccharide structure of this N-linked glycosaminoglycan. This structure is deduced from chemical analyses of fragments that were isolated after hydrazinolysis and subsequent nitrous acid deamination or after mild acidic hydrolysis of purified Pronase-derived glycosaminoglycan-peptides. The halobacterial glycosaminoglycan consists, on the average, of 10 repeating pentasaccharide units of the following structure. (formula: see text) The reducing end N-acetylgalactosamine residue is linked directly to the asparagine, without a special saccharide linker region.

Carbohydrate Conformation↗
PubMed1987

Occupational exposure to animals and antibodies against Pasteurella multocida.

The relation between occupational exposure to cattle and prevalence of antibodies against Pasteurella multocida was evaluated in 680 workers. Three groups of exposed workers in abattoirs and slaughterhouses (S), in industrial breeding (I), and in traditional breeding (T) were compared with control workers not exposed to cattle or chicken (C). The prevalence of antibodies against capsular antigen A determined by indirect haemagglutination was significantly higher in the exposed groups (S: 26.2%; I: 29.0%; T: 32.1%) than in the control group (C: 14.0%). The prevalence of antibodies against capsular antigen D did not differ significantly between the groups. The prevalence of antibodies against one or more somatic antigens 1,2,3,7,8, or 9 was higher in the exposed groups with a significant difference only for group T versus group C (p less than 0.05). There was also a significant relation between antibodies against capsular antigen A and the contacts with pets. This high prevalence of antibodies against P multocida suggests that the infection is frequently subclinical and not only a disease associated with pets but also an occupationally related infection.

Abattoirs↗
PubMed1987

Specific antibody response to Pasteurella multocida.

Six patients with culturally proven Pasteurella multocida infection were evaluated serologically. The infections were 1 foot abscess, 1 septicemia, 3 bronchitis and 1 bronchopneumonia. Most of them were elderly women closely exposed to pets or domestic animals. The serotypes of the strains were determined in 5 cases (3 A3, 2 A7). Specific antibodies against capsular and somatic antigens of P. multocida were determined by indirect hemagglutination and agglutination respectively. The antibodies were strictly directed against the capsular and somatic specificities of the isolated strain. The range of the serum antibody titers were 20 to 2,560 to capsular antigens and 5 to 640 to somatic antigens within 2 weeks after the first clinical signs of infection. Several months after successful treatment, the capsular antibodies were lower while the somatic antibodies had almost disappeared. These findings suggest a good sensitivity for these serologic methods in active cases. Declining antibody titers follow healing. Cross-reactivity of the serologic tests with other bacteria was not observed. Serologic diagnosis of P. multocida infections is a possible alternative to direct diagnosis when cultures are negative or when unusual localizations must be confirmed.

Adult↗
PubMed1987

[Titration curves of beta-lactamases using pH gradient electrophoresis].

The molecular relationships of two types of plasmid-mediated beta-lactamases, TEM-1 (R 111), TEM-2 (RP 4) and OXA-1 (RGN 238), OXA-4 (pMG 90) were analysed by combined isoelectrofocusing-electrophoresis. Titration curves of TEM-1 (pI 5.4) and TEM-2 (pI 5.6) together were consistent with the known substitution of a glutamic acid in the former by a lysin in the latter. When OXA-1 (pI 7.4) and OXA-4 (pI 7.45) were titrated, one single mobility curve was obtained reflecting their structural homogeneity. The titration curve technique will be usefull for the study of structure of beta-lactamases.

Electrophoresis, Polyacrylamide Gel↗
PubMed1987

[Campylobacter pyloridis and gastroduodenal pathology].

After the first report by Marshall and Warren of the presence of gastritis associated Campylobacter pyloridis in antral mucosa, many groups have found the same association in many countries of Europe, USA, Japan. In France, too C.P. is found in antral mucosa. We have studied 119 dyspeptic patients; during endoscopy 3 biopsy specimens were taken, one for microaerophilic culture and 2 for pathologic examination. We found the germ in 27 p. 100 of 22 normal subjects but no culture was positive. In chronic interstitial gastritis it is found in 90 p. 100 of cases and in 98 p. 100 if a duodenal ulcer is associated. Ten patients with healed duodenal ulcer have been treated by V Penicillin: 3 millions unit/day during 2 weeks. In five cases C.P. disappeared but 2 of them relapse 2 months later.

Adult↗
PubMed1986

[Mechanism of enzymatic resistance to beta-lactam antibiotics].

The resistance of bacteria, particularly Gram-negative bacteria, to beta-lactam antibiotics is principally caused by enzymes. Beta-lactamases inactivate these antibiotics by opening, more or less rapidly, the beta-lactam ring. The chronology of therapeutic discoveries is governed by natural and acquired resistance. The first step was to establish the characteristics of beta-lactamases (location, biogenesis, enzymatic profile, affinity constant, inhibition profile, isoelectric point, molecular weight, genetic determination, etc.). Advances in the selection of natural or semi-synthetic compound are centred on the following points: increased stability to beta-lactamases, inhibitory effect, reduced inducibility, low affinity for the enzyme, greater speed of penetration through the bacterial wall, increased tropism for targets. Notable among the new beta-lactam antibiotics are acylureidopenicillins, beta-lactamase inhibitors and carbapenems. The antibacterial activity of third generation cephalosporins is 10 to 1000 times higher than that of previous cephalosporins; the result is a wider spectrum including, in particular, cephalosporinase-producing organisms. Concerning acquired resistance, the behaviour of new antibiotics must be examined by comparing the minimum inhibitory concentrations of isogeneic and clinical strains, and according to phenotype or mechanism: sensitive, penicillinase producer, cephalosporinase producer or producer of both penicillinases and cephalosporinases. During synthesis of a penicillinase, penicillins and some cephalosporins are more or less inactivated. With a constitutive cephalosporinase, all cephalosporins are inactivated as are, to a lesser degree, penicillins and monobactams, e.g. aztreonam. The emergence of new enzymes, including broad-spectrum beta-lactamases, and their extension to sensitive bacteria show that the enzymatic mechanism still has potentials for development.

Anti-Bacterial Agents↗
PubMed1986

Asparaginyl-N-acetylgalactosamine. Linkage unit of halobacterial glycosaminoglycan.

The cell surface glycoprotein of Halobacteria contains two different types of sulfated saccharides: hexuronic acid-containing oligosaccharides linked to the protein via asparaginylglucose, and a serially repeated saccharide unit containing amino sugars that resembles the animal glycosaminoglycans. Here we report that 1) the sulfated repeating unit saccharide is linked to the cell surface glycoprotein via asparaginyl-N-acetylgalactosamine, 2) the amino acid sequence surrounding this linkage region is -Asn-Ala-Ser-, and thus in agreement with the acceptor sequence ASN-X-Thr(Ser) common to all eucaryotic N-glycosidically bound saccharides determined so far; 3) in addition to galactose, galacturonic acid, N-acetylglucosamine, and N-acetylgalactosamine, the methylated hexuronic acid 3-O-methylgalacturonic acid occurs as a stoichiometric constituent of the sulfated building block of the glycosaminoglycan chain.

Acetylgalactosamine↗
PubMed1986

[Bacterial flora in gastric juice taken at endoscopy in 93 normal subjects].

Bacteriologic examination of gastric juice samples taken during endoscopy in ninety-three subjects free of endoscopically-detectable disease was performed. Mucosal pH was determined using bromocresol green dye. Among the 17 subjects with a mucosal pH exceeding 4, 11 (64%) had more than 10(5) organisms/ml. In contrast, similar counts were found in only 10 of the 76 subjects with a normal mucosal pH. The pathogens recovered were normal hosts of the upper digestive tract and a few nitrate reductase + Enterobacteriaceae. Questions still to be resolved are whether these pathogens can induce disease and whether bacterial colonization correlates with the increased gastric nitrosamine levels and microscopic mucosal lesions previously described in patients with a gastric pH above 4.

Adult↗
PubMed1985

Halobacterial flagellins are sulfated glycoproteins.

The cell-surface glycoprotein of Halobacteria contains oligosaccharides of the type Glc4----1GlcA4----1GlcA4----1GlcA (where GlcA indicates glucuronic acid) with a sulfate group attached to each of the GlcA residues. We report here that in addition to this cell-surface glycoprotein, the halobacterial flagellar proteins (recently described by Alam, M., and Oesterhelt, D. (1984) J. Mol. Biol. 176, 459-475) also contain the same type of sulfated oligosaccharides. These flagellins have the following features. All of the individual flagellar proteins contain identical sulfated saccharide moieties linked to the amido nitrogen of Asn through a Glc residue (the novel type of N-glycosidic linkage that has been found in the cell-surface glycoprotein from Halobacteria (Wieland, F., Heitzer, R., and Schaefer, W. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 5470-5474)). The amino acid sequence of one carbohydrate-binding region is Gln-Ala-Ala-Gly-Ala-Asp-Asn-Jle-Asn-Leu-Thr-Lys. This surrounding sequence CHO is consistent with the general formula Asn-X-Thr(Ser), common to all N-linked glycopeptides determined so far. Biosynthesis of flagellar glycoconjugates involved sulfated oligosaccharides linked to dolichol monophosphate. The individual glycoproteins making up the flagella are structurally closely related to one another.

Amino Acid Sequence↗
PubMed1985

[Enterobacter cloacae and E. aerogenes septicemia: emergence of resistant variants (derepressed cephalosporinase) during treatment with third-generation cephalosporins].

From three patients hospitalised in intensive care units with Enterobacter septicaemia (two cases with E. cloacae, and one with E. aerogenes), cefotaxime therapy, alone or in combination with an aminoglycoside, selected variants (R) with increased resistance to beta-lactam antibiotics. The cross-resistance extended to all the beta-lactam antibiotics tested, penicillins and cephalosporins, including third-generation cephalosporins. The crude extracts of uninduced cultures of R variants showed high beta-lactamase activity and of the cephalosporinase type. These variants were selected in vitro with a frequency of 10(-6) to 10(-7) and may result from a mutation involving the regulation of Enterobacter cephalosporinases, usually inducible. Data from the literature indicated that this new type of resistance is actually emerging and observed not only in Enterobacter sp. The problem of emergence of R variants exhibiting cross-resistance to beta-lactam antibiotics should be considered when third-generation cephalosporins are used.

Adult↗