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Biomedical subjects

J L Gaillard

Publications and source records attributed to J L Gaillard.

At least 127 records · Page 7Linked to original sources

In vitro model of penetration and intracellular growth of Listeria monocytogenes in the human enterocyte-like cell line Caco-2.

Penetration and replication of Listeria monocytogenes within intestinal epithelial cells were studied by infecting the human enterocyte-like cell line Caco-2. Entry was due to directed phagocytosis, as suggested by the inhibiting effect of cytochalasin D on bacterial entry and by electron microscopy showing bacteria inside membrane-limiting vacuoles at the early stage of infection. Only bacteria from pathogenic species (L. monocytogenes and Listeria ivanovii) were able to induce their own phagocytosis by Caco-2 cells, as opposed to Listeria seeligeri, Listeria welshimeri, and Listeria innocua. L. monocytogenes multiplied readily within Caco-2 cells, with an apparent generation time of about 90 min. Listeriolysin O was found to be a major factor promoting intracellular growth of L. monocytogenes. After being internalized at the same rate as that of its hemolytic revertant strain, a nonhemolytic mutant from L. monocytogenes failed to replicate significantly within Caco-2 cells. Electron microscopic study demonstrated that bacteria from the nonhemolytic mutant remained inside phagosomes during cellular infection, whereas hemolytic bacteria from L. monocytogenes were released free within the cytoplasm. This indicates that disruption of vacuole membranes by listeriolysin O-producing strains of L. monocytogenes might be a key mechanism allowing bacteria to escape from phagosomes and to multiply unrestricted within cell cytoplasm.

Hemolysin Proteins↗

Identification of the structural gene encoding the SH-activated hemolysin of Listeria monocytogenes: listeriolysin O is homologous to streptolysin O and pneumolysin.

By immunoblotting with an antiserum raised against purified listeriolysin O, we have detected the presence of a truncated protein of 52 kilodaltons in culture supernatants of a Tn1545-induced nonhemolytic mutant of Listeria monocytogenes (J.L. Gaillard, P. Berche, and P. Sansonetti, Infect. Immun. 52:50-55, 1986). The region of insertion of the transposon has been cloned and sequenced. The transposon had inserted in an open reading frame the listeriolysin O gene. The deduced amino acid sequence of this open reading frame revealed that listeriolysin O is homologous to streptolysin O and pneumolysin, although homologies were not detectable at the DNA level.

Bacterial Proteins↗

Purification, characterization, and toxicity of the sulfhydryl-activated hemolysin listeriolysin O from Listeria monocytogenes.

We purified and characterized an extracellular hemolysin produced by Listeria monocytogenes. Hemolysin production was greatly enhanced by growing bacteria in resin (Chelex)-treated medium. This hemolysin was separated as a homogeneous protein of 60,000 daltons by using thiol-disulfide exchange affinity chromatography. This protein was a sulfhydryl-activated toxin, termed listeriolysin O, which shared the classical properties of other bacterial sulfhydryl-activated toxins: inhibition by very low amounts of cholesterol; activation by reducing agents and suppression of the lytic activity by oxidation; antigenic cross-reactivity with streptolysin O. However, listeriolysin O differed remarkably from the other sulfhydryl-activated toxins in that its cytolytic activity towards erythrocytes from various animal species was maximum at low pH (approximately 5.5) and was undetectable at pH 7.0. This suggests that the lytic activity of the toxin in host tissues might be better expressed in the acidic microenvironment, including macrophage phagosomes where bacteria presumably replicate. Listeriolysin O was lethal to mice (50% lethal dose of ca. 0.8 microgram) and induced a rapid inflammatory reaction when injected intradermally. These results favor the view that listeriolysin O might play a major role during intracellular replication of L. monocytogenes, ultimately promoting death of infected macrophages.

Animals↗

The natural history of gastroschisis during fetal life: development of the fibrous coating on the bowel loops.

Patients with gastroschisis have a paraumbilical defect of the anterior abdominal wall through which bowel loops protrude. These bowel loops are edematous and covered by a fibrous coating. The moment of occurrence of gastroschisis as well as the development of the fibrous coating are unknown. This prompted an investigation of 26 human embryos and fetuses with gastroschisis at various developmental stages (crown-rump length 25-240 mm) and two stillborn fetuses (gestational age 30 weeks) with gastroschisis, as well as resected material from ten newborns (gestational age 33-40 weeks) operated for gastroschisis. Progressive changes of the serosa were only noted after the 30th week of gestation and consisted of an amniotic fluid peritonitis and progressive fibrosis. The changes are in agreement with experimental data and correlate with changes in the composition of amniotic fluid. The findings prove that gastroschisis is a very early occurrence, while the fibrous coating is a late development.

Abdominal Muscles↗

The importance of mesenteric vascular insufficiency in meconium peritonitis.

The etiology of bowel perforations leading to meconium peritonitis was investigated in an attempt to explain the occurrence of such perforations in the absence of primary intestinal obstruction. Bowel specimens from 22 patients who had presented with meconium peritonitis during a 15-year period, as well as specimens from five patients with intestinal atresia without associated meconium peritonitis, were re-evaluated microscopically. An extensive review of the literature concerning meconium peritonitis, involving 1,084 patients, was compared with the results of a retrospective study of 69 patients from The Netherlands. In approximately 50 per cent of these cases there was no detectable primary cause of the bowel perforation. The pathologic findings, in combination with earlier experimental studies, indicate that vascular insufficiency may result in bowel wall perforation without prior intestinal obstruction. It is suggested that temporary decrease of mesenteric blood flow could lead to intestinal atresia and/or meconium peritonitis.

Birth Weight↗

Transposon mutagenesis as a tool to study the role of hemolysin in the virulence of Listeria monocytogenes.

The role of hemolysin in the virulence of Listeria monocytogenes was studied by using transposon mutagenesis. The 26-kilobase conjugative transposon Tn1545, originally found in Streptococcus pneumoniae, was transferred to a hemolytic virulent strain of L. monocytogenes. The frequency of transfer was estimated to be about 10(-8) per recipient. This allowed us to isolate a nonhemolytic mutant which most likely harbors a single copy of Tn1545. Loss of hemolysin production was associated with loss of virulence. The 50% lethal dose of the mutant was assessed to about 10(9.6) bacteria per mouse after intravenous challenge. Nonhemolytic bacteria were unable to grow in host tissues and were rapidly eliminated from the spleen and liver of infected mice. Virulence was restored in hemolysin-producing revertant obtained by spontaneous loss of transposon Tn1545. These results strongly suggest that hemolysin is a major virulence factor implicated in the intracellular growth of L. monocytogenes.

Animals↗

[In vitro activity of cefotaxime, latamoxef and ceftriaxone on hospital strains of Enterobacteriaceae resistant to cefalotine and cefoxitine].

An in vitro study of the sensitivity of three cephalosporins of the third generation was performed on 119 wild strains of enterobacteriae selected because of their resistance to cefalotine and cefoxitine. Cefotaxime, latamoxef and cetriaxone remain very active on such strains since almost all of the strains were inhibited by a dose of 4 micrograms/ml and CI 50 p. cent was below 0.20 micrograms/ml. The activity of these three cephalosporins was comparable on groups E. coli, Klebsiella-Enterobacter-Serratia and C. freudii. Ceftriaxone appeared clearly more active than latamoxef and cefotaxime on Proteus stains.

Cefotaxime↗

Primary restrictive foramen ovale.

A newborn infant with primary restrictive foramen ovale, tubular hypoplasia of the aortic arch, and some other developmental defects is described. This combination resulted in fetal hydrops, as was shown by ultrasonography. The child died 24 h after birth due to low output syndrome and extensive bronchopneumonia. The pathogenesis of this clinical entity is discussed.

Aorta, Thoracic↗

[Self dialysis: a new method of treatment for end-stage renal disease].

Self-hemodialysis in a limited-care facility could be a good alternative for patients who are reluctant to home dialysis for several reasons. Through reduction of nursing personnel and elimination of physician attention at each dialysis, self-hemodialysis in a limited-care facility, where the patient dialyses himself and cleans his own machine without assistance, has reduced the cost to about one-half of center cost. From March 1980 to December 1982, out of 65 dialysed patients from Beauce and Perche Area, 33 patients were treated in the Hemodialysis Unit-Chartres Hospital (50.8%), only 5 were on home dialysis (7.6%), 15 were on CAPD (23.1%) and 12 were on self-hemodialysis in a limited-care facility (18.5%). Self-hemodialysis is a practical addition to various modalities treating end-stage renal disease and, in our experience, full compliance to the dialysis regimen was achieved in all patients.

Adult↗

Specific inhibition of phosphatidate cytidylyltransferase from Bacillus subtilis membranes by cytidine monophosphate.

In Bacillus subtilis, the phosphatidate cytidylyltransferase was localized exclusively in the membrane fraction prepared by sucrose density gradient fractionation. A single enzyme could synthesize the two liponucleotides: CDPdiacylglycerol and dCDPdiacylglycerol. Kinetic experiments and isotopic exchange reactions suggested a ping-pong mechanism. Among the nucleosides monophosphate, CMP specifically reduced the synthesis of both liponucleotides. This inhibition was non-competitive and might be involved in regulation of phospholipid synthesis.

Bacillus subtilis↗

[Pharmacology of anti-platelet agents].

A new class of drugs has appeared alongside classical anti-thrombotic agents such as heparin and oral anticoagulants, characterised by their ability to modify the behaviour of platelets: "anti-platelet" agents. This article reviews the platelet actions, pharmacokinetics, conditions of use and side effects of the four chief agents available: acetylsalicylic acid (ASA), sulfinpyrazone, dipyridamole and ticlopidine. The mode of action of the first of them is that best studied. ASA opposes the conversion of arachidonic acid to prostaglandins and thromboxane, by the irreversible acetylation of cyclo-oxygenase. Nevertheless, major therapeutic trials involving ASA have yielded only poor results. There are at least two possible explanations for this state of affairs: --aggregation may occur even when thromboxane is blocked, in particular in response to thrombin; --ASA has been used at doses also capable of inhibiting the formation by the vascular wall of an anti-aggregant prostaglandin, PGI2. Current efforts by pharmacologists which should result in better adapted and hence more effective anti-thrombotic methods, are essentially concerned with the following points: --to understand why sulfinpyrazone, which in principle has the same mode of action as ASA, seems sometimes more active and sometimes less active than the latter according to whether coronary or cerebrovascular accidents are involved; --to propose a rational prescription programme for ASA, in such a way that it inhibits only little, and for as short a time as possible, the production of PGI2 (e.g. 200 mg every three days): --to perfect more active combinations; --synthesis of new substances, e.g. thromboxane synthetase inhibitors, or stable analogues of PGI2. The reasons which suggest that such substances could be used more beneficially in man are expanded.

Animals↗

[Bicarbonate dialysis: comparative study of its long-term effects].

Changes in blood bicarbonate, phosphate and lipid were followed up on 9 patients as they are dialyzed with an acetate containing dialysate (AC) during 2 years and with a bicarbonate containing dialysate (BC) during 2 more years. The mean (+/- SD) predialysis concentration of blood bicarbonate was 23.11 +/- 1.09 mmol/L on AC period and 26.72 +/- 1.26 mmol/L on BC period. The new bicarbonate concentration steady state was reached with a delay of about 3 months. The mean (+/- SD) predialysis phosphate concentration was lower during BC period (1.73 +/- 0.17 vs 1.95 +/- 1.26 mmol/L). Although the changes were not significant, less aluminium hydroxide (4.8 +/- 0.8 vs 6.0 +/- 1.3 g per day) was necessary to control blood phosphate during BC period. The most striking changes in this long term study was the tolerance of the patients on bicarbonate dialysis, where hypotension episodes and muscles cramps were reduced by 50% and headache, nausea and vomiting disappeared almost completely. Conversely, no significant changes in lipid status with changing dialysate could be found. The results of this long term study provide strong support for promoting bicarbonate containing dialysate for all hemodialyzed patients.

Acetates↗

Effect of bicarbonate-containing dialysate on chronic hemodialysis patients: a comparative study.

Changes in pH and blood gases were studied during hemodialysis with both acetate and bicarbonate dialysates. During acetate dialysis, PaO2 and PaCO2 decreased significantly (P less than 0.05) from 101 +/- 2 to 93 +/- 3 mmHg and from 34.4 +/- 1.0 to 31.8 +/- 0.9 mmHg, respectively, whereas during bicarbonate dialysis neither parameter changed significantly. The final pH was 7.45 +/- 0.01 during acetate dialysis and 7.50 +/- 0.02 during bicarbonate dialysis. Plasma bicarbonate rose immediately and progressively from 18.9 +/- 0.8 to 26.8 +/- 0.9 mmol/L with bicarbonate dialysis, whereas the increase was moderate, from 19.6 +/- 0.6 to 22.3 +/- 0.5 mmol/L, with acetate dialysis. These data indicate that dialysis-induced hypoxemia was prevented and correction of acidosis was more adequate with bicarbonate dialysis. During a two-year period on bicarbonate dialysis, total cholesterol, HDL-cholesterol, and triglycerides did not change significantly when compared to acetate dialysis. The most striking change was the increased tolerance to dialysis with bicarbonate dialysis, which included a 50% reduction in hypotensive episodes and muscle cramps and an almost complete absence of headache, nausea, and vomiting.

Acetates↗

The "microscopic" type of meconium peritonitis.

An evaluation of patients with meconium peritonitis shows that, apart from the fibro-adhesive type, the (Pseudo) cystic and the generalized type, a fourth type can be distinguished. In a case of this fourth type, the "microscopic" type of meconium peritonitis, no signs of a peritonitis are found on macroscopic examination of the abdominal cavity. Conversely, microscopic examination will reveal meconium components focally outside the bowel. The clinical and histological data of 14 patients are discussed. It is pointed out that a significantly large number of patients with meconium peritonitis also have atresia of the small bowel. Based on the patient evaluation, a hypothesis is brought forward concerning the pathogenesis of these atresias.

Female↗

[Ketamine administered as an IV infusion. Use in infants weighing less and more than 10 kg (author's transl)].

The hemodynamic respiratory results and analgesic quality of ketamine administered as an IV infusion are studied. For the infants weighing less than 10 kg. The increases in arterial pressure and heart rate are not readily acceptable all the less as the ketamine requirement for good analgesia is very important. For the infant weighing more than 10 kg, the procedure of this technique is approximatively the same for the adult. The explanation of these problems is perhaps connected to the larger extra-cellular fluid volumes of young children and to their brain immaturity.

Anesthesia, Intravenous↗

[Spontaneous fracture in a hemodialyzed woman probably associated with the oral intake of aluminium gel (author's transl)].

A hemodialyzed woman with radiologically and histologically proven osteomalacia presents a spontaneous fracture that is associated with aluminium intoxication. The hyperalbuminemia (16,6 mumol/1) was not caused by the aluminium contained in the dialysate fluid but by oral ingestion of aluminium gel in a patient presenting hyperabsorption of this metal. Increased absorption could be demonstrated by oral administration of aluminium hydroxide (2 x 12 g A1 (OH)3 spread over 48 hrs) whereas the same test failed to reveal hyperabsorption in two other hemodialyzed patients. The precise mechanism of increased absorption of aluminium is not known. It is concluded that increased digestive absorption of aluminium should be investigated in patients with kidney failure treated with aluminium gel and presenting high blood levels of this metal.

Adult↗