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Biomedical subjects

J Clain

Publications and source records attributed to J Clain.

17 recordsLinked to original sources
PubMed2006

[Antimalarial drug resistance].

Drug resistant malaria is mostly due to Plasmodium falciparum, the highly prevalent species in tropical Africa, Amazon, and Southeast Asia. P. falciparum is responsible for severe involvement of fever or anemia causing more than a million deaths per year. Rationale for treatment is becoming weak as multiple drug resistance against well-tolerated drugs develops. P. falciparum drug resistant malaria originates from chromosomal mutations. Analyses using molecular, genetic and biochemical approaches showed that: 1) impaired uptake of chloroquine by the parasite vacuole is a common characteristic of resistant strains, this phenotype correlates with pfmdr1 and pfcrt gene mutations; 2) one S108N to four (N51I, C59R, I164L) point mutations of dihydrofolate reductase, the enzyme target of antifolinics (pyrimethamine and proguanil), give moderate to high level of resistance to these drugs; 3) resistance to sulfonamides and sulfones involves mutations of dihydropteroate synthase (A437G, K540E), their enzyme target, impairing their capacity to potentiate antifolinic drugs; 4) resistance to atovaquone plus proguanil involves one single mutation on atovaquone target, cytochrome b (Y268S, C or N); 5) resistance to mefloquine is thought to be linked to the over expression of pfmdr1, a pump expelling toxic waste from eukaryotic cells. P. falciparum resistance levels may differ according to places and time, depending on malaria transmission and drug pressure. Coupling in vivo to in vitro tests, and using molecular tests is essential for the surveillance of replacement drugs. Low cost biochemical tools are urgently needed for a prospective monitoring of resistance.

Animals↗
PubMed2003

Formation of adhesive contacts: spreading versus dewetting.

A soft bead (radius Rb) is pressed with a force F against a hydrophobic glass plate through a water drop ("wet" JKR set-up). We observe with a fast camera the growth of the contact zone bridging the rubber bead to the glass. Depending on the approach velocity V, two regimes are observed: i) at large V a liquid film is squeezed at the interface and dewets by nucleation and growth of a dry contact; ii) at low velocities, the bead remains nearly spherical. As it comes into contact, the rubber bead spreads on the glass with a characteristic time (in the range of one millisecond) tau approximately eta Rb2/F, where eta is the liquid viscosity. The laws of spreading are interpreted by a balance of global mechanical and viscous forces.

Computer Simulation↗
PubMed2002

Wetting transitions at soft, sliding interfaces.

We observe (by optical interferometry) the contact of a rubber cap squeezing a nonwetting liquid against a plate moving at velocity U. At low velocities, the contact is dry. It becomes partially wet above a threshold velocity V(c1), with two symmetrical dry patches on the rear part. Above a second velocity V(c2), the contact is totally wet. This regime U>V(c2) corresponds to the hydroplaning of a car (decelerating on a wet road). We interpret the transitions at V(c1), V(c2) in terms of a competition between (a) liquid invasion induced by shear (b) spontaneous dewetting of the liquid (between nonwettable surfaces).

Journal Article↗
PubMed2000

Two mild cystic fibrosis-associated mutations result in severe cystic fibrosis when combined in cis and reveal a residue important for cystic fibrosis transmembrane conductance regulator processing and function.

The number of complex cystic fibrosis transmembrane conductance regulator (CFTR) genotypes identified as having double-mutant alleles with two mutations inherited in cis has been growing. We investigated the structure-function relationships of a severe cystic fibrosis (CF)-associated double mutant (R347H-D979A) to evaluate the contribution of each mild mutation to the phenotype. CFTR mutants expressed in HeLa cells were analyzed for protein biosynthesis and Cl(-) channel activity. Our data show that R347H is associated with mild defective Cl(-) channel activity and that the D979A defect leads to misprocessing. The mutant R347H-D979A combines both defects for a dramatic decrease in Cl(-) current. To decipher the molecular mechanism of this phenotype, single and double mutants with different charge combinations at residues 347 and 979 were constructed as charged residues were involved in this complex genotype. These studies revealed that residue 979, located in the third cytoplasmic loop, is critical for CFTR processing and Cl(-) channel activity highlighting the role of charged residues. These results have also important implications for CF, as they show that two mutations in cis can act in concert to alter dramatically CFTR function contributing to the wide phenotypic variability of CF disease.

Cystic Fibrosis↗
PubMed1999

Structure-function analysis of a double-mutant cystic fibrosis transmembrane conductance regulator protein occurring in disorders related to cystic fibrosis.

A number of disorders related to cystic fibrosis have been described since the cloning of the cystic fibrosis gene, including infertility due to the congenital bilateral absence of the vas deferens. We have identified, in several patients, complex cystic fibrosis transmembrane conductance regulator genotypes like double-mutant alleles. We have now analyzed the structure-function relationships of one of these mutants, R74W-D1270N cystic fibrosis transmembrane conductance regulator, expressed in HeLa cells, to evaluate the contribution of each mutation in the phenotype. We found that R74W cystic fibrosis transmembrane conductance regulator appears to be a polymorphism, while D1270N cystic fibrosis transmembrane conductance regulator could be responsible for the congenital bilateral absence of the vas deferens phenotype. The combination of the two produced a more severe effect on the chloride conductance pathway as well as on the phenotype.

Alleles↗
PubMed1999

Increased incidence of cycloguanil resistance in malaria cases entering France from Africa, determined as point mutations in the parasites' dihydrofolate-reductase genes.

The incidence of cycloguanil resistance in 501 Plasmodium falciparum isolates from individuals entering France from Africa was estimated by a method based on PCR-restriction-fragment-length polymorphisms. None of the subjects had taken antifol prophylaxis. Annual incidence of the resistance, detected as a point mutation at codon 108 in the parasite's dihydrofolate-reductase gene, increased from 19.8% in 1995 to 43.6% in 1997 (P < 0.001). The proportion of isolates found to be susceptible (i.e. wild-type) among travellers returning from the African countries known as Group 2 in France (i.e. Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Guinea, Liberia, Madagascar, Mali, Mauritania, Niger, Senegal, Sierra Leone, Tchad and Togo) was reasonably high (62.9%) and much higher than in the other subjects returning from other identifiable countries in Africa (35.3%). The antimalarial prophylaxis recommended in France to those travelling to Group-2 countries, chloroquine-proguanil, therefore still seems reasonable, although cycloguanil resistance may seriously undermine the efficacy of this drug combination in the future.

Africa↗
PubMed1997

[Optimum quinine therapy in falciparum malaria attacks contracted in Africa].

A review about the use of quinine for uncomplicated falciparum malaria contracted in Africa is proposed. The dose of 8 mg/kg of quinine base 3 times a day seems to be admitted by all. On the other way, the duration of treatment fluctuates from 2 to 10 days without evidence of difference in efficacy between 3, 5 and 7 days. The pharmacodynamic and pharmacokinetic properties of quinine are reviewed and suggest that 3, 5 and 7 days are efficient at least on, respectively, 1, 2 and 3 parasite cycles and suggest that a five day treatment may be curative for all kind of patients infested with a quinine-sensitive strain of P. falciparum in Africa.

Africa↗
PubMed1976

Urgent fibre-optic panendoscopy in upper gastro-intestinal haemorrhage.

Urgent fibre-optic panendoscopy was performed in 400 patients within 24 hours of their admission to hospital for upper gastro-intestinal haemorrhage. The cause of bleeding was established by endoscopy in 87%. No cause was found in 10% and endoscopy failed in 3%. Twenty-five per cent of the patients had an additional lesion which was not the cause of bleeding. Complications owing to endoscopy occurred in 2% of the patients. Only 27% of the patients still had blood present in the stomach at the time of endoscopy. Chronic gastric ulcer was causative in 22%, and duodenal ulcer in 20% of the patients. Haemorrhagic gastritis accounted for 13%, Mallory-Weiss tear for 8%, acute ulceration for 5% and varices for 4% of the patients. Only 60% of the patients with dyspepsia were bleeding from peptic ulcers and only 64% of the patients bleeding from ulcers had a history of dyspepsia. Follow-up studies revealed that endoscopy, in experienced hands, is an accurate investigation which allows for an improved approach to management, and which probably also reduces the mortality rate.

Acute Disease↗
PubMed1976

The use of gamma-glutamyl transpeptidase in differentiating liver from bone isoenzymes of alkaline phosphatase.

Sixty-one patients with elevated alkaline phosphatase activity due to liver or bone diseases were studied. An attempt was made to identify the origin of the increased alkaline phosphatase by chemical inhibition, by inactivation by heat and urea, and by electrophoretic separation. The results obtained from these procedures were correlated with the gamma-glutamyl transpeptidase activities performed on each patient. We concluded from this study that gamma-glutamyl transpeptidase determination, together with alkaline phosphatase electrophoretic separations, are useful laboratory procedures for accurately identifying the origin of elevated alkaline phosphatase activity.

Alkaline Phosphatase↗
PubMed1976

Fibreoptic endoscopy and the use of the Sengstaken tube in acute gastrointestinal haemorrhage in patients with portal hypertension and varices.

The value of emergency upper gastrointestinal fibre-endoscopy, followed where required by the use of a modified Sengstaken tube, was studied during 84 episodes of acute bleeding in 75 patients who had evidence of portal hypertension with varices. The portal hypertension was due to alcoholic cirrhosis in 80% and to cryptogenic cirrhosis in 9% of the patients. By definition, varices were present in all patients, but in only 66% of episodes were the varices the cause of the bleed. The correct diagnosis of the source of bleeding was made at endoscopy in 89%. A Boyce modification of the Sengstaken-Blakemore tube was passed in 73% of the episodes of variceal bleeding. It effectively stopped the bleeding primarily in 85% of patients but was successful as a final definitive measure only in 46%. Furthermore, only 40% of the patients in whom the tube was passed, survived. Mortality rate could be related to the severity of the bleed and to hepatocellular dysfunction. Survival increased from 23% in those patients with jaundice, ascites, and encephalopathy on admission to 92% in those without these manifestations. The in-hospital survival rate was 52% in patients bleeding from varices and 64% in those bleeding from other causes, with an overall survival rate of 56%, indicating the poor prognosis in cirrhotic patients with gastrointestinal bleeding, irrespective of the cause.

Adolescent↗
PubMed1974

A comparison between secretin alone and sequential and simultaneous secretin and cholecystokinin administration in the assessment of pancreatic function.

Pancreatic volume, bicarbonate and enzyme secretion were studied after sequential and after simultaneous secretin and cholecystokinin (CCK) stimulation and the results compared. No statistical difference between sequential or simultaneous stimulation was noted. A comparison of secretin alone with simultaneous secretin plus cholecystokinin stimulation showed that the combination yielded a significantly higher trypsin concentration. Volume and bicarbonate were unchanged.

Bicarbonates↗