Search PubMed⌕ Search

Biomedical subjects

F Gay

Publications and source records attributed to F Gay.

At least 91 records · Page 5Linked to original sources

Evidence for tumor necrosis factor-alpha involvement in the optimal induction of class I allospecific cytotoxic T cells.

We have investigated the functional interaction between IL-2 and TNF on the generation of alloreactive CTL. The study was performed by using primary mixed cultures of lymphocytes from a MHC-recombinant sibling identical for MHC class II Ag (DR, DP, DQ) and displaying MHC class I disparity. Our data show that MHC class I disparity can trigger the induction of TNF receptor without promoting significant TNF production. Addition of exogenous TNF at the sensitizing phase of the primary mixed lymphocyte reaction did not result in CTL activation. However, when simultaneously added with IL-2, TNF could promote an optimal induction of cytotoxic T cell generation. The enhanced lytic ability of MHC class-I primed CTL by TNF was associated with a selective up-regulation of Tac Ag and subsequent amplification of cell proliferation. Furthermore, TNF was also found to induce a considerable increase in IL-2-induced intracellular benzyloxycarbonyl-L-lysine thiobenzylester-esterase activity by MHC class I-primed cells. TNF did not affect the expression of LFA1, CD2, CD4, and CD8, molecules that are associated with CTL-target interactions, on responder cells. These results extend our earlier observations on the role of class I MHC molecules that may function to transduce activation signals and suggest that TNF may be a potent mediator involved in the IL-2-induced acquisition of optimal lytic competence by precursor cytotoxic T cells.

Antigens, CD↗

Functional interactions between interleukin-4, interleukin-2, and tumor necrosis factor-alpha for lymphokine-activated killer cell generation.

The purpose of the present study was to explore the interaction between interleukin-2 (IL-2), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF) on the differentiation of human large granular lymphocytes (LGL) into lymphokine-activated killer cells (LAK). The data show that recombinant human IL-4 (100-1,000/ml) was able to induce the differentiation of human LGL into LAK effectors. The levels of the IL-4-induced cytotoxicity are significantly lower than those observed after stimulation of LGL by optimal doses of IL-2. This LAK activity generation by IL-4 was not associated with LGL proliferation. When TNF was added in LGL culture in the presence of suboptimal concentrations of IL-4, the lytic capacity of the activated killer cells was significantly enhanced, suggesting an apparent synergy between these two factors. Most interestingly, our data indicate that exogenous TNF can partially overcome the known inhibitory effect of IL-4 on IL-2-induced LGL differentiation into LAK effectors. These findings suggest a role for TNF in the process of LAK induction.

Cell Differentiation↗

Involvement of cyclic adenosine monophosphate in the interleukin 4 inhibitory effect on interleukin 2-induced lymphokine-activated killer generation.

In previous studies, IL-4 has been reported to interfere with IL-2-driven generation of lymphokine-activated killer (LAK) activity. In this investigation, we have demonstrated that IL-4 inhibited the IL-2-induced differentiation of large granular lymphocytes (LGL) into LAK effectors by a mechanism involving, at least in part, an increase in LGL intracellular cAMP levels. In contrast, with its capacity to induce cAMP accumulation in resting LGL, IL-4 had a very negligible effect on LAK activity induction, and cAMP levels increase in LGL that had been preincubated with IL-2. Furthermore, the inhibitory effect of IL-4 on LAK activity generation also correlated with a marked decrease in N-CBZ-L-lysine thiobenzylester esterase activity, with an inhibition of tumor necrosis factor (TNF) mRNA expression and TNF production by IL-2-stimulated LGL. These results strongly suggest that complex signaling processes could be ascribed to the dual activities of cytokines and their interplay in LAK promotion.

Cell Differentiation↗

[Results of the surgical treatment of tetralogy of Fallot before 6 months of age. A consecutive series of 62 cases with 49 complete repairs].

From January 1980 to July 1988, 62 infants aged under 6 months with an uncomplicated Tetralogy of Fallot (single ventricular septal defect, normal coronary arteries, no localised pulmonary artery branch stenosis) underwent 64 surgical procedures. The indications for surgery were increasing cyanosis and/or anoxic spells. Fourteen systemic-pulmonary shunts (21.5%), 49 complete repairs (75.4%) and one enlargement of the right ventricular outflow tract and of the main pulmonary artery without closure of the ventricular septal defect, were performed. The results of palliative shunts are preoccupying: cumulative mortality of 36 per cent; high rate of early reoperation for complete repair: 14 per cent. Complete repair was associated with an operative mortality of 14 per cent. Only one child had to be reoperated. There was no late death after complete repair compared with 2 late deaths after shunt. Ultimate results of complete repairs are good. Some risk factors were statistically significantly associated with complete repair: age (2.5 months or less), weight (4,500 g or less), measurements of the pulmonary arteries estimated by the diameter of the right pulmonary artery (5 mm or less). Conversely there was no death in the subgroup of 31 infants aged more than 2.5 months without major pulmonary hypoplasia (diameter of the right pulmonary artery over 3.5 mm). One-stage complete repair give the best short and medium-term surgical results in treatment of uncomplicated Tetralogy of Fallot in infants, irrespective of age and weight providing they have no diminutive pulmonary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

[Cross resistance to mefloquine and halofantrine in a case of P. falciparum malaria contracted in Sierra Leone].

Malaria caused by P. falciparum occurred during prophylaxis with mefloquine upon return from Sierra Leone (zone II). A typical and not recognized, with negative results of initial hematological examinations. Diagnosed on D.26 with parasitemia of 0.2%. Successful treatment of clinical symptoms with halofantrine but increased anemia and positive parasitemia at D.7. Successful treatment with chloroquine. Chemosensitivity tests confirmed sensitivity to chloroquine, threshold sensitivity to quinine (IC50 = 297), resistance to mefloquine (IC50 = 76) despite high levels in bloods, and to halofantrine (IC50 = 7-laboratory normal value = 1). This cross-resistance of P. falciparum originating from Sierra Leone to mefloquine-halofantrine seems to be the first observation of this danger in Africa. Prescription of chloroquine is still imperative in zone 11 countries.

Adult↗

[Plasmodium falciparum drug resistance in the Congo. Evaluation of surveys carried out from 1985 to 1989].

Surveys on drug sensitivity of Plasmodium falciparum carried out between 1985 and 1989 included 7-day in vitro tests and in vivo tests. 485 in vivo tests were carried out in eight surveys conducted in Brazzaville and in several inland regions. The subjects were congolese children aged between 3 months and 15 years old. They were recruited in hospital, mother-child clinics or at school. The drugs studied were chloroquine, amodiaquine and the sulfadoxine-pyrimethamine combination. 182 strains were tested in vitro in two surveys (December 1985 and January 1987); amino-4-quinolines, quinine and mefloquine were studied. Although resistance to amino-4-quinolines is a recent occurrence, by 1985 it had spread widely in the indigenous population in the Centre and South of the country. Resistance has since increased gradually, especially for chloroquine which undergoes specific surveillance. The situation is less serious in the North, a less densely populated region which is still enclosed. In an in vivo comparative study with chloroquine conducted in Brazzaville in November 1986, amodiaquine was found to be only slightly more effective at a similar dosage. At that time, certain isolated observations already seem to imply that the sulfadoxine-pyrimethamine combination was also affected by resistance. This was not corroborated in an in vivo study carried out in 1989 on 40 children presenting with a malarial attack. Although the sensitivity to quinine may probably be decreased. This drug cannot yet be considered as being truly affected by resistance. The activity of mefloquine, the use of which is still limited, was satisfactory in 1987 in two different regions of the country.

Adolescent↗

[Failure of prevention of malaria by mefloquine in West Africa].

Mefloquine (Lariam) is extensively prescribed for the prevention of malaria in chloroquine-resistant areas. However, in west Africa, most of the strains of Plasmodium falciparum are still sensitive to chloroquine. In addition, a few of these strains are inherently resistant to mefloquine. Under these conditions, we must expect to see the failure of mefloquine prophylaxis in travellers returning from west Africa. We report here 5 such failures. The in vitro susceptibility of Plasmodium falciparum isolates from 4 of these patients was evaluated and showed that all 4 had normal sensitivity to chloroquine and quinine, 3 were resistant to mefloquine and one had reduced susceptibility to mefloquine. Mefloquine blood levels (measured 3 times) were within the normal protective range. These case reports indicate that mefloquine should be used cautiously for malaria prevention in west Africa. They also point out that, regardless of the prophylactic method used, fever in a traveller returning from endemic malaria regions always dictates the analysis of a thick blood smear to rule out the diagnosis of malaria.

Adult↗

Purification and characterization of proteins with associated tyrosine protein kinase activity from human B lymphocytes.

Burkitt lymphoma cells and their counterpart of normal origin contain proteins with associated tyrosine protein, kinase activity. These proteins were isolated by affinity chromatography and Fast Pressure Liquid Chromatography. Proteins with enzyme activity had an app. M. W. of 47 KDa. This protein in extracts of Burkitt lymphoma cells differed by overall charge and phosphorylation from the 47 KDa protein isolated from B lymphocytes of normal origin. Before and after purification the 47 KDa protein of Burkitt lymphoma cells reacted with an antibody directed against the dodecapeptide Arg-Arg-Leu-Ile-Glu-Asp-Asn-Glu-Tyr-Thr-Ala-Arg (conserved region of pp60src), the 47 KDa protein from B cells of normal origin did not; the same protein from both cell lines reacted with anti-pp60src antibody. These results suggest that a tyrosine protein kinase, related to the products of the src family of oncogenes, is modified in Burkitt lymphoma cells.

Antibodies, Neoplasm↗

[Atresia of the left coronary ostium. Repair in a 2-month-old infant].

A case of atresia of the left coronary ostium revealed by neonatal heart failure is reported. The initial diagnosis was anomalous origin of the left coronary artery from the pulmonary artery. At surgery performed in this 6-week old infant the diagnosis was amended and the malformation was repaired. Soon after the operation the child rapidly developed hypertrophic "myocardiopathy" of the left ventricle. Seven and a half months later, he is asymptomatic and the echocardiographic parameters of left ventricular systolic function are gradually returning to normality. Atresia of the left coronary ostium is an exceptional anomaly which must be considered, together with the other anomalous origins of the left coronary artery, when confronted with a case of severe heart failure caused by coronary ischaemia during the first months of life. The diagnosis rests on opacification of the coronary network during cardiac catheterization. Coronary "revascularization" may be performed either by aortocoronary bypass or by anatomical repair of the malformation.

Angiocardiography↗

[Malaria in Guiana. I. General status of the endemic].

Before 1949 malaria was highly prevalent in the whole territory of French Guiana. When malaria control based on house-spraying and drug prophylaxis was implemented in 1950 the disease sharply dropped below 20 cases per year. Since 1976 despite vector control malaria is rising again. In 1987, 3,269 cases have been notified giving an incidence of 37.6 per thousand for the whole country population; only four deaths were recorded. All the age groups were concerned but the transmission was restricted to some foci along the Oyapock river (prevalence rate 25%), along the Maroni river (prevalence 2.3%) and in a few places of the coastal area. The main cities remain malaria free. In vivo resistance to chloroquine was observed in 22% of the cases which could be cleared by amodiaquine or quinine.

Adolescent↗

[Malaria in Guiana. II. The characteristics of different foci and antimalarial control].

In French Guiana, the distribution of malaria in foci inhabited by quite different ethnic groups calls for specific studies. Along the Oyapock on the Brasilian border and along the Litani on the Surinam border, incidence among American Indians and Creoles ranges from 300 and 900 per thousand; Plasmodium falciparum accounts for 65% and P. vivax for 35%. Along the middle and lower Maroni on the Surinam border, the Boni and Ndjukas Negroes move freely through the frontier and since the civil strife Surinamese used to attend health centres of Guiana. Therefore it is difficult to find the sources of contamination and the incidence among French citizens; P. falciparum is the only parasite recorded in this focus. In 1987 a small outbreak mainly due to P. vivax, occurred in a Lao refugees village in the hinterland. The coastal foci harbour large communities of Haitian and Brazilian migrants. The vector is Anopheles darlingi and up to now there is no evidence that other species could be involved. The rise of malaria despite of control measures involves several factors: the house spraying is no more accepted by a large percentage of house holders and the alternative larviciding has only a limited efficacy; the houses of American Indians have no walls to be sprayed; there is a continuous introduction of parasites by migrants. It has been said that vectors have change their behaviour toward exophily but such a statement has not yet been supported by evidence. All these factors should be taken in account to improve malaria control.

Animals↗

[Development of chloroquine resistance in Plasmodium falciparum in Gabon between 1984 and 1987-88 (in vivo evaluation in a school environment)].

Unknown in 1980, suspected in 1983 and scarcely present in 1984-85, Plasmodium falciparum resistance to chloroquine as studied in vivo in schoolchildren in Gabon, has strongly developed in 4 years time. In 1987-88, administration of 25 mg/kg of chloroquine leaves one strain out of four with a parasitic load greater than 10/1.000 red blood cells examined by thick drop technique. The present, unfortunately provisional attitude tends to maintain chloroquine at efficient doses for as long as the resistant strains are ethically and practically controllable. The dispersion without strict control of new and for the time being very efficient drugs might rapidly give rise to a polychemoresistance which would leave us without defence.

Animals↗

[Low levels of chloroquine resistance of Plasmodium falciparum in the province of Zou in Benin].

An in vivo test using the WHO protocol (chloroquine 25 mg/kg within 3 days, trial over 7 days) was performed in 72 children in the province of Zou, Benin, in July-August 1987. The blood concentration of chloroquine was dosed before, during and after treatment by a sensitive method. This study showed a low rate of drug resistance (4.2%), even though surveys in Cotonou exhibited a high level of chloroquine resistance.

Animals↗

[Cardiac transplantation in the infant and young child. Preliminary results].

Between January and December, 1987, a programme of heart transplantation in paediatrics was designed and carried out in 9 children by the medical and surgical teams of the Necker/Enfants Malades-Laënnec hospitals group, Paris. Six of the patients were infants of less than 2 years (4 were under one year), and the oldest child was 10 years old. All patients seemed to be condemned to an early death either because their congenital heart disease was beyond the resources of conventional surgery (6 cases) or because their dilated cardiomyopathy was refractory to all medical treatments. Three children died at the end of the operation or a few days afterwards, due to poor quality graft (1 case), fulminating bacterial superinfection (1 case) or intractable pulmonary hypertension (1 case). The remaining 6 children are now living as normally as possible in their respective families. The long-term immunosuppressive treatment consists of cyclosporine and azathrioprine; corticosteroids are only used at the very beginning of treatment or in case of graft rejection. Only two episodes of rejection, confirmed by endomyocardial biopsy, were observed in the same patient during the first postoperative month. Biopsy was never performed systematically in order to spare the patient's vein, and the diagnosis of rejection was suspected on clinical grounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗