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Biomedical subjects

G Delage

Publications and source records attributed to G Delage.

At least 19 recordsLinked to original sources

Epstein-Barr virus transmission from a blood donor to an organ transplant recipient with recovery of the same virus strain from the recipient's blood and oropharynx.

A previous study (Savoie et al, Blood 83:2715, 1994) identified eight transplant patients who acquired Epstein-Barr virus (EBV) infection during the peritransplant period. Three of these patients subsequently developed B-cell lymphoproliferative disease within 4 months of transplantation. Among these, there was a 16-year-old liver transplant patient who was negative for EBV at the time of transplant and who received an EBV-negative organ. After transplant, this patient was transfused with 9 U of packed red blood cells. Eight of the donors were EBV-positive and one was EBV-negative. We succeeded in obtaining spontaneous lymphoblastoid cell lines (LCLs) from the blood of three of these donors, one of whom also yielded a cord-blood line established with his throat-wash EBV. Blood from a fourth donor did not yield an LCL, but his throat washing did have transforming activity when inoculated onto cord-blood leukocytes. We initially could establish spontaneous LCLs only from the recipient's blood. However, a throat-wash sample taken 11 weeks later did show transforming activity. The recipient was shown to have acquired the EBV infection from one of eight EBV-seropositive blood donors. Analysis of fragment length polymorphisms after polymerase chain reaction amplification of the EBV BamHI-K fragment was used to establish strain identity. Western blot analysis for existence of size polymorphisms in three classes of Epstein-Barr nuclear antigens (EBNA-1, EBNA-2, and EBNA-3) confirmed the DNA results. It is noteworthy that the blood donor responsible for transmitting his EBV strain to the recipient had experienced clinical infectious mononucleosis 15 months before donating blood. Our results may, thus, indicate a requirement for leukodepletion of blood destined for immunosuppressed EBV-negative patients. Finally, blood donors with a recent history of infectious mononucleosis should probably be identified so that their blood is not given to EBV-negative transplant patients.

Adolescent

Biological and clinicopathological features associated with hepatitis C virus type 5 infections.

BACKGROUND/AIMS: The biological and clinicopathological features of hepatitis C virus infections of type 1 and type 2 have been well documented. However, little is known about the nature of HCV type 5 infections, which have been found to occur in South Africa but rarely elsewhere. METHODS: We investigated the HCV genotypes in 125 viremic blood donors and 125 viremic patients by restriction endonuclease analysis of amplified 5' non-coding region sequences. Donors and patients infected with type 5 were further studied. Serum HCV RNA levels were assessed by a differential-size PCR-aided transcript titration assay. RESULTS: HCV type 5 infections were identified in seven (5.6%) of the blood donors and in five (4.0%) of the patients. Sera from these 12 persons reacted with the core and NS3 antigens in both RIBA-2 and RIBA-3 tests. Six (50%) and 10 (83%) sera reacted with the NS4 antigens in RIBA-2 and RIBA-3 tests, respectively. HCV type 5 was found to replicate to high titers that ranged from 10(6.0) to 10(8.0) molecules/ml. Transfusion was the most frequently observed risk factor (5 of 12) and persons infected with type 5 were generally older than those infected with other types (< 40 years vs. > or = 40 years, p = 0.01). Cirrhosis was found in two of six (33%) donors and three of four (75%) patients. The duration of infection appeared to be an important determinant for the presence of cirrhosis. CONCLUSIONS: In this small group of Canadians infected with HCV type 5, a high proportion developed severe liver disease.

Adult

Immuno-endocrine interactions in early pregnancy.

First we recall briefly the status of inflammatory cytokines in the early implantation period. We then describe the status of leukaemia inhibiting factor (LIF) production in an in-vitro, relatively short-term, human decidual explant culture system. We show that in most infertile women with recurrent implantation failure following successful in-vitro fertilization, LIF production is statistically much lower than normal. Other parameters of LIF production in vitro are summarized briefly, and the effects of RU486 are shown. The TH2 status of normal pregnancy is described, together with the production of TH2 cytokines by decidua and placenta. These cytokines are deficient in the CBAXDBA/2 model of murine spontaneous early pregnancy loss. The defect can be corrected by alloimmunization, and more importantly by the injection of tau interferon. The significance of these data for early pregnancy signalling is discussed.

Animals

In-vitro endometrial secretion of human interleukin for DA cells/leukaemia inhibitory factor by explant cultures from fertile and infertile women.

Human interleukin for DA cells/leukaemia inhibitory factor (HILDA/LIF) is a cytokine with pleiotropic effects involved in successful murine implantation. We evaluated human uterine HILDA/LIF production by monitoring its in-vitro secretion by endometrial explant cultures obtained from individuals in either normal or pathological conditions. The cytokine secretion was standardized using the day 5:day 1 ratio of HILDA/LIF concentration in supernatants of such cultures, hereby termed HILDA/LIF production index (HLPI). Our results confirmed that HILDA/LIF is secreted by the human endometrium as assessed by secretion at every phase of the cycle in either normal fertile women, or women bearing intrauterine devices. This was also the case for samples obtained from infertile women presenting repeated failures of embryonic implantation or unexplained primary sterility. However, the HLPI were significantly lower in those latter two groups when compared to fertile women. These results suggest an abnormal regulation of HILDA/LIF secretion in such circumstances, and the clinical implication of those data is discussed.

Adult

Alloimmunization against well defined polymorphic major histocompatibility or class I MHC transfected L cells antigens can prevent poly IC induced fetal death in mice.

METHOD: It is possible to induce increased fetal resorption in a number of inbred murine matings by injecting Poly (I) Poly (C12U) 3.5 days postconception, a maneuver associated with natural killer-mediated damage to the feto placental unit such as occurs in spontaneous fetal resorptions. RESULTS: We show here that alloimmunization can block this effect. In addition, maternal immune responses induced by alloimmunization against isolated mutant class I or class II, as well as by immunization with class I MHC alloantigens (Kd) transfected L cells are sufficient to restore normal fetal viability. It is not necessary that the maternal immune response be specifically directed against paternal alloantigens fr the fetal protection to ensue, since the effect occurs in inbred matings when the mother is immunized against unrelated class I or class II alloantigens. As in previous studies conducted in the murine species, not all MHC alloimmunizations are protective. In addition, as control, immunization with a monomorphic class I MHC molecular (37), transfected L cells, sheep red blood cells or hen egg lysozyme is without effect. CONCLUSION: These results indicate that defined MHC antigens can mediate fetal protection from induced fetal resorption, and suggest that one driving force in promoting MHC antigen polymorphism in mammals is their capacity to confer protection from NK mediated fetal demise.

Animals

[In vitro modulation of the production of the cytokine HILDA/LIF, secreted by human endometrial explants: preliminary results].

Human endometrium from fertile women secrete HILDA/LIF in vitro. In endometrial explants from women suffering from an unexplained sterility or women whose fertilized eggs do not implant the in vitro secretion is significantly reduced. HILDA/LIF secretion is increased by IL-1 and decreased by IL-4. CSF-1 has little effects on secretion from fertile women but clearly inhibits secretion from some infertile women. Altogether, the results suggest that HILDA/LIF might be involved in human implantation.

Adult

Ontogeny of the humoral immune response to human immunodeficiency virus type 1 in infants.

In a cohort of infants born to human immunodeficiency virus type 1 (HIV-1)-infected mothers, changes in the levels of HIV-1 specific antibodies were measured during the first year of life. In uninfected children, the level of antibodies to six HIV-1 antigens (gp120, p66, p41, p31, p24, and p17) decreased continuously until becoming negative. In contrast, rising levels of one or more specific antibodies were detected in 9 of 12 infected children at a median age of 6 months. At 1 year of age, 8 infants were still asymptomatic and classified as P-1. All had serologic profiles consistent with de novo specific antibody production. In contrast, among the 4 infants who had early disease (class P-2), 3 had no significant rise in antibody to HIV-1. These results indicate that poor immune response, which could result from early infection of the infant, is often associated with rapid clinical progression.

Cohort Studies

Combined active-passive immunization against the hepatitis B virus: five-year follow-up of children born to hepatitis B surface antigen-positive mothers.

In order to evaluate the duration of "protective" concentrations (i.e. > or = 10 IU/liter) of antibody to hepatitis B surface antigen (HBsAg) in children vaccinated against hepatitis B in infancy, we followed 146 children born to HBsAg-positive mothers from birth to age 60 months. Children were seen at yearly intervals and tested for hepatitis B virus serologic markers. Of the children included in the study, 134 were protected against infection with development of antibody to HBsAg, 5 became HBsAg-positive and 6 failed to respond to the vaccine but did not become infected. Antibody concentrations fell progressively with the passage of time. The probability of maintaining a "protective" concentration of antibody in vaccine responders at age 60 months was 86% (95% confidence interval, 80 to 93%). Gender, ethnic origin, HBeAg status of the mother and immunization schedule had no influence on the rate of antibody loss. We conclude that in developed countries, the great majority of children vaccinated in infancy remain protected against infection at least until age 60 months. The need for booster doses of vaccine in this population will be determined by long term follow-up of immunized cohorts.

Carrier State

Randomized, controlled trial of antibiotic therapy for Escherichia coli O157:H7 enteritis.

We undertook a prospective, controlled study to evaluate the effect of trimethoprim-sulfamethoxazole in children with proven Escherichia coli O157:H7 enteritis on the duration fo symptoms, on fecal excretion of pathogen, and on the risk of progression to hemolytic-uremic syndrome. There was no statistically significant effect of treatment on progression of symptoms, fecal pathogen excretion, or the incidence of HUS (2/22 vs 4/25; p = 0.67). Our results suggest that a multicentric trial using rapid diagnostic methods to permit early randomization should be carried out.

Child

Diagnosis of vertical HIV-1 transmission using the polymerase chain reaction and dried blood spot specimens.

We have used the polymerase chain reaction (PCR) to detect HIV proviral sequences in minute amounts of peripheral blood collected onto newborn screening blotters. Forty-three newborns, infants, and children of HIV-infected mothers were serially studied: dried blood spot (DBS) specimens were processed for PCR; serum was assayed for HIV antibodies, p24 antigen, and immunoglobulins; mononuclear cells were cultured and CD4 cells were quantitated by immunofluorescence. There was excellent agreement between the results of blood spot PCR, viral culture, and clinical and immunological indicators of HIV infection. Eighteen of 19 infected children tested positive by both PCR and culture, including six asymptomatic infants who were less than 10 weeks of age. As expected, p24 antigen capture assays were insensitive, detecting only 13 of the 19 infected children. One infected infant tested positive by PCR, but negative by culture and antigen. This infant was seropositive at 27 months and had pronounced hypergammaglobulinemia in association with non-specific symptoms. Twenty-four of the 43 infants were asymptomatic with normal immune profiles, declining antibody levels and no evidence of infection. These children tested repeatedly negative by PCR, culture, and p24 antigen assays. Our results indicate that DBS PCR is a sensitive, specific, and cost-effective alternative to viral culture for the early diagnosis (or exclusion) of perinatal HIV infection. DBS sampling opens the way for large-scale prospective studies to determine the exact rates of vertical HIV transmission in industrialized, as well as, nonindustrialized countries.

Child, Preschool

A murine model of NK cell mediated resorption.

There is increasing evidence that some models of immunologically mediated murine embryo demise involve nonspecific lytic effector cells. In this paper, we use two double stranded synthetic RNAs, known as potent interferon inducers and NK cell activators, the Poly (I). Poly (C) and the less toxic Poly (I). Poly (C12U). These polynucleotides enhance fetal resorption rates in both resorption prone and none-resorption prone strains of mice. We have studied the kinetics of the phenomenon, and observed an anti-implantation-like effect of early injection during early pregnancy. The abortifacient effects can be adoptively transferred to naive recipients by spleen cells from Ds RNA injected donors. Such effects are abrogated if the cells are pretreated with anti-NK cell antiserum. The relevance of these findings to the survival of the conceptus is suggested.

Animals

[Giardia lamblia infestation at child day care centers. Nutritional impact in infested children].

Seventy-five children attending a day care center (42 girls and 33 boys, aged from 6 to 65 months) were surveyed for excretion of Giardia lamblia cysts. Cyst excretion was found in 17 (23%) of the children, 9 of whom were still positive 6 months later. Weight, height and arm skinfold thickness of each subject were obtained and compared to normal values in the Québec population; a questionnaire concerning gastrointestinal symptoms was filled out for each child. No difference in weight, height, skinfold thickness or in frequency of gastrointestinal symptoms was found when comparing cyst excretors to children with a negative stool examination. This study suggests that G. lamblia infestation has little or no nutritional impact. This should be confirmed by a larger study.

Age Factors