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Biomedical subjects

G Leroux-Roels

Publications and source records attributed to G Leroux-Roels.

At least 55 records · Page 3Linked to original sources
PubMed1997

Distribution of lymphocyte subsets in bone marrow and peripheral blood is associated with haptoglobin type. Binding of haptoglobin to the B-cell lectin CD22.

Haptoglobin is an acute phase protein showing a genetic polymorphism with 3 major types: Hp 1-1, Hp 2-1, and Hp 2-2. In this study, flow cytometric analysis demonstrated that all three haptoglobin types bind to CD22 on human B-lymphocytes with equal affinity. Comparison of reference values for lymphocyte subsets in peripheral blood and bone marrow showed significant differences between haptoglobin types. Haptoglobin 2-2 is associated with higher peripheral B-lymphocyte counts (P < 0.001) and CD4+ T-lymphocyte counts (P < 0.05). In bone marrow, CD4+ T-cell percentages were highest (P < 0.001) but B-cell percentages were lowest (P < 0.001) in haptoglobin 2-2 type. A negative correlation between serum haptoglobin 1-1 concentration and peripheral B-cell counts was observed (r = -0.663). Our results suggest that haptoglobin is involved in lymphocyte distribution. The present findings are a potential cause of over- or underestimation of lymphocyte subset counts in the clinical staging of immunodeficiency diseases.

Adult↗
PubMed1996

Lymphoproliferative responses to hepatitis C virus core, E1, E2, and NS3 in patients with chronic hepatitis C infection treated with interferon alfa.

The quality of the hepatitis C virus (HCV)-specific T-cell response may greatly determine the course of an HCV infection. An adequate T-cell response may contribute to a successful clearance of the virus and a rapid recovery from the disease. An inadequate response may lead to viral persistence and may eventually contribute to the pathogenesis of hepatocellular damage in chronic disease. The effect of interferon alfa (IFN-alpha), presently the most popular therapeutic agent for chronic HCV infections, on HCV-specific T-cell responses is completely unknown. To demonstrate the presence of HCV-specific T lymphocytes during chronic HCV infections, to know their antigenic specificities, and to examine possible effects of IFN-alpha treatment on their presence and antigen recognition patterns, we have stimulated peripheral blood mononuclear cells (PBMC) from 35 chronic HCV patients with nine pools of synthetic peptides representing the HCV Core, E1, and E2 proteins as well as with a recombinant NS3 protein. The proliferative responses of PBMC from 16 healthy control subjects toward these antigens were measured for comparison. Lymphoproliferative responses of patients with chronic HCV infections were assayed either before (in 10 patients), during (in 13 patients), or after (in 21 patients) treatment with IFN-alpha. The analysis showed that PBMC from most HCV patients consistently recognized the COOH-terminal part of the core protein. E1, E2, and NS3 were recognized less frequently. This recognition pattern was not related to the therapy with IFN-alpha nor to the clinical response of the patient toward this therapy. The response to the Core protein could be fine-mapped to the COOH-terminal region encompassing amino acids (aa) 73 to 92, 121 to 140, 145 to 164, and 157 to 176.

Adult↗
PubMed1996

In vitro TNF-alpha, IL-2 and IFN-gamma production as markers of relapses in multiple sclerosis.

In 22 patients with definite multiple sclerosis (MS) we determined with monthly intervals over a period of 24 months the in vitro tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-2 (IL-2) production and the serum neopterin levels. The results were compared with normative data collected from 14 healthy controls over the same period. Twenty-nine relapses in 13 patients were noticed. We found increased in vitro TNF-alpha production from 4 weeks on prior to the day of an exacerbation. There was a significant correlation with in vitro IFN-gamma release, the absolute blood monocyte count and the serum neopterin levels, suggesting that monocytes stimulated by IFN-gamma play an important role in the TNF-alpha production. Serial analysis of in vitro TNF-alpha production proved to be a helpful tool in predicting relapses in MS patients. Furthermore, elevated levels of IFN-gamma and IL-2 after stimulation with OKT3 during exacerbations were demonstrated. Serial analysis of these two biological markers revealed to be of no value in predicting relapses.

Adult↗
PubMed1996

Hepatitis C virus in a hemodialysis unit: molecular evidence for nosocomial transmission.

Between February 1991 and January 1992, elevated alanine aminotransferase (ALT) levels were observed in several hemodialysis patients in a dialysis center in Dendermonde, Belgium. By the end of 1992, 25 out of 68 patients had seroconverted for HCV antibodies. The HCV strains from 23 of these seroconverters were genotyped and classified as genotype 1b. Sequence analysis of the HCV Core region was carried out in 12 patients, 9 of whom were infected with a strain bearing a unique sequence motif as compared with the currently known HCV 1b strains. A new 5' UR/Core line probe assay was designed to screen for such variations. Twenty patients tested positively for this special sequence motif, while the other 3 showed the regular subtype 1b sequence. Phylogenetic analysis of the Core sequences further revealed that the latter three were neither related to the main special strain of the infection, nor to each other. These three strains could be traced to two patients already infected at the time of residence in other dialysis units and to one patient who already showed ALT elevations in 1989. Epidemiological studies revealed no traceable source for this outbreak. In conclusion, molecular analysis demonstrates nosocomial transmissions by a peculiar genotype 1b strain in a dialysis center. Three other genotype 1b strains were also present in the unit, but were not responsible for the outbreak.

Alanine Transaminase↗
PubMed1996

Hepatitis C virus (HCV) genotype analysis in apparently healthy anti-HCV-positive Parisian blood donors.

BACKGROUND: As only a few studies have examined the prevalence of various hepatitis C virus (HCV) subtypes in blood donors, information about the variability and route of infection in apparently healthy persons is limited. STUDY DESIGN AND METHODS: Blood donations collected at a large Parisian hospital (52,441) were investigated for antibodies to HCV. Serum samples were screened with an enzyme immunoassay. All HCV-positive donations were retested with a second enzyme immunoassay and confirmed by immunoblot. The HCV genotype was determined for all polymerase chain reaction-positive subjects. Untypable genotypes were sequenced in the NS5B region. RESULTS: In total, 83 (0.26%) blood donors were anti-HCV positive. Men (0.34%) were significantly more likely to be infected (p < 0.001) than women (0.19%). Prevalence rates in men between 20 and 39 years of age were higher than those in similar women (p = 0.01), but greater in women aged from 50 to 65 years (p = 0.05). Fifty-five sera were viremic, of which 49 could be genotyped by a line probe assay. One new HCV type 1 subtype and three new HCV type 2 subtypes were discovered. In total, 28, 10, 11, 5, and 1 serum samples were grouped into HCV types 1 through 5, respectively, involving a total of 13 subtypes. The mean age of HCV type 2-infected donors was 42 +/- 11 years, but that for type 3-infected subjects was only 30 +/- 4 years (p = 0.0048). Forty-nine subjects showed elevated alanine aminotransferase levels; 39 (80%) of these subjects were viremic (p < 0.05). CONCLUSION: Among the sampled population, an HCV prevalence rate of 0.26 percent was found, with the five most common European genotypes causing the infections. Four new subtypes were discovered. Correlation between genotype and risk factors was not apparent, but links with age, sex, and ethnic origin emerged.

Adult↗
PubMed1996

Safety and immunogenicity of a combined hepatitis A and hepatitis B vaccine in young healthy adults.

BACKGROUND: A combination of hepatitis A and hepatitis B monovalent vaccines could offer advantages for disease control programs in terms of convenience, compliance and cost. METHODS: Under randomized, double-blind conditions, 156 healthy young adults were divided into 3 groups to receive 1 of 3 lots of a combined hepatitis A/hepatitis B vaccine administered at months 0, 1, and 6. Safety and immunogenicity were assessed after each dose. RESULTS: Transient and predominantly mild reactions were reported by slightly more than half the vaccinees; no serious adverse effects were relate to vaccination. One month after dose 2, all subjects had converted to the hepatitis A component. Geometric mean titers (GMTs) of antibodies of hepatitis A virus varied from 4415 to 4882 mIU/ml in the three groups. For hepatitis B, most vaccinees (73%-92%) had protective levels of antibodies to hepatitis B virus (anti-HBs) after the second dose, and all were sero-protected after the booster. Anti-HBs GMTs at month 7 ranged from 1917 to 3298 mIU/ml. CONCLUSIONS: No statistically significant differences were observed between vaccine lots. The combined hepatitis A/hepatitis B vaccine was safe and clinically well tolerated and induced immune responses quantitatively similar to those obtained with the respective monovalent vaccines.

Adolescent↗
PubMed1996

Interference of soluble TNF-alpha receptors in immunological detection of tumor necrosis factor-alpha.

We have studied the interference of soluble tumor necrosis factor-alpha receptor p55 (sTNF-R55) on the quantification of tumor necrosis factor-alpha (TNF-alpha) in three immunoassays: the commercially available enzyme amplified-sensitivity immunoassay (EASIA) of Medgenix and the ELISA of Boehringer Mannheim, and an assay based on electrochemiluminescence (ECL) technology. TNF-alpha measurements by EASIA and ELISA were not affected by the presence of sTNF-R55, but results by the ECL method were clearly influenced by the receptor. We then performed a second set of experiments with the ECL system to examine what factors might influence the importance of interference from sTNF-R55 and soluble TNF-alpha receptor p75 (sTNF-R75), which influences TNF-alpha measurements the same as sTNF-R55. We found that extending the incubation time and increasing the concentration of capture antibody decreased the interfering capacity of sTNF-R55 and sTNF-R75. A clear insight into these phenomena is of utmost importance for correct interpretation of cytokine quantification.

Enzyme-Linked Immunosorbent Assay↗
PubMed1995

Nonresponders to hepatitis B vaccine can present envelope particles to T lymphocytes.

The mechanisms causing nonresponsiveness to hepatitis B surface Ag (HBsAg) vaccines in humans remain largely unknown. The increased incidence of nonresponsiveness in subjects with HLA-DR3 or -DR7 haplotype suggests that immune response mechanisms governed by genes of the MHC are involved. It is conceivable that APC of nonresponders are defective in the presentation of HBsAg because they are unable to adequately take up, process, or present this Ag. To examine this hypothesis we have used PBMC from nonresponders to present recombinant particles containing S or PreS2-S sequences to HBsAg-specific T cell lines from haplo-identical responder vaccinees. The proliferative response of these lines was used to evaluate the efficacy of Ag presentation. Unfractionated PBMC from five DR2+ and six DR7+ nonresponders did not proliferate to HBsAg in vitro, whereas they vigorously proliferated upon stimulation with tetanus toxoid, thus ruling out the presence of a generalized immunodeficiency. All DR2(15)+ nonresponders were able to present hepatitis B envelope Ag to HBsAg-specific, DR1501-restricted T cells. PBMC from six DR7+ nonresponders were all able to present HBsAg to DR07-restricted T cell lines and PBMC from three DPw4+ nonresponders were able to present HBsAg to DP0402-restricted T cell lines. Additional experiments showed that PBMC from two nonresponders presented HBsAg equally well and sometimes better than PBMC from two partially HLA-matched high responders. We conclude that HLA-DR2+, -DR7+, and -DPw4+ nonresponder vaccinees are able to take up, process and present HBsAg to allogeneic, haplo-identical T cell lines in vitro.

Adult↗
PubMed1995

MN blood group, a genetic marker for essential arterial hypertension in young adults.

The MN blood group has been linked with blood pressure levels and sodium-lithium counter-transport in red blood cells of normotensives. The aim of the study was to compare the distribution of MN phenotypes according to age at diagnosis of essential hypertension and to investigate the relationship between MN phenotypes, severity of complications and therapeutic needs. MN blood group polymorphism was studied in 386 Caucasians with established essential arterial hypertension, treated for at least one year. In 285 healthy normotensive blood donors, blood pressure was measured and MN blood group was typed. MN blood groups were typed with polyclonal antisera and confirmed with monoclonal antisera. MN blood group phenotype frequencies in hypertensives were 0.207 (MM), 0.601 (MN), and 0.192 (NN), which differs (P < 0.000002) from the distribution in the controls: 0.270 (MM), 0.540 (MN) and 0.189 (NN). The relative MN phenotype frequency was strongly over-represented (P < 0.05). Age at detection of hypertension was significantly lower for MN patients (P < 0.0005). With increasing age of detection, the relative frequency of MN phenotype gradually decreases from 0.73 in those detected before age 40 to 0.50 for patients detected after 60. This observation holds true for both male and female hypertensive. Furthermore, hypertensives with a MM blood group had a lower (P < 0.05) prevalence of cerebrovascular accidents. In controls, blood pressure was comparable for the three MN phenotypes. The present study suggests that the MN phenotype is a genetic factor associated with early detection of essential hypertension.

Adolescent↗
PubMed1994

Deficient T-cell responses in non-responders to hepatitis B vaccination: absence of TH1 cytokine production.

The inability to mount a protective level (> or = 10 IU/l) of hepatitis B surface antigen (HBsAg)-specific antibodies after vaccination is presumably the consequence of a defect in the cellular immune regulation. We compared the in vitro immune responses of peripheral blood mononuclear cells (PBMC) from high, intermediate and non-responders, after stimulation with recombinant HBsAg. The absence of a proliferative response in non-responders was not reversed by removal of CD8+ T cells, indicating that HBsAg-specific CD8+ T-cell-induced suppression was not the underlying cause of non-responsiveness. Non-responders did not produce cytokines after HBsAg stimulation. High responders displayed a typical Th1-like profile since their PBMC produced interleukin-2 (IL-2) and gamma-interferon (IFN gamma) and no detectable IL-4 or IL-5 upon stimulation with HBsAg.

Adult↗
PubMed1994

Correlation between in vivo humoral and in vitro cellular immune responses following immunization with hepatitis B surface antigen (HBsAg) vaccines.

To study the regulation of the human immune response to hepatitis B surface antigen (HBsAg) we have carefully monitored the in vivo humoral and in vitro cellular immune responses to HBsAg in 50 subjects receiving four doses of hepatitis B vaccine according to a 0, 1, 2, 12 month vaccination scheme. Twenty-three subjects were given a plasma-derived vaccine (Hevac B) and 27 received a recombinant HBsAg vaccine (yeast-derived; Engerix-B). The humoral and cellular immune responses were measured before vaccination (day 0); 6 days after the second dose (day 36); 6 days (day 66), 2 months (day 120) and 10 months (day 365) after the third dose and 1 month after the fourth dose (day 395). Based on the kinetics of the humoral immune responses, the vaccinees could be classified into fast, intermediate and slow/non-responders. Based on the magnitude of the immune response (anti-HBs titre) on day 395, the vaccinees could be divided into high (> or = 2000 U l-1) and low (< or = 2000 U l-1) responders. A close correlation between the kinetics and the magnitude of the humoral immune response was observed. The in vivo anti-HBs response was measured using commercially available immunoradiometric assays. The in vitro cellular immune response was measured using an HBsAg-specific lymphoproliferation assay. Because of interassay variability the results were considered as dichotomous variables (proliferation versus non-proliferation) for further data analysis. A statistically significant correlation was observed between the kinetics and magnitude of the humoral immune response on the one hand and the in vitro anti-HBs response on the other hand.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Hepatitis B virus-specific cytotoxic T lymphocyte responses in patients with acute and chronic hepatitis B virus infection.

An in vitro model was developed that allowed the analysis of hepatitis B virus-specific cytotoxic T lymphocyte responses in patients suffering from acute and chronic hepatitis B virus infections. Since virus-specific cytotoxic T lymphocytes recognize endogenously synthesized and processed antigen only when it is presented in the context of autologous HLA class I molecules and since hepatitis B virus does not infect human cells in vitro, a panel of recombinant vaccinia viruses was constructed to induce the expression of hepatitis B virus envelope and nucleocapsid proteins in cultured primary cells or cell lines derived from the patients to be studied. In order for a cytotoxic T lymphocyte response to be detectable with the currently available techniques, a sufficient number of activated cytotoxic T lymphocytes is required. To meet this requirement, lymphocytes freshly isolated from venous blood were stimulated in vitro with recombinant vaccinia-infected and formaldehyde-fixed autologous T lymphoblasts. The presence of hepatitis B virus-specific cytotoxic T lymphocytes, amplified and activated during this induction culture, was demonstrated in a microcytotoxicity assay using 51Cr-labeled, recombinant vaccinia-infected Epstein-Barr virus-immortalized, autologous B lymphocytes as target cells. Using this in vitro model, we were able to demonstrate the presence of hepatitis B virus envelope- and nucleocapsid-specific cytotoxic T lymphocytes in venous blood from one subject who had recently recovered from an acute hepatitis B virus infection and in three patients suffering from chronic hepatitis B virus infections. No hepatitis B virus-specific cytotoxic T lymphocytes activity was discernible in the venous blood from two vaccine recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Performance of the Coulter STKS and the Sysmex NE-1500 in a paediatric population.

The Coulter STKS and the Sysmex NE-1500 were evaluated for their performance in paediatric samples. Special attention was paid to the ability of both instruments to detect white blood cell morphology abnormalities. Therefore a population with a high frequency of pathologies was selected. The studied population included children aged between 1 month and 14 years, 45% of which suffered from oncological and/or haematological diseases. Two hundred and forty blood samples were analysed. The leukocyte differentiation results from the Coulter STKS and the Sysmex NE-1500 were compared with the manual microscopic method. The differentials compared very well for neutrophils, lymphocytes and eosinophils. Sensitivity and specificity for the detection of blasts, immature granulocytes, left shift and atypical lymphocytes were examined. While specific morphology flagging showed a rather low sensitivity, blasts and immature granulocytes were mostly detected by the two systems, taking into account white blood cell alarm flags other than the two mentioned above. The overall sensitivity for the detection of white blood cell abnormalities was better with the Coulter STKS, whereas the Sysmex NE-1500 showed a higher specificity. In an ancillary study which was performed exclusively on neonatal samples, of which 80% originated from preterm infants, we found a limited sensitivity for the detection of low percentages of nucleated red blood cells for both analysers. The high frequency of abnormalities, together with the limited sensitivity mentioned above, prompted us to review all neonatal samples in the future.

Adolescent↗
PubMed1993

Haptoglobin polymorphism and the immune response after hepatitis B vaccination.

One hundred healthy Caucasian medical students (age 22 +/- 1 years) were vaccinated with a recombinant hepatitis B vaccine and their haptoglobin types were determined. A relationship between haptoglobin type and immune response to the vaccine was observed. Subjects with a 2-2 haptoglobin phenotype produced significantly lower hepatitis B antibody titres than those having a 1-1 or 2-1 haptoglobin phenotype. The haptoglobin phenotypes not only influenced the magnitude but also the kinetics of the anti-HBs response. For all haptoglobin types, haptoglobin concentration and immune response to the vaccine behaved independently.

Adult↗
PubMed1993

Laboratory assessment of five glucose meters designed for self-monitoring of blood glucose concentration.

We describe a laboratory assessment of five blood glucose meters. The instruments' analytical characteristics under optimum laboratory conditions and examination of potential sources of errors were intercompared. All glucometers produced precise results, and in all but one meter the CV values varied between 1.5% and 6%. CV's for reproducibility and within-day precision of Glucometer Gx were 10.5% and 7.3%. Sample volume, blood incubation time and colour stability of the strip may influence the results of blood glucose measurements with glucose meters. Underloading the sample strip had statistically significant effects on normal blood glucose values for all meters. One Touch II gave also significantly different results when the strip was overloaded. Incubation times shorter or longer than those recommended by the manufacturer influenced the results of all glucose meters. After colour development of the strip, changes were small for Haemo-Glukotest 20-800R strips and Glucotrix, whereas Accutrend glucose strips had to be read immediately following the prescribed incubation time. Comparison of the glucose meter results with those obtained by the hexokinase method showed good correlation coefficients for Reflolux S (r = 0.992), Accutrend (r = 0.988), One Touch II (r = 0.942), Glucometer Gx (r = 0.986) and Glucocard (r = 0.976). Error grid analysis showed that the results of all meters were clinically correct. Variations in haematocrit are known to be a source of errors when blood glucose is determined with a test strip. In the normoglycaemic range the results obtained with Accutrend and Glucocard were not influenced by even extreme haematocrit values. In the high glucose concentration range there was a decrease in blood glucose values with increasing haematocrit for all meters. This error was smaller with Accutrend and Glucocard than with the other meters. Although the new versions of the monitors are easier to use, their analytical performance is not superior to earlier models.

Blood Glucose Self-Monitoring↗
PubMed1992

Granulocyte elastase, tumor necrosis factor-alpha and urokinase levels as prognostic markers in severe infection.

We have examined the prognostic value of the levels in the blood of granulocyte elastase-alpha 1-proteinase inhibitor (E-alpha 1-PI) complex, tumor necrosis factor-alpha (TNF-alpha) and urokinase-type plasminogen activator (u-PA) in 35 patients with severe infection upon admission to an Intensive Care Unit. Fourteen patients died. No differences for E-alpha 1-PI complex were found between survivors and nonsurvivors, but in all patients the levels on admission were eight-fold higher than the reference value. TNF-alpha levels, measured by immunoassay, on admission were four times higher in the nonsurvivors than in the survivors (p = 0.0003) and correlated with the severity of the disease (APACHE II score, r = 0.43, p less than 0.05). TNF-alpha was not detectable by bioassay. Total u-PA antigen (u-PA Ag), plasmin-activatable single-chain u-PA (scu-PA) and inactive, nonactivatable u-PA (u-PA#) were on admission all two-fold higher in the nonsurvivors (p = 0.0006, 0.003 and 0.0003, respectively), while normal in the survivors. In both, survivors and nonsurvivors, the ratio between scu-PA and u-PA Ag was significantly decreased (p less than 0.001, compared to a reference group of healthy volunteers), indicative for enhanced conversion of scu-PA to active two-chain u-PA (tcu-PA) and inactive u-PA# during severe infectious disease. tcu-PA was detected in nine of the 35 patients, while virtually undetectable in controls. scu-PA correlated with the Child-Pugh score on admission (r = 0.42, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗