Blood and nasal epigenetics correlate with allergic rhinitis symptom development in the environmental exposure unit.

BACKGROUND: Epigenetic alterations may represent new therapeutic targets and/or biomarkers of allergic rhinitis (AR). Our aim was to examine genome-wide epigenetic changes induced by controlled pollen exposure in the environmental exposure unit (EEU). METHODS: 38 AR sufferers and eight nonallergic controls were exposed to grass pollen for 3 hours on two consecutive days. We interrogated DNA methylation at baseline and 3 hours in peripheral blood mononuclear cells (PBMCs) using the Infinium Methylation 450K array. We corrected for demographics, cell composition, and multiple testing (Benjamini-Hochberg) and verified hits using bisulfite PCR pyrosequencing and qPCR. To extend these findings to a clinically relevant tissue, we investigated DNA methylation and gene expression of mucin 4 (MUC4), in nasal brushings from a separate validation cohort exposed to birch pollen. RESULTS: In PBMCs of allergic rhinitis participants, 42 sites showed significant DNA methylation changes of 2% or greater. DNA methylation changes in tryptase gamma 1 (TPSG1), schlafen 12 (SLFN12), and MUC4 in response to exposure were validated by pyrosequencing. SLFN12 DNA methylation significantly correlated with symptoms (P < 0.05), and baseline DNA methylation pattern was found to be predictive of symptom severity upon grass allergen exposure (P = 0.029). Changes in MUC4 DNA methylation in nasal brushings in the validation cohort correlated with drop in peak nasal inspiratory flow (Spearman's r = 0.314, P = 0.034), and MUC4 gene expression was significantly increased (P < 0.0001). CONCLUSION: This study revealed novel and rapid epigenetic changes upon exposure in a controlled allergen challenge facility, and identified baseline epigenetic status as a predictor of symptom severity.

[Knowledge, attitudes and practices about blood donation. A sociological study among the population of Lomé in Togo]. / Etude des connaissances, attitudes et pratiques en matière de don de sang. Enquête sociologique dans la population de Lomé (Togo).

GOALS: 1) analyse the knowledge, attitudes and practices of Lome population about blood donation; 2) identify obstacles to blood donation among the population of Lome; 3) suggest some solutions to improve the performance of the National Blood Transfusion Centre (CNTS). METHODOLOGY: We have conducted a sample survey among the population of Lome from the 6th to 21st October 2003. Three hundred persons filled a questionnaire. RESULTS: In the sample, 183 (61%) were males. Their age ranged from 18 to 67 years with 2/3 of young peoples between 18 and 37 years. Pupils/students were 24,33%, wage-earners, 55% and the unemployed, 17,67%. More than the half of the investigated persons (54,67%) were unmarried and 96, 33% persons were literate. Nearly all the people (96,33%) knew about blood donation in Lome and they have received information mainly from friends, media and sensitization by the CNTS. Sixty-one percent of the investigated knew where blood is donated. All the investigated were unanimous about the vital role of blood. Whatever their religion, they recognized its sacred nature. The majority of the investigated (85%) were willing to donate blood. Only 95 people were donors. The reasons for non-donation were mainly related to the fear of catching diseases (31,71%) especially the HIV (9,76%), the lack of information (25,37%), the religious beliefs (19,51%) and the fear of knowing the result of one's HIV test. 277 people (92,33%) said that blood should be donated without remuneration. CONCLUSION: There is a growing interest in the blood donation among the population of Lome but new strategies must be elaborated to inform the population and motivate blood donors.

[Good practices for the study of hemoglobin]. / Bonnes pratiques de l'étude de l'hémoglobine.

Hemoglobinopathies have become a significant national health problem in France. The biologists have a pivotal role in the genetic diagnoses. Although sickle cell disease (SCD) is the most frequent abnormality found: not less than 200 new cases are observed each year at birth, many other globin gene variations are found in the various ethnic groups. Since 1995 a neonatal sickle cell screening program has been established for at risk newborns. This programme is supported by the "Association française de dépistage et prévention des handicaps de l'enfant" (AFDPHE). The characterization of hemoglobin genetic variations requires a comprehensive set of laboratory techniques for which we specify here main clinical and technical recommendations.

[Beta-thalassemia in metropolitan France]. / Les beta-thalassémies en France métropolitaine.

OBJECTIVES: Update the data collected in 1990 in order to assess the distribution and management of thalassemic patients presently living in Metropolitan France. METHODS: A survey conducted in France in the clinical and biological departments of haematology permitted collection of epidemiological, clinical and biological data in a population of thalassemic patients followed-up in metropolitan France. RESULTS: Analysis of the replies revealed a total of 362 thalassemia with 249 beta-thalassemia major, 81 beta-thalassemia intermedia and 32 E-beta thalassemia. These patients predominated in the East of France and in the large cities. The total number of patients has remained stable over the last decade and new cases are decreasing. Among the 249 patients presenting with a ss-thalassemia major, 42 had received a bone marrow graft, whereas 207 were systematically transfused and 189 regularly underwent iron chelating. COMMENTS: Management is standardised and efficient but could be improved on with regard to iron chelating therapy.

A comparative evaluation of the sensitivity of five anti-hepatitis C virus immunoblot assays.

BACKGROUND AND OBJECTIVES: In order to compare sensitivity, five anti-hepatitis C virus (HCV) immunoblot assays were tested (Deciscan plus, Inno-Lia III, Matrix, Murex Western blot and RIBA-3). MATERIALS AND METHODS: The test panel (50 samples for each assay) included 6 anti-HCV-negative samples and 44 samples from 36 HCV-infected subjects. RESULTS: There were minor differences in core reactivity among the assays. The smallest number of NS3-reactive results occurred with the Murex and Matrix assays, and the smallest number of NS4 reactives with RIBA-3 and Matrix. Among the 20 discrepant results for NS5 there was one clear false-negative with Inno-Lia. Only 28 of the 50 samples of the panel gave the same results in all the assays: 5 negatives and 23 positives. One of the 6 negative samples were indeterminate in 3 assays. Eighteen of the 21 other divergent results were interpreted as either indeterminate or positive, a common reactivity being exhibited by all 5 assays. The most important discrepancies occurred on 3 HCV-RNA-positive samples which came up negative in some assays: 2 samples with isolated NS3 reactivity were negative by Matrix and Murex Western blot, 1 of them being also negative by Inno-Lia III; another sample was negative by RIBA-3 and Matrix due to weak signals (< 1) on core and NS3 proteins, which did not exceed 1+ with the other assays. CONCLUSIONS: With more uniform criteria for interpretation, the results would have been less divergent. Some assays should improve their sensitivity to the NS3 protein.

[Assessment of 32 months of continuous control of detection kits for anti-HIV and anti-HTLV antibodies and Hbs antigen used most commonly in transfusion biology. Retrovirus Study Group and Viral Hepatitis Study Group]. / Bilan de 32 mois de contrôle continu des trousses de dépistage des anticorps anti-VIH, anticorps anti-htlv et antigène hbs les plus utilisées en biologie transfusionnelle. Rétrovirus et Hépatites Virales de la SFTS.

Controls were performed using a common internal panel specific for anti-HIV, anti-HTLV and HBs Ag. During the past 32 months, 5 anti-HIV1 + 2 antibody kits (Abbott, Behring, Biotest, Murex D. and Organon T., total of 199 lots), 4 anti-HTLV I/II antibody kits (Abbott, Murex D., Organon T. and Ortho C.D., total of 153 lots) and 5 HBs Ag kits (Abbott, S.D. Pasteur, Murex D., Organon T. and Ortho C.D., total of 244 lots) were used and controlled by the 14 participating laboratories. Analysis of the results showed the values obtained for the most representative sample of each panel to be within the limits m +/- 2 SD in 95 to 100% of the HIV1 + 2 kits, in 94 to 97% of the HTLV kits and in 92 to 100% of the HBs Ag kits. The specificity of the kits evaluated was on an average equal or superior to 99.5%, as required by the French Drug Agency in a blood donor population.

Germline mosaicism for an alanine to valine substitution at residue beta 140 in hemoglobin Puttelange, a new variant with high oxygen affinity.

Hb Puttelange [beta 140(H18)Ala-->Val] was found as a de novo mutation in two siblings of a French family suffering from polycythemia. Both parents were phenotypically normal and exclusion of paternity has been ruled out by the study of several polymorphic markers located on different chromosomes. The structural modification of Hb Puttelange was established by reversed-phase HPLC analysis of the tryptic digest of the abnormal chain. The amino acid composition of an abnormal beta T14 peptide revealed that one of the four residues of Ala was replaced by a Val. Tandem mass spectrometry demonstrated that the substitution concerned position beta 140 (H18). This hemoglobin displays an increased oxygen affinity that is responsible for the polycythemia. De novo mutations, as demonstrated again in the case of this variant, have the highest probabilities of detection when they lead to pathological manifestations. They may result either from a somatic mutation in a very early stage of the embryological development of the propositus or may have a parental origin with occurrence of a germline mosaicism. The study of the beta-globin gene indicated that this case of Hb Puttelange probably arose from a mutation affecting a part of the germline of the father, therefore leading to a true recurrence risk.

[Epidemiology of genetic hemoglobin diseases in metropolitan France]. / Epidémiologie des maladies génétiques de l'hémoglobine en France métropolitaine.

The number of subjects with heterozygous beta-thalassaemia and sickle-cell anaemia in metropolitan France can be evaluated by the distribution of populations originating from countries with a high prevalence of genetic haemoglobinopathies. Taking into account the movements of these populations observed since the 1982 census, the current prevalences of beta-thalassaemic and drepanocytic traits are higher than the figures of 180,000 and 130,000 respectively found at that date. On the other hand, it appears from episodic screenings performed during the last few years that the percentage of subjects with heterozygous beta-thalassaemia is 3.09% in Corsica, 0.77% in school-age population in the Marseille area, and 0.72% in the general population of Marseille, Toulon and Nice. In 1992, the number of patients with heterozygous beta-thalassaemia and with major sickle-cell syndrome is estimated at 250-350 and 1000-3000 respectively. Patients with sickle-cell anemia predominate in the Paris area, whereas those with heterozygous beta-thalassemia predominate in the provinces, notably in the Provence-Côte d'Azur and Corsica regions.

[Cooley's syndrome in a Togolese nursing infant. Clinical and biological considerations]. / La maladie de Cooley chez un nourrisson togolais. Considérations cliniques et biologiques.

Several possible diagnoses are proposed to explain the symptomatology observed in a slightly jaundiced 10 month-old suckling infant suffering from fever and anaemia. Major beta-thalassaemia in its most severe form (Cooley's syndrome) proved to be the correct diagnosis. The importance of family background is stressed for these haemolytic cases.

[Prevalence and epidemiologic features of subjects found to be infected with HIV when donating blood. CTS of the "Retrovirus" Study Group of the Société Nationale de Transfusion Sanguine]. / Prévalence et caractéristiques épidémiologiques des sujets découverts infectés par le VIH à l'occasion d'un don de sang. CTS du Groupe de travail "Rétrovirus" de la SNTS.

HIV seroprevalence decreased from 0.62% in 1985 to 0.11% in the first 1990 semester. However, the number of regular blood donors screened as seropositive remains constant since 1988: 48 in 1988, 49 in 1989 and 25 in the first 6 months of 1990. From these data, from reports on recipients and due to the exclusion of 30% of such donors by anti-HBc screening, the residual risk to transmit HIV by blood transfusion was estimated to 17 blood donations per year in France. No significant change was observed throughout these years either in sex ratio or in the repartition into age groups. The number of HIV-infected subjects through the heterosexual route has not increased. The number of homosexuals and of IVDA has dramatically decreased since 1985, homosexuals still representing the major at-risk group.

[New methods of interlaboratory monitoring of HIV-1 ELISA kits. Comparative study of 2 periods: 1/12/1988 to 15/4/1989 and 15/4/1989 to 31/8/1989. Le Groupe Rétrovirus de la Sociètè Nationale de Transfusion Sanguine]. / Neuf mois de contrôle interlaboratoire des trousses Elisa VIH 1. Etude comparative de deux périodes: 1/12/1988 au 15/4/1989 et 15/4/1989 au 31/8/1989. Le Groupe Rétrovirus de la Société Nationale de Transfusion Sanguine.

Since december 1st 1988, the Retrovirus study Group of the French Society of Blood Transfusion has initiated a systematic multicentric control of all anti-HIV screening EIA test kits lots used by each member of the group. For this purpose a special panel (GRV) has been designed and forwarded to each laboratory. From december 1st 1988 to august 8 1989, 6 HIV-1 kits have been in use (Diagnostics Pasteur Elavia 1; Diagnostics Pasteur Rapid'Elavia; Organon Vironostika; Abbott HIV recombinant; Du Pont env 9; Wellcome Wellcozyme). The GRV panel has been run 204 times on 102 different lots in 12 laboratories. Results after 9 months show that these 6 kits almost always properly recognize the 5 HIV 1 positive samples of the panel. However they differ in their ability to recognize HIV 2 positive samples. Variations in results are observed from lot to lot as well as between the first half of this period and the second.

A randomized study of combined 5-fluorouracil and plasma perfusion over protein A-sepharose in human advanced colorectal carcinoma.

To evaluate the advantage with regard to toxicity, response rate, time to progression and survival of combination chemoimmunotherapy over single-agent chemotherapy in patients with metastatic colorectal carcinoma (CRC), 30 patients were randomized to receive a combination of 5-fluorouracil (5-FU) by continuous i.v. infusion and plasma perfusion (PP) over protein A-Sepharose (group A), or a combination of 5-FU and PP over sepharose (group B) or 5-FU alone (group C). 5-FU was given at 1,000 mg/m2/d on days 1-5 of a 4-weekly cycle until progression. Patients of groups A and B received bi-weekly on-line PPs until disease progression or for a maximum of 19 treatments. PP was well tolerated and no severe or life-threatening toxicity was observed. The response rates were 10% for the group A (1 PR), 0% for the group B and 20% for the group C (1 CR + 1 PR). The times to tumor progression for patients in groups A and C were 22 months, 12 and 11 months, respectively and the median survival times were 17 months, 10 months and 9 months. Although the time to progression and survival tended to be higher in patients treated with protein A. PP, these differences were not statistically significant. This is the first report of a randomized trial showing some therapeutic advantage in combining protein A. PP with 5-FU in CRC patients. Further randomized studies are required to demonstrate the real true value of this chemoimmunotherapeutic approach.

Alpha-1-antitrypsin deficiency in a large sibship.

We studied alpha 1-antitrypsin deficiency in a large family of 10 siblings: 3 subjects had PiZZ phenotype, but only 1 had emphysema; 2 subjects had no respiratory complaint. The patient with emphysema was a heavy smoker. According to the literature, this case suggests that, in PiZZ phenotype, emphysema appears earlier and is more severe if the patients smoke.

Hb J-Cordoba [alpha 2A beta 2(95)(FG2)Lys----Met]. A new Hb variant found in Argentina.

Hb J-Cordoba [alpha 2A beta 2(95)(FG2)Lys----Met], is one of the few hemoglobin variants discovered in Argentina. The structure and functional abnormalities are described. Hb J-Cordoba exhibits a slightly increased oxygen affinity, low cooperativity, and normal interaction with heterotropic cofactors.