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Biomedical subjects

B Blondel

Publications and source records attributed to B Blondel.

At least 91 records · Page 5Linked to original sources

Molecular characterization of mouse-virulent poliovirus type 1 Mahoney mutants: involvement of residues of polypeptides VP1 and VP2 located on the inner surface of the capsid protein shell.

Most poliovirus (PV) strains, including PV PV-1/Mahoney, are unable to cause paralysis in mice. Determinants for restriction of PV-1/Mahoney in mice have been identified by manipulating PV-1 cDNA and located on the viral capsid protein VP1. These determinants consist of a highly exposed amino acid sequence on the capsid surface corresponding to the B-C loop (M. Murray, J. Bradley, X. Yang, E. Wimmer, E. Moss, and V. Racaniello, Science 241:213-215, 1988; A. Martin, C. Wychowski, T. Couderc, R. Crainic, J. Hogle, and M. Girard, EMBO J. 7:2839-2847, 1988) and of residues belonging to the N-terminal sequence located on the inner surface of the protein shell (E. Moss and V. Racaniello, EMBO J. 10:1067-1074, 1991). Using an in vivo approach, we isolated two mouse-neurovirulent PV-1 mutants in the mouse central nervous system after a single passage of PV-1/Mahoney inoculated by the intracerebral route. Both mutants were subjected to two additional passages in mice, plaque purified, and subsequently characterized. The two cloned mutants, Mah-NK13 and Mah-NL32, retained phenotypic characteristics of the parental PV-1/Mahoney, including epitope map, heat lability, and temperature sensitivity. Mah-NK13 exhibited slightly smaller plaques than did the parental virus. The nucleotide sequences of the mutant genomes were determined, and mutations were identified. Mutations were independently introduced into the parental PV-1/Mahoney genome by single-site mutagenesis. Mutated PV-1/Mahoney viruses were then tested for their neurovirulence in mice. A single amino acid substitution in the capsid proteins VP1 (Thr-22-->Ile) and VP2 (Ser-31-->Thr) identified in the Mah-NK13 and Mah-NL32 genomes, respectively, conferred the mouse-virulent phenotype to the mouse-avirulent PV-1/Mahoney. Ile-22 in VP1 was responsible for the small-plaque phenotype of Mah-NK13. Both mutations arose during the first passage in the mouse central nervous system. We thus identified a new mouse adaptation determinant on capsid protein VP1, and we showed that at least one other capsid protein, VP2, could also express a mouse adaptation determinant. Both determinants are located in the inside of the three-dimensional structure of the viral capsid. They may be involved in the early steps of mouse nerve cell infection subsequent to receptor attachment.

Animals↗

A mutation in the RNA polymerase of poliovirus type 1 contributes to attenuation in mice.

The attenuated Sabin strain of poliovirus type 1 (PV-1) differs from the neurovirulent PV-1 Mahoney strain by 55 nucleotide mutations. Only one of these mutations (A-480-->G, in the 5' noncoding (5' NC) region of the genome, is well characterized, and it confers a strong attenuating effect. We attempted to identify genetic attenuation determinants in the 3'-terminal part of the Sabin 1 genome including the 3D polymerase (3Dpol) gene and the 3' NC region. Previous studies suggested that some of the 11 mutations in this region of the Sabin 1 genome, and in particular a mutation in the polymerase gene (U-6203-->C, Tyr-73-->His), are involved to some extent in the attenuation of PV-1. We analyzed the attenuating effect in the mouse model by using the mouse-adapted PV-1/PV-2 chimeric strain v510 (a Mahoney strain carrying nine amino acids of the VP1 capsid protein from the Lansing strain of PV-2). Mutagenesis of locus 6203 was performed on the original v510 (U-6203-->C) and also on a hybrid v510/Sabin 1 (C-6203-->U) carrying the downstream 1,840 nucleotides of the Sabin 1 genome including the 3Dpol and 3' NC regions. Statistical analysis of disease incidence and time to disease onset in numerous mice inoculated with these strains strongly suggested that nucleotide C-6203 is involved in the attenuation of the Sabin 1 strain. Results also suggested that, among the mutations located in the 3Dpol and 3' NC regions, nucleotide C-6203 may be the principal or the only one to be involved in attenuation in this mouse model. We also found that the effect of C-6203 was weaker than that of nucleotide G-480; the two nucleotides acted independently and may have a cumulative effect on attenuation. The U-6203-->C substitution also appeared to contribute to the thermosensitivity of the Sabin 1 strain.

Amino Acid Sequence↗

A comparison of prenatal care use in the United States and Europe.

OBJECTIVES: We sought to describe prenatal care use in the United States and in three European countries where accessibility to prenatal care has been reported to be better than it is in the United States. METHODS: We analyzed the 1980 US National Natality Survey, the 1981 French National Natality Survey, a 1979 sample of Danish births, and a survey performed from 1979 to 1980 in one Belgian province. RESULTS: The proportion of women who began prenatal care late (after 15 weeks) is highest in the United States (21.2%) and lowest in France (4.0%). This contrasts with the median number of visits, which is greater in the United States (11) than in Denmark (10) or in France (7). Across all maternal ages, parities, and educational levels, late initiation of prenatal care is more frequent in the United States, and median number of visits in the United States is equal to or higher than that in the other countries. CONCLUSIONS: In countries that offer nearly universal access to prenatal care, women begin care earlier during pregnancy and have fewer visits than women in the United States.

Adult↗

[To be born or not to be. Epidemiologic, judicial and psychological aspects].

The requisites for filling up birth certificates in France (> or = 180 days of pregnancy and vitality at the registration of birth) are different from the criteria recommended by the World Health Organisation (WHO) (at least 500 g) for national statistics. The number of stillborn babies and neonatal deaths known from two different sources in the Nord-Pas de Calais Region in 1988-1989 have been compared ie: the vital statistics published by INSEE and the data of a survey carried out in hospitals according to the WHO criteria. Among the 808 known perinatal deaths in the survey, 305 (37.7%) were ignored or were not classified in the same categories by the registration services for vital statistics. 230 children including 29 born alive had not been registered and 75 children born alive had been registered as still born. The disparity in these definitions between INSEE and the WHO has serious consequences: the perinatal mortality measured by INSEE is underestimated by 28%, in comparison with mortality registered according to the WHO criteria. The 180 day threshold of viability reduces the social rights of employed women and makes it more difficult for them to have the money they spent on medical care refunded. Finally, as it is impossible to find a trace of these children who were not legally registered since they were under the threshold of viability, the mourning response of parents to perinatal deaths is all the more difficult. Current evolution in the threshold of viability observed in maternity units, makes it necessary to change the criteria which are applied for the legal registration of births.

Attitude to Death↗

Home uterine activity monitoring in France: a randomized, controlled trial.

OBJECTIVES: We assessed the effectiveness of ambulatory tocodynamometry in reducing the preterm delivery rate in women at risk of preterm delivery such as women with risk factors and women previously hospitalized and discharged. STUDY DESIGN: In four public maternity units these women were randomly allocated to two groups: 84 had home uterine activity monitoring and daily midwife contact and 84 were given the standard care for high-risk women, which generally includes home visits by community midwives. RESULTS: The proportion of deliveries before 37 weeks' gestation was slightly higher in the monitored group than in the control group (32% vs 22%). The corresponding odds ratio was 1.7 (95% confidence interval: 0.9 to 3.5). CONCLUSION: Although the sample was small, these results suggest that home uterine activity monitoring was probably not beneficial to the population studied, or at least that any benefit would have been too small to justify extending this monitoring in this high-risk population.

Cardiotocography↗

Assessment at 1 year of the psychological consequences of having triplets.

The purpose of this study was to assess the psychological difficulties encountered by mothers 1 year after the birth of triplets. Twelve mothers entered the study having delivered triplets in a public hospital in Paris. Nine pregnancies had been initiated after in-vitro fertilization (IVF) or gamete intra-Fallopian transfer (GIFT), two after ovarian stimulation and one was spontaneous. The method consisted of tape-recorded semi-structured interviews at the mothers' homes. At 1 year, a majority of mothers reported considerable fatigue and stress. In most cases, home help was no longer provided by social services or by relatives. A majority suffered from social isolation and had difficulties in going out because of a lack of help, and inquisitive looks and questions from other people. Most mothers said that having triplets placed a strain on the marital relationship. The relationship with the children was often disturbed. Mothers reported that it was difficult to give adequate attention to the three children at the same time. Most of them tended to become emotionally detached. Eight mothers expressed psychological difficulties and three of them were treated for depression. Families with triplets should be provided with increased help, special attention, counselling and support, either at home, in clubs or in special clinics.

Emotions↗

Home visits for pregnancy complications and management of antenatal care: an overview of three randomized controlled trials.

OBJECTIVE: To examine whether a policy of home visits reduces the amount of antenatal care provided by hospital maternity units. DESIGN: A meta-analysis of three randomized controlled trials. SETTING: 9 maternity units in France. SUBJECTS: 1410 women with pregnancy complications. INTERVENTION: 1 or 2 home visits a week by a midwife. MAIN OUTCOME MEASURES: Admission rate and length of stay in hospital. RESULTS: The home-visiting system did not affect the hospital admission rate (typical odds ratio = 0.9; 95% CI = 0.7-1.2). In each trial, the length of hospital stay did not differ between the intervention and the control groups. CONCLUSIONS: The home-visiting system did not greatly alter the practice of antenatal hospital admission in the maternity units studied. The results question the way the health services were used and suggest that a better integration of hospital and home services is needed to make a more rational use of health care resources.

Female↗

Comparison of vaginal examination findings in two antenatal clinics.

Findings of routine vaginal examinations during pregnancy were compared in two teaching hospitals located in the same area of Paris. We selected 2943 women who had had at least one antenatal visit between 29 and 31 weeks of gestation. Large differences in the frequency of maturation signs were observed between the two hospitals for mid-position, soft consistency and expanded lower uterine segment, although the higher frequency of each sign was not found in the same hospital. No difference was observed for dilatation of the internal os. A better reliability in assessing dilatation than other signs of maturation may explain our results and the role of dilatation in the prediction of preterm delivery.

Adult↗

An indicator of adverse pregnancy outcome in France: not receiving maternity benefits.

STUDY OBJECTIVE: The aim was to compare the social characteristics, the pregnancy outcome, and the antenatal care of women in France who did not receive maternity benefits to women who did. These benefits (860 FF, approx 86 pounds per month) are given to every pregnant woman, starting in the second trimester. Payments are made on the condition that at least three antenatal visits are made, the first being before the end of the first trimester. DESIGN: The study involved a random sample of women who were interviewed after delivery during their stay in hospital. Data on pregnancy outcome were collected from medical records. SETTING: The study was carried out in four public maternity units in different regions of France. PARTICIPANTS: 1692 women were included in the analysis (86.8% of the selected sample). Of 257 exclusions, 40 had multiple pregnancies, 189 had missing data, and 28 did not answer the question concerning maternity benefits. MEASUREMENTS AND MAIN RESULTS: 4.3% of the women did not receive any maternity benefits. These women lived in poorer social conditions than the women who received the benefits. They had a higher preterm delivery rate, after controlling for risk factors in a logistic regression. Women without maternity benefits were characterised by a lower level of care, yet the majority began their antenatal care during the first trimester or had more than six visits. CONCLUSIONS: Not receiving maternity benefits during pregnancy is an index of an underprivileged situation and a risk factor for pregnancy outcome.

Age Factors↗

Effect of angiotensin II on cytosolic free calcium in neonatal rat cardiomyocytes.

The effect of angiotensin II (ANG II) on cytosolic free Ca2+ concentration ([Ca2+]i) was studied in cultured neonatal rat ventricular myocytes. [Ca2+]i was estimated in groups of one to three cells by dual-wavelength microfluorometry or in cell populations using conventional fluorometry. ANG II (10(-8) M) produced an acute short-lived increase over the control basal diastolic [Ca2+]i and increased the frequency of the [Ca2+]i transients. The amplitude of the [Ca2+]i transients was decreased to 64.4% of basal values. The effect of ANG II on [Ca2+]i was blocked by the selective AT1 receptor subtype antagonist Du Pont 753 but not by the AT2 antagonist PD 123319. Removal of extracellular Ca2+ or blockade of voltage-gated Ca2+ channels in cells cultured for 5-7 days abolished the [Ca2+]i transients, but only partially diminished the effect of ANG II on [Ca2+]i. Thapsigargin, an inhibitor of sarcoplasmic reticulum Ca(2+)-Mg(2+)-ATPase, reduced or abolished the [Ca2+]i response to ANG II. Phorbol 12-myristate 13-acetate (PMA), 10(-6) and 10(-7) M, also decreased the amplitude of the Ca2+ transients similar to ANG II. Pretreatment with 10(-6) M PMA or 10(-6) M 1-oleoyl-2-acetyl-glycerol (OAG) inhibited the initial rise in [Ca2+]i and the Ca2+ transients. Thus ANG II produces an acute rise in [Ca2+]i which is derived predominantly from sarcoplasmic reticulum intracellular stores. This acute effect is followed by a significant reduction in the amplitude for the Ca2+ transient and may be mediated by activation of protein kinase C.

Angiotensin II↗

[Psychological and social evaluation].

The purpose of psychological and social assessment of health programs is the measurement of psychological well-being and lifestyle in targeted populations (i.e. pregnant women, mothers, children or teenagers) and interactive effects on other family members. A psychological and social evaluation should contain the following elements: social and/or cultural factors that facilitate participation in a health program, the opinion of and satisfaction with the program, the psychological and social consequences of the program. Three types of tools can be utilized to measure psychological and social indicators: standardized questionnaires, questionnaires designed specifically for the study in question, and interviews. Study protocols, data collection and analyses must be done using the same methods as those used in any other type of medical evaluation. The investigator must be particularly sensitive to the quality of the measurement tools, the size of the sample and the effects of confounding factors. Social and psychological aspects are essential in the evaluation of a health program. On the one hand, they allow for an understanding of how a health program is accepted and applied within a population. On the other hand, they enable the verification of whether or not there has been any change in the quality of life among individuals and their families.

Adult↗

[Evaluation of screening programs].

This paper discusses the specific aspects involved in the assessment of screening programmes, compared to the assessment of other types of public health interventions. Screening programmes are aimed at healthy asymptomatic individuals, who, in case of a positive test, will be exposed to subsequent investigations or treatments. This paper stresses upon the several aspects to be taken into consideration when assessing the potential benefits and hazards of a screening programme, especially in order to limit hazards linked to false positive results: predictive value of the test according to its diagnostic value and the disease prevalence, existence of effective "treatments" in case of positive test. It underlines the need for adequate methods to evaluate positive and negative health effects, and psychological and social consequences.

Anxiety↗

Stromal influences on transformation of human mammary epithelial cells overexpressing c-myc and SV40T.

The proto-oncogene c-myc and the oncogene SV40T, both of which have been implicated in the process of cellular immortalization in vitro, have been introduced via amphotropic retroviral expression vectors into the human mammary epithelial cell (HMEC) line 184A1N4 (A1N4). Two stable cell lines were established by growth in selective medium and were found to overexpress either c-myc (A1N4-myc) or SV40T antigen (A1N4-T). Neither the A1N4, A1N4-myc, or A1N4-T cells will grow in soft agar or form tumors in nude mice. However, A1N4-T or A1N4-myc cells, but not the parental A1N4 cells, form colonies in soft agar in response to either epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), or basic fibroblast growth factor (bFGF). Like EGF and TGF alpha, bFGF is moderately mitogenic for the anchorage-dependent growth (ADG) of all three cell lines. Further, co-cultivation of A1N4-T or A1N4-myc cells with primary diploid mammary fibroblasts can also induce the anchorage-independent growth (AIG) and stimulate the ADG of A1N4-T or A1N4-myc. In addition, conditioned medium obtained from these mammary fibroblasts also stimulated the AIG of the A1N4-T and A1N4-myc cells and was found to contain immunoreactive TGF alpha and bioactive FGF. The mammary fibroblasts express specific mRNA transcripts for bFGF and acidic FGF (aFGF). These results suggest that growth factors such as TFG alpha or FGF, which may be derived from the adjacent mammary stroma, might influence in a paracrine manner the phenotypic characteristics of a population of human mammary epithelial cells toward transformation.

Agar↗

Prediction of preterm delivery: is it substantially improved by routine vaginal examinations?

The ability of routine vaginal examinations to improve the prediction of preterm delivery was assessed in a group of 6909 women who were registered at each prenatal visit and on whom this examination had been carried out. We compared two risk scores, one including known risk factors (maternal characteristics and symptoms reported by women), and the other including these factors and the findings of vaginal examination. These risk scores were computed by multiplying the adjusted odds ratio estimations obtained by logistic regressions. The prediction of preterm delivery was improved significantly by vaginal examination at 25 to 28 weeks' and 29 to 31 weeks' gestation. However, the improvement was not very large: when 30% of nulliparous women were classified as high risk at 29 to 31 weeks, the sensitivity was 55% when considering only the risk factors and 63% when adding the findings of vaginal examination; the percentages were 52% and 55%, respectively, for parous women. These results partially explain why the medical practice of routine vaginal examinations varies from country to country.

Adolescent↗

Structural factors modulate the activity of antigenic poliovirus sequences expressed on hybrid hepatitis B surface antigen particles.

We have studied the functional expression of antigenic poliovirus fragments carried by various hybrid hepatitis B surface antigen (HBsAg) particles. Several constructions were made by using two different insertion sites in the HBsAg molecule (amino acid positions 50 and 113) and two different sequences, one derived from poliovirus type 1 (PV-1) and the other from PV-2. The inserted fragments each encompassed residues 93 to 103 of the capsid protein VP1, a segment which includes the linear part of the neutralization antigenic site 1 of the poliovirus. The antigenicity and immunogenicity of the hybrid particles were evaluated and compared in terms of poliovirus neutralization. A high level of antigenic and immunogenic activity of the PV-1 fragment was obtained by insertion at position 113 but not at position 50 of HBsAg. However, a cooperative effect was observed when two PV-1 fragments were inserted at both positions of the same HBsAg molecule. Antibodies elicited by the PV-2 fragment inserted at amino acid position 113 did not bind or neutralize the corresponding poliovirus strain. They did, however, bind a chimeric poliovirus in which the homologous antigenic fragment of PV-1 had been replaced by that of PV-2. The only virions that were neutralized by these antibodies were certain mutants carrying amino acid substitutions within the PV-2 fragment. These results show that position, constraints from the carrier protein, and nature of the inserted sequences are critically important in favoring or limiting the expression of antigenic fragments as viral neutralization immunogens.

Amino Acid Sequence↗