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Biomedical subjects

B Blondel

Publications and source records attributed to B Blondel.

At least 109 records · Page 6Linked to original sources

Inverse relationship between glucose metabolism and glucose-induced insulin secretion in rat insulinoma cells.

Slowly growing X-ray-induced rat insulinomas and derived cell lines have been used as a model system for glucose-induced insulin release. During perfusions of tumors transplanted under the kidney capsule, the carbohydrates glucose and D-glyceraldehyde increased insulin secretion. These stimuli and the amino acids leucine and alanine also provoked insulin release in freshly isolated tumor cells. Under these conditions, glucose utilization had a Km of 4.6 mM and maximal velocity of 0.9 nmol/min/10(6) cells. A continuous cell line was established from such a preparation. In culture, glucose-induced insulin secretion was no longer detectable while responses to D-glyceraldehyde and amino acids were retained. Glucose metabolism in the cell line showed a decrease in Km to 0.7 mM glucose and an increased maximal velocity of 1.4 nmol/min/10(6) cells. Attempts to revert these alterations were undertaken using glucose-deficient culture medium to diminish glycolytic flux. Basal insulin release was lowered, while the growth pattern of the cells remained unchanged. Another approach involved the use of sodium butyrate which has been demonstrated to promote differentiation in other cell systems. Whereas sodium butyrate markedly increased cellular insulin content, the secretory responses were not improved. These results provide evidence that the loss of glucose-induced insulin secretion is paralleled by alterations in glucose metabolism.

Animals↗

Effect of maternal and fetal characteristics on diagnosis of intrauterine growth retardation.

We studied the fetal and maternal characteristics that affect the diagnosis of intrauterine growth retardation and lead to variations in the sensitivity, specificity and predictive values. The population comprised the 18,166 women who consulted and delivered in two teaching hospitals in Paris from 1978 to 1983. Specificity was lower when a child was born before 37 weeks, with a small weight-for-gestational age, and when the mother had experienced complications during either her obstetric history or current pregnancy. Conversely, sensitivity was higher when these maternal and fetal characteristics were present. Positive predictive values rose in the presence of a risk factor for small-for-dates, but the rise was smaller than would have been expected if sensitivity and specificity had remained at the levels observed in the low-risk group.

Birth Weight↗

Efficient induction of focus formation in a subclone of NIH3T3 cells by c-myc and its inhibition by serum and by growth factors.

In both experimental and spontaneous tumors, c-myc expression is often enhanced following its amplification or its rearrangement adjacent to a strong promotor/enhancer. However, c-myc by itself does not induce foci efficiently in fibroblast cultures. The effect of high levels of c-myc expression from a retroviral construct was investigated in several rodent fibroblast cell lines grown in medium containing 10% fetal calf serum or in serum-free PC-1 medium. c-myc-infected NIH3T3 clone 7 cells exhibited efficient quantitative focus formation when grown in PC-1 medium, whereas foci were not detected when grown in serum-supplemented medium. NIH3T3 clone 7 was the only cell line found to be sensitive to c-myc; other clones of NIH3T3 or other rodent fibroblast cell lines proved to be resistant to c-myc focus formation. At least two major types of morphologically distinct c-myc-induced foci were observed; the first was similar to ras-transformed foci induced in NIH3T3 and other fibroblast cell lines, and the second type was composed of adipocyte-like cells similar to NIH3T3 L1 cells. The c-myc infected cells cloned from these two types of foci expressed high levels of retrovirus-derived c-myc RNA and exhibited elevated levels of immunoreactive myc protein, as detected by immunofluorescent staining with an anti-myc polyclonal antibody. c-myc-transformed clones displayed only a limited ability to grow in soft-agar in the presence of serum and were not tumorigenic in nude mice. Focus formation by c-myc was quantitatively inhibited by the addition of interferon alpha + beta (INF alpha, beta), tumor necrosis factor alpha (TNF alpha) or transforming growth factor beta 1 (TGF beta 1) to the serum-free PC-1 medium, and, in correlation, NIH3T3 clone 7 cells produced the lowest level of endogenous TGF beta of the various cell lines tested.

Animals↗

Ultrasound in obstetrics: do the published evaluative studies justify its routine use?

A review of surveys assessing the use of ultrasound in obstetrics was undertaken to determine why this examination has spread so rapidly. Seven randomized controlled trials (RCTs) published to date as well as 182 papers published in four obstetric journals between 1979 and 1984 were reviewed. The value of routine ultrasound scanning to improve the diagnosis of intrauterine growth retardation or gestational age was demonstrated in the RCTs, but the results of the RCTs measuring the effects on health of this screening procedure did not give strong evidence for its routine use. Of the 182 papers identified, 137 were related to the diagnostic assessment of ultrasound, 14 concerned the effects on medical practice and only nine papers studied the effects of ultrasound scanning on health. Most of these 137 papers came out in favour of this procedure. Thus the spread of ultrasound scanning was based mainly on evaluative surveys which assessed its diagnostic value.

Evaluation Studies as Topic↗

The use of ultrasound examinations, intrapartum fetal heart rate monitoring and beta-mimetic drugs in France.

We conducted a survey of French obstetricians to document their attitudes towards routine ultrasound, intrapartum fetal monitoring and beta-mimetics in 1987. A questionnaire was sent to 582 obstetricians or gynaecologists who were members of two French medical associations. The response rate was 85%. Of the respondents 92% prescribed two or three routine ultrasound examinations; only one doctor did not use electronic fetal monitoring and 99% of the respondents prescribed beta-mimetics to prevent preterm delivery. Some obstetricians reported a decrease in their use of ultrasound and more dramatically in the use of beta-mimetics. Side-effects were reported to be the major reason for the change in beta-mimetic use. Obstetricians who read English language journals were more likely to have reduced their use of ultrasound and beta-mimetics than those who read only French language journals.

Female↗

Construction and characterization of hybrid hepatitis B antigen particles carrying a poliovirus immunogen.

The hepatitis B surface antigen (HBsAg) has the unique property of assembling with cellular lipids into spherical or elongated particles of 22 nm diameter which are secreted by mammalian cells expressing HBsAg. We have studied the structural requirements for particle formation and secretion by creating in-phase insertions into different regions of the S gene of the hepatitis B virus, coding for HBsAg. Modified genes were integrated into an appropriate vector and expressed in mouse L cells. Various single and double inserts in the two major hydrophilic domains of HBsAg were compatible with particle synthesis and secretion. The level of secretion was influenced by the length of the insert, its primary structure, and the site of insertion into the HBsAg molecule. One of the inserted sequences was a synthetic DNA fragment encoding a continuous type 1 poliovirus neutralization epitope (the C3 epitope). Mammalian cells expressing the modified hepatitis B virus S gene secreted hybrid particles carrying the poliovirus antigen. The hybrid polio-HBsAg particles reacted with a monoclonal antibody specific for the C3 epitope and induced poliovirus neutralizing antibodies at low, but significant, titers in mice and at high titers in rabbits. However, the immune response to HBsAg was weaker to hybrid particles than to unmodified HBsAg particles. By cotransfection with two different plasmids carrying either modified or unmodified genes, we obtained phenotypically mixed particles containing both polio-HBsAg and HBsAg molecules. Inoculated into rabbits, the mixed particles induced high antibody titers against both poliovirus and HBsAg.

Amino Acid Sequence↗

Management of pregnancy and childbirth in England and Wales and in France.

This paper reviews national data on obstetric and neonatal practices in England and Wales, and in France between 1970 and 1980. The data have been derived from national statistics and surveys on national samples of births in 1970, 1975 and 1980 in England and Wales, and 1972, 1976 and 1981 in France. The analysis shows that there was no major difference in pregnancy outcome, but wide variations in medical practices, and their trend over time. The main differences were: in England and Wales a higher number of antenatal visits, a higher percentage of inpatient admissions during pregnancy, a higher rate of induction, more episiotomies, a higher rate of resuscitation at birth, and admission to neonatal special care units; in France, a higher rate of caesarean sections before and during labour, some evidence of a more active management of labour, and a longer hospital post-natal stay. These differences in practice reflect differences in objectives and assessment of the effectiveness of care between the two countries: they point out the need for better monitoring and evaluation of obstetric and neonatal practices.

Delivery, Obstetric↗

Marital status and cohabitation during pregnancy: relationship with social conditions, antenatal care and pregnancy outcome in France.

A survey of a representative sample of 5508 births in France in 1981 permitted the study of social characteristics of pregnant women, the medical care they received during their pregnancy and their pregnancy outcome, as a function of their marital status and whether or not they lived with the father of the child. Unmarried women living with the father (n = 412) like unmarried women living alone (n = 171), were more often younger, having their first baby and had a lower educational level than did married women living with the father (n = 4590). However, among the unmarried women, those living alone were in a more unfavourable position than those living with the father; in particular, they were more often less than 20 years old, had the minimum educational level required and were unemployed. Both groups of unmarried women had a higher preterm delivery rate than did married women, even after taking other risk factors into account in a logistic regression. The odds ratios (95% confidence interval) for pre-term delivery among unmarried mothers living without the father was 1.9 (1.0-3.4) and that for the unmarried cohabiting with the father was 1.6 (1.0-2.4). Thus, to fully appreciate the perinatal risks and medical needs during pregnancy, both the marital and cohabitational status of the women should be considered.

Adolescent↗

Presentation and immunogenicity of the hepatitis B surface antigen and a poliovirus neutralization antigen on mixed empty envelope particles.

Insertion of a synthetic DNA fragment encoding a poliovirus neutralization epitope into the S gene encoding the major envelope protein of hepatitis B virus has yielded hybrid (HBsPolioAg) particles closely resembling authentic 22-nm antigen (HBsAg) particles by expression of the modified gene in mammalian cells. In mice, these hybrid particles induce neutralizing antibodies against poliovirus but only weak immune response to HBsAg (F. Delpeyroux, N. Chenciner, A. Lim, Y. Malpièce, B. Blondel, R. Crainic, S. Van der Werf, and R. E. Streeck, Science 233:472-474, 1986). By cotransfection with different plasmids carrying either modified or unmodified S genes, we have now obtained mixed particles presenting both HBsAg and HBsPolioAg. When such particles were inoculated into rabbits, antibodies to both poliovirus and to HBsAg were induced. Moreover, the titers of neutralizing antibodies to poliovirus induced by HBsPolioAg were much higher than those previously obtained in mice. The design of multivalent particles carrying various peptide sequences or presenting several heterologous epitopes may therefore be possible.

Animals↗

Hexokinase isoenzymes of RIN-m5F insulinoma cells. Expression of glucokinase gene in insulin-producing cells.

We have analysed the pattern of expression of the hexokinase isoenzyme group in RIN-m5F insulinoma cells. Three hexokinase forms were resolved by DEAE-cellulose chromatography. The most abundant isoenzyme co-eluted with hexokinase type II from rat adipose tissue and displayed a Km for glucose of 0.15 mM, similar to the adipose-tissue enzyme. Hexokinase type II was in large part associated with a particulate subcellular fraction in RIN-m5F cells. The two other hexokinases separated by ion-exchange chromatography were an enzyme similar to hexokinase type I from brain and glucokinase (or hexokinase type IV). The latter isoenzyme was identified as the liver-type glucokinase by the following properties: co-elution with hepatic glucokinase from DEAE-cellulose and DEAE-Sephadex; sigmoid saturation kinetics with glucose with half-maximal velocity at 5.6 mM and Hill coefficient (h) of 1.54; suppression of enzyme activity by antibodies raised against rat liver glucokinase; apparent Mr of 56,500 and pI of 5.6, as shown by immunoblotting after one- and two-dimensional gel electrophoresis; peptide map identical with that of hepatic glucokinase after proteolysis with chymotrypsin and papain. These data indicate that the gene coding for hepatic glucokinase is expressed in RIN-m5F cells, a finding consistent with indirect evidence for the presence of glucokinase in the beta-cell of the islet of Langerhans. On the other hand, the overall pattern of hexokinases is distinctly different in RIN-m5F cells and islets of Langerhans, since hexokinase type II appears to be lacking in islets. Alteration in hexokinase expression after tumoral transformation has been reported in other systems.

Adenoma, Islet Cell↗

Pregnancy outcome and social conditions of women under 20: evolution in France from 1972 to 1981.

Two studies based on national samples of births in France in 1972 and 1981 have enabled a comparison of the changes in perinatal risk and social situation of women under 20 years of age with those of women 20 and over. Preterm delivery among women under 20 remained stable during the 10-year period, while it declined significantly among older women. Also, the social situation of teenagers deteriorated in terms of occupational activity, educational level, presence of the child's father in the home, and his occupation. The changes in these social characteristics do not adequately explain the increased relative risk of preterm delivery among women under 20.

Adolescent↗

Contribution of specialists to antenatal care in France: impact on level of care during pregnancy and delivery.

This study was based on a survey of a national sample of births in France in 1981 which included 5508 women. Four pathways of antenatal care were defined according to the stage of pregnancy at first intervention of a specialist, as opposed to a general practitioner, in the care of the pregnancy. Taking into account the sociodemographic and medical characteristics of the women in a logistic regression, a large number of antenatal visits, an ultrasound examination, and hospitalisation during pregnancy were more frequent when the degree of specialisation of the pathway increased. But the influence of pathways was less significant for deliveries. Caesarean section rates, for example, did not vary according to pathway. However, induction of labour and intrapartum electronic fetal monitoring were less frequent among women cared for solely by a general practitioner than among those who had consulted a specialist at least once during pregnancy. The increase in medical care and the role of the specialist in antenatal care are discussed.

Delivery, Obstetric↗