Search PubMed⌕ Search

Biomedical subjects

T Moreau

Publications and source records attributed to T Moreau.

At least 127 records · Page 7Linked to original sources

Aryl hydrocarbon hydroxylase activity in human placenta of passive smokers.

The levels of smoke components and metabolites in maternal blood and urine are useful in assessing direct exposure but they do not appear to be sufficiently sensitive as a long-term indicator of passive smoke exposure. Induction of aryl hydrocarbon hydroxylase (AHH) activity in the placenta as a result of maternal smoking has been well documented. This enzyme oxidizes various polycyclic aromatic hydrocarbons abundantly present in cigarette smoke. We hypothesized that passively inhaled tobacco smoke may induce placental AHH activity. Placental AHH levels were determined in 207 pregnancies at birth. As has been found in previous studies, we demonstrated that smoking during pregnancy is associated with a marked increase in placental AHH activity. A relationship was found between the recorded number of cigarettes smoked per day and the placental AHH activity. Moreover, AHH activity was significantly higher in pregnant women passively exposed to tobacco smoke relative to controls. The usefulness of analysis of placental AHH activity as a biological marker of in utero smoke exposure in epidemiological studies is considered.

Aryl Hydrocarbon Hydroxylases↗

Cysteine-proteinase-inhibiting function of T kininogen and of its proteolytic fragments.

Previous attempts to liberate T kinin from T kininogen [Moreau et al. (1986) Eur. J. Biochem. 159, 341-346; Gutman et al. (1988) Eur. J. Biochem. 171, 577-582] have shown that complete fragmentation of the precursor molecule into inhibitory peptides was achieved before any vasoactive peptide was released, suggesting a possible physiological significance for this phenomenon. In this study, cysteine-proteinase-inhibiting properties of rat T kininogen and of its proteolytic fragments issuing from trypsin and submaxillary gland endopeptidase k hydrolysis, have been investigated using rat lysosomal cathepsins B, H and L, papain and bovine calpains I and II. All three lysosomal cathepsins were inhibited by T kininogen but tighter interactions were observed with cathepsin L and papain. Though higher Ki values were obtained for cathepsins B and H, rate constants for association were found to have high and almost similar values (in the 10(6) M-1 s-1 range) whatever the enzyme used. Proteolytic fragments also inhibited cathepsin L and papain very strongly and even better than the entire molecule for some of them, but no significant inhibition of cathepsins B and H was observed. Bovine calpains were not inhibited by T kininogen nor by its proteolytic fragments. From the results of this kinetic analysis, which indicates that both the association and the dissociation of lysosomal cysteine proteinases with T kininogen may occur rapidly, an hypothesis has been put forward on the possible in vivo functioning of T kininogen as a proteinase inhibitor.

Amino Acid Sequence↗

T-kinin release from T-kininogen by rat-submaxillary-gland endopeptidase K.

Submaxillary gland extracts have been fractionated to characterize the enzyme responsible for the T-kininogenase activity previously reported in this tissue [Damas, J. & Adam, A. (1985) Mol. Physiol 8, 307-316] and to know whether this activity could be of physiological relevance, since no enzyme reacting in catalytic amounts has been described so far to be able to release a vasoactive peptide from T-kininogen. The purified enzyme, provisionally called endopeptidase K, has an apparent Mr of 27,000 when not reduced prior to analysis but 21,000 after reduction and an acidic pI of 4.3 +/- 0.1. Antigenically, it is not related to tissue kallikrein. Upon incubation with purified T-kininogen it may induce a complete liberation of T-kinin from the precursor provided it is added in stoichiometric amounts. However, in parallel with the liberation of immunoreactive kinin, a proteolysis of T-kininogen is observed which is not restricted to the site of insertion of T-kinin as would be expected using a specific kininogenase. In agreement with these results, no change of the mean blood pressure was observed upon injection of endopeptidase K into the circulation of normal rats even if the amount of injected enzyme was up to ten times that required for tissue kallikrein to induce a significant fall in blood pressure. However, in spite of the large proteolysis induced by incubation with stoichiometric amounts of endopeptidase K, the total papain inhibiting capacity of T-kininogen as well as the value of the apparent inhibition constant, Ki, with this proteinase remained unchanged. Proteolytic fragments which retain cysteine-proteinase-inhibiting activity may therefore be released from T-kininogen by endopeptidase K more easily than immunoreactive kinin, thus emphasizing a prominent function of proteinase inhibitor or of proteinase inhibitor precursor for this molecule.

Amino Acids↗

Blood pressure and erythrocyte Na+ transport systems in a French urban male population.

This paper reports an investigation of blood pressure (taken as a continuous variable) as a function of: erythrocyte Na+ content; Na+,K+ pump; Na+,K+ cotransport and Na+,Li+ countertransport fluxes, and passive cation permeabilities in fresh erythrocytes from 129 French males who were living in an urban area and were not under treatment for any medical condition (after allowing for the effects of age, body mass index, alcohol and tobacco consumption). In contrast with previous findings in a North American population, we were unable to confirm that blood pressure was correlated with erythrocyte Na+ content and Na+,K+-AT-Pase activity. Conversely, the only transport parameter correlated (negatively) with blood pressure was outward Na+,K+ cotransport [r = -0.20, P less than 0.05 and r = -0.19, P less than 0.05, for systolic (SAP) and diastolic arterial pressure (DAP), respectively; n = 114]. When allowing for age, body mass index and alcohol consumption, the correlation coefficient between the Na+,K+ cotransport system and blood pressure increased from -0.20 to -0.28 (P less than 0.01) for SAP and from -0.19 to -0.28 (P less than 0.01) for DAP (n = 105). We conclude that the correlations between blood pressure and erythrocyte Na+ transport function could differ between North American and French (or Mediterranean) populations. In any case, a decreased pump or outward Na+,K+ cotransport activity may lead hypertensive subjects to a similar increase in cell Na+ (and Ca2+) content in the vascular wall.

Adult↗

Influence of membrane sodium transport upon the relation between blood lead and blood pressure in a general male population.

Five red blood cell cation transport systems (RBCTS), together with blood lead level and blood pressure, were measured in 129 male adult subjects who were not occupationally exposed to lead or subsequent to a course of treatment for hypertension. Blood lead was positively related with systolic blood pressure, and to a lesser degree with diastolic blood pressure. Blood lead was found significantly negatively related to one of the RBCTS, Na+,K+ cotransport, and in addition, Na+,K+ cotransport appeared negatively related to blood pressure. Final results showed that blood lead no longer accounts for an increase in systolic blood pressure when Na+,K+ cotransport was taken into account; the same trend was observed with diastolic blood pressure. These findings suggest that a blood lead-related Na+,K+ cotransport impairment could explain the blood pressure increase observed to parallel the blood lead increase.

Adult↗

Possible relationship between the restricted biological function of rat T kininogen (thiostatin) and its behaviour as an acute phase reactant.

Studies on biological properties of rat T kininogen have shown that the role of this peculiar kininogen so far specific to the rat probably differs significantly from that of other low molecular mass kininogens. In particular the kinin precursor function has been either lost or considerably reduced as a result of structural modifications during evolution. The calpain inhibiting function demonstrated for other low and high molecular mass kininogens has also probably disappeared from T kininogen, and since T genes do not allow the synthesis of high molecular mass kininogens [Kitagawa et al. (1987) J. Biol. Chem. 262, 2190-2198], the procoagulant function devoted to the light chain of high molecular mass kininogen has also been lost by T genes products. The only remaining function of rat T kininogen would be therefore that of a lysosomal cysteine proteinase inhibitor which is expressed either by the native molecule or by proteolytic products which appear to be more easily released than vasoactive peptides. Such a specialization for a given function could be related to the behaviour of T kininogen as an acute phase reactant, the dramatic changes in concentration of which could at the same time serve certain functions and be damageable for others.

Acute-Phase Reaction↗

Auditory-visual equivalence by mentally retarded and intellectually average older children.

Auditory-visual information equivalence in 15 mentally retarded and 15 intellectually average 12- to 13-year-old children were compared using nine matching tasks. Intellectually average subjects were more accurate on both intra- and intersensory tasks. Retarded subjects were more accurate on intra- than on intersensory tasks, whereas there was no such difference for the average subjects. Tasks involving transposition were more difficult for the retarded children than those not involving transposition. The intellectually average children behaved similarly on intrasensory tasks but on intersensory tasks were more accurate when transposition was involved. There was no association between IQ and intra- or intersensory performance when data from the two groups were examined separately.

Acoustic Stimulation↗

Relationship between the cysteine-proteinase-inhibitory function of rat T kininogen and the release of immunoreactive kinin upon trypsin treatment.

The potential kininogenic function of rat T kininogen has been studied in parallel with the cysteine-proteinase-inhibitory function also carried by this molecule. Proteolytic cleavage of the molecule was observed upon incubation with catalytic amounts of trypsin. These conditions do not permit any significant release of immunoreactive kinin and do not modify the total papain-inhibiting capacity of T kininogen. As trypsin concentration increases in the reaction mixture, immunoreactive kinin is liberated and the total papain-inhibiting capacity decreases accordingly, as indicated by titration studies. This decrease, however, does not exceed 50% of the initial value even at a trypsin concentration as high as 75 microM, indicating that only one of the two inhibitory sites has been inactivated. The remaining inhibitory fragment corresponds to a peptide of apparent Mr 24 000, which binds papain at least as well as native T kininogen. T kininogen, therefore, appears as a potent proteinase inhibitor and/or a proteinase inhibitor precursor, whereas its kininogenic function remains questionable since no specific kininogenase able to release T kinin or another kinin under physiologically compatible conditions has been found so far.

Animals↗

Cox's regression model: computing a goodness of fit statistic.

A simple test for goodness of fit of the proportional hazards regression model has recently been proposed. This article indicates how a large number of programs in current use to fit this model can be easily adapted to incorporate this goodness of fit statistic.

Clinical Trials as Topic↗

Effects of pregnancy on the inter-individual variations in blood levels of lead, cadmium and mercury.

Blood samples to be analysed for lead, cadmium and mercury were taken from 417 pregnant women not occupationally exposed to these metals. Each subject was paired with a non-pregnant woman of the same age (+/- 2 years), socio-economic status, alcohol and tobacco status. Most of the inter-individual variations observed in earlier studies were confirmed in the control group. Among the pregnant women, however, such variations in blood metal levels appeared to be somewhat different compared to the control women according to the parameters studied: age of the women, alcohol and tobacco consumption. Furthermore, the study of the evolution of blood levels of lead, cadmium and mercury throughout pregnancy revealed a significant decrease in cadmium levels during the first half of pregnancy. A similar tendency was observed for lead but this did not attain statistical significance.

Adolescent↗

The combined effect of tobacco and alcohol consumption on the level of lead and cadmium in blood.

This study deals with the person-to-person variation in the levels of lead and cadmium in the blood of 6437 subjects (2883 men and 3554 women). The lead level (Pb-B) is clearly higher in men than in women, and the cadmium level (Cd-B) is a little higher in men than in women. Only the Pb-B varies according to age for both sexes. The results reveal that the consumption of alcohol could play an important part in the variation of lead and cadmium levels in the blood; the consumption of alcohol is associated with an increase in Pb-B but a decrease in Cd-B. These variations involving alcohol consumption remain significant regardless of smoking habits. On the other hand, an increase in Pb-B and Cd-B has been noted among smokers and, to a lesser degree, among former smokers, compared with non-smokers.

Adolescent↗

[Estimation of the hazards ratio in two grouped samples].

A simple estimator of the hazards ratio of two grouped samples is proposed. If the number of time grouping intervals is fixed, the following asymptotics hold: unbiasedness, and full efficiency when the true hazards ratio is 1 and the probability of failure in each interval is small. Under the latter condition, the estimator is equivalent to "MHP" estimator (Mantel-Haenszel estimator for a Poisson model). Simulations show that this estimator performs better than others when grouping is coarse. An asymptotically unbiased estimator of its variance is proposed.

Biometry↗

Effect of blood storage on lymphocyte subpopulations.

In the evaluation of helper and suppressor T lymphocyte subpopulations testing of the cells may not be carried out until the day following collection of the blood. The possibility that changes occur during overnight storage at 4 degrees C or 22 degrees C has been investigated. No statistical differences in percentages of helper and suppressor T cells between fresh samples and overnight stored samples were found if the blood was kept at 22 degrees C.

Antibodies, Monoclonal↗

Testing the proportional hazards regression model against some general alternatives.

A class of goodness of fit tests for the proportional hazards regression model is proposed. The alternatives considered permit the parameters of the model to vary as step functions with time. Restricting the type of step function allowed gives rise to tests against more specific alternatives. Computational details are given.

Models, Theoretical↗