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Biomedical subjects

T Moreau

Publications and source records attributed to T Moreau.

At least 109 records · Page 6Linked to original sources

Joint effect of gestational age and maternal lead exposure on psychomotor development of the child at six years.

A prospective study has been carried out to assess the psychomotor deficit resulting from a moderate decrease in gestational age and pre-natal lead exposure. The general cognitive index of the McCarthy psychometric scale (adjusted for confounders) in six-year-old children was related to gestational age. Most of the psychomotor scores showed smoothing variations with gestational age ranging from 37 to 39 weeks, whereas sharp changes occurred between 39 to 40 weeks, with plateau values above such a cut-off for all spheres of development examined. Maternal hair lead content, used as an indicator of lead exposure during pregnancy, was found to be negatively related to general cognitive, verbal, quantitative, and memory subscales (p less than 0.01), whereas its relationship with perceptual and motor subscales was close to 0.05 significance level. Control for gestational age did not change the significance level of the associations. When controlling for maternal hair lead levels, the significance of the association between gestational age and the McCarthy subscales also remained stable, only the general cognitive index and verbal subscale reaching the conventional significance level.

Child↗

[Etiology of multiple sclerosis].

The risk of developing Multiple Sclerosis is under the combined influence of environmental and endogenous factors, as shown by epidemiological and genetic studies. Immunological abnormalities are a salient feature of the disease but their myelinotoxic effect is still to be demonstrated. The pathogenesis of the disease remains unknown. The auto-immune theory as well as the infectious theory are arguable but they may, also, be both valid. Multiple sclerosis could be a post-infectious auto-immune disease, "final common way" of common childhood infections. Anyway, no infectious agent is demonstrable inside the central nervous system at the overt disease stage.

Humans↗

Discrimination between rat thiostatin (T-kininogen) and one of its cystatin-like inhibitory fragments by a monoclonal antibody, and localization of the epitope.

A monoclonal antibody (mAb D3) raised against rat thiostatin (T-kininogen) strongly interacted with a fragment, identified as cystatin-like domain 3, which inhibits cysteine proteinases but did not recognize intact, native thiostatin. The antigen-antibody reaction requires cleavage of the single peptide chain of thiostatin in its inter-domain 2-3 region. This mAb can also differentiate between the two molecular varieties of thiostatin, reacting only with immobilized domain 3 from T1 thiostatin, which differs from the T2 variety by only 10 out of 125 residues. mAb D3 did not react with an N-terminally truncated domain 3 of T1 thiostatin prepared by submaxillary gland kallikrein k10 proteolysis. This suggests that the epitope, or an essential part of it, is located on a stretch of 12 residues at the N-terminal of the T1 thiostatin domain 3. This sequence in T1 thiostatin differs from that in T2 thiostatin by four amino acids, two of which are arginyl residues in T1. Chemical modification of these residues located at positions 246 and 250 decreased the reactivity of T1 domain 3 towards the antibody, suggesting that at least one of them is a critical residue of the epitope. Arginine 246 is part of a small disulfide loop between cysteines 245 and 248 which is also necessary for antibody recognition. This antibody does not change the inhibitory properties of purified domain 3 towards papain or rat liver cathepsin L, indicating that the N-terminal part of domain 3 is not involved in inhibition. mAb D3 was used to demonstrate the presence of inhibitory thiostatin fragments in ascites fluid but not in plasma from normal or turpentine-injected rats.

Amino Acid Sequence↗

Comparative efficiency of a survival-based case-control design and a random selection cohort design.

Ambidirectional studies are useful when information about disease status is available on a cohort but a risk factor has still to be recorded. An example is the study of the influence of HLA phenotypes on the progression of HIV carriers towards AIDS. An ambidirectional design is proposed in which the cases and controls are defined by the survival duration of the subjects; it includes as special cases some other ambidirectional designs. Its efficiency is compared with that of a random selection cohort design both analytically and by computer simulation. It is shown that when the size of the cohort is large, appreciable gains in power can be achieved by this type of design even when there is no censoring.

Acquired Immunodeficiency Syndrome↗

Simulation of the inhibitory cystatin surface by a synthetic peptide.

An inhibitory dodecameric peptide was designed which tentatively mimics the inhibitory site of cystatin C-like structures. Succinylated and mansylated derivatives were also synthesised and assayed for their inhibiting properties towards papain and rat cathepsins B, H and L. All peptides preferentially inhibit cathepsin L and papain as their naturally occurring inhibitor model. A significant increase in inhibition was obtained after mansylation of the crude peptide with Ki values in the micromolar or 0.1 micromolar range. The use and interest of such peptide inhibitors are discussed.

Amino Acid Sequence↗

Influence of environmental lead on membrane ion transport in a French urban male population.

Red cell cation transports (Na(+)-K+ pump, Na(+)-K+ cotransport system, Na(+)-Li+ countertransport, and Na+ and K+ passive permeabilities) and blood and hair lead levels were measured in 129 healthy adult Caucasians not occupationally exposed to lead. In agreement with previously reported in vitro results showing a lead-induced Na(+)-K+ ATPase inhibition, Na(+)-K+ pump activity was inversely correlated with hair lead (r = -0.18, P less than 0.05); it was not significantly correlated with blood lead. Na(+)-K+ cotransport activity was inversely correlated with blood lead contents (r = -0.23, P less than 0.05) but not with hair lead. No significant correlation was found between the remaining cation transport pathways and lead levels. It is hypothesized that environmental, long-term exposure to lead may result in pump inhibition, while a recent exposition to lead may result in inhibition of the Na(+)-K+ cotransport system. Further research is required in order to determine if red cell Na(+)-K+ pump and Na(+)-K+ cotransport activities are sensitive indicators of chronic and recent exposures to lead, respectively.

Adult↗

Evaluation of pulsed Doppler common carotid blood flow as a noninvasive method for brain death diagnosis: a prospective study.

Among the main causes for the relatively small number of organ donors, the delay in the diagnosis of brain death plays a major role. This prospective study was designed to evaluate whether pulsed Doppler mean and phasic common carotid blood flow (CCBF) combined with arterial and jugular venous blood gases could rapidly and specifically establish a diagnosis of brain death. CCBF was measured by an 8 MHz pulsed Doppler flowmeter, allowing measurement of the vessel diameter via a double transducer probe, which fixed the ultrasonic incidence angle. From an initial series of patients (n = 28) with an established diagnosis [brain death n = 14; severe coma with a Glasgow Coma Scale (GCS) less than 7, n = 14], the results of the logistic regression analysis process yielded the most discriminating parameters for brain death diagnosis: end-diastolic velocity (Ved - 1.4 vs. 12.7 cm/s; t = 7.67, P = 0.001) and blood flow (Qed - 13.6 vs. 121.4 ml/min). These parameters were then tested in a blind fashion on a second series of 28 comatose patients (GCS = 7). They resulted in correct diagnosis (brain death n = 14 or severe coma n = 14) for all patients. Brain death diagnosis was confirmed by clinical signs, EEG, and/or angiography. From the analysis of the overall population (n = 56), a value of Qed of less than 31.4 ml/mn indictes brain death. The authors conclude, that pulsed Doppler measurements of CCBF represent an early, low cost and noninvasive technique, the results of which may prompt legally accepted procedures, which in turn would reduce the delay required before brain death is diagnosed. Moreover, this technique could help in deciding on discontinuation of active therapy in severely injured patients.

Adult↗

Erythrocyte cation transport systems and plasma lipids in a general male population.

The relationships between five erythrocyte cation transport systems (Na(+)-K+ pump, Na(+)-K+ cotransport, Na(+)-Li+ countertransport and Na+ and K+ passive permeabilities) and plasma lipids (total plasma cholesterol, high-density lipoprotein cholesterol and triglycerides) were investigated in 129 male adult subjects with no known history of hypertension. Na+ and K+ erythrocyte contents were also considered for their possible relationships with plasma lipids. Na(+)-K+ cotransport and passive Na+ permeability were both significantly correlated with plasma triglycerides. Conversely, no significant correlation was found between erythrocyte cation transport systems or erythrocyte cation contents and total cholesterol. These findings suggest that plasma lipids can modulate erythrocyte ion transport activity in the general population.

Adult↗

[The Cox model: limitations and extensions].

The proportional hazards model (Cox's model) does not fit the data in many situations. Its limits are reviewed, together with the main goodness-of-fit techniques. Some possibilities of extending the proportional hazards analysis are also described.

Clinical Trials as Topic↗

[Pseudomyasthenic pre-Basedow ophthalmoplegia].

A 67-year old woman presented with isolated and bilateral external ophthalmoplegia of the myasthenic type following a subacute course and resistant to anticholesterinases and corticosteroids. A biological hyperthyroidism with immunological markers was discovered. An intensive care of corticosteroids was partially effective, but fatal bone marrow aplasia attributed to carbimazole developed. Pure ophthalmoplegia without local signs of inflammation may be the sole manifestation of dysthyroid orbitopathy.

Aged↗

Limited proteolysis of T-kininogen (thiostatin). Release of comparable fragments by different endopeptidases.

Limited proteolysis of T-kininogen by heterologous and homologous endopeptidases (bovine trypsin, human leukocyte elastase, rat submaxillary gland endopeptidase k, and rat mast cell chymase) produced similar fragmentation. Amino-terminal sequence analysis of whole T-kininogen lysates and purified proteolytic fragments identified four susceptible regions which contained all the preferential cleavage sites for these proteinases. Two of these susceptible regions were close to the junction between heavy chain cystatin-like domains, the third was in the kinin-containing region, and the fourth was close to the carboxyl terminus of the T-kininogen light chain. There was only one primary site for each proteinase in the kinin-containing region, which explains why catalytic amounts of these proteinases did not release immunoreactive kinin from this kininogen. However, preferential cleavage of T-kininogen close to the junction between cystatin-like domains released fragments which, provided they included cystatin-like domains 2 and/or 3, strongly inhibited papain and cathepsin L. The fragments were inhibitory even when parts of the amino-terminal ends of the domains were lacking. The highly conserved glycyl residue, thought to be involved in the inhibitory reactive site of cystatin-like inhibitors, was not required in purified domain 3 for inhibition of cathepsin L.

Amino Acid Sequence↗

Efficiency of the logistic regression and Cox proportional hazards models in longitudinal studies.

Both logistic regression and Cox proportional hazards models are used widely in longitudinal epidemiologic studies for analysing the relationship between several risk factors and a time-related dichotomous event. The two models yield similar estimates of regression coefficients in studies with short follow-up and low incidence of event occurrence. Further, with just one dichotomous covariate and identical censoring times for all subjects, the asymptotic relative efficiency of the two models is very close to 1 unless the duration of follow-up is extended. We generalize this result to several qualitative or quantitative covariates. This was motivated by the analysis of mortality data from a study where all subjects are followed up during the same fixed period without loss except by death. Logistic and Cox models were applied to these data. Similar results were obtained for the two models in shorter periods of follow-up of five years or less, but not in longer periods of ten years or more, where the survival rate was lower.

France↗