We previously reported a functional defect of von Willebrand factor (vWF) in a new variant of von Willebrand disease (vWD) tentatively named vWD "Normandy." The present work has attempted to characterize the molecular abnormality of this vWF that fails to bind factor VIII (FVIII). The immunopurified vWF from normal and patient's plasma were digested by trypsin and the resulting peptides were compared. The electrophoresis of "vWF Normandy" showed a shift in the band corresponding to a polypeptide from amino acid 1 to 272. Consequently, we performed the molecular analysis of the portion of the vWF gene of this patient encoding this amino acid sequence. Exons 18-24 were amplified by the use of polymerase chain reaction and their nucleotide sequences corresponding to 1.8 kb were determined. Our analysis showed a point mutation C to T at codon 791, resulting in the substitution of Methionine for Threonine at position 28 of the mature vWF subunit. Because this nucleotide substitution destroyed a Mae II restriction site, this mutation was conveniently sought in various individual DNAs. The patterns obtained were consistent with the homozygous and heterozygous state of this mutation in the patient and in her son, respectively, and with its absence in 28 normal individuals. We conclude that Threonine at position 28 in plasma vWF may be crucial for the conformation and FVIII-binding capacity of its cystine-rich N-terminal domain.

Base Sequence↗

PubMed1991

Influence of anthropometric characteristics on changes in maximal exercise ventilation and breathing pattern during growth in boys.

The aim of this study was to investigate the effect of growth on ventilation and breathing pattern during maximal exercise oxygen consumption (VO2max) and their relationships with anthropometric characteristics. Seventy six untrained schoolboys, aged 10.5-15.5 years, participated in this study. Anthropometric measurements made included body mass, height, armspan, lean body mass, and body surface area. During an incremental exercise test, maximal ventilation (VEmax), tidal volume (VTmax), breathing frequency (fmax), inspiratory and expiratory times (tImax and tEmax), total duration of respiratory cycle (tTOTmax), mean inspiratory flow (VT/tImax), and inspiration fraction (tI/tTOTmax) were measured at VO2max. A power function was calculated between anthropometric characteristics and ventilatory variables to determine the allometric constants. The results showed firstly, that VEmax, VTmax, tImax, tEmax, tTOTmax, and VT/tImax increased with age and anthropometric characteristics (P less than 0.001), fmax decreased (P less than 0.001), and tI/tTOTmax remained constant during growth; secondly that lean body mass explained the greatest percentage of variance of VEmax (62.1%), VTmax (76.8%), and VT/tImax (70.6%), while anthropometric characteristics explained a slight percentage of variance of fmax and timing; and thirdly that VEmax, VTmax, and VT/tImax normalized by lean body mass did not change significantly with age. We concluded that at VO2max there were marked changes in ventilation and breathing pattern with growth. The changes in VEmax, VTmax, and VT/tImax were strongly related to the changes in lean body mass.

Adolescent↗

PubMed1991

Blood lactate increase during the force velocity exercise test.

Venous blood lactate concentration was measured during the force velocity exercise test in order to determine whether this test is strictly alactic or whether it draws upon lactic anaerobic metabolism. Nine trained male subjects, aged from 23 to 29 years, participated in this study. Two blood samples were drawn at rest, and then for each work load (1 kg to 10 kg): at the end of each sprint (S1) and at the 5th minute of recovery (S2). From the first braking force, venous blood lactate concentration increased very significantly during the force velocity test (p less than 0.001) and, once the peak of power has been obtained, the venous blood lactate concentration remained steady. The lactate increase for each load (delta[LA]) decreased significantly (p less than 0.01). From the beginning of the exercise to the peak of power, a significant positive correlation between the increase of power and the increase of blood lactate concentration measured at S2 existed (r = 0.71, p less than 0.001), whereas there was a negative correlation between the decrease of delta[LA] and the increase of power (r = -0.45, p less than 0.01). In conclusion, the repetition of sprints during the force velocity test induced a recruitment of lactic anaerobic metabolism. Maximal power must be considered as an alactic and lactic anaerobic power. The consequences of lactate accumulation in muscle may be a limitation of the maximal anaerobic power.

Acceleration↗

PubMed1991

Identification of two point mutations in the von Willebrand factor gene of three families with the 'Normandy' variant of von Willebrand disease.

Plasma von Willebrand factor (vWf) is a multi-domain multimerized glycoprotein which has a dual role in haemostasis: it promotes platelet adhesion to subendothelium and is the carrier of blood coagulation factor VIII (FVIII). We previously characterized a functional defect of vWf, limited to its ability to bind FVIII, in two families whose affected members have the same phenotype that mimics mild haemophilia A and was tentatively named von Willebrand's disease (vWD) 'Normandy'. A homozygous point mutation C----T converting Thr 28 to Met in mature vWf subunit was identified in one of these patients who was born of third-cousin parents. In the present studies we report two unrelated new cases of vWD 'Normandy' and characterize, using the analysis of the vWf gene intron 40 region containing a variable number of tandem repeats, the recessive inheritance of the disease in two affected families without known consanguinity. Exons 18-24 of the vWf gene encoding for the first 311 amino acids of mature vWf subunit were amplified by the polymerase chain reaction method and sequenced. Two new missense mutations, both corresponding to a C----T transition and predicting respectively an Arg 53----Trp and an Arg 91----Gln substitution, were characterized. The three patients from family 1 were homozygous for the first-mentioned mutation while the patient from family 3 was homozygous for the second. The patient from family 2 was found a compound heterozygote for the two mutations. None of the two point mutations reported, both destroying a MspI restriction site, could be detected in DNA from 50 normal controls screened by restriction endonuclease analysis. Our data show that different mutations may be found in patients with the 'Normandy' phenotype. The mutations characterized so far are all localized on the N-terminal region of mature vWf subunit, within or near the major FVIII binding domain, and some of them occur within the epitope of monoclonal antibodies inhibiting the vWf/FVIII interaction. These observations suggest a causal relationship between these mutations and the vWD 'Normandy' phenotype.

Adult↗

PubMed1991

[Glioblastoma after radiotherapy of meningioma].

A cerebellar glioblastoma was discovered in a 28 year old woman, 5 years after a focal 50 grays brain irradiation for meningioma of the clivus. This case fulfilled the accepted criteria for radiation-induced neoplasms of the central nervous system, namely a second histologically-proven tumor different from the first lesion, a location within the irradiated area and a long latent period.

Adult↗

PubMed1990

An MspI polymorphism in the von Willebrand factor gene.

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Base Sequence↗

PubMed1990

Direct PCR from whole blood, without DNA extraction.

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DNA↗

PubMed1990

Visual corticopontine and tectopontine projections in the macaque.

We studied projections from extrastriate visual areas and the superior colliculus to the pontine nuclei of monkeys using degeneration staining and transport of wheatgerm agglutinin horseradish peroxidase, and 3H amino acids. The superior colliculus and the extrastriate cortical visual areas both project to the ipsilateral dorsolateral region of the pontine nuclei. The projections from extrastriate visual cortex occupy a much larger territory within the pontine nuclei than those from the superior colliculus. The superficial laminae of the superior colliculus project only to the ipsilateral pontine nuclei. The projection to the contralateral nucleus reticularis tegmenti pontis arises from cells in deeper laminae within the superior colliculus.

Animals↗

PubMed1990

[Force-velocity test: effect of a heavy-load start on maximal anaerobic power and blood lactate levels].

The purpose of this study was to determine the effect of starting the force-velocity test with a heavy load on both maximal anaerobic power and blood lactate concentration. Nine male subjects aged 23.4 +/- 1.3 yr (mean +/- sem) participated in a first force-velocity test (FV1) which had an initial load of 1 kg (classical protocol). Then a week later in a second force-velocity test (FV2) which had an initial load corresponding to maximal power developed during FV1 (W1). The increase in load was of 1 kg for FV1 and FV2. Our results show that during FV2, compared to FV1: 1) maximal anaerobic power developed (W2) is superior to W1 (W1 = 1,165.2 +/- 70.4 W; W2 = 1,278.6 +/- 92.3 W; p less than 0.02); 2) blood lactate concentration after the first load is inferior (p less than 0.001); 3) blood lactate concentration is not significantly different at the peak of power. Thus, starting the force-velocity test with a heavy load allows an increase of maximal anaerobic power until a blood lactate concentration which may be compared to the one obtained during the classic force-velocity test. In conclusion, maximal anaerobic power measured during the force-velocity test seems to depend on protocol used.

Adult↗

PubMed1989

Corticopontine projection in the rat: the distribution of labelled cortical cells after large injections of horseradish peroxidase in the pontine nuclei.

The distribution of cortical cells projecting to the pontine nuclei in rats was studied by making large injections of horseradish peroxidase that filled the basilar pons and measuring the density of labelled cells in each cortical area. All retrogradely labelled cells were layer V pyramidal cells. The highest densities of labelled cells were observed in the motor areas. The lowest densities were in temporal association cortex and perirhinal cortex. Visual cortical areas, including the primary visual cortex, provided a major source of pontine projections. The distribution of corticopontine cells within the primary visual cortex was studied in more detail. In all cases the highest density of labelled cells was observed in the region of cortex that represents the nasal visual field. Control injections into brainstem regions adjacent to the pontine nuclei produced a much lower absolute density of retrogradely labelled cortical cells and the distribution of those cells was different from that observed following pontine injections. We conclude that every area of the rat's cerebral cortex projects to the pontine nuclei and that there are consistent variations in the density of the projections both between and within areas.

Animals↗

PubMed1989

[Participation of lactic anaerobic metabolism during short and intense repeated exercises].

The evolution of blood lactate concentrations has been studied during a force/velocity test on a cycloergometer in order to specify if the repetition of short (6 s) and intense exercises induced an important participation of lactic anaerobic metabolism. Seven moderately trained male subjects, aged from 23 to 29 years (mean = 24.92 +/- 0.79) participated in this study. Two blood samples (venous catheter) were performed, at rest, then for each work load (1 kg to 10 kg): at the end of the exercise (P1) and during the recovery at 5 min (P2). From the lowest work load, blood lactate concentration increased significantly, at the end of the exercise (F = 16.21; P less than 0.001) and during the recovery (F = 22.62; P less than 0.001). The mean values were respectively at the peak of power: 9.84 +/- 0.85 et 10.19 +/- 0.75 mmol.l-1. Once the peak of power was obtained, the blood lactate concentration remained steady. In conclusion, the repetition of short and intense exercises induced an important participation of lactic anaerobic metabolism. The lactate could be the limiting factor of the maximal power.

Adult↗

PubMed1988

[A new case of hydatidiform mole occurring on one of the ova of a twin pregnancy].

The authors report here a new case of hydatid mole in one of the eggs of a mole pregnancy. 48 other cases have been reported in 13 publications. The birth of a viable, well-developed fetus is described in 13 instances (27%), fetal death in utero in 22 instances (46%), birth of a non-viable fetus 11 times (23%) and malignant degeneration twice (4%). Medical interruption of the pregnancy is indicated for the slightest sign of fetal anomaly or maternal complication. Prostaglandins may be used for that purpose. However, it is possible to let such a pregnancy follow its course.

Female↗

PubMed1986

[Sarcoidosis disclosed by trigeminal neuralgia].

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Adult↗