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C Legrand

Publications and source records attributed to C Legrand.

At least 163 records · Page 9Linked to original sources

Platelet aggregation: its relation with ADP-induced fibrinogen binding to platelets and ADP-related membrane enzyme activities.

The receptor for ADP on the platelet membrane, which triggers exposure of fibrinogen-binding sites and platelet aggregation, has not yet been identified. Two enzymes with which ADP interacts on the platelet surface, an ecto-ATPase and nucleosidediphosphate kinase, have been proposed as possible receptors for ADP in ADP-induced platelet aggregation. In the present study, experiments were conducted with washed human platelets to examine if a relationship existed between platelet aggregation, fibrinogen binding and the enzymatic degradation of ADP. With 12 different platelet suspensions, a good correlation (P less than 0.01) was found between the extent of platelet aggregation and the amount of 125I-fibrinogen bound to platelets after ADP stimulation. No correlation was found between these parameters and the rate or extent of transformation of [14C]ADP to [14C]ATP or [14C]AMP. The binding of fibrinogen to platelets was inhibited in parallel with aggregation when ADP stimulation was impaired by the enzymatic degradation of ADP by the system creatine phosphate/creatine phosphokinase, or by the use of specific antagonists, such as ATP and AMP. These antagonists also influenced the enzymatic degradation of ADP. This effect occurred at lower concentrations of ATP or AMP than those required to inhibit ADP-induced platelet aggregation and fibrinogen binding. Our results demonstrate that ATP and AMP may be used as specific antagonists of the ADP-induced fibrinogen binding to platelets. They do not provide evidence to suggest that enzymes which metabolize ADP on the platelet surface are involved in the mechanism of ADP-induced platelet aggregation.

Adenosine Diphosphate↗

Microtubules in the cochlea of the hypothyroid developing rat.

In order to study the effects of hypothyroidism on the development of microtubules in the cochlea, rat pups were rendered hypothyroid by daily administration of propylthiouracil. Microtubules were studied by immunofluorescence and electron microscopy. The absence of immunostaining of pillar cells with antimicrotubule or antitubulin antibodies was correlated with a retarded morphological development of microtubules within these same structures. The above alterations induced an abnormal development of pillar cells, non-appearance of the tunnel of Corti, and stunted epithelial growth. In contrast, a distinct immunoreaction was observed under the outer hair cells. This was attributed to abnormal persistence of afferent dendrites containing microtubules. The results suggest that, while the effect of thyroid hormone on microtubules in afferent cochlear dendrites could not be demonstrated, thyroid hormone is necessary for the normal development of microtubules in epithelial structures.

Animals↗

Testosterone, dihydrotestosterone, androstenedione and dehydroepiandrosterone concentrations in placentae, ovaries and plasma of the rat in late pregnancy.

Testosterone (T), dihydrotestosterone (DHT), androstenedione (delta 4) and dehydroepiandrosterone (DHA) were measured by radioimmunoassay in peripheral plasma, uterine vein plasma, ovary and placentae within the last 3-4 days of pregnancy in Sprague-Dawley rats. In the uterine vein, T and delta 4 levels were significantly higher than those reported in the peripheral plasma at any particular day of late pregnancy. In peripheral plasma as in uterine vein plasma delta 4 and T gradually decreased from day 20 to term (-63% for delta 4 and approximately -45% for T) whereas DHT concentrations were unchanged. This decline is concomitant with a similar pattern of change in the placentae; indeed placental concentrations of delta 4 and T decreased significantly from day 19 to 22 (-63 and -79%, respectively) and were positively correlated with the levels of both androgens in uterine venous and peripheral plasma. Thus it was concluded that in the late phase of pregnancy in the rat circulating delta 4 and T originate from placentae. In contrast, ovarian androgen concentrations showed a sharp increase from day 21 to term: 58% for DHA, 49% for delta 4, 87% for T and 24% for DHT. It is suggested that these increasing concentrations of ovarian androgens could be related to the next ovulatory cycle.

Androstenedione↗

Presence of EBV-DNA sequences in nasopharyngeal cells of individuals without IgA-VCA antibodies.

Exfoliated nasopharyngeal (NP) cells from 62 normal Cantonese Chinese having IgA/VCA antibodies for more than a year and from 39 similar persons without IgA/VCA antibodies, were tested for the presence of EBV/DNA sequences by spot followed by blot hybridization tests, using the cloned internal repeat of B95-8 viral DNA as probe. Thirteen out of 62 specimens from IgA/VCA-positive (21%) and six out of 39 specimens (15.4%) from IgA/VCA-negative individuals were found to contain EBV/DNA sequences. Forty-six cases (20 IgA/VCA-positive and 26 IgA/VCA-negative) were followed a year later for EBV/DNA sequences and EBV serology. Half of the individuals having EBV/DNA sequences in their exfoliated NP cells in 1981 did not have detectable EBV sequences a year later, and to out of 15 negative individuals became EBV/DNA-positive. There was no obvious correlation between EBV/DNA detectability and EBV serology. (We conclude that the best marker for NPC risk remains the increasing IgA/VCA and/or EA antibody titers.

Antigens, Viral↗

Immunocytochemical detection of calcium-binding protein in the cochlear and vestibular hair cells of the rat.

Specific antibodies raised against human cerebellar calcium-binding protein (CaBP) intensely labelled the cochlear hair cells of the rat. The vestibular hair cells also stained weakly. In both inner and outer cochlear hair cells, the cuticular plate was the most stained area. These results suggest that CaBP may prevent excessive concentrations of intracellular calcium and thus modulate some Ca2+-mediated biochemical processes, especially at the level of the cuticular plate and stereocilia; CaBP could be involved in the mechanochemical coupling of hearing or vestibular function.

Animals↗

Calcium-binding protein in the developing rat cerebellum. An immunocytochemical study.

Specific antibodies raised against a human 28 000 dalton cerebellar calcium-binding protein (CaBP) were used in an immunocytochemical study during development of the rat cerebellum. Both light and electron microscopy showed (1) that labelling was entirely restricted to the Purkinje cells, (2) that it appeared very early in Purkinje cell development, (3) that the entire cell was labelled from the tip of the smallest dendrites to the axonal terminals, and (4) that with increasing age, the immunoreaction appeared to be progressively restricted to the cell and organelle membranes.

Animals↗

Cochlear synaptogenesis in the hypothyroid rat.

The effects of congenital hypothyroidism on cochlear synaptogenesis were studied using transmission electron microscopy in 30 propylthiouracil-treated rat pups 1-35 days of age. No difference with controls was observed at the level of the inner hair cells which are known to mature essentially during the prenatal period. On the contrary, hypothyroidism resulted in numerous abnormalities in synaptogenesis at the level of the outer hair cells: abnormal persistence of numerous afferent dendrites and presynaptic specializations, incomplete development of efferent terminals and absence of formation of postsynaptic cisterns. It can be concluded that hypothyroidism results in severe retardation in the postnatal development of the innervation of outer hair cells.

Animals↗

Maturational and degenerative processes in the organ of Corti after neonatal hypothyroidism.

In order to study the long-term effects of neonatal hypothyroidism on the organ of Corti, rats were given propylthiouracil (PTU) during the first 30 days after birth. Cochlear changes occurring after the cessation of antithyroid treatment were studied by both physiological (brainstem auditory evoked responses: BAERs, electrocochleography) and morphological techniques (transmission and scanning electron microscopy). The first appearance of BAERs was noted between days 37 and 45. Maturation of auditory potentials was achieved within 10-15 days but was incomplete since the animals definitely demonstrated elevated thresholds around 60-70 dB SPL. Morphological results indicated that some structures, like the inner sulcus epithelium, were able to restart maturational processes that had been interrupted during the period of hypothyroidism. However, these maturational changes were considerably limited and rapidLy accompanied by severe degenerative changes involving almost all cochlear structures. Degenerative changes included the deposition of an amorphous substance within the organ of Corti, severe alterations in pillar cells (absence of formation of the tunnel of Corti, distortion of microtubules), severe outer hair cell losses with abnormalities in their innervation (absence of development of efferents and loss of afferent dendrites).

Aging↗

A critical period in the onset of parturition in rats and uterine sensitivity to estradiol and progesterone.

The purpose of this paper was to impair normal parturition in rats in order to measure tissue levels of progestins and estrogens and compare these results with those of normal parturition in rats. Abnormal parturition was obtained by injection of isotonic saline into the uterine lumen of pregnant rats at the end of pregnancy or by handling the uterus. After each of these treatments on day 21 of pregnancy, parturition was impaired in 70 to 98% of the rats. When the treatments were carried out earlier or later in pregnancy, there was little or no impairment. Our results indicate transient discrepancies in plasma and tissue levels of steroids 6 h after treatment on day 21: 20 alpha-HP concentrations increased in treated rats compared to controls (uteri: 470%; p less than 0.01; ovaries: 89%; p less than 0.001); concomitantly, there was a sharp rise in P concentrations in uteri (+ 74% : p less than 0.05) and ovaries (+ 52%; p less than 0.05). Inversely, uterine concentrations of E2 decreased 6 h after treatment compared to controls (- 30%; p less than 0.05), although there was a transient rise of E2 in the ovaries (+ 30%; p less than 0.05). Twenty-four hours later, E2 concentrations were always lower in the uteri (- 30%; p less than 0.01). No change in E2 levels was noted in the uteri or ovaries of either the control or treated rats. The physiological significance of these changes and their consequences on uterine reactivity at term have been discussed. The data demonstrate that day 21 was a critical period in the parturient activity of the rat uterus which appears to be primarily affected by uterine levels of E2 between days 21 and 22 of pregnancy.

20-alpha-Dihydroprogesterone↗

Correlation between noradrenaline fluxes, metabolism and compartmentalisation in human platelets.

(3H) noradrenaline was taken up by human platelets and partially converted into sulfoconjugated noradrenaline. This uptake was inhibited by drugs which have been previously shown to impair the uptake of 5-HT (ouabain, chlorimipramine) or the storage of 5-HT (tyramine, reserpine) by platelets. In addition, tyramine and reserpine stimulated the formation of sulfoconjugated noradrenaline. The efflux of noradrenaline from platelets was measured in parallel and was found to be directly related to the proportion of non metabolized to metabolized noradrenaline in the cells. Unlike tyramine, which induced a similar release of noradrenaline and 5-HT, reserpine was less effective at inducing noradrenaline release than 5-HT release. This study indicates a preferential localization of noradrenaline in the granular pool of human platelets with the existence of an extragranular sulfoconjugated pool which is increased when the granular storage of noradrenaline is impaired. Studies of noradrenaline fluxes and metabolism may be useful in the understanding of both acquired and inherited platelet storage pool defects.

Blood Platelets↗

Influence of altered thyroid and nutritional states on early histogenesis of the rat cerebellar cortex with special reference to synaptogenesis.

On day of birth, the synaptic density of the rat cerebellar cortex in experimental, as compared to control, rats was slightly reduced or increased, respectively, after propylthiouracil treatment of the dam or thyroxine injection of the fetus. The stimulation of synaptogenesis in thyroxine-treated neonates was particularly obvious at the level of the ganglionic layer containing Purkinje cell bodies and was accompanied at the same level by accelerated growth of the presynaptic endings and perisomatic processes of the Purkinje cells. Undernourishment of the dam from day 6 of gestation led to an unexpected stimulation of synaptogenesis in the cerebellar cortex of the neonates; synaptic density was significantly increased above the normal value and much more markedly than in the thyroxine-treated neonates, but there was no abnormal proliferation of the neuronal processes. Different mechanisms underlay the transient stimulation of synaptogenesis in these two conditions. These results have been related to the disturbances in the development of Bergmann glia previously found soon after birth in altered thyroid and nutritional states.

Animal Nutritional Physiological Phenomena↗

Foetal and maternal plasma adrenaline and noradrenaline concentrations in the late pregnant rat: effects of intra-uterine isotonic saline or uterine handling.

The catecholamines adrenaline (A) and noradrenaline (NA) were determined in plasma samples of late pregnant rats and rat foetuses using a radioenzymatic procedure. In maternal plasma of control rats, values of A were stable during the last three days of gestation (between 5.64 and 6.90 ng/ml) whereas NA values increased just before parturition (+ 70%) and on day 23 post-coitum NA was the main plasma catecholamine. In foetal plasma of control rats, values of A and NA were constant during the last three days of gestation and A was always higher than NA. For both catecholamines, values in foetal plasma were lower than in maternal plasma. Blood of rats injected with isotonic saline into the uterus on day 21 of gestation contained 24 h and 48 h later about 2-3 times more A, and no more NA, than blood of control rats. In foetal plasma the levels of both catecholamines especially of NA were greatly increased after the handling of the uterus or the intra-uterine isotonic saline injection. Both treatments had the same prolonged effect upon A and NA values in foetal plasma. There is no increase of A and NA in maternal and foetal plasma after sham-operation. Although the values of plasma A and NA were high in control rats because of blood sampling was carried out under stressful conditions, these results showed that handling of the uterus or injection of intrauterine isotonic saline was a severe aggression for the mother and foetus.

Animals↗

Effects of thyroid state on the formation and early morphological development of Bergmann glia in the developing rat cerebellum.

The formation and morphological maturation of Bergmann glia cells, which might play an important role in the histogenesis of the cerebellar cortex, was studied by histological and electron microscopic techniques in the cerebellum of normal young rats and animals made hypothyroid since the 18th day of gestation or hyperthyroid since birth. In comparison with controls, an acceleration in the morphological development of Bergmann glia cells was observed in the hyperthyroid animals; on the contrary, in the thyroid-deficient rats, the formation and morphological maturation of these cells were retarded and their final number was increased.

Animals↗

Interaction of adenosine and adenylnucleotides with the human platelet membrane. Further characterization of the ADP binding sites.

The binding of adenosine and adenylnucleotides to the human platelet membrane has been measured and the subsequent effect on the binding of 14C-ADP has been determined. The following conclusions have been drawn: (1) Two reactions with different velocities (t 1/2 = 15--30 sec and t 1/2 = 4--6 min) seem to be involved in the binding of ADP to the platelet membrane. (2) AMP binds to the platelet membrane and partially inhibits binding of ADP in a competitive manner. These two findings suggest that ADP binding sites on the platelet membrane may be of more than one type. (3) At concentrations up to 10(-5) M, ATP does not itself bind to the platelet membrane but is rapidly transformed into ADP which, in turn, binds to the membrane and inhibits the binding of 14C-ADP. (4) Adenosine does not significantly interfere with the binding of 14C-ADP and has not been shown to bind to the platelet membrane.

Adenosine↗