Search PubMed⌕ Search

Biomedical subjects

J M Launay

Publications and source records attributed to J M Launay.

At least 145 records · Page 8Linked to original sources
PubMed1991

Prosomatostatin is processed in the Golgi apparatus of rat neural cells.

Proteolytic processing of somatostatin precursor produces several peptides including somatostatin-14 (S-14), somatostatin-28 (S-28), and somatostatin-28 (1-12) (S-28(1-12)). The subcellular sites at which these cleavages occur were identified by quantitative evaluation of these products in enriched fractions of the biosynthetic secretory apparatus of rat cortical or hypothalamic cells. Each of the major cellular compartments was obtained by discontinuous gradient centrifugation and was characterized both by specific enzyme markers and electron microscopy. The prosomatostatin-derived fragments were measured by radioimmunoassay after chromatographic separation. Two specific antibodies were used, allowing the identification of either S-28(1-12) or S-14 which results from peptide bond hydrolysis at a monobasic (arginine) and a dibasic (Arg-Lys) cleavage site, respectively. These antibodies also revealed prosomatostatin-derived forms containing at their COOH terminus the corresponding dodeca- and tetradecapeptide sequences. Whereas the reticulum-enriched fractions contained the highest levels of prosomatostatin, the proportion of precursor was significantly lower in the Golgi apparatus. In the latter fraction, other processed forms were also present, i.e. S-14 and S-28(1-12) together with the NH2-terminal domain (1-76) of prosomatostatin (pro-S(1-76). Inhibition of the intracellular transport either by monensin or by preincubation at reduced temperature resulted in an increase of prosomatostatin-derived peptides in the Golgi-enriched fractions. Finally, immunogold labeling using antibodies raised against S-28(1-12) and S-14 epitopes revealed the presence of these forms almost exclusively in the Golgi-enriched fraction mainly at the surface of saccules and vesicles. Together these data demonstrate that in rat neural cells, prosomatostatin proteolytic processing at both monobasic and dibasic sites is initiated at the level of the Golgi apparatus.

Animals↗
PubMed1990

[Plasma releasing factors in common migraine].

Many platelet abnormalities have been described in migraine, but they are now regarded as secondary phenomena rather than primary causative factors. In this study, we attempted to assess the presence of bioamine-releasing factors in the plasma of patients with common, non-dietary migraine. Blood samples were collected from 17 such patients, either during attacks (n = 9) or during attack-free periods (n = 8). Ten healthy volunteers served as controls. Release experiments were performed by adding 1 volume as controls. Release experiments were performed by adding 1 volume of migraineur's platelet-poor plasma to 1 volume of either control's whole blood (histamine release) or isolated platelets (catecholamines or serotonin release). Endogenous unconjugated bioamines were measured in whole blood and in isolated platelets from migraineurs' blood collected during and between attacks. We also measured plasma levels of histamine and of unconjugated and conjugated serotonin and catecholamines, as well as the inhibition of serotonin uptake and labelled serotonin release from controls' platelets in the presence of migraineurs' plasma collected during or between attacks. The results obtained suggest the presence of two plasma bioamine-releasing factors: a histamine-releasing factor present in migraineurs' blood during and between attacks, and a catecholamine and serotonin releasing factor present only during attacks in migraineurs' platelet-poor plasma. The latter factor is thermolabile and dialysable, with an apparent molecular weight lower than 16 kd. Gel-filtered fractions of semi-purified catecholamine-serotonin releasing factor induced the same events as the migraineurs' platelet-poor plasma from which they were obtained.

Adult↗
PubMed1990

Serotonin uptake, storage, and synthesis in an immortalized committed cell line derived from mouse teratocarcinoma.

We report the isolation and characterization of a serotoninergic cell line, 1C11, derived from a mouse teratocarcinoma. The clone 1C11 was immortalized through the expression of the simian virus 40 oncogenes. 1C11 presents two states: an immature epithelial-like state (1C11 precursor) and a more differentiated state (1C11). After induction by dibutyryl cyclic AMP and cyclohexanecarboxylic acid, almost 100% of 1C11 cells continue to divide and have acquired a neural-like phenotype. 1C11* cells coexpress several neural markers, such as synaptophysin (the membrane constituent of synaptic vesicles), the neuropeptide [Met5]enkephalin, and the neurotransmitter serotonin. 1C11* cells store endogenous serotonin and are able to synthesize serotonin from L-tryptophan and to catabolize it by monoamine oxidase B. Moreover, the cells take up serotonin by a carrier-mediated mechanism very similar to that of serotoninergic neurons. The expression of the simian virus 40 oncogenes, which promoted immortalization, does not therefore prevent further differentiation. This inducible cell line constitutes a valuable model for cellular and molecular studies concerning the physiology and the pharmacological modulation of the serotoninergic phenotype.

Animals↗
PubMed1990

[A strategy for immortalizing lines committed to endoderm, neuroectoderm or mesoderm from mouse teratocarcinoma].

With the aim of immortalizing embryonic cells fixed at early embryonic stages, various plasmids carrying the SV40 early region were introduced into the mouse embryonal carcinomas (EC) F9 and 1003. Only the construction PK4, in which the SV40 oncogenes are placed under the control of the adenovirus E1A promoter, led to the immortalization of the cells at the onset of differentiation. Clones corresponding to committed precursors of each embryonic lineage (neuroectoderm, mesoderm and endoderm) were then selected with high efficiency according to the following strategy: selection of immature cells which: have lost EC cell markers, keep a stable phenotype, are immortalized by the expression of the SV40 oncogenes and are still able to differentiate along a restricted lineage in vitro or in vivo. Examples of an endodermal precursor (H7) which differentiates into extraembryonic and embryonic endoderm, of a neuroectodermic clone (ICII) committed to a serotoninergic differentiation, and of a mesodermal osteogenic clone (CI) which gives rise to bone in vivo and in vitro, are given.

Adenoviridae↗
PubMed1990

[Proteins, genes and early diagnosis of Alzheimer's disease].

Proteic (neuritic plaques, amyloid substances...) and genetic characteristics of Alzheimer's disease are reviewed. An infectious origin appears unlikely. After production of specific antibodies, the reported abnormal Tau proteins might represent peripheral markers of the disease. Changes in olfactory neurons, accessible for biopsy specimens, might give rise to new biological diagnosis of Alzheimer's disease.

Alzheimer Disease↗
PubMed1989

Circulating gastrin, endocrine cells, histamine content, and histidine decarboxylase activity in atrophic gastritis.

Thirty-five patients with fundic atrophic gastritis and achlorhydria were classified in two groups according to the presence or absence of fundic argyrophil, mostly enterochromaffinlike cell hyperplasia. Among the biologic and histologic parameters studied, the hyperplasic group differed only by a circulating hypergastrinemia and an antral G-cell hyperplasia. The histamine content, the histidine decarboxylase activity, and the mast cell number of fundic biopsies were determined in 10 controls, 16 of the preceding patients (11 with and 5 without fundic argyrophil-cell hyperplasia), and 5 patients with fundic atrophic gastritis and neither achlorhydria nor hyperplasia. Histamine content and histidine decarboxylase activity were increased only in the hyperplasic group despite an unchanged mast cell number. For all fundic biopsies the argyrophil-cell density was positively related to the histamine content. Finally, the argyrophil-cell hyperplasia occurring in fundic atrophic gastritis with achlorhydria is associated not with the gastritis intensity, as assessed by histologic and secretory criteria, but with a circulating hypergastrinemia and an increase of both fundic histamine content and histidine decarboxylase activity.

Adult↗
PubMed1989

Homologous regulation of human platelet vasopressin receptors does not occur in vivo.

Large variations in the functional responsiveness of human platelets to arginine vasopressin (AVP), related to maximal platelet AVP-binding capacity, have been observed among individuals. The effects of dehydration and overhydration on maximal platelet AVP-binding capacity, plasma AVP, platelet-associated AVP, and AVP-induced platelet aggregation were examined in healthy human volunteers to determine whether homologous regulation of platelet AVP receptors occurs in vivo within the physiological range of circulating AVP fluctuations. Although significant variations of plasma AVP were observed under both conditions, no correlation could be found in the same individual with any change in 1) the maximal AVP-binding capacity, 2) platelet aggregatory responses to AVP, or 3) the platelet AVP fraction. Moreover, there was no relationship between the number of detectable platelet AVP receptors and the amount of AVP associated with platelets. These data show that homologous regulation of platelet AVP receptors by AVP does not occur in vivo over the time investigated, at least within the physiological range of AVP. Nonetheless, regulation at the platelet precursor stage appears to be highly probable in view of the relationship between plasma AVP and platelet AVP binding capacity observed among different individuals.

Adult↗
PubMed1989

Serotonin and human immunodeficiency viruses.

This preliminary study shows, for the first time to our knowledge, decreased whole blood serotonin levels in AIDS patients as compared to healthy controls and cancer patients. The lowest serotonin levels were found in AIDS patients with neuropsychiatric symptoms. Finally the present data suggest an inverse relationship between serotonin level and AIDS severity.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Platelets as a model for neurones?

The multiple biochemical and pharmacological similarities existing between blood platelets and 5-hydroxytryptamine (5-HT)-containing neurones of the CNS point to the platelets as a reliable model for the biochemical characterization of 5-HT releasers and uptake blockers which interfere with the storage and the active carrier mechanism of 5-HT in the neurones, respectively. In addition, the affinity displayed by dopamine and by dopaminergic neurotoxin MPP+ for the platelet 5-HT transport and storage indicates also some similarities between platelets and the dopaminergic system of the CNS. Since human platelets contain almost exclusively monoamine oxidase type B (MAO-B), they can be used as a source for the purification and characterization of this human enzyme. Human platelets thus offer an excellent peripheral model to indirectly assess the degree and duration of MAO-B inhibition occurring in the CNS. To date, knowledge of the many biochemical mechanisms underlying platelet physiology is still fragmentary. In fact, the functional role of binding sites located on the platelet cytoplasmic membrane, i.e. their coupling to a specific transmembrane signalling mechanism, is still in need of a precise biochemical and physiological characterization.

Animals↗
PubMed1988

Damaging effects of Clostridium perfringens delta toxin on blood platelets and their relevance to ganglioside GM2.

The lytic effect of Clostridium perfringens delta toxin was investigated on goat, human, rabbit, and guinea pig platelets. In contrast to erythrocytes from the latter three species, which are insensitive to the toxin, the platelets were equally lysed by the same amount of toxin. These results suggest the presence of GM2 or GM2-like ganglioside(s) as a specific recognition site of the toxin on platelet plasmic membrane as previously established for sensitive erythrocytes. Plasmic membrane damage of human platelets was evidenced by the release of entrapped alpha-[14C]aminoisobutyric acid used as a cytoplasmic marker. The specific binding of hemolytically active 125I-delta toxin by human and rabbit platelets was practically identical, dose dependent, and inhibitable by GM2. Labeled toxin was also bound by various subcellular organelles separated from rabbit platelets except the 5-hydroxytryptamine (5-HT)-containing dense bodies, suggesting the absence or inaccessibility of GM2 on the surface of the latter organelles. This result correlates with the low amounts of 5-[3H]HT liberated after platelet challenge with delta toxin whereas this mediator was massively liberated upon lysis by the sulfhydryl-activated toxin alveolysin. The levels of M and P forms of phenol sulfotransferase (PST), involved in 5-HT catabolism, were determined in human platelet lysates after challenge with delta toxin, alveolysin, and other disruptive treatments. The low PST-M activities detected after lysis by delta toxin suggest that this isoenzyme is very likely associated to dense bodies in contrast to PST-P which is cytoplasmic. Platelet lysis by the toxin allows easy separation of these organelles.

Aminoisobutyric Acids↗
PubMed1988

Congenital dyschromia with erythrocyte, platelet, and tryptophan metabolism abnormalities.

The case of a female child with a unique generalized congenital dyschromia is reported. She had hypopimented skin, with hypomelanosis and hypomelanocytosis, and many pigmented macules, which consisted of epidermal and dermal hypermelanosis without hypermelanocytosis. Biochemical investigations revealed normal catecholamine metabolism but abnormal tryptophan metabolism, including a decrease in blood serotonin and melatonin. A slight platelet storage pool disease was demonstrated, and a recurrent megaloblastic folate-related anemia occurred. The possible relationship between the pigmentary disease and the biochemical abnormalities is discussed. We suggest that this case represents a previously undescribed association of dyschromia, erythrocyte, platelet, and tryptophan metabolism abnormalities.

Blood Platelets↗