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Biomedical subjects

J M Launay

Publications and source records attributed to J M Launay.

At least 181 records · Page 10Linked to original sources

[Neuroendocrine tumors. Biochemical and physiopathological aspects].

Neuroendocrine tumors (secreting bioamines, peptides, hormones, prostaglandins...) represent rather homogeneous group since they correspond to a benign or malignant proliferation of cells belonging to the diffuse neuroendocrine system. This system might be considered as an extension of the concept (APUD System) proposed by Pearse to account for the common properties of these largely distributed cells. Among neuroendocrine tumors we focused since some years on apudomas and particularly carcinoïd tumors. The determination of their various secretion products in biological fluids allows the early and efficient detection of such tumors exhibiting a very slow growth. Finally the in vitro culture of carcinoïd cells appears to be of great interest in various research fields such as oncology, biochemistry and pharmacology.

Apudoma↗

Effects of in vitro infection of mouse glial and neuroblastoma cells with the scrapie agent.

Mouse glial and neuroblastoma cells were infected with the mouse adapted strains C506 and 139A of scrapie agent. Lysates of the in vitro infected cells (from the 3rd to the 16th passage) intracerebrally inoculated into CD-1 mice, caused the development of a neurological disease, with characteristic signs of scrapie. Morphological changes in scrapie-infected neural cells were observed after about fifteen in vitro passages. In liquid medium, the cloning efficiency of these cells increased. They acquired the capacity to form large tridimensional colonies in agar. Heating the infectious brain extracts at 60 and 80 degrees C for 30 minutes did not inhibit these changes thus showing the involvement of the thermoresistant scrapie agent. Supernatants of scrapie-infected glial cells promoted colony formation in liquid medium with different types of normal cells. Analysis of supernatants of scrapie-infected mouse neuroblastoma cells showed a profound modification of neurotransmitter metabolism.

Animals↗

Serotonin-secreting and insulin-secreting ileal carcinoid tumor and the use of in vitro culture of tumoral cells.

The authors report the case of a patient with a typical carcinoid syndrome and a severe hypoglycemia due to hyperinsulinism. He was found to have an ileal carcinoid tumor with hepatic metastasis and no evidence of pancreatic insulinoma at surgery and autopsy. By assaying serotonin and insulin in the tumor and in the supernatants of the culture derived from hepatic metastasis, the authors have been able to show that both hormones were produced by the carcinoid tissue. Cultured cells also synthesized minute amounts of gastrin and thyrocalcitonin.

Blood Glucose↗

Purified -SH-activated toxins (streptolysin O, alveolysin): new tools for determination of platelet enzyme activities.

The purpose of this study was to examine the lytic effect on human platelet preparations (washed, gel-filtered and dextran-isolated) of two sulfhydryl-activated bacterial protein toxins, streptolysin 0 and and alveolysin, and to compare their efficacy with that of other disruptive procedures (freezing and thawing, ultrasonic, mechanical, or nystatin-toluene treatment) as a method for the determination of various platelet enzyme activities. The enzymes assayed were alkaline and acid phosphatases, monoamine oxidase, phenolsulfotransferase, N-acetyltransferase, hydroxyindole-O-methyltransferase, glutathione peroxidase and lactate dehydrogenase. In all cases, the lowest activities were found after freezing and thawing and/or ultrasonic disruption. The highest activities were always observed in the platelet lysates obtained after toxin, and in some instances after nystatin-toluene treatment. Intermediate values were obtained for mechanical disruption. The -SH-activated cytolysins thus appear to be appropriate and gentle tools for the assay of platelet enzymes when compared to the physical or chemical procedures generally employed.

Bacterial Proteins↗

[Blood serotonin and histamine in sheep with endemic scrapie: initial results].

The whole blood histamine levels of sheep without clinical scrapie but living in infected farms, control, and scrapie infected sheep are not significantly different. By contrast whole blood serotonin is decreased both in sheep living in infected farms and in scrapie-infected sheep as compared to controls. Thrombopenia may account for the hyposerotoninemia of sheep living in infected farms except those genetically linked to scrapie-infected sheep for which, as for scrapie-infected sheep, platelet serotonin appears also to be diminished. Whole blood serotonin determination might therefore be useful to detect sheep living in infected farms (these sheep probably play an important role in scrapie infection) and perhaps also humans with high susceptibility to Creutzfeldt-Jakob disease.

Animals↗

[Role of platelet serotonin in common migraine. Concentrations and uptake].

Concentrations and uptake of platelet conjugated and unconjugated serotonin were measured in 15 healthy subjects and in 19 patients with common migraine. Venous blood was taken between migrainous attacks in all patients and during attacks in 8 of them. A significant decrease in unconjugated serotonin concentrations was observed during the attacks, whereas conjugated serotonin concentrations were the same as in controls. In addition, migrainous attacks were accompanied by a significant decrease in serotonin uptake by the platelets, with fall in Km, Vmax and -y. This abnormality was corrected when platelets removed from patients during attacks were incubated in plasma from controls, but it persisted when platelets from controls were incubated in plasma taken from patients during attacks. These findings suggest that one or several factors present in plasma are responsible for the decrease in serotonin uptake observed during migrainous attacks. Finally a study of correlations between these changes and the time elapsed since the last migrainous attacks demonstrated cyclic variations in abnormalities between attacks.

Adult↗

Exploration of the role of phenolsulfotransferase in the disposition of serotonin in human platelets: implications for a novel therapeutic strategy against depression.

Human platelets have been used as models to evaluate a possible role for phenolsulfotransferase (PST) in the disposition of 5-hydroxytryptamine (5HT). The platelet M-type PST, which prefers biogenic amines as substrates, appears to be unique in its ability to O-sulfate dopamine and 4,6-difluoro-5HT (diF-5HT) at rates 6-20 times faster than 5HT. The assay technique employed can make a critical difference in the measured rates of sulfation of these amines, however. For example, use of purified alveolysin toxin to disrupt cell membranes can result in as much as a 20-fold increase in the observed velocity of 5HT O-sulfation. In intact platelets, only 1-3% of the total amount of radiolabelled material (as measured by a thin-layer chromatographic procedure) is the O-sulfate conjugate of 5HT. Up to 20% of the total H3-5HT taken up by cells becomes O-sulfated following treatments such as reserpine which lead to a large increase in the extra-vesicular (cytoplasmic) pool of H3-5HT. Availability of a compound producing irreversible inhibition of M-type PST activity would facilitate exploration of intra-platelet 5HT metabolism, but compounds reported to inhibit essentially 100% of the PST activity in other systems do not appear to interfere with the action of human platelet M-type PST. Because of the apparent similarity between PST present in human platelets and in nerve microsacs prepared from guinea pig brains, PST inhibitors effective in human platelets might also be valuable for studies of amine metabolism in brain tissue. Possible candidates are discussed. Furthermore, the behavioral effects of compounds proving to be PST inhibitors could provide novel therapeutic approaches to the problem of depressive illness.

Antidepressive Agents↗

Total IgE, specific IgE and prick-tests against foods in common migraine--a prospective study.

A prospective study of total IgE, specific IgE against 12 common foods, and prick-tests with 11 common food allergens was performed on 50 consecutive migraine sufferers. Total IgE levels were found above 100 kU/l for seven patients, but five of them were atopic. Prick-tests and RAST were positive for four and six patients (class 1), respectively. Food challenge on these six patients did not cause any migraine attacks. This study thus indicates a very low frequency of allergic dietary migraine to common foods.

Adolescent↗

The diffuse neuroendocrine (APUD) system.

The bulk of experimental evidence indicates that the APUD series of cells is a distinct system based upon common pathophysiological features. The diffuse nature of this system with elements in the central and peripheral nervous system suggests a more complex interaction of the body's homeostasis than has been established. It is probable that as radioimmunological and radioenzymatic assays become more widely available and standardized, other apudomas will be described. Finally, an understanding of the APUD concept, with its peculiar pluripotential for the production of biogenic amines and peptides, the multicentric nature of the disease and the possibility of multiple cell involvement, is of key importance in managing patients. Studies of the apudomas will also advance the understanding of the normal physiologic interrelationships of the APUD cells.

APUD Cells↗

Melatonin synthesis by rabbit platelets.

Platelets of reserpinized rabbits, incubated in buffer containing tritiated 5-hydroxytryptamine (3H-5HT), have the ability to convert 3H-5HT into labeled compound(s) extractable with alkaline-chloroform. The bulk of the chloroform-extractable radioactivity showed a Rf value similar to authentic melatonin on silicagel thin-layer chromatography. The labelled product eluted with ethanol from the silicagel area where melatonin was suspected to reside was identified as melatonin by mass spectrometry and radioimmunoassay. Our in vitro experiments demonstrate that rabbit platelets are capable of converting 5-HT into melatonin apparently because they possess the enzymatic equipment necessary for this biosynthesis i.e. serotonin N-acetyltransferase and hydroxyindole-O-methyltransferase.

Animals↗

Platelet serotonin uptake and migraine.

Platelet serotonin uptake characteristics (Km, Vmax, y) were determined in platelet-rich plasma for 11 common migraineurs and 15 health volunteers. All three parameters were decreased only for the three patients having a migraine attack during blood collection, Migrainous platelets isolated on dextran or resuspended in control plasma exhibited normal serotonin uptake. This finding suggests that plasmatic factor(s) may be responsible for the decrease of platelet serotonin uptake observed during migraine attacks.

Blood Platelets↗

Serotonin and histamine production by human carcinoid cells in culture.

We are reporting on the first human carcinoid cells ever cultured in vitro. These cells, termed CGP, originated from a jejunal carcinoid tumor. Before tumor resection, the 29-year old male patient presented high levels of blood serotonin and histamine and also of urinary serotonin and 5-hydroxyindole-acetic acid; values returned to normal 9 days after resection. CGP cells exhibit a very slow multiplication rate; generation time is about 10 days. From the first subculture, the main cytological, ultrastructural, and biochemical features of CGP cultures remain unchanged. The cells show most of the enterochromaffin cell histomorphological characteristics; for example, cytoplasmic granulations, specific of argyrophilic cells, can be seen both by electron microscopy and by light microscopy (preceded by silver impregnation). The high amounts of serotonin and histamine found by highly specific radioenzymatic assay in the supernatant of CGP cultures indicate that, after 6 months (25 subcultures), CGP cells have retained the main metabolic characteristics of the original tumor, i.e., the ability to synthesize, store, and release both serotonin and histamine.

Adult↗

Low serotonin uptake by platelets in leprosy and a new approach to prevent it.

The plasma of leprosy patients contains high levels of mucoproteins which are deficient in sialic acid. However, due to the increased mucoprotein level, the total sialic acid content of leprous plasma, calculated on protein, is increased when compared with normal human plasma. The low serotonin uptake observed with isolated platelets is probably due to their low sialic acid content. The inability of normal human plasma to correct the diminished serotonin uptake by isolated leprous platelets is in favor of a definite structural change in leprous platelets, related to their low sialic acid content. In patients with active disease and in those with lepra reactions, leprous plasma itself can correct the diminished uptake of serotonin by the isolated platelets. In patients with subsided lepra reactions, the leprous plasma is much less effective. In severe cases, where serotonin uptake is decreased even in platelet rich plasma, desoxyfructo-serotonin increased the uptake of serotonin.

Blood Platelets↗

Modifications of biochemical parameters in blood platelets of schizophrenic and depressive patients.

The blood platelet may be considered as an interesting model of the serotoninergic neuron in biology and pharmacology. We studied some platelet parameters in neuropsychiatric patients (depressive and schizophrenic ones): serotonin (5-HT) uptake was abnormal for all schizophrenics and lowered for depressive patients; uptake of mepacrine, a marker of 5-HT passive diffusion, was diminished for manic patients; MAO and glutathione peroxidase activities were modified, essentially for paranoid schizophrenics and some alterations of the platelet hydroxyindole level were noticed; during treatment with neuroleptics of antidepressants biological parameters led to 'normality'. These results are discussed with clinical data and a hypothesis is proposed to join the biological modifications of paranoid schizophrenics.

Blood Platelets↗

Biochemical and ultrastructural study of the disruption of blood platelets by streptolysin O.

The membrane-damaging protein toxin, streptolysin O, proved highly lytic on human, guinea-pig and rabbit platelets. About 15 molecules of toxin were sufficient to lyse one cell. Platelet disruption was assessed by electron microscopy, clearing of cell suspensions and assay of lactate dehydrogenase, serotonin, monoamine oxidase and glutathione peroxidase released in the extracellular fluid. This egress reflected the damage of both plasmic and organelle membranes. A quantitative study of lactate dehydrogenase and serotonin liberation taken as respective markers of the cytosol and dense bodies was undertaken as a function of toxin concentration. No platelet aggregation or shape change was elicited by streptolysin O. The ghosts resulting from platelet lysis retained properties of the native membrane such as aggregability and serotonin uptake. Dense bodies were easily separated after gentle disruption of the plasmic membrane by small amounts of toxin. Platelet lysis by streptolysin O proved a useful procedure for the determination of protein content, enzyme activities and serotonin assay on the same lysate in contrast to usual methods.

Animals↗