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Biomedical subjects

J J Legros

Publications and source records attributed to J J Legros.

At least 91 records · Page 5Linked to original sources
PubMed1991

Colocalization of immunoreactive oxytocin, vasopressin and interleukin-1 in human thymic epithelial neuroendocrine cells.

Monoclonal antibodies to oxytocin (OT) and vasopressin (VP) revealed some positively staining stromal cells in the subcapsular cortex and in the medulla of the human thymus. We further demonstrated that these cells are a subset of epithelial endocrine cells and also contain immunoreactive interleukin-1 together with the neuropeptides. In addition, the thymic cells stained by monoclonal antibodies directed to the cyclic part of oxytocin or vasopressin also contained some immunoreactive neurophysins. These data support the concept of intrathymic synthesis of neurohypophyseal-like peptides fitting the hypothalamic model. However, we observed that, contrary to the situation in the brain, OT- and VP-like peptides colocalized in the same thymic cells. Furthermore, one monoclonal antibody, specific for the tail part of oxytocin, did not label thymic cells. Therefore, thymic neuropeptide(s) could be related to, but distinct from, authentic OT and VP. These observations suggest some molecular differences between hypothalamic and thymic oxytocin biosynthetic pathways which need to be further investigated.

Antibodies, Monoclonal↗
PubMed1990

Plasmatic vasopressin neurophysin in depression: basic levels and relations with HPA axis.

A decreased secretion of arginine vasopressin (AVP) has been implicated in depression. In order to further investigate this hypothesis, we studied the plasma level of the specific peptidergic carrier of AVP, vasopressin neurophysin (hNpI), in 26 depressed inpatients and 16 matched normal controls. On the other hand, AVP has also been involved in the pathophysiology of the cortisol postdexamethasone nonsuppression frequently observed in depression. Therefore, we investigated concomitantly hNpI and cortisol during a dexamethasone (DXM) suppression test. hNpI and cortisol were assessed by radioimmunoassay at 8 AM and 8 PM during 4 consecutive days. From days 2 to 3, 4 mg (DXM) was given orally. hNpI values were not affected by DXM administration. Compared with controls, patients showed higher pre- and post-DXM cortisol values and lower hNpI values. No difference in hNpI values was observed between DXM escapers or nonescapers. Our results are consistent with an impaired AVP secretion in depression and fail to support a role of AVP in the early cortisol escape.

Adult↗
PubMed1990

Development of neurophysin-containing neurons in primary cultures of rat hypothalami is related to the age of the embryo: morphological study and comparison of in vivo and in vitro neurophysins, oxytocin, and vasopressin content.

The morphological development of immunocytochemically identified neurophysin neurons and the evolution of neuropeptide content (neurophysins, vasopressin, and oxytocin) were studied in primary cultures of hypothalami obtained from 15- to 19-day-old embryos. According to their perikaryal surface, two populations of neurons were distinguished: large and small cells. Full development (defined by the perikaryal surface) of these neurons was reached at day 21 only in cultures from 15- or 16-day-old embryos. These two types of neurons may correspond to the magnocellular and parvocellular neurons described in vivo. Total neurophysins, vasopressin, and oxytocin content were measured by specific radioimmunoassays. Ontogeny of neurophysins and vasopressin showed a good correlation between cells cultured from 15- to 16-day-old embryos and hypothalami from age-matched rats. However, oxytocin was never detected in any of the cultures whatever the age of the embryos. Under our experimental conditions, hypothalamic primary cultures from 15- to 16-day-old embryos therefore appeared to be suitable for studying the differentiation and regulation of neurophysin- and vasopressin-containing neurons.

Animals↗
PubMed1990

Neurophysins as markers of vasopressin and oxytocin release. A study in carcinoma of the lung.

Vasopressin-neurophysin (hNpI), oxytocin-neurophysin (hNpII) and blood osmolality were assayed before any treatment in basal conditions in 35 patients suffering from lung carcinoma (20 oat cell, 6 undifferentiated and 9 well-differentiated epidermoid cell carcinomas). Plasma vasopressin (antidiuretic hormone, ADH) was also assayed in 7 of the 20 patients suffering from oat cell carcinoma. We found a close correlation (r = 0.98) between plasma ADH and hNpI levels in the 7 patients. Further, hNpI was elevated in 13 out of the 20 oat cell carcinoma patients and in none of the epidermoid-cell carcinoma group; however, searching for an abnormality of ADH secretion as reflected by a detectable plasma hNpI level together with subnormal plasma osmolality revealed 2 additional positive results in the oat cell carcinoma group, and 2 out of the 6 in the undifferentiated-cell carcinoma group. hNpII was increased together with an increase in hNpI in 6 oat cell carcinoma patients; it was specifically increased without hNpI increment in 2 additional oat cell carcinoma patients and in 2 patients of the undifferentiated-cell carcinoma group (different from the 2 positive for the hNpI-osmolality ratio). hNpI and hNpII were normal in the majority of undifferentiated and all of the differentiated epidermoid-cell carcinoma group. Hence, our results show that simultaneous measurements of hNpI, hNpII, and blood osmolality could detect abnormalities in 17 out of 20 oat cell carcinoma patients, in 4 of the 9 undifferentiated-cell carcinoma patients, but in none of the differentiated epidermoid-cell carcinoma patients, suggesting that the neurophysin assay can be used for the early detection of oat cell- and possibly other neuroendocrine-derived carcinomas.

Biomarkers, Tumor↗
PubMed1990

Expression of preprotachykinin-A and neuropeptide-Y messenger RNA in the thymus.

The preprotachykinin-A gene, the common gene of mRNAs encoding both substance-P (SP) and neurokinin-A (NKA), was shown to be expressed in Sprague-Dawley rat thymus by detection of specific mRNA in gel-blot analyses. In situ hybridization revealed dispersed PPT-A-labeled cells in sections from rat thymus, with a concentration of grains over a subpopulation of cells in the thymic medulla. Also, neuropeptide-Y mRNA-expressing cells were found in the rat thymus, primarily in the thymic medulla. Rat thymic extracts contained SP-like immunoreactivity (SP-LI), and the major part of the immunoreactivity coeluted with authentic SP and SP sulfoxide standards. SP-LI was also detected in human thymus, which contained between 0.09-0.88 ng SP-LI/g wet wt. Evidence for translation of preprotachykinin-A mRNA in the rat thymus was obtained from the demonstration of NKA-LI in thymic cells with an epithelial-like cell morphology. Combined with previous observations on the immunoregulatory roles of tachykinin peptides and the existence of specific receptors on immunocompetent cells, the demonstration of intrathymic synthesis of NKA suggests a role for NKA-LI peptides in T-cell differentiation in the thymus.

Animals↗
PubMed1990

[Neurophysins].

Neurophysins are neuropeptides (MW +/- 10,000) synthetized together with active nonapeptides vasopressin (AVP) and oxytocin (OT). The original description of the radioimmunoassay for neurophysins in 1969 allowed us to demonstrate the concomitant, equimolecular, release of them together with AVP and OT, thus bringing strong arguments in favour of neurohypophyseal exocytosis. Beside the use of those RIAs as direct indexes of neurohypophyseal release in various physiological and pathological conditions, we have been interested these last two years, to the putative use of neurophysins RIA as direct neuroendocrine markers in various neuropsychiatric diseases (depression, mania, schizophrenia) and paraneoplastic syndromes (SIADH).

Exocytosis↗
PubMed1989

Treatment outcome, seizure duration, and the neurophysin response to ECT.

Serum concentrations of immunoreactive neurophysin (IRN) and vasopressin-associated neurophysin (hNpI) were measured before and after the first treatment in a course of electroencephalographically monitored electroconvulsive therapy (ECT) given to 19 depressed patients. The difference (DIFF) between the serum concentrations of IRN and hNpI is equivalent to the concentration of oxytocin-associated neurophysin. Before ECT the six patients who had a good outcome at 2 months after the course of ECT had a mean serum IRN concentration one-half (p less than 0.05) and a mean serum DIFF concentration one-third (p less than 0.05) that of the 13 patients who had a poor outcome. The increase in serum DIFF concentration (but not IRN or hNpI) after the first ECT correlated with the improvement on the Hamilton Rating Scale for Depression (r = -0.73, p less than 0.005) and the Montgomery and Asberg Depression Rating Scale (r = -0.49, p less than 0.05). The peak percentage increase in serum DIFF concentrations after ECT was 4 times greater (p less than 0.001) in the good outcome group than in the poor outcome group. None of the neurophysin responses to ECT correlated with electroencephalogram-measured seizure duration.

Adult↗
PubMed1989

Increased basal plasma vasopressin-neurophysin in mania.

Basal plasma vasopressin-neurophysin (hNpI) was estimated in 50 drug-free neuropsychiatric patients classified according to the Research Diagnostic Criteria. The hNpI concentration was higher in the 5 manics (0.76 +/- 0.15 ng/ml) than in the 16 schizophrenics (0.53 +/- 0.08), 12 minor depressed (0.54 +/- 0.06) and 17 major depressed (0.48 +/- 0.10; p less than 0.05). Thus, those results confirm our initial observation of an increased vasopressinergic function in the manic compared to the depressed phase in one bipolar patient. Whether this increase in the vasopressin release is a consequence of the neuropsychiatric disorders or initiates and/or participates in their pathophysiology remains to be elucidated. The hypothetic consequence on water metabolism of such an increase remains also to be defined.

Adolescent↗
PubMed1989

Neuroendocrinology of the thymus.

The neuropeptides oxytocin (OT) and vasopressin (VP) are synthesized in the human thymus in a similar way as in the hypothalamo-neurophypophyseal system. Immunocytochemistry with polyclonal and monoclonal antibodies revealed that immunoreactive OT- and VP-producing cells are localized in the subcapsular cortex and medulla of human and murine thymuses. The epithelial nature of the neuroendocrine thymic cells is demonstrated by their immunostaining with a monoclonal antibody against cytokeratin. An original example of a neuroendocrine-immune microenvironment is given by the thymic nurse cells which are composed of a large neuroendocrine epithelial cell enclosing numerous mitotic immature thymocytes. These observations and the previously reported mitogenic and immunomodulatory properties of VP and OT upon mature T cells and thymocytes strongly support the existence of a neuroendocrine thymo-lymphoid axis and an active role of thymic VP and OT in T cell differentiation and activation.

Humans↗
PubMed1988

The neuroendocrine thymus. Abundant occurrence of oxytocin-, vasopressin-, and neurophysin-like peptides in epithelial cells.

Certain subtypes of thymic epithelial cells--the medullary epithelium, the cortical surface epithelium, and some intracortical epithelial cells--show strong immunohistochemical reactivity with antisera against oxytocin, Arg-vasopressin and neurophysin. The epithelial nature of the neuropeptide containing cells is shown by their morphology and their reactivity with monoclonal anti-cytokeratin AE1/E3. Hassall's corpuscles are positive as well. The immunoreactivity patterns for the three neuropeptides are identical, suggesting a parallel distribution. The vast majority of cortical epithelial cells are negative, emphasizing the tightly controlled microenvironment for T-cell development. The possibility of a neuroendocrine role of the thymus is discussed.

Adolescent↗
PubMed1988

Vasopressin and vasopressin analogues for treatment of memory disorders in clinical practice.

1. Beyond its antidiuretic and vasopressor effects, vasopressin has central nervous system effects, first described in rats by David de Wied in 1965. 2. Its first clinical use in humans, in 1978, confirmed its stimulant action in normal individuals, especially in middle-aged male subjects. 3. Its utility in mnemic problems is also worht considering when the pathology is relatively recent (less than 2 years prior) and unaccompanied by major neurological lesions. Behavioral modifications, such as improvement of "sociability", "mood" improvement, independent of its effects on memory have been described, and would justify complementary clinical investigation. 4. New synthetic vasopressin derivatives which would eliminate metabolic effects while maintaining behavioral effects intact, and the definition of clinical, neuroendocrine, and neurophysiological prognostic criteria, will be the two most important paths for investigation over the next years.

Cognition↗
PubMed1988

Inhibitory influence of oxytocin infusion on contingent negative variation and some memory tasks in normal men.

A double-blind study combining electrophysiological and psychometrical approaches was carried out to investigate the central effects of an intravenous oxytocin (OT) infusion in normal men. Contingent negative variation (CNV) was selected as the measure of central cognitive evoked potential, and the psychometric tests measured mood, vigilance and memory. OT infusion induced a significant decrease of CNV amplitude and an increase of post-imperative positive potentials in vertex derivations. A similar effect was still evidenced one week after treatment in frontal derivations, suggesting a long time effect of OT on human brain. No significant influence of OT on mood or vigilance tests was apparent; only one item of a memory test revealed a significant impairment of some mnesic performances. These observations provide new electrophysiological arguments supporting a central action of peripheral OT administration in man.

Adult↗
PubMed1988

[Modifications of contingent negative variation (CNV) induced by oxytocin infusion].

The central effects of an intravenous infusion of oxytocin (OT), 3,680 mIU in 45 min, were investigated in 20 male volunteers in a double-blind study combining an electrophysiological and a psychometrical approach. The electrophysiological approach consisted in the simultaneous recording of the CNV (Fz-A1 and Cz-A1) and the spontaneous EEG (bipolar P3-P4) recording on which was carried out an FFT analysis. On the other hand, various psychometric tests allowed to assess memory (Rey's tests), attention (K-T test) processes and mood changes (visual analogue scales). Within the hour following the infusion, OT induced a significant decrease of CNV amplitude and an increase of the post-imperative positive component at Cz-A1. A similar effect was still observed one week later, but was more marked at Fz-A1. Neither mood nor attention tests evidenced any significant effect of OT. Only one item of the memory test PRM (item 4) revealed a significant impairment after OT infusion. There were no subjective effects reported. These observations provide new electrophysiological arguments supporting a central action of peripheral OT administration in man. This action, which may be characterized as an acceleration of CNV "habituation" is the opposite of the one described with vasopressin.

Brain↗
PubMed1988

[Relationship between dexamethasone suppression test and contingent negative variation in major depressive patients].

We tried to relate two different indexes sensitive to the perturbations induced by major depression: the Dexamethasone Suppression Test or DST (Caroll, 1982) and the Contingent Negative Variation (CNV). The question was whether abnormalities in cortisol levels, following dexamethasone would enlight the modifications observed in CNV parameters and other electrophysiological indexes (EEG spectrum, reaction time). In 61 major depressive patients, 29 being DST-non-suppressors, we calculated differences in electrophysiological variables according to DST suppression or not, but we were not able to evidence significant differences between the groups. However, there were correlations between log-transformed levels of cortisol and on the one hand, CNV slope (r = -0.34, P less than 0.03) and on the other hand, reaction time (r = 0.45, P less than 0.01). Correlations between electrophysiological variables appeared in the sole suppressors group (e.g. CNV amplitude and alpha rythm reactivity; post-imperative variation and percent beta of the EEG spectrum). These results underline the complementary aspect of the two methods.

Adult↗