Collaborative study of mosaic tetrasomy 12p or Pallister-Killian syndrome (nineteen fetuses or children).

The difficulties in the diagnosis of Pallister-Killian syndrome are illustrated in this study of nineteen fetuses and children. Diagnosis based on clinical appearance alone is often difficult due to the broad spectrum of clinical anomalies not specific to this syndrome. Due to mosaicism, it is altogether necessary to examine several tissues for the presence of tetrasomy 12p, including circulating lymphocytes in which mosaicism can be as low as 1-3%, amniocytes, chorionic cells and skin fibro-blasts in which mosaicism ranges from 6-100%. When highly suspected on ultrasound examination, the diagnosis recommends prenatal cytogenetic studies because survivors are severely mentally retarded. All the cases are sporadic with only a single preliminary report of recurrence. The cytogenetic diagnosis is therefore helpful in order to reassure family members in regard to genetic counseling.

Pallister Killian--mosaic tetrasomy 12 p syndrome. Another prenatally diagnosed case.

A new case of mosaic tetrasomy 12 p (46,XY/47,XY, +i12 p), diagnosed during pregnancy from ultrasonographic signs, is reported. We emphasize the peculiar position of the diaphragmatic hernia in this syndrome. Its presence or absence determines the vital prognosis and the age of diagnosis. The knowledge of its possible association with tetrasomy 12 p can contribute considerably to the neonatal diagnosis by directing the work of the cytogeneticist to tissue cultures which enable him to detect the presence of the tetrasomy.

[Organotypic culture of human corneal epithelium. Preliminary results]. / Culture organotypique d'épithélium cornéen humain. Résultats préliminaires.

The authors compared the growth of limbal and central explants removed from human cornea. Epithelial growth began on the third day, was greater during the first week and was subsequently slightly invaded by fibroblasts. This study demonstrated that peripheral corneal epithelial cells growth better than central cells. In this study, the cytologic and histologic features of the cells were examined. However, epithelial immunofluorescence staining by anti-cytokeratin antibodies was rather poor. This in vitro system may provide a suitable model for epithelial human corneal cell culture, allowing further biocompatibility studies.

Cloning of cDNAs encoding a rat neuropeptide immunologically related to salmon melanin-concentrating hormone.

In order to identify the neuropeptide related to melanin-concentrating hormone (MCH) synthetized by neurons of the posterior hypothalamus in the mammals, we have screened rat hypothalamus and rat brain cDNA expression libraries using MCH antiserum. We isolated 5 distinct immunopositive recombinants with cross-hybridizing cDNA inserts. One of them hybridized to RNAs exclusively located in neurons stained by the same antiserum, as seen by successively performing in situ hybridization and then an immunocytochemical technique on the same section. Sequencing of this MCH-like cDNA is in progress.

[Cloning of the cDNA, while encoding a hypothalamic neuropeptide in the rat, related to the melanin-concentrating hormone in the salmon]. / Clonage d'un ADNc codant un neuropeptide hypothalamique de rat apparenté à l'hormone de mélano-concentration du Saumon.

In order to identify the neuropeptide related to salmon melanin-concentrating hormone (MCH) synthetized by neurons of the posterior hypothalamus in the mammals, we have screened rat hypothalamus and rat brain cDNA expression libraries using MCH antiserum. Five recombinants were isolated, which cDNAs were amplified using the polymerase chain reaction. One of them hybridized to RNAs exclusively located in hypothalamic neurons stained by the same antiserum, as seen by performing in situ hybridization and immunocytochemical techniques on the same section. The sequence analysis showed that this cDNA corresponds to the end of the open reading frame encoding a MCH-like peptide and to the 3' untranslated region. The rat MCH is very similar to salmon MCH (greater than 85% homologies in the 14C-terminal residues).

[Contribution of immunocytochemistry to the study of the development of neuroglandular peptidergic systems in the human fetal hypothalamus]. / Apport de l'immunocytochimie à l'étude du développement de systèmes neuroglandulaires peptidergiques dans l'hypothalamus foetal humain.

Immunohistochemistry makes possible the in situ detection of neuropeptides in the cell bodies were they are synthesized, in the fibers that carry them, and in endings. Immunohistochemistry appears necessary to identify and map peptidergic neurons and to study their ontogeny. From 1975, we have carried the immunohistochemical study of several hypothalamic neuronal populations in the human fetus: LH-RH (1976), somatostatin (1977), pro-opiocortin (1978), vasopressin and oxytocin (1979), corticoliberin (1982), somatocrinin (1983), and hypothalamic neurons containing an unidentified peptide (1984). Comparative ontogenetical studies have also been performed in rats.

The CRF neuron: immunocytochemical study.

In the central nervous systems of several species belonging to different vertebrate classes, immunocytochemical stainings with an antiserum to ovine CRF 41 show multiple location of CRF perikarya and various areas containing CRF fibres and terminals. These stainings reflect species and interspecies functional adaptations of the CRF neurones which constitute a prominent hypothalamo-infundibular system involved in pituitary gland control, and also interneurone systems as attested to by extrahypothalamic perikarya and by CRF perisomatal endings in several brain areas. Perikarya of the hypothalamo-infundibular system are mainly packed in the paraventricular nucleus (mammals, birds) or in homologous areas, e.g.: paraventricular organ (turtle) where they are CSF-contacting neurones and preoptic nucleus (amphibians, fishes). In all species but fish, CRF fibres end in the median eminence (ME) against portal vessels. In fish, CRF processes terminate in the peripheral areas of proadenohypophyseal neurodigitations, close to corticotrophs. In all species these stainings are abolished by preabsorption of the serum by CRF. In fishes, reptiles and amphibians they are also suppressed by urotensin I, which is thought to be the teleost's CRF. Adrenalectomy experiments in the rat provided evidence for a corticosteroid regulation of ME CRF: short term (12-24 hr) adrenalectomy induces a complete depletion of CRF immunoreactivity followed by a secondary accumulation (5-20 days). This biphasic evolution is prevented by a dexamethasone replacement therapy. Inhibitory role of catecholamines on CRF release was indicated by: disappearance of ME CRF, induced by a single reserpine injection and suppression of this effect by monoamineoxidase inhibitor (pargyline or tranylcypromine) pretreatment. CRF fibres were first observed in the ME at the 16th week of fetal development in the human, and at the 18th day in the rat fetus. Thus, immunoreactive CRF system develops later than pituitary corticotrophs.

Corticoliberin neurons: cytophysiology, phylogeny and ontogeny.

In the rat hypothalamus, antibodies to ovine CRF41 stain neurons of a paraventriculo-infundibular neuroglandular pathway. CRF like immunoreactivity (CLI)-containing perikarya are mostly packed in the parvocellular division of the paraventricular nucleus. Their morphology and topography differ from that of other peptidergic neurons. However a few CLI perikarya are also stained with vasopressin antibodies. CLI neurons project massively to the external layer of the median eminence (ELME). Adrenalectomy induced a total depletion of ELME CLI 12 to 24 h after surgery, followed by a secondary accumulation already conspicuous 5 days later. This biphasic evolution, identical to that of ELME vasopressin, is totally prevented by a replacement therapy with dexamethasone. Reserpine also induces an acute depletion of ELME CLI and vasopressin, that can be prevented by a monoamine oxidase inhibitor pretreatment. These results indicate the involvement of CLI neurons in the corticotropic axis, suggesting that they are indeed corticoliberin neurons. Among the extrahypothalamic locations of CLI neurons their abundance in the amygdala central nucleus is of interest since it is involved in the corticotropic axis. A similar pattern of CLI was noticed in several mammalian brains and also in lower vertebrates (birds, reptiles, amphibians, fishes). Species adaptations of CLI neurons were observed: CLI neurons are of the cerebrospinal fluid contacting type in the turtle. CLI fibres terminate close to corticotrophs in the fish pituitary. This suggests a direct excitosecretory role of CRF on these cells and concurs with a CRF function of CLI peptide even in fishes. CLI processes and terminals appear in the human fetal ELME at the 16th week of development and increase in number during the following weeks. Perikarya are seen at 19 weeks. In the rat CLI fibers and perikarya were detected as early as the 18th day of fetal development. Thus, paraventriculo-infundibular CLI system develops later than corticotrophs. This chronology perfectly concurs with the results of previous physiological and experimental studies.

Immunocytochemical demonstration of a novel peptidergic neurone system in the cat brain with an anti-growth hormone-releasing factor serum.

In 15-day-, 1-month- and 1.5-month- old cats an antiserum against hpGRF-44 stained a novel hypothalamo-infundibular neuroglandular system. Its intra-eminential processes present an important development between 15 and 30 days of age. Perikarya and nerve fibres, which are abundant in several brain areas as early as the 15th day, suggest that the peptide revealed by hpGRF-44 antibodies also acts as a neuromodulator.

Changes in corticoliberin and vasopressin-like immunoreactivities in the zona externa of the median eminence in adrenalectomized rats. Immunocytochemical study.

The zona externa of the median eminence was found completely depleted of corticoliberin-like immunoreactivity (CLI) and of vasopressin-like immunoreactivity (VLI) 12-14 h and 22-24 h after bilateral adrenalectomy. Amount of CLI increased to the level of untreated rats 5 days after this operation while amount of VLI rose higher than in control animals. The same was found 20 days after surgery. These results emphasize the involvement of two infundibular neurosecretory systems--CLI and VLI--in the regulation of the pituitary--adrenal axis.

[Demonstration of a neuronal peptide system reactive with anti-CRF41 immune serum, in fresh water and marine teleosts]. / Mise en évidence d'un système neuronal peptidergique réactif à un immun-serum anti-CRF41, chez les téléostéens dulcicoles et marins.

CRF41 antibodies stained a peptidergic neurone system in the brain of several species of Teleost Fish. Perikarya are localized in the preoptic nucleus. Processes terminate mainly in the neurodigitations of the proadenohypophysis, close to corticotrophs. There are fewer ending in the neural lobe in contact with pars intermedia cells. CRF +/- nerve profiles and perisomatal endings were also observed in various brain areas.

[Comparative immunocytochemical study of the neuroglandular hypothalamic CRF system in the postnatal period in dogs and cats]. / Etude immunocytochimique comparée du système neuroglandulaire hypothalamique à CRF en période post-natale chez le Chien et le Chat.

Immunocytochemical visualization, and comparative morphological analysis of the paraventriculo-infundibular CRF-positive system was performed in new-born dogs and young cats. Our studies underline the identity of this system and its structural similarity among Mammals. They confirm the interspecificity of the antigenic sites recognized by our ovine CRF-antibodies.

Immunocytochemical demonstration of corticoliberin-like immunoreactivity (CLI) in neurones of the rat amygdala central nucleus (ACN).

Anti-corticotropin-releasing factor (CRF) antibodies revealed numerous perikarya in the amygdala central nucleus (ACN) of colchicine-injected rats. Most of the immunoreactive processes emerging from these neurone bodies seemed to project to the lateral hypothalamus by the ventral amygdalo-hypothalamic pathway. As well as parvocellular areas of the hypothalamic paraventricular nucleus where numerous neurones containing corticoliberin-like immunoreactivity (CLI) were demonstrated, ACN is densely innervated by beta-endorphin fibres originating from pro-opiomelanocortin neurones of the hypothalamic arcuate nucleus. The facilitatory influences of the amygdala on the corticotropic axis are most probably mediated by the ACN CLI neurones, the possible infundibular projections of which remain to be demonstrated.

[Immunocytochemical study of the ontogenesis of the CRF-containing neuroglandular system in the rat (author's transl)]. / Etude immunocytochimique de l'ontogenèse du système neuroglandulaire à CRF chez le rat.

In the Rat, immunoreactive CRF-containing processes appear in the median eminence between the 18 and the 19th day of the fetal development. They seem to become functional as early as the 19th day since they establish neuro-hemal junctions with the capillaries of the Mantel Plexus. During the pre- and post-natal periods, the number of these fibers increases greatly in the median eminence where they extend in all parts of the zona externa, and in the pituitary stalk. At birth they display a biphasic evolution made up of a disappearance of the corticoliberin immunoreactivity followed by an accumulation accompanied by the appearance of a few immunoreactive perikarya in the paraventricular nucleus.

[Immunocytochemical detection of the CRF-containing neurons in the rat brain (author's transl)]. / Mise en évidence immunocytochimique du système neuroglandulaire à-CRF dans l'hypothalamus du rat.

Immunocytochemical studies on Rat brains using an antiserum against CRF revealed a new hypothalamo-infundibular neuroglandular system: its perikarya are mainly located in the paraventricular nucleus; its nerve endings are very numerous around the blood vessels in all region of the external zone of the median eminence and in the periphery of the pituitary stalk.

[Ontogenesis of pro-opio-melano-cortin neurons in the rat]. / Ontogenèse des neurones à pro-opio-mélano-cortine chez le rat.

Immunocytochemical study of the pro-opio-melano-cortin neurones in rat fetuses and newborns indicates that: 1) they appear precociously in the mediobasal hypothalamus, as early as day 13 of fetal development, that is to say 3 days before pro-opio-melano-cortin-containing pituitary cells; 2) between day 13 and day 17 they display synchronous changes in their intracellular patterns of immunoreactivity, arguing in favour of their cyclic secreting activity, which precedes the establishing of their projections; 3) beginning with day 18 until birth, the somatal immunoreactivity disappears transitorily; during the same period and the first postnatal days, their immunoreactive fibres extend in various brain regions.

[Corticoliberin neurons in the rat brain]. / Les neurones à corticolibérine (CRF) du cerveau de rat.

A new peptidergic paraventriculo-infundibular system has been revealed using anti-corticoliberin (CRF) antibodies. The localization of its perikarya in the paraventricular nuclei as well as the distribution of its fibres and perivascular nerve-endings within the median eminence are different from those of other systems stained with antibodies directed against gonadoliberin, somatostatin, vasopressin or oxytocin.