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A natural history of melanomas and dysplastic nevi: an atlas of lesions in melanoma-prone families.

BACKGROUND: Few long-term clinical and histologic data for melanocytic lesions have been available based on the mutation status of families at an increased risk of melanoma. In the current study, the authors describe the clinical and histologic features of dysplastic nevi and melanoma over time in families at an increased risk of melanoma with differing germline mutations in CDKN2A, CDK4, or not yet identified genes. METHODS: Thirty-three families with > 2 living members with invasive melanoma were evaluated clinically and followed prospectively for up to 25 years. All the participants were evaluated by the same study team at the Clinical Center of the National Institutes of Health or in local clinics. After informed consent was obtained, family members (n = 844) were examined and photographed. Blood was obtained for genetic studies; genotyping for CDKN2A and CDK4 was performed. Sequential photographs of melanocytic lesions were taken as part of the clinical evaluations. When melanocytic lesions were removed, the histology was reviewed. Representative photographs and photomicrographs were selected for six classes of lesions and three mutation groups. RESULTS: All the families were found to have members with dysplastic nevi and melanoma; 17 had mutations in CDKN2A, 2 had mutations in CDK4, and 14 had no mutations in either gene identified. The majority of dysplastic nevi either remain stable or regress; few change in a manner that should cause concern for melanoma. With careful surveillance, melanomas can be found early. CONCLUSIONS: The melanomas and dysplastic nevi that were found to occur in the study families did not appear to vary by the type of mutation identified in the families.

Cyclin-Dependent Kinase 4↗

A three-dimensional atlas of pituitary gland development in the zebrafish.

The pituitary gland is unique to Chordates, with significant variation within this group, offering an excellent opportunity to increase insight into phylogenetic relationships within this phylum. The structure of the pituitary in adult Teleosts (class: Osteichthyes) is quite different from that in other chordates and is also variable among members of the class. Therefore, a complete description of the structure and development of the pituitary in members of this class is a critical component to our overall understanding of this gland. An obvious teleost model organism is the zebrafish, Danio rerio, as a significant amount of work has been done on the molecular control of pituitary development in this fish. However, very little work has been published on the morphological development of the pituitary in the zebrafish; the present study aims to fill this void. The pituitary develops from cells on the rostrodorsal portion of the head and reaches its final position, ventral to the hypothalamus, as the cephalic flexure occurs and the jaws and mouth form. The pituitary placode is juxtaposed to cells that will form the olfactory vesicles, the stomodeum, and the hatching gland. The volume of the pituitary is greatest at 24 hours post fertilization (hpf). From 24 to 120 hpf, the pituitary decreases in height and width as it undergoes convergent extension, increasing in length with the axis. The adenohypophysis is a morphologically distinct structure by 24 hpf, whereas the neurohypophysis remains indistinct until 72 hpf. The findings of this study correlate well with the available molecular data.

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Atlas of the distribution of monoamine-containing nerve cell bodies in the brain stem of the cat.

The distribution and morphological characteristics of monoamine (MA)-containing neuronal somata in the brain stem of kittens and of adult cats were studied by means of the Falck-Hillarp histofluorescence method. This investigation has shown, among other things, that in the midbrain of the cat the catecholamine (CA) perikarya are chiefly confined to the pars compacta of the substantia nigra, the ventromedial tegmental area, the nucleus linearis rostralis and the nucleus parabrachialis pigmentosus. Numerous CA neurons are also present in the dorsolateral part of the pontine tegmentum but also within the nucleus subcoeruleus, in nuclei lemnisci lateralis dorsalis and in nuclei parabrachialis lateralis and medialis. In the medulla, a few CA neuronal somata are lying near the hypoglossal nucleus whereas a larger number of CA cell bodies occur at the level of nucleus reticularis lateralis and in nucleus paragigantocellularis lateralis. On the other hand, most of the serotonin (5-HT) perikarya are confined to the raphe nuclei of the brain stem: nuclei raphe dorsalis, centralis superior, raphe pontis, raphe magnus, raphe pallidus and raphe obscurus. Some 5-HT neuronal somata are also found lateral to the pyramidal tract and to the inferior olivary complex. The various similarities and differences in respect to the pattern of the topographical distribution of MA neurons in the brain stem of the cat as compared to that of other mammals are discussed.

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Topographic atlas of somatostatin-containing neurons system in the avian brain in relation to catecholamine-containing neurons system. I. Telencephalon and diencephalon.

The morphological organization of the somatostatin (SRIF)-positive neurons in the forebrain (telencephalon and diencephalon) of the warbling grass parakeet (Melopsittacus undulatus) was studied using the indirect immunohistochemical technique of Coons and co-workers ('58). In the telencephalon, a number of SRIF-positive neurons was detected in the lobus paraolfactorius, hippocampus, and paleostriatum. Furthermore, scattered SRIF-labeled cells were noticed in the area corticoidea dorsolateralis and area temporoparieto-occipitalis. A moderate density of immunoreactive fibers was found in the above areas. In addition, although the septal areas was devoid of SRIF-positive neurons, this area contained a moderate occurred in the following hypothalamic areas: (1) nucleus medialis hypothalami posterior, (2) lateral hypothalamus, and (3) mammillary nucleus. The bird hypothalamus also received a strikingly massive SRIF innervation. The heaviest concentration of SRIF-labeled fibers was detected in the medial eminence. Many SRIF-labeled fibers were also observed in other hypothalamic regions. Their locations roughly corresponded in many cases to the areas in which SRIF-positive neurons were disclosed. The overall distribution of the catecholamine system (CA) of the avian forebrain is also represented by means of histofluorescent technique. A possible interaction between SRIF and CA neurons systems is briefly discussed.

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Topographic atlas of somatostatin-containing neuron system in the avian brain in relation to catecholamine-containing neuron system. II. Mesencephalon, rhombencephalon, and spinal cord.

With the indirect immunofluorescence technique of Coon's and collaborators, overall distribution of the somatostatin (SRIF)-positive neurons system in the avian lower brain stem was explored. Numerous cell somata containing SRIF were identified in the interpeduncular nucleus and substantia grisea centralis (GCT) at the level of the nucleus nervi trochlearis. Furthermore, a moderate number of SRIF-positive neurons were seen in the tectum opticum, nucleus tractus solitarii, and spinal cord. Scattered labeled cells were noticed in the rhombencephalon. A dense network of SRIF-positive fibers was distributed widely in the lower brain stem of birds. Their locations corresponded in many cases to the areas where SRIF-positive neurons were found. The present study also presents the distribution of the catecholamine (CA) neuron system in the avian lower brain stem. Possible interactions between SRIF and CA neurons systems are briefly discussed.

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Atlas of catecholamine perikarya, varicosities and pathways in the brainstem of the cat.

By application of a modified glyoxylic acid--paraformaldehyde histofluorescence technique, catecholamine perikarya, varicosities, and pathways were delineated within the brainstem of kittens that were either untreated, pretreated pharmacologically, or injected intracerebrally with 6-OHDA. Three principle catecholamine cell groups were identified within the medulla and pons; the dorsomedial medullary cell group, the dorsolateral pontine cell group, and a ventrolateral cell group extending from the medulla into the pons. Induced axonal accumulation of catecholamines with intracerebral 6-OHDA injections revealed a major longitudinal catecholamine bundle which courses in a dorsolateral position through the entire brainstem tegmentum. The dorsomedial medullary and dorsolateral pontine cell groups contribute ascending and descending fibers to this bundle. Axons of the ventrolateral pontomedullary cells also feed into the bundle at successive levels through radially coursing transverse fibers. Via this major dorsolateral conduit and its ventrally and medially coursing tributaries, catecholamine fibers and terminals are distributed to multiple nuclei through the brainstem. The regions of the catecholamine cell groups and the serotonin raphe nuclei all receive a dense catecholamine innervation. Varicosities are also dense in the visceral cranial nerve nuclei, moderately dense in most somatic spinal and cranial nerve motor nuclei, and moderate to light in sensory cranial nerve and relay nuclei. The lateral and ventromedial reticular formation are moderately innervated by varicose catecholamine fibers that traverse these regions. The longitudinal catecholamine bundle continues caudally into the lateral funiculus to descend into and innervate the spinal cord. Rostrally it continues into the tegmental fascicles of the midbrain to ascend into and innervate the diencephalon and there join the medial forebrain bundle to ascend into the telencephalon. Thus, the catecholamine neurons utilize this dorsolateral longitudinal bundle to distribute collaterals to multiple bulbar nuclei and to travel beyond the brainstem to innervate the spinal cord and forebrain.

Animals↗

An atlas of aromatase mRNA expression in the zebra finch brain.

Neural conversion of androgen to estrogen by aromatase is an important step in the development and expression of masculine behavior in mammals and birds. In contrast to the low telencephalic levels of aromatase in adult mammals and nonsongbirds, the zebra finch telencephalon possesses high aromatase activity. This study maps, by in situ hybridization, cells that express aromatase mRNA in the adult zebra finch telencephalon, diencephalon, midbrain, and pons. High aromatase mRNA expression was observed in the caudal neostriatum, limbic archistriatum, and hypothalamus. The hippocampus, parahippocampal area, and hyperstriatum accessorium contained cells expressing moderate amounts of aromatase message. Weakly labeled cells were found in the rostral neostriatum, lobus parolfactorius, and mesencephalic reticular formation. These findings are consistent with aromatase activity measurements of zebra finch tissue and document with anatomical precision both the widespread expression of aromatase mRNA in the brain and novel sites of brain aromatase. This study identifies the caudal neostriatum as a major site of telencephalic aromatase. A previous survey (Gahr et al., 1993: J. Comp. Neurol. 327:112-122) of several avian species found that the presence of estrogen receptors in parts of the caudal neostriatum is unique to songbirds, which are the only birds to possess the elaborated telencephalic song system. Together, these findings suggest that the heightened estrogen synthesis and estrogen sensitivity of the passerine caudal neostriatum may have some functional relation with the telencephalic circuits responsible for song.

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