Annals of the New York Academy of Sciences
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The somatic marker hypothesis proposes that both the amygdala and the orbitofrontal cortex are parts of a neural circuit critical for judgment and decision-making. Although both structures couple exteroceptive sensory information with interoceptive information concerning somatic/emotional states, they do so at different levels, thus making different contributions to the process. We define "primary inducers" as stimuli that unconditionally, or through learning (e.g., conditioning and semantic knowledge), can (perceptually or subliminally) produce states that are pleasurable or aversive. ⋯ However, once this orbitofrontal system is developed, the induction of somatic states by secondary inducers via the orbitofrontal system is less dependent on the amygdala system. Perhaps the amygdala is equivalent to the hippocampus with regard to emotions, that is, necessary for acquiring new emotional attributes (anterograde emotions), but not for retrieving old emotional attributes (retrograde emotions). Given the numerous lesion and functional neuroimaging studies illustrating the involvement of the amygdala in complex cognitive and behavioral functions, including "social cognition," we suggest that this involvement is a manifestation of a more fundamental function mediated by the amygdala, which is to couple stimuli/entities with their emotional attributes, that is, the processing of somatic states from primary inducers.
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Ann. N. Y. Acad. Sci. · Dec 2002
Vestibularly evoked climbing-fiber responses modulate simple spikes in rabbit cerebellar Purkinje neurons.
The nodulus receives a primary vestibular afferent input from the ipsilateral labyrinth and a vestibularly related climbing-fiber input originating from the contralateral labyrinth. Previously we demonstrated that increased discharge of vestibularly evoked climbing-fiber responses (CFRs) in nodular Purkinje cells was correlated with decreased discharge of simple spikes (SSs). This left unresolved the question of whether vestibularly evoked antiphasic behavior of CFRs and SSs reflects a common neural mechanism or the activation of two separate parallel pathways. ⋯ SSs continued to respond to contralateral roll-tilt even when the primary vestibular afferent mossy-fiber pathway was destroyed by the unilateral labyrinthectomy. Although the discharge of SSs recorded in the contralateral uvula-nodulus was increased by contralateral roll-tilt, this modulation was reduced relative to that observed in Purkinje cells recorded in the ipsilateral uvula-nodulus. We conclude that vestibularly evoked CFRs caused the modulation of SS discharge.
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Ann. N. Y. Acad. Sci. · Sep 2002
ReviewNew insights into the genetics of familial chromaffin cell tumors.
We review genetic aspects and recent advances in our understanding of the molecular pathogenesis of familial chromaffin cell tumors (pheochromocytoma, paraganglioma). About 10 percent of pheochromocytomas are familial and occur as part of multiple endocrine neoplasia type 2 (MEN 2), von Hippel-Lindau (VHL) disease, and neurofibromatosis type 1 (NF 1). A subset of paragangliomas, tumors that can also produce and secrete catecholamines, are also familial and occur in patients with germline mutations in genes that encode subunits of the mitochondrial complex II. ⋯ Tumorigenesis of NF1-associated pheochromocytomas remains unknown, as does tumor formation (i.e., carotid body tumor) in patients with germline mutations in SDHB, SDHC, and SDHD, genes that encode subunits of the mitochondrial complex II, the smallest complex in the respiratory chain. Many genetic alterations have been found in sporadic chromaffin cell tumors. However, at present such genetic changes are difficult to place into context with regard to tumor formation and progression.
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Ann. N. Y. Acad. Sci. · Sep 2002
ReviewAssociation of hypertension and hypokalemia with Cushing's syndrome caused by ectopic ACTH secretion: a series of 58 cases.
Cushing's syndrome is associated with hypertension in approximately 80% of cases. Hypertension contributes to the marked increased mortality risk of past or current Cushing's syndrome, largely because of increased cardiovascular risk. Observation of the pathophysiological effect of chronically elevated ACTH and cortisol values in patients with ectopic ACTH secretion complements the available data from acute studies of the effects of ACTH and glucocorticoid infusions in normal volunteers. ⋯ In addition, we did not find blood pressure severity to be related to UC excretion or ACTH levels. Urine and plasma cortisol and cortisol metabolite measurements suggest that cortisol may act as a mineralocorticoid when in excess, perhaps by saturating the 11beta-hydroxysteroid-dehydrogenase (11beta-HSD2 enzyme) that inactivates cortisol at the renal tubule. The current data suggest that high cortisol levels may be the principal cause of hypokalemic alkalosis in Cushing's syndrome, rather than inhibition of the 11betaHSD2 enzyme by ACTH or the effects of adrenal steroid biosynthetic intermediaries with mineralococorticoid activity.
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A chronic minor imbalance between energy intake and energy expenditure may lead to obesity. Both lean and obese subjects eventually reach energy balance and their body weight regulation implies that the adipose tissue mass is "sensed", leading to appropriate responses of energy intake and energy expenditure. The cloning of the ob gene and the identification of its encoded protein, leptin, have provided a system signaling the amount of adipose energy stores to the brain. ⋯ Conversely, it is unlikely that leptin has evolved to prevent obesity when plenty of palatable foods are available because the elevated plasma leptin levels resulting from the increased adipose tissue mass do not prevent the development of obesity. In conclusion, in humans, the leptin signaling system appears to be mainly involved in maintenance of adequate energy stores for survival during periods of energy deficit. Its role in the etiology of human obesity is only demonstrated in the very rare situations of absence of the leptin signal (mutations of the leptin gene or of the leptin receptor gene), which produces an internal perception of starvation and results in a chronic stimulation of excessive food intake.