The Nup84p complex consists of five nucleoporins (Nup84p, Nup85p, Nup120p, Nup145p-C, and Seh1p) and Sec13p, a bona fide subunit of the COPII coat complex. We show that a pool of green fluorescent protein–tagged Sec13p localizes to the nuclear pores in vivo, and identify sec13 mutant alleles that are synthetically lethal with nup85Δ and affect the localization of a green fluorescent protein–Nup49p reporter protein. In the electron microscope, sec13 mutants exhibit structural defects in nuclear pore complex (NPC) and nuclear envelope organization. For the assembly of the complex, Nup85p, Nup120p, and Nup145p-C are essential. A highly purified Nup84p complex was isolated from yeast under native conditions and its molecular mass was determined to be 375 kD by quantitative scanning transmission electron microscopy and analytical ultracentrifugation, consistent with a monomeric complex. Furthermore, the Nup84p complex exhibits a Y-shaped, triskelion-like morphology 25 nm in diameter in the transmission electron microscope. Thus, the Nup84p complex constitutes a paradigm of an NPC structural module with distinct composition, structure, and a role in nuclear mRNA export and NPC bio- genesis.

CEREBRAL blood vessels are innervated by adrenergic nerve fibers from the cervical sympathetic chain.1 -2 The main source of this sympathetic innervation is the superior cervical ganglion, 3 with a small contribution in dogs from the stellate ganglion. 4 Although cerebral vessels are densely innervated, the significance of these sympathetic nerves in regulation of cerebral blood flow (CBF) is controversial.Several previous studies have evaluated the functional significance of sympathetic nerves by examining regulation of cerebral flow after acute 5 -6 or chronic 7 -8 sympathetic denervation. Acute cervical sympathectomy has been reported to increase CBF over a wide range of arterial pressure, 5 particularly at normal and elevated levels of pressure. In contrast, a recent report suggests that acute cervical sympathectomy does not increase CBF at normal levels of arterial pressure but does increase flow during hypotension." Chronic sympathetic denervation has been reported to have no effect on CBF,' 1 " 8 but effectiveness of denervation was not confirmed by demonstrating depletion of vascular catecholamines. It seems reasonable to suggest that previous studies have not resolved the question of the effect of sympathetic denervation on control of CBF. Furthermore, the methods that were used to measure CBF have not allowed examination of the effect of denervation on distribution of blood flow within the brain.In this study, we have examined effects of acute and chronic unilateral sympathetic denervation on total and regional CBF. Labeled microspheres were used to measure CBF. 9 The microsphere technique circumvents the problems created by the presence of multiple vessels to and from the brain and allows measurement of both total and regional CBF. The measurement of regional CBF allowed us to compare distribution of CBF simultaneously in the hemisphere ipsilateral to the sympathetic denervation and in the contralateral "control" hemisphere. We postulated that unilateral acute sympathetic denervation or depletion of cerebral vascular catecholamines might increase CBF to the ipsilateral hemisphere or redistribute CBF in the ipsilateral hemibrain.Several studies were performed to test this hypothesis. Total and regional CBF were measured during control

SUMMARY Disruption of the blood-brain barrier (BBB) daring acutehypertension may contribute to hypertensive encephailopathy. In this study we tested the hypothesis that, in chronic hypertension, vascular changes might influence the susceptibility of the BBB to disruption. Spontaneously hypertensive rats (SHR) and normotensive rats (WKY), 3-4 months of age, were anesthetized and acute hypertension was produced by infusing phenylephrine intravenously (i.v.). Permeability of the BBB was studied with radioactive iodine serum albumin (RISA) injected i.v. The ratio of brain-to-blood RISA was used as an index of permeability of the BBB expressed as protein transfer. In both SHR and WKY at resting arterial pressure, the protein transfer was < 0.10%. In WKY exposed to acute hypertension (mean arterial pressure increased by 87 ± 7 mm Hg), the protein transfer was 2.77 ± 0.60%. In SHR with acute hypertension superimposed on chronic hypertension (arterial pressure increased by 80 ± 7 mm Hg), the protein transfer was 1.16 ± 0.45% (p < 0.05, SHR vs WKY). These data suggest that cerebral vessels are less susceptible to disruption of the BBB by acute hypertension in SHR than in WKY. We speculate that the finding of reduced susceptibility to BBB disruption in chronic hypertension may explain, in part, the apparent susceptibility of previously normotensive patients to acute hypertensive encephalopathy. 1 ' 2 Although most studies have been performed in skeletal muscle beds, recent work suggests that these changes also occur in cerebral vessels. 8 -* The increase in vascular muscle results in an increase in wall-tolumen ratio.5 During constrictor stimuli, hypertrophied vessels constrict more than normal vessels."The physiological significance of structural changes may not be the same in all vascular beds. Folkow and others* 1T attribute, in part, the maintenance of hypertension to these structural alterations. In this

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The purpose of this study was to determine the effect of activation of sympathetic pathways during seizures on cerebral blood flow and integrity of the blood-brain barrier. We measured cerebral blood flow with microspheres and disruption of the blood-brain barrier with labeled albumin in cats. One cerebral hemisphere was denervated by cutting the superior cervical sympathetic trunk on one side. During bicuculline-induced seizures, superior cervical sympathetic nerve activity increased about threefold. Blood flow to the innervated hemibrain was significantly lower than flow to denervated hemibrain. However, in relation to the total increase in flow, this effect of nerves was minor. Blood-brain barrier permeability increased about sixfold during seizures, but there was no difference between the innervated and denervated sides of the brain. We conclude that sympathetic nerves attenuate the increase in cerebral blood flow during seizures, despite the increase in metabolism, but this effect is small. Activation of sympathetic nerves does not reduce disruption of the blood-brain barrier during seizures.