Abstract-The objective of this study was to elucidate the long-term prognostic significance of ambulatory blood pressure.Ambulatory and casual blood pressure values were obtained from 1332 subjects (872 women and 460 men) aged Ն40 years from the general population of a rural Japanese community. Survival was then followed for 14 370 patient years and analyzed by a Cox hazard model adjusted for possible confounding factors. There were 72 cardiovascular deaths during the 10.8-year follow-up. The relationship between 24-hour systolic blood pressure and the cardiovascular mortality risk was U-shaped in the first 5 years, then changed to J-shaped over the rest of the 10.8-year follow-up. After censoring the first 2 years of data, the risk flattened until it again increased for the fifth quintile of 24-hour systolic blood pressure for the 10.8-year follow-up period. For 24-hour diastolic blood pressure, the J-shaped relationship remained unchanged, regardless of follow-up duration and censoring. Ambulatory systolic blood pressure values consistently showed stronger predictive power for cardiovascular mortality risk than did casual systolic blood pressure in the 10.8-year follow-up data, whereas such relationships became more marked after censoring the first 2 years. When nighttime and daytime systolic blood pressure values were simultaneously included in the same Cox model, only nighttime blood pressure significantly predicted the cardiovascular mortality risk for the 10.8-year follow-up data. We conclude that the relationship between ambulatory systolic blood pressure and cardiovascular mortality is not U-shaped or J-shaped, and that nighttime blood pressure has better prognostic value than daytime blood pressure. Key Words: blood pressure monitoring, ambulatory Ⅲ cardiovascular diseases Ⅲ prospective studies A mbulatory blood pressure (BP) has been used widely to diagnose and evaluate hypertension and to monitor treatment in the clinical setting. 1,2 Moreover, ambulatory BP is known to provide more reproducible information than does casual BP for individual patients with hypertension, 3,4 and is more strongly correlated with target-organ damage than casual BP in hypertensive subjects. Furthermore, the international guidelines for hypertension have emphasized the usefulness of ambulatory BP. 5,6 However, in contrast to the plethora of evidence about casual BP, there is still a lack of data that address the long-term prognostic significance of ambulatory BP. Few longitudinal studies, after Ն10 years, have so far examined the relationship between 24-hour BP and prognosis. Since 1987, we have been conducting a prospective cohort study to investigate the relationship between ambulatory BP and survival in the general population of Ohasama, Japan (the Ohasama Study). [7][8][9] In a previous report, we presented the results from a 5.1-year follow-up period. 8 The objective of the present study was to determine the prognostic significance of ambulatory BP for cardiovascular mortality risk based on a longer follow-up period, o...

By DNA cloning, we have identified the BSRP (brainspecific receptor-like proteins) family of three members in mammalian genomes. BSRPs were predominantly expressed in the soma and dendrites of neurons and localized in the endoplasmic reticulum (ER). Expression levels of BSRPs seemed to fluctuate greatly during postnatal cerebellar maturation. Triple-knockout mice lacking BSRP members exhibited motor discoordination, and Purkinje cells (PCs) were often innervated by multiple climbing fibers with different neuronal origins in the mutant cerebellum. Moreover, the phosphorylation levels of protein kinase Ca (PKCa) were significantly downregulated in the mutant cerebellum. Because cerebellar maturation and plasticity require metabotropic glutamate receptor signaling and resulting PKC activation, BSRPs are likely involved in ER functions supporting PKCa activation in PCs.

Abstract. We extend Kobayashi and Sumii's type system for the deadlock-free π-calculus and develop a type reconstruction algorithm. Kobayashi and Sumii's type system helps high-level reasoning about concurrent programs by guaranteeing that communication on certain channels will eventually succeed. It can ensure, for example, that a process implementing a function really behaves like a function. However, because it lacked a type reconstruction algorithm and required rather complicated type annotations, applying it to real concurrent languages was impractical. We have therefore developed a type reconstruction algorithm for an extension of the type system. The key novelties that made it possible are generalization of usages (which specifies how each communication channel is used) and a subusage relation.

Junctional membrane complexes (JMCs) composed of the plasma membrane and endoplasmic͞sarcoplasmic reticulum seem to be a structural platform for channel crosstalk. Junctophilins (JPs) contribute to JMC formation by spanning the sarcoplasmic reticulum membrane and binding with the plasma membrane in muscle cells. In this article, we report that mutant JP double-knockout (JP-DKO) mice lacking neural JP subtypes exhibited an irregular hindlimb reflex and impaired memory. Electrophysiological experiments indicated that the activation of small-conductance Ca 2؉ -activated K ؉ channels responsible for afterhyperpolarization in hippocampal neurons requires endoplasmic reticulum Ca 2؉ release through ryanodine receptors, triggered by NMDA receptor-mediated Ca 2؉ influx. We propose that in JP-DKO neurons lacking afterhyperpolarization, the functional communications between NMDA receptors, ryanodine receptors, and small-conductance Ca 2؉ -activated K ؉ channels are disconnected because of JMC disassembly. Moreover, JP-DKO neurons showed an impaired long-term potentiation and hyperactivation of Ca 2؉ ͞calmodulin-dependent protein kinase II. Therefore, JPs seem to have an essential role in neural excitability fundamental to plasticity and integrated functions.hippocampus ͉ learning and memory ͉ long-term potentiation ͉ ryanodine receptor ͉ SK channel F unctional communication between cell-surface and intracellular channels is an essential feature of excitable cells (1). During initiation of contraction in striated muscle cells, the activation of cell-surface dihydropyridine receptor (DHPRs) channels opens ryanodine receptors (RyRs) and triggers Ca 2ϩ release from the sarcoplasmic reticulum via either the ''Ca 2ϩ -induced Ca 2ϩ release'' or the ''voltage-induced Ca 2ϩ release'' mechanism (2). The functional couplings between the channels take place in junctional membrane complexes (JMCs), designated as the ''triad junction'' in skeletal muscle, ''diad'' in cardiac muscle, and ''peripheral coupling'' in immature striated and smooth muscles (3, 4). Recent studies indicated that junctophilin (JP) subtypes, namely JP-1-JP-4, contribute to JMC formation in muscle cells (5, 6). In JP-1 knockout mice with perinatal lethality, mutant skeletal muscle shows deficiency of triad junctions and insufficient contraction probably caused by impaired communication between DHPRs and RyRs (7). In JP-2 knockout embryos showing cardiac arrest, mutant cardiac myocytes exhibit deficiency of peripheral couplings and arrhythmic Ca 2ϩ signaling probably caused by functional uncoupling between DHPRs and RyRs (5). In the brain, both JP-3 and JP-4 are expressed in similar discrete neuronal sites and may collaboratively contribute to JMC formation (8, 9). However, the role of neural JP subtypes is largely unknown. Using knockout mice lacking both JP-3 and JP-4 (JP-DKO mice), we report their essential contributions to the tuning of excitability and plasticity in hippocampal pyramidal neurons. ResultsGeneration of JP-DKO Mice Bearing Lethality. JP-4 knockou...