It is known that autonomic nervous activities change in correspondence with sleep stages. However, the characteristics of continuous fluctuations in nocturnal autonomic nerve tone have not been clarified in detail. The study aimed to determine the possible correlation between the electroencephalogram (EEG) and autonomic nervous activities, and to clarify in detail the nocturnal fluctuations in autonomic nerve activities. Overnight EEGs and electrocardiograms of seven healthy males were obtained. These EEGs were analyzed by fast Fourier transformation algorithm to extract delta, sigma and beta power. Heart rate and heart rate variability (HRV) were calculated in consecutive 5-min epochs. The HRV indices of low frequency (LF), high frequency (HF) and LF/HF ratio were calculated from the spectral analysis of R-R intervals. The sleep stages were manually scored according to Rechtschaffen and Kales' criteria. Low frequency and LF/HF were significantly lower during non-rapid eye movement (NREM) than REM, and were lower in stages 3 and 4 than in stages 1 and 2. Furthermore, delta EEG showed inverse correlations with LF ( r = -0.44, P < 0.001) and LF/HF ( r = -0.41, P < 0.001). In contrast, HF differed neither between REM and NREM nor among NREM sleep stages. Detailed analysis revealed that correlation was evident from the first to third NREM, but not in the fourth and fifth NREM. Delta EEG power showed negative correlations with LF and LF/HF, suggesting that sympathetic nervous activities continuously fluctuate in accordance with sleep deepening and lightening.

The IFI system enables on-site assessment of graft patency, providing both morphologic and functional information. This technique may help reduce procedure-related, early graft failures in off-pump bypass patients.

Variants in TGFBR1 have been reported to induce two completely distinct diseases, namely Loeys-Dietz syndrome (LDS) and multiple self-healing squamous epithelioma (MSSE). However, detailed mechanisms underlying this effect remain unknown. We report a Japanese familial case of LDS with a novel splice donor site variant in TGFBR1 gene (c.973 + 1 G > A; NG_007461.1). The intronic variant was predicted to mediate in-frame exon 5 skipping within the serine/threonine kinase (STK) domain, which may also be mediated by a similar TGFBR1 variant of a splice acceptor site in intron 4 (c.806-2 A > C), identified in a British familial case of MSSE. Therefore, ex vivo splicing and functional assays were performed in mammalian cells to evaluate the effect of these sequence variants. The MSSE variant activated a cryptic acceptor site at 76 bp downstream of the 3' natural splice acceptor site, which produced an out-of-frame transcript (r.807_882del, p.Asn270Thrfs*8). In contrast, the LDS variant generated two types of in-frame transcription products, r.[806_973del, 965_973 del], and produced two functionally inactivated proteins, p.[Asp269_Gln324del, Thr323_Gly325del], as a result of exon 5 skipping and the activation of a cryptic donor splice site at 9 bp upstream of the 5' natural splice donor site, respectively. Our results support the previously proposed but not yet approved mechanism that dominant-negative and truncating variants in STK domain induce LDS and MSSE, respectively.

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Objective-N-(3Ј4Ј-dimethoxycinnamoyl)-anthranilic acid (tranilast) is a drug that has been shown to reduce the incidence of restenosis after angioplasty in middle-scale clinical trials. Despite clinical interest in this drug, the pharmacological actions of tranilast remain relatively unexplored at a molecular level. Methods and Results-We evaluated the effects of tranilast on vascular smooth muscle cell (VSMC) proliferation in wild-type mice and in mice lacking a cyclin-dependent kinase inhibitor, p21 WAF1 (p21). Tranilast potently inhibited the proliferation of VSMC cultures derived from wild-type mice, but VSMCs derived from p21-deficient (p21Ϫ/Ϫ) mice were unaffected by this treatment. In a mouse femoral artery model of vascular injury, tranilast administration to wild-type mice led to an upregulation of p21 expression and a decrease in the number of proliferating VSMCs, as determined by immunostaining for proliferating cell nuclear antigen. In contrast, tranilast had no effect on the number of proliferating cell nuclear antigen-positive cells in the injured arteries of p21Ϫ/Ϫ mice. Administration of tranilast significantly reduced the neointimal VSMC hyperplasia in wild-type mice at 4 weeks but had no effect on lesion formation in p21Ϫ/Ϫ mice. Conclusions-Our findings provide genetic evidence that tranilast inhibits intimal hyperplasia via a p21-dependent pathway, an activity that may contribute to its efficacy in the prophylactic treatment of postangioplasty restenosis. Key Words: pharmacology Ⅲ genetically altered mice Ⅲ smooth muscle cells Ⅲ restenosis Ⅲ proliferation P ercutaneous transluminal angioplasty has been widely adopted as a treatment of atherosclerosis. However, in a significant number of cases, the procedure fails because of postangioplasty restenosis. 1 Although the increasing use of new devices to dilate stenosed arteries has lowered the incidence of acute complications, restenosis still limits the long-term outcome of percutaneous interventions. 2 Although much effort has been devoted to the development of strategies to prevent postangioplasty restenosis, 3 as yet, no pharmacological treatment has been approved to reduce postangioplasty restenosis.N-(3Ј4Ј-Dimethoxycinnamoyl)-anthranilic acid (tranilast) is a drug that may be effective in preventing angiographic restenosis after percutaneous transluminal coronary revascularization, inasmuch as the results of middle-scale, randomized, double-blind, placebo-controlled trials have shown that oral administration of tranilast significantly lowers the incidence of restenosis after conventional balloon angioplasty, 4 directional coronary atherectomy, 5 and coronary stenting. 6 A multicenter, phase-3, double-blind, placebo-controlled trial is currently under way to evaluate the effects of tranilast on clinical, angiographic, and intravascular ultrasound findings of restenosis. 7 Despite the clinical interest in this drug, the pharmacological actions of tranilast remain relatively unexplored, particularly regarding its action in the vasculature. It h...

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A review of admission records identified 194 episodes of infective endocarditis (IE) from January 1980 to December 1999 at a community hospital in Tokyo. The cases were divided into decades, and the clinical picture and short-term outcomes were compared and analyzed. The mean age of patients in the 1990s was older (45.5 +/-13.2 vs 55.1+/-12.6 years, p<0.001), and prosthetic valve endocarditis was significantly more frequently seen (14.4% vs 31.8%, p=0.004). None had a history of intravenous drug abuse (IVDA). Patients on chronic hemodialysis comprised 5.8% of IE cases in the 90s. Overall, dental procedure or caries still remained the main presumed source of infection. Staphylococcal IE showed a tendency to increase, and methicillin-resistant staphylococcal IE was significantly prominent in the 90s (0% vs 10.4%, p=0.0006). The overall in-hospital mortality was similar between the 2 groups (13.6% vs 18.8%, NS). Multivariate analysis found neurological abnormality, renal insufficiency and staphylococcal IE as predictors of in-hospital mortality. The characteristics of IE in Japan have changed, even among non-IVDA patients, and it appears to occur in a more high-risk patient population, which may warrant a more aggressive therapeutic approach to its management and treatment.