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INTRODUCTIONSince Riva-Rocci invented indirect brachial cuff sphygmomanometry in 1896 1 and Korotkoff proposed the auscultatory method in 1905, 2 the method for blood pressure (BP) measurements has remained essentially unchanged for the past 100 years.In 1969, Posey et al. 3 identified mean BP on the basis of the cuff-oscillometric method. With subsequent theoretical and technical improvements, the method to determine systolic and diastolic BP (S and D, respectively) was introduced to the cuff-oscillometric method. As a result, many of the automatic electronic sphygmomanometers available today have adopted this method, and those different from the auscultatory method have begun to be used in general clinical practice. Since the advent of indirect methods for sphygmomanometry, the past century has developed the practical and clinical sciences of hypertension. However, BP information necessary for the diagnosis and treatment of hypertension is still obtained essentially on the basis of casual measurements at the outpatient clinic (clinic BP). However, the reliability of clinic BP was called into question 40 years after the advent of indirect sphygmomanometry. In 1940, Ayman and Goldshine 4 widely adopted the concept of self-BP measurements in the field of clinic BP measurements and demonstrated discrepancies between clinic BP and self-BP measurements. Bevan, 5 in the United Kingdom, first reported the results of ambulatory BP (ABP) monitoring (ABPM) using a direct arterial BP measurement method in 1969, and showed that human BP changes markedly with time. The quantity and quality of BP information vary greatly according to different methods, and the problem of interpreting clinic BP, which is obtained specifically in a medical environment, has been an issue in the clinical practice of hypertension during the past 50 years.However, the practice and epidemiology of hypertension still depend entirely on BP information obtained in a medical environment (clinic BP/BP at a health examination), resulting in the

Inflammatory responses in the kidney lead to tubulointerstitial fibrosis, a common feature of chronic kidney diseases. Here we examined the role of prostaglandin E(2) (PGE(2)) in the development of tubulointerstitial fibrosis. In the kidneys of wild-type mice, unilateral ureteral obstruction leads to progressive tubulointerstitial fibrosis with macrophage infiltration and myofibroblast proliferation. This was accompanied by an upregulation of COX-2 and PGE(2) receptor subtype EP(4) mRNAs. In the kidneys of EP(4) gene knockout mice, however, obstruction-induced histological alterations were significantly augmented. In contrast, an EP(4)-specific agonist significantly attenuated these alterations in the kidneys of wild-type mice. The mRNAs for macrophage chemokines and profibrotic growth factors were upregulated in the kidneys of wild-type mice after ureteral obstruction. This was significantly augmented in the kidneys of EP(4)-knockout mice and suppressed by the EP(4) agonist but only in the kidneys of wild-type mice. Notably, COX-2 and MCP-1 proteins, as well as EP(4) mRNA, were localized in renal tubular epithelial cells after ureteral obstruction. In cultured renal fibroblasts, another EP(4)-specific agonist significantly inhibited PDGF-induced proliferation and profibrotic connective tissue growth factor production. Hence, an endogenous PGE(2)-EP(4) system in the tubular epithelium limits the development of tubulointerstitial fibrosis by suppressing inflammatory responses.

Both the appearance of cytoplasmic inclusions containing phosphorylated TAR DNA-binding protein (TDP-43) and inefficient RNA editing at the GluR2 Q/R site are molecular abnormalities observed specifically in motor neurons of patients with sporadic amyotrophic lateral sclerosis (ALS). The purpose of this study is to determine whether a link exists between these two specific molecular changes in ALS spinal motor neurons. We immunohistochemically examined the expression of adenosine deaminase acting on RNA 2 (ADAR2), the enzyme that specifically catalyzes GluR2 Q/R site-editing, and the expression of phosphorylated and non-phosphorylated TDP-43 in the spinal motor neurons of patients with sporadic ALS. We found that all motor neurons were ADAR2-positive in the control cases, whereas more than half of them were ADAR2-negative in the ALS cases. All ADAR2-negative neurons had cytoplasmic inclusions that were immunoreactive to phosphorylated TDP-43, but lacked non-phosphorylated TDP-43 in the nucleus. Our results suggest a molecular link between reduced ADAR2 activity and TDP-43 pathology.

The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies.