Our aim is to determine the optimal time schedule for home blood pressure (BP) monitoring that best predicts stroke and coronary artery disease in general practice. The Japan Morning Surge-Home Blood Pressure (J-HOP) study is a nationwide practice-based study that included 4310 Japanese with a history of or risk factors for cardiovascular disease, or both (mean age, 65 years; 79% used antihypertensive medication). Home BP measures were taken twice daily (morning and evening) over 14 days at baseline. During a mean follow-up of 4 years (16 929 person-years), 74 stroke and 77 coronary artery disease events occurred. Morning systolic BP (SBP) improved the discrimination of incident stroke ( C statistics, 0.802; 95% confidence interval, 0.692–0.911) beyond traditional risk factors including office SBP (0.756; 0.646–0.866), whereas the changes were smaller with evening SBP (0.764; 0.653–0.874). The addition of evening SBP to the model (including traditional risk factors plus morning SBP) significantly reduced the discrimination of incident stroke ( C statistics difference, −0.008; 95% confidence interval: −0.015 to −0.008; P =0.03). The category-free net reclassification improvement (0.3606; 95% confidence interval, 0.1317–0.5896), absolute integrated discrimination improvement (0.015; SE, 0.005), and relative integrated discrimination improvement (58.3%; all P <0.01) with the addition of morning SBP to the model (including traditional risk factors) were greater than those with evening SBP and with combined morning and evening SBP. Neither morning nor evening SBP improved coronary artery disease risk prediction. Morning home SBP itself should be evaluated to ensure best stroke prediction in clinical practice, at least in Japan. This should be confirmed in the different ethnic groups. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr/ . Unique identifier: UMIN000000894.

No abstract

To study whether sleep blood pressure (BP) self‐measured at home is associated with organ damage, the authors analyzed the data of 2562 participants in the J‐HOP study who self‐measured sleep BP using a home BP monitoring (HBPM) device, three times during sleep (2 am, 3 am, 4 am), as well as the home morning and evening BPs. The mean sleep home systolic BPs (SBPs) were all correlated with urinary albumin/creatinine ratio (UACR), left ventricular mass index (LVMI), brachial‐ankle pulse wave velocity (baPWV), maximum carotid intima‐media thickness, and plasma N‐terminal pro‐hormone pro–brain‐type natriuretic peptide (NTproBNP) (all P<.001). After controlling for clinic SBP and home morning and evening SBPs, associations of home sleep SBP with UACR, LVMI, and baPWV remained significant (all P<.008). Even in patients with home morning BP <135/85 mm Hg, 27% exhibited masked nocturnal hypertension with home sleep SBP ≥120 mm Hg and had higher UACR and NTproBNP. Masked nocturnal hypertension, which is associated with advanced organ damage, remains unrecognized by conventional HBPM.

Morning BP and evening BP provide equally useful information for subclinical target organ damage, yet multivariate modeling highlighted the stand-alone predictive ability of morning BP.

We previously demonstrated that a loosely restricted 45%-carbohydrate diet led to greater reduction in hemoglobin A1c (HbA1c) compared to high-carbohydrate diets in outpatients with mild type 2 diabetes (mean HbA1c level: 7.4%) over 2 years. To determine whether good glycemic control can be achieved with a 30%-carbohydrate diet in severe type 2 diabetes, 33 outpatients (15 males, 18 females, mean age: 59 yrs) with HbA1c levels of 9.0% or above were instructed to follow a low-carbohydrate diet (1852 kcal; %CHO:fat:protein = 30:44:20) for 6 months in an outpatient clinic and were followed to assess their HbA1c levels, body mass index and doses of antidiabetic drugs. HbA1c levels decreased sharply from a baseline of 10.9 ± 1.6% to 7.8 ± 1.5% at 3 months and to 7.4 ± 1.4% at 6 months. Body mass index decreased slightly from baseline (23.8 ± 3.3) to 6 months (23.5 ± 3.4). Only two patients dropped out. No adverse effects were observed except for mild constipation. The number of patients on sulfonylureas decreased from 7 at baseline to 2 at 6 months. No patient required inpatient care or insulin therapy. In summary, the 30%-carbohydrate diet over 6 months led to a remarkable reduction in HbA1c levels, even among outpatients with severe type 2 diabetes, without any insulin therapy, hospital care or increase in sulfonylureas. The effectiveness of the diet may be comparable to that of insulin therapy.

When the concentrations of alpha-S100 (alpha subunit of S100 protein) and beta-S100 (beta subunit) proteins in various tissues of human and rat were determined by the immunoassay method, immunoreactive beta-S100 was present at high levels in the CNS, adipose tissue, and cartilaginous tissue. In contrast, the alpha-S100 was found in the heart and skeletal muscles at concentrations much higher than in the CNS. The concentration of alpha-S100 protein was also high in the heart and skeletal muscles of bovine, porcine, canine, and mouse. Since beta-S100 protein levels in those tissues were low, it was suggested that S100 protein in the muscle tissues is present mainly as the alpha alpha form (S100a0 protein). To confirm the above findings, immunoreactive alpha-S100 protein was purified from human pectoral muscle by employing column chromatographies with butyl-Sepharose, diethylaminoethyl (DEAE)-Sepharose, Sephadex G-75, and finally with an anion-exchange Mono Q column in a HPLC system. The elution profile of alpha-S100 protein from the Mono Q column suggested some heterogeneity of the final preparation. However, each of these fractions traveled with a single band at a position similar to that of bovine S100a0 protein on slab-gel electrophoresis. The amino acid composition of the final preparation was very similar to the composition of bovine S100a0 protein. The purified alpha-S100 protein was eluted from a gel-filtration column (Superose 12) in the same fraction as bovine S100a0 protein.(ABSTRACT TRUNCATED AT 250 WORDS)

SlOO protein, an acidic and calcium-binding protein, was believed to be localized in the nervous tissue, but recently it has been reported to be mainly present in the cardiac and the skeletal muscles of various mammals in the act form (S1OOao) at much higher levels than the nervous tissues. We isolated here SlOO protein from human cardiac muscles. The isolated cardiac muscle SlOO protein showed a single band on electrophoresis at the same position as that of human skeletal muscle S1OOao. The amino acid composition of the purified SlOO protein was quite similar to that of human skeletal muscle SIOOao or bovine brain S1OOao. The immunohistochemical study by use of antibodies monospecific to the a subunit of SlOO protein (S100-a) revealed that S100-a was strongly labeled in human myocardial cells, whereas the p subunit of SlOO protein (SlOO-p) was not detected in the cells.These results suggest that a predominant form of SlOO protein in human myocardial cells is not SlOOa (up) or SlOOb (pp), but SIOOao (aa). In order to determine the ultrastructural localization of SIOOao in mouse cardiac muscle, the direct peroxidase-labeled antibody method was employed. S 1 OOao was mainly localized in the polysomes in the interfibrillar spaces, the fine filamentous structure of the Z line and fascia adherens of the intercalated disc and in the lumen of junctional sarcoplasmic reticulum. SlOO protein, discovered by Moore [l], is an acidic and calcium-binding protein with a molecular mass of approximately 20 kDa, and belongs to a family of EF-hand type calcium-binding proteins [2] such as troponin C, calmodulin, parvalbumin and light-chain of myosin. SlOO protein is known to be composed of at least three forms, S1OOao, SlOOa and SlOOb, which are dimers with the subunit composition au, ap and pp respectively [3 -51. Although SlOO protein was believed to be specific to glial cells, it has been revealed immunologically that SlOO protein is also distributed in a wide variety of non-nervous cells and tissues [6, 71. Most of these immunochemical findings, however, show the localization of SlOOb rather than that of S1OOao, because the antibodies used in the previous reports were raised with a SlOO protein mixture purified from bovine brain, which is mostly composed of SlOOb and S100a. The SIOOao content in the brain is only a few percent of the total SlOO protein [8].There are a few immunohistochemical reports describing differential localization of the a subunit (S100-a) and the p subunit (SlOO-p) [9, lo]. These studies fail to reflect the precise distribution of S100-a, since immunohistochemical methods have disadvantages for quantitative analysis. We recently determined the quantitative distributions of S100-a and SlOO-p in human tissues by employing an enzyme immunoassay system consisting of specific antibodies to each subunit, and found that immunoreactive SIOOao is pre-

We previously showed that, in contrast to the distribution of S100b (beta beta), S100a0 (alpha alpha) is mainly present in human skeletal and heart muscles at the level of 1-2 micrograms/mg of soluble protein and is universally distributed at high levels in skeletal and heart muscles of various mammals. To elucidate cellular and ultrastructural localizations of the alpha subunit of S100 protein (S100-alpha) in skeletal muscle, we used immunohistochemical and enzyme immunoassay methods. The immunohistochemical study revealed that S100-alpha is mainly localized in slow-twitch muscle fibers, whereas the beta subunit of S100 protein (S100-beta) was not detected in both types of muscle fibers, an observation indicating that the predominant form of S100 protein in the slow-twitch muscle fiber is not S100a or S100b, but S100a0. The quantitative analysis using enzyme immunoassay corroborates the immunohistochemical finding: The S100-alpha concentration of mouse soleus muscle (mainly composed of slow-twitch muscle fibers) is about threefold higher than that of mouse rectus femoris muscle (mainly composed of fast-twitch muscle fibers). At the ultrastructural level, S100-alpha is associated with polysomes, sarcoplasmic reticulum, the plasma membrane, the pellicle around lipid droplets, the outer membrane of mitochondria, and thin and thick filaments, by immunoelectron microscopy.