Objectives In a computed tomographic (CT) angiography study, we identified the characteristics of atherosclerotic lesions that were associated with subsequent development of acute coronary syndrome ...(ACS). Background The CT characteristics of culprit lesions in ACS include positive vessel remodeling (PR) and low-attenuation plaques (LAP). These 2 features have been observed in the lesions that have already resulted in ACS, but their prospective relation to ACS has not been previously described. Methods In 1,059 patients who underwent CT angiography, atherosclerotic lesions were analyzed for the presence of 2 features: PR and LAP. The remodeling index, and plaque and LAP areas and volumes were calculated. The plaque characteristics of lesions resulting in ACS during the follow-up of 27 ± 10 months were evaluated. Results Of the 45 patients showing plaques with both PR and LAP (2-feature positive plaques), ACS developed in 10 (22.2%), compared with 1 (3.7%) of the 27 patients with plaques displaying either feature (1-feature positive plaques). In only 4 (0.5%) of the 820 patients with neither PR nor LAP (2-feature negative plaques) did ACS develop. None of the 167 patients with normal angiograms had acute coronary events (p < 0.001). ACS was independently predicted by PR and/or LAP (hazard ratio: 22.8, 95% confidence interval: 6.9 to 75.2, p < 0.001). Among 2- or 1-feature positive segments, those resulting in ACS demonstrated significantly larger remodeling index (126.7 ± 3.9% vs. 113.4 ± 1.6%, p = 0.003), plaque volume (134.9 ± 14.1 mm3 vs. 57.8 ± 5.7 mm3 , p < 0.001), LAP volume (20.4 ± 3.4 mm3 vs. 1.1 ± 1.4 mm3 , p < 0.001), and percent LAP/total plaque area (21.4 ± 3.7 mm2 vs. 7.7 ± 1.5 mm2 , p = 0.001) compared with segments not resulting in ACS. Conclusions The patients demonstrating positively remodeled coronary segments with low-attenuation plaques on CT angiography were at a higher risk of ACS developing over time when compared with patients having lesions without these characteristics.
Multislice Computed Tomographic Characteristics of Coronary Lesions in Acute Coronary Syndromes Sadako Motoyama, Takeshi Kondo, Masayoshi Sarai, Atsushi Sugiura, Hiroto Harigaya, Takahisa Sato, Kaori ...Inoue, Masanori Okumura, Junichi Ishii, Hirofumi Anno, Renu Virmani, Yukio Ozaki, Hitoshi Hishida, Jagat Narula We interrogated, by multislice computed tomography, the characteristics of culprit lesions in 38 patients presenting with acute coronary syndromes (ACS) and compared them with 33 stable angina patients. Positive remodeling, low plaque attenuation, and spotty calcification were significantly more frequent in the ACS lesions. Presence of such plaques in absence of ACS should indicate a high likelihood of plaques vulnerable to rupture.
Helicobacter pylori East Asian CagA is more closely associated with gastric cancer than Western CagA. Here we show that, upon tyrosine phosphorylation, the East Asian CagA-specific EPIYA-D segment ...binds to the N-SH2 domain of pro-oncogenic SHP2 phosphatase two orders of magnitude greater than Western CagA-specific EPIYA-C. This high-affinity binding is achieved via cryptic interaction between Phe at the +5 position from phosphotyrosine in EPIYA-D and a hollow on the N-SH2 phosphopeptide-binding floor. Also, duplication of EPIYA-C in Western CagA, which increases gastric cancer risk, enables divalent high-affinity binding with SHP2 via N-SH2 and C-SH2. These strong CagA bindings enforce enzymatic activation of SHP2, which endows cells with neoplastic traits. Mechanistically, N-SH2 in SHP2 is in an equilibrium between stimulatory “relaxed” and inhibitory “squeezed” states, which is fixed upon high-affinity CagA binding to the “relaxed” state that stimulates SHP2. Accordingly, East Asian CagA and Western CagA exploit distinct mechanisms for SHP2 deregulation.
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•East Asian CagA binds to SHP2 100-fold more strongly than type I Western CagA•East Asian CagA binds to SHP2 via a high-affinity monovalent interaction with N-SH2•Type II Western CagA binds to SHP2 via divalent interactions with N-SH2 and C-SH2•Oncogenic CagA binding fixes N-SH2 to the “relaxed” state that activates SHP2
Helicobacter pylori CagA binds and deregulates SHP2 to promote gastric carcinogenesis. Hayashi et al. examine the structural and molecular determinants underpinning the CagA-SHP2 interaction and find that totally distinct mechanisms of SHP2 binding are differentially exploited by two major oncogenic CagA isoforms, revealing highly plastic evolution in bacterial virulence acquisition.
Abstract
The effect of the skin–capsular distance (SCD) on the controlled attenuation parameter (CAP) for diagnosis of liver steatosis in patients with nonalcoholic fatty liver disease (NAFLD) ...remains unclear. The SCD was measured using B-mode ultrasound, and the CAP was measured using the M probe of FibroScan
®
. According to the indications of the M probe, 113 patients with an SCD of ≤ 25 mm were included in the present study. The association between the SCD and CAP was investigated, and the diagnostic performance of the SCD-adjusted CAP was tested. The SCD showed the most significant positive correlation with the CAP (ρ = 0.329, p < 0.001). In the multiple regression analysis, the SCD and serum albumin concentration were associated with the CAP, independent of pathological liver steatosis. According to the multivariate analysis, two different formulas were developed to obtain the adjusted CAP using the SCD and serum albumin concentration as follows: adjusted CAP (dB/m) = CAP − (5.26 × SCD) and adjusted CAP (dB/m) = CAP − (5.35 × SCD) − (25.77 × serum albumin concentration). The area under the receiver operating characteristic curve for diagnosis of a steatosis score ≥ 2 of adjusted CAP was 0.678 and 0.684 respectively, which were significantly greater than the original CAP (0.621: p = 0.030 and p = 0.024). The SCD is associated with the CAP independent of liver steatosis. Adjustment of the CAP using the SCD improves the diagnostic performance of the CAP in NAFLD.
Cerebellar injuries can cause syntax impairments. Cortical dysfunction due to cerebello-cerebral diaschisis is assumed to play a role in this phenomenon. Functional magnetic resonance imaging studies ...have repeatedly shown the activation of Broca's area in response to syntactic tasks. However, there have been no reports of selective syntax impairment and hypoperfusion restricted to this area after cerebellar injury. We herein report a patient with right cerebellar hemorrhage that led to marked syntax impairment along with severe hypoperfusion confined to the Brodmann area (BA) 45 (anterior part of Broca's area) and BA46.
Extracellular ATP regulates proliferation and differentiation, functioning as an important messenger via purinergic (P2) receptors in keratinocytes. In this study, we investigated the effects of ATP ...on cytokine production in cultured normal human epidermal keratinocytes (NHEKs). Adenosine 5′-O-(3-thiotriphosphate) (ATPγS), adenosine 5′-O-2-(thio)diphosphate (ADPβS), ADP, ATP, and 2′, 3′-O-(4-benzoyl-benzoyl) ATP (BzATP) significantly increased the release of IL-6. The P2 antagonists, suramin-, reactive blue 2-, and periodate-oxidized ATP, inhibited ATP-induced IL-6 release, whereas pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid, adenosine 3′-phosphate 5′-phosphate, 1-N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl-4-phenylpiperazine, and pertussis toxin did not. SQ22563, an adenylate cyclase inhibitor, inhibited ATP-induced IL-6 release. ATPγS, ADPβS, ATP, and BzATP significantly increased the intracellular cAMP content. Reverse transcription-PCR showed expression of P2Y1, P2Y2, P2Y4, P2Y11, P2Y12, P2Y13, P2X1, P2X4, P2X5, P2X6, and P2X7 receptor subtypes. Additionally, UVB radiation evoked the release of ATP from NHEKs. The release of IL-6 and the expression of IL-6 mRNA were increased after UVB radiation, and these increases were also inhibited by P2 receptor antagonists. These results suggest that cAMP-generating P2Y receptors are likely functional in ATP-induced IL-6 production in NHEKs. Furthermore, in UVB-radiated cells, we note the possibility that P2 receptor antagonists may reduce skin inflammation.
The prevalence of diabetes mellitus is a growing public health concern in Japan. We developed a simulation model to predict the number of people with diabetes and those on dialysis due to diabetic ...nephropathy. In addition, we used the model to simulate the impact of possible interventions on the number of people with diabetes and those on dialysis due to diabetic nephropathy in the near future.
A simulation model with aging chains for diabetes management was built using system dynamics. The model was calibrated to population data from 2000 to 2015 (sex- and age category-specific population, the prevalence of diabetes, and the number of patients on dialysis due to diabetic nephropathy). We extrapolated the model up to 2035 in order to predict future prevalence of diabetes and related dialysis (base run). We also ran the model, hypothesizing that incidence of diabetes and/or related dialysis would be reduced by half from 2015 to 2025 and that this rate would be maintained until 2035, in order to investigate the effects of hypothetical interventions on future prevalence.
The developed model forecasted the population with diabetes to increase until 2028 (5.58 million males and 3.34 million females), and the population on dialysis due to diabetic nephropathy to increase until 2035 (113,000 males and 48,000 females). Simulation experiments suggested that diabetes prevention interventions would decrease the number of patients on dialysis in 2035 by 13.8% in males and 12.6% in females compared to the base run. In contrast, interventions aiming to avoid dialysis initiation for patients with diabetes would decrease the number of patients on dialysis by 37.8% in males and 38.1% in females.
We successfully developed a simulation model to project the number of patients with diabetes and those on dialysis due to diabetic nephropathy. Simulation experiments using the model suggested that, as far as the perspective of the next 20 years, intervention to prevent dialysis is an important means of bending the increasing curve of dialysis in the population with diabetes. Simulation analysis may be useful when making and evaluating health policies related to diabetes and other chronic diseases.
SUMMARY
The cyanobacterium Nostoc commune is adapted to terrestrial environments and has a cosmopolitan distribution. Four genotypes of N. commune can be identified based on differences in their 16S ...rRNA genes, and these genotypes are distributed throughout Japan without regional specificity. Mycosporine‐like amino acids (MAAs) are UV‐absorbing pigments, and novel glycosylated MAA derivatives with radical scavenging activities have been identified in N. commune. In this study, we investigated the consistency of the relationship between MAA compositions and N. commune genotypes. The MAA compositions were different in a genotype‐specific manner, suggesting that the types of MAA derivatives can feasibly be used as chemotaxonomic markers to characterize N. commune. The novel 756‐Da MAA, which was identified as an aglycone of the 1050‐Da MAA and named nostoc‐756, occurred in genotype C of N. commune. Nostoc‐756 functioned as a radical scavenger in vitro. In conclusion, N. commune is classified into four groups representing genetically different chemotypes, namely, the arabinose‐bound porphyra‐334 producer (chemotype A), the glycosylated nostoc‐756 producer (chemotype B), the nostoc‐756 producer (chemotype C) and the glycosylated palythine‐threonine producer (chemotype D). Either the molecular taxonomical method or chemical analysis of a characteristic secondary metabolite is sufficient to identify the types of N. commune; however, there are no obvious ecophysiological differences that allow us to distinguish them.
Glycated hemoglobin (HbA1c) and glycated albumin (GA) are frequently used as glycemic control markers. These markers are influenced by either altered hemoglobin metabolism or albumin metabolism. We ...investigated the correlation between HbA1c and GA by collecting only data that had not been affected by the turnover of either HbA1c or GA and proposed a novel equation for accurately estimating the extrapolated HbA1c (eHbA1c) value based on the GA value. Data sets for a total of 2461 occasions were obtained from 731 patients (including non-diabetes patients) whose HbA1c and GA values were simultaneously measured. Data sets obtained from patients undergoing hemodialysis, patients with hematological malignancies, pregnancy, chronic liver diseases, hyperthyroidism, steroid treatment or a blood transfusion during the past 3 months, or patients without albumin, hemoglobin, eGFR, or urinary protein measurements and data sets with an eGFR of less than 30 mL/min/1.73 m2, a hemoglobin level of less than 10 mg/dL, an albumin level of below 3.0 g/mL, or a urinary protein level of 3+ were excluded. Finally, we selected 284 data sets. We then analyzed these data sets, performed a scatter plot to examine the correlation between HbA1c and GA, and established an equation describing the resulting correlation. Based on all the data points, the resulting equation was HbA1c = 0.216 × GA + 2.978 R2 = 0.5882, P < 0.001.
Calcium dynamics in the epidermis play a crucial role in barrier homeostasis and keratinocyte differentiation. We have recently suggested that the electro-physiological responses of the keratinocyte ...represent the frontier of the skin sensory system for environmental stimuli. In the present study, we have evaluated the responses of proliferating and differentiated human keratinocytes to mechanical stress by measuring the intracellular calcium level. Before differentiation, mechanical stress induces a calcium wave over a limited area; this is completely blocked by apyrase, which degrades ATP. In the case of differentiated keratinocytes, the calcium wave propagates over a larger area. Application of apyrase does not completely inhibit this wave. Thus, in differentiated cells, the induction of calcium waves might involve not only ATP, but also another factor. Immunohistochemical studies indicate that connexins 26 and 43, both components of gap junctions, are expressed in the cell membrane of differentiated keratinocytes. Application of octanol or carbenxolone, which block gap junctions, significantly reduces calcium wave propagation in differentiated keratinocytes. Thus, signaling via gap junctions might be involved in the induction of calcium waves in response to mechanical stress at the upper layer of the epidermis.
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