Non-linear association between ankle-brachial pressure index and prevalence of silent cerebral infarction in Japanese patients with type 2 diabetes

ObjectivePatients with peripheral artery disease (PAD), defined as having low ankle-brachial pressure index (ABI), have increased risk for incident stroke compared with those without PAD. We aimed to reveal whether ABI abnormality, especially high ABI is associated with prevalent silent cerebral infarction (SCI) in type 2 diabetic patients.MethodsWe studied 538 Japanese type 2 diabetic patients, 227 women and 311 men, with a mean [±SD] age of 64 ± 11 years. All patients underwent cranial magnetic resonance imaging (MRI). Values of ABI were classified as low (<0.9), normal (0.9≤ and <1.3), and high (1.3≤). Logistic regression model was used to calculate odds ratio and 95% confidence interval (95% CI) for prevalent SCI.ResultsThe mean ABI among the overall 538 patients was 1.09 ± 0.16. Low and high ABI values were found in 52 (9.7%) and 33 (6.1%) patients, respectively. SCI was detected in 297 (55.2%) patients. The prevalence in patients with low, normal, and high ABI values were 88.5%, 49.7%, and 78.8 (p < 0.001), respectively. In the multivariate logistic regression analysis, both patients with high and low ABI were significantly increased risk of prevalent SCI (odds ratio 4.53, 95% CI 1.67–12.34, p = 0.003 and odds ratio 3.50, 95% CI 1.50–10.29, p = 0.005), independently of other traditional cardiovascular risk factors, than those with normal ABI.ConclusionsBoth high and low ABI may be strongly associated with prevalent SCI in Japanese patients with type 2 diabetes.     

Ehrlichia chaffeensis induces monocyte inflammatory responses through MyD88, ERK, and NF-κB but not through TRIF, interleukin-1 receptor 1 (IL-1R1)/IL-18R1, or toll-like receptors

Human monocytic ehrlichiosis, an influenza-like illness accompanied by signs of hepatitis, is caused by infection of monocytes/macrophages with a lipopolysaccharide-deficient bacterium, Ehrlichia chaffeensis. The E. chaffeensis strain Wakulla induces diffuse hepatitis with neutrophil infiltration in mice with severe combined immunodeficiency, which is accompanied by strong CXCL2 (mouse functional homolog of interleukin-8 [IL-8]) and tumor necrosis factor alpha (TNF-α) expression in the liver. In this study, we found that expression of IL-1β, CXCL2, and TNF-α was induced by strain Wakulla in mouse bone marrow-derived macrophages; this expression was dependent on MyD88, but not on TRIF, TLR2/4, IL-1R1/IL-18R1, or endosome acidification. When the human leukemia cell line THP-1 was exposed to E. chaffeensis, significant upregulation of IL-8, IL-1β, and TNF-α mRNA and extracellular regulated kinase 2 (ERK2) activation were detected. U0126 (inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 [MEK1/2] upstream of ERK), manumycin A (Ras inhibitor), BAY43-9006 (Raf-1 inhibitor), and NS-50 (inhibitor of NF-κB nuclear translocation) inhibited the cytokine gene expression. A luciferase reporter assay using HEK293 cells, which lack Toll-like receptors (TLRs), showed activation of both the IL-8 promoter and NF-κB by E. chaffeensis. Activation of the IL-8 promoter in transfected HEK293 cells was inhibited by manumycin A, BAY43-9006, U0126, and transfection with a dominant-negative Ras mutant. These results indicate that the E. chaffeensis Wakulla strain can induce inflammatory responses through MyD88-dependent NF-κB and ERK pathways, without the involvement of TRIF and TLRs.     

The relationship between serum uric acid and spirometric values in participants in a health check: the Takahata study

Background: Tissue hypoxia induces the degradation of adenosine triphosphate, resulting in the production of uric acid (UA). Patients with chronic obstructive pulmonary disease (COPD) have been reported to have high serum levels of UA (sUA), compared with control subjects. However, the relationship between sUA levels and spirometric measures has not been investigated in detail in a general population.Methods: Subjects aged 40 years or older (n = 2,917), who had participated in a community-based annual health check in Takahata, Japan, in 2004 and 2005, were enrolled in the study. These subjects performed spirometry, their blood pressure was measured, and a blood sample was taken.Results: sUA levels were significantly higher in males than in females. Percent predicted forced vital capacity [FVC %predicted] (r = -0.13) and forced expiratory volume in 1 s [FEV₁ %predicted] (r = -0.118) were inversely correlated with sUA levels in females but not in males. Univariate regression analysis indicated that age, body mass index (BMI), ethanol intake, mean blood pressure (BP), and serum creatinine (sCr) were significantly associated with sUA levels in males. In females, age, BMI, mean BP, hemoglobin A1c, sCr, FVC %predicted, and FEV₁ %predicted were significantly associated with sUA levels. Multiple linear regression analysis showed that for both genders, FVC %predicted and FEV₁ %predicted were predictive for sUA levels, independently of the other clinical parameters. Subjects with lung restriction had higher sUA levels than subjects without lung restriction. In addition, subjects with moderate and severe airflow limitation had higher sUA levels than subjects without airflow limitation or those with mild airflow limitation.Conclusion: FVC %predicted and FEV₁ %predicted were significantly associated with sUA levels in a general population.     

Final report of the working group for the future planning of the Japanese Association of Anatomists

The working group for the future planning of the Japanese Association of Anatomists (JAA) has been working to address the issues that were consulted from the president of JAA since October 2009. After making the interim report in March 2010, a public hearing for general members of the JAA was held and a final report was submitted to the President in January 2011. The report contains the analysis of the current situation, the directions in which we should proceed, and recommendations of concrete actions that JAA should take for each issue. The issues discussed were as follows: 1. Future prospects of anatomy and morphological sciences. How can we maintain the specialties of morphological and anatomical sciences in the rapidly advancing field of life sciences and develop collaborations with other fields? 2. Improvement of the JAA academic meetings. How can we increase JAA members and young participants in the academic meetings of the JAA? 3. Fostering the next generation of young researchers. How can we increase young researchers graduated from the schools of Medicine or Dentistry? 4. Future prospects of education of gross anatomy. Prospects of education in gross anatomy and the body donation registration system in relation with some new cadaver-related movements.     

Experimental vaccine activities of recombinant E1 and E2 glycoproteins and hypervariable region 1 peptides of hepatitis C virus in chimpanzees

Summary.  A chimpanzee was immunized with two recombinant envelope glycoproteins E1 and E2 of hepatitis C virus (HCV), strain HCV-N2, and the hypervariable region 1 (HVR1) peptides of a different isolate, HCV-#6, then received an intravenous inoculation of 10 chimpanzee infectious doses of HCV-#6. With high humoral immune response against E1 and E2 but a low response against HVR1, the vaccinee became infected with the HCV. However, after increasing the titer of anti-HVR1 against HCV-#6, the vaccinee showed protection. Neutralization of HCV-#6 with the antiserum from this protected vaccinee was achieved by inoculation of this mixture into another chimpanzee. These results suggest that vaccination with a peptide-vaccine of homologous HVR1 is effective in the chimpanzee. Received December 4, 1998 Accepted January 12, 1999     

Regulation of activity of P2X7 receptor by its splice variants in cultured mouse astrocytes

Of purinergic receptors, P2X7 receptor (P2X7R, defined as a full‐length receptor) has unique characteristics, and its activation leads to ion channel activity and pore formation, causing cell death. Previously, we demonstrated that P2X7R expressed by nonstimulated astrocyte cultures obtained from SJL‐strain mice exhibits constitutive activation, implying its role in maintenance of cellular homeostasis. To obtain novel insights into its physiological roles, we examined whether constitutive activation of P2X7R is regulated by expression of its splice variants in such resting astrocytes, and whether their distinct expression profiles in different mouse strains affect activation levels of astrocytic P2X7Rs. In SJL‐ and ddY‐mouse astrocytes, spontaneous YO‐PRO‐1 uptake, an indicator of pore activity of P2X7R, was detected, but the uptake by the formers was significantly greater than that by the latter. Between the two mouse strains, there was a difference in their sensitivity of YO‐PRO‐1 uptake to antagonists, but not in the expression levels and sequences of P2X7R and pannexin‐1. Regarding expression of splice variants of P2X7R, expression of P2X7R variant‐3 (P2X7R‐v3) and ‐4 (P2X7R‐v4), but not variant‐2 and ‐k, was lower in SJL‐mouse astrocytes than in ddY‐mouse ones. On transfection of P2X7R‐v3 and ‐v4 into SJL‐mouse astrocytes, the pore activity was attenuated as in the case of the HEK293T cell‐expression system. These findings demonstrate that basal activity of P2X7R expressed by resting astrocytes is negatively regulated by P2X7R‐v3 and ‐v4, and that their distinct expression profiles result in the different activation levels of astrocytic P2X7Rs in different mouse strains. GLIA 2014;62:440–451     

Prenatal diagnosed cyst of the quadrigeminal cistern in Aicardi syndrome

Aicardi syndrome is an X-linked dominant disorder characterized by the pathognonomic association of three clinical signs: agenesis of the corpus callosum, infantile spasms, and chorioretinal lacunae. This is a severe syndrome with an estimated survival rate of 76% at 6 years and 40% at 14 years and a maximum developmental level like a 12-month-old baby in 91% of cases. We illustrate a case of Aicardi syndrome with bilateral, small chorioretinal lacunae, infantile spasms with a typical hypsarrhythmia, defects of thoracic vertebra and bilateral absence of the12th rib associated with an arachnoid cyst of the quadrigeminal cistern, and presence of the corpus callosum with a favorable outcome.