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.     

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.     

Effects of calorie restriction on the age-dependent accumulation of mutations in the small intestine of lacZ-transgenic mice

To understand the effect of calorie restriction on genome maintenance systems, the age-dependent accumulation of mutations in animals maintained on high and low calorie diets was examined using lacZ-transgenic mice. Mice were fed a diet of 95 kcal/w or 65 kcal/w from 2 to 17 months of age. The mutation frequencies in the lacZ gene in epithelial tissues from the small intestine were examined at 12 and 17 months. Mutation frequencies were found to be lower in mice fed with a low calorie diet than in mice fed with a high calorie diet at the two age points. The molecular nature of the mutations was examined with DNA sequencing. It showed a predominance of transversions from G:C to T:A, and this is a typical type of mutation induced by reactive oxygen species. The fraction of this type of mutation among the different types of mutations detected was not affected by calorie restriction. The percentage of the other types of mutation was not influenced either. These results suggest that calorie restriction reduces the age-dependent accumulation of mutations by stimulating or inducing various types of DNA protection and repair systems rather than protecting cells against any specific type of DNA alteration.     

Reconstructive surgery for a fusiform common celiomesenteric trunk aneurysm and coexistent abdominal aortic aneurysm: Report of a case

A celiomesenteric trunk (CMT) accounts for fewer than 1% of all visceral artery anomalies. Aneurysms involving a CMT are exceptionally rare: our search of the literature found only eight cases reported. We treated a 73-year-old man with both a fusiform CMT aneurysm and an abdominal aortic aneurysm (AAA). The celiac artery and superior mesenteric artery were reconstructed by performing a retrograde prosthetic-graft bypass originating from the right limb of the bifurcated aortic graft used to repair the AAA. To our knowledge, this is the first report of successful surgical treatment of a CMT aneurysm and coexistent AAA.     

Strategies for Maximizing Heart and Lung Transplantation Opportunities in Japan

Introduction

Because the donor shortage is extremely severe in Japan because of a strict organ transplantation law, special strategies must be established to maximize heart transplantation (HTx) and lung transplantation (LTx) opportunities. The purpose of this study was to review our strategies to identify and manage heart and lung donors.

Method

Transplantation doctors themselves assessed their own donor heart and lung function before starting the procurement operation; skillful staff surgeons harvested the organs. Since November 2002, a special transplantation consultant doctor assessed donor organ function to identify useful organs and intensively cared for the donor to improve cardiac and lung function.

Results

Only 63 brain-dead donors have been available in Japan. However, 49 HTx (77.7%) and 39 LTx (19 bilateral and 20 single) were performed from 36 donors (57.1%). Thirty-six HTx donors were marginal, requring sustained high doses of inotropes (n = 26), low left ventricular ejection fraction (n = 5), cardiopulmonary resuscitation (n = 15), and age older than 55 years (n = 6). Twenty LTx donors had infected sputa or showed pneumonia using chest X-ray. None of 49 HTx recipients died of primary graft failure (PGF). Patient survival at 3 years after HTx was 98.0%. Although 5/39 LTx died early, including 2 of PGF, patient survival rate at 3 years was 66.9%.

Conclusion

Although the number of cases was still small, the availability of hearts and lungs has been high and the transplantation outcomes were acceptable. These strategies may be useful to maximize HTx/LTx opportunities.     

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.     

Follicular dendritic cell sarcoma with microtubuloreticular structure and virus-like particle production in vitro

Neoplasm of follicular dendritic cells (FDC), follicular dendritic cell sarcoma (FDCS), is a rare tumor of intermediate to high-grade malignancy in lymph nodes and visceral organs. Reported herein is a case of FDCS arising from cervical lymph nodes in a 16-year-old Japanese boy, who died of the disease 3 years after diagnosis. The tumor cells were pale eosinophilic and elongated with euchromatic nuclei and were positive for CD21, clusterin, and CNA-42 on immunohistochemistry, as well as desmosome-like junctions on electron microscopy. The presence of microtubuloreticular structures (MTRS) in the tumor cells and associated lymphocytes characterized this case, suggesting some viral infection, although qualitative polymerase chain reaction of genomic and complementary DNA obtained from the tumor failed to demonstrate any viral infection at the laboratory level. The stimulation of dispersed tumor cells and peripheral blood mononuclear cells with mAb to CD3 and interleukin-2 was attempted; and the cell line established by the authors (FDCS-Sa) was stimulated with iododeoxyuridine. Virus-like particles (VLP) were successfully induced from each cellular source. The VLP, 100 nm in diameter, showed an electron-dense thorny envelope and granular core. This is the first case of FDCS with MTRS accompanying VLP production in vitro .     

Role of ornithine decarboxylase antizyme inhibitor in vivo

Ornithine decarboxylase (ODC) antizyme inhibitor (AZI) has been shown to regulate ODC activity in cell cultures. However, its biological functions in an organism remain unknown. An embryonic stem (ES) cell clone was established, in which the Azin1 gene was disrupted by the gene trap technique. To identify the function of Azin1 gene in vivo , a mutant mouse line was generated using these trapped ES cells. Homozygous mutant mice died at P0 with abnormal liver morphology. Further analysis indicated that the deletion of Azin1 in homozygous mice resulted in the degradation of ODC, and reduced the biosynthesis of putrescine and spermidine. Our results thus show that AZI plays an important role in regulating the levels of ODC, putrescine and spermidine in mice, and is essential for the survival of mice.     

Distribution of certified perfusionists in core training institutions accredited by the Japanese Board of Cardiovascular Surgery in Japan

In 2008, the 22nd qualifying examination for certified perfusionist was conducted on extracorporeal circulation techniques. A total of 647 people had passed the qualifying examination and become certified perfusionists by the end of 2008.     

Serofendic acid protects from iodinated contrast medium and high glucose probably against superoxide production in LLC-PK1 cells

BACKGROUND: It is well known that patients with chronic kidney disease, including diabetic nephropathy, often develop cardiovascular diseases. In case of radiographic procedures, reduced renal function may be deteriorated by the use of iodinated contrast medium (CM). This is known as CM-induced nephropathy. In this study, we have focused on the mechanisms of this type of injury in diabetic nephropathy and the preventive effects of serofendic acid. METHODS: We evaluated the cytotoxicity of CM and high glucose on tubular epithelial cells using an LLC-PK1 cell line, and measured cell viability with an alamarBlue assay. We further evaluated superoxide production levels measured by dihydroethidium. We also examined the protective effects of serofendic acid on cytotoxicity with superoxide production of CM and high glucose. RESULTS: CM reduced cell numbers in a dose-dependent and time-dependent manner in LLC-PK1 cells. Furthermore, cytotoxicity of CM in diluted concentration was additively influenced by high glucose. CM and high glucose increased superoxide production, which was evaluated by the response to dihydroethidium, and was suppressed by serofendic acid. Cytotoxicity of CM, high glucose, and H(2)O(2) was suppressed by serofendic acid, as well as the suppression by N-acetylcysteine on CM toxicity. Interestingly, the recovery by serofendic acid in H(2)O(2)- and high glucose-induced cellular injury was to the basal level, in contrast with the partial recovery from CM-induced injury. Finally, serofendic acid suppressed CM-induced injury and high glucose-induced apoptosis. CONCLUSIONS: These results suggest that CM and high glucose induce cytotoxicity and oxidative stress in LLC-PK1 cells and that serofendic acid protects the injury probably from superoxide generation.