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Niimi K.,Nagoya City University | Yasui T.,Nagoya City University | Hirose M.,Kainan Hospital | Hamamoto S.,Nagoya City University | And 8 more authors.
Free Radical Biology and Medicine | Year: 2012

Renal tubular cell injury induced by oxidative stress via mitochondrial collapse is thought to be the initial process of renal calcium crystallization. Mitochondrial collapse is generally caused by mitochondrial permeability transition pore (mPTP) opening, which can be blocked by cyclosporine A (CsA). Definitive evidence for the involvement of mPTP opening in the initial process of renal calcium crystallization, however, is lacking. In this study, we examined the physiological role of mPTP opening in renal calcium crystallization in vitro and in vivo. In the in vitro study, cultured renal tubular cells were exposed to calcium oxalate monohydrate (COM) crystals and treated with CsA (2 μM). COM crystals induced depolarization of the mitochondrial membrane potential and generated oxidative stress as evaluated by Cu-Zn SOD and 4-HNE. Furthermore, the expression of cytochrome c and cleaved caspase 3 was increased and these effects were prevented by CsA. In the in vivo study, Sprague-Dawley rats were administered 1% ethylene glycol (EG) to generate a rat kidney stone model and then treated with CsA (2.5, 5.0, and 10.0 mg/kg/day) for 14 days. EG administration induced renal calcium crystallization, which was prevented by CsA. Mitochondrial collapse was demonstrated by transmission electron microscopy, and oxidative stress was evaluated by measuring Cu-Zn SOD, MDA, and 8-OHdG generated by EG administration, all of which were prevented by CsA. Collectively, our results provide compelling evidence for a role of mPTP opening and its associated mitochondrial collapse, oxidative stress, and activation of the apoptotic pathway in the initial process of renal calcium crystallization. © 2012 Elsevier Inc.


Takeuchi M.,Nagoya City University | Sasaki S.,Nagoya City West Medical Center | Naiki T.,Nagoya City University | Kawai N.,Nagoya City University | And 3 more authors.
Journal of Magnetic Resonance Imaging | Year: 2013

Treatment decisions for bladder cancer patients are mainly based on the depth of bladder wall invasion by the tumor. In this article, we review the conventional MRI and exhibit a recently emerged diffusion-weighted imaging (DWI) of urinary bladder cancer for T-staging. We discuss limitations of conventional MRI, scanning protocols of DWI, normal pelvic findings on DWI, determination of T-stage using DWI, and pitfalls of DWI. DWI provides high contrast between bladder cancer and background tissue because the cancer shows markedly high SI. DWI has high sensitivity for detecting the stalk seen in stage Ta or T1. An inflammatory change or fibrosis surrounding the tumor mimics the invasion of bladder cancer on T2-weighted imaging or enhanced MRI and could lead to over-staging, but DWI could differentiate them clearly because these benign changes do not show high SI on DWI. DWI is also useful for detecting ureteral, urethral, and prostatic extension by means of the urethra. DWI provides more accurate information on the extent of bladder cancer and contributes to determination of the treatment strategy. © 2013 Wiley Periodicals, Inc.


Itoh Y.,Nagoya City West Medical Center
Clinical calcium | Year: 2011

In 2002, speedy elimination of ureterolithiasis in the lower part of ureter was first reported with the alpha 1 blocker. Thereafter, there are a lot of reports including meta-analysis about tamsulosin. In 2011 EAU Guidelines on Urolithiasis, it is the most important to establish effective MET (medical expulsive therapy) to facilitate spontaneous stone passage. Alpha 1 blockers are the preferred agents for MET. As a basic evidence for MET, we reported that alpha 1a and 1d AR subtype mRNA was highly expressed in the human ureter and that alpha 1A AR is the main participant in the human ureteral contraction. It is published newly in Japanese Guidelines on Urolithiasis revised edition to schedule to be published soon.


Fujimoto K.,Kurume University | Hara M.,Nagoya City West Medical Center | Tomiyama N.,Osaka University | Kusumoto M.,National Cancer Center Hospital | And 2 more authors.
Oncology Reports | Year: 2014

There is no existing worldwide published method for mediastinum compartment classification based on transverse section images for the differential diagnosis of mediastinal tumors. Herein, we describe a new method for anatomic mediastinal compartment classification using transverse section computed tomography (CT) images and the use of this method to classify mediastinal lesions, and thus evaluate whether the method is sufficiently user-friendly and useful. In a publication of the Japanese Association for Research on the Thymus (JART), we proposed the following four mediastinal compartments based on transverse CT images: superior portion of mediastinum, anterior mediastinum (prevascular zone), middle mediastinum (peri-tracheoesophageal zone), and posterior mediastinum (paravertebral zone). In the present study, we retrospectively analyzed 445 pathologically proven mediastinal mass lesions, and categorized them into the proposed four compartments by consensus reading. Mass lesions were classified into compartments based on the location of the lesion centroid, and each lesion was satisfactorily categorized into a compartment. Almost all thymic epithelial tumors (99%, 244/246), all 24 thymic malignant lymphomas and a majority of germ cell neoplasms (93%, 54/58) were classified as being in the anterior mediastinum compartment. The majority of intrathoracic goiters (82%, 14/17) were categorized as being in the superior portion of the mediastinum compartment. Approximately two-thirds of mass lesions in the middle mediastinum were cysts, including foregut and pericardial cysts. Approximately 80% of 37 mass lesions in the posterior mediastinum were neurogenic tumors. Correspondingly, 29 of the 49 neurogenic tumors (60%) were categorized as being in the posterior mediastinum, while 10 (20%) were in the superior portion of the mediastinum, 4 (8%) in the anterior mediastinum, and 6 (12%) in the middle mediastinum. Our findings showed that the newly proposed mediastinal compartment classification using transverse images appears to be user-friendly enough for practical clinical application and may be helpful in differential diagnoses.


Kobayashi S.,Nagoya City West Medical Center | Sugiura H.,Nagoya City West Medical Center | Ando Y.,Nagoya City West Medical Center | Shiraki N.,Nagoya City West Medical Center | And 3 more authors.
Breast Cancer | Year: 2012

The fact that reproductive factors have significant influence on the risk of breast cancer is well known. Early age of first full-term birth is highly protective against late-onset breast cancers, but each pregnancy, including the first one, increases the risk of early-onset breast cancer. Estradiol and progesterone induce receptor activator of NF-kappa B ligand (RANKL) in estrogen receptor (ER)- and progesterone receptor (PgR)-positive luminal cells. RANKL then acts in a paracrine fashion on the membranous RANK of ER/PgR-negative epithelial stem cells of the breast. This reaction cascade is triggered by chorionic gonadotropin during the first trimester of pregnancy and results in the morphological and functional development of breast tissue. On the other hand, the administration of non-steroidal anti-inflammatory drugs in the early steps of weaning protects against tumor growth through reduction of the acute inflammatory reaction of post lactation remodeling of breast tissue. This is experimental evidence that may explain the short-term tumor-promoting effect of pregnancy. The protective effect of prolonged breast feeding may also be explained, at least in a part, by a reduced inflammatory reaction due to gradual weaning. Delay of first birth together with low parity and short duration of breast feeding are increasing social trends in developed countries. Therefore, breast cancer risk as a result of reproductive factors will not decrease in these countries in the foreseeable future. In this review, the significance of reproductive history with regard to the risk of breast cancers will be discussed, focusing on the age of first full-term birth and post lactation involution of the breast. © 2012 The Author(s).

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