Osteocyte-Driven Downregulation of Snail Restrains Effects of Drd2 Inhibitors on Mammary Tumor Cells

While bone is a frequent target of breast cancer-associated metastasis, little is known about the effects of tumor-bone interactions on the efficacy of tumor-suppressing agents. Here we examined the effect of two FDA-approved dopamine modulators, fluphenazine and trifluoperazine, on mammary tumor cells, osteoclasts, osteoblasts, and osteocytes. These agents suppressed proliferation and migration of mammary tumor cells chiefly by antagonizing dopamine receptor D2 and reduced bone resorption by downregulating nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1). Three-dimensional spheroid formation assays revealed that tumor cells have high affinity to osteocytes and type I collagen, and interactions with osteocytes as well as administration of fluphenazine and trifluoperazine downregulated Snail and suppressed migratory behaviors. Unlike the inhibitory action of fluphenazine and trifluoperazine on tumor growth, tumor-osteocyte interactions stimulated tumor proliferation by upregulating NFκB and Akt. In the bone microenvironment, osteocytes downregulated Snail and acted as an attractant as well as a stimulant to mammary tumor cells. These results demonstrate that tumor-osteocyte interactions strengthen dopamine receptor-mediated suppression of tumor migration but weaken its inhibition of tumor proliferation in the osteocyte-rich bone microenvironment.Significance: These findings provide novel insight into the cellular cross-talk in the bone microevironment and the effects of dopamine modulators on mammary tumor cells and osteocytes. Cancer Res; 78(14); 3865-76. ©2018 AACR

Non-Invasive Prenatal Genetic Testing (NIPT) Leading to Prenatal Diagnosis of Trisomy 21 Mosaicism and 18q Deletion Syndrome: Two Cases

NIPT is non-definitive testing to estimate the possibility that fetuses have trisomy 21, trisomy 18, or trisomy 13. However, in NIPT-positive and indeterminate cases, rare chromosomal disease may become apparent, requiring advanced genetic considerations and counseling skills. We experienced two such cases, a trisomy 21 mosaicism case triggered by NIPT-positive status and 18q deletion syndrome triggered by NIPT-indeterminate status. These cases have two clinical implications for NIPT. First, it was revealed that trisomy mosaicism might be found in NIPT-positive cases that have lower Z-Scores than those inferred from the fraction of fetal cfDNA in the case of standard trisomy. Second, it is possible that microdeletion syndrome could be the reason for an indeterminate NIPT result. Today’s genetic counseling requires more expertise in ethics and communication as well as genetic science because NIPT can lead to totally unexpected results

Subcutaneous Single Injection Digital Block with Epinephrine

The aim of this study was to investigate the anesthetic effect and risk of epinephrine for subcutaneous single injection digital block. Either 3.0 mL 1.0% Lidocaine or a 3.0 mL 1.0% Lidocaine with (1 : 100,000) epinephrine was injected into the subcutaneous space at the middle point of the palmar digital crease of the 18 middle fingers of 9 healthy volunteers. The SpO2 of the fingers decreased to a maximum of 97. No subjects showed any symptoms of ischemic injury. The time to anesthesia for the fingers was significantly shorter (P < 0.05), and the duration of anesthesia was significantly longer (P < 0.01) for the fingers in the epinephrine group. In conclusion, a subcutaneous single injection digital blocks with 3.0 mL of 1.0% Lidocaine and (1 : 100,000) epinephrine were safe, reducing the time to the onset of anesthesia, while also markedly prolonging the anesthesia

高齢夜間頻尿患者における夜間尿産生に対する閉塞性睡眠時無呼吸症候群の影響

OBJECTIVE: To investigate the impact of obstructive sleep apnea syndrome (OSAS) on night-time secretion of brain natriuretic peptide (BNP) and antidiuretic hormone (ADH) in older men with nocturia accompanied by nocturnal polyuria. MATERIALS AND METHODS: One hundred six men with nocturia aged ≥ 60 years underwent full-night polysomnography to determine whether they had OSAS. Blood count, standard chemistry panel, BNP, urinary ADH, urinary creatinine (u-Cre), and urinary osmolarity were measured at 6:00 AM, and a frequency volume chart was recorded on the same day that polysomnography was performed. RESULTS: We evaluated 83 patients after excluding 18 with mild OSAS and 5 with nocturnal polyuria index <0.35. Participants with OSAS had higher apnea-hypopnea index (P < .0001) than those without OSAS. Body mass index and systolic blood pressure were higher in OSAS patients than those in the control group. BNP was higher in the OSAS patients than in the control patients (48.6 ± 41.4 vs 30.7 ± 31.5; P = .0006). On urinalysis, OSAS patients showed higher urinary sodium and u-Cre secretion than controls (24.7 ± 11.3 vs 16.2 ± 5.1; P <.0001). Urine osmolarity was also higher in OSAS patients than in the control patients (616 ± 172 vs 516 ± 174; P = .0285). There was no significant difference in urinary ADH and u-Cre (6.7 ± 10.4 vs 6.8 ± 7.8; P = .3617) between the 2 groups. CONCLUSION: Our results indicated that older men with nocturnal polyuria and OSAS did not compensate their fluid imbalance presented with decreased secretion of ADH but increased BNP level.博士（医学）・乙第1349号・平成26年12月3日Copyright © 2014 Elsevier Inc. All rights reserved

Authentic role of ATP signaling in micturition reflex

Adenosine triphosphate (ATP) is a signaling molecule that regulates cellular processes. Based on previous studies of bladder function over the past decade, bladder ATP signaling was thought to have an essential role in the normal micturition reflex. In this study, we performed detailed analyses of bladder function in purinergic receptor-deficient mice using the automated voided stain on paper method and video-urodynamics. Unexpectedly, a lack of P2X2 or P2X3 receptors did not affect bladder function under normal physiological conditions, indicating that bladder ATP signaling is not essential for normal micturition reflex. In contrast, we found that lipopolysaccharide (LPS) induced markedly high levels of ATP release from the urothelium. In addition, LPS-induced rapid bladder hyperactivity was attenuated in P2X2 -/- and P2X3 -/- mice. Contrary to the previous interpretation, our present findings indicate that bladder ATP signaling has a fundamental role in the micturition reflex, especially in bladder dysfunction, under pathological conditions. Therefore, the bladder ATP signaling pathway might be a highly promising therapeutic target for functional bladder disorders. This study newly defines an authentic role for bladder ATP signaling in the micturition reflex

Introduction for Fisheries and Aquatic Biology

Chapter I. Aquatic Environment. Ken FURUYA and Ichiro YASUDA : chapter_1.pdfChapter II. Biology and Ecology of Aqua-Shere. Toyoji KANEKO, Katsumi TSUKAMOTO, Atsushi TSUDA, Yuzuru SUZUKI and Katsufumi SATOH : chapter_2.pdfChapter III. Aquatic Resource and Production. Ichiro AOKI, Kazuo OGAWA, Taku YAMAKAWA and Tomoyoshi YOSHINAGA : chapter_3.pdfChapter IV. Chemistry of Aquatic Organism and Their Utilization. Hiroki ABE, Shugo WATABE, Yoshihiro OCHIAI, Shigeru OKADA, Naoko YOSHIKAWA, Yoshiharu KINOSHITA, Gen KANEKO and Shigeki MATSUNAGA : chapter_4.pdfChapter V. Relation between Aqua-Shere and Human Life. Hisashi KUROKURA, Hirohide MATSUSHIMA, Shingo KUROHAGI, Haruko YAMASHITA, Akinori HINO, Kazumasa IKUTA, Satoquo SEINO, Masahiko ARIJI, Ken FURUYA, Junichiro OKAMOTO and Nobuyuki YAGI : chapter_5.pdfPart of "Introduction for Fisheries and Aquatic Biology

Some japanese flowers

Copia digital. España : Ministerio de Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 2021Datos de tít. y mención de resp. tomados de la cub.Datos de publicación tomados de la cub.Fecha de 1897 tomada del Worldca

Kamibashi Bridge, the Otani River

This image is a scan taken from a hand coloured lantern slide. For more information about lantern slides see link below. Ogawa Kazumasa (小川 一眞, September 29, 1860 - September 7, 1929), also known as Ogawa Kazuma or Ogawa Isshin, was a Japanese photographer, printer and publisher who was a pioneer in photomechanical printing and photography in the Meiji era. The red painted Kami bridge built over Daiya River is located at the entrance of Nikko Shaji. There were joints on the bridge girders, as in the photo, before the Kami bridge was destroyed by a flood in 1902. The present Kami bridge does not have joints in the bridge girders. There is an electric pole to the side of Rinoji in the right side of the photo, showing that it was taken after 1891 when the Nikko hydraulic power plant was built

Motomiya Garden, Hikone, Japan

This image is a scan taken from a hand coloured lantern slide. For more information about lantern slides see link below. The Hakkeitei from the lake. A woman leans on the handrail of the Hakkeitei veranda and looks at the camera. A boat comes nearby, with three women dressed in kimono. One sits, and two others stand holding umbrellas. The boatman stands at the helm and the man in the stern holds a pole