Nagoya, Japan
Nagoya, Japan

Aichi Medical University is a private university at Nagakute, Aichi, Japan, founded in 1971. Wikipedia.


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Miettinen M.,Aichi Medical University
American Journal of Surgical Pathology | Year: 2017

Most gastrointestinal stromal tumors (GISTs) occur in the tubular gastrointestinal (GI) tract, but some present apparently outside the GI tract. In this study, we analyzed 112 GISTs located in the retroperitoneum. These tumors occurred in 55 women and 57 men with a median age of 65 years (range: 21 to 89 y). On the basis of clinically or histologically detected connections to GI tract, 15 tumors were considered likely of gastric, 9 duodenal, and 13 of small intestinal origin. The remaining cases were categorized by location as peripancreatic (n=25), pelvic (n=11), mesenteric (n=4), and of unspecified/miscellaneous sites (n=35). The tumors varied in size 3 to 35 cm (median, 15 cm) and by mitotic rate per 5 mm, 0 to >100 (median, 10). Histologically the tumors apparently arising outside the GI tract had features of intestinal (n=41) and gastric GISTs (n=25); 9 cases had indeterminate histology. The histologic variants included spindled, epithelioid, vacuolated, nested, and myxoid potentially simulating other tumors such as liposarcoma and solitary fibrous tumor. Most GISTs were KIT-positive (106/112 cases), and the remaining 6 tumors were DOG1/Ano1-positive. Five cases showed focal nuclear positivity for MDM2. KIT mutations were detected in 42/59 cases, and PDGFRA mutations in 4/16 KIT wild-type and 3/5 of the KIT-negative tumors analyzed. One pelvic retroperitoneal GIST was succinate dehydrogenase deficient. All 79 patients were dead at last follow-up with a median survival of 14 months, with few survivals >5 years. Only operable versus inoperable tumor was a statistically favorable factor in univariate analysis (P<0.01). In multivariate analysis, mitotic rate >50/5 mm was significant for a shorter survival (hazard ratio, 5.25; 95% confidence interval, 1.65-16.8; P<0.01). Histologic and clinicopathologic similarity of extragastrointestinal retroperitoneal GISTs with GISTs of GI tract suggests their GI tract origin. Potentially overlapping features between GIST and other retroperitoneal tumors necessitate use of multiple diagnostic markers and molecular genetic studies. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Treatment of pain will be guided by the KIBIT artificial intelligence engine. Judgment criteria of a multidisciplinary chronic pain management team will be utilized to develop algorithms for the diagnosis and management of chronic pain. TOKYO, May 08, 2017 (GLOBE NEWSWIRE) -- Aichi Medical University, Nippon Zoki Pharmaceutical Co., Ltd., and FRONTEO Healthcare, Inc. (“FRONTEO Healthcare”), a subsidiary of FRONTEO, Inc. (NASDAQ:FTEO) (TSE:2158) that provides medical data analysis solutions using the artificial intelligence (“AI”) engine “KIBIT”, announced today that the three parties have begun their joint research to develop an AI system that supports the diagnosis and management of chronic pain. Chronic pain arises from a spectrum of both known and unknown etiologies. In addition to the tremendous morbidity which results, it is also a major driver of the increase in healthcare costs. Optimal diagnosis and treatment of chronic pain requires a multidisciplinary approach encompassing medical, neurological, psychosocial, and occupational expertise.  As Japan is an aging society with high stress levels, the number of patients with chronic pain is expected to increase dramatically over the next few decades. Aichi Medical University established Japan’s first multidisciplinary management and research facility for chronic pain, the Multidisciplinary Pain Center (the “Pain Center”). The Pain Center includes anesthesiologists, orthopedic surgeons, psychiatrists, nurses, physiotherapists, and clinical psychologists, all highly focused on the management of pain. In addition, approximately 7,000 patients are cared for annually at the Pain Center. The KIBIT joint research will develop algorithms focused on the diagnosis and treatment of chronic pain. Aichi Medical University will provide anonymous medical records of patients with pain and their corresponding multidisciplinary management. FRONTEO Healthcare will be responsible for the analysis and optimization of algorithms incorporating this knowledge base into KIBIT. Nippon Zoki will provide financial support and business development expertise. After a one-year initiation phase, the involved parties will proceed with the development of a commercialized diagnostic platform to support pain management in Japanese clinics and hospitals. Ultimately, this project will enable better and more cost effective care of pain management across Japan. About Aichi Medical University Aichi Medical University opened in 1972 as a single-subject university having only a medical department, with the primary founding principle of “training physicians that can respond to the needs of a new age, and providing medical service to the local community.” In the year 2000, with the opening of the Department of Nursing in order to “train nursing staff with a broad perspective and high level of education, to respond rapidly and proactively to a variety of social needs,” it became a medical university with two departments. The ethos and objective of the university is “to train personnel to work in medicine and healthcare in a new era, within a fully-equipped education and research environment, and to contribute to social welfare, particularly regional healthcare, and cooperate to international progress and improvements in healthcare, reflecting the characteristics of a private university.” Aichi Medical University will continue to develop these activities even further in the future, with the fundamental policy of being “a winning medical university that is highly regarded in society,” and work on new reforms to reach greater heights in all areas, whether in education, research or treatment, to win out in the modern competitive age. URL: http://www.aichi-med-u.ac.jp/ About Nippon Zoki Pharmaceutical Co., Ltd. Founded over 75 years ago, with the motto of “Creativity and Safety,” Nippon Zoki Pharmaceutical Co., Ltd. is a research-and-development-based pharmaceutical manufacturer involved in the development, manufacture and sale of prescription pharmaceuticals and drugstore pharmaceuticals rooted in the needs of patients and physicians, mainly in the fields of pain treatment, skin disease, and allergic disease. Its drug Neurotropin is recommended by the Japan Society of Pain Clinicians as the first-line treatment for post-herpetic neuralgia, and boasts top-class figures among analgesics for domestic prescriptions and sales. In addition to the Japanese market, in 1994 Nippon Zoki expanded its business to China, and is developing its business manufacturing and selling its own products in the ASEAN market, centered on the business in Vietnam it started in 2008. In the future, it aims to move into the health-tech business, including management of patient healthcare, support for treatment by healthcare professionals, and the development of software healthcare devices to reduce workloads, to contribute further to clinical practice. URL: http://www.nippon-zoki.co.jp/. About FRONTEO, Inc. FRONTEO, Inc. (“FRONTEO”) (Nasdaq:FTEO) (TSE:2158) supports the analysis of big data based on behavior informatics by utilizing its technology, "KIBIT". FRONTEO's KIBIT technology is driven by FRONTEO artificial intelligence based on knowledge acquired through its litigation support services. KIBIT incorporates experts' tacit knowledge, including their experiences and intuitions, and utilizes that knowledge for big data analysis. FRONTEO continues to expand its business operations by applying KIBIT to new fields such as healthcare and marketing. FRONTEO was founded in 2003 as a provider of e-discovery and international litigation support services. These services include the preservation, investigation and analysis of evidence materials contained in electronic data, and computer forensic investigation. FRONTEO provides e-discovery and litigation support by making full use of its data analysis platform, "Lit i View", and its Predictive Coding technology adapted to Asian languages. The company name was changed from UBIC, Inc. to FRONTEO, Inc. as of July 1, 2016. For more information about FRONTEO, contact global_pr@fronteo.com or visit http://www.fronteo.com/global/. Safe Harbor Statement This announcement contains forward-looking statements. These forward-looking statements are made under the "safe harbor" provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates" and similar statements. Among other things, the amount of data that FRONTEO expects to manage this year and the potential uses for FRONTEO's new service in intellectual property-related litigation, contain forward-looking statements. FRONTEO may also make written or oral forward-looking statements in its reports filed with, or furnished to, the U.S. Securities and Exchange Commission, in its annual reports to shareholders, in press releases and other written materials and in oral statements made by its officers, directors or employees to third parties. Statements that are not historical facts, including statements about FRONTEO's beliefs and expectations, are forward-looking statements. Forward-looking statements involve inherent risks and uncertainties. A number of factors could cause actual results to differ materially from those contained in any forward-looking statement, including but not limited to the following: FRONTEO's goals and strategies; FRONTEO's expansion plans; the expected growth of the data center services market; expectations regarding demand for, and market acceptance of, FRONTEO's services; FRONTEO's expectations regarding keeping and strengthening its relationships with customers; FRONTEO's plans to invest in research and development to enhance its solution and service offerings; and general economic and business conditions in the regions where FRONTEO provides solutions and services. Further information regarding these and other risks is included in FRONTEO's reports filed with, or furnished to the Securities and Exchange Commission. FRONTEO does not undertake any obligation to update any forward-looking statement, except as required under applicable law. All information provided in this press release and in the attachments is as of the date of this press release, and FRONTEO undertakes no duty to update such information, except as required under applicable law.


Treatment of pain will be guided by the KIBIT artificial intelligence engine. Judgment criteria of a multidisciplinary chronic pain management team will be utilized to develop algorithms for the diagnosis and management of chronic pain. TOKYO, May 08, 2017 (GLOBE NEWSWIRE) -- Aichi Medical University, Nippon Zoki Pharmaceutical Co., Ltd., and FRONTEO Healthcare, Inc. (“FRONTEO Healthcare”), a subsidiary of FRONTEO, Inc. (NASDAQ:FTEO) (TSE:2158) that provides medical data analysis solutions using the artificial intelligence (“AI”) engine “KIBIT”, announced today that the three parties have begun their joint research to develop an AI system that supports the diagnosis and management of chronic pain. Chronic pain arises from a spectrum of both known and unknown etiologies. In addition to the tremendous morbidity which results, it is also a major driver of the increase in healthcare costs. Optimal diagnosis and treatment of chronic pain requires a multidisciplinary approach encompassing medical, neurological, psychosocial, and occupational expertise.  As Japan is an aging society with high stress levels, the number of patients with chronic pain is expected to increase dramatically over the next few decades. Aichi Medical University established Japan’s first multidisciplinary management and research facility for chronic pain, the Multidisciplinary Pain Center (the “Pain Center”). The Pain Center includes anesthesiologists, orthopedic surgeons, psychiatrists, nurses, physiotherapists, and clinical psychologists, all highly focused on the management of pain. In addition, approximately 7,000 patients are cared for annually at the Pain Center. The KIBIT joint research will develop algorithms focused on the diagnosis and treatment of chronic pain. Aichi Medical University will provide anonymous medical records of patients with pain and their corresponding multidisciplinary management. FRONTEO Healthcare will be responsible for the analysis and optimization of algorithms incorporating this knowledge base into KIBIT. Nippon Zoki will provide financial support and business development expertise. After a one-year initiation phase, the involved parties will proceed with the development of a commercialized diagnostic platform to support pain management in Japanese clinics and hospitals. Ultimately, this project will enable better and more cost effective care of pain management across Japan. About Aichi Medical University Aichi Medical University opened in 1972 as a single-subject university having only a medical department, with the primary founding principle of “training physicians that can respond to the needs of a new age, and providing medical service to the local community.” In the year 2000, with the opening of the Department of Nursing in order to “train nursing staff with a broad perspective and high level of education, to respond rapidly and proactively to a variety of social needs,” it became a medical university with two departments. The ethos and objective of the university is “to train personnel to work in medicine and healthcare in a new era, within a fully-equipped education and research environment, and to contribute to social welfare, particularly regional healthcare, and cooperate to international progress and improvements in healthcare, reflecting the characteristics of a private university.” Aichi Medical University will continue to develop these activities even further in the future, with the fundamental policy of being “a winning medical university that is highly regarded in society,” and work on new reforms to reach greater heights in all areas, whether in education, research or treatment, to win out in the modern competitive age. URL: http://www.aichi-med-u.ac.jp/ About Nippon Zoki Pharmaceutical Co., Ltd. Founded over 75 years ago, with the motto of “Creativity and Safety,” Nippon Zoki Pharmaceutical Co., Ltd. is a research-and-development-based pharmaceutical manufacturer involved in the development, manufacture and sale of prescription pharmaceuticals and drugstore pharmaceuticals rooted in the needs of patients and physicians, mainly in the fields of pain treatment, skin disease, and allergic disease. Its drug Neurotropin is recommended by the Japan Society of Pain Clinicians as the first-line treatment for post-herpetic neuralgia, and boasts top-class figures among analgesics for domestic prescriptions and sales. In addition to the Japanese market, in 1994 Nippon Zoki expanded its business to China, and is developing its business manufacturing and selling its own products in the ASEAN market, centered on the business in Vietnam it started in 2008. In the future, it aims to move into the health-tech business, including management of patient healthcare, support for treatment by healthcare professionals, and the development of software healthcare devices to reduce workloads, to contribute further to clinical practice. URL: http://www.nippon-zoki.co.jp/. About FRONTEO, Inc. FRONTEO, Inc. (“FRONTEO”) (Nasdaq:FTEO) (TSE:2158) supports the analysis of big data based on behavior informatics by utilizing its technology, "KIBIT". FRONTEO's KIBIT technology is driven by FRONTEO artificial intelligence based on knowledge acquired through its litigation support services. KIBIT incorporates experts' tacit knowledge, including their experiences and intuitions, and utilizes that knowledge for big data analysis. FRONTEO continues to expand its business operations by applying KIBIT to new fields such as healthcare and marketing. FRONTEO was founded in 2003 as a provider of e-discovery and international litigation support services. These services include the preservation, investigation and analysis of evidence materials contained in electronic data, and computer forensic investigation. FRONTEO provides e-discovery and litigation support by making full use of its data analysis platform, "Lit i View", and its Predictive Coding technology adapted to Asian languages. The company name was changed from UBIC, Inc. to FRONTEO, Inc. as of July 1, 2016. For more information about FRONTEO, contact global_pr@fronteo.com or visit http://www.fronteo.com/global/. Safe Harbor Statement This announcement contains forward-looking statements. These forward-looking statements are made under the "safe harbor" provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates" and similar statements. Among other things, the amount of data that FRONTEO expects to manage this year and the potential uses for FRONTEO's new service in intellectual property-related litigation, contain forward-looking statements. FRONTEO may also make written or oral forward-looking statements in its reports filed with, or furnished to, the U.S. Securities and Exchange Commission, in its annual reports to shareholders, in press releases and other written materials and in oral statements made by its officers, directors or employees to third parties. Statements that are not historical facts, including statements about FRONTEO's beliefs and expectations, are forward-looking statements. Forward-looking statements involve inherent risks and uncertainties. A number of factors could cause actual results to differ materially from those contained in any forward-looking statement, including but not limited to the following: FRONTEO's goals and strategies; FRONTEO's expansion plans; the expected growth of the data center services market; expectations regarding demand for, and market acceptance of, FRONTEO's services; FRONTEO's expectations regarding keeping and strengthening its relationships with customers; FRONTEO's plans to invest in research and development to enhance its solution and service offerings; and general economic and business conditions in the regions where FRONTEO provides solutions and services. Further information regarding these and other risks is included in FRONTEO's reports filed with, or furnished to the Securities and Exchange Commission. FRONTEO does not undertake any obligation to update any forward-looking statement, except as required under applicable law. All information provided in this press release and in the attachments is as of the date of this press release, and FRONTEO undertakes no duty to update such information, except as required under applicable law.


Treatment of pain will be guided by the KIBIT artificial intelligence engine. Judgment criteria of a multidisciplinary chronic pain management team will be utilized to develop algorithms for the diagnosis and management of chronic pain. TOKYO, May 08, 2017 (GLOBE NEWSWIRE) -- Aichi Medical University, Nippon Zoki Pharmaceutical Co., Ltd., and FRONTEO Healthcare, Inc. (“FRONTEO Healthcare”), a subsidiary of FRONTEO, Inc. (NASDAQ:FTEO) (TSE:2158) that provides medical data analysis solutions using the artificial intelligence (“AI”) engine “KIBIT”, announced today that the three parties have begun their joint research to develop an AI system that supports the diagnosis and management of chronic pain. Chronic pain arises from a spectrum of both known and unknown etiologies. In addition to the tremendous morbidity which results, it is also a major driver of the increase in healthcare costs. Optimal diagnosis and treatment of chronic pain requires a multidisciplinary approach encompassing medical, neurological, psychosocial, and occupational expertise.  As Japan is an aging society with high stress levels, the number of patients with chronic pain is expected to increase dramatically over the next few decades. Aichi Medical University established Japan’s first multidisciplinary management and research facility for chronic pain, the Multidisciplinary Pain Center (the “Pain Center”). The Pain Center includes anesthesiologists, orthopedic surgeons, psychiatrists, nurses, physiotherapists, and clinical psychologists, all highly focused on the management of pain. In addition, approximately 7,000 patients are cared for annually at the Pain Center. The KIBIT joint research will develop algorithms focused on the diagnosis and treatment of chronic pain. Aichi Medical University will provide anonymous medical records of patients with pain and their corresponding multidisciplinary management. FRONTEO Healthcare will be responsible for the analysis and optimization of algorithms incorporating this knowledge base into KIBIT. Nippon Zoki will provide financial support and business development expertise. After a one-year initiation phase, the involved parties will proceed with the development of a commercialized diagnostic platform to support pain management in Japanese clinics and hospitals. Ultimately, this project will enable better and more cost effective care of pain management across Japan. About Aichi Medical University Aichi Medical University opened in 1972 as a single-subject university having only a medical department, with the primary founding principle of “training physicians that can respond to the needs of a new age, and providing medical service to the local community.” In the year 2000, with the opening of the Department of Nursing in order to “train nursing staff with a broad perspective and high level of education, to respond rapidly and proactively to a variety of social needs,” it became a medical university with two departments. The ethos and objective of the university is “to train personnel to work in medicine and healthcare in a new era, within a fully-equipped education and research environment, and to contribute to social welfare, particularly regional healthcare, and cooperate to international progress and improvements in healthcare, reflecting the characteristics of a private university.” Aichi Medical University will continue to develop these activities even further in the future, with the fundamental policy of being “a winning medical university that is highly regarded in society,” and work on new reforms to reach greater heights in all areas, whether in education, research or treatment, to win out in the modern competitive age. URL: http://www.aichi-med-u.ac.jp/ About Nippon Zoki Pharmaceutical Co., Ltd. Founded over 75 years ago, with the motto of “Creativity and Safety,” Nippon Zoki Pharmaceutical Co., Ltd. is a research-and-development-based pharmaceutical manufacturer involved in the development, manufacture and sale of prescription pharmaceuticals and drugstore pharmaceuticals rooted in the needs of patients and physicians, mainly in the fields of pain treatment, skin disease, and allergic disease. Its drug Neurotropin is recommended by the Japan Society of Pain Clinicians as the first-line treatment for post-herpetic neuralgia, and boasts top-class figures among analgesics for domestic prescriptions and sales. In addition to the Japanese market, in 1994 Nippon Zoki expanded its business to China, and is developing its business manufacturing and selling its own products in the ASEAN market, centered on the business in Vietnam it started in 2008. In the future, it aims to move into the health-tech business, including management of patient healthcare, support for treatment by healthcare professionals, and the development of software healthcare devices to reduce workloads, to contribute further to clinical practice. URL: http://www.nippon-zoki.co.jp/. About FRONTEO, Inc. FRONTEO, Inc. (“FRONTEO”) (Nasdaq:FTEO) (TSE:2158) supports the analysis of big data based on behavior informatics by utilizing its technology, "KIBIT". FRONTEO's KIBIT technology is driven by FRONTEO artificial intelligence based on knowledge acquired through its litigation support services. KIBIT incorporates experts' tacit knowledge, including their experiences and intuitions, and utilizes that knowledge for big data analysis. FRONTEO continues to expand its business operations by applying KIBIT to new fields such as healthcare and marketing. FRONTEO was founded in 2003 as a provider of e-discovery and international litigation support services. These services include the preservation, investigation and analysis of evidence materials contained in electronic data, and computer forensic investigation. FRONTEO provides e-discovery and litigation support by making full use of its data analysis platform, "Lit i View", and its Predictive Coding technology adapted to Asian languages. The company name was changed from UBIC, Inc. to FRONTEO, Inc. as of July 1, 2016. For more information about FRONTEO, contact global_pr@fronteo.com or visit http://www.fronteo.com/global/. Safe Harbor Statement This announcement contains forward-looking statements. These forward-looking statements are made under the "safe harbor" provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates" and similar statements. Among other things, the amount of data that FRONTEO expects to manage this year and the potential uses for FRONTEO's new service in intellectual property-related litigation, contain forward-looking statements. FRONTEO may also make written or oral forward-looking statements in its reports filed with, or furnished to, the U.S. Securities and Exchange Commission, in its annual reports to shareholders, in press releases and other written materials and in oral statements made by its officers, directors or employees to third parties. Statements that are not historical facts, including statements about FRONTEO's beliefs and expectations, are forward-looking statements. Forward-looking statements involve inherent risks and uncertainties. A number of factors could cause actual results to differ materially from those contained in any forward-looking statement, including but not limited to the following: FRONTEO's goals and strategies; FRONTEO's expansion plans; the expected growth of the data center services market; expectations regarding demand for, and market acceptance of, FRONTEO's services; FRONTEO's expectations regarding keeping and strengthening its relationships with customers; FRONTEO's plans to invest in research and development to enhance its solution and service offerings; and general economic and business conditions in the regions where FRONTEO provides solutions and services. Further information regarding these and other risks is included in FRONTEO's reports filed with, or furnished to the Securities and Exchange Commission. FRONTEO does not undertake any obligation to update any forward-looking statement, except as required under applicable law. All information provided in this press release and in the attachments is as of the date of this press release, and FRONTEO undertakes no duty to update such information, except as required under applicable law.


Patent
University of Tokyo, Institute Of Immunology Co. and Aichi Medical University | Date: 2014-09-03

It is an object of the present invention to provide a monoclonal antibody, which is suitable for the quantitative analysis of asparagine synthetase in a cell. The present invention provides a monoclonal antibody which specifically recognizes asparagine synthetase that is present in a cell.


Patent
University of Tokyo, Aichi Medical University and Institute Of Immunology Co. | Date: 2012-10-03

It is an object of the present invention to provide a monoclonal antibody, which is suitable for the quantitative analysis of asparagine synthetase in a cell. The present invention provides a monoclonal antibody which specifically recognizes asparagine synthetase that is present in a cell.


Takahashi E.,Aichi Medical University
Journal of clinical and experimental hematopathology : JCEH | Year: 2013

Histiocytic sarcoma (HS) is an extremely rare malignant neoplasm showing morphologic and immunophenotypic evidence of histiocytic differentiation. The vast majority of previously reported HSs are now generally recognized to be misdiagnosed examples of non-Hodgkin lymphomas, predominantly diffuse large B-cell lymphoma or anaplastic large cell lymphoma. The recognition of such tumors parallels the development and widespread use of immunohistochemical techniques, along with the development of molecular genetic methods to detect immunoglobulin (IG) or T-cell receptor (TCR) gene rearrangement. The 2001 World Health Organization (WHO) definition of HS requires the absence of clonal B/T-cell receptor gene rearrangements. However, the 2008 WHO classification no longer strictly requires the absence of clonal immunoglobulin heavy chain (IGH) or TCR gene rearrangement for the diagnosis of HS. Recent studies demonstrated that HSs that occur subsequent to or concurrent with B- or T-lymphoblastic lymphoma/leukemia or mature B-cell neoplasms generally show clonal IgH and/or TCR gene rearrangement. These findings suggest the possibility of transdifferentiation of the two otherwise morphologically and immunohistochemically distinctive neoplasms. In addition, a recent study suggested clonal IG gene rearrangements may be detected at a high frequency in sporadic HS, indicating that a large subset of sporadic HSs may inherit the B-lymphocyte genotype. These findings provide new insights into the pathogenesis of HS, although the etiology of HS is still unknown. HS is a diagnosis of exclusion. It is necessary to rule out other diseases that could be misdiagnosed as HS with extensive immunophenotypical analysis before diagnosing HS.


Yokochi T.,Aichi Medical University
Innate Immunity | Year: 2012

We have recently established a new experimental murine model for lipopolysaccharide (LPS)-mediated lethal shock with lung-specific injury. Severe lung injury is induced by administration of LPS into α-galactosylceramide (α-GalCer)-sensitized mice; the mice died with acute lung injury and respiratory distress within 24 h. α-GalCer activates natural killer T (NKT) cells in the lungs and liver, and induces the production of interferon (IFN)-γ. However, IFN-γ signaling is only triggered in the lungs and makes them susceptible to LPS. On the other hand, IFN-γ signaling is inhibited in liver and results in few hepatic lesions. Unlike liver NKT cells, lung NKT cells fail to produce interleukin (IL)-4, which down-regulates the IFN-γ signaling, in response to α-GalCer. The differential cytokine profile between lung and liver NKT cells may lead to organ-specific lung lesions. The experimental system using α-GalCer sensitization could be a useful experimental model for clinical endotoxic or septic shock as it presents respiratory failure, a typical manifestation in severe septic patients. In this review, key evidence and the introducuction of the detailed mechanism of LPS-mediated lung-specific injury in α-GalCer-sensitized mice is provided. In particular, the molecular background of organ-specific development of lung injury in the model is focused on. © The Author(s) 2011.


Yamamoto T.,Aichi Medical University
Transplantation | Year: 2015

BACKGROUND: It is unclear whether all donor-specific antibodies (DSA) can cause chronic antibody-mediated rejection (AMR). Subclinical stage before manifestation of renal dysfunction may be a critical period for reversing AMR. The aim of our study was to identify factors related to the development of subclinical AMR and to clarify the characteristics of de novo DSA. METHODS: Eight hundred ninety-nine renal transplants were screened for HLA antibody. De novo DSA were detected in 95 patients. Forty-three patients without renal dysfunction who underwent renal biopsies were enrolled in this study. Eighteen patients (41.9%) were diagnosed with biopsy-proven subclinical AMR and treated with plasmapheresis and rituximab-based therapy, whereas 25 showed no findings of AMR. RESULTS: Significant subclinical AMR-related factors were younger recipients, history of acute T cell–mediated rejection and DSA class II, especially DR-associated DSA. Mean fluorescence intensity (MFI) values of DR-DSA were significantly higher, whereas DQ-DSA was not different between subclinical AMR and no AMR. The ΔMFI (>50%), DSA-MFI values greater than 3000, and C1q binding DSA were also significant subclinical AMR-related factors (P < 0.05). Among 18 patients treated for subclinical AMR, 8 patients (44.4%) obtained over 50% reduction of DSA-MFI and/or improvement or no deterioration of pathological findings. In contrast, 25 patients without subclinical AMR did not show renal dysfunction clinically. Moreover, all of the 8 patients with rebiopsy after 2 years continued to demonstrate no AMR. CONCLUSIONS: About 40% of patients with de novo DSA demonstrated biopsy-proven subclinical AMR, leading to progressive graft injury. To validate the intervention and treatment for de novo DSA-positive patients without renal dysfunction, further study is necessary. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Sato M.,Aichi Medical University
Circulation Journal | Year: 2013

Signal processing via heterotrimeric G-proteins is one of the most widely used systems for signal transfer across the cell membrane. This signaling system regulates most physiological and pathophysiological processes in mammals and is therefore the primary target of many pharmaceutical agents. The heterotrimeric G-protein signaling system includes the G-protein-coupled receptor (GPCR), heterotrimeric G-proteins, and effectors. The G-proteins are activated by the GPCR to mediate a signal to effector molecules. However, other players in this system that regulate the activation status of heterotrimeric G-proteins independently of GPCR have been identified. Such accessory proteins for heterotrimeric G-protein can provide additional signal input to the G-protein signaling system, or may act as alternative binding partners of G-protein subunits serving as yet unknown roles in cells. It has been reported that this class of proteins is expressed in the cardiovascular system and contributes to signal integration involved in the various diseases. This review provides an overview of the current understanding of accessory proteins for heterotrimeric G-proteins in their 4 functional subsets, including guanine nucleotide exchange factors (GEFs), guanine nucleotide dissociation inhibitors (GDIs), GTPase-activating proteins (GAPs), and Gβγ-interacting proteins, and discusses their roles in the development of cardiovascular diseases. Better understanding of these components may contribute new insight into the complex network of molecules governing GPCR signaling in the cardiovascular system.

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