98 results on '"Hitoshi Kitayama"'
Search Results
2. The RECK tumor-suppressor protein binds and stabilizes ADAMTS10
- Author
-
Tomoko Matsuzaki, Hitoshi Kitayama, Akira Omura, Emi Nishimoto, David B. Alexander, and Makoto Noda
- Subjects
RECK ,ADAMTS10 ,Tumor suppressor ,Fibronectin ,MT1-MMP ,Yeast two-hybrid assay ,Science ,Biology (General) ,QH301-705.5 - Abstract
The tumor suppressor protein RECK has been implicated in the regulation of matrix metalloproteinases (MMPs), NOTCH-signaling and WNT7-signaling. It remains unclear, however, how broad the spectrum of RECK targets extends. To find novel RECK binding partners, we took the unbiased approach of yeast two-hybrid screening. This approach detected ADAMTS10 as a RECK-interactor. ADAMTS10 has been characterized as a metalloproteinase involved in fibrillin-rich microfibril biogenesis, and its mutations have been implicated in the connective tissue disorder Weill-Marchesani syndrome. Experiments in vitro using recombinant proteins expressed in mammalian cells indicated that RECK indeed binds ADAMTS10 directly, that RECK protects ADAMTS10 from fragmentation following chemical activation and that ADAMTS10 interferes with the activity of RECK to inhibit MT1-MMP. In cultured cells, RECK increases the amount of ADAMTS10 associated with the cells. Hence, the present study has uncovered novel interactions between two molecules of known clinical importance, RECK and ADAMTS10. This article has an associated First Person interview with the first author of the paper.
- Published
- 2018
- Full Text
- View/download PDF
3. The transformation suppressor gene Reck is required for postaxial patterning in mouse forelimbs
- Author
-
Mako Yamamoto, Tomoko Matsuzaki, Rei Takahashi, Eijiro Adachi, Yasuhiro Maeda, Sachiyo Yamaguchi, Hitoshi Kitayama, Michiko Echizenya, Yoko Morioka, David B. Alexander, Takeshi Yagi, Shigeyoshi Itohara, Takashi Nakamura, Haruhiko Akiyama, and Makoto Noda
- Subjects
Mouse ,Reck ,Wnt7a ,Limb patterning ,Cutaneous horn ,Teratogens ,Science ,Biology (General) ,QH301-705.5 - Abstract
Summary The membrane-anchored metalloproteinase-regulator RECK has been characterized as a tumor suppressor. Here we report that mice with reduced Reck-expression show limb abnormalities including right-dominant, forelimb-specific defects in postaxial skeletal elements. The forelimb buds of low-Reck mutants have an altered dorsal ectoderm with reduced Wnt7a and Igf2 expression, and hypotrophy in two signaling centers (i.e., ZPA and AER) that are essential for limb outgrowth and patterning. Reck is abundantly expressed in the anterior mesenchyme in normal limb buds; mesenchyme-specific Reck inactivation recapitulates the low-Reck phenotype; and some teratogens downregulate Reck in mesenchymal cells. Our findings illustrate a role for Reck in the mesenchymal-epithelial interactions essential for mammalian development.
- Published
- 2012
- Full Text
- View/download PDF
4. Cardiac Resynchronization for Corrected Transposition of the Great Arteries with Systemic Right Ventricle Failure after Tricuspid Valve Replacement and Ventricle Septal Defect Closure
- Author
-
Kosuke Fujii, MD, Toshihiko Saga, MD, Hitoshi Kitayama, MD, Susumu Nakamoto, MD, Toshio Kaneda, MD, Hiroshi Kawasaki, MD, Kiyoaki Takaba, MD, Masato Imura, MD, Takako Nishino, MD, Shintaro Yukami, MD, and Junzo Iemura, MD
- Subjects
Cardiac resynchronization therapy ,Corrected TGA ,Systemic right ventricular failure ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
A 32-year-old man developed systemic right ventricular (RV) heart failure after ventricular septal defect (VSD) closure and tricuspid valve replacement for corrected transposition of the great arteries with VSD and Ebstein anomaly. He subsequently experienced RV failure with wide QRS and atrial fibrillation (AF). Because corrective surgery for this condition seemed over risky, we decided to perform cardiac resynchronization therapy with implantation of an implantable cardioverter defibrillator (CRT-D). After CRT-D device implantation, the patient showed improved performance status in terms of New York Heart Association functional class, B-type brain natriuretic peptide levels, RV ejection fraction and cardiac electrical rhythm. CRT-D implantation is a useful approach for systemic RV failure with wide QRS duration showing right bundle branch block and AF.
- Published
- 2010
- Full Text
- View/download PDF
5. Mid-Term Patency of Spiral Saphenous Vein Graft for Malignant Superior Vena Cava Syndrome
- Author
-
Takehiro Inoue, Kosuke Fujii, Toshio Kaneda, and Hitoshi Kitayama
- Subjects
Male ,Superior Vena Cava Syndrome ,Treatment Outcome ,Anticoagulants ,Humans ,Saphenous Vein ,Surgery ,Vascular Diseases ,General Medicine ,Cardiology and Cardiovascular Medicine ,Aged - Abstract
Reports documenting the mid-term patency of spiral saphenous vein grafts for superior vena cava syndrome in patients with advanced thoracic malignancy are, so far, scarce. The present report describes a 69-year-old man who suffered superior vena cava syndrome due to malignant invasion by advanced lung cancer. Since the huge mass in the anterior mediastinum was unresectable, a bypass from the left innominate vein to the right atrium using an autologous spiral saphenous vein graft was surgically created. Postoperatively, the patient received chemoradiotherapy and maintenance anticoagulant therapy, resulting in survival for 4 years without graft occlusion or recurrence of superior vena cava syndrome.
- Published
- 2022
6. Severe Regurgitant Bicuspid Aortic Valve in a Patient with Overlapping Left Ventricular Noncompaction and Asymmetrical Septal Hypertrophy.
- Author
-
Takehiro Inoue, Takuma Satsu, and Hitoshi Kitayama
- Abstract
Overlapping of left ventricular noncompaction (LVNC) and hypertrophic cardiomyopathy in the same patient is rare and is associated with a more severe clinical course and unfavorable prognosis. The present report describes the case of a severely regurgitant bicuspid aortic valve in a 68-year-old man with overlapping LVNC and asymmetrical septal hypertrophy. Aortic valve replacement controlled the left ventricular dilatation that occurred secondary to the volume overload induced by the valvular disease. However, even 3 years postoperatively, severe systolic dysfunction persisted due to the preexisting myocardial disease, requiring close and lifelong follow-up with special attention to life-threatening arrhythmias and thromboembolism. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
7. Hybrid Repair for Mega-Aortic Syndrome due to Giant Cell Aortitis in a Heart Failure Patient
- Author
-
Naoya Miyashita, Shintaro Yukami, Kosuke Fujii, Takehiro Inoue, Shigeo Kino, and Hitoshi Kitayama
- Subjects
medicine.medical_specialty ,hybrid repair ,giant cell aortitis ,business.industry ,Case Report ,mega-aortic syndrome ,General Medicine ,Regurgitation (circulation) ,medicine.disease ,Giant Cell Aortitis ,Surgery ,Steroid therapy ,Heart failure ,medicine ,business ,Stroke - Abstract
The present report describes a case of mega-aortic syndrome accompanied with severe aortic regurgitation in a 75-year-old man who underwent a two-stage hybrid repair. Intraoperative pathologic findings at the first repair, consisting of Bentall operation and total arch replacement with a Lupiae graft, aided the identification of the giant cell aortitis. Despite complicating hemorrhagic stroke, steroid therapy was initiated and endovascular repair was subsequently completed. Over more than 2 years of follow-up, the patient continued steroid therapy and is doing well without any reintervention.
- Published
- 2020
8. Giant Ascending Aortic Aneurysm and Pulmonary Arteriovenous Malformation in the Left Upper Lung Lobe
- Author
-
Takehiro Inoue, Takuma Satsu, and Hitoshi Kitayama
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung ,Aortic Aneurysm, Thoracic ,business.industry ,Pulmonary Artery ,medicine.disease ,Lung lobe ,Arteriovenous Malformations ,Aortic aneurysm ,Text mining ,medicine.anatomical_structure ,Cardiothoracic surgery ,Pulmonary Veins ,medicine ,Humans ,Surgery ,Female ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Pulmonary arteriovenous malformation ,Aged - Published
- 2020
9. Five-Year Clinical Outcome of Asymptomatic vs. Symptomatic Severe Aortic Stenosis After Aortic Valve Replacement
- Author
-
Junichiro Nishizawa, Kengo Korai, Naritatsu Saito, Michiya Hanyu, Kenji Ando, Katsuhisa Ishii, Shogo Nakayama, Takao Kato, Mitsuru Kitano, Kotaro Shiraga, Kenji Minakata, Toshihiko Saga, Keiichi Fujiwara, Norio Kanamori, Hitoshi Kitayama, Eri Minamino-Muta, Hiroyuki Nakajima, Tatsuhiko Komiya, Fumio Yamazaki, Moriaki Inoko, Koji Ueyama, Noboru Nishiwaki, Tsukasa Inada, Chisato Izumi, Shinichi Shirai, Koichiro Murata, Yuichi Kawase, Kazuo Yamanaka, Genichi Sakaguchi, Tadaaki Koyama, Tomohiko Taniguchi, Takeshi Kimura, Ryuzo Sakata, Senri Miwa, Takeshi Kitai, Atsushi Iwakura, and Takeshi Morimoto
- Subjects
Male ,medicine.medical_specialty ,Comorbidity ,030204 cardiovascular system & hematology ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Aortic valve replacement ,Risk Factors ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Aged ,Retrospective Studies ,Outcome ,Aged, 80 and over ,Heart Valve Prosthesis Implantation ,business.industry ,Aortic stenosis ,Age Factors ,General Medicine ,Aortic Valve Stenosis ,Middle Aged ,medicine.disease ,Valvular disease ,Surgery ,Stenosis ,Echocardiography ,Heart failure ,Landmark analysis ,Aortic Valve ,Cardiology ,Female ,medicine.symptom ,Operative risk ,Symptom Assessment ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background:There is discordance regarding the effect of symptom status before aortic valve replacement (AVR) on long-term outcome after AVR in severe aortic stenosis (AS). Methods and Results:The CURRENT AS registry is a multicenter retrospective registry enrolling 3, 815 consecutive patients with severe AS. Among 1, 196 patients managed with the initial AVR strategy, long-term clinical outcomes were compared between the symptomatic patients (n=905), and asymptomatic patients (n=291). Median follow-up interval was 1337 days with a 91% follow-up rate at 2 years. AVR was performed in 886 patients (98%) in the symptomatic group and in 287 patients (99%) in the asymptomatic group. Symptomatic patients were older and more often had comorbidities than asymptomatic patients with similar echocardiographic AS severity. The cumulative 5-year incidences of all-cause death and heart failure (HF) hospitalization were significantly higher in symptomatic patients than in asymptomatic patients (25.6% vs. 15.4%, P=0.001, and 14.2% vs. 3.8%, P
- Published
- 2017
10. Prognostic Impact of Aortic Valve Area in Conservatively Managed Patients With Asymptomatic Severe Aortic Stenosis With Preserved Ejection Fraction
- Author
-
Norio Kanamori, Tomohiko Taniguchi, Takeshi Morimoto, Hirotoshi Watanabe, Hiroki Shiomi, Kenji Ando, Koichiro Murata, Takeshi Kitai, Yuichi Kawase, Chisato Izumi, Makoto Miyake, Hirokazu Mitsuoka, Masashi Kato, Yutaka Hirano, Shintaro Matsuda, Kazuya Nagao, Tsukasa Inada, Hiroshi Mabuchi, Yasuyo Takeuchi, Keiichiro Yamane, Mamoru Toyofuku, Mitsuru Ishii, Eri Minamino‐Muta, Takao Kato, Moriaki Inoko, Tomoyuki Ikeda, Akihiro Komasa, Katsuhisa Ishii, Kozo Hotta, Nobuya Higashitani, Yoshihiro Kato, Yasutaka Inuzuka, Chiyo Maeda, Toshikazu Jinnai, Yuko Morikami, Naritatsu Saito, Kenji Minatoya, Takeshi Aoyama, Takeshi Kimura, Ryuzo Sakata, Masao Imai, Junichi Tazaki, Toshiaki Toyota, Hirooki Higami, Tetsuma Kawaji, Shinichi Shirai, Kengo Korai, Takeshi Arita, Shiro Miura, Kyohei Yamaji, Kitae Kim, Keiichiro Iwasaki, Hiroshi Miyawaki, Ayumi Misao, Akimune Kuwayama, Masanobu Ohya, Takenobu Shimada, Hidewo Amano, Masashi Amano, Yusuke Takahashi, Yusuke Yoshikawa, Shunsuke Nishimura, Maiko Kuroda, Tetsu Mizoguchi, Takafumi Yokomatsu, Akihiro Kushiyama, Hidenori Yaku, Toshimitsu Watanabe, Sachiko Sugioka, Naoki Takahashi, Kohei Fukuchi, Teruki Takeda, Tomoko Sakaguchi, Keiko Maeda, Masayuki Yamaji, Motoyoshi Maenaka, Yutaka Tadano, Makoto Motooka, Ryusuke Nishikawa, Mitsunori Kawato, Minako Kinoshita, Kenji Aida, Kousuke Takahashi, Euihong Ko, Nobutoyo Masunaga, Hisashi Ogawa, Moritake Iguchi, Takashi Unoki, Kensuke Takabayashi, Yasuhiro Hamatani, Yugo Yamashita, Shuhei Tsuji, Soji Nishio, Jyunya Seki, Miho Yamada, Akira Kawamoto, Kouji Sogabe, Michiya Tachiiri, Yukiko Matsumura, Chihiro Ota, Kenji Minakata, Michiya Hanyu, Fumio Yamazaki, Tadaaki Koyama, Tatsuhiko Komiya, Kazuo Yamanaka, Noboru Nishiwaki, Hiroyuki Nakajima, Motoaki Ohnaka, Hiroaki Osada, Katsuaki Meshii, Toshihiko Saga, Masahiko Onoe, Hitoshi Kitayama, Shogo Nakayama, Genichi Sakaguchi, Atsushi Iwakura, Kotaro Shiraga, Koji Ueyama, Keiichi Fujiwara, Atsushi Fukumoto, Senri Miwa, Junichiro Nishizawa, Mitsuru Kitano, Kenji Nakatsuma, and Tomoki Sasa
- Subjects
medicine.medical_specialty ,Aortic Valve Replacement/Transcather Aortic Valve Implantation ,aortic valve stenosis ,030204 cardiovascular system & hematology ,Severity of Illness Index ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Aortic valve replacement ,Internal medicine ,medicine ,asymptomatic ,echocardiography ,Humans ,aortic valve replacement ,030212 general & internal medicine ,Adverse effect ,Original Research ,Heart Valve Prosthesis Implantation ,Ejection fraction ,business.industry ,Background data ,Stroke Volume ,Prognosis ,medicine.disease ,Stenosis ,Aortic valve area ,Valvular Heart Disease ,Aortic Valve ,Aortic valve stenosis ,Asymptomatic Diseases ,Cardiology ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,aortic valve area - Abstract
Background Data are scarce on the role of aortic valve area (AVA) to identify those patients with asymptomatic severe aortic stenosis (AS) who are at high risk of adverse events. We sought to explore the prognostic impact of AVA in asymptomatic patients with severe AS in a large observational database. Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study included 1309 conservatively managed asymptomatic patients with left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on AVA (group 1: AVA >0.80 cm2, N=645; group 2: 0.8 cm2 ≥AVA >0.6 cm2, N=465; and group 3: AVA ≤0.6 cm2, N=199). The prevalence of very severe AS patients (peak aortic jet velocity ≥5 m/s or mean aortic pressure gradient ≥60 mm Hg) was 2.0%, 5.8%, and 26.1% in groups 1, 2, and 3, respectively. The cumulative 5‐year incidence of AVR was not different across the 3 groups (39.7%, 43.7%, and 39.9%; P=0.43). The cumulative 5‐year incidence of the primary outcome measure (a composite of aortic valve–related death or heart failure hospitalization) was incrementally higher with decreasing AVA (24.1%, 29.1%, and 48.1%; P, See Editorial by Tribouilloy et al
- Published
- 2019
11. The RECK tumor-suppressor protein binds and stabilizes ADAMTS10
- Author
-
Emi Nishimoto, Akira Omura, David B. Alexander, Makoto Noda, Hitoshi Kitayama, and Tomoko Matsuzaki
- Subjects
0301 basic medicine ,QH301-705.5 ,Two-hybrid screening ,Science ,Biology ,Matrix metalloproteinase ,General Biochemistry, Genetics and Molecular Biology ,law.invention ,03 medical and health sciences ,law ,MT1-MMP ,Biology (General) ,RECK ,Fibronectin ,Metalloproteinase ,ADAMTS10 ,Tumor suppressor ,In vitro ,Cell biology ,030104 developmental biology ,biology.protein ,Recombinant DNA ,Suppressor ,General Agricultural and Biological Sciences ,Yeast two-hybrid assay ,Biogenesis ,Research Article - Abstract
The tumor suppressor protein RECK has been implicated in the regulation of matrix metalloproteinases (MMPs), NOTCH-signaling and WNT7-signaling. It remains unclear, however, how broad the spectrum of RECK targets extends. To find novel RECK binding partners, we took the unbiased approach of yeast two-hybrid screening. This approach detected ADAMTS10 as a RECK-interactor. ADAMTS10 has been characterized as a metalloproteinase involved in fibrillin-rich microfibril biogenesis, and its mutations have been implicated in the connective tissue disorder Weill-Marchesani syndrome. Experiments in vitro using recombinant proteins expressed in mammalian cells indicated that RECK indeed binds ADAMTS10 directly, that RECK protects ADAMTS10 from fragmentation following chemical activation and that ADAMTS10 interferes with the activity of RECK to inhibit MT1-MMP. In cultured cells, RECK increases the amount of ADAMTS10 associated with the cells. Hence, the present study has uncovered novel interactions between two molecules of known clinical importance, RECK and ADAMTS10. This article has an associated First Person interview with the first author of the paper., Summary: RECK plays critical roles in tumor suppression and embryogenesis, while its mechanisms of actions remain largely obscure. This study has revealed the novel interaction between RECK and ADAMTS10.
- Published
- 2018
12. Prognostic Impact of Peak Aortic Jet Velocity in Conservatively Managed Patients With Severe Aortic Stenosis: An Observation From the CURRENT AS Registry
- Author
-
Kenji Nakatsuma, Tomohiko Taniguchi, Takeshi Morimoto, Hiroki Shiomi, Kenji Ando, Norio Kanamori, Koichiro Murata, Takeshi Kitai, Yuichi Kawase, Chisato Izumi, Makoto Miyake, Hirokazu Mitsuoka, Masashi Kato, Yutaka Hirano, Shintaro Matsuda, Tsukasa Inada, Kazuya Nagao, Tomoyuki Murakami, Yasuyo Takeuchi, Keiichiro Yamane, Mamoru Toyofuku, Mitsuru Ishii, Eri Minamino‐Muta, Takao Kato, Moriaki Inoko, Tomoyuki Ikeda, Akihiro Komasa, Katsuhisa Ishii, Kozo Hotta, Nobuya Higashitani, Yoshihiro Kato, Yasutaka Inuzuka, Chiyo Maeda, Toshikazu Jinnai, Yuko Morikami, Naritatsu Saito, Kenji Minatoya, Takeshi Kimura, Masao Imai, Junichi Tazaki, Toshiaki Toyota, Hirooki Higami, Tetsuma Kawaji, Shinichi Shirai, Kengo Korai, Takeshi Arita, Shiro Miura, Kyohei Yamaji, Kitae Kim, Keiichiro Iwasaki, Hiroshi Miyawaki, Ayumi Misao, Akimune Kuwayama, Masanobu Ohya, Takenobu Shimada, Hidewo Amano, Masashi Amano, Yusuke Takahashi, Yusuke Yoshikawa, Shunsuke Nishimura, Maiko Kuroda, Tetsu Mizoguchi, Takafumi Yokomatsu, Akihiro Kushiyama, Hidenori Yaku, Toshimitsu Watanabe, Sachiko Sugioka, Naoki Takahashi, Kohei Fukuchi, Hiroshi Mabuchi, Teruki Takeda, Tomoko Sakaguchi, Masayuki Yamaji, Motoyoshi Maenaka, Yutaka Tadano, Makoto Motooka, Ryusuke Nishikawa, Mitsunori Kawato, Minako Kinoshita, Kenji Aida, Kousuke Takahashi, Euihong Ko, Nobutoyo Masunaga, Hisashi Ogawa, Moritake Iguchi, Takashi Unoki, Kensuke Takabayashi, Yasuhiro Hamatani, Yugo Yamashita, Shuhei Tsuji, Soji Nishio, Jyunya Seki, Miho Yamada, Akira Kawamoto, Kouji Sogabe, Michiya Tachiiri, Yukiko Matsumura, Chihiro Ota, Ryuzo Sakata, Kenji Minakata, Michiya Hanyu, Fumio Yamazaki, Tadaaki Koyama, Tatsuhiko Komiya, Kazuo Yamanaka, Noboru Nishiwaki, Motoaki Ohnaka, Hiroaki Osada, Katsuaki Meshii, Toshihiko Saga, Hitoshi Kitayama, Shogo Nakayama, Genichi Sakaguchi, Atsushi Iwakura, Kotaro Shiraga, Koji Ueyama, Keiichi Fujiwara, Atsushi Fukumoto, Senri Miwa, Junichiro Nishizawa, Mitsuru Kitano, Hirotoshi Watanabe, and Tomoki Sasa
- Subjects
Male ,Aortic valve ,Time Factors ,Hemodynamics ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Severity of Illness Index ,Ventricular Function, Left ,0302 clinical medicine ,Japan ,Risk Factors ,Registries ,030212 general & internal medicine ,Original Research ,Aged, 80 and over ,Stroke volume ,clinical outcomes ,Hospitalization ,Treatment Outcome ,medicine.anatomical_structure ,Aortic Valve ,Aortic valve stenosis ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,peak aortic jet velocity ,medicine.medical_specialty ,03 medical and health sciences ,Internal medicine ,Severity of illness ,medicine ,Humans ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Heart Failure ,Chi-Square Distribution ,business.industry ,aortic stenosis ,Stroke Volume ,Retrospective cohort study ,Aortic Valve Stenosis ,medicine.disease ,Surgery ,Stenosis ,Valvular Heart Disease ,Heart failure ,Asymptomatic Diseases ,business - Abstract
Background There are limited data regarding the risk stratification based on peak aortic jet velocity (Vmax) in patients with severe aortic stenosis ( AS ). Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the study population consisted of 1075 conservatively managed patients with Vmax ≥4.0 m/s and left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on Vmax (group 1, 4.0 ≤ Vmax AS ‐related events (aortic valve–related death or heart failure hospitalization) was incrementally higher with increasing Vmax (entire population; 38.0%, 49.4%, and 62.8%, P P =0.008; and asymptomatic patients; 29.4%, 38.9%, and 47.7%, P =0.005). After adjusting for confounders, the excess risk of group 2 and group 3 relative to group 1 for AS ‐related events remained significant (hazard ratio, 1.39; 95% CI , 1.07–1.81; P =0.02, and hazard ratio, 1.53; 95% CI , 1.17–2.00; P =0.002, respectively). The effect size of group 3 relative to group 1 for AS ‐related events in asymptomatic patients (N=479) was similar to that in symptomatic patients (N=596; hazard ratio, 1.59; 95% CI , 1.01–2.52; P =0.047, and hazard ratio, 1.67; 95% CI , 1.16–2.40, P =0.008, respectively), and there was no significant overall interaction between the symptomatic status and the effect of the Vmax categories on AS ‐related events (interaction, P =0.88). Conclusions In conservatively managed severe AS patients with preserved left ventricular ejection fraction, increasing Vmax was associated with incrementally higher risk for AS ‐related events. However, the cumulative 5‐year incidence of the AS ‐related events remained very high even in asymptomatic patients with less greater Vmax.
- Published
- 2017
13. The transformation suppressor gene Reck is required for postaxial patterning in mouse forelimbs
- Author
-
Eijiro Adachi, Sachiyo Yamaguchi, Yoko Morioka, Michiko Echizenya, Haruhiko Akiyama, Shigeyoshi Itohara, David B. Alexander, Mako Yamamoto, Hitoshi Kitayama, Takeshi Yagi, Tomoko Matsuzaki, Makoto Noda, Rei Takahashi, Takashi Nakamura, and Yasuhiro Maeda
- Subjects
animal structures ,Mouse ,QH301-705.5 ,Science ,Mesenchyme ,Mutant ,Ectoderm ,Biology ,General Biochemistry, Genetics and Molecular Biology ,law.invention ,Downregulation and upregulation ,law ,Wnt7a ,medicine ,Biology (General) ,Anatomy ,Phenotype ,Cell biology ,body regions ,medicine.anatomical_structure ,WNT7A ,Teratogens ,Cutaneous horn ,Suppressor ,Forelimb ,General Agricultural and Biological Sciences ,Reck ,Limb patterning ,Research Article - Abstract
Summary The membrane-anchored metalloproteinase-regulator RECK has been characterized as a tumor suppressor. Here we report that mice with reduced Reck-expression show limb abnormalities including right-dominant, forelimb-specific defects in postaxial skeletal elements. The forelimb buds of low-Reck mutants have an altered dorsal ectoderm with reduced Wnt7a and Igf2 expression, and hypotrophy in two signaling centers (i.e., ZPA and AER) that are essential for limb outgrowth and patterning. Reck is abundantly expressed in the anterior mesenchyme in normal limb buds; mesenchyme-specific Reck inactivation recapitulates the low-Reck phenotype; and some teratogens downregulate Reck in mesenchymal cells. Our findings illustrate a role for Reck in the mesenchymal-epithelial interactions essential for mammalian development.
- Published
- 2012
14. Early and Late Results of Surgical Treatment for Ventricular Septal Rupture With and Without Use of the Infarction Exclusion Technique-Experience With Two- and Three-Sheet Modification
- Author
-
Takako Nishino, Kohsuke Fujii, Takuma Satsu, Toshio Kaneda, Susumu Nakamoto, Toshihiko Saga, Hitoshi Kitayama, and Shintaro Yukami
- Subjects
Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Infarction ,Kaplan-Meier Estimate ,Hospital mortality ,Ventricular geometry ,Hospital records ,Ventricular Septal Rupture ,Humans ,Medicine ,Hospital Mortality ,Cardiac Surgical Procedures ,Surgical treatment ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Suture Techniques ,Middle Aged ,medicine.disease ,Late results ,Surgery ,Treatment Outcome ,Female ,Cardiology and Cardiovascular Medicine ,business ,Shunt (electrical) - Abstract
Background: Ventricular septal rupture (VSR) is an infrequent but life-threatening situation. Although outcomes have improved with the introduction of infarction exclusion, we have experienced difficulty in determining the optimal patch size and shape for obtaining good outcomes. Therefore, we modified the infarction exclusion technique. Herein, we review our experience on the basis of early closure of VSR with and without use of the infarction exclusion technique. Methods: We retrospectively analyzed the hospital records of 33 patients who underwent surgical treatment for VSR. We employed Dagget's method from 1982 to 1995, and then introduced the infarction exclusion technique in 1995. We have developed two modifications: the two-sheet single-patch technique and the three-sheet double-patch technique. Results: Overall hospital mortality was 41.9% and that of the infarction exclusion group was significantly lower than the hospital mortality rate of the noninfarction exclusion group (21% and 63%, respectively, p = 0.0266). Late mortality of survivors was low in all groups during the observation period. The three-sheet double-patch group showed no residual shunt. This difference in outcomes between the single-patch and double-patch groups was statistically significant (p = 0.0174). Conclusions: The two-sheet method facilitates the restoration of ventricular geometry. A double-patch using the three-sheet method may be useful for reducing residual shunt. (J Card Surg 2012;27:34–38)
- Published
- 2012
15. VNCOP-B plus rituximab therapy in elderly patients with aggressive B-cell non-Hodgkin lymphoma: A multicenter experience
- Author
-
Masaru Shibano, Yasuaki Nagare, Hidetsugu Kimura, Tatsuya Katsurada, Fumiaki Urase, Atsuko Mugitani, Shosaku Nomura, Masahiro Manabe, Machiko Tsukaguchi, Hirofumi Teshima, Kunio Hayashi, Hitoshi Kitayama, Kazuyoshi Ishii, and Toshiya Yagi
- Subjects
Male ,Aging ,medicine.medical_specialty ,Vincristine ,Lymphoma, B-Cell ,Neutropenia ,Health (social science) ,CHOP ,Gastroenterology ,Antibodies, Monoclonal, Murine-Derived ,Bleomycin ,International Prognostic Index ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,Humans ,Medicine ,Cyclophosphamide ,Aged ,Etoposide ,Aged, 80 and over ,business.industry ,Remission Induction ,medicine.disease ,Surgery ,Regimen ,Prednisolone ,Prednisone ,Female ,Rituximab ,Mitoxantrone ,Geriatrics and Gerontology ,business ,Gerontology ,Febrile neutropenia ,medicine.drug - Abstract
CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) plus rituximab is a standard chemotherapy used to treat patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). However, among elderly patients, this regimen has not been completely satisfactory in its efficacy and safety. We report our clinical experience in 8 collaborative institutions to determine if the VNCOP-B (etoposide, mitoxantrone, cyclophosphamide, vincristine, prednisolone, and bleomycin) combination therapy plus rituximab was effective and safe to treat elderly patients with aggressive B-NHL. Between September 2004 and December 2007, 23 previously untreated patients, median age 73 years, 50.0% classified as high-intermediate/high-risk on the standard International Prognostic Index (IPI) entered this trial. Complete remission rate was 90.5%, with a 100% overall response rate (RR) at the end of induction therapy; overall survival (OS) rate at 3 years was 76.4% (median follow-up 744 days), with an 82.6% 3-year progression-free survival (PFS) rate (median follow-up 744 days). The most common grade 3/4 toxicities were hematologic, including neutropenia in 75.0% of the patients despite prophylactic administration of granulocyte colony-stimulating factor (G-CSF), febrile neutropenia in 30.0%, respectively. There was no treatment-related mortality (TRM). Rituximab not only combined with chemotherapy but also given sequentially improved survival. R-VNCOP-B could be another option for elderly patients who are not considered to tolerate in receiving R-CHOP.
- Published
- 2010
16. A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs
- Author
-
Yoko Morioka, Ryuya Murai, Shinae Kondoh, Hitoshi Kitayama, Yoko Yoshida, Yoshinori Kawazoe, Emi Nishimoto, Makoto Noda, Masahiro Hiraoka, Teruyuki Muraguchi, and Motonari Uesugi
- Subjects
Tumor suppressor gene ,Oncogene ,Transgene ,Cancer ,Biology ,medicine.disease ,Molecular biology ,Metastasis ,Oncology ,Cell culture ,Cancer cell ,medicine ,Cancer research ,Fibrosarcoma - Abstract
Received: July 9, 2010 , Accepted: July 30, 2010 , Published: August 6, 2010 // The membrane-anchored matrix metalloproteinase-regulator RECK is often downregulated in various types of cancers; the levels of residual RECK in resected tumors often correlate with better prognosis. Forced expression of RECK in cancer cells suppresses tumor angiogenesis, invasion, and metastasis in xenograft models. RECK is therefore a promising marker for benignancy and a potential effector in cancer therapy. We established a cell line containing two transgene systems: (1) the secreted alkaline phosphatase (SEAP) gene fused to Reck promoter and (2) the HRAS12V oncogene driven by the Tet-off promoter system. This cell line exhibits transformed phenotype in regular medium and flat morphology with increased SEAP activity in the presence of doxycycline, allowing the assessment of RECK-inducing activity of chemicals in the contexts of both transformed and untransformed cells. Our pilot experiments with 880 known bioactive compounds detected 34 compounds that activate RECK promoter; among these, 10 were authentic anticancer drugs. Four selected compounds up-regulated endogenous RECK protein in several human cancer cell lines. The top-ranking compound, disulfiram, strongly suppressed spontaneous lung-metastasis of human fibrosarcoma cells in nude mice. Our data demonstrate the value of this screen in discovering effective cancer therapeutics.
- Published
- 2010
17. Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate, the RECK tumor-suppressor protein through microRNAs
- Author
-
Hitoshi Kitayama, Yasuko Yoshida, Chiaki Takahashi, Tomoko Matsuzaki, Makoto Noda, and Fabricio Loayza-Puch
- Subjects
Cancer Research ,Regulator ,Down-Regulation ,Biology ,GPI-Linked Proteins ,Metastasis ,law.invention ,Mice ,Downregulation and upregulation ,law ,microRNA ,Gene expression ,Genetics ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Extracellular Signal-Regulated MAP Kinases ,Molecular Biology ,Mice, Inbred BALB C ,Membrane Glycoproteins ,Tumor Suppressor Proteins ,Twist-Related Protein 1 ,Nuclear Proteins ,Proto-Oncogene Proteins c-met ,medicine.disease ,Molecular biology ,Cell Hypoxia ,MicroRNAs ,Cancer cell ,ras Proteins ,Cancer research ,Suppressor ,Female ,Signal transduction ,Signal Transduction - Abstract
Cancer cells show characteristic gene expression profiles. Recent studies support the potential importance of microRNA (miRNA) expression signatures as biomarkers and therapeutic targets. The membrane-anchored protease regulator RECK is downregulated in many cancers, and forced expression of RECK in tumor cells results in decreased malignancy in animal models. RECK is also essential for mammalian development. In this study, we found that RECK is a target of at least three groups of miRNAs (miR-15b/16, miR-21 and miR-372/373); that RECK mutants lacking the target sites for these miRNA show augmented tumor/metastasis-suppressor activities; and that miR-372/373 are upregulated in response to hypoxia through HIF1alpha and TWIST1, whereas miR-21 is upregulated by RAS/ERK signaling. These data indicate that the hypoxia- and RAS-signaling pathways converge on RECK through miRNAs, cooperatively downregulating this tumor suppressor and thereby promoting malignant cell behavior.
- Published
- 2010
18. Cardiac Resynchronization for Corrected Transposition of the Great Arteries with Systemic Right Ventricle Failure after Tricuspid Valve Replacement and Ventricle Septal Defect Closure
- Author
-
Masato Imura, Kiyoaki Takaba, Takako Nishino, Susumu Nakamoto, Iemura J, Shintaro Yukami, Hitoshi Kitayama, Toshio Kaneda, Toshihiko Saga, Kosuke Fujii, and Hiroshi Kawasaki
- Subjects
medicine.medical_specialty ,lcsh:Diseases of the circulatory (Cardiovascular) system ,medicine.medical_treatment ,Cardiac resynchronization therapy ,Systemic right ventricular failure ,Internal medicine ,medicine ,cardiovascular diseases ,Ejection fraction ,Corrected TGA ,business.industry ,Atrial fibrillation ,Right bundle branch block ,medicine.disease ,Implantable cardioverter-defibrillator ,Surgery ,medicine.anatomical_structure ,Great arteries ,Ventricle ,lcsh:RC666-701 ,Heart failure ,Cardiology ,cardiovascular system ,Cardiology and Cardiovascular Medicine ,business - Abstract
A 32-year-old man developed systemic right ventricular (RV) heart failure after ventricular septal defect (VSD) closure and tricuspid valve replacement for corrected transposition of the great arteries with VSD and Ebstein anomaly. He subsequently experienced RV failure with wide QRS and atrial fibrillation (AF). Because corrective surgery for this condition seemed over risky, we decided to perform cardiac resynchronization therapy with implantation of an implantable cardioverter defibrillator (CRT-D). After CRT-D device implantation, the patient showed improved performance status in terms of New York Heart Association functional class, B-type brain natriuretic peptide levels, RV ejection fraction and cardiac electrical rhythm. CRT-D implantation is a useful approach for systemic RV failure with wide QRS duration showing right bundle branch block and AF.
- Published
- 2010
- Full Text
- View/download PDF
19. Transplantation of cultured choroid plexus epithelial cells via cerebrospinal fluid shows prominent neuroprotective effects against acute ischemic brain injury in the rat
- Author
-
Yumi Watanabe, Yutaka Itokazu, Masayoshi Ohta, Naoya Matsumoto, Hitoshi Kitayama, Yoshihisa Suzuki, Chizuka Ide, Tomoyuki Yoshihara, Hisashi Sugimoto, Mari Dezawa, Akihiko Taguchi, and Makoto Noda
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Neuroimmunomodulation ,Central nervous system ,Apoptosis ,Hippocampal formation ,Biology ,Fourth ventricle ,Neuroprotection ,Brain Ischemia ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,medicine ,Animals ,Brain Tissue Transplantation ,RNA, Messenger ,Rats, Wistar ,Cells, Cultured ,Cerebrospinal Fluid ,030304 developmental biology ,Fourth Ventricle ,0303 health sciences ,General Neuroscience ,Brain ,Epithelial Cells ,Infarction, Middle Cerebral Artery ,Rats ,Transplantation ,Nitric oxide synthase ,Treatment Outcome ,medicine.anatomical_structure ,Anesthesia ,Choroid Plexus ,biology.protein ,Choroid plexus ,030217 neurology & neurosurgery - Abstract
Choroid plexus (CP) epithelial cells (CPECs) produce cerebrospinal fluid (CSF) to provide the CNS with a specialized microenvironment. Our previous study showed that the conditioned medium of cultured CPECs enhanced the survival and neurite extension of hippocampal neurons. The present study examined the ability of cultured CPECs to protect against ischemic brain injury when transplanted into the CSF. Rats were subjected to a transient occlusion of the middle cerebral artery, followed by an injection of cultured CPECs into the fourth ventricle. The injection markedly reduced neurological deficits and infarction volume within 24 h. Other beneficial effects were (1) a reduction in number of apoptotic and inflammatory cells, (2) an up-regulation of the mRNA expression of an anti-apoptotic effecter, cAMP-response element binding protein, and (3) a down-regulation of the production of pro-inflammatory factors such as interleukin-1 beta and inducible nitric oxide synthase. The injected CPECs were located within the ventricles and on the brain's surface, not in the ischemic foci, suggesting that they exert their effects by releasing diffusible neuroprotective factors into the CSF. The transplantation of CPECs via CSF is a potential new strategy for protecting against ischemic brain injury.
- Published
- 2010
20. ABSTRACTS OF ORAL PRESENTATIONS
- Author
-
Yasuo Sakusai, Tomoka Wachi, Ryuichi Mizuno, Harubumi Kasai, Kazuhiro Abeyama, Satoshi Hara, Satoshi Suzuki, Yoshihiro Numa, Takashi Ryu, Hidemi Kada, Mamitaro Ohtsuki, M. Iwasawa, Shinji Hirotsune, Tomohiko Asano, Keiji Kawamoto, Yusuke Furukawa, Kahei Sato, Dairo Maruyama, Isamu Ishiwata, Takushi Tadakuma, Hitoshi Kitayama, Masaru Murai, E. Sakaguchi, K. Sato, Keiichi Aduma, Hidemi Nakagawa, Satoshi Iino, Yukiko Kobayashi, Naoki Otani, Tomoharu Tamagawa, Yoshihisa Yano, Takayuki Inagaki, Ken Marumo, Namiko Nomura, Sonshin Takao, Hideshi Ishii, Noriyuki Yoshida, Hirotaka Matsuo, Akio Horiguchl, Takashi Aikou, Masamichi Hayakawa, Nobuhiro Deguchi, Mototsugu Oya, Kyo Li, Krittaya Sutheesophon, Shusei Ikegami, Shigeo Saito, Yasuo Yamanouchi, Hiroshi Nawashiro, Munehisa Ueno, Hidetoshi Ooigawa, Hideyuki Motohashi, Nariyoshi Shinomiya, and Yasuhiko Kano
- Subjects
0303 health sciences ,Cancer Research ,medicine.medical_specialty ,business.industry ,General surgery ,Reproductive medicine ,Cell Biology ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Medicine ,Stem cell ,business ,030304 developmental biology - Published
- 2008
21. Role of soluble tumor necrosis factor-related apoptosis-inducing ligand concentrations after stem cell transplantation
- Author
-
Nobuhiko Uoshima, Kazuyoshi Ishii, Takao Yoshihara, Hitoshi Kitayama, Hiroyuki Ishida, Kunio Hayashi, Norihito Inami, and Shosaku Nomura
- Subjects
Adult ,Male ,Programmed cell death ,Fas Ligand Protein ,Adolescent ,Lymphoma ,Immunology ,Graft vs Host Disease ,Enzyme-Linked Immunosorbent Assay ,Inflammation ,Endothelial Growth Factors ,Biology ,TNF-Related Apoptosis-Inducing Ligand ,Immune system ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Humans ,Immunology and Allergy ,Child ,Aged ,Transplantation ,Leukemia ,Tumor Necrosis Factor-alpha ,Endothelial Cells ,Middle Aged ,Haematopoiesis ,surgical procedures, operative ,Apoptosis ,Cytokines ,Female ,Tumor necrosis factor alpha ,Stem cell ,medicine.symptom ,Stem Cell Transplantation - Abstract
Although stem cell transplantation (SCT) is being used for hematopoietic reconstitution following high-dose chemotherapy for malignancy, it involves certain serious transplant-related complications such as graft-versus-host disease (GVHD). Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) plays important roles in regulating cell death, immune response, and inflammation. However, the role of soluble TRAIL (sTRAIL) after SCT is poorly understood. In this study, 42 patients underwent SCT; 22 patients received allogeneic SCT, while the remaining 20 received autologous SCT. In these patients, levels of sTRAIL, cytokines, and soluble factors were measured by enzyme-linked immunosorbent assay (ELISA). In addition, a basic study of the generation of endothelial cell-derived microparticle (EDMP) by TNF-alpha and soluble Fas ligand (sFasL) was conducted. sFasL and EDMP exhibited significant elevation in the early phase (2-3 weeks) after SCT. In addition, the elevation of IL-6, TNF-alpha, and sIL-2R after allogeneic SCT was observed. EDMP also exhibited changes similar to sFasL. The patients with high sTRAIL exhibited significant decrease of sFasL and EDMP as compared with those without high sTRAIL. TNF-alpha and sFasL induced an increase in procoagulant and apoptotic markers in endothelial cells, and EDMP shedding was observed. Furthermore, sTRAIL inhibited the EDMP elevation caused by TNF-alpha and sFasL. The apoptotic markers such as sFasL and sTRAIL exhibited particular changes after SCT. Our results suggest that sTRAIL generation after allogeneic SCT relates to the prevention of GVHD.
- Published
- 2007
22. [Isolation and applications of transformation suppressor genes]
- Author
-
Makoto, Noda, Tomoko, Matsuzaki, Yoko, Yoshida, and Hitoshi, Kitayama
- Subjects
Pancreatitis-Associated Proteins ,GPI-Linked Proteins ,Mice ,Cell Transformation, Neoplastic ,Antigens, Neoplasm ,Neoplasms ,Drug Discovery ,Mutation ,Biomarkers, Tumor ,Animals ,Humans ,Genes, Tumor Suppressor ,Lectins, C-Type ,Cloning, Molecular ,Gene Library - Abstract
A common strategy to identify tumor suppressor genes has been positional cloning, taking advantages of chromosomal abnormalities, linkage to polymorphic markers, etc. We have been taking another approach, based on shotgun cloning with cDNA-expression library, to isolate genes suppressing an aspect of transformed phenotypes. Genes identified in such an artificial system, however, require subsequent validation for their clinical relevance through independent approaches, such as finding mutations and altered expression in human cancers. Whether the parental genes act as oncogenes or tumor suppressors needs to be deduced from available annotations and/or new experimental data. Once validated, such genes, being isolated by virtue of their biological activities, are likely to be useful in developing new strategies for tumor prognosis, tumor stratification, and drug discovery.
- Published
- 2015
23. Functional genomics reveals genes involved in protein secretion and Golgi organization
- Author
-
Kota Saito, Franz Wendler, Yue Hu, Hitoshi Kitayama, Gianni Guizzunti, Norbert Perrimon, Laetitia Casano, Vivek Malhotra, Ramanuj DasGupta, Arrate Mallabiabarrena, Erin K. Wallace, and Frederic Bard
- Subjects
Golgi Apparatus ,Genes, Insect ,Protein Sorting Signals ,Biology ,Endoplasmic Reticulum ,Cell Line ,symbols.namesake ,Genes, Reporter ,Animals ,Drosophila Proteins ,Secretion ,Gene ,Horseradish Peroxidase ,Secretory pathway ,Multidisciplinary ,Endoplasmic reticulum ,Golgi organization ,Genomics ,Intracellular Membranes ,Golgi apparatus ,Cell biology ,Secretory protein ,symbols ,Drosophila ,RNA Interference ,Functional genomics - Abstract
Yeast genetics and in vitro biochemical analysis have identified numerous genes involved in protein secretion1,2. As compared with yeast, however, the metazoan secretory pathway is more complex and many mechanisms that regulate organization of the Golgi apparatus remain poorly characterized. We performed a genome-wide RNA-mediated interference screen in a Drosophila cell line to identify genes required for constitutive protein secretion. We then classified the genes on the basis of the effect of their depletion on organization of the Golgi membranes. Here we show that depletion of class A genes redistributes Golgi membranes into the endoplasmic reticulum, depletion of class B genes leads to Golgi fragmentation, depletion of class C genes leads to aggregation of Golgi membranes, and depletion of class D genes causes no obvious change. Of the 20 new gene products characterized so far, several localize to the Golgi membranes and the endoplasmic reticulum.
- Published
- 2006
24. Antegrade selective cerebral perfusion with mild hypothermic systemic circulatory arrest during thoracic aortic surgery
- Author
-
Toshihiko Saga, Kousuke Fujii, Hitoshi Kitayama, Masahiko Onoe, Masato Imura, Terufumi Matsumoto, Takako Nishino, Toshio Kaneda, Takehiro Inoue, Susumu Nakamoto, and Tatsuya Ogawa
- Subjects
Male ,Aortic arch ,medicine.medical_specialty ,Risk Assessment ,Brain Ischemia ,Cohort Studies ,Aortic aneurysm ,Hypothermia, Induced ,medicine.artery ,Internal medicine ,Ascending aorta ,Humans ,Medicine ,Thoracic aorta ,Hospital Mortality ,Cerebral perfusion pressure ,Intraoperative Complications ,Aged ,Probability ,Retrospective Studies ,Aortic Aneurysm, Thoracic ,business.industry ,Middle Aged ,Thoracic Surgical Procedures ,Hypothermia ,Prognosis ,medicine.disease ,Survival Analysis ,Radiography ,Treatment Outcome ,Cardiothoracic surgery ,Cerebrovascular Circulation ,Anesthesia ,Circulatory system ,Cardiology ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Vascular Surgical Procedures - Abstract
Antegrade selective cerebral perfusion (ASCP) and retrograde cerebral perfusion (RCP) have proven to be reliable methods of brain protection during aortic surgery. These techniques are usually accompanied by systemic circulatory arrest with moderate hypothermia (24-28 degrees C) or deep hypothermia (18-24 degrees C). However, hypothermia can lead to various problems. The present study therefore reports results for thoracic aorta replacement using ASCP with mild hypothermic systemic arrest (28-32 degrees C).Between 1995 and 2003, 68 consecutive patients underwent repair of the ascending aorta and/or aortic arch. Mild hypothermic ASCP was utilized in 31 cases, moderate hypothermic ASCP in 20, and deep hypothermic RCP in 17. Various parameters were compared between the mild hypothermic ASCP, moderate hypothermic ASCP, and RCP.Hospital mortality was 10.3%, with no significant differences observed between any groups. Permanent neurological dysfunction was 8.8%, and no significant differences were observed between any groups. Mild hypothermic ASCP displayed significantly decreased transfusion volume, intubation time, and ICU stay.Use of ASCP with mild hypothermic systemic circulatory arrest during aortic surgery resulted in acceptable hospital mortality and neurological outcomes. ASCP with mild hypothermic arrest allows decreased transfusion volume and reduced duration of intubation and ICU stay.
- Published
- 2005
25. Rap1 mutants with increased affinity for the guanine-nucleotide exchange factor C3G
- Author
-
Shuliang Shi, Makoto Noda, and Hitoshi Kitayama
- Subjects
endocrine system ,Cancer Research ,Mutant ,Mutagenesis (molecular biology technique) ,Biology ,medicine.disease_cause ,Serine ,Mice ,Guanine Nucleotide-Releasing Factor 2 ,Two-Hybrid System Techniques ,Genetics ,medicine ,Animals ,Guanine Nucleotide Exchange Factors ,Humans ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,DNA Primers ,Mutation ,Base Sequence ,rap1 GTP-Binding Proteins ,Signal transducing adaptor protein ,Cytoskeletal Proteins ,enzymes and coenzymes (carbohydrates) ,Biochemistry ,Mutagenesis ,NIH 3T3 Cells ,Rap1 ,Signal transduction ,Protein Binding ,Signal Transduction - Abstract
The mutant of Ras protein with serine to asparagine mutation at residue 17 (Ras-17N) is known to interfere with the signaling function of the wild-type Ras protein by sequestering its guanine-nucleotide exchange factors (GEFs). The similar mutant of another Ras family protein Rap1 (Rap1-17N) fails to effectively interfere with the interaction between the wild-type Rap1 and one of its GEFs, C3G, in vitro. In the present study, we have attempted to isolate Rap1 mutants with increased affinity for C3G using random mutagenesis and yeast two-hybrid screening. Based on the pattern of mutations found among these mutants, we could design a potent C3G-binder, named Rap1-AGE, harboring mutations in three sites (17A, 29G, and 117E). The association of Rap1-AGE with C3G in the cells was confirmed by co-immunoprecipitation experiments. The ability of Rap1-AGE to inhibit C3G-mediated Rap1-activation and cell spreading was also demonstrated. On the other hand, Rap1 activation mediated by two other GEFs, Epac and smgGDS, was not inhibited by Rap1-AGE. These results suggest that Rap1-AGE acts as a dominant interfering factor against C3G and serves as a useful tool in analyzing the roles of C3G-Rap1 signaling pathway in various biological processes.
- Published
- 2004
26. Effects of ras and rap1 on electrical excitability of differentiated ng108-15 cells
- Author
-
Hitoshi Kitayama, Makoto Noda, Naoya Matsumoto, Shunya Kondo, and Yukio Imamura
- Subjects
Sodium channel activity ,General Neuroscience ,Cellular differentiation ,Mutant ,Action Potentials ,rap1 GTP-Binding Proteins ,Cell Differentiation ,Biology ,Molecular biology ,Serine ,Mice ,Cell Line, Tumor ,ras Proteins ,Animals ,Rap1 ,Patch clamp ,Asparagine ,Protein kinase A - Abstract
Effects of two small G-proteins, Rap1 and Ras, on the sodium channel activity in NG108-15 cells were studied using sindbis virus-mediated gene transfer. When an activated Rap1A mutant (Rap1-12V, the activated mutant of Rap1 carrying glycine to valine substitution at codon 12) or a dominant-negative H-Ras mutant (Ras-17N, carrying serine to asparagine substitution at codon 17) was expressed in differentiated NG108-15 cells, the proportion of cells generating action potential decreased and the amplitudes of sodium current diminished. This effect was sensitive to an inhibitor of protein kinase A. The effects of a cyclic AMP (cAMP) analog (dibutyl cAMP) on sodium current in these cells were biphasic: inhibitory at lower concentrations (
- Published
- 2004
27. Isolation of a set of genes expressed in the choroid plexus of the mouse using suppression subtractive hybridization
- Author
-
Hitoshi Kitayama, Kazushi Kimura, Chizuka Ide, Naoya Matsumoto, Masaaki Kitada, and Makoto Noda
- Subjects
Male ,biology ,General Neuroscience ,Sequence Analysis, DNA ,In situ hybridization ,ABCA8 ,Molecular biology ,Blot ,Mice ,Transthyretin ,Suppression, Genetic ,Cerebrospinal fluid ,Gene Expression Regulation ,Suppression subtractive hybridization ,Choroid Plexus ,biology.protein ,Animals ,Choroid plexus ,sense organs ,Gelsolin ,In Situ Hybridization ,Gene Library - Abstract
The choroid plexus produces cerebrospinal fluid, providing a specialized environment for the CNS. We previously demonstrated that choroid plexus ependymal cells can enhance nerve regeneration in vivo and promote neurite outgrowth in vitro. To understand the molecular mechanisms of choroid plexus functions, we isolated genes predominantly expressed in the mouse choroid plexus using suppression subtractive hybridization. Out of the 49 complementary DNA (cDNA) fragments isolated in two types of screening, 43 matched known sequences in the database and six were novel. In one type of screening where choroid plexus cDNAs were subtracted with cerebral cortex cDNAs, transthyretin and phosphodiesterase I alpha were predominant. This is consistent with previous reports and supports the authenticity of our approach. In the other type of screening, cDNAs derived from the choroid plexus of neonatal (postnatal day 5) mice were subtracted with cDNAs from the choroid plexus of adult mice. RNA blot and/or in situ hybridization confirmed abundant expression, in the mouse choroid plexus, of the mRNA encoding gelsolin, phospholipid transfer protein, ATP-binding cassette transporter A8 (ABCA8), androgen-inducible aldehyde reductase, and Na(+)/sulfate cotransporter SUT-1. Also, one novel gene (FS88) was found to be expressed in the choroid plexus from neonatal mice. Our data suggest that the choroid plexus cells produce molecules involved in processes such as prevention of fibrillization of amyloid beta-protein (transthyretin and gelsolin), lipid metabolism (phospholipid transfer protein and ABCA8), and detoxification (androgen-inducible aldehyde reductase).
- Published
- 2003
28. [Untitled]
- Author
-
Shunya Kondo, Rei Takahashi, Hitoshi Kitayama, Junseo Oh, Chiaki Takahashi, and Makoto Noda
- Subjects
Cancer Research ,Oncogene ,Tumor suppressor gene ,Angiogenesis ,Biology ,Matrix metalloproteinase ,medicine.disease ,Metastasis ,Extracellular matrix ,Oncology ,Cancer cell ,Cancer research ,medicine ,Signal transduction - Abstract
RECK was first isolated as a transformation suppressor gene by cDNA expression cloning in a mouse fibroblast cell line transformed by an activated RAS oncogene. Subsequently, reduced expression of RECK in transformed cells and cancer cells were demonstrated. Moreover, in several types of tumors, positive correlation between RECK expression and survival of patients have been noted. RECK encodes a GPI-anchored glycoprotein harboring three protease inhibitor-like domains. The RECK protein regulates at least three members of the matrix metalloproteinase (MMP) family, MMP-2, MMP-9, and MT1-MMP, in vitro or in cultured cells. Restored expression of RECK in cancer cell lines results in strong suppression of invasion, metastasis, and tumor angiogenesis. Mice lacking RECK die in utero with reduced integrity of blood vessels, the neural tube, and mesenchymal tissues. In these mice, MMP activity is elevated, and the amount of collagen type I greatly reduced. The RECK null phenotype is partially rescued (half day delay of death and marked recovery of tissue integrity) by MMP-2 null mutation, demonstrating functional interaction between RECK and MMP-2 in vivo and involvement of other target(s) for RECK in the lethal phenotype. These findings indicate that (i) RECK is an important regulator of extracellular matrix remodeling and that (ii) down-regulation of RECK by oncogenic signaling leads to the excessive activation of MMPs thereby promoting malignant behavior of cancer cells such as invasion, metastasis, and angiogenesis.
- Published
- 2003
29. DEVELOPMENT OF A NEW FLEXIBLE JOINT STRUCTURE FOR SUBMERGED TUNNELS
- Author
-
Hitoshi Kitayama, Hiroshi Yokota, and Mitsuyasu Iwanami
- Subjects
Structure (mathematical logic) ,Engineering ,Development (topology) ,Water tightness ,business.industry ,General Medicine ,Structural engineering ,business ,Civil engineering ,Joint (geology) - Published
- 2002
30. Stent Graft Repair of a Ruptured Aberrant Right Subclavian Artery after Open Repair
- Author
-
Kosuke Fujii, Shintaro Yukami, Susumu Nakamoto, Hitoshi Kitayama, Toshihiko Saga, Toshio Kaneda, and Takako Nishino
- Subjects
Aortic arch ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Stent ,Vascular ring ,Aberrant right subclavian artery ,medicine.disease ,Surgery ,surgical procedures, operative ,medicine.artery ,cardiovascular system ,medicine ,Thoracic aorta ,Open repair ,In patient ,Thoracotomy ,business - Abstract
An aberrant right subclavian artery arising from the proximal portion of the descending thoracic aorta is the most common congenital anomaly of the aortic arch. Open repair is typically performed in such cases; however, it may be associated with a high rate of neurological complications and mortality, particularly in patients contraindicated for major open vascular reconstruction. We successfully treated a ruptured aberrant right subclavian artery using stent grafts in an 81-year-old female patient who had previously undergone open aortic arch repair. The stent graft technique is useful for patients without vascular ring symptoms who require repeat thoracotomy.
- Published
- 2014
31. The Membrane-Anchored MMP Inhibitor RECK Is a Key Regulator of Extracellular Matrix Integrity and Angiogenesis
- Author
-
Tom Horan, Sachiko Nishimura, Chiaki Takahashi, Chizuka Ide, Hisahito Yoshida, Makoto Noda, Shin-Ichi Nishikawa, Tsutomu Arakawa, Rei Takahashi, Yukio Imamura, Akira Mizoguchi, David B. Alexander, Hitoshi Kitayama, Regina Maki Sasahara, Shunya Kondo, Junseo Oh, Shigeyoshi Itohara, Motoharu Seiki, Eijiro Adachi, and Yoshifumi Itoh
- Subjects
Matrix Metalloproteinases, Membrane-Associated ,Angiogenesis ,Down-Regulation ,Mice, Nude ,Neovascularization, Physiologic ,Matrix Metalloproteinase Inhibitors ,Biology ,Matrix metalloproteinase ,GPI-Linked Proteins ,Transfection ,Muscle, Smooth, Vascular ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,Extracellular matrix ,Mice ,Downregulation and upregulation ,Matrix Metalloproteinase 14 ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Fibrosarcoma ,Cells, Cultured ,chemistry.chemical_classification ,Membrane Glycoproteins ,Neovascularization, Pathologic ,Biochemistry, Genetics and Molecular Biology(all) ,Metalloendopeptidases ,Neoplasms, Experimental ,Embryo, Mammalian ,medicine.disease ,Immunohistochemistry ,Molecular biology ,Matrix Metalloproteinases ,Extracellular Matrix ,Cell biology ,medicine.anatomical_structure ,Matrix Metalloproteinase 9 ,chemistry ,Gene Targeting ,Mutation ,Matrix Metalloproteinase 2 ,Basal lamina ,Glycoprotein ,Neoplasm Transplantation - Abstract
Matrix metalloproteinases (MMPs) are essential for proper extracellular matrix remodeling. We previously found that a membrane-anchored glycoprotein, RECK, negatively regulates MMP-9 and inhibits tumor invasion and metastasis. Here we show that RECK regulates two other MMPs, MMP-2 and MT1-MMP, known to be involved in cancer progression, that mice lacking a functional RECK gene die around E10.5 with defects in collagen fibrils, the basal lamina, and vascular development, and that this phenotype is partially suppressed by MMP-2 null mutation. Also, vascular sprouting is dramatically suppressed in tumors derived from RECK-expressing fibrosarcoma cells grown in nude mice. These results support a role for RECK in the regulation of MMP-2 in vivo and implicate RECK downregulation in tumor angiogenesis.
- Published
- 2001
32. Disseminated Cholesterol Embolism After Coronary Artery Bypass Grafting
- Author
-
Hiroshi Oka, Takehiro Inoue, Susumu Nakamoto, Masaki Otaki, Masahiko Onoe, Toshio Kaneda, Hidetaka Oku, Hitoshi Kitayama, Terufumi Matumoto, and Zhiwei Zhang
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Blue Toe Syndrome ,medicine.medical_treatment ,Postoperative Complications ,Internal medicine ,medicine.artery ,Ascending aorta ,medicine ,Humans ,Popliteal Artery ,Renal Insufficiency ,Coronary Artery Bypass ,Aged ,Embolism, Cholesterol ,Cardiac catheterization ,Cerebral infarction ,business.industry ,Cerebral Infarction ,medicine.disease ,Intermittent claudication ,Surgery ,Femoral Artery ,medicine.anatomical_structure ,Embolism ,Cardiology ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Cholesterol embolism ,business ,Artery - Abstract
Blue toe syndrome caused by cholesterol emboli is a relatively benign disease. However, disseminated cholesterol embolism is a life-threatening condition. We describe here the case of a 71-year-old female admitted because of anterior chest pain and intermittent claudication. Following cardiac catheterization, warfarin potassium was administered. However, the patient's toes soon darkened bilaterally, and BUN and creatinine levels increased from the normal value. Skin discoloration and renal failure were improved after stopping warfarin potassium administration. The patient underwent coronary artery bypass grafting and left femoropopliteal bypass. Cerebral infarction and renal failure occurred postoperatively due to disseminated cholesterol embolism. The patient died from renal failure on the 16th postoperative day without regaining consciousness following surgery. For high risk patients, interventional procedures to the ascending aorta must be avoided. When CABG cannot be avoided for coronary revascularization, off-pump bypass and use of arterial grafts are recommended.
- Published
- 2001
33. Surgical strategy for left ventricular free wall rupture after acute myocardial infarction
- Author
-
Masaki Otaki, Toshihiko Kaneda, Iemura J, Hidetaka Oku, Hitoshi Kitayama, and Takehiro Inoue
- Subjects
Pulmonary and Respiratory Medicine ,Ventricular Septal Perforation ,medicine.medical_specialty ,Surgical strategy ,Heart disease ,business.industry ,Ventricular Free Wall Rupture ,Hemodynamics ,medicine.disease ,Surgery ,Suture (anatomy) ,Internal medicine ,medicine ,Cardiology ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,business ,Complication - Abstract
Background . Left ventricular free wall rupture is usually fatal without surgical intervention. However, the most appropriate surgical procedure remains controversial. Methods . Seventeen patients (14 men, 3 women) who developed left ventricular free wall rupture after acute myocardial infarction were treated surgically. Their mean age was 65.4 years (range, 55 to 79 years). The following surgical procedures were performed: infarctectomy and patch reconstruction in 1 patient, direct closure with or without patch covering in 4 patients, simple patch covering anchored by running suture in 4 patients, and a sutureless technique in 7 patients. Endventricular patch closure was performed in 1 patient with ventricular septal perforation. Results . One of 3 patients with a blow-out type rupture and 1 of 13 patients with an oozing type rupture died shortly after operation. The overall surgical mortality rate was 11.8%. Conclusions . Selection of the optimal procedure for each cardiac condition is important for obtaining good results. For patients with ongoing squirting bleeding, patch covering is the technique of choice. For oozing, the sutureless technique is preferable.
- Published
- 2001
34. A case of gastric cancer with non-islet cell tumor hypoglycemia detected by insulin-like growth factor II
- Author
-
Izumi Fukuda, Toru Kameya, Kunio Uematsu, Mitsutoshi Tatsumi, Hiroshi Maruyama, Hiroki Kuniyasu, Hitoshi Kitayama, Yoichi Konishi, and Yasunori Enomoto
- Subjects
medicine.medical_specialty ,geography ,geography.geographical_feature_category ,business.industry ,Cancer ,General Medicine ,Hypoglycemia ,medicine.disease ,Islet ,Pathology and Forensic Medicine ,Endocrinology ,Internal medicine ,medicine ,Cell tumor ,business ,Insulin-like growth factor-II - Published
- 2010
35. Symmetrical papillary muscle approximation for functional mitral regurgitation with idiopathic dilated cardiomyopathy
- Author
-
Takehiro, Inoue, Kosuke, Fujii, Shintaro, Yugami, Hitoshi, Kitayama, and Toshihiko, Saga
- Subjects
Cardiomyopathy, Dilated ,Male ,Mitral Valve Insufficiency ,Middle Aged ,Papillary Muscles ,Echocardiography, Doppler, Color ,Intraoperative Period ,Treatment Outcome ,Chordae Tendineae ,Humans ,Mitral Valve ,Female ,Cardiac Surgical Procedures ,Aged - Abstract
The cases are reported of mitral valve repair with symmetrical papillary muscle approximation from heads to bases close to cardiac apex for functional mitral regurgitation (FMR). The two papillary heads attaching the chordae to both leaflets from the posteromedial papillary muscle were approximated parallel to the solitary head of the anterolateral papillary muscle. This procedure permits an even reduction of lateral shift of the papillary muscle, resulting in an elimination of mitral tethering, and provides a satisfactory and durable mitral valve repair with good outcomes in patients with idiopathic dilated cardiomyopathy and FMR.
- Published
- 2013
36. Experimental Orthotopic Heart and Bilateral Lung Transplantation Completed Without Cardiopulmonary Bypass
- Author
-
Hidetaka Oku, Takehiro Inoue, Terufumi Matsumoto, Hitoshi Kitayama, and Masaki Otaki
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Cardiac output ,Vena Cava, Superior ,Aorta, Thoracic ,Vena Cava, Inferior ,Anastomosis ,Critical Care and Intensive Care Medicine ,Inferior vena cava ,law.invention ,Dogs ,Superior vena cava ,law ,medicine.artery ,Internal medicine ,Ascending aorta ,medicine ,Cardiopulmonary bypass ,Animals ,Heart Atria ,Cardiac Output ,Aorta ,Cardiopulmonary Bypass ,business.industry ,Anastomosis, Surgical ,Graft Survival ,Tissue Donors ,Surgery ,Trachea ,Transplantation ,medicine.vein ,cardiovascular system ,Cardiology ,Feasibility Studies ,Heart Transplantation ,Blood Gas Analysis ,Cardiology and Cardiovascular Medicine ,business ,Lung Transplantation - Abstract
Introduction: Most experimental studies of orthotopic heart and lung graft failure are complicated by an inability to eliminate the rejection-specific inflammatory mediator from the cardiopulmonary bypass. Methods: The following model was developed in our laboratory to investigate the feasibility of performing an orthotopic heart and bilateral lung transplantation without performing a cardiopulmonary bypass. Nineteen transplants were attempted using 19 pairs of mongrel dogs. The recipient dog (mean weight, 23 kg) was anesthetized, and the ascending aorta, the superior vena cava (SVC), the inferior vena cava (IVC), and the main bronchus were dissected. Then, the donor dog (mean weight, 20 kg) was anesthetized, and the heart and lung block was prepared and explanted from the chest under cardioplegic arrest. A Gore-tex shunt (W. L. Gore; Flagstaff, AZ) was placed side-to-side between the recipient IVC and SVC, and then the donor right atrium was anastomosed to the Gore-tex shunt. The donor ascending aorta was anastomosed to the recipient ascending aorta with a partial clamp. On completion of these anastomoses, the donor heart was reperfused by the recipient heart and allowed to beat. When hemodynamic conditions were stable with double hearts, the recipient SVC and IVC were ligated just proximal to the venous anastomosis and the recipient aorta was ligated proximal to the anastomotic site. The recipient trachea was anastomosed to the donor trachea with an end-to-end anastomosis. Finally, the recipient heart and lungs were removed from the chest and the sternum was closed. Results: Four of the 19 transplants failed. Three died due to left ventricular dysfunction, and one died due to bleeding. Mean (6 SD) ischemic time was 67 6 11 min with a mean (6 SD) anastomotic time of 54 6 12 min. The 15 survivors were hemodynamically stable with or without the minimal use of inotropic support (dopamine, 2 to 3 mg/kg/min) 6 h after grafting, with normal cardiac output, satisfactory oxygenation, and normal wall motion. The sternotomy was repaired without loss of cardiopulmonary function. Conclusions: On the basis of our experiences, the experimental model of orthotopic heart and bilateral lung transplantation completed “off pump” can be technically feasible without the loss of cardiac and pulmonary functions. (CHEST 1999; 116:1360‐1364)
- Published
- 1999
37. Activating Mutation in the Catalytic Domain of c-kit Elicits Hematopoietic Transformation by Receptor Self-Association Not at the Ligand-Induced Dimerization Site
- Author
-
Yukihiko Kitamura, Hiroyuki Sugahara, Yuzuru Kanakura, Hitoshi Kitayama, Itaru Matsumura, Hirokazu Ikeda, Tohru Tsujimura, Tsuneyasu Kaisho, Koji Hashimoto, and Nobuyuki Terada
- Subjects
Mutation ,biology ,Immunology ,Receptor Protein-Tyrosine Kinases ,Mutant ,Cell Biology ,Hematology ,medicine.disease_cause ,Biochemistry ,Molecular biology ,Receptor tyrosine kinase ,Protein kinase domain ,biology.protein ,medicine ,Tyrosine ,Signal transduction ,Receptor - Abstract
The c- kit receptor tyrosine kinase (KIT) is constitutively activated by naturally occurring mutations in either the juxtamembrane domain or the kinase domain. Although the juxtamembrane domain mutations led to ligand-independent KIT dimerization, the kinase domain mutations (Asp 814 → Val or Tyr) did not. In an effort to determine if the kinase domain mutant could transfer oncogenic signaling without receptor dimerization, we have constructed the truncated types of c- kit Wild and c- kit Tyr814 cDNAs (c- kit Del-Wild and c- kit Del-Tyr814 cDNAs, respectively), in which ligand-binding and ligand-induced dimerization domains were deleted. When c- kit Del-Wild and c- kit Del-Tyr814 genes were introduced into a murine interleukin-3 (IL-3)–dependent cell line Ba/F3, KIT Del-Tyr814 was constitutively phosphorylated on tyrosine and activated, whereas KIT Del-Wild was not. In addition, Ba/F3 cells expressing KIT Del-Tyr814 (Ba/F3 Del-Tyr814 ) grew in suspension culture without the addition of exogenous growth factor, whereas Ba/F3 cells expressing KIT Del-Wild (Ba/F3 Del-Wild ) required IL-3 for growth. The factor-independent growth of Ba/F3 Del-Tyr814 cells was virtually abrogated by coexpression of KIT W42 that is a dominant-negative form of KIT, but not by that of KIT Wild , suggesting that KIT Del-Tyr814 may not function as a monomer but may require receptor dimerization for inducing factor-independent growth. Furthermore, KIT Del-Tyr814 was found to be coimmunoprecipitated with KIT Wild or KIT W42 by an ACK2 monoclonal antibody directed against the extracellular domain of KIT. Moreover, KIT W42 was constitutively associated with a chimeric FMS/KIT Tyr814 receptor containing the ligand-binding and receptor dimerization domain of c- fms receptor (FMS) fused to the transmembrane and cytoplasmic domain of KIT Tyr814 , but not with a chimeric FMS/KIT Wild receptor even after stimulation with FMS-ligand. These results suggest that constitutively activating mutation of c- kit at the Asp 814 codon may cause a conformation change that leads to receptor self-association not in the extracellular domain and that the receptor self-association of the Asp 814 mutant may be important for activation of downstream effectors that are required for factor-independent growth and tumorigenicity.
- Published
- 1999
38. Modified Single Patch: Don’t We Have to Worry about Subaortic Stenosis Any More?
- Author
-
Hitoshi Kitayama
- Subjects
business.industry ,Medicine ,business ,Biomedical engineering - Published
- 2015
39. Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK
- Author
-
Masatoshi Maki, Yoji Ikawa, Zeqi Sheng, Tom Horan, Regina Maki Sasahara, Chiaki Takahashi, Setsuo Takai, Barry J. Ratzkin, Hitoshi Kitayama, Kiyotaka Hitomi, Makoto Noda, Tsutomu Arakawa, Aki Horimoto, and Yasuyuki Kitaura
- Subjects
DNA, Complementary ,Molecular Sequence Data ,Mice, Nude ,Biology ,GPI-Linked Proteins ,Transfection ,Gene Expression Regulation, Enzymologic ,3T3 cells ,Mice ,Complementary DNA ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Secretion ,Amino Acid Sequence ,Collagenases ,Cloning, Molecular ,Neoplasm Metastasis ,Fibroblast ,Gene Library ,chemistry.chemical_classification ,Mice, Inbred ICR ,Membrane Glycoproteins ,Multidisciplinary ,Sequence Homology, Amino Acid ,3T3 Cells ,Neoplasms, Experimental ,Oncogenes ,Biological Sciences ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Mice, Inbred C57BL ,Membrane glycoproteins ,Cell Transformation, Neoplastic ,Genes, ras ,medicine.anatomical_structure ,Matrix Metalloproteinase 9 ,chemistry ,Cell culture ,Lymphatic Metastasis ,biology.protein ,Glycoprotein ,Sequence Alignment - Abstract
A human fibroblast cDNA expression library was screened for cDNA clones giving rise to flat colonies when transfected into v-Ki- ras -transformed NIH 3T3 cells. One such gene, RECK , encodes a membrane-anchored glycoprotein of about 110 kDa with multiple epidermal growth factor-like repeats and serine-protease inhibitor-like domains. While RECK mRNA is expressed in various human tissues and untransformed cells, it is undetectable in tumor-derived cell lines and oncogenically transformed cells. Restored expression of RECK in malignant cells resulted in suppression of invasive activity with concomitant decrease in the secretion of matrix metalloproteinase-9 (MMP-9), a key enzyme involved in tumor invasion and metastasis. Moreover, purified RECK protein was found to bind to, and inhibit the proteolytic activity of, MMP-9. Thus, RECK may link oncogenic signals to tumor invasion and metastasis.
- Published
- 1998
40. A Murine Neural-Specific Homolog Corrects Cholinergic Defects inCaenorhabditis elegans unc-18Mutants
- Author
-
Hitoshi Kitayama, Keiko Gengyo-Ando, Yoji Ikawa, and Masahiro Mukaida
- Subjects
Transgene ,Molecular Sequence Data ,Vesicular Transport Proteins ,Nerve Tissue Proteins ,medicine.disease_cause ,Animals, Genetically Modified ,Mice ,Munc18 Proteins ,Antibody Specificity ,medicine ,Animals ,Humans ,RNA, Messenger ,Cloning, Molecular ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Gene ,Peptide sequence ,gamma-Aminobutyric Acid ,Acetylcholine receptor ,Genetics ,Neurotransmitter Agents ,Mutation ,Base Sequence ,Sequence Homology, Amino Acid ,biology ,cDNA library ,General Neuroscience ,Genetic Complementation Test ,Helminth Proteins ,Articles ,Phosphoproteins ,biology.organism_classification ,Cholinergic Fibers ,Cholinergic ,Synaptic Vesicles ,Carrier Proteins - Abstract
Caenorhabditis elegansUNC-18 protein, homologous to yeast Sec1p, is important in neurotransmitter release, because theunc-18mutation leads to severe paralysis and presynaptic acetylcholine (ACh) accumulation. To examine the functional conservation in mammals, we tried to isolateunc-18isoforms from mouse and human brain cDNA libraries and obtained two classes of isoforms—neural genes and ubiquitous genes. Neural genes were identical to Munc-18 (also known as n-Sec1 or rbSec1), identified in rat and bovine brains as a syntaxin-binding protein. According to “Munc-18” terminology, we call the neural genes Munc-18-1 and the ubiquitous genes Munc-18-3. These mammalian isoforms exhibit 58% (Munc-18-1) and 42–43% (Munc-18-3) amino acid sequence identity with UNC-18. Next, we constructed transgenicunc-18mutants to test biological activity of mouse Munc-18-1 and Munc-18-3 under the control ofC. elegans unc-18promoter. Munc-18-1 compensates for severe locomotion disability and cholinergic defects, e.g., abnormal sensitivities to cholinesterase inhibitors and cholinergic receptor agonists inunc-18mutants, but Munc-18-3 fails. These data suggest that Munc-18-1 andC. elegans unc-18may play positive roles in ACh release and that the molecular mechanism of neuronal regulated secretion has been partially conserved from nematodes to mammals.
- Published
- 1996
41. Constitutive activation of c-kit in FMA3 murine mastocytoma cells caused by deletion of seven amino acids at the juxtamembrane domain
- Author
-
Yasuhiro Moriyama, Koji Hashimoto, Yuji Matsuzawa, Hitoshi Kitayama, Tohru Tsujimura, Yuzuru Kanakura, Yukihiko Kitamura, and Masahiro Morimoto
- Subjects
Molecular Sequence Data ,Immunology ,Mast-Cell Sarcoma ,Mice, Nude ,Stem cell factor ,Transfection ,Biochemistry ,Receptor tyrosine kinase ,Mice ,Species Specificity ,Complementary DNA ,Proto-Oncogenes ,medicine ,Tumor Cells, Cultured ,Animals ,Amino Acid Sequence ,Phosphorylation ,Peptide sequence ,Sequence Deletion ,Stem Cell Factor ,biology ,Base Sequence ,Sequence Homology, Amino Acid ,Point mutation ,Mastocytoma ,DNA, Neoplasm ,Cell Biology ,Hematology ,medicine.disease ,Molecular biology ,Recombinant Proteins ,Neoplasm Proteins ,Protein Structure, Tertiary ,Enzyme Activation ,Mice, Inbred C57BL ,Proto-Oncogene Proteins c-kit ,Cell culture ,Vertebrates ,biology.protein ,Interleukin-3 ,Protein Processing, Post-Translational ,Sequence Alignment ,Cell Division ,Neoplasm Transplantation - Abstract
A peculiar point mutation results in constitutive activation of c-kit receptor tyrosine kinase (KIT) in three different tumor mast cell lines; ie, the HMC-1, P-815, and RBL-2H3. Because constitutive activation of KIT was also observed in the FMA3 mouse mastocytoma cell line, we investigated the molecular mechanism. Sequencing of the whole coding region of the c-kit showed that the point mutation found in HMC- 1, P-815, and RBL-2H3 cells was absent in FMA3 cells and that the c-kit cDNA of FMA3 cells carried an in-frame deletion of 21 base pairs (bp) encoding Thr-Gln-Leu-Pro-Tyr-Asp-His at codons 573 to 579 at the juxtamembrane domain. The FMA3-type c-kit cDNA with 21 bp deletion was introduced into the IC-2 cell line, which was derived from murine cultured mast cells. IC-2 cells were dependent on interleukin (IL)-3 and did not express KIT on the surface. In IC-2 cells introduced with the FMA3-type c-kit cDNA, KIT was constitutively phosphorylated on tyrosines and activated. Moreover, the FMA3-type KIT was dimerized without the stimulation by stem cell factor (SCF), a ligand for KIT. The spontaneously dimerized FMA3-type KIT without SCF binding was not internalized even after the activation. IC-2 cells expressing the FMA3- type KIT grew in suspension culture without IL-3 and SCF and became leukemic in nude athymic mice. The deletion of seven amino acids at the juxtamembrane domain appeared to be a new activating mutation of KIT that might be involved in neoplastic growth of mast cells.
- Published
- 1996
42. Identification of Rap1 as a Target for the Crk SH3 Domain-Binding Guanine Nucleotide-Releasing Factor C3G
- Author
-
Shun Nakamura, Seisuke Hattori, Hitoshi Kitayama, Michiyuki Matsuda, Hideki Matsui, Osamu Hatase, Takeshi Kurata, Yoshimi Takai, Kozo Kaibuchi, Makoto Noda, Takaya Gotoh, and Hidehiro Takahashi
- Subjects
Guanine ,Molecular Sequence Data ,Guanosine ,Cell Cycle Proteins ,Spodoptera ,Biology ,Transfection ,Guanosine Diphosphate ,Polymerase Chain Reaction ,SH3 domain ,Cell Line ,Substrate Specificity ,chemistry.chemical_compound ,Adapter molecule crk ,GTP-Binding Proteins ,Guanine Nucleotide-Releasing Factor 2 ,Proto-Oncogene Proteins ,Phosphoprotein Phosphatases ,Animals ,Guanine Nucleotide Exchange Factors ,Molecular Biology ,DNA Primers ,Binding Sites ,Base Sequence ,ras-GRF1 ,Activator (genetics) ,Membrane Proteins ,Proteins ,Cell Biology ,Proto-Oncogene Proteins c-crk ,Molecular biology ,Recombinant Proteins ,RALA ,Kinetics ,rap GTP-Binding Proteins ,chemistry ,Guanosine 5'-O-(3-Thiotriphosphate) ,Protein Biosynthesis ,Son of Sevenless Proteins ,ras Guanine Nucleotide Exchange Factors ,Rap1 ,Research Article - Abstract
C3G, which was identified as a Crk SH3 domain-binding guanine nucleotide-releasing factor, shows sequence similarity to CDC25 and Sos family proteins (S. Tanaka, T. Morishita, Y. Hashimoto, S. Hattori, S. Nakamura, M. Shibuya, K. Matuoka, T. Takenawa, T. Kurata, K. Nagashima, and M. Matsuda, Proc. Natl. Acad. Sci. USA 91:3443-3447, 1994). The substrate specificity of C3G was examined by in vitro and in vivo experiments. C3G markedly stimulated dissociation of bound GDP from Rap1B but marginally affected the same reaction of other Ras family proteins (Ha-Ras, N-Ras, and RalA). C3G also stimulated binding of GTP-gamma S [guanosine 5'-3-O-(thio)triphosphate] to Rap1B. When C3G and Rap1A were expressed in COS7 cells, marked accumulation of the active GTP-bound form of Rap1A was observed, while Sos was not effective in the activation of Rap1A. These results clearly show that C3G is an activator for Rap1. Furthermore, expression of C3G with a membrane localization signal in a v-Ki-ras transformant, DT, induced a reversion of the cells to the flat form, possibly through the activation of endogenous Rap1.
- Published
- 1995
43. Constitutively activating mutations of c-kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factor-dependent hematopoietic cell lines
- Author
-
Hiroyuki Ikeda, Hitoshi Kitayama, Hiroyuki Sugahara, Yoshio Kanayama, Yukihiko Kitamura, Takuma Furitsu, Tohru Tsujimura, Kenji Oritani, Hideki Mitsui, and Yuzuru Kanakura
- Subjects
Cell Transplantation ,Immunology ,Mice, Nude ,Stem cell factor ,Transfection ,medicine.disease_cause ,Biochemistry ,Receptor tyrosine kinase ,Cell Line ,Mice ,Proto-Oncogene Proteins ,Proto-Oncogenes ,Receptors, Colony-Stimulating Factor ,medicine ,Animals ,Humans ,Point Mutation ,Amino Acid Sequence ,Aspartic Acid ,Mice, Inbred BALB C ,Mutation ,biology ,Point mutation ,Receptor Protein-Tyrosine Kinases ,Valine ,Cell Biology ,Hematology ,Molecular biology ,Kinetics ,Proto-Oncogene Proteins c-kit ,Haematopoiesis ,Cell Transformation, Neoplastic ,Mutagenesis, Site-Directed ,biology.protein ,Female ,Tyrosine kinase ,Cell Division - Abstract
The c-kit receptor tyrosine kinase (KIT) is activated upon ligand binding, thereby leading to a variety of signaling events that play a fundamental role in hematopoiesis. In addition to ligand-dependent activation, we have previously shown that KIT is constitutively activated in a ligand-independent manner by two point mutations, Val- 559-->Gly (G559) mutation in the juxtamembrane domain and Asp-814-->Val (V814) mutation in the phosphotransferase domain. To investigate the biochemical consequence and biologic significance of these mutations, retroviral vectors encoding KITG559 or KITV814 were introduced into murine pro-B-type Ba/F3 cells and myeloid FDC-P1 cells, both of which require interleukin-3 (IL-3) for their growth and survival. In the cells, KITG559 or KITV814 were found to be constitutively phophorylated on tyrosine in the absence of stem cell factor (SCF) that is a ligand for KIT. Chemical cross-linking analysis showed that a substantial fraction of the phosphorylated KITG559 underwent dimerization even in the absence of SCF, whereas the phosphorylated KITV814 did not, suggesting the distinct mechanisms underlying constitutive activation of KIT by G559 and V814 mutations. Furthermore, the cells expressing either KITG559 or KITV814 were found to show a factor-independent growth, whereas the cells expressing wild-type KIT (KITWT) proliferated in response to SCF as well as IL-3. Moreover, subcutaneous injection of Ba/F3 cells expressing KITG559 or KITV814 into nude mice resulted in production of large tumors at all sites of the injection within 2 weeks, and all nude mice quickly succumbed to leukemia and died. These results suggest that, although the mechanisms underlying constitutive activation of KITG559 or KITV814 may be different, both of the activating mutations have a function to induce a factor-independent and tumorigenic phenotype. Also, the data of this study raise the possibility that the constitutively activating mutations of c-kit may play a causal role in development of hematologic malignancies.
- Published
- 1995
44. [Acute aortic dissection with anomalous coronary artery]
- Author
-
Takako, Nishino, Toshihiko, Saga, Hitoshi, Kitayama, Toshio, Kaneda, Susumu, Nakamoto, Kiyoaki, Takaba, Masato, Imura, Tatsuya, Ogawa, Takuma, Satsu, Kousuke, Fujii, and Shintaro, Yukami
- Subjects
Adult ,Male ,Aortic Dissection ,Coronary Vessel Anomalies ,Humans ,Emergencies ,Aortic Aneurysm - Abstract
A 38-year-old man was diagnosed with acute type A aortic dissection and severe aortic regurgitation, and taken immediately to the operating room for repair of the ascending aorta using the Bentall procedure. The presence of the anomalous right coronary artery was revealed at the time of the procedure, and was repaired with single coronary button technique. Some case reports have described anomalous coronary artery in association with acute myocardiac infarction or angina pectoris. This report describes a case of anomalous coronary artery diagnosed during an emergency operation for aortic dissection.
- Published
- 2012
45. Successful closure of a patent ductus arteriosus using an aortic stent graft
- Author
-
Kosuke Fujii, Takako Nishino, Susumu Nakamoto, Shintaro Yukami, Hitoshi Kitayama, Toshihiko Saga, and Toshio Kaneda
- Subjects
Pulmonary and Respiratory Medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,health care facilities, manpower, and services ,Closure (topology) ,Contrast Media ,Aortic stent ,Aortic disease ,Blood Vessel Prosthesis Implantation ,medicine.artery ,Ductus arteriosus ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Ductus Arteriosus, Patent ,Polytetrafluoroethylene ,Aged ,Aorta ,business.industry ,Gastroenterology ,General Medicine ,Stent grafting ,Blood Vessel Prosthesis ,medicine.anatomical_structure ,Echocardiography ,cardiovascular system ,Cardiology ,Surgery ,Female ,Stents ,sense organs ,Cardiology and Cardiovascular Medicine ,business ,Tomography, X-Ray Computed - Abstract
Closure of patent ductus arteriosus (PDA) in the elderly is a high-risk procedure due to the fragility of the aorta and aneurysmal changes in the ductus. Stent grafting has emerged as a method for treating aortic disease. We describe a case in which this endovascular technique was successfully performed for closure of a PDA with aneurismal change in a high-risk patient. This approach may comprise the armamentarium for treating this pathology in adults.
- Published
- 2011
46. Regulation of basophilic and erythroid-differentiation of a human chronic myelogenous leukemia-cell line, ku812f, by interleukin-3 and stem-cell factor
- Author
-
Yoshio Kanayama, Yuzuru Kanakura, Yukihiko Kitamura, Yuji Matsuzawa, Atsushi Yamatodani, Hitoshi Kitayama, Hiroyuki Sugahara, Seiichi Hirota, Takuma Furitsu, and Hirokazu Ikeda
- Subjects
Cancer Research ,Stem cell factor ,In situ hybridization ,Cell sorting ,Biology ,medicine.disease ,Cell biology ,Basophilic ,Oncology ,Cell culture ,biology.protein ,medicine ,Antibody ,Interleukin 3 ,Chronic myelogenous leukemia - Abstract
We have investigated the effects of c-kit ligand (stem cell factor [SCF]) and interleukin-3 (IL-3) on proliferation and differentiation of a human chronic myelogenous leukemia cell line, KU812F, which can differentiate toward erythroid and basophilic lineages. When purified c-kit-positive cells (approximately 20% of KU812F cells) were used as a target, SCF induced not only proliferation but also augumented erythroid differentiation of the cells, while IL-3 did promote basophilic differentiation. Further, analyses of in situ hybridization and cell sorting with anti-c-kit antibody showed that the expression of c-kit decreased along with differentiation from immature to mature basophils and erythroid cells.
- Published
- 2011
47. Semilunar Valve Replacement with a Cylindrical Valve
- Author
-
Shirotani H, Masao Ueda, Hidetaka Oku, Toshihiko Saga, Matsumoto T, and Hitoshi Kitayama
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Regurgitation (circulation) ,Prosthesis Design ,Truncus arteriosus ,medicine ,Animals ,Humans ,Pericardium ,cardiovascular diseases ,Child ,Polytetrafluoroethylene ,Tetralogy of Fallot ,Bioprosthesis ,Pulmonary Valve ,business.industry ,Infant ,Anatomy ,medicine.disease ,Truncus Arteriosus, Persistent ,Pulmonary Valve Insufficiency ,Pulmonary Valve Stenosis ,Stenosis ,medicine.anatomical_structure ,Child, Preschool ,Heart Valve Prosthesis ,Pulmonary valve ,Pulmonary valve stenosis ,cardiovascular system ,Female ,Surgery ,Cardiology and Cardiovascular Medicine ,business - Abstract
A cylindrical valve was designed to prevent regurgitation of the semilunar valve. The valve is made of a sheet of polytetrafluoroethylene (PTFE) or porcine pericardium, and has three cusps and three commissures. The diameter of the valve is equal to the height of the cusps. We have used these valves in pulmonary stenosis after Jatene's operation and total correction of tetralogy of Fallot, and for truncal valve regurgitation. Regurgitation was trivial on color Doppler echocardiography in all cases. Advantages in comparison with the implantation of commercially available artificial valves include the ability to insert a larger size and no compression of the valve ring when closing the sternum. Outflow tract obstruction does not occur even when the valve is implanted in a small infant. In the present report, we describe this simple technique.
- Published
- 1993
48. [Application of partial median sternotomy in cardiac surgery in patients with tracheostoma]
- Author
-
Toshio, Kaneda, Toshihiko, Saga, Hitoshi, Kitayama, Susumu, Nakamoto, Hiroshi, Kawasaki, Kiyoaki, Takaba, Masato, Imura, Kosuke, Fujii, Takako, Nishino, and Shintaro, Yukami
- Subjects
Adult ,Male ,Tracheostomy ,Humans ,Cardiac Surgical Procedures ,Middle Aged ,Sternotomy ,Aged - Abstract
Median full-sternotomy carries a risk of sternal infection and lethal mediastinitis in cardiac surgery. We performed open-heart surgery through partial median sternotomy in 5 patients with tracheostomy. Coronary artery bypass grafting (CABG) was performed in 3 patients, aortic valve replacement in 1, and mitral valve replacement in 1. No operative deaths or complications related to wound infection occurred. Partial sternotomy represents a safe alternative in cardiac surgery in patients with tracheostoma.
- Published
- 2010
49. [Resection and reconstruction of intimal sarcoma of the pulmonary artery with autologous pericardial roll]
- Author
-
Noriko, Takai, Yoshio, Yamamoto, Hitoshi, Kitayama, and Tatsushi, Nakagawa
- Subjects
Aged, 80 and over ,Male ,Humans ,Sarcoma ,Pulmonary Artery ,Tunica Intima ,Pericardium ,Transplantation, Autologous ,Vascular Surgical Procedures ,Vascular Neoplasms - Abstract
Tumors of the pulmonary artery (PA) are rare and their prognosis is poor. Proper diagnosis is often delayed or made post mortem despite diagnostic advances. Although the only treatment of choice is radical surgical resection, local recurrences are soon recognized after the operation. There is no standard regimen of perioperative additional therapy, and its effectiveness is still unknown. We report a case of an 80-year-old male whose PA was almost completely obstructed by the intimal sarcoma. It was resected and reconstructed with autologous pericardial roll. His postoperative course was uneventful.
- Published
- 2010
50. Involvement of the Reck tumor suppressor protein in maternal and embryonic vascular remodeling in mice
- Author
-
Hitoshi Kitayama, Tomoko Matsuzaki, Makoto Noda, Rei Takahashi, Akihiko Ueda, Hiroshi Kiyonari, Mako Yamamoto, E. P. S. Chandana, Yasuhiro Maeda, Shunya Kondo, Yoko Yoshida, Satoshi Kawashima, Chiaki Takahashi, Naoko Oshima, Yasuhiko Tabata, David B. Alexander, and Junseo Oh
- Subjects
medicine.medical_specialty ,Angiogenesis ,Neovascularization, Physiologic ,Biology ,GPI-Linked Proteins ,Small hairpin RNA ,Mice ,Pregnancy ,Intussusception (blood vessel growth) ,Internal medicine ,Conditional gene knockout ,medicine ,Animals ,Embryo Implantation ,lcsh:QH301-705.5 ,Metalloproteinase ,Membrane Glycoproteins ,Uterus ,Embryo ,Embryo, Mammalian ,Embryonic stem cell ,Phenotype ,Cell biology ,Endocrinology ,lcsh:Biology (General) ,Blood Vessels ,Female ,Research Article ,Developmental Biology - Abstract
Background Developmental angiogenesis proceeds through multiple morphogenetic events including sprouting, intussusception, and pruning. Mice lacking the membrane-anchored metalloproteinase regulator Reck die in utero around embryonic day 10.5 with halted vascular development; however, the mechanisms by which this phenotype arises remain unclear. Results We found that Reck is abundantly expressed in the cells associated with blood vessels undergoing angiogenesis or remodelling in the uteri of pregnant female mice. Some of the Reck-positive vessels show morphological features consistent with non-sprouting angiogenesis. Treatment with a vector expressing a small hairpin RNA against Reck severely disrupts the formation of blood vessels with a compact, round lumen. Similar defects were found in the vasculature of Reck-deficient or Reck conditional knockout embryos. Conclusions Our findings implicate Reck in vascular remodeling, possibly through non-sprouting angiogenesis, in both maternal and embyornic tissues.
- Published
- 2010
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.