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Article ; Online: A New Horizon in Vitamin K Research.

Okano, Toshio

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

2016 Volume 136, Issue 8, Page(s) 1141–1159

Abstract: Vitamin K is a cofactor for γ-glutamyl carboxylase, which catalyzes the posttranslational conversion of specific glutamyl residues to γ-carboxyglutamyl residues in a variety of vitamin K-dependent proteins (VKDPs) involved in blood coagulation, bone and ... ...

Abstract	Vitamin K is a cofactor for γ-glutamyl carboxylase, which catalyzes the posttranslational conversion of specific glutamyl residues to γ-carboxyglutamyl residues in a variety of vitamin K-dependent proteins (VKDPs) involved in blood coagulation, bone and cartilage metabolism, signal transduction, and cell proliferation. Despite the great advances in the genetic, structural, and functional studies of VKDPs as well as the enzymes identified as part of the vitamin K cycle which enable it to be repeatedly recycled within the cells, little is known of the identity and roles of key regulators of vitamin K metabolism in mammals and humans. This review focuses on new insights into the molecular mechanisms underlying the intestinal absorption and in vivo tissue conversion of vitamin K1 to menaquinone-4 (MK-4) with special emphasis on two major advances in the studies of intestinal vitamin K transporters in enterocytes and a tissue MK-4 biosynthetic enzyme UbiA prenyltransferase domain-containing protein 1 (UBIAD1), which participates in the in vivo conversion of a fraction of dietary vitamin K1 to MK-4 in mammals and humans, although it remains uncertain whether UBIAD1 functions as a key regulator of intracellular cholesterol metabolism, bladder and prostate tumor cell progression, vascular integrity, and protection from oxidative stress.
MeSH term(s)	Animals ; Cell Transformation, Neoplastic/drug effects ; Cholesterol/metabolism ; Dimethylallyltranstransferase/chemistry ; Dimethylallyltranstransferase/metabolism ; Dimethylallyltranstransferase/pharmacology ; Dimethylallyltranstransferase/physiology ; Enterocytes/metabolism ; Humans ; Intestinal Absorption ; Mice ; Neoplasms/pathology ; Oxidative Stress/drug effects ; Vitamin K/metabolism ; Vitamin K/physiology ; Vitamin K 2/analogs & derivatives ; Vitamin K 2/metabolism
Chemical Substances	Vitamin K 2 (11032-49-8) ; Vitamin K (12001-79-5) ; menatetrenone (27Y876D139) ; Cholesterol (97C5T2UQ7J) ; Dimethylallyltranstransferase (EC 2.5.1.1) ; UBIAD1 protein, human (EC 2.5.1.1.)
Language	Japanese
Publishing date	2016-08-01
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	200514-1
ISSN	1347-5231 ; 0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
ISSN (online)	1347-5231
ISSN	0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
DOI	10.1248/yakushi.16-00014
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Article: [The role of the liver in vitamin D metabolism].

Okano, Toshio

Clinical calcium

2015 Volume 25, Issue 11, Page(s) 1613–1618

Abstract: Vitamin D₃is generated in the skin, and subsequently metabolized to 25OHD₃in the liver and then to 1α,25(OH)2D₃in the kidney, and thereafter, 1α,25(OH)₂D₃exerts its biological functions by regulating gene transcription via binding to nuclear receptor, ... ...

Abstract	Vitamin D₃is generated in the skin, and subsequently metabolized to 25OHD₃in the liver and then to 1α,25(OH)2D₃in the kidney, and thereafter, 1α,25(OH)₂D₃exerts its biological functions by regulating gene transcription via binding to nuclear receptor, VDR in target cells. 1α,25(OH)₂D₃plays a critical role in this vitamin D endocrine system. However, it has become obvious in the recent years that plasma concentrations of 25OHD₃but not 1α,25(OH)₂D₃, significantly associate with the incident risk of life style-related diseases such as osteoporosis and diabetes. Moreover, it appears that 25OHD₃itself acts as a ligand for VDR. Based on the findings that liver is not only the major productive organ for 25OHD₃but also the sole productive organ for DBP which serves to deliver 25OHD₃to tissues and stores 25OHD₃in the blood circulation, it is believed that liver plays important roles in vitamin D metabolism and vitamin D functions. The roles of the liver in vitamin D metabolism including the regulatory mechanism of the expression and activation of a 25OHD₃biosynthetic enzyme, CYP2R1, remain largely unsolved.
MeSH term(s)	Animals ; Biological Transport ; Cholestanetriol 26-Monooxygenase/metabolism ; Diet ; Humans ; Liver/metabolism ; Receptors, Calcitriol/metabolism ; Vitamin D/metabolism
Chemical Substances	Receptors, Calcitriol ; Vitamin D (1406-16-2) ; Cholestanetriol 26-Monooxygenase (EC 1.14.15.15)
Language	Japanese
Publishing date	2015-11
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	2386417-5
ISSN	0917-5857
ISSN	0917-5857
DOI	CliCa151116131618
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Article: [Gla-containing proteins].

Okano, Toshio

Clinical calcium

2014 Volume 24, Issue 2, Page(s) 241–248

Abstract: To date, 16 Gla-containing proteins have been discovered in humans, 7 and 9 of which are involved or not-involved in the blood coagulation cascade, respectively. They have a common feature that the carbon at the γ-position of glutamic acid in the ... ...

Abstract	To date, 16 Gla-containing proteins have been discovered in humans, 7 and 9 of which are involved or not-involved in the blood coagulation cascade, respectively. They have a common feature that the carbon at the γ-position of glutamic acid in the specific amino acid sequence of the protein molecule is carboxylated. γ-Glutamyl carboxylase catalyzes this reaction in the presence of vitamin K as a cofactor. Similar to phosphorylation and glycosylation, γ-carboxylation of the glutamic acid has been thought to be one of the post-translational modification for the activation of proteins. However, undercarboxylated, but not highly carboxylated osteocalcin has been found to exhibit regulatory activities of glucose metabolism and insulin sensitivity in mice, suggesting that there would be more comprehensive mechanisms in the regulation of protein functions by the carboxylation of glutamic acid and the decarboxylation of γ-glutamic acid.
MeSH term(s)	Animals ; Bone and Bones/metabolism ; Carbon-Carbon Ligases/biosynthesis ; Glutamic Acid/genetics ; Glutamic Acid/metabolism ; Humans ; Osteocalcin/chemistry ; Osteocalcin/metabolism ; Protein Processing, Post-Translational/drug effects ; Vitamin K/metabolism
Chemical Substances	Osteocalcin (104982-03-8) ; Vitamin K (12001-79-5) ; Glutamic Acid (3KX376GY7L) ; Carbon-Carbon Ligases (EC 6.4.-) ; glutamyl carboxylase (EC 6.4.-)
Language	Japanese
Publishing date	2014-02
Publishing country	Japan
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	2386417-5
ISSN	0917-5857
ISSN	0917-5857
DOI	CliCa1402241248
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Article: [Bone metabolism and cardiovascular function update. Role of vitamin D in the bone and vascular intercommunication].

Okano, Toshio

Clinical calcium

2014 Volume 24, Issue 7, Page(s) 45–52

Abstract: Vascular calcification, hypertension and cardiac hypertrophy have been often complicated in osteoporotic patients with low bone mass. Since there are many similarities among the processes of bone formation and vascular calcification, vitamin D ... ...

Abstract	Vascular calcification, hypertension and cardiac hypertrophy have been often complicated in osteoporotic patients with low bone mass. Since there are many similarities among the processes of bone formation and vascular calcification, vitamin D insufficiency has been thought to be deeply involved in the pathogenesis of these diseases. Indeed, in animal studies, vitamin D receptor gene knockout mice have been shown to display severe vascular calcification, high blood pressure, and left ventricular hypertrophy. On the other hand, in clinical studies, active vitamin D restores vascular calcification and improves heart function in dialysis patients. Whether 1,25 (OH) ₂D₃ acts directly on vascular smooth muscle cells and cardiomyocytes or acts indirectly on them via regulating calcium metabolism remains unclear. The elucidation of the role of vitamin D in the bone and vascular intercommunication and its application toward drug development could be an important step forward in the realization of health and longevity society.
MeSH term(s)	Animals ; Bone and Bones/metabolism ; Cardiovascular Diseases/metabolism ; Cell Communication ; Humans ; Hypertension/metabolism ; Osteoporosis/metabolism ; Vascular Calcification/metabolism ; Vitamin D/metabolism
Chemical Substances	Vitamin D (1406-16-2)
Language	Japanese
Publishing date	2014-07
Publishing country	Japan
Document type	English Abstract ; Journal Article
ZDB-ID	2386417-5
ISSN	0917-5857
ISSN	0917-5857
DOI	CliCa140710131020
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Article: [Clinical application of serum 25OHD].

Okano, Toshio

Clinical calcium

2013 Volume 23, Issue 3, Page(s) 377–384

Abstract: Serum 25OHD concentration is considered to be an appropriate measure for judging vitamin D insufficiency/sufficiency. It is hard to set its reference value. Nowadays, two reference values, namely 50 nmol/L for prevention of bone fracture and 75 nmol/L ... ...

Abstract	Serum 25OHD concentration is considered to be an appropriate measure for judging vitamin D insufficiency/sufficiency. It is hard to set its reference value. Nowadays, two reference values, namely 50 nmol/L for prevention of bone fracture and 75 nmol/L for lowering serum PTH concentration have been proposed. In the elderly, if the former value is used for the assessment, almost half of the population will be classified as insufficient, while the latter is used, almost all the population will be classified as insufficient. Precise and reliable measurements for serum 25OHD are critical for the clinical use of the reference value and the reimbursement of serum 25OHD measurement with the national health care system are required in the treatment of osteoporosis.
MeSH term(s)	Fractures, Bone/blood ; Fractures, Bone/diagnosis ; Fractures, Bone/drug therapy ; Humans ; Osteoporosis/blood ; Osteoporosis/diagnosis ; Osteoporosis/drug therapy ; Parathyroid Hormone/blood ; Reference Values ; Vitamin D/analogs & derivatives ; Vitamin D/blood ; Vitamin D Deficiency/diagnosis
Chemical Substances	Parathyroid Hormone ; Vitamin D (1406-16-2) ; 25-hydroxyvitamin D (A288AR3C9H)
Language	Japanese
Publishing date	2013-03
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	2386417-5
ISSN	0917-5857
ISSN	0917-5857
DOI	CliCa1303377384
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Article ; Online: Key Pathways and Regulators of Vitamin K Function and Intermediary Metabolism.

Shearer, Martin J / Okano, Toshio

Annual review of nutrition

2018 Volume 38, Page(s) 127–151

Abstract: Vitamin K (VK) is an essential cofactor for the post-translational conversion of peptide-bound glutamate to γ-carboxyglutamate. The resultant vitamin K-dependent proteins are known or postulated to possess a variety of biological functions, chiefly in ... ...

Abstract	Vitamin K (VK) is an essential cofactor for the post-translational conversion of peptide-bound glutamate to γ-carboxyglutamate. The resultant vitamin K-dependent proteins are known or postulated to possess a variety of biological functions, chiefly in the maintenance of hemostasis. The vitamin K cycle is a cellular pathway that drives γ-carboxylation and recycling of VK via γ-carboxyglutamyl carboxylase (GGCX) and vitamin K epoxide reductase (VKOR), respectively. In this review, we show how novel molecular biological approaches are providing new insights into the pathophysiological mechanisms caused by rare mutations of both GGCX and VKOR. We also discuss how other protein regulators influence the intermediary metabolism of VK, first through intestinal absorption and second through a pathway that converts some dietary phylloquinone to menadione, which is prenylated to menaquinone-4 (MK-4) in target tissues by UBIAD1. The contribution of MK-4 synthesis to VK functions is yet to be revealed.
MeSH term(s)	Animals ; Gene Expression Regulation, Enzymologic ; Humans ; Intestinal Absorption/physiology ; Mutation ; Vitamin K/metabolism ; Vitamin K Epoxide Reductases/genetics ; Vitamin K Epoxide Reductases/metabolism
Chemical Substances	Vitamin K (12001-79-5) ; Vitamin K Epoxide Reductases (EC 1.17.4.4)
Language	English
Publishing date	2018-06-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	406980-8
ISSN	1545-4312 ; 0199-9885
ISSN (online)	1545-4312
ISSN	0199-9885
DOI	10.1146/annurev-nutr-082117-051741
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Article: Intestinal Behçet's and suspected intestinal Behçet's disease: a report of four surgical cases.

Ono, Rika / Tominaga, Tetsuro / Nonaka, Takashi / Takamura, Yuma / Oishi, Kaido / Shiraishi, Toshio / Hashimoto, Shintaro / Noda, Keisuke / Sawai, Terumitsu / Okano, Shinji / Nagayasu, Takeshi

Surgical case reports

2024 Volume 10, Issue 1, Page(s) 3

Abstract: Background: Intestinal Behçet's disease (BD) is often associated with ulceration that requires surgery, including perforation and abscess formation. However, no consensus has been reached on the optimal extent of resection or treatment strategy. This ... ...

Abstract	Background: Intestinal Behçet's disease (BD) is often associated with ulceration that requires surgery, including perforation and abscess formation. However, no consensus has been reached on the optimal extent of resection or treatment strategy. This study reviewed four cases of intestinal or suspected intestinal BD. Case presentations: In Case 1, a 74-year-old woman diagnosed with BD 2 years earlier was treated with anti-tumor necrosis factor α antibody (Infliximab) and steroids. She had oral and pubic ulcers. After close investigation of abdominal pain, perforation of the gastrointestinal tract was suspected and surgery was performed. Multiple perforating ulcers and abscesses were found in the distal ileum, and the small intestine was resected. Postoperatively, the patient was treated with an increased steroid dose and symptoms have remained stable. Case 2 involved a 69-year-old woman with oral and pubic ulcers, ocular ulcer, and skin lesions. She experienced sudden onset of abdominal pain during treatment for lymphoma. She showed multiple perforating ulcers throughout the ileum and underwent resection of the small intestine and ileostomy. Upper abdominal pain appeared during postoperative treatment for high-output syndrome. The patient underwent omentoplasty after perforation of the upper gastrointestinal tract was diagnosed. Postoperatively, anti-interleukin-1 beta antibodies (canakinumab) was administered to control the disease. Case 3 involved an 81-year-old, previously healthy woman. She presented to her previous physician with complaints of pubic ulcer, hemorrhage and abdominal pain. Colonoscopy showed multiple ulcers throughout the entire colon. Steroid therapy was started, but bleeding proved difficult to control and total proctocolectomy was performed. Histopathology revealed multiple perforating ulcers and BD was diagnosed. Postoperatively, the patient remains under steroid control. Case 4 involved a 43-year-old man with abdominal pain who showed abscess formation in the ileocecal region. After excision of the ileocecal area, multiple ulcers were diagnosed. Two years later, abdominal pain recurred and free air was found in the abdomen on close imaging. Emergency anastomotic resection was performed due to ulceration and perforation of the anastomosis. Conclusions: Intestinal BD may flare up after surgical treatment and require multiple surgeries. Introducing pharmacotherapy as soon as possible after surgical treatment is important to control the disease.
Language	English
Publishing date	2024-01-02
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2809613-7
ISSN	2198-7793
ISSN	2198-7793
DOI	10.1186/s40792-023-01798-2
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Article ; Online: Development of gamma-ray-induced positron age-momentum correlation measurement.

Taira, Yoshitaka / Yamamoto, Ryohei / Sugita, Kento / Okano, Yasuaki / Hirade, Tetsuya / Namizaki, Shogo / Ogawa, Toshio / Adachi, Yoshitaka

The Review of scientific instruments

2022 Volume 93, Issue 11, Page(s) 113304

Abstract: In conventional positron annihilation spectroscopy using radioisotopes, source contributions are unavoidable since positrons annihilate in the material covering the radioisotopes. Part of the positrons annihilate within the radioisotopes even when ... ...

Abstract	In conventional positron annihilation spectroscopy using radioisotopes, source contributions are unavoidable since positrons annihilate in the material covering the radioisotopes. Part of the positrons annihilate within the radioisotopes even when radioisotopes are deposited directly on a sample. Gamma-ray-induced positron annihilation spectroscopy makes it possible to measure only the spectra of a sample without source contributions since positrons are directly generated inside the sample from the gamma rays by pair production and annihilate inside the same sample. In this study, a new positron age-momentum correlation measurement system using ultrashort pulsed gamma rays is developed. The gamma rays with an energy of 6.6 MeV are generated by the inverse Thomson scattering of laser photons by high-energy electrons and are irradiated to the sample. The laser pulse can fully control the timing of gamma-ray generation. This characteristic and the use of a digital oscilloscope with a 12-bit vertical resolution enable us to develop a simple measurement system. Time-resolved momentum distributions for stainless steel with no defects and deformed interstitial free steel show the explicit differences reflecting the type of defect; for BaF
Language	English
Publishing date	2022-11-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	209865-9
ISSN	1089-7623 ; 0034-6748
ISSN (online)	1089-7623
ISSN	0034-6748
DOI	10.1063/5.0105238
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Article ; Online: Controlling nutritional status score predicts postoperative complications after hip fracture surgery.

Yagi, Toshio / Oshita, Yusuke / Okano, Ichiro / Kuroda, Takuma / Ishikawa, Koji / Nagai, Takashi / Inagaki, Katsunori

BMC geriatrics

2020 Volume 20, Issue 1, Page(s) 243

Abstract: Background: Controlling Nutritional Status (CONUT) score is calculated using laboratory values, including serum albumin, total cholesterol concentration, and total lymphocyte count; it is reportedly valuable for making nutritional assessments. One ... ...

Abstract	Background: Controlling Nutritional Status (CONUT) score is calculated using laboratory values, including serum albumin, total cholesterol concentration, and total lymphocyte count; it is reportedly valuable for making nutritional assessments. One advantage of CONUT score over other nutritional assessments is that it can be calculated retrospectively using only objective laboratory values. Studies demonstrated that CONUT score was a useful tool for predicting prognosis and complications in various surgical conditions. Nevertheless, few studies utilized the score as a potential predictive marker for postoperative complications among hip fracture patients. The purpose of this study was to determine the association between CONUT score and postoperative complications in hip fracture patients. Methods: We retrospectively reviewed 211 elderly patients who underwent hip fracture surgery at a single institution from 2013 to 2018. CONUT score was calculated using preoperative routine laboratory tests for serum albumin, total cholesterol concentration, and total lymphocyte count. As potential confounders, we extracted data such as patient age, sex, fracture type, and general conditions/comorbidities, as defined by the American Society of Anesthesiologists Physical Status (ASA-PS) classification and the Charlson Comorbidity Index (CCI). Postoperative complications were defined as a Clavien-Dindo classification of 1 or more. Simple and multivaribale logistic regression analyses were performed to assess the incidence of postoperative complications as the outcome measures. Results: The mean age [IQR] was 86 [80-90], and 80.1% of the reviewed patients were female. Based on the CONUT scores, 78.7% of hip fracture patients were classified as malnourished; 18% experienced postoperative complications. Simple analyses revealed significant risk factors for postoperative complications, including age, the ASA-PS, the CCI, and the CONUT score. Multivariable analysis found that CONUT score was the independent risk factor for postoperative complications (odd ratio = 1.21, 95% confidence interval = 1.01-1.45, p = 0.04). Conclusions: Preoperative CONUT scores are independently associated with the incidence of postoperative complications. CONUT score can be used for risk assessment in hip fracture patients to predict early postoperative complications.
MeSH term(s)	Aged ; Female ; Humans ; Malnutrition ; Nutrition Assessment ; Nutritional Status ; Postoperative Complications/diagnosis ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology ; Prognosis ; Retrospective Studies
Language	English
Publishing date	2020-07-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2059865-8
ISSN	1471-2318 ; 1471-2318
ISSN (online)	1471-2318
ISSN	1471-2318
DOI	10.1186/s12877-020-01643-3
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Article: [Vitamin D, K and bone mineral density].

Okano, Toshio

Clinical calcium

2005 Volume 15, Issue 9, Page(s) 1489–1494

Abstract: Both vitamin D and vitamin K are essential nutrients for bone health. It is believed that vitamin D deficiency is responsible for rickets in infants and osteomalacia in adults, and chronic vitamin D insufficiency induces hyperparathyroidism and reduces ... ...

Abstract	Both vitamin D and vitamin K are essential nutrients for bone health. It is believed that vitamin D deficiency is responsible for rickets in infants and osteomalacia in adults, and chronic vitamin D insufficiency induces hyperparathyroidism and reduces bone mineral density, resulting in an increased risk of osteoporosis. Vitamin K deficiency is thought to cause impaired activation of bone matrix protein osteocalcin, and reduction of osteoblast function, resulting in impaired bone formation. Recently, we reported that a high prevalence of low vitamin D status (low serum 25-hydroxyvitamin D concentration) . low bone mineral density, and a high prevalence of low vitamin K status (high serum undercarboxylated osteocalcin concentration) . high frequency of bone fracture in elderly women in Japan. However, no correlation between low vitamin K status and low bone mineral density was observed in this subjects.
MeSH term(s)	Aged ; Bone Density/physiology ; Female ; Humans ; Vitamin D/blood ; Vitamin D Deficiency/metabolism ; Vitamin K/blood
Chemical Substances	Vitamin K (12001-79-5) ; Vitamin D (1406-16-2)
Language	Japanese
Publishing date	2005-09
Publishing country	Japan
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	2386417-5
ISSN	0917-5857
ISSN	0917-5857
DOI	CliCa14891500
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