shikoku acta medica vol.75 , no.1,2shikoku acta medica vol.75 , no.1,2(april 25,2019)...

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SHIKOKU ACTA MEDICA Vol. 75 , No. 1,2 April 25, 2019 特集:健康長寿を目指して 第75巻第1,2号平成314 25日) 徳 島 医 学 会 Tokushima Medical Association Tokushima, Japan

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Page 1: SHIKOKU ACTA MEDICA Vol.75 , No.1,2SHIKOKU ACTA MEDICA Vol.75 , No.1,2(April 25,2019) 特集:健康長寿を目指して 第75巻第1,2号(平成31年4月25日) 徳 島

SHIKOKU ACTA MEDICAVol. 75 , No.1,2(April 25, 2019)

特集:健康長寿を目指して

第75巻 第1,2号(平成31年4月25日)

徳 島 医 学 会Tokushima Medical Association

Tokushima, Japan

SHIKOKUACTAMEDICAVol.��,

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Page 2: SHIKOKU ACTA MEDICA Vol.75 , No.1,2SHIKOKU ACTA MEDICA Vol.75 , No.1,2(April 25,2019) 特集:健康長寿を目指して 第75巻第1,2号(平成31年4月25日) 徳 島

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SHIKOKU ACTAMEDICA

Editorial BoardEditor-in-Chief : Tetsuro Ohmori

Editors : Kokichi ARISAWA Masato UTSUNOMIYAHiroyoshi SEI Hiroshi SAKAUEMasahito TOMOTAKE Ichiro HASHIMOTOToshiaki MORI

Published by Tokushima Medical Associationin Tokushima University Faculty of Medicine,3 Kuramoto-cho, Tokushima 770-8503, JapanTel : 088-633-7104 Fax : 088-633-7115e-mail : [email protected]

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Page 3: SHIKOKU ACTA MEDICA Vol.75 , No.1,2SHIKOKU ACTA MEDICA Vol.75 , No.1,2(April 25,2019) 特集:健康長寿を目指して 第75巻第1,2号(平成31年4月25日) 徳 島

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�cTanaka, S., Kuroda, T., Yamazaki, Y., Shiraki, Y., etal . : Serum��­hydroxyvitamin D below��ng/mL isa risk factor for long bone fracture comparable tobone mineral density in Japanese postmenopausalwomen. J. Bone Miner. Metab.�¬�«®­� ���«®

¯cNakamura, K., Saito, T., Oyama, M., Oshiki, R., et al . :Vitamin D sufficiency is associated with low incidenceof limb and vertebral fractures in community-dwellingelderly Japanese women : the Muramatsu Study.Osteoporos Int.�¬°�­«� ���««

®cTamaki, J., Iki, M., Sato, Y., Kajita, E., et al . : JPOSStudy Group. Total��­hydroxyvitamin D levels pre-dict fracture risk : results from the«�­year follow-up of the Japanese Population-based OsteoporosisbJPOScCohort Study. Osteoporos Int.��¬«°�­« ���«�

�cTsugawa, N., Uenishi, K., Ishida, H., Ozaki, R., et al . :Association between vitamin D status and serumparathyroid hormone concentration and calcanealstiffness in Japanese adolescents : sex differences insusceptibility to vitamin D deficiency. J. Bone Miner.Metab.��¬®d®­�®���«d

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��Bischoff-Ferrari, H. A., Willett, W. C., Wong, J. B., Stuck,A. E., et al . : Prevention of nonvertebral fractureswith oral vitamin D and dose dependency : a meta-analysis of randomized controlled trials. Arch. Intern.Med.�������������

��Bischoff-Ferrari, H. A., Willett, W. C., Orav, E. J., Lips,P., et al . :A pooled analysis of vitamin D dose require-ments for fracture prevention. N. Engl. J. Med.����� ����

��Avenell, A., Gillespie, W. J., Gillespieet, L. D., O�Connell,D. : Vitamin D and vitamin D analogues for preven-ting fractures associated with involutional and post-menopausal osteoporosis. The Cochrane Databaseof Systematic Reviews. Issue. Art. No. : CD�.DOI :�.�/� ������. CD�. pub�,�

��Bischoff-Ferrari, H. A., Kiel, D. P., Dawson-Hughes,B., Orav, J, E., et al . : Dietary calcium and serum��hydroxyvitamin D status in relation to BMD amongU.S. adults. J. Bone Miner. Res.�������� ��

��Bischoff-Ferrari, H. A., Dietrich, T., Orav, E. J., Dawson�Hughes, B. : Positive association between��hydroxyvitamin D levels and bone mineral density : a popula-tion-based study of younger and older adults. Am. J.Med.������� ����

���Okazaki, R., Ozono, K., Fukumoto, S., Inoue, D., et al . :Assessment criteria for vitamin D deficiency/in-sufficiency in Japan : proposal by an expert panelsupported by the Research Program of IntractableDiseases, Ministry of Health, Labour and Welfare,Japan, the Japanese Society for Bone and MineralResearch and the Japan Endocrine Society�Opinion�.J. Bone Miner. Metab.���������

��Ohta, H., Kuroda, T., Tsugawa, N., Onoe, Y., et al . :Optimal vitamin D intake for preventing serum��hydroxyvitamin D insufficiency in young Japanesewomen. J. Bone Miner. Metab.����������

���Kuwabara, A., Tsugawa, N., Tanaka, K., Fujii, M., etal . : Improvement of vitamin D status in Japaneseinstitutionalized elderly by supplementation with�IU of vitamin D�. J. Nutr. Sci. Vitaminol.�� ������

� �Shiraishi, M., Haruna, M., Matsuzaki, M., Murayama,R. : Demographic and lifestyle factors associated with

vitamin status in pregnant Japanese women. J. Nutr.Sci. Vitaminol.�Tokyo���� ����

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�������������� !" #�2015$%������&' http : //www.josteo.com/ja/guideline/doc/��_�.pdf

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�Macdonald, H. M., Reid, I. R., Gamble, G. D., Fraser,W. D., et al . :��Hydroxyvitamin D Threshold for theEffects of Vitamin D Supplements on Bone Density

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Secondary Analysis of a Randomized ControlledTrial. J. Bone Miner. Res.�������������

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of vitamin D deficiency in Japanese adults;VitaminD Deficiency questionnaire for Japanese : VDDQ-J .J. Bone Miner. Metab.���<Epub ahead of print=

: Holick, M. F., The vitamin D deficiency pandemic :Approaches for diagnosis, treatment and prevention.Rev. Endocr. Metab. Disord.������9�����:

Osteoporosis and Vitamin D

Naoko Tsugawa

Laboratory of Public Health, Department of Health and Nutrition, Faculty of Health and Nutrition, Osaka Shoin Women’sUniversity, Osaka, Japan

SUMMARY

Vitamin D plays a critical role in calcium and bone metabolism. Vitamin D is supplied fromintake of vitamin D rich food and sunlight exposure in skin, and subsequently metabolized to��hydroxyvitamin D;�OHD in liver and to 1,25�dihydroxyvitamin D, active vitamin D, in kidney.Serum�OHD concentration is most useful marker for estimating nutritional status of vitamin D.Although�OHD is not active form, many epidemiological studies have clearly shown that low��hydroxyvitamin D;�OHD concentrations are associated with low bone mineral density andincidence of fracture. Recently, the Japanese Society for Bone and Mineral Research and the JapanEndocrine Society have proposed the guidelines for assessment criteria for vitamin D deficiency/insufficiency using serum�OHD concentration in Japan as follows. ;1 Serum�OHD concentra-tion equal to or above9ng/ml is considered to be vitamin D sufficient. ;2 Serum�OHD con-centration less than9ng/ml but not less thanng/ml is considered to be vitamin D insufficient.;3 Serum�OHD concentration less thanng/ml is considered to be vitamin D deficient. Accor-ding to this criteria, many recent studies have reported that more than�> of Japanese people arein vitamin D deficiency defined by lower than ng/mL. Declines of fish intake and sunlightexposure in recent Japanese life style would be risk factors of vitamin D deficiency. However, mostpeople unaware their own vitamin D status. Regarding requirement of vitamin D for prevention ofosteoporosis or to ensure a sufficient vitamin D status, the recommendations are not fully consistentbut at least��µg;���IU of vitamin D per day can be recommended in the general. Toprevent osteoporosis, nutritional self-care in vitamin D should be strongly recommended by takingvitamin D rich foods or by effective sunlight exposure.

Key words : vitamin D, osteoporosis,��hydroxyvitamin D, vitamin D deficiency, vitamin D intake

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01Ikemoto, M., Nikawa, T., Takeda, S., Watanabe, C., etal . : Space shuttle flight.STS�Ì�1enhances degra-dation of rat myosin heavy chain in association withactivation of ubiquitin-proteasome pathway. FASEB J���Ë7ÍÎÌ�7ÍÏ7�Í��7

�1Nikawa, T., Ishidoh, K., Hirasaka, K., Ishihara, I., etal . : Skeletal muscle gene expression in space-flownrats. FASEB J���Ë0ÍÍ�0Í��Í���

Î1Okamoto, K., Shaw, J. M. : Mitochondrial morphologyand dynamics in yeast and multicellular eukaryotes.Annu Rev Genet�� Ë0���0���Í��0

Ï1Romanello, V., Guadagnin, E., Gomes, L., Roder, I., etal . : Mitochondrial fission and remodelling contribu-tes to muscle atrophy. EMBO J� Ë7ÎÎ��7ÎÏ0�Í�77

Ì1Praefcke, G. J., McMahon, H. T. : The dynamin super-family : universal membrane tubulation and fissionmolecules? Nat Rev Mol Cell Biol��Ë7���7�Î�Í���

7�1Uchida, T., Sakashita, Y., Kitahata, K., Yamashita, Y.,et al . : Reactive oxygen species upregulate expre-ssion of muscle atrophy-associated ubiquitin ligaseCbl-b in rat L� skeletal muscle cells. Am J PhysiolCell Physiol����ËCÎÍ7�CÎ�7�Í�7Ï

771Ochi, A., Abe, T., Nakao, R., Yamamoto, Y. et al . : N-myristoylated ubiquitin ligase Cbl-b inhibitor pre-vents on glucocorticoid-induced atrophy in mouseskeletal muscle. Arch Biochem Biophys����ËÍ���7�Í�70

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The mechanism of skeletal muscle atrophy : finding from space experiment

Takayuki Uchida

Department of Nutritional Physiology, Institute of Medical Nutrition, Tokushima University Graduate School, Tokushima, Japan

SUMMARY

Skeletal muscle atrophy is a response to decreased physical signals�unloading�, such as undermicrogravity, bed rest and neural inactivation, and is characterized by muscle volume loss andmuscle fiber-type switching.

We previously demonstrated that elevated ubiquitin ligase casitas B-lineage lymphoma-b�Cbl-b�resulted in the loss of muscle volume. Here, we showed that the ROS-mediated signal transduc-tion caused by microgravity or its simulation contributes to Cbl-b expression.

In L6 myotubes, the assessment of redox status revealed that oxidized glutathione wasincreased under microgravity conditions, and simulated microgravity caused a burst of ROS,implicating ROS as a critical upstream mediator linking to downstream atrophic signaling. ROSgeneration activated the ERK 1/2 early-growth response protein�Egr�1/2-Cbl-b signaling pathway.

Our results suggest that under microgravity conditions, elevated ROS may be a crucialmechanotransducer in skeletal muscle cells, regulating muscle mass through Cbl-b expressionactivated by the ERK-Egr signaling pathway.

Key words : Unloading stress, Muscle atrophy, Mitochondria, Reactive oxygen species

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Page 23: SHIKOKU ACTA MEDICA Vol.75 , No.1,2SHIKOKU ACTA MEDICA Vol.75 , No.1,2(April 25,2019) 特集:健康長寿を目指して 第75巻第1,2号(平成31年4月25日) 徳 島

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Japan Alteplase Clinical Trial II Group. Residualvessel length on magnetic resonance angiographyidentifies poor responders to alteplase in acute middlecerebral artery occlusion patients : exploratory ana-lysis of the Japan Alteplase Clinical Trial II. Stroke.������ ��������

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Page 24: SHIKOKU ACTA MEDICA Vol.75 , No.1,2SHIKOKU ACTA MEDICA Vol.75 , No.1,2(April 25,2019) 特集:健康長寿を目指して 第75巻第1,2号(平成31年4月25日) 徳 島

For the prevention of stroke and dementia

Yuishin Izumi, and Nobuaki Yamamoto

Department of Neurology, Tokushima University Hospital, Tokushima, Japan

SUMMARY

It became an important issue how we can live long in good health. Because stroke and demen-tia bring physical disability and cognitive functional decline and often need care, the treatment andprevention of those diseases are important.

The number of stroke patients is increasing, but treatments for acute stroke has remarkablyprogressed, especially those by the endovascular therapy. Managing hypertension, diabetes mellitus,dyslipidemia and atrial fibrillation is key of the prevention.

Because dementia patients are increasing remarkably, the countermeasures become the impor-tant problem of the country. Of the causes of dementia, Alzheimer disease is the most frequentfollowed by vascular dementia. Vascular dementia occurs due to cerebrovascular diseases. The-refore, it is important to manage hypertension, diabetes mellitus, dyslipidemia and atrial fibrillationfor preventing vascular dementia. The etiology of Alzheimer disease is still unknown. A recentstudy suggests the possibility that hypertension, diabetes mellitus and dyslipidemia are involved inan etiology of Alzheimer disease. It may be effective for the prevention of Alzheimer disease tomanage hypertension, diabetes mellitus and dyslipidemia.

Key words : stroke, endovascular therapy, dementia, diabetes mellitus, prevention

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racic Society.���� ¡¢£  �)��¤

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tion of Cancer Prevention Strategies in Japan. :

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tion based on a systematic review of epidemiological

evidence among the Japanese population. Japanese

Journal of Clinical Oncology.��������¢£�)¡�)��¦

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Page 32: SHIKOKU ACTA MEDICA Vol.75 , No.1,2SHIKOKU ACTA MEDICA Vol.75 , No.1,2(April 25,2019) 特集:健康長寿を目指して 第75巻第1,2号(平成31年4月25日) 徳 島

Prevention of COPD and lung cancer

Hisatsugu Goto��, Masahiko Azuma����, Katsunori Nakase��, Matome Toyosaki��, Masato Utsunomiya��, andYasuhiko Nishioka��

��Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University,Tokushima, Japan

��Department of Medical Education, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan��Tokushima City Medical Association, Tokushima, Japan

SUMMARY

Chronic obstructive pulmonary disease�COPD�is a long-standing, crippling disease characte-rized by the accelerated decline of lung function, commonly brought by aging and long-time inhalationof toxic chemicals such as tobacco smoking. Consequently, most COPD patients suffer from chroniccough, sputum and dyspnea on exertion. Moreover, in addition to the decline of lung function due tothe destruction of the alveolar structure, COPD is closely related to other diseases such asosteoporosis, cardiovascular diseases, diabetes, muscle dysfuncion, and lung cancer. Therefore,COPD is currently recognized as a systemic disease that the comprehensive management and careare necessary. Although COPD represents an increasing burden throughout the world and is oneof the major causes of death word-wide, the issue has been arisen that the recognition of COPD inthe general society is still low, especially in Japan. On the other hand, lung cancer is a life-threatening disease with the leading cause of malignancy-related death world-wide, the etiology ofwhich is also closely related to tobacco smoking. Because the pathogenesis and the mortality ofCOPD and lung cancer are closely related each other, the action to prevent these diseases could bemade simultaneously, primarily by the smoking cessation and the detection survey. In this article,we describe the present situation of COPD and lung cancer, the importance of smoking cessation,and the effort of Tokushima City Medical Association to manage COPD in Tokushima.

Key words : COPD, lung cancer, smoking cessation, detection survey

� � ��

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�[Girgis, C. M., Clifton-Bligh, R. J., Hamrick, M.W., Holick,M. F., et al . : The roles of vitamin D in skeletal mus-cle : form, function, and metabolism. Endocr Rev.����¦FF§F�YZ�F

Y[Endo, I., Inoue, D., Mitsui, T., Umaki, Y., et al . : Dele-tion of vitamin D receptor gene in mice results inabnormal skeletal muscle development with deregu-lated expression of myoregulatory transcription fac-tors. Endocrinology.��� �¦4�F§©©�YZZF

F[Buitrago, C., Pardo, V. G., Boland, R. : Role of VDR in�α,Y4§dihydroxyvitamin DF§dependent non-genomicactivation of MAPKs, Src and Akt in skeletal musclecells. J Steroid Biochem Mol Biol.,���¦�Y4§FZ�YZ�F

©[Garcia, L. A., King, K. K., Ferrini, M. G., Norris, K. C.,et al . :��Y4jOH[Yvitamin DF stimulates myogenicdifferentiation by inhibiting cell proliferation andmodulating the expression of promyogenic growthfactors and myostatin in CYC�Yskeletal muscle cells.Endocrinology.��� ��¦Yk�ª§ª�YZ��

4[Bischoff-Ferrari, H. A., Dawson-Hughes, B., Willett,

W. C., Staehelin, H. B., et al . : Effect of Vitamin D onfalls : a meta-analysis. JAMA.� �����¦�kkk§YZZª�YZZ©

ª[Scott, D., Ebeling, P. R., Sanders, K. M,, Aiken, D., etal . : Vitamin d and physical activity status : associa-tions with five-year changes in body compositionand muscle function in community-dwelling olderadults. J Clin Endocrinol Metab.���� �¦ª�Z§�YZ�4

�[Akter, S., Eguchi, M., Kurotani, K., Kochi, T., et al . :SerumY4§hydroxyvitamin D andmetabolic syndromein a Japanese working population : The FurukawaNutrition and Health Study. Nutrition.���¦Yª§FY�YZ��

¨[Brown, E., Gamba, G., Riccardi, D., Lombardi, M., etal . : Cloning and characterization of an extracellularCaY+-sensing receptor from bovine parathyroid. Na-ture.����¦4�4§Z��kkF

k[Roszko, K. L., Bi, R. D., Mannstadt, M. : AutosomalDominantHypocalcemiajHypoparathyroidism[Types�andY. Front Physiol.��¦©4 �YZ�ª

�Z[Letz, S., Rus, R., Haag, C., Dörr, H. G., et al . : Novel ac-tivating mutations of the calcium-sensing receptor :the calcilytic NPS§Y�©F mitigates excessive signaltransduction of mutant receptors. J Clin EndocrinolMetab.������¦EYYk§FF�YZ�Z

��[Leach, K., Wen, A., Cook, A. E., Sexton, P. M., et al . :Impact of clinically relevant mutations on the phar-macoregulation and signaling bias of the calcium-sensing receptor by positive and negative allostericmodulators. Endocrinology.�����¦��Z4§�ª�YZ�F

�Y[Nakamura, A., Hotsubo, T., Kobayashi, K., Mochizuki,H., et al . : Loss-of-function and gain-of-function muta-tions of calcium-sensing receptor : functional analysisand the effect of allosteric modulators NPS R§4ªand NPSY�©F. J Clin Endocrinol Metab.������¦«�ªkY§�Z��YZ�F

�F[Dong, B., Endo, I., Ohnishi, Y., Kondo, T., et al . : Cal-cilytic Ameliorates Abnormalities of Mutant Calcium-Sensing ReceptorjCaSR[Knock-In Mice MimickingAutosomal Dominant HypocalcemiajADH[. J BoneMiner Res.������¦�kZ§kF�YZ�4

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Pulmonary Hypertension. Front Physiol.������������Kurahashi, K., Endo, I., Namakura, M., Ohnishi, Y., et

al . : ASBMR���Annual meeting Abstract�Dong, B., Endo, I., Ohnishi, Y., Ooguro, Y., et al . : Per-

sistent activation of calcium-sensing receptor supp-resses bone turnover, increases microcracks anddecreases bone strength. JBMR Plus in press�����

��Kido, S., Kuriwaka-Kido, R., Umino-Miyatani, Y., Endo,I., et al . : Mechanical stress activates Smad pathwaythrough PKCδ to enhance interleukin���gene transc-ription in osteoblasts. PLoS One.����� pii : e����������

��Takeuchi, Y., Watanabe, S., Ishii, G., Takada, S., et al . :Interleukin���as a stimulatory factor for bone forma-tion prevents bone loss with advancing age in mice.

J Biol Chem.�����������������������Endo, I., Fukumoto, S., Ozono, K., Namba, N., et al . :

Clinical usefulness of measurement of fibroblastgrowth factor���FGF��in hypophosphatemic pa-tients : proposal of diagnostic criteria using FGF��measurement. Bone.����������������

��Endo, I., Fukumoto, S., Ozono, K., Namba, N., et al . :Nationwide survey of fibroblast growth factor ���FGF��-related hypophosphatemic diseases in Japan :prevalence, biochemical data and treatment. EndocrJ.���������������

��Carpenter, T. O. : New perspectives on the biologyand treatment of X-linked hypophosphatemic rickets.Pediatr Clin North Am .������������

��������������� !"#$��%&'()*+ ��

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Basic and clinical research for Endocrine and Metabolic disorders by a clinician

Itsuro Endo

Department of Chronomedicine, Tokushima University Graduate School of Medical Sciences, Tokushima, JapanDepartment of Endocrinology and Metabolism, Tokushima University Hospital, Tokushima, Japan

SUMMARY

In our country, the management of lifestyle-related diseases and muscloskeletal disorders inbecoming more important with the rapidly advancing aging society. I have conducted both basicand clinical research that could contribute to the amelioration of these diseases from the point ofview of a clinician. Specifically, I have identified that skeletal muscle differentiation and develop-mental abnormalities in vitamin D receptor knockout mice, activated calcium-sensing receptorknock-in mice showed various metabolic abnormalities, regulation of stem cell differentiation by IL��� and so on. We also conducted nationwide survey of fibroblast growth factor ���relatedhypophosphatemic diseases to clarify the prevalence and the clinical presentations of the disorders.In this review, I show an overview of my research works, also including the relation to the latestfindings.

Key words : Vitamin D, CaSR, Interleukin���, FGF��

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:�Raabe, A., Beck, J., Gerlach, R., Zimmermann, M., etal . : Near-infrared indocyanine green video angiogra-phy : a new method for intraoperative assessment ofvascular flow. Neurosurgery.����Jan ;�����N�����Odiscussion����

��Takagi, Y., Kikuta, K., Nozaki, K., Sawamura, K., etal . : Detection of a residual nidus by surgical micro-scope-integrated intraoperative near-infrared indoc-yanine green videoangiography in a child with acerebral arteriovenous malformation. J Neurosurg.����Nov ;�����Suppl�N��:���

��Takagi, Y., Tokime, T., Nozaki, K., Gon, Y., et al . : Re-dox control of neuronal damage during brain

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ischemia after middle cerebral artery occlusion inthe rat : immunohistochemical and hybridizationstudies of thioredoxin. J Cereb Blood Flow Metab.����Feb ;�����������

��Takagi, Y., Mitsui, A., Nishiyama, A., Nozaki, K., etal . : Overexpression of thioredoxin in transgenicmice attenuates focal ischemic brain damage. ProcNatl Acad Sci U S A.����Mar �������� ��.

���Yoshimura, S., Takagi, Y., Harada, J., Teramoto, T.,et al . : FGF� regulation of neurogenesis in adulthippocampus after brain injury. Proc Natl Acad SciU S A.����May�������������

���Qiu, J., Takagi, Y., Harada, J., Topalkara, K., et al . :p��Kip�constrains proliferation of neural progenitorcells in adult brain under homeostatic and ischemic

conditions. Stem Cells.����Apr ;�������������Qiu, J., Takagi, Y., Harada, J., Rodrigues, N., et al . :

Regenerative response in ischemic brain restrictedby p��cip�/waf�. J Exp Med.���Apr��������� ���

� �Takagi, Y., Takahashi, J., Saiki, H., Morizane, A., etal . : Dopaminergic neurons generated from monkeyembryonic stem cells function in a Parkinson pri-mate model. J Clin Invest.����Jan�������������

��Chihara, H., Takagi, Y., Nishino, K., Yoshida, K., et al . :Factors Predicting the Effects of Hybrid AssistiveLimb Robot Suit during the Acute Phase of CentralNervous System Injury. Neurol Med Chir�Tokyo�.����������� ��

New approach of Department of Neurosurgery, Graduate School of Biomedical Sciences,Tokushima University

Yasushi Takagi

Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan

SUMMARY

Well-balanced development of clinical medicine, research and education is important inNeurosurgical department of University. In this article, we introduce the importance ofintraoperative neuroradiological assessment in safe and secure surgical treatment of brainarteriovenous malformations. In addition, we show the usefulness of multimodal treatment againstskull base tumors. And research projects of our department are shown.

Key words : intraoperative neuroradiological assessment, arteriovenous malformations, multimodaltreatment, skull base tumors, regenerative medicine

� � � �

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Page 50: SHIKOKU ACTA MEDICA Vol.75 , No.1,2SHIKOKU ACTA MEDICA Vol.75 , No.1,2(April 25,2019) 特集:健康長寿を目指して 第75巻第1,2号(平成31年4月25日) 徳 島

Role of medical informatics in future medical care

Jun Hirose

Department of Medical Informatics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

SUMMARY

Medical information has been digitally formatted and it has been properly stored and managedby a computer system with the progress of information communication technology�ICT�. Hospitalinformation systems and regional medical liaison systems can be cited as the main components ofthe system, and the clinical task of the medical informatics department is the construction,management and operation of these systems. Recently, medical real world data�RWD�accumulated in these systems is focused not only as a primary use but also as a secondary use ofmedical information. However, there are many problems such as standardization, collection,cleaning, and analysis of medical information. Internet of things�IoT�and artificial intelligence�AI�are applied to the collection and analysis of RWD, and help to resolve the above problems.Using these new technologies expected further progress in the future, medical care is about toreach a new era.

Key words : medical informatics, real world data, medical care

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Regional cooperation for cancer patients : A questionnaire clarifying the roles of commu-nity doctor

Hiroaki Toba������, Hiromitsu Takizawa������, Takahiro Yoshida��, Masami Morimoto��, Mariko Aoyama��,Kyoko Nishiguchi��, Chizu Miyakoshi��, Hirokazu Takechi��, and Akira Tangoku��

��Department of General Thoracic Surgery, Tokushima, Japan��Department of Esophagus, Breast and Thyroid Surgery, Tokushima, Japan��Cancer Management Center, Tokushima University Hospital, Tokushima, Japan

SUMMARY

It was suggested long ago that regional cooperation is necessary for cancer patients. Bothdoctors in base hospitals and community doctors understand the importance of such cooperation.Here we report the results of our widely distributed questionnaire designed to clarify the division ofphysicians� roles and to strengthen the relationships between base hospital and community doctors.The questionnaire asks whether community doctors can accept cancer patients and what types ofmedical treatment the doctors can provide for patients with esophageal cancer, lung cancer, breastcancer, and thyroid cancer. The doctors in 289 of 550�53%�facilities completed and returned thequestionnaire. About half of the community doctors responded that they can accept patients withany of the four cancers and can provide most types of the necessary medical examinations andtreatments in their daily practices. Most of the community doctors indicated that they could notprovide some anti-cancer drugs and supportive drug therapies for breast cancer patients. Thedevelopment and implementation of a clinical pathway system could enable the participation ofmore community doctors and base hospital doctors. Although our findings are preliminary, theywill contribute to a foundation for building better regional corporative relationships with communitydoctors who treat cancer patients.

Key words : A widely distributed questionnaire, Regional corporation, Cancer patient, CommunityDoctor

� � � �

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1`Doi, T., Moriya, T., Fujita, Y., Tominaga, T., et al . :Urinary IgG/ and Smad1Are Specific Biomarkersfor Renal Structural and Functional Changes in EarlyStages of Diabetic Nephropathy. Diabetes .$�����¢£�¤¥££�$¦§1�

¦`Pavenstädt, H., Kriz, W., Kretzler, M. : Cell biology ofthe glomerular podocyte. Physiol Rev .$���¢¦�¥�§_$¦§§�

�`Kanwar, Y. S., Liu, Z. Z., Kashihara, N., Wallner, E. I. :Current status of the structural and functional basisof glomerular filtration and proteinuria. Semin Nephrol.$�����¢�£§¥/1�$1££1

/`Kanwar, Y. S., Farquhar, M. G. : Presence of heparansulfate in the glomerular basement membrane. ProcNatl Acad Sci USA .$����¢1�§�¥1�§_$1£_£

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the integral membrane protein podocalyxin throughNa+/H+-exchanger regulatory factor ¦ and ezrin.Clin Exp Nephrol .$����¢¦¤§¥¦¤£$¦§§�

_`Kriz, W., Shirato, I., Nagata, M., Lemley, K. V., et al . :The podocyte�s response to stress:the enigma of footprocess effacement. Am J Physiol Renal Physiol.$ ����¢F���¥�/_$¦§1�

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15`Michos, O., Goncalves, A., Lopez-Rios, J., Zeller, R., etal . : Reduction of BMP/activity by gremlin1enablesureteric bud outgrowth and GDNF/WNT11 feed-back signalling during kidney branching morphoge-nesis. Development .$�����¢¦�£_¥¦/§ $¦§§_

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Activation of bone morphogenetic protein� signal-ing leads to glomerulosclerosis that mimics diabeticnephropathy. J Bio Chem .�����������������������

18�Fujita, Y., Tominaga, T., Abe, H., Doi, T., et al . : Anadjustment in BMP� function represents a treat-ment for diabetic nephropathy and podocyte injury.Sci Rep.���������������

19�Siddiqi, F. S., Advani, A. : Endothelial-podocyte cro-sstalk : the missing link between endothelial dysfunc-tion and albuminuriain diabetes. Diabetes.������������������

20�Matsusaka, T., Xin, J., Niwa, S., Ichikawa, I., et al . :Genetic engineering of glomerular sclerosis in themouse via control of onset and severity of podocyte-specific injury. J Am Soc Nephrol.��������������������

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22�Peti-Peterdi, J., Sipos, A. : A high-powered view ofthe filtration barrier. J Am Soc Nephrol.��������� ���������

BMP�in Diabetic Nephropathy �

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BMP4 regulates both podocyte injury and mesangial expansion in the diabetic nephropathy

Yui Fujita��, Tatsuya Tominaga��, Yumi Kangawa��, Kojiro Nagai��, Hideharu Abe��, and Toshio Doi��

��Department of Nephrology, Graduate School of Medical Science, Tokushima University Graduate School, Tokushima, Japan��Department of Chronomedicine, Graduate School of Biomedical Sciences, Tokushima University Graduate School, Tokushima,Japan

��Department of Nephrology, Tokushima University, Professor Emeritus, Tokushima, Japan

SUMMARY

Podocyte injury and loss have been indicated as constituting the crucial pathogenesis ofglomerular injury ; however, it remains necessary to elucidate the detailed molecular mechanismsand cell-to-cell response because multiple factors may cause podocyte injury. In the glomerulus,three kinds of cells�endothelial, mesangial, and parietal epithelial�react to podocyte injury.Endothelial and mesangial cells are connected with podocyte cells across the glomerular basementmembrane. However, the detailed mechanisms regarding the interaction of the mesangium andpodocyte injury are unclear.

Diabetic nephropathy is characterized by mesangial matrix expansion caused by an excessivedeposition of extracellular matrix proteins in the mesangial area, which can be observed throughthe increased expression of type � collagen. We have shown that bone morphogenetic protein��BMP��signaling leads to the glomerular changes characteristic of this disorder. To analyze theeffect of BMP�was investigated in vitro and in vivo using streptozotocin�STZ�-induced and Bmp�heterozygous knockout�Bmp�+/��diabetic mice or podocyte-specific Bmp� knockout mice, andBmp�-induced or podocyte-specific transgenic mice. BMP� positive area and mesangial areafraction showed positively correlation. Furthermore, mesangial area fraction was significantly andnegatively correlated with, WT�positive cell number, and nephrin-positive area.

We also demonstrated that the induction of podocyte apoptosis by BMP�may be mediated byp� activation and that of caspase� through cleavage. In mesangial cells, BMP� stimulation alsoinduced phosphorylation of p�and Smad�and increased cleaved caspase�, with similar significantinhibition of Smad�activation and decreased cleaved caspase�mediated by dorsomorphin.

These data suggest that the BMP� signaling pathway plays important roles for the develop-ment of both podocyte injury and mesangial expansion in diabetic nephropathy.

Key words : BMP�, diabetic nephropathy, podocyte, apotosis, mesangial expansion

� � � ���

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� Barbaresi, W. J., Katusic, S. K., Colligan, R. C., Pankratz,V. S., et al . : How common is attention-deficit/hype-ractivity disorder? Incidence in a population-basedbirth cohort in Rochester, Minn. Arch PediatrAdolesc Med.���������

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Prognosis of growth and neurological development in small for gestational age infants

Shunsuke Takeuchi����, Kenichi Suga��, Miki Shono��, Ryuji Nakagawa��, and Shoji Kagami��

��The post-graduate Education Center, Tokushima University Hospital, Tokushima, Japan��Department of Pediatrics, Tokushima University Hospital, Tokushima, Japan

SUMMARY

�Background�Small for gestational age�SGA�infants have multiple risk factors for short stature,developmental disorders, and metabolic diseases in adulthood. Our institute which plays centralroles in perinatal medicine in Tokushima prefecture has many high risk pregnant women, thereforea relatively large number of SGA infants admitted to neonatal intensive care unit�NICU�andgrowth care unit�GCU�.�Objective�To elucidate the prognosis such as short stature, neurodevelopmental disorder andmental retardation of SGA infants discharged from NICU and GCU in our hospital.�Method�SGA patients discharged from NICU and GCU in our hospital between��� and��were enrolled in this study. Clinical data were collected from medical charts.�Results�There were �� SGA infants��� �%�discharged from NICU/GCU for � years. Weexcluded patients with congenital malformation syndrome, chromosomal abnormality, neuro-muscular disorder, death and lost of follow-up, and finally��SGA infants were enrolled. Four SGAinfants��%�required growth hormone�GH�treatment for short stature and all of them werepromoted growth significantly. Three SGA infants�%�showed attention deficit hyperactivitydisorder and/or autism spectrum disorder, and�SGA infants��%�presented with mental retarda-tion.�Conclusion�This study revealed the prognosis of SGA infants discharged from NICU and GCU inour hospital. Further large cohort with long-term observation is required.

Key words : small for gestational age, low stature, growth hormone, developmental disorder,mental retardation

� � � � ���

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Adrenal insufficiency. Lancet.���������������

��Bleicken, B., Hahner, S., Ventz, M., Quinckler, M. :

Delayed Diagnosis of Adrenal Insufficiency is

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A case of isolated ACTH deficiency that required 6 months for the diagnosis from onset

Hiroya Matsuda��, Kiyoe Kurahashi��, Furi Endo��, Shiho Masuda��, Yukari Mitsui��, Sumiko Yoshida��,Yuko Akehi��, Itsuro Endo��, and Seiji Fukumoto��

��The Medical Education Center, Tokushima University Hospital, Tokushima, Japan��Department of Endocrinology and Metabolism, Tokushima University Hospital, Tokushima, Japan

SUMMARY

A��-year-old man noticed anorexia, nausea, and arthralgia of the upper limbs in April,���X.Since these symptoms persisted, he visited general hospital and clinic and was examined for bloodchemistry, ECG, echocardiography and so on. However, he did not get a definitive diagnosis andwas followed up with drip infusion of saline. The symptoms did not subside and fatigue andsyncope with hypotension developed. Furthermore, he also suffered weight loss of��kg in fewmonths and was referred to our hospital for more detailed examinations in October,���X. Uponthe initial examination, all his symptoms matched those of adrenal insufficiency and notabledecreases of both plasma ACTH and serum cortisol level were observed. Prompt glucocorticoidsupplementation improved his symptoms and the abnormal laboratory data immediately. He wasdiagnosed adrenal insufficiency due to isolated ACTH deficiency from the results of CRH loadingtest and insulin tolerance test.

Since most of the symptoms and laboratory findings are non-specific, diagnosis of adrenalinsufficiency is often delayed. However, adrenal insufficiency could worsen when the patient isunder stress�e.g. infection�and often be life-threatening. Glucocorticoid replacement therapyshould be initiated as soon as the diagnosis is confirmed. Furthermore, educating patients and hisfamilies plays a very important role in the management of chronic adrenal insufficiency, in particularto the prevention of adrenal crisis.

Key words : isolated ACTH deficiency, adrenal insufficiency, anorexia, nausea, arthralgia

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Reprographic Reproduction outside JapanMaking a copy of this publicationPlease obtain permission from the following Reproduction Rights OrganizationsGRROsJto which the copyright holderhas consigned the management of the copyright regarding reprographic reproduction.Obtaining permission to quote, reproduce ; translate, etc.Please contact the copyright holder directly.Users in countries and regions where there is a local RRO under bilateral contract with Japan Academic

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Vol����No����Contents

Special Issue�To enjoy a long healthy lifeM. Abe and Y. Taketani : Preface to the Special Issue �N. Tsugawa : Osteoporosis and Vitamin D T. Uchida : The mechanism of skeletal muscle atrophy :finding from space experiment ��

Y. Izumi, and N. Yamamoto : For the prevention of stroke and dementia ��H. Goto, et al. : Prevention of COPD and lung cancer �

Reviews�I . Endo : Basic and clinical research for Endocrine and Metabolic disordersby a clinician �

Y. Takagi : New approach of Department of Neurosurgery, Graduate School of BiomedicalSciences, Tokushima University �

J . Hirose : Role of medical informatics in future medical care ��

Originals�H. Toba, et al. : Regional cooperation for cancer patients : A questionnaire clarifying theroles of community doctor ��

Y. Fujita, et al. : BMP4 regulates both podocyte injury and mesangial expansionin the diabetic nephropathy ��

S . Takeuchi, et al. : Prognosis of growth and neurological development in smallfor gestational age infants

Case report�H. Matsuda, et al. : A case of isolated ACTH deficiency that required 6 monthsfor the diagnosis from onset �

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