厚生労働科研費での不正行為１

厚生労働科学研究成果データベース
http://mhlw-grants.niph.go.jp/niph/search/NIST00.do

200401371A0001.pdf（平成１６年度総括研究報告書）

文献番号	200401371A
研究課題	各種高脂血症治療薬の糖尿病性心血管病進展予防効果の総合的検討
研究年度	平成16(2004)年度
主任研究者(所属機関)	服部　良之(独協医科大学内分泌代謝内科)
研究区分	厚生労働科学研究費補助金 疾病・障害対策研究分野 循環器疾患等総合研究【若手医師・協力者活用に要する研究】（健）
開始年度	平成16(2004)年度
終了予定年度	平成18(2006)年度
研究費	3,488,000円

研究成果

論文番号	著者名	論文タイトル名	発表雑誌名	巻、号	ページ	出版年
論文#20	Hattori Y, Kasai K	Disruption of the Actin Cytoskeleton Up-Regulates iNOS Expression in Vascular Smooth Muscle Cells.	J Cardiovasc Pharmacol	43	209-213	2004
論文#21	Hattori Y, Kasai K, Gross SS	NO suppresses while peroxynitrite sustains NF-kB: A paradigm to rationalize cytoprotective and cytotoxic actions attributed to NO	Cardiovasc Res	63	31-40	2004
論文#22	Kato T, Hashikabe H, Iwata C, Akimoto K, HattoriY	Statin blocks Rho/Rho-kinase signalling and disrupts the actin cytoskeleton: relationship to enhancement of LPS-mediated nitric oxide synthesis in vascular smooth muscle cells	Biochim Biophys Acta	1689	267-272	2004

二つの実験は、別々に行われた実験であるにも関わらず、画像が類似しているため、極めて不自然であり、データの流用の可能性と、少なくともどちらかの論文が捏造である可能性が疑われる。

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論文撤回Watch様にて、詳しく、解説がなされています。

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赤で囲んだ二つの図が同一であることが、明らかです。
上の図は論文#20のFigure3。下の図は論文#22のFigure5です。
画像の流用（データ捏造、改竄）が疑われます。

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↓上記論文#20のFigure3


Hattori Y et. al. Journal of Cardiovascular Pharmacology. 43(2):209-213, February 2004.
Figure 3 Latrunculin B (Lat B) inhibits F-actin polymerization. VSMC were either untreated or treated with 0.5 [mu]M Lat B for 1 hour, and then either unstimulated or stimulated with LPS (30 [mu]g/ml) and interferon-[gamma] (10 ng/ml) for 1 hour. Cells were then fixed with 3.7% formaldehyde solution, washed with acetone, and stained with 165 nM NBD-phallacidin. Stained F-actin was imaged using a Nikon epifluorescent microscope.
J Cardiovasc Pharmacol. 2004 Feb;43(2):209-13.

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↓上記論文#22のFigure5


Biochimica et Biophysica Acta 1689 (2004) 267– 272
Copyright 2004 Elsevier B.V. All rights reserved.
Fig. 5. Fluvastatin inhibits F-actin polymerization. VSMC were either untreated or treated with 25 AM fluvastatin for 6 h, after which they were either
unstimulated or stimulated with LPS (30 Ag/ml) and IFN (10 ng/ml) for 1 h. Cells were then fixed with a 3.7% formaldehyde solution, washed with acetone,
and stained with 165 nM NBD-phallacidin. Stained F-actin was imaged using a Nikon epifluorescent microscope.

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論文#21に関する研究不正（捏造）については、「捏造論文１」の記事を参照されたし。

厚生労働科研費での不正行為２

厚生労働科学研究成果データベース
http://mhlw-grants.niph.go.jp/niph/search/NIST00.do

200500571A0001.pdf（平成１７年度総括研究報告書）

文献番号	200500571A
研究課題	各種高脂血症治療薬の糖尿病性心血管病進展予防効果の総合的検討（臨床研究実施チームの整備）
研究年度	平成17(2005)年度
主任研究者(所属機関)	服部　良之(独協医科大学内分泌代謝内科)
研究区分	厚生労働科学研究費補助金 疾病・障害対策研究分野 循環器疾患等総合研究 【脳卒中・生活習慣病臨床研究】若手医師・協力者活用に要する研究
開始年度	平成16(2004)年度
終了予定年度	平成18(2006)年度
研究費	5,068,000円

研究成果

論文番号	著者名	論文タイトル名	発表雑誌名	巻、号	ページ	出版年
論文#16	Kase H, Hashikabe Y, Uchida K, Nakanishi N, Hattori Y.	Supplementation with tetrahydrobiopterin prevents the cardiovascular effects of angiotensin II-induced oxidative and nitrosative stress	J Hypertens	23	1375-1382	2005
論文#17	Hattori Y, Akimoto K, Gross SS, Hattori S, Kasai K	Angiotensin-II-induced oxidative stress elicits hypoadiponectinaemia in rats	Diabetologia	48	1066-1074	2005
論文#18	Xi SW, Satoh H, Kase H, Suzuki K, Hattori Y	Stimulated HSP90 binding to eNOS and activation of the PI3-Akt pathway contribute to globular adiponectin-induced NO production: Vasorelaxation in response to globular adiponectin	Biochem Biophys Res Common	332	200-205	2005
論文#19	Hattori S, Hattori Y, Kasai K	Hypoadiponectinemia is caused by chronic blockade of nitric oxide synthesis in rats	Metabolism	54	482-487	2005

上記論文#17のFigure 3(A)が、上記論文#19のFigure 3(A)と、同一である。

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上記論文#17のFigure 3(B)のadiponectinのmRNAの６列の画像のうち、右３列（左から４列目、５列目、６列目）がそれぞれ互いに類似しており、不自然である。
さらに、上記論文#17のFigure 3(B)が、上記論文#19のFigure 2(B)と、類似している。
論文#17では、AngIIとAngII＋Tempol(or BH4)の効果を見ているのに対し、
論文#19では、L-NAMEの効果を見ている。
それにもかかわらず、二つの画像が類似していることは不自然である。

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また、
論文#17のFigure 3(C)が、論文#19のFigure 3(B),(C)と、類似している。
論文#17では、AngIIと、AngII＋Tempol(or BH4)の効果を見ているのに対し、
論文#19では、L-NAMEと、L-NAME＋pioglitazone(or allopurinol)の効果を見ている。
それにもかかわらず、二つの画像が類似していることは極めて不自然であり、少なくともどちらかの論文が捏造されたものであると断定できる（データの流用）。

---

↓上記論文#17のFigure 3(a)


Hattori Y et. al. DIABETOLOGIA Volume 48, Number 6, 1066-1074, Figure 3b
Copyright © 2005, Springer Berlin / Heidelberg
Fig. 3 a Plasma adiponectin levels in adipose tissue as determined by ELISA using a kit for the measurement of rat/mouse adiponectin. The results are expressed as means±SEM (n=7). b, c Adiponectin mRNA levels in adipose tissue as assessed by northern blot analysis. The results are expressed as means±SEM (n=3). *p<0.01 vs the control value<br />

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↓上記論文#17のFigure 3(b)


Hattori Y et. al. DIABETOLOGIA Volume 48, Number 6, 1066-1074, Figure 3b
Copyright © 2005, Springer Berlin / Heidelberg
Fig. 3 a Plasma adiponectin levels in adipose tissue as determined by ELISA using a kit for the measurement of rat/mouse adiponectin. The results are expressed as means±SEM (n=7). b, c Adiponectin mRNA levels in adipose tissue as assessed by northern blot analysis. The results are expressed as means±SEM (n=3). *p<0.01 vs the control value<br />

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↓上記論文#17のFigure 3(c)


Copyright © 2005, Springer Berlin / Heidelberg
Hattori Y et. al.DIABETOLOGIA Volume 48, Number 6, 1066-1074, Figure 3c
Fig. 3 a Plasma adiponectin levels in adipose tissue as determined by ELISA using a kit for the measurement of rat/mouse adiponectin. The results are expressed as means±SEM (n=7). b, c Adiponectin mRNA levels in adipose tissue as assessed by northern blot analysis. The results are expressed as means±SEM (n=3). *p<0.01 vs the control value<br />

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↓上記論文#19のFigure 2


Copyright 2005 Elsevier Inc. All rights reserved.
Metabolism Clinical and Experimental 54 (2005) 482– 487
Fig. 2. Plasma adiponectin concentration (n = 8) (A) and adiponectin mRNA levels in adipose tissue (n = 3) (B). *P

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↓上記論文#19のFigure 3

Copyright 2005 Elsevier Inc. All rights reserved.
Metabolism Clinical and Experimental 54 (2005) 482– 487
Fig. 3. Effects of pioglitazone and allopurinol on plasma adiponectin concentration (n = 8) (A) and adiponectin mRNA levels in adipose tissue (B and C). *P

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上記論文#18のFigure 2（A)の上から３段目のHSP90の画像において、
一番左の列の画像と一番右の列の画像が類似しており、
画像の流用（データの捏造）が疑われる。

↓上記論文#18のFigure 2


(C) 2005 Elsevier Inc. All rights reserved.
Biochemical and Biophysical Research Communications 332 (2005) 200–205
Fig. 2. (A) Time course of eNOS–HSP90–Akt complex formation. BAE were stimulated with globular adiponectin for the indicated times. eNOS
was immunoprecipitated at each time point, and eNOS, HPS90, and Akt were evaluated by immunoblotting. (B) Globular adiponectin-induced
eNOS activation and eNOS–HSP90–Akt complex formation in BAE. BAE were pretreated with GA and then stimulated with globular adiponectin
for 10 min. eNOS was immunoprecipitated, and eNOS, peNOS, HSP90, and pAkt were evaluated by immunoblotting.

 

 

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論文#10のFigure 3 (C)の再下段のMCP-１の画像全６列分は、
論文#13のFigure 4 (A)のiNOSの画像全６列分（Fruct, Fruct/BH4の画像）や、
上記論文#16のFigure 5 (b)のiNOS Proteinの画像右６列分（BH4 only, AngII, AngII/BH4の画像）と、
類似しており、画像の流用（データ捏造）が疑われる。


また、
論文#13のFigure 4 (A) のeNOSの画像全６列分は、
上記論文#16のFigure 5 (a)のeNOS Proteinの画像右６列分（BH4 only, AngII, AngII/BH4の画像）と、類似いる。
さらに、この二つの画像は、
論文#14のFigure 4(B)のMCP-1の画像の右８列分の画像を左右逆にした画像にも、類似しており、
画像の流用（データ捏造）が疑われる。

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↓論文#10のFigure 3 (C)

Copyright (C) Elsevier Inc. All rights reserved.
Life Sciences 81 (2007) 939–943
Fig. 3. SKase activation is involved in globular adiponectin-induced activation
of NF-κB and adhesion molecule expression. (A) Treatment of cells with SKase
siRNA inhibited globular adiponectin-induced NF-κB activation. Data are
means±SD of at least three independent repetitions. ⁎Pb0.01 compared with
the value of gAd. (B) Treatment of cells with SKase siRNA markedly decreased
adiponectin-induced mRNA levels of adhesion protein expression. White bars:
control, grey bars: control treated with SKase siRNA, black bars: gAd, hatched
bars: gAd treated with SKase siRNA. Data are means±SD of at least three
independent repetitions and are shown as ratios against GAPDH. ⁎Pb0.01
compared with the value of gAd. (C) Treatment of cells with siRNA suppressed
globular adiponectin-induced protein levels of VCAM-1, ICAM-1, E-selectin,
and MCP-1. Experiments were performed in duplicate.

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↓上記論文#13のFigure 4 

Copyright (C) 2006 Elsevier B.V. All rights reserved.
European Journal of Pharmacology 555 (2007) 48–53
Fig. 4. Protein levels of eNOS and iNOS in aortic tissue were evaluated by
Western blot analysis. Results are expressed as means±S.D. of n=4 rats.
aPb0.05 vs. control rats. bPb0.05 vs. fructose+BH4 rats. C: control, F: fructose,
F/B: fructose/BH4.

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↓上記論文#14のFigure 4 
© 2006 American Heart Association, Inc. Hypertension. 2006;47:1183-1188. Figure 4. (A) Effects of metformin on TNF-–induced VCAM-1, E-selectin, ICAM-1, and MCP-1 mRNA expression. Metformin dose-dependently inhibited VCAM-1, E-selectin, ICAM-1, and MCP-1 mRNA levels. Each bar represents the meanSEM (n4). *P0.01. (B) Effects of metformin on TNF-–induced MCP-1 expression. Metformin dose-dependently inhibited MCP-1 protein levels.

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↓上記論文#16のFigure 5 

Copyright (C) 2005 Lippincott Williams & Wilkins
Journal of Hypertension 2005, 23:1375–1382

厚生労働科研費での不正行為３

厚生労働科学研究成果データベース
http://mhlw-grants.niph.go.jp/niph/search/NIST00.do
200618009A0001.pdf （平成１８年度総括研究報告書）
200618009B0001.pdf （平成１８年度総合研究報告書）

文献番号	200618009A
研究課題	各種高脂血症治療薬の糖尿病性心血管病進展予防効果の総合的検討（若手医師・協力者活用に要する研究）
研究年度	平成18(2006)年度
主任研究者(所属機関)	服部　良之(独協医科大学内分泌代謝内科)
研究区分	厚生労働科学研究費補助金 厚生科学基盤研究分野 臨床研究基盤整備推進研究
開始年度	平成16(2004)年度
終了予定年度	平成18(2006)年度
研究費	4,140,000円

研究成果

論文番号	著者名	論文タイトル名	発表雑誌名	巻、号	ページ	出版年
論文#14	Hattori Y, Suzuki K, Hattori S, Kasai K.	Metformin inhibits Cytokine-Induced NF-kB Activation via AMPK Activation in Vascular Endothelial Cells	Hypertension	47	1183-1188	2006
論文#36	Hattori Y, Hattori S, Kasai K.	Globular Adiponectin Activates Nuclear Factor-{Kappa}B in Vascular Endothelial Cells, which in Turn Induceds Expression of Proinflammatory and Adhesion Molecule Genes.	Diabetes Care	29	139-141	2006
論文#37	Hattori Y, Akimoto K, Nishikimi T, Matsuoka H, Kasai K.	Activation of AMP-Activated Protein Kinase Enhances Angiotensin II-Induced Proliferation in Cardiac Fibroblasts.	Hypertension	47	265-270	2006
論文#15	Hattori Y, Nakanishi	Statin increases GTP cyclohydrolase I mRNA and 5,6,7,8-tetrahydrobiopterin in vascular endothelial cells.	Pteridines	68	65-68	2006
論文#38	Hattori Y, Satoh H, Namatame T, Hattori S, Kasai K.	A Patient With Extreme Insulin Resistance Syndrome Treated With Pioglitazone	Diabetes Care	29	238-239	2006
論文#39	Hashikabe Y, Suzuki K, Jojima T, Uchida K, Hattori Y.	Aldosterone impairs vascular endothelial cell function.	J Cardiovasc Pharmacol.	47	609-613	2006

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上記論文#15のFigure 2と、論文#24のFigure 3Aが、同一データである。

上記論文#15のFigure 3と、論文#24のFigure 3が、同一データである。

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論文#4のFigure 4(A)のPhospho-IkBαの画像と、
論文#8のFigure 5(A)のPhospho-IkB-αの画像と、
上記論文#14のFigure 3(A)のPhospho-IkBaの画像と、
論文#21のFigure 6(A)のPhospho IκB-αの画像の、
４つの画像は全て同一画像であり、データの捏造（流用）が疑われる。
さらに、この上記論文#21のFigure 6(A)の上から２段目のPhospho IκB-αの画像の右３列分（左から４列目、５列目、６列目）の画像は、
同論文のFigure 6(A)の最下段のPhospho IkB-αの画像の左３列分（左から１列目、２列目、３列目）の画像と同一であり、データの捏造（流用）が疑われる。


また、
論文#4のFigure 4(B)のIkBαの画像と、
論文#8のFigure 5(B)のIkB-αの画像と、
上記論文#14のFigure 3(B)のIkBaの画像と、
論文#21のFigure 6(A)のONOO- IκB-αの画像の左４列の画像の、
４つの画像は全て同一画像であり、データの捏造（流用）が疑われる。

また、
上記論文#14のFigure 3(C)の最上段のIkB-aの画像の右３列分（左から２列目、３列目、４列目）の画像と、
論文#21のFigure 6(B)の最上段のIκB-αの画像の中央３列分（左から２列目、３列目、４列目）の画像とが、
同一画像である。
さらに、この上記論文#21のFigure 6(B)の最上段のIkB-αの画像の左から２列目のバンド画像は、
論文#21のFigure 6(B)の下から３段目のIκB-αの画像の左から２列目のバンド画像と、
同一画像であり、画像の流用（データ捏造）が疑われる。


また、
上記論文#14のFigure 3(C)のIKKa/bの画像の左３列分（左から１列目、２列目、３列目）の画像と
論文#21のFigure 6(B)の下から５段目のIKKα/βの画像の左３列分（左から１列目、２列目、３列目）の画像と、
論文#21のFigure 6(B)の下から２段目のIKKα/βの画像が、
同一画像であり、画像の流用（データ捏造）が疑われる。


また、
上記論文#14のFigure 3(C)の最下段のIkB-aの画像の左３列分（左から１列目、２列目、３列目）の画像と、
論文#21のFigure 6(B)の下から４段目のIκB-αの画像の左３列分（左から１列目、２列目、３列目）の画像と、
論文#21のFigure 6(B)の最下段のIκB-αの画像が、
同一画像であり、画像の流用（データ捏造）が疑われる。

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↓論文#3のFigure 2

Journal of Atherosclerosis and Thrombosis
Vol. 17 (2010) , No. 5 503-509
Copyright (c) 2010 Japan Atherosclerosis Society
(A) Cilostazol-mediated activation of AMPK in rat VSMC. VSMC were treated with colostazol (100μM) for the indicated time periods before lysis, after which samples of cell lysate were probed with antibodies specific for the phosphorylated forms of AMPK and acetyl-CoA carboxylase (ACC). (B) HUVEC treated with cilostazol (100 μM) alone or in the presence of an adenylate cyclase inhibitor SQ22536 (10 μM) or a cell-permeable cAMP analog pCTP-cAMP (100 μM). After 15 min of incubation, the cells were lysed and p-AMPK activity was analyzed. Three independent studies showed similar results.

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↓論文#4のFigure 1(A)（画像クリックで解像度の高い画像が表示されます。）

Figure 1
(A) Cilostazol activates AMP-activated protein kinase (AMPK) in vascular endothelial cells. Human umbilical vein endothelial cells (HUVEC) were treated with cilostazol (100 μM) for the indicated time periods before lysis, after which each cell lysate sample was probed with antibodies specific for phosphorylated forms of AMPK and acetyl-CoA carboxylase (ACC). 
Hattori Y et al. Cardiovasc Res 2009;81:133-139
Copyright　the European Society of Cardiology. 

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↓論文#4のFigure 4

Hattori Y et al. Cardiovasc Res 2009;81:133-139
Copyright the European Society of Cardiology. 
Figure 4
(A) Human umbilical vein endothelial cells (HUVEC) were incubated with tumour necrosis factor alpha (TNFα) for 0–180 min. The cells were lysed and subjected to western blot analysis using anti-IκB-α and anti-phospho-IκB-α antibodies. (B) The effect of cilostazol on IκB-α degradation in HUVEC. Cells were incubated for 30 min with cilostazol (30 and 100 μM), followed by TNFα for 30 min. Cells were then lysed and subjected to western blot analysis using anti-IκBα antibody. (C) The effect of cilostazol on IKK activity in HUVEC. Cells were incubated for 30 min with cilostazol (30 and 100 μM), followed by TNFα for 15 min. Cells were then lysed and immunoprecipitated with anti-IKKα/β antibody and used for kinase assay using recombinant IκBα as a substrate. Note that equal band densities for IKKα/β and GST-IκBα were observed. Three independent studies showed similar results.

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↓論文#5のFigure 3(B)

Figure 3 (b) Effect of the AMPK inhibitor compound C (CC) on
the telmisartan-mediated inhibition of TNFa-induced NF-kB activation.
Inset: Time course analysis for pAMPK by telmisartan or metformin. Data
represent the means±s.d. (n¼4). **Po0.01 compared with the control
value (TNFa only). NS, not significant between the absence and presence
of CC.
Copyright 2009 The Japanese Society of Hypertension
Hypertension Research (2009) 32, 765–769

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↓論文#8のFigure 1(A)(B)

Fig. 1. (A) Fenofibrate activates AMPK in vascular endothelial cells. HUVEC were treated with 100 μmol/L fenofibrate for the indicated time periods before lysis, after which cell lysates were probed with antibodies specific for AMPK, ACC, Akt, or eNOS, or their phosphorylated forms. (B) WY14643 (100 μmol/L) activates AMPK in HUVEC. 

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↓論文#8のFigure 5

Fig. 5. (A) HUVEC were incubated with TNFα for 0–180 min. The cells were lysed and subjected to Western blot analysis using anti-IκB-α and anti-phospho-IκB-α antibodies. (B) The effect of fenofibrate on IκB-α degradation in HUVEC. Cells were incubated for 30 min with fenofibrate (30 and 100 μM), followed by TNFα for 30 min. Cells were then lysed and subjected to Western blot analysis using anti-IκB-α antibody. (C) The effect of fenofibrate on IKK activity in HUVEC. Cells were incubated for 30 min with metformin (30 and 100 μM), followed by TNFα for 15 min. Cells were then lysed and immunoprecipitated with anti-IKKα/β antibody and used for kinase assay using recombinant IκB-α as a substrate. Note that equal band densities for IKKα/β- and IκB-α were observed. Three independent experiments for (A) and (B) and two independent experiments for (C) were performed. Similar results were obtained in each experiment and representative photos were shown. 

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↓論文#9のFigure 1（A)

Figure 1 | Cilostazol activates AMP-activated protein kinase (AMPK) in
vascular endothelial cells. (a) human umbilical vein endothelial cells (HUVECs)
were treated with 100 μmol/l cilostazol for the indicated time periods before
lysis, after which cell lysates were probed with antibodies specific for AMPK,
acetyl-CoA carboxylase (ACC), Akt, or endothelial nitric oxide synthase
(eNOS), or their phosphorylated forms.

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↓論文#14のFigure 3 （画像クリックで解像度の高い画像が表示されます。）

Hattori, Y. et al. Hypertension 2006;47:1183-1188
Copyright ©2006 American Heart Association
Figure 3. (A) HUVECs were incubated with TNF- for 0 to 180 minutes. The cells were lysed and subjected to Western blot analysis using anti-IkB- and anti-phospho-IkB- antibodies. (B) The effect of metformin on IB-degradation in HUVECs. Cells were incubated for 30 minutes with metformin (3 and 10 mmol/L), followed by TNF- for 30 minutes. Cells were then lysed and subjected to Western blot analysis using anti-IkB- antibody. (C) The effect of metformin on IKK activity in HUVECs. Cells were incubated for 30 minutes with metformin (3 and 10 mmol/L), followed by TNF- for 15 minutes. Cells were then lysed and immunoprecipitated with anti-IKK/ß antibody and used for kinase assay using recombinant IkB- as a substrate. Note that equal band densities for IKK/ß and IkB- were observed.

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↓論文#21のFigure 6（画像をクリックすると解像度の高い画像が表示されます。）

Hattori Y et al. Cardiovasc Res 2004;63:31-40
Copyright © 2004, European Society of Cardiology
Fig. 6
(A) Effect of NOR3 and SIN-1 on degradation and phosphorylation of I B-α in rat VSMC. Cells were incubated for 45 min with various concentrations of NOR3 (1 mM) or SIN-1 (1 mM), followed by LPS (30 μg/ml) for 0–180 min. Cell were lysed and subjected to Western blot analysis using anti-I B-α antibody and anti-phospho-I B-α. (B) Effect of NOR3 and SIN-1 on IKK activity in rat VSMC. Cells were incubated for 45 min with various concentrations of NOR3 (0.25–1 mM) or SIN-1 (1 mM), followed by LPS (30 μg/ml) for 15 min. Cells were lysed and immunoprecipitated with anti-IKKα/β antibody and used for kinase assay using recombinant I B-α as substrate. Note that equal intensities of IKKα/β- and I B-α-specific bands are obtained.