Depar t ment of Labor at or y Medi ci ne
Masato Suzuki,Professor Akihiro Ohnishi,Associate Professor Sadayori Hoshina,Associate Professor Ken Kaito,Associate Professor Hironari Sue,Associate Professor Hiroshi Yoshida,Associate Professor Kenichi Sugimoto,Associate Professor Tomokazu Matsuura,Assistant Professor Hashizume Toshihiko,Assistant Professor
Gener al Summar y
Re s e a r c h pr oj e c t s i n our de pa r t me nt i n 2 0 0 7 we r e c onc e r ne d wi t h c l i ni c a l phy s i ol og y , c l i ni c a l mi c r obi ol og y ,c l i ni c a l c he mi s t r y ,c l i ni c a l bi oc he mi s t r y ,he ma t ol og y ,c a r di ol og y , c l i ni c a l c e l l bi ol og y ,a nd c l i ni c a l ps y c hi a t r y . Re s e a r c h a c hi e v e me nt s i n e a c h di v i s i on a r e de s c r i be d be l ow.
Res ear ch Act i v i t i es Cl i ni c al p hy s i o l o g y
The pr e s e nt s t udy i nv e s t i g a t e d t he e f f e c t s of a c i d- ba s e di s t ur ba nc e on bl ood l a c t a t e ki ne t i c s ,t he ons e t of bl ood l a c t a t e a c c umul a t i on( OBLA) ,t he l a c t a t e t hr e s hol d( LT) , a nd t he v e nt i l a t i on t hr e s hol d( VT)dur i ng i nc r e me nt a l c y c l e e x e r c i s e . Ni ne he a l t hy ma l e v ol unt e e r s pa r t i c i pa t e d i n t hi s s t udy . Subj e c t s we r e or a l l y g i v e n NH Cl , Na HCO, a nd Na Cl a t dos e s of 1 . 8 7 mM/ kg body we i g ht . Ex e r c i s e wa s s t a r t e d a t a l oa d of 8 0 W a nd wa s s ubs e que nt l y i nc r e a s e d by 1 0 W pe r mi nut e us i ng t he r a mp me t hod unt i l v ol unt a r y e x ha us t i on 6 0 mi nut e s a f t e r NH Cl ,Na HCO,a nd Na Cl we r e a dmi ni s t e r e d.
Bot h LT a nd OBLA we r e s i g ni f i c a nt l y hi g he r i n s ubj e c t s who r e c e i v e d a c i dot i c t r e a t me nt a nd we r e l owe r i n s ubj e c t s who r e c e i v e d a l ka l ot i c t r e a t me nt t ha n i n s ubj e c t s who r e c e i v e d c ont r ol t r e a t me nt . Ac i d- ba s e di s t ur ba nc e i nduc e d di f f e r e nc e s i n t he bl ood l a c t a t e r e s pons e t o t he s a me e x e r c i s e l oa d a nd a f f e c t e d LT,OBLA,a nd VT. Ca r e mus t be t a ke n whe n us i ng LT,OBLA,a nd VT a s i ndi c e s of a e r obi c c a pa c i t y i n s ome pa t i e nt s wi t h a c i d- ba s e di s or de r s ,s uc h a s t hos e who a r e unde r g oi ng he modi a l y s i s ,a r e obe s e ,or ha v e di a be t e s .
Cl i ni c al mi c r o b i o l o g y
The DNA di a g nos i s of c l i ni c a l f ung a l i nf e c t i on wa s e s t a bl i s he d wi t h my c ot i c uni v e r s a l s e que nc i ng a nd a ppl i e d t o t i s s ue s of pa t i e nt wi t h my c os i s . The mi ni mum i nhi bi t or y c onc e nt r a t i on of f os phomy c i n wi t h c i pr of l ox a c i n f or mul t i dr ug - r e s i s t a nt Ps e udo mo nas ae r ug i no s a wa s me a s ur e d wi t h a n ox y g e n pot e nt i a l e l e c t r ode s y s t e m a nd a ppl i e d t o t he pa t i e nt . The di ox i n c he mi c a l s t r uc t ur e wa s pr opos e d f or a nt i - i nf l a ma t or y ,a nt i pr ol i f e r - a t i v e a g e nt s v e r s us t he r e s i s t a nc e me c ha ni s ms of t he t he r mophi l i c ba c t e r i um Bac i l l us mi do us uj i .
Cl i ni c al c he mi s t r y
To i nv e s t i g a t e how l i v e r di s e a s e a l t e r s s e r um g l y c a t e d pr ot e i ns a s ma r ke r s of di a be t i c
c ont r ol ,we s t udi e d s e r um g l y c a t e d a l bumi n( GA) ,he mog l obi n A1 c( A1 c ) ,a nd,e s pe - c i a l l y ,t he GA
/A1 c r a t i o i n 2 5 5 pa t i e nt s wi t h a n a l a ni ne a mi not r a ns f e r a s e l e v e l g r e a t e r t ha n 3 5 I U
/L i n c ompa r i s on wi t h t hos e i n 8 2 9 pa t i e nt s wi t h t y pe 2 di a be t e s me l l i t us i n a c r os s - s e c t i ona l ma nne r . The 2 5 5 pa t i e nt s wi t h l i v e r di s e a s e we r e di v i de d i nt o g r oups of 6 9 pa t i e nt s wi t h bi ops y - pr ov e n l i v e r c i r r hos i s ,6 6 pa t i e nt s wi t h c hr oni c he pa t i t i s ,a nd 1 2 0 pa t i e nt s wi t h f a t t y l i v e r di a g nos e d wi t h a bdomi na l e c hog r a phy . The me a n GA
/A1 c r a t i o(
±SD)wa s s i g ni f i c a nt l y hi g he r( p
<0 . 0 0 0 1 )i n pa t i e nt s wi t h c i r r hos i s ( 3 . 7 1
±1 . 0 3 )t ha n i n pa t i e nt s wi t h he pa t i t i s( 3 . 0 3
±0 . 4 5 )or di a be t e s( 3 . 0 5
±0 . 4 2 ) , whe r e a s t he me a n GA
/A1 c r a t i o i n pa t i e nt s wi t h f a t t e r l i v e r( 2 . 7 4
±0. 3 1 )wa s s i g ni f i - c a nt l y l owe r( p
<0. 0 0 0 1 )t ha n t ha t i n pa t i e nt s wi t h di a be t e s . I n pa t i e nt s wi t h c i r r hos i s t he GA
/A1 c r a t i o i nc r e a s e d s i g ni f i c a nt l y de pe ndi ng upon r e duc t i ons i n t he s e r um a l bumi n l e v e l or t he pl a t e l e t c ount or bot h. The GA
/A1 c r a t i o wa s s i g ni f i c a nt l y c or r e l a t e d wi t h ot he r l a bor a t or y v a r i a bl e s ,s uc h a s s e r um l e v e l s of a l bumi n,c hol i ne s t e r - a s e ,a nd t ot a l c hol e s t e r ol ,a nd wa s we a kl y c or r e l a t e d wi t h t he bl ood he mog l obi n l e v e l . We a l s o f ol l owe d t he s e r um l e v e l s of GA a nd A1 c a nd t he GA
/A1 c r a t i o f or 1 3 mont hs ( bl ood wa s c ol l e c t e d 5 t i me s )i n 1 8 pa t i e nt s e nr ol l e d i n t hi s s t udy . The c oe f f i c i e nt of v a r i a t i on of t he GA
/A1 c r a t i o wa s s ma l l e r t ha n t ha t of GA or A1 c . The r e c e i v e r ope r a t i ng c ha r a c t e r i s t i c c ur v e of t he GA
/A1 c r a t i o f or pa t i e nt s wi t h c i r r hos i s v e r s us t hos e wi t h f a t t y l i v e r wa s t he mos t r e l i a bl e be t we e n t he 4 g r oups ,a nd t he c ut - of f v a l ue f or pa t i e nt s wi t h c i r r hos i s v e r s us t hos e wi t h f a t t y l i v e r wa s 2 . 9 4 . The s e r e s ul t s s ug g e s t t ha t t he GA
/A1 c r a t i o c oul d be a us e f ul ma r ke r f or t he di f f e r e nt i a l di a g nos i s of pa t i e nt s wi t h a bnor ma l s e r um l e v e l s of a l a ni ne a mi not r a ns f e r a s e .
Cl i ni c al b i o c he mi s t r y
We pe r f or me d s e v e r a l r e s e a r c h s t udi e s a nd obt a i ne d t he f ol l owi ng r e s ul t s .
1 . Cur r e nt i s s ue s of l ow- de ns i t y l i popr ot e i n homog e nous a s s a y we r e hi g hl i g ht e d by l i popr ot e i n a na l y s i s wi t h a me t hod of hi g h- pe r f or ma nc e l i qui d c hr oma t og r a phy we de v e l ope d.
2 . Supe r v i s e d,r e g ul a r e x e r c i s e t r a i ni ng f or 4 mont hs c a n i nc r e a s e d a di pone c t i n l e v e l s , but e x e r c i s e f or 2 mont hs pr oduc e s l e s s s i g ni f i c a nt i nc r e a s e s .
3 . Ev a l ua t i on of v e r y l ow de ns i t y l i popr ot e i n c hol e s t e r ol i s us e f ul f or moni t or i ng l i popr ot e i n a me l i or a t i on.
4 . Suba na l y s i s of t he J a pa ne s e I nv e s t i g a t i on of Ki ne t i c Ev a l ua t i on i n Hy pe r t e ns i v e Ev e nt And Re mode l i ng Tr e a t me nt St udy s howe d t ha t t r e a t me nt wi t h a n a ng i ot e ns i n I I r e c e pt or a nt a g oni s t c a n pr e v e nt c a r di ov a s c ul a r e v e nt s i n J a pa ne s e wome n.
He mat o l o g y
Abnor ma l c hr omos ome pa t t e r ns i n mul t i pl e my e l oma we r e c ompa r e d a c c or di ng t o g e nde r a nd a g e . The hy podi pl oi d pa t t e r n wa s mos t f r e que nt l y f ound a nd wa s f ol l owe d by hy pe r ,ps e udo,a nd t r i
/t e t r a pa t t e r ns . The hy podi pl oi d pa t t e r n wa s c ommonl y f ound i n y oung e r pa t i e nt s ,whe r e a s t he hy pe r di pl oi d pa t t e r n wa s f r e que nt l y de t e c t e d i n ol de r pa t i e nt s . I n ol de r pa t i e nt s ,c ha ng e s of
+15 a nd−1 3 we r e mos t c ommon a nd we r e f ol l owe d by
+1 1 ,
+1 9 ,a nd
+3 i n bot h g e nde r s a nd i n ol de r pa t i e nt s . De l e t i on of a s e x c hr omos ome wa s f ound i n 5 6 %of me n a nd 4 0 %of wome n a nd wa s c ommon
i n y oung e r pa t i e nt s . Ba nd 1 4 q3 2 wa s mos t c ommon a nd wa s f ol l owe d by 1 1 q1 3 ,1 p2 2 , a nd 8 q2 4 . The r e we r e ma ny c ha r a c t e r i s t i c s of g e nde r a nd a g e ,s uc h a s ba nd 1 1 q1 3 i n me n,a nd ba nd 8 p1 1 i n y oung e r pa t i e nt s . The s e r e s ul t s i ndi c a t e s e v e r a l c ha r a c t e r i s t i c s i n moda l numbe r ,i mba l a nc e ,c ompl e x i t y ,a nd br e a kpoi nt s t ha t we r e r e l a t e d t o t he g e nde r a nd a g e of pa t i e nt s . The s e c ha r a c t e r i s t i c s s houl d be r e c og ni z e d whe n t he ka r y ot y pe of mul t i pl e my e l oma i s e v a l ua t e d.
Car di o l o g y
We a r e s t udy i ng c a t he t e r i nt e r v e nt i on f or a t r i a l f i br i l l a t i on. To e l i mi na t e a t r i a l f i br i l l a - t i on, s e g me nt a l os t i a l c a t he t e r a bl a t i on( SOCA)wa s pe r f or me d t o e l e c t r i c a l l y i s ol a t e t he pul mona r y v e i ns f r om t he l e f t a t r i um. Our a i m i s t o i mpr ov e t he me t hod of SOCA.
Thi s y e a r we s howe d t he e f f i c a c y of 2 ne w me t hods of SOCA. One me t hod i s s e g me nt a l pul mona r y v e i n a nt r um i s ol a t i on us i ng t he l a r g e l a s s o c a t he t e r ,a nd t he ot he r me t hod i s r e duc i ng t he r e c ur r e nc e of a t r i a l f i br i l l a t i on by e l i mi na t i ng ATP- i nduc e d t r a ns i e nt v e nous r e c onduc t i on.
Cl i ni c al c e l l b i o l o g y
1 . I mmunohi s t oc he mi c a l s t udy of l e c i t hi n r e t i nol a c y l t r a ns f e r a s e i n he pa t i c s t e l l a t e c e l l s i n l i v e r di s e a s e s
2 . Ex a mi na t i ons of he pa t i c me t a bol i s m a nd t he t ox i c i t y of dr ug s by me a ns of a mi ni - bi oa r t i f i c i a l l i v e r a nd s t a bl e i s ot ope c ompounds
3 . De v e l opme nt of a n i mpl a nt - t y pe bi oa r t i f i c i a l l i v e r 4 . C- g l uc os e br e a t h t e s t f or di a g nos i s of i ns ul i n r e s i s t a nc e 5 . Ul t r a s ound mol e c ul a r i ma g i ng f or di a g nos i ng s ma l l c a nc e r s
6 . Pl a s ma e x a mi na t i on f or t he t r a ns f or mi ng g r owt h f a c t or
βa c t i v a t i ng r e a c t i on t o di a g nos e l i v e r da ma g e
Cl i ni c al p s y c hi at r y
We r e por t e d on t he e f f e c t s of ps y c hot r opi c dr ug s( a nt i de pr e s s a nt s or a nt i ps y c hot i c s )on e l e c t r oe nc e pha l og r a phy( EEG)f r om t he v i e wpoi nt of t he r a di or e c e pt or bi ndi ng( hi s - t a mi ne H1 )pr of i l e .
A r e t r os pe c t i v e s t udy i s unde r wa y t o c l a r i f y t he c l i ni c a l s i g ni f i c a nc e of t he 6 - Hz s pi ke a nd wa v e on EEG. We ha v e c ont i nue d t o i nv e s t i g a t e e pi l e pt i c s e i z ur e s a nd c hr onol og i - c a l EEG c ha ng e s i n me nt a l l y ha ndi c a ppe d pa t i e nt s . We r e por t e d on a pa t i e nt wi t h e pi l e ps y a nd a ps y c hi a t r i c di s or de r who unde r we nt t e mpor a l l obe c t omy a nd wa s s uc c e s s f ul l y t r e a t e d a nd r e por t e d on a pa t i e nt wi t h a bnor ma l be ha v i or dur i ng s l e e p who l i ke l y ha d e pi l e ps y . Mor e ov e r ,we e x a mi ne d pr e moni t or y s i g ns a nd s y mpt oms a s e pi l e pt i c pr odr ome s .
Publications
Suzuki M,Ishiyama I(Kokugakui n Tochigi Junior Coll),Seino T (Kisarazu Natl Coll Technol), Nishikawa E, Matsubara S (Nihon Univ). Cardio-pulmonary responses to increasing wor-
kload exercise on a cycl e ergometer in healthy men.Adv Exerc Sports Physiol 2007;13:19‑ 24.
Tsubota A,Yoshikawa T,Nariai K,Mitsunaga M,
Yumoto Y,Fukushima K,Hoshina S,Fujise K.
Bovine lactoferrin potently inhibits liver mito- chondrial 8-OHdG level s and retrieves hepatic OGG1 activities in Long-Evans Cinnamon rats. J Hepatol 2008;48:486‑93.[Epub 2007 Dec 27.]
Kobayashi A,Utsunomiya Y,Kono M,Ito Y, Yamamoto I,Osaka N,Hasegawa T,Hoshina S, Yamaguchi Y,Kawaguchi Y,Hosoya T.Malako- plakia of the kidney.Am J Kidney Dis 2008;51: 326‑30.
Iwase T,Hoshina S,Seki K,Shinji H,Masuda S, Mizunoe Y.Rapid ident ification and specific quantification of Staphyl ococcus epidermidis by 5′nuclease real-time polymerase chain reaction with a minor groove binder probe.Diagn Microbiol Infect Dis 2008;60:217‑9.[Epub 2007 Oct 22]
Kisugi R,Touzuma T,Yamamoto T,Akizuki S, Miyamoto H,Someya Y,Yokoyama J,Abe I,Hirai N,Ohnishi A.Structur al and glycation site changes of albumin in diabetic patient with very high glycated albumin.Clin Chim Acta 2007;
382:59‑64.
Akizuki S,Ohnishi A.Nicotine metabolic capa- bility following cigarette smoking in Japanese smokers with CYP2A64/9 genotype.Jikeikai Med J 2007;54:11‑9.
Mamori S,Nagatsuma K,Matsuura T,Ohkawa K, Hano H,Fukunaga M,Matsushima M,Masui Y, Fushiya N,Onoda H,Sear ashi Y,Takagi I,Tagiri H.Useful detection of CD147(EMMPRIN)for pathological diagnosis of early hepatocellular carcinoma in needle biopsy samples.World J Gastroenterol 2007;13:2913‑7.
Saito M,Matsuura T,Nagatsuma K,Tanaka K, Maehashi H,Shimizu K,Hataba Y,Kato F,Ka- shimori I,Tajiri H,Braet F.The functional inter- relationship between gap junctions and fenestrae in endothelial cells of the liver organoid.J Membr Biol 2007;217:115‑21.
Braet F,Nagatsuma K,Saito M,Soon L,Wisse E, Matsuura T.The hepatic sinusoidal endothelial lining and colorectal liver metastasis.World J Gastroenterol 2007;13:821‑5.
Murakami K,Inoue Y,Hmwe SS,Omata K,Hongo T,Ishii K,Yoshizaki S,Aizaki H,Matsuura T, Shoji I,Miyamura T,Suzuki T.Dynamic behav- ior of hepatitis C virus quasispecies in a long- term culture of the three-dimensional radial-flow bioreactor system.J Virol Methods 2008;148:
174‑81.
Yanai H,Yoshida H,Hirowatari Y (TOSOH Co, Japan),Tomono Y,Tada N.Oxidized low den- sity lipoprotein elevates platelet serotonin release.Am J Hematol 2007;82:686‑7.
Yanai H,Tada N,Yoshida H,Tomono Y.Diacyl- glycerol oil for apolipoprotein C-II deficiency. QJM 2007;100:247‑8.
Kurosawa H,Yoshida H,Yanai H,Ogura Y, Hirowatari Y (TOSOH Co,Japan),Tada N.
Comparative study between anion-exchange HPLC and homogeneous assay methods in
regard to the accuracy of high-and low-density lipoprotein cholesterol measurement.Clin Bio- chem 2007;40:1291‑6.
Yanai H,Yoshida H,Tomono Y,Hirowatari Y (TOSOH Co,Japan),Kurosawa H,Matsumoto A (Jyosai Univ),Tada N.Effects of diacylglycerol on glucose,lipid metabolism,and plasma ser- otonin levels in lean Japanese.Obesity(Silver Spring)2008;16:47‑51.
Tada N,Yoshida H. Clinical significance of triglyceride-rich lipoproteins in metabolic syn- drome.Rinsho Byori 2007;55:43‑46.
Matsuo S,Yamane T,Date T,Inada K,Kanzaki Y, Tokuda M,Shibayama K,Mi yanaga S,Miyazaki H,Sugimoto K,Mochizuki S.Reduction of AF recurrence after pulmonary vein isolation by eliminating ATP-induced transient venous re- conduction.J Cardiovasc Electrophysiol 2007;
18:704‑8.
Yamane T,Date T,Kanzaki Y,Inada K,Matsuo S, Shibayama K,Miyanaga S,Mi yazaki H,Sugimoto K,Mochizuki S.Segmental pulmonary vein antrum isolation using the “large-size” lasso catheter in patients with atrial fibrillation.Circ J 2007;71:753‑60.
Reviews
Suzuki M,Shibasaki T (Kyoritsu Univ Pharm). Management of daily activity in patients with renal disease(in Japanese).Clin Rehabil 2007;
16:684‑8.
Yanai H,Yoshida H,Tomono Y,Tada N.Ather- osclerosis imaging in statin intervention trials. QJM 2007;100:253‑62.
Yanai H,Tomono Y,Ito K,Furutani N,Yoshida H, Tada N.Diacylglycerol oil for the metabolic syndrome.Nutr J 2007;6:43.
Yoshida H,Shoda T,Yanai H,Tada N.Apolipo- protein C-II deficiency.Nippon Rinsho 2007;
65(Suppl 7):279‑84.
Yanai H,Tada N,Tomono Y,Yoshida H.Envi- ronmental factors associ ated with the onset of lipid metabolism disorders.Nippon Rinsho 2007;65(Supp l7):136‑40.
Yoshida H.Definition and concept of metabolic syndrome.J-JSMUFF 2007;4:71-7.
Yoshida H.The issues of drug therapy in the elderly patients with metabolic and endocrine diseases.Jpn J Clin Pharmacol Ther 2008;39:
6‑12.
Yoshida H,Kageyama S.Actions and effects of cannabinoid receptor antagonists. In:Kana- zawa Y,Taketani Y,Sekihara H,Yamada N, editors. Annual Review on Diabetes,Metabo- lism,and Endocrinology.2008.p.104‑1. Yanai H,Yoshida H.Bl ood pressure,glucose and cholesterol as the s urrogate markers for the cardiovascular events;review of the associations between these parameters and the outcome of the intervention studies.2007;38:299‑304.
Yoshida H.Pathophysiology for and interven-
tion to impaired metabolism in metabolic syn-
drome:perspectives from recently accumulated evidences.Jikei University Kashiwa Hospital Annual Report 2008;15:59‑63.