99mTc-sestamibi retention characteristics during pharmacologic hyperemia in human myocardium: Comparison with coronary flow reserve measured by Doppler flowire

金沢大学大学院医学系研究科The aim of the study was to investigate the increase in myocardial 99mTc-methoxyisobutylisonitrile (sestamibi) retention in humans during pharmacologic vasodilation. Methods: For calculation of the increase in 99mTc-sestamibi retention during hyperemia, baseline and adenosine triphosphate (ATP)-induced hyperemic stress sestamibi studies were performed using a same-day rest-stress protocol. On the injection of sestamibi, left ventricular dynamic data were obtained for 90 s. The increase in sestamibi retention from baseline to hyperemia was calculated by the formula Cmh(t) ∫01 Cbb(τ)dτ/Cmb(t) ∫01 Cbh(τ)dτ, where Cmh(t) and Cmb(t) are myocardial counts on the tomographic image, and Cbb(τ) and Cbh(τ) are the left ventricular blood-pool counts during the first transit of sestamibi at baseline and during hyperemia, respectively. Coronary flow increase during intravenous ATP stress was measured using intracoronary Doppler flow guide wire and compared with the scintigraphic results of 28 measurements in 22 patients. Results: Sestamibi retention increased as coronary flow velocity increased but plateaued at >2.5-3 times baseline flow velocity. The relationship between the increase in sestamibi retention (Y) and the increase in flow (X) is expressed as follows: Y = 0.44 + 0.60X - 0.068X2 (r = 0.82). Conclusion: In humans, the increase in 99mTc-sestamibi myocardial retention underestimates coronary flow reserve, particularly at high flow rates. Knowledge of these tracer retention characteristics will contribute to a more comprehensive understanding of the manner and interpretation of stress sestamibi imaging

1H-MRI and 1H-MRS in ferritin transgenic mice

Iron homeostasis is tightly regulated by iron-binding proteins, as iron excess exhibits toxicity in cells. Ferritin is an intracellular iron storage protein that plays various roles such as controlling iron concentration in vivo. It is well-known that ferritin is involved in the pathogenesis of some human disorders, for example, aberrant ferritin expression has shown to be involved in neurodegenerative diseases. We generated transgenic (Tg) mice of human ferritin heavy chain (FTH) gene and investigated the effects of ferritin overexpression by 1H-MRI and 1H-MRS. The mice displayed no apparent neurological symptoms, no specific morphological and T2 alterations in the brain were found in MRI, and not even in histological studies.1H-MRS, however, revealed that some metabolic markers were significantly altered in FTH-Tg brains compared to wild-type brains, such as decreases in myo-inositol and glutamine, and an increase in lactate. Our findings provide the evidence that ferritin overexpression affects brain metabolism.World Molecular Imaging Congress 201

Evaluation of ferritin-overexpressing brain in newly developed transgenic mice

Aberrant expression of ferritin, a major iron-binding protein, has shown to be involved in neurodegenerative diseases. In this study, wegenerated transgenic (Tg) mice of human ferritin heavy chain (FTH) gene and investigated the effects of ferritin overexpression in FTH-Tgbrain by 1H-MRI and 1H-MRS. The mice displayed no apparent neurological symptoms, and no specific morphological and T2 alterationswere found in the brain by MRI, and not even by histological studies. 1H-MRS, however, revealed that some metabolic markers weresignificantly altered in FTH-Tg brains compared to wild-type control brains, such as decreases in myo-inositol and glutamine, and an increasein lactate. Our present studies suggested that despite the absence of neurological, morphological, T2, and histological signatures, brainmetabolisms were significantly affected in FTH-Tg mice. This study also highlights the usefulness of 1H-MRS in the analysis of transgenicmouse models

Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3.

This study sought to clarify the contributions of organic anion-transporting polypeptide (OATP) 1B1 and 1B3 to the liver uptake of chenodeoxycholic acid (CDCA). We synthesized a fluorescent version of CDCA, chenodeoxychilyl-(Nepsilon-NBD)-lysine (CDCA-NBD), to characterize transporter-mediated uptake. CDCA-NBD is efficiently transported by OATP1B1 and OATP1B3 with high affinities. The Michaelis-Menten constants for CDCA-NBD uptake by OATP1B1 and OATP1B3 were 1.45 +/- 0.39 microM and 0.54 +/- 0.09 microM, respectively. By confocal laser scanning microscopy, CDCA-NBD, which is taken up by OATP1B1 and OATP1B3, was observed to localize to the cytosol. We also examined the transport of newly synthesized fluorescent bile acids. NBD-labeled bile acids, including cholic acid, deoxycholic acid, lithocholic acid, and ursodeoxycholic acid, were all transported by OATP1B1 and OATP1B3. CDCA-NBD exhibited the highest rate of transport of the five NBD-labeled bile acids examined in OATP1B1- and OATP1B3-expressing cells. Our results suggest that OATP1B1 and OATP1B3 play important roles in CDCA uptake into the liver. Fluorescent bile acids are useful tools to characterize the uptake properties of membrane transporters

サイトカインの変更により異なる反応を呈した進行性腎癌の1例

雑誌掲載版 著作権は学会に帰属73歳男性.患者は肉眼的血尿で近医を受診,CT上で右腎腫瘍,腹部リンパ節転移を疑われ紹介入院となった.CTでは右腎に11×9×9cmの内部不整な充実性腫瘤を認め,下大静脈背側,傍大動脈,縦隔に多発するリンパ節転移を認めた.cT3bN2M1(stage IV)の腎癌と診断し,選択的右腎動脈塞栓術を施行後に天然型インターフェロンα(IFN-α:スミフェロン)の週3回筋注とシメチジン内服を開始したが,4ヵ月後のCTで腹部・縦隔リンパ節の増大を認め,スミフェロンをインターロイキン2(IL-2:イムネース)の週5日間点滴に変更した.しかし,その後,投与5週目にCTで両肺野に多発する転移と腹部・縦隔リンパ節の更なる増大を認めた.IFN-α,IL-2の免疫療法の無効から別の天然型IFN-α(OIF)の週3回筋注に変更し,シメチジン内服も継続したところ,1ヵ月後に肺転移巣は著明に縮小し,3ヵ月後には完全消失を認め,腹部・縦隔リンパ節転移巣は増大を認めなかった.現在,OIF投与より9ヵ月経過でリンパ節転移の不変状態を維持してい

膀胱癌に対する膀胱全摘除術から16年後に回腸新膀胱による尿路再建を行った1例

雑誌掲載版 著作権は学会帰属症例は59歳、男性。1989年(43歳時)に膀胱癌に対し他院で膀胱全摘除術および両側尿管皮膚瘻造設術が施行された。その後難治性のストーマ周囲皮膚炎が出現し、当科紹介となった。2003年に両側尿管結紮および経皮的腎瘻造設術が施行された。しかし、腎瘻カテーテルによる腎盂腎炎が頻回に発生し、また患者のQOLも障害されていたため、2005年に残存する尿道を利用して回腸新膀胱(Hautmann法)による尿路再建を施行し、カテーテルフリーとなった。長期間、腎瘻カテーテルが留置された症例において、カテーテル留置に伴う合併症のためにQOLの低下を認めた場合には、患者の意思・基礎疾患・全身状態を考慮した上で、カテーテルフリーを目指した尿路再建を施行し、腎機能の保持とともに、QOLの改善を目指すべきであると思われる