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A NOVEL TIME-SHARED FLUOROMETER GIVES THE MITOCHONDRIAL REDOX STATE AS THE RATIO OF TWO COMPONENTS OF THE RESPIRATORY CHAIN OF THE ANIMAL AND HUMAN BUCCAL CAVITY WITH QUANTITATIVE MEASURES OF THE REDOX ENERGY STATE

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Journal of Innovative Optical Health Sciences 2010年第4期3卷 235-245页

作者： BRITTON CHANCE shoko nioka AQUO JENQ-RUEY HORNG University of Pennsylvania Philadelphia PA 19104USA South Taiwan University 1 Nantai RoadYong KangTainan 71005Taiwan

The source of energy for life is the tissue mitochondria and they demand a complex chain of biochemicals to ensure proper physiological ***,the blood levels,and not the tissue levels of these metabolites,are determined by expensive and time-consuming biochemical *** the tissue mitochondria are the consumers of the substrates of glycolysis and of fatty acid metabolism,their redox state is a unique accessible monitor of tissue metabolism and its blockade due to toxins.

关键词： Redox state mitochondria optical methods fluorometer

ANAGRAM PROBLEM-SOLVING AND LEARNING IN ANTERIOR PREFRONTAL CORTEX

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Journal of Innovative Optical Health Sciences 2008年第2期1卷 157-175页

作者： shoko nioka JOSEPH I.TRACY SHANE RAINES SCOTT BUNCE BRITTON CHANCE Department of Biochemistry-Biophysics Biostatistics University of PennsylvaniaPAUSA Department of Neurology and Radiology Thomas Jefferson University§Department of PsychologyDrexel University PhiladelphiaPAUSA

We utilized Near-Infrared(NIR)spectroscopy to closely investigate the activation change in anterior prefrontal cortex(aPFC)during verbal anagram problem-solving and *** used a parametric design of anagram-solving with three difficulty levels and evaluated anagram skill with two sets of subjects and *** first protocol was a one-time evaluation of untrained subjects(n=10)and the second protocol evaluated subjects over 6 weeks of training(n=6).The untrained subjects in the first protocol demonstrated blood oxygenation corresponding to neuronal activation in the aPFC in response to medium and hard difficulty levels of the stimuli,while the easy anagram task deoxygenated the aPFC bilaterally,corresponding to *** performers have more aPFC activation than lower performers in the medium difficulty level anagram-solving *** weeks of training in the second protocol showed that training reduced oxygenation in *** particular,subjects with lower baseline skill in anagram production showed a larger reduction in oxygenation where true performance gains occurred(medium difficulty)and smaller reduction where the performance gains were limited(hard anagrams).Association of the aPFC activation with the difficulty of the complex task suggests that aPFC is a part of a circuit for execution of task *** addition,more use of aPFC by untrained high performers suggests that the role of the aPFC is to increase efficiency of a problem-solving ***,the NIR spectroscopy showed that the aPFC is a key structure in the circuit implementing the development of anagram skill.

关键词： Anagram anterior prefrontal cortex hemoglobin NIR oxygenation training effects difficulty

Citation analysis of the scientific publications of Britton Chance in ISI citation indexes

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Journal of Innovative Optical Health Sciences 2014年第2期7卷 129-142页

作者： Lin Z.Li Loet Leydesdorff shoko nioka Nannan Sun Eugene Garfield Departiment of Radiology PerelmanSchool of Medicine University of Penn.syluaninPhiladelphiaPA 19104USA Briton Chance Laboratory of Redoa Imaging Johnson Research FoundationDepartment of Biochemistryand BiophysicsPereiman School of Medicine University of Penn syluaniaPhiladelphiaPA 19104USA University of Amsterdam Amsterdam School of Communications Research(ASCoR) Netherlands Briton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan 430074P.R.China Inste for Scientific Informationo-Thomson Reuters Philadelphia PA 19180USA

Britton Chance was a pioneer in many scientifc fields such as enzymatic reaction kinetis,bioenergetics,metabolism,in vivo NMr,and *** an engineer,physical chemist,physicist,physiologist,biophysicist,biochemist,innovator and educator,he had worked indiversifed fields over extended periods bet ween 1926 until his death in 2010,at the age of *** to illustrate his scientific career and great impact on research from a new perspective,weemploy scientometric analysis tools to analyze the publications of Britton Chance with datadownloaded from the ISI Citation Indexes in April *** included articles,reviews andproceding papers but excluded meeting *** total,we obtained 1023 publication recordswith 1236 authors in 266 joumals with 17,114 citations from 1945 to *** show the annualpublications and citations that Britton Chance received from 1945 to 2013,and generate HistCitemaps on the basis of the global citations(GCS)and local(sel)citations(LCS)to show thecitation relationships among the top-30 publications of Britton *** and the development of physical methods to probe it appear to be the commecting thread of the lifelongresearch of Britton ***,we generate the joumal map and co-authorship maptoshow the broad scope of research topics and collaborators and the high impacts of the scientificoeuvre of Britton Chance ranging from physics,engineering,chemistry and biology to medicine.

关键词： Scientometric analysis impact Hist Cite citation tree metabolism mitochondria.

MITOCHONDRIAL REDOX IMAGING FOR CANCER DIAGNOSTIC AND THERAPEUTIC STUDIES

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Journal of Innovative Optical Health Sciences 2009年第4期2卷 325-341页

作者： LIN Z.LI HE N.XU MAHSA RANJI shoko nioka BRITTON CHANCE Department of Radiology School of Medicine University of PennsylvaniaB6 Blockley Hall423 Guardian Drive PhiladelphiaPA 19104-6069USA The Institute for Translational Medicine and Therapeutics School of Medicine University of Pennsylvania PhiladelphiaPA 19104USA Biophotonics Laboratory Department of Electrical Engineering and Computer Science University of Wisconsin-Milwaukee MilwaukeeWI 53211USA Johnson Research Foundation Department of Biochemistry and Molecular Biophysics School of Medicine University of Pennsylvania 250 Anatomy Chemistry BuildingPhiladelphiaPA 19104USA

Mitochondrial redox states provide important information about energy-linked biological processes and signaling events in tissues for various disease phenotypes including *** redox scanning method developed at the Chance laboratory about 30 years ago has allowed 3D highresolution(∼50×50×10µm^(3))imaging of mitochondrial redox state in tissue on the basis of the fluorescence of NADH(reduced nicotinamide adenine dinucleotide)and Fp(oxidized flavoproteins including flavin adenine dinucleotide,i.e.,FAD).In this review,we illustrate its basic principles,recent technical developments,and biomedical applications to cancer diagnostic and therapeutic studies in small animal *** developed calibration procedures for the redox imaging using reference standards allow quantification of nominal NADH and Fp concentrations,and the concentration-based redox ratios,e.g.,Fp/(Fp+NADH)and NADH/(Fp+NADH)in *** calibration facilitates the comparison of redox imaging results acquired for different metabolic states at different times and/or with different instrumental settings.A redox imager using a CCD detector has been developed to acquire 3D images faster and with a higher in-plane resolution down to 10µ*** vivo imaging and in vivo imaging of tissue mitochondrial redox status have been demonstrated with the CCD *** of tissue redox imaging in small animal cancer models include metabolic imaging of glioma and myc-induced mouse mammary tumors,predicting the metastatic potentials of human melanoma and breast cancer mouse xenografts,differentiating precancerous and normal tissues,and monitoring the tumor treatment response to photodynamic *** future directions for the development of redox imaging are also discussed.

关键词： Redox ratio reduced nicotinamide adenine dinucleotide NADH flavoprotein flavin adenine dinucleotide FAD calibration

QUANTITATIVE REDOX SCANNING OF TISSUE SAMPLES USING A CALIBRATION PROCEDURE

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Journal of Innovative Optical Health Sciences 2009年第4期2卷 375-385页

作者： HE N.XU BAOHUA WU shoko nioka BRITTON CHANCE LIN Z.LI Molecular Imaging Laboratory Department of Radiology University of PennsylvaniaPhiladelphia PA 19104USA Johnson Research Foundation Department of Biochemistry and Biophysics University of Pennsylvania PA 19104USA

The fluorescence properties of reduced nicotinamide adenine dinucleotide(NADH)and oxidizedflavoproteins(Fp)including flavin adenine dinucleotide(FAD)in the respiratory chain are sensitive indicators of intracellular metabolic states and have been applied to the studies of mitochondrial function with energy-linked *** redox scanner,a three-dimensional(3D)low temperature imager previously developed by Chance et al.,measures the in vivo metabolicproperties of tissue samples by acquiring fluorescence images of NADH and *** redox ratios,***/(Fp+NADH)and NADH/(Fp+NADH),provided a sensitive index of the mitochondrialredox state and were determined based on relative signal intensity *** we report thefurther development of the redox scanning technique by using a calibration method to quantifythe nominal concentration of the fluorophores in *** redox scanner exhibited very goodlinear response in the range of NADH concentration between 165–1318µM and Fp between90–720µM using snap-frozen solution *** samples such as human tumor mousexenografts and various mouse organs were redox-scanned together with adjacent NADH and Fpstandards of known concentration at liquid nitrogen *** nominal NADH and Fpconcentrations as well as the redox ratios in the tissue samples were quantified by normalizing the tissue NADH and Fp fluorescence signal to that of the snap-frozen solution *** calibration procedure allows comparing redox images obtained at different time,independent of instrument *** quantitative multi-slice redox images revealed heterogeneity inmitochondrial redox state in the tissues.

关键词： NADH flavoprotein redox ratio mitochondria tissue heterogeneity

This research was supported by ***6 Integrated Project“Molecular Imaging”LSHG-CT-2003-503259 and ***7 Collaborative Project“FMT-XCT”.*** support from the Marie Curie Program EST-MolecImag Early Stage Training MEST-CT-2004-007643.

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Journal of Innovative Optical Health Sciences 2009年第4期2卷 365-374页

作者： MAHSA RANJI shoko nioka HE N.XU BAOHUA WU LIN Z.LI DWIGHT L.JAGGARD BRITTON CHANCE Biophotonics Laboratory Department of Electrical Engineering and Computer Science University of Wisconsin-Milwaukee MilwaukeeWI 53211USA Department of Electrical and Systems Engineering University of Pennsylvania PhiladelphiaPA 19104USA Department of Biochemistry and Biophysics University of Pennsylvania PhiladelphiaPA 19104USA Department of Radiology University of Pennsylvania PhiladelphiaPA 19104USA

We have imaged mitochondrial oxidation-reduction states by taking a ratio of mitochondrial fluorophores:NADH(reduced nicotinamide adenine dinucleotide)to Fp(oxidized flavoprotein).Although NADH has been investigated for tissue metabolic state in cancer and in oxygen deprived tissues,it alone is not an adequate measure of mitochondrial metabolic state since the NADH signal is altered by dependence on the number of mitochondria and by blood *** redox ratio,NADH/(Fp+NADH),gives a more accurate measure of steady-state tissue metabolism since it is less dependent on mitochondrial number and it compensates effectively for hemodynamic *** ratio provides important diagnostic information in living *** this study,the emitted fluorescence of mouse colon in situ is passed through an emission filter wheel and imaged on a CCD *** ratio images of the healthy and hypoxic mouse intestines clearly showed significant ***,the corrected redox ratio indicated an increase from an average value of 0.51±0.10 in the healthy state to 0.92±0.03 in dead tissue due to severe ischemia(N=5).We show that the CCD imaging system is capable of displaying the metabolic differences in normal and ischemic tissues as well as quantifying the redox ratio in vivo as a marker of these changes.

关键词： Optical diagnosis NADH flavoprotein in vivo ischemia fluorescence.

IMAGING REDOX STATE HETEROGENEITY WITHIN INDIVIDUAL EMBRYONIC STEM CELL COLONIES

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Journal of Innovative Optical Health Sciences 2011年第3期4卷 279-288页

作者： HE N.XU RUSSELL C.ADDIS DAVIDA F.GOINGS shoko nioka BRITTON CHANCE JOHN D.GEARHART LIN Z.LI Molecular Imaging Laboratory Department of Radiology University of PennsylvaniaSchool of Medicine PhiladelphiaPA 19104USA Institute for Regenerative Medicine and Department of Cell and Developmental Biology University of Pennsylvania School of Medicine PhiladelphiaPA 19104USA Britton Chance Laboratory of Redox Imaging Johnson Research Foundation Department of Biochemistry and Biophysics University of Pennsylvania School of Medicine PhiladelphiaPA 19104USA Institute of Translational Medicine and Therapeutics University of Pennsylvania PhiladelphiaPA 19104USA

Redox state mediates embryonic stem cell(ESC)differentiation and thus offers an important complementary approach to understanding the pluripotency of stem *** redox ratio(NADH/(Fp t NADH)),where NADH is the reduced form of nicotinamide adenine dinucleotide and Fp is the oxidizedflavoproteins,has been established as a sensitive indicator of mitochondrial redox *** this paper,we report our redox imaging data on the mitochondrial redox state of mouse ESC(mESC)colonies and the implications *** low-temperature NADH/Fp redox scanner was employed to image mESC colonies grown on a feeder layer of gamma-irradiated mouse embryonicfibroblasts(MEFs)on glass cover *** result showed significant heterogeneity in the mitochondrial redox state within individual mESC colonies(size:~200-440μm),exhibiting a core with a more reduced state than the *** more reduced state positively correlates with the expression pattern of Oct4,a well-established marker of *** observation is thefirst to show the heterogeneity in the mitochondrial redox state within a mESC colony,suggesting that mitochondrial redox state should be further investigated as a potential new biomarker for the stemness of embryonic stem cells.

关键词： Redox imaging pluripotency NADH flavoproteins redox ratio

INTRODUCTION SPECIAL ISSUE IN MEMORY OF PROFESSOR BRITTON CHANCE

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Journal of Innovative Optical Health Sciences 2011年第3期4卷 I0001-I0003页

作者： Lin Z.Li shoko nioka Molecular Imaging Lab Department of Radiology Britton Chance Lab of Redox Imaging Johnson Foundation Department of Biochemistry and Biophysics University of Pennsylvania

Britton Chance:One of the Most Outstanding Scientists in the World On June 3rd and 4th,2011,over 300 scientists and professionals from all over the world gathered at the Translational Research Center of the University of Pennsylvania to attend a memorial symposium on\Britton Chance:His Life,Times and Legacy"and a\Molecular Spectroscopy/Imaging Workshop:from bench top to bedside"dedicated to Britton Chance as well.

关键词： Times Chance symposium

To Gate, or Not to Gate： Regulatory Mechanisms for Intercellular Protein Transport and Virus Movement in Plants

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Molecular Plant 2011年第5期4卷 782-793页

作者： shoko Ueki Vitaly Citovsky Institute of Plant Science and Resources Okayama University 2-20-1 Chuo Kurashiki Okayama 710-0046 Japan Department of Biochemistry and Cell Biology State University of New York Stony Brook NY 11794-5215 USA

Cell-to-cell signal transduction is vital for orchestrating the whole-body physiology of multi-cellular organ- isms, and many endogenous macromolecules, proteins, and nucleic acids function as such transported signals. In plants, many of these molecules are transported through plasmodesmata （Pd）, the cell wall-spanning channel structures that interconnect plant cells. Furthermore, Pd also act as conduits for cell-to-cell movement of most plant viruses that have evolved to pirate these channels to spread the infection. Pd transport is presumed to be highly selective, and only a limited repertoire of molecules is transported through these channels. Recent studies have begun to unravel mechanisms that actively regulate the opening of the Pd channel to allow traffic. This macromolecular transport between cells comprises two consecutive steps： intracellular targeting to Pd and translocation through the channel to the adjacent cell. Here, we review the current knowledge of molecular species that are transported though Pd and the mechanisms that control this traffic. Generally, Pd traffic can occur by passive diffusion through the trans-Pd cytoplasm or through the membrane/lu- men of the trans-Pd ER, or by active transport that includes protein-protein interactions. It is this latter mode of Pd trans- port that is involved in intercellular traffic of most signal molecules and is regulated by distinct and sometimes interdependent mechanisms, which represent the focus of this article.

关键词： Plasmodesmata cell-to-cell transport plant viruses transcription factors