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Role of Sphingolipids and Metabolizing Enzymes in Hematological Malignancies
Kitatani, Kazuyuki,Taniguchi, Makoto,Okazaki, Toshiro Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.6
Sphingolipids such as ceramide, sphingosine-1-phosphate and sphingomyelin have been emerging as bioactive lipids since ceramide was reported to play a role in human leukemia HL-60 cell differentiation and death. Recently, it is well-known that ceramide acts as an inducer of cell death, that sphingomyelin works as a regulator for microdomain function of the cell membrane, and that sphingosine-1-phosphate plays a role in cell survival/proliferation. The lipids are metabolized by the specific enzymes, and each metabolite could be again returned to the original form by the reverse action of the different enzyme or after a long journey of many metabolizing/synthesizing pathways. In addition, the metabolites may serve as reciprocal biomodulators like the rheostat between ceramide and sphingosine-1-phosphate. Therefore, the change of lipid amount in the cells, the subcellular localization and the downstream signal in a specific subcellular organelle should be clarified to understand the pathobiological significance of sphingolipids when extracellular stimulation induces a diverse of cell functions such as cell death, proliferation and migration. In this review, we focus on how sphingolipids and their metabolizing enzymes cooperatively exert their function in proliferation, migration, autophagy and death of hematopoetic cells, and discuss the way developing a novel therapeutic device through the regulation of sphingolipids for effectively inhibiting cell proliferation and inducing cell death in hematological malignancies such as leukemia, malignant lymphoma and multiple myeloma.
Measurement of (γ,n) Cross Sections of Se Isotopes Using Laser-Compton Scattering γ-rays
F. Kitatani,S. Goko,H. Harada,H. Utsunomiya,H. Akimune,H. Toyokawa,K. Yamada 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.59 No.23
The photo-nuclear cross sections of Se isotopes (^(80)Se, ^(78)Se, ^(77)Se, ^(76)Se) were measured with laser-Compton scattering (LCS) γ-rays to supply fundamental data for the estimation of the inverse reaction cross sections, i.e., the ^(79)Se(n,γ)^(80)Se cross section. Enriched Se isotope samples were irradiated with LCS γ-rays whose maximum energy was varied from each near neutron separation energy to each threshold energy (γ, 2n) of reaction. The energy distributions of LCS γ-rays were precisely determined using a high-resolution high-energy photon spectrometer (HHS). Emitted neutrons were detected by a high efficiency 4π - ^3He detector. The excitation functions of the photo-nuclear cross section of Se isotopes were determined. The energy point corresponding to each cross section was deduced using the accurately determined energydistribution of LCS γ-rays.
Role of Sphingolipids and Metabolizing Enzymes in Hematological Malignancies
Kazuyuki Kitatani,Toshiro Okazaki,Makoto Taniguchi 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.6
Sphingolipids such as ceramide, sphingosine-1-phosphate and sphingomyelin have been emerging as bioactive lipids since ceramide was reported to play a role in human leukemia HL-60 cell differentiation and death. Recently, it is well-known that ceramide acts as an inducer of cell death, that sphingomyelin works as a regulator for microdomain function of the cell membrane, and that sphingosine-1- phosphate plays a role in cell survival/proliferation. The lipids are metabolized by the specific enzymes, and each metabolite could be again returned to the original form by the reverse action of the different enzyme or after a long journey of many metabolizing/synthesizing pathways. In addition, the metabolites may serve as reciprocal biomodulators like the rheostat between ceramide and sphingosine-1-phosphate. Therefore, the change of lipid amount in the cells, the subcellular localization and the downstream signal in a specific subcellular organelle should be clarified to understand the pathobiological significance of sphingolipids when extracellular stimulation induces a diverse of cell functions such as cell death, proliferation and migration. In this review, we focus on how sphingolipids and their metabolizing enzymes cooperatively exert their function in proliferation, migration, autophagy and death of hematopoetic cells, and discuss the way developing a novel therapeutic device through the regulation of sphingolipids for effectively inhibiting cell proliferation and inducing cell death in hematological malignancies such as leukemia, malignant lymphoma and multiple myeloma.
Design of a 4πLaBr_3(Ce) Spectrometer for Neutron Capture Cross Section Measurements
J. Goto,H. Harada,F. Kitatani,Y. Nagai,M. Oshima,M. Segawa,Y. Toh 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.59 No.23
A 4πLaBr_3(Ce) spectrometer was designed for the measurements of neutron capture cross sections using a prompt γ-ray spectroscopic method with a time-of-flight technique. An optimum configuration for the 4πLaBr_3(Ce) spectrometer was chosen from four possible configurations based on comparison of simulated performance and cost of construction. Further simulations were performed to demonstrate performance of the 4πLaBr_3(Ce) spectrometer.
The (γSF) Method - Determination of Radiative Neutron Capture Cross Sections for Unstable Nuclei
H. Utsunomiya,S. Goriely,H. Akimune,H. Harada,F. Kitatani,S. Goko,H. Toyokawa,K. Yamada 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.59 No.23
An indirect method of determining radiative neutron-capture cross sections for unstable nuclei which we refer to as the γ-ray strength function (γSF) method is outlined and applied to Zr and Sn isotopes. Photoneutron cross sections for ^(91,92,94,96)Zr and ^(117,116)Sn near neutron threshold show the presence of extra γ-ray strengths known as giant M1 and pygmy E1 resonances on top of the low-energy γSF of GDR. Based on the γSF method, we present (n,γ) cross sections for two radioactive nuclei, a long-lived fission product, ^(93)Zr with T^(1/2) = 1.5 × 10^6 y and an s-process branching point nucleus, ^(95)Zr with T^(1/2) = 64.0 d.
Measurements of Neutron-Capture Cross Sections of ^(244)Cm and ^(246)Cm at J-PARC/MLF/ANNRI
A. Kimura,K. Furutaka,S. Goko,H. Harada,T. Kin,F. Kitatani,M. Koizumi,S. Nakamura,M. Ohta,M. Oshima,Y. Toh,T. Fujii,S. Fukutani,J. Hori,K. Takamiya,M. Igashira,T. Katabuchi,M. Mizumoto,T. Kamiyama,K. 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.59 No.23
For developments of innovative nuclear reactors, strong demands exist for the improvement of the accuracy of the neutroncapture cross sections of minor actinides (MAs) and long-lived fission products. We have constructed a Ge-spectrometer using the Accurate Neutron-Nucleus Reaction measurement Instrument (ANNRI) in the J-PARC materials and life science experimental facility (MLF). Preliminary neutroncapture cross sections of ^(244)Cm and ^(246)Cm were obtained in the neutron energy range from 1.0 eV up to 300 eV.
T. Kin,K. Furutaka,S. Goko,H. Harada,A. Kimura,F. Kitatani,S. Nakamura,M. Ohta,M. Oshima,Y. Toh,J. Hori,M. Igashira,T. Katabuchi,M. Koizumi,M. Mizumoto,T. Kamiyama,K. Kino,Y. Kiyanagi 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.59 No.23
A ``4π germanium spectrometer'' was developed for measurements of neutron capture cross sections of minor actinides and long-lived fission products. It was installed on the Beam Line No. 04 of the Materials and Life Science Experimental Facility of the Japan Proton Accelerator Research Complex. The time-of-flight method is used to measure the cross sections. To obtain characteristics of the spectrometer, a measurement was done of prompt gamma rays emitted following neutron capture reactions of gold whose cross section was well studied. In the present paper, we show the procedure of analysis of the data obtained with the spectrometer and discuss the characteristics to measure neutron capture cross section.
Study of Neutron Capture Reactions Using the 4π Ge Spectrometer
H. Harada,S. Goko,A. Kimura,M. Ohta,M. Oshima,F. Kitatani,M. Igashira,T. Katabuchi,M. Mizumoto,T. Ohsaki,J. Hori,T. Fujii,K. Takamiya,J. Goto,Y. Kiyanagi,K. Kino,M. Furusaka,F. Hiraga,T. Kamiyama 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.59 No.23
The 4π Ge spectrometer composed of 22-30 Ge detectors was developed, and it has been used to study neutron capture reactions with a neutron time-of-flight (TOF) technique. Since the distances between the sample position and the Ge detectors are variable, it can be used as a multifunctional spectrometer. At first, it was used as a sum energy spectrometer, and resonances in ^(nat)Ag were identified as those of ^(1070Ag or ^(109)Ag. In second, it was used to deduce γ-ray intensity distribution for each resonance, and the results for ^(238)U were presented. In third, it was used to measure neutron capture cross sections of minor actinides and fission products at the electron linear accerelator facility of KURRI and at the accurate neutron-nucleus reaction measurement instrument (ANNRI) in MLF of J-PARC The preliminary results are discussed mainly based on measurements of neutron capture cross section for ^(241)Am, together with related techniques.
Measurements of Neutron-Capture Cross Sections of Palladium Isotopes at the J-PARC/MLF/ANNRI
S. Nakamura,K. Furutaka,S. Goko,H. Harada,A. Kimura,T. Kin,F. Kitatani,M. Koizumi,M. Ohta,M. Oshima,Y. Toh,J. Hori,T. Fujii,S. Fukutani,K. Takamiya,M. Igashira,T. Katabuchi,M. Mizumoto,T. Kamiyama,K. 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.59 No.23
The operation of a new experimental apparatus called ``Accurate Neutron-Nucleus Reaction measurement Instrument (ANNRI)''in the Material and Life science experimental Facility (MLF) at the Japan Proton Accelerator Research Complex (J-PARC) has been started for neutroncapture crosssection measurements of minor actinides and long-lived fission products. As a part of the measurements, we have measured the time-of-flight spectra of palladium-105, 106, 107 and 108 with a ``4π Ge spectrometer'' installed at the ANNRI. We obtained preliminary results of the cross sections for palladium-107 and 105 in neutron energies ranging from 0.1 eV to 300 eV.