Ultradiscretization of the solution of periodic Toda equation

A periodic box-ball system (pBBS) is obtained by ultradiscretizing the periodic discrete Toda equation (pd Toda eq.). We show the relation between a Young diagram of the pBBS and a spectral curve of the pd Toda eq.. The formula for the fundamental cycle of the pBBS is obtained as a colloraly.Comment: 41 pages; 7 figure

In vivo detection of γ-glutamyl-transferase up-regulation in glioma using hyperpolarized γ-glutamyl-[1-13C]glycine.

Glutathione (GSH) is often upregulated in cancer, where it serves to mitigate oxidative stress. γ-glutamyl-transferase (GGT) is a key enzyme in GSH homeostasis, and compared to normal brain its expression is elevated in tumors, including in primary glioblastoma. GGT is therefore an attractive imaging target for detection of glioblastoma. The goal of our study was to assess the value of hyperpolarized (HP) γ-glutamyl-[1-13C]glycine for non-invasive imaging of glioblastoma. Nude rats bearing orthotopic U87 glioblastoma and healthy controls were investigated. Imaging was performed by injecting HP γ-glutamyl-[1-13C]glycine and acquiring dynamic 13C data on a preclinical 3T MR scanner. The signal-to-noise (SNR) ratios of γ-glutamyl-[1-13C]glycine and its product [1-13C]glycine were evaluated. Comparison of control and tumor-bearing rats showed no difference in γ-glutamyl-[1-13C]glycine SNR, pointing to similar delivery to tumor and normal brain. In contrast, [1-13C]glycine SNR was significantly higher in tumor-bearing rats compared to controls, and in tumor regions compared to normal-appearing brain. Importantly, higher [1-13C]glycine was associated with higher GGT expression and higher GSH levels in tumor tissue compared to normal brain. Collectively, this study demonstrates, to our knowledge for the first time, the feasibility of using HP γ-glutamyl-[1-13C]glycine to monitor GGT expression in the brain and thus to detect glioblastoma

Oxidative Modification to Cysteine Sulfonic Acid of Cys111 in Human Copper-Zinc Superoxide Dismutase

Copper-zinc superoxide dismutase (SOD1) plays a protective role against oxidative stress. On the other hand, recent studies suggest that SOD1 itself is a major target of oxidative damage and has its own pathogenicity in various neurodegenerative diseases, including familial amyotrophic lateral sclerosis. Only human and great ape SOD1s among mammals have the highly reactive free cysteine residue, Cys111, at the surface of the SOD1 molecule. The purpose of this study was to investigate the role of Cys111 in the oxidative damage of the SOD1 protein, by comparing the oxidative susceptibility of recombinant human SOD1 modified with 2-mercaptoethanol at Cys111 (2-ME-SOD1) to wild-type SOD1. Wild-type SOD1 was more sensitive to oxidation by hydrogen peroxide-generating fragments, oligomers, and charge isomers compared with 2-ME-SOD1. Moreover, wild-type SOD1, but not 2-ME-SOD1, generated an upper shifted band in reducing SDS-PAGE even by air oxidation. Using mass spectrometry and limited proteolysis, this upper band was identified as an oxidized subunit of SOD1; the sulfhydryl group (Cys-SH) of Cys111 was selectively oxidized to cysteine sulfinic acid (Cys-SO2H) and to cysteine sulfonic acid (Cys-SO3H). The antibody raised against a synthesized peptide containing Cys111-SO3H reacted with only the Cys111-peroxidized SOD1 by Western blot analysis and labeled Lewy bodylike hyaline inclusions and vacuole rims in the spinal cord of human SOD1-mutated amyotrophic lateral sclerosis mice by immunohistochemical analysis. These results suggest that Cys111 is a primary target for oxidative modification and plays an important role in oxidative damage to human SOD1, including familial amyotrophic lateral sclerosis mutants.This work was supported by Grants-in-aid for Scientific Research 17500242 and 19500313; a Hitech Research Center grant and the 21st Century Centers of Excellence program from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and in part by a Grant for the Research Group on Development of Novel Therapeutics for ALS from the Ministry of Health, Labor and Welfare of Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact

A Young Boy with Neck Pain

Case Presentation: A five-year-old boy presented to our emergency department with severe posterior neck pain that was exacerbated upon neck movement. Cervical spine radiography revealed calcification in the cervical intervertebral disk 3-4.Discussion: Pediatric idiopathic intervertebral disk calcification is a benign, rare condition that might be complicated by associated severe neurological symptoms. In this case, the symptoms gradually subsided with conservative management alone

A Young Boy with Neck Pain

Case Presentation: A five-year-old boy presented to our emergency department with severe posterior neck pain that was exacerbated upon neck movement. Cervical spine radiography revealed calcification in the cervical intervertebral disk 3-4.Discussion: Pediatric idiopathic intervertebral disk calcification is a benign, rare condition that might be complicated by associated severe neurological symptoms. In this case, the symptoms gradually subsided with conservative management alone

STAP-2 positively regulates Fc epsilon RI-mediated basophil activation and basophil-dependent allergic inflammatory reactions

Basophils are an important cell type in the regulation of T(h)2 immune responses. Recently, we revealed that signal-transducing adaptor protein-2 (STAP-2) negatively regulates mast cell activation via Fc epsilon RI. However, the role of STAP-2 in basophil maturation and activation remained unclear. In this study, we demonstrated the normal development of basophils in STAP-2-deficient (STAP-2(-/-)) mice. We also demonstrated in vitro normal basophil differentiation and FceRI expression in STAP2(-/-) mice, suggesting that STAP-2 is dispensable for basophil maturation. Using bone marrow-derived cultured basophils (BMBs), we showed that degranulation and cytokine production of STAP-2(-/-) BMBs were lower than those of wild-type (WT) BMBs upon stimulation with IgE/Ag. In accordance with the reduction of degranulation and cytokine production, phosphorylation of several signal molecules such as Lyn, PLC-gamma 2 and Erk was reduced in STAP-2(-/-) BMBs after stimulation via Fc epsilon RI. Finally, it was observed that IgE-dependent chronic allergic inflammation of STAP-2(-/-) mice was significantly inhibited compared with WT mice. Taken together, we conclude that STAP-2 is an adaptor molecule that positively regulates FceRI-mediated basophil activation and basophil-dependent allergic inflammatory reactions

Epiploic appendagitis as an uncommon cause of lower abdominal pain

AuthorEpiploic appendagitis should be considered to be an uncommon cause of lower abdominal pain. To diagnose accurately, typical CT findings are needed, and total colonoscopy should be done later to rule out the possibility of diverticulosi

Assessing γ-glutamyl transpeptidase activity in kidney using hyperpolarized γ-Glu-[1-13C]Gly

Hyperpolarized γ-Glu-[1-13C]Gly provides a non-invasive means to detect γ-glutamyl transpeptidase (GGT) enzyme activity in vivo with potential for application in functional imaging. Since GGT is most abundant in the proximal tubules of the kidney, and since the properties of γ-Glu-[1-13C]Gly are suitable for in vivo hyperpolarized 13C metabolic analysis, it was proposed as a molecular probe to study kidney function. The aim of the present study is to identify the dose of γ-Glu-[1-13C]Gly that gives high NMR sensitivity in the unsaturated state of the GGT enzyme. Therefore γ-Glu-[1-13C]Gly was polarized with the stable trityl radical OX63 in a custom-designed DNP polarizer (7T, 1.1K) using microwave irradiation at 196.59 GHz and 50 mW. As a first approach to analyze the HP data, method used in [3] was applied. Herein, the reaction rates were calculated by multiplying the kinetic rate constants with the corresponding substrate concentrations, in which the kinetic rate constant is the product of the 13C longitudinal relaxation rate of glycine (~45s) and the ratio of the integrated γ-Glu-[1-13C]Gly and [1-13C]Gly signal amplitude. Benefiting from a narrow spectral linewidth of the hyperpolarized signal (~20 Hz, FWHM), conversion of γ-Glu-[1-13C]Gly to [1-13C]Gly was measurable down to an estimated blood concentration of 32 μM. To address the possibility of substrate saturation of the GGT enzyme in the kidney, different doses of γ-Glu-[1-13C]Gly were administered, corresponding to a blood concentration range of 32 to 500 μM. The variability of the apparent reactions rates between animals is high for all doses of administered γ-Glu-[1-13C]Gly. The rate, however, was proportional with the dose in 7 of 8 rats, and complete saturation of the GGT enzyme cannot be seen in the dosage range tested. This study shows that HP γ-GluGly senses GGT activity with excellent NMR sensitivity and that a broad range of substrate concentrations can be applied to study kidney function. To understand better the distribution of the initial reaction rates and to estimate the dose required to saturate the GGT enzyme, a broader range of substrate doses will be tested, along with simultaneous functional quantification

Probing renal pH using hyperpolarized [1-13C]alaninamide

Hyperpolarized molecular probes can be effectively used as pH markers. To date, the only two probes reported in vivo as extracellular pH sensors are 13C-bicarbonate, and [1,5-13C2]zymonic acid. Alaninamide is a derivative of alanine which is found to be sensitive to variations of pH in the physiological range. The aim of the present study was to assess the feasibility of using alaninamide as a pH probe in vivo. The alaninamide titration curve was determined by performing 13C NMR measurements at 9.4 T, 37° on a set of 500 mM Ala-NH2∙HCl samples of varying pH referenced to 13C urea. [1-13C]Alaninamide was polarized at 1 K in a 7 T polarizer, then rapidly dissolved in a buffered solution and injected IV into a Sprague Dawley rat (n=6) located in a 9.4 T animal scanner. 13C FIDs were acquired with 30° BIR4 pulses using a single loop 1H / quadrature 13C surface coil placed over the left kidney. The pH was perturbed by injecting acetazolamide IV (10 mg/kg) one hour prior to infusion. The alaninamide titration curve shows a 13C1 chemical shift change of ≈ 8.4 ppm, and a pKa of 7.9. The pH sensitivity of 13C1 results in three distinct alaninamide spectral peaks, corresponding to three different extracellular pH compartments within the kidney (pH = 7.46, pH = 7.22, pH = 6.58) that can be tentatively assigned to the cortex/blood, medulla and calyx/ureter. With acetazolamide treatment, the pH in the first compartment follows the change in pH of the blood, while the pH in the third compartment does not reflect the urine pH and shifts during the brief experiment. No change is observed in the pH value of the second compartment