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1.
Phys Rev Lett ; 125(12): 122501, 2020 Sep 18.
Article in English | MEDLINE | ID: mdl-33016755

ABSTRACT

We performed the first direct mass measurements of neutron-rich scandium, titanium, and vanadium isotopes around the neutron number 40 at the RIKEN RI Beam Factory using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{58-60}Sc, ^{60-62}Ti, and ^{62-64}V were measured for the first time. The experimental results show that the two-neutron separation energies in the vicinity of ^{62}Ti increase compared to neighboring nuclei. This shows that the masses of Ti isotopes near N=40 are affected by the Jahn-Teller effect. Therefore, a development of Jahn-Teller stabilization appears below the Cr isotopes, and the systematics in Sc, Ti, and V isotopes suggest that ^{62}Ti is located close to the peak of the Jahn-Teller effect.

2.
Phys Rev Lett ; 121(2): 022506, 2018 Jul 13.
Article in English | MEDLINE | ID: mdl-30085708

ABSTRACT

We perform the first direct mass measurements of neutron-rich calcium isotopes beyond neutron number 34 at the RIKEN Radioactive Isotope Beam Factory by using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{55-57}Ca are determined for the first time to be -18650(160), -13510(250), and -7370(990) keV, respectively. We examine the emergence of neutron magicity at N=34 based on the new atomic masses. The new masses provide experimental evidence for the appearance of a sizable energy gap between the neutron 2p_{1/2} and 1f_{5/2} orbitals in ^{54}Ca, comparable to the gap between the neutron 2p_{3/2} and 2p_{1/2} orbitals in ^{52}Ca. For the ^{56}Ca nucleus, an open-shell property in neutrons is suggested.

3.
Phys Rev Lett ; 117(16): 162501, 2016 Oct 14.
Article in English | MEDLINE | ID: mdl-27792367

ABSTRACT

In an experiment with the BigRIPS separator at the RIKEN Nishina Center, we observed two-proton (2p) emission from ^{67}Kr. At the same time, no evidence for 2p emission of ^{59}Ge and ^{63}Se, two other potential candidates for this exotic radioactivity, could be observed. This observation is in line with Q value predictions which pointed to ^{67}Kr as being the best new candidate among the three for two-proton radioactivity. ^{67}Kr is only the fourth 2p ground-state emitter to be observed with a half-life of the order of a few milliseconds. The decay energy was determined to be 1690(17) keV, the 2p emission branching ratio is 37(14)%, and the half-life of ^{67}Kr is 7.4(30) ms.

4.
Curr Pharm Biotechnol ; 12(6): 931-45, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21506915

ABSTRACT

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio A, is a rare, autosomal recessive disorder caused by a deficiency of the lysosomal enzyme N-acetylgalatosamine-6-sulfate-sulfatase (GALNS), which catalyzes a step in the catabolism of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate (C6S). It leads to accumulation of the KS and C6S, mainly in bone and cornea, causing a systemic skeletal chondrodysplasia. MPS IVA has a variable age of onset and variable rate of progression. Common presenting features include elevation of urinary and blood KS, marked short stature, hypoplasia of the odontoid process, pectus carinatum, kyphoscoliosis, genu valgum, laxity of joints and corneal clouding; however there is no central nervous system impairment. Generally, MPS IVA patients with a severe form do not survive beyond the third decade of life whereas those patients with an attenuated form may survive over 70 years. There has been no effective therapy for MPS IVA, and care has been palliative. Enzyme replacement therapy (ERT) and hematopoietic stem cell therapy (HSCT) have emerged as a treatment for mucopolysaccharidoses disorders, including Morquio A disease. This review provides an overview of the clinical manifestations, diagnosis and symptomatic management of patients with MPS IVA and describes potential perspectives of ERT and HSCT. The issue of treating very young patients is also discussed.


Subject(s)
Enzyme Replacement Therapy/methods , Hematopoietic Stem Cell Transplantation/methods , Mucopolysaccharidosis IV/diagnosis , Mucopolysaccharidosis IV/therapy , Animals , Humans , Keratan Sulfate/metabolism , Mucopolysaccharidosis IV/metabolism
5.
J Nanosci Nanotechnol ; 7(8): 2748-52, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17685292

ABSTRACT

Polyimide particles were fabricated through the two-steps imidization of poly(amic acid) particles prepared by using reprecipitation method. PAA and PI nanoparticles were all spherical, and the changes of particle size, its distribution, and morphology were not observed before and after the imidization. The preparation of PI nanoparticles size-controlled between ca. 20-500 nm was also achieved by changing the experimental conditions, temperature of the poor solvent, the composition of two kind of poor solvent, and PAA-NMP solution concentration.


Subject(s)
Imides/chemistry , Nanoparticles/chemistry , Nanotechnology/methods , Electrochemistry/methods , Microscopy, Electron, Scanning , Nanostructures , Particle Size , Solvents , Spectrophotometry, Infrared , Surface Properties , Temperature
6.
Gut ; 53(7): 1001-9, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15194652

ABSTRACT

BACKGROUND AND AIM: Significant telomere shortening of hepatocytes is associated with replicative senescence and a non-dividing state in chronic liver disease, resulting in end stage liver failure and/or development of hepatocellular carcinoma. To prevent critical telomere shortening in hepatocytes, we have focused on oestrogen dependent transactivation of the human telomerase reverse transcriptase (hTERT) gene as a form of telomerase therapy in chronic liver disease. METHODS: We examined expression of hTERT mRNA and its protein, and telomerase activity (TA) in three human normal hepatic cell lines (Hc-cells, h-Nheps, and WRL-68) before and after treatment with 17beta-oestradiol. The effects of exogenous oestradiol administration were examined in a carbon tetrachloride (CCl(4)) induced model of liver fibrosis in rats. RESULTS: Expression of hTERT mRNA and its protein was upregulated by oestradiol treatment. Telomere length decreased in Hc-cells and h-Nheps with accumulated passages whereas with long term oestradiol exposure it was greater than without oestradiol. The incidence of beta-galactosidase positive cells, indicating a state of senescence, decreased significantly in oestradiol treated cells in comparison with non-treated cells (p<0.05). TA in both male and female rats with CCl(4) induced liver fibrosis was significantly higher with oestradiol administration than without (p<0.05). Long term oestradiol administration markedly rescued the hepatic telomere from extensive shortening in both male and female rats. CONCLUSION: These results suggest that oestradiol acts as a positive modulator of the hTERT gene in the liver. Oestrogen dependent transactivation of the hTERT gene is a new strategy for slowing the progression of chronic liver disease.


Subject(s)
Cellular Senescence/drug effects , Estradiol/pharmacology , Hepatocytes/drug effects , Liver Cirrhosis, Experimental/pathology , Telomere/drug effects , Animals , Carbon Tetrachloride , Cell Line , DNA-Binding Proteins , Estrogen Receptor alpha , Female , Gene Expression Regulation/drug effects , Hepatocytes/metabolism , Humans , Liver Cirrhosis, Experimental/chemically induced , Liver Cirrhosis, Experimental/genetics , Male , RNA, Messenger/genetics , Rats , Rats, Inbred F344 , Receptors, Estrogen/metabolism , Telomerase/genetics , Telomerase/metabolism , beta-Galactosidase/metabolism
7.
J Dent Res ; 83(1): 45-9, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14691112

ABSTRACT

Tooth crown size may be determined by both genetic and environmental factors. The aim of this study was to identify quantitative trait loci (QTLs) affecting dental crown size and determine whether there is genetic independence between upper and lower teeth, using SMXA recombinant inbred strains of mice. Mesiodistal and buccolingual crown diameters (MD and BL, respectively) of the upper and lower first molars (M(1) and M(1), respectively) were measured. For each trait, mean values of substrains showed a continuous spectrum of distribution. Genome-wide scan detected QTLs exceeding suggestive threshold levels for MD of M(1) (chromosomes 7, 13, and 17), BL of M(1) (chromosomes 8 and 13), MD of M(1) (chromosomes 7 and 13), and BL of M(1) (chromosomes 3 and 15). These findings suggest that tooth crown size is controlled by multiple genes, and that there is some independence of genetic control between M(1) and M(1).


Subject(s)
Molar/anatomy & histology , Tooth Crown/anatomy & histology , Animals , Chromosome Mapping , Chromosomes, Mammalian/genetics , Female , Genetic Linkage/genetics , Genome , Male , Mandible , Maxilla , Mice , Mice, Inbred A , Mice, Inbred Strains , Odontometry , Quantitative Trait, Heritable , Recombination, Genetic/genetics
8.
Curr Med Chem ; 9(22): 2033-53, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12369869

ABSTRACT

The recent progress in synthetic and SAR studies of the specific protein phosphatase inhibitors tautomycin and tautomycetin is reviewed. This article covers the total synthesis of tautomycin and synthetic studies of the spiroketal and the anhydride segments and tautomycetin, and SAR studies on PP inhibition and apoptosis-inducing activity of tautomycin.


Subject(s)
Antifungal Agents/chemical synthesis , Phosphoprotein Phosphatases/antagonists & inhibitors , Pyrans , Spiro Compounds , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Furans , Humans , Lipids , Structure-Activity Relationship
10.
Biosci Biotechnol Biochem ; 65(8): 1920-3, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11577745

ABSTRACT

Macrophomate synthase catalyzes an extraordinary four-step transformation from oxalacetate and 2-pyrone to macrophomic acid by an intermolecular Diels-Alder reaction. The absolute configuration of the most potent macrophomate synthase inhibitor; (-)-2-carboxylmethyl-1-methoxybicyclo[2.2.2]oct-5-ene-2-carboxylic acid, was determined to be (1S, 2R, 4R) by using an axial chiral reagent.


Subject(s)
Carboxylic Acids/chemistry , Enzyme Inhibitors/chemistry , Multienzyme Complexes/antagonists & inhibitors , Crystallography, X-Ray , Indicators and Reagents , Magnetic Resonance Spectroscopy , Models, Molecular , Protein Conformation , Stereoisomerism
11.
Biochem Biophys Res Commun ; 287(2): 328-31, 2001 Sep 21.
Article in English | MEDLINE | ID: mdl-11554729

ABSTRACT

Here we isolated tautomycetin, TC, and examined its phosphatase inhibitory activity. Recently we have reported that the left-hand moiety of tautomycin, TM, and the right one containing the spiroketal are essentially required for inhibition of protein phosphatase, PP, and induction of apoptosis, respectively. TC is structurally almost identical to TM except that TC is lacking the spiroketal, which has the potential apoptosis-inducing activity. TC specifically inhibited PP1 activity, IC50 values for purified PP1 and PP2A enzymes being 1.6 and 62 nM, respectively, whereas the IC50 values of TM were 0.21 and 0.94 nM, respectively. These results demonstrate that TC is the most specific PP1 inhibitor out of over 40 species of natural phosphatase inhibitors reported, strongly suggesting that TC is a novel powerful tool to elucidate the physiological roles of PP1 in various biological events.


Subject(s)
Antifungal Agents/pharmacology , Enzyme Inhibitors/pharmacology , Phosphoprotein Phosphatases/antagonists & inhibitors , Animals , Antifungal Agents/chemistry , Brain/enzymology , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Furans , Lipids , Phosphoprotein Phosphatases/metabolism , Phosphoric Monoester Hydrolases/antagonists & inhibitors , Rats , Streptomyces/chemistry
12.
Biosci Biotechnol Biochem ; 65(5): 1244-7, 2001 May.
Article in English | MEDLINE | ID: mdl-11440150

ABSTRACT

The drimane sesquiterpenes, (+)-albicanol (2) and (+)-albicanyl acetate (3), were synthesized from an optically active bicyclic diol [(+)-1] that had been obtained via the recently developed optical resolution of a general synthetic intermediate for drimane sesquiterpenes. The crucial step in the previous syntheses was markedly improved by the modified Wittig methylenation of a silyloxy ketone (7). The high overall yield (77% in 4 or 5 steps from (+)-1) by this total synthesis makes it possible to synthesize the other biologically active drimane sesquiterpenes.


Subject(s)
Naphthalenes/chemical synthesis , Sesquiterpenes/chemical synthesis , Ketones/chemistry , Molecular Structure , Naphthalenes/chemistry , Sesquiterpenes/chemistry , Spectrum Analysis
15.
Neuroradiology ; 43(2): 151-5, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11326562

ABSTRACT

We describe MRI findings in two patients with disorganised foliation of one cerebellar hemisphere, with folia running vertically rather than horizontally. The thickness of individual folia and corticomedullary interdigitations were normal. These patients have no cerebellar neurological deficit. This rare abnormality is probably a maldevelopment of the hemispheric part of the posterior lobe of the developing cerebellum, and no clinical significance can be elicited.


Subject(s)
Cerebellar Cortex/abnormalities , Magnetic Resonance Imaging , Adult , Female , Humans , Male , Middle Aged
16.
Neuroradiology ; 43(3): 205-10, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11305751

ABSTRACT

We looked at abnormalities in the circuit of Papez in patients with the mesial temporal sclerosis (MTS). We reviewed the MRI studies of 15 patients with probable MTS, seeking changes in the fornix, mamillary body, mamillothalamic tract, thalamus and cingulate and parahippocampal gyri. We correlated any abnormalities with each other and with clinical severity. Atrophy and/or signal change in one or more structures in the circuit of Papez were found in five patients. They involved the parahippocampal gyri in all five, the fornices in four, mamillary bodies in three, the thalamus in two and the cingulate gyrus in one. Changes in the fornix, mamillary body, thalamus or cingulate gyrus were always accompanied by hippocampal and parahippocampal atrophy. The patients with abnormalities of the circuit of Papez did not have more severe epilepsy than those without. Changes in the parahippocampal gyrus, including the entorhinal cortex and subiculum, in which forniceal fibres originate, may be crucial in causing abnormalities more distally in the circuit.


Subject(s)
Epilepsy, Temporal Lobe/pathology , Limbic System/pathology , Temporal Lobe/pathology , Adolescent , Adult , Atrophy , Child , Child, Preschool , Epilepsy, Temporal Lobe/etiology , Female , Humans , Infant , Magnetic Resonance Imaging , Male , Retrospective Studies , Sclerosis
17.
J Gastroenterol Hepatol ; 15(11): 1344-7, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11129233

ABSTRACT

Focal nodular hyperplasia of the liver is a lesion characterized by a well-circumscribed region of hyperplastic liver parenchyma and contains a stellate fibrous scar. The lesion is thought to be because of liver-cell hyperplasia that is caused by focal circulatory disturbances. We describe here a pediatric case of this lesion that provided direct histopathologic evidence of circulatory disturbances. We identified arterial and portal thrombi, as well as recanalization of arteries in the nodule. Hepatic necrosis was also seen in the lesion. We speculate that thrombosis of the hepatic artery and/or portal vein was the cause of hepatic necrosis and that reperfusion following hepatic arterial recanalization resulted in nodule formation. Although there was no stellate scar present in our case, the presence of bile ductular proliferation at the periphery of the nodule was helpful in distinguishing this lesion from adenoma and hepatocellular carcinoma. The early stage of nodular formation may explain the lack of a stellate scar in our case. The patient was treated earlier with actinomycin D and vincristine following surgical excision of Wilms' tumor. It is possible that such chemotherapy contributed to thrombosis in our case.


Subject(s)
Focal Nodular Hyperplasia/etiology , Focal Nodular Hyperplasia/pathology , Antineoplastic Agents/therapeutic use , Female , Focal Nodular Hyperplasia/diagnosis , Hepatic Artery , Humans , Infant , Liver/blood supply , Necrosis , Portal Vein , Thrombosis/complications , Thrombosis/diagnosis , Wilms Tumor/complications , Wilms Tumor/drug therapy
18.
Int J Radiat Oncol Biol Phys ; 48(4): 1059-67, 2000 Nov 01.
Article in English | MEDLINE | ID: mdl-11072163

ABSTRACT

PURPOSE: The correlation between the frequency of spontaneous and radiation-induced apoptosis, and the precedence between those for predicting prognosis were studied at clinical level. METHODS AND MATERIALS: Twenty-one patients (mean age, 65.8 years; 16 men and 5 women) with bladder cancer (transitional cell carcinoma Grade 3, T3bN0M0, Stage IIIb) underwent intraoperative radiotherapy: single 30-Gy 12-MV electron beam irradiation to bladder, followed by total cystectomy 6 h after irradiation. The specimens of pretreatment and irradiated bladder cancer were assayed for apoptosis, using TUNEL staining with counter staining of hematoxylin. The apoptotic index (AI) was calculated by dividing the number of apoptotic cells by the total number of cells and multiplying by 100. The Pearson's linear fitting was used to test the correlation between spontaneous and radiation-induced apoptosis. The Kaplan-Meier product-limit estimation was used for overall survival (OS) and freedom from recurrence (FFR). The precedence between spontaneous and radiation-induced apoptosis for predicting the clinical prognosis was estimated using the proportional hazard regression. RESULTS: The mean AI of spontaneous and radiation-induced apoptosis was 1.18 +/- 0.16 and 2.63 +/- 0.45, respectively, which was significantly different. There was strong correlation between spontaneous and radiation-induced apoptosis (r(2) = 0.864, adjusted r(2) = 0.857). Radiation-induced apoptosis was estimated by equation: y (radiation-induced apoptosis) = 2.67 x (spontaneous apoptosis) -0.52. However, the proportional hazard regression test indicated that only spontaneous apoptosis was significant for predicting OS and FFR (&z.sfnc;t&z.sfnc; > 0.2), but radiation-induced apoptosis was not. CONCLUSION: Estimating AI in radiation-induced apoptosis from AI in spontaneous apoptosis is possible. However, spontaneous apoptosis is more accurate in predicting clinical prognosis.


Subject(s)
Apoptosis , Carcinoma, Transitional Cell/radiotherapy , Urinary Bladder Neoplasms/radiotherapy , Aged , Analysis of Variance , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/physiopathology , Cystectomy , Female , Follow-Up Studies , Humans , In Situ Nick-End Labeling , Intraoperative Period , Male , Middle Aged , Neoplasm Staging , Prognosis , Regression Analysis , Survival Analysis , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/physiopathology
19.
Forensic Sci Int ; 113(1-3): 183-7, 2000 Sep 11.
Article in English | MEDLINE | ID: mdl-10978622

ABSTRACT

Pulmonary neuroendocrine cells (PNECs) are supposed to play an essential role in development of fetal lung and neonatal respiratory adaptation. Some previous studies have suggested the close relation between PNECs and sudden infant death syndrome (SIDS). To investigate how PNECs distribute to the thermal bronchioli of fetal lung may be a clue to clarify this relation. Since it is difficult to distinguish bronchiole from alveolus in fetal lung, we performed double immunostaining with antibody against chromogranin A (CGA) and alpha-smooth muscle actin (SMA) which can make clear distinction between them. In this study, formalin-fixed, paraffin-embedded lung tissues from 18 autopsy cases from 16 to 28 weeks of gestation were assessed. CGA immunopositive cells were counted and the length of basement membranes of terminal bronchioli was measured with computed image analyzer. Density of PNECs was expressed as the number of immunopositive cells per millimeter of basement membrane. Terminal bronchiole stained with SMA was clearly distinguished from alveolus at 16 weeks. With gestational age, CGA immunopositive PNECs were gradually increased in 2 folds by the 25th week. After that, their density wasn't changed significantly until termination. It is suggested that PNECs in terminal bronchiole was playing an important role in morphogenesis of alveolar ducts and alveolar sacks.


Subject(s)
Actins/analysis , Autopsy/methods , Bronchi/chemistry , Bronchi/cytology , Chromogranins/analysis , Embryonic and Fetal Development , Immunohistochemistry/methods , Neurosecretory Systems/cytology , Pulmonary Alveoli/chemistry , Pulmonary Alveoli/cytology , Sudden Infant Death/pathology , Basement Membrane/cytology , Bronchi/growth & development , Cell Count , Chromogranin A , Cytological Techniques , Female , Gestational Age , Humans , Male , Pulmonary Alveoli/growth & development
20.
J Biol Chem ; 275(49): 38393-401, 2000 Dec 08.
Article in English | MEDLINE | ID: mdl-10984474

ABSTRACT

Macrophomate synthase from the fungus Macrophoma commelinae IFO 9570 is a Mg(II)-dependent dimeric enzyme that catalyzes an extraordinary, complex five-step chemical transformation from 2-pyrone and oxalacetate to benzoate involving decarboxylation, C-C bond formation, and dehydration. The catalytic mechanism of the whole pathway was investigated in three separate chemical steps. In the first decarboxylation step, the enzyme loses oxalacetate decarboxylation activity upon incubation with EDTA. Activity is fully restored by addition of Mg(II) and is not restored with other divalent metal cations. The dissociation constant of 0.93 x 10(-)(7) for Mg(II) and atomic absorption analysis established a 1:1 stoichiometric complex. Inhibition of pyruvate formation with 2-pyrone revealed that the actual product in the first step is a pyruvate enolate, which undergoes C-C bond formation in the presence of 2-pyrone. Incubation of substrate analogs provided aberrant adducts that were produced via C-C bond formation and rearrangement. This strongly indicates that the second step is two C-C bond formations, affording a bicyclic intermediate. Based on the stereospecificity, involvement of a Diels-Alder reaction at the second step is proposed. Incubation of the stereospecifically deuterium-labeled malate with 2-pyrones in the presence of malate dehydrogenase provided information for the stereochemical course of the reaction catalyzed by macrophomate synthase, indicating that the first decarboxylation provides pyruvate (Z)-[3-(2)H]enolate and that dehydration at the final step occurs with anti-elimination accompanied by concomitant decarboxylation. Examination of kinetic parameters in the individual steps suggests that the third step is the rate-determining step of the overall transformation.


Subject(s)
Benzoates/metabolism , Multienzyme Complexes/metabolism , Pyrones/metabolism , Benzoates/chemistry , Catalysis , Edetic Acid/pharmacology , Kinetics , Magnesium/metabolism , Mitosporic Fungi/enzymology , Molecular Structure , Pyrones/chemistry
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