Publications by authors named "Wataru Okumura"

8 Publications

  • Page 1 of 1

The N-terminal region of Jaw1 has a role to inhibit the formation of organized smooth endoplasmic reticulum as an intrinsically disordered region.

Sci Rep 2021 01 12;11(1):753. Epub 2021 Jan 12.

Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, Tokyo, 183-8509, Japan.

Jaw1/LRMP is a type II integral membrane protein that is localized at the endoplasmic reticulum (ER) and outer nuclear membrane. We previously reported that a function of Jaw1 is to maintain the nuclear shape as a KASH protein via its carboxyl terminal region, a component of linker of nucleoskeleton and cytoskeleton complex in the oligomeric state. Although the oligomerization of some KASH proteins via the cytosolic regions serves to stabilize protein-protein interactions, the issue of how the oligomerization of Jaw1 is regulated is not completely understood. Therefore, we focused on three distinct regions on the cytosolic face of Jaw1: the N-terminal region, the coiled-coil domain and the stem region, in terms of oligomerization. A co-immunoprecipitation assay showed that its coiled-coil domain is a candidate for the oligomerization site. Furthermore, our data indicated that the N-terminal region prevents the aberrant oligomerization of Jaw1 as an intrinsically disordered region (IDR). Importantly, the ectopic expression of an N-terminal region deleted mutant caused the formation of organized smooth ER (OSER), structures such as nuclear karmellae and whorls, in B16F10 cells. Furthermore, this OSER interfered with the localization of the oligomer and interactors such as the type III inositol 1,4,5-triphosphate receptor (IPR3) and SUN2. In summary, the N-terminal region of Jaw1 inhibits the formation of OSER as an IDR to maintain the homeostatic localization of interactors on the ER membrane.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-80258-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804115PMC
January 2021

Characterization of reemergent anti-B red blood cell antibodies in a patient with recurrent acute myeloid leukemia with ABO-incompatible allogeneic peripheral blood stem cell transplantation.

Transfusion 2019 11 10;59(11):3319-3323. Epub 2019 Sep 10.

Department of Laboratory Medicine, Yamagata Prefectural Central Hospital, Yamagata, Japan.

Background: Isohemagglutinins against ABO antigens absent on both recipient and donor red blood cells (RBCs) increase or decrease after ABO-incompatible hematopoietic stem cell transplantation (HSCT). However, few reports have described the changes in the isohemagglutinin titers and the characteristics in patients with recurrent hematologic conditions after ABO-incompatible HSCT.

Case Report: A 59-year-old female with acute erythroid leukemia received a peripheral blood stem cell transplant from her HLA-haploidentical daughter. The patient was typed as group O with anti- A (4+) and B (4+) isohemagglutinins, while the donor was typed as group B. The bone marrow cells achieved complete donor cell chimerism on Day 13 after HSCT. On Day 120, the patient showed 97% B RBC type with persistent anti-A (3+) and without anti-B antibodies. On Day 375, her leukemia relapsed, and recipient type O RBCs and anti-B antibodies sequentially reemerged. However, clinicolaboratory hemolysis and erythroid aplasia were not detected in the patient.

Results: The post-HSCT sera agglutinated the allo B RBCs, but not the donor B RBCs, while the pre-HSCT sera agglutinated both RBCs. The burst-forming/colony-forming units of erythroid formation from the donor peripheral blood stem cells were impaired by only the pre-HSCT sera and not by the post-HSCT sera.

Conclusion: To our knowledge, this is the first report investigating the characteristic changes of isohemagglutinins between the pre- and post-HSCT sera in a patient with recurrent acute myeloid leukemia. The present study suggests that the plasma cells producing anti-donor B RBCs in the patient have been selectively eliminated or induced into an anergic state by the post-HSCT immunologic reconstruction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.15510DOI Listing
November 2019

Jaw1/LRMP has a role in maintaining nuclear shape via interaction with SUN proteins.

J Biochem 2018 Oct;164(4):303-311

Department of Food and Energy Systems Science, Graduate School of Bio-Applications Systems Engineering, 3-5-8 Saiwai-cho, Fuchu, Tokyo, Japan.

Jaw1/LRMP is characterized as a Type II integral membrane protein that is localized to endoplasmic reticulum, however, its physiological functions have been poorly understood. An alignment of amino acid sequence of Jaw1 with Klarsicht/ANC-1/Syne/homology (KASH) proteins, outer nuclear membrane proteins, revealed that Jaw1 has a partial homology to the KASH domain. Here, we show that the function of Jaw1 is to maintain nuclear shape in mouse melanoma cell line. The siRNA-mediated knockdown of Jaw1 caused a severe defect in nuclear shape, and the defect was rescued by ectopic expression of siRNA-resistant Jaw1. Since co-immunoprecipitation assay indicates that Jaw1 interacts with Sad-1/UNC-84 (SUN) proteins that are inner nuclear proteins and microtubules, this study suggests that Jaw1 has a role in maintaining nuclear shape via interactions with SUN proteins and microtubules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jb/mvy053DOI Listing
October 2018

Three cases of vasospastic angina that developed following the initiation of corticosteroid therapy.

Intern Med 2014 ;53(3):221-5

Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Japan.

Three patients diagnosed as having remitting seronegative symmetrical synovitis with pitting edema syndrome, pemphigus erythematosus and idiopathic interstitial pneumonia were treated with oral prednisolone. Several weeks after starting the treatment, they experienced repeated chest pain attacks between midnight and early morning, although none of the patients had a past history of ischemic heart disease. One of the patients exhibited aggravation of symptoms soon after increasing the dose of prednisolone. A definitive diagnosis of vasospastic angina was made using electrocardiograms, coronary angiography and vasospasm provocation tests. These cases emphasize that clinicians should be aware of the possible occurrence of vasospastic angina following the initiation of corticosteroid therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.53.1008DOI Listing
October 2014

Multiple spontaneous coronary artery ruptures and cardiac tamponade in vascular Ehlers-Danlos syndrome.

J Cardiol Cases 2011 Feb 12;3(1):e29-e32. Epub 2010 Nov 12.

Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan.

We report a case of a 45-year-old woman with Ehlers-Danlos syndrome (EDS) type IV, the vascular type, who presented with multiple coronary artery ruptures causing cardiac tamponade. She had sudden onset of chest pain soon after transarterial embolization for right carotid-cavernous fistula. Transthoracic echocardiography confirmed cardiac tamponade and hypokinetic inferolateral wall. Enhanced CT and transesophageal echocardiography ruled out aortic dissection. Coronary angiography showed contrast extravasation from multiple sites of the right coronary artery and left circumflex coronary artery. We suspected EDS type IV, and a skin biopsy for DNA and RNA analysis was done after taking written informed consent. Polymerase chain reaction (PCR) and sequencing of the PCR product showed a heterozygous missense mutation of codon 85 in the gene, which converted glycine to aspartic acid, and thus a diagnosis of EDS type IV was established. To our best knowledge, this is the first case of EDS type IV causing multiple coronary artery ruptures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jccase.2010.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265209PMC
February 2011

Visualizing L-glutamate fluxes in acute hippocampal slices with glutamate oxidase-immobilized coverslips.

Anal Biochem 2009 Feb 8;385(2):326-33. Epub 2008 Nov 8.

Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo, Japan.

We used a glutamate oxidase (GluOx)-immobilized glass coverslip for reducing diffusional blur and improving the temporal resolution of visualizing L-glutamate fluxes in acute brain slices. The immobilization of GluOx on an avidin modified glass coverslips was achieved by optimized the amine coupling method. The GluOx coverslip was applied to the imaging of L-glutamate fluxes in acute hippocampal slices under hypoxia and KCl stimulation. A slice from mouse brain was loaded with horseradish peroxidase (HRP) and substrate DA-64, and placed on the GluOx coverslip for stimulation. The regional distribution of hypoxia-induced L-glutamate fluxes was analyzed. The maximum flux at 3 min after the onset of hypoxia increased in the order CA1>CA3>DG. The time-courses of the L-glutamate fluxes at CA1 and DG were biphasic, while that at CA3 decreased monotonously. The KCl-stimulated release of L-glutamate in the presence of the DL-TBOA uptake inhibitor was imaged. While no noticeable change was observed in the absence of DL-TBOA, L-glutamate fluxes in the presence of the inhibitor increased in the order CA1>CA3>DG, reflecting the effect of uptake processes. The present approach suppressed diffusional blur of the glutamate signal and improved the temporal resolution as compared with the BSA-HRP membrane method described earlier.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ab.2008.10.047DOI Listing
February 2009

Glucose oxidase-immobilized glass disks for imaging of D-glucose in acute brain slices.

Anal Sci 2007 Jan;23(1):39-44

Department of Chemistry, College of Humanities and Sciences, Nihon University, Tokyo, Japan.

A biotinylated glucose oxidase (bGOD)-immobilized glass disk was prepared for visualizing D-glucose fluxes in acute brain slices. A mouse hippocampal slice was placed on the bGOD disk and stimulated with a stimulant solution containing horseradish peroxidase (HRP) and a substrate DA-64, followed by capturing digital images of Bindschedler's Green (BG), an oxidized form of DA-64, with a CCD camera. The bGOD membranes responded proportionally to D-glucose, ranging from 2.0 to 5.0 mM. Sucrose, GABA, L-glutamic acid, L-aspartic acid, glycine, acetylcholine and L-ascorbic acid at 10 mM did not cause any responses. The D-glucose fluxes in mouse hippocampal slices stimulated by a hypoxia solution were neuronal region-dependent, i.e., dentate gyrus (DG), cornu ammonis 1 (CA1) and cornu ammonis 3 (CA3), while those stimulated by KCl was independent of the neuronal regions. The response of bGOD disks is discussed in terms of the principle, concentration dependence and selectivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2116/analsci.23.39DOI Listing
January 2007

Usefulness of fasting 18F-FDG PET in identification of cardiac sarcoidosis.

J Nucl Med 2004 Dec;45(12):1989-98

Second Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Gunma 371-8511, Japan.

Unlabelled: Cardiac PET using (18)F-FDG under fasting conditions (fasting (18)F-FDG PET) is a promising technique for identification of cardiac sarcoidosis and assessment of disease activity. The aim of this study was to investigate the usefulness of fasting (18)F-FDG PET in detecting inflammatory lesions of cardiac sarcoidosis from a pathophysiologic standpoint.

Methods: Twenty-two patients with systemic sarcoidosis were classified into 2 groups of 11 each according to the presence or absence of sarcoid heart disease. Cardiac sarcoidosis was diagnosed according to the Japanese Ministry of Health and Welfare guidelines for diagnosing cardiac sarcoidosis with the exception of scintigraphic criteria. Nuclear cardiac imaging with fasting (18)F-FDG PET, (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) SPECT, and (67)Ga scintigraphy were performed in all patients. PET and SPECT images were divided into 13 myocardial segments and the standardized uptake value (SUV) of (18)F-FDG was calculated and defect scores (DS) for (99m)Tc-MIBI uptake were assessed for each segment. The total SUV (T-SUV) and total DS (TDS) were calculated as the sum of measurements for all 13 segments, and the diagnostic accuracy of fasting (18)F-FDG PET was compared with that of the other nuclear imaging modalities. In addition, pathophysiologic relationships between inflammatory activity and myocardial damage were examined by segmental comparative study using the SUV and DS.

Results: In patients with cardiac sarcoidosis, fasting (18)F-FDG PET revealed a higher frequency of abnormal myocardial segments than (99m)Tc-MIBI SPECT (mean number of abnormal segments per patient: 6.6 +/- 3.0 vs. 3.0 +/- 3.2 [mean +/- SD], P < 0.05). The sensitivity of fasting (18)F-FDG PET in detecting cardiac sarcoidosis was 100%, significantly higher than that of (99m)Tc-MIBI SPECT (63.6%) or (67)Ga scintigraphy (36.3%). The accuracy of fasting (18)F-FDG PET was significantly higher than (67)Ga scintigraphy. The T-SUV demonstrated a good linear correlation with serum angiotensin-converting enzyme levels (r = 0.83, P < 0.01), and the TDS showed a significant negative correlation with the left ventricular ejection fraction (r = -0.82, P < 0.01). In abnormal myocardial segments on the nuclear scan, the SUV showed a significant negative correlation with the DS (r = -0.63, P < 0.0001).

Conclusion: This study suggests that fasting (18)F-FDG PET can detect the early stage of cardiac sarcoidosis, in which fewer perfusion abnormalities and high inflammatory activity are noted, before advanced myocardial impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2004
-->