Publications by authors named "Hiroko Nakata"

20 Publications

  • Page 1 of 1

[Revascularization of the Right Common Carotid Artery Prior to Central Repair for Stanford Type A Acute Aortic Dissection with Brain Malperfusion:Report of a Case].

Kyobu Geka 2021 Jul;74(7):558-560

Department of Cardiovascular Surgery, Yokosuka Municipal Uwamachi Hospital, Yokosuka, Japan.

A 67-year-old woman had sudden loss of consciousness and chest and back pain. She was transported by ambulance about two hours later. Computed tomography (CT) showed dissection of the aorta, the brachiocephalic artery and the right common carotid artery (RCCA). RCCA was completely obstructed. Emergency surgery was conducted one hour later. RCCA's blood flow was reestablished prior to hemi-arch replacement. Postoperative CT revealed diminishment of the false lumen and recovery of the blood flow of RCCA, and she was discharged on foot without any complications.
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July 2021

Incidence and Clinical Features of Venous Thromboembolism in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) in Japan.

Circ J 2021 11 20;85(12):2208-2214. Epub 2021 May 20.

Kuwana City Medical Center.

Background: Coronavirus disease 2019 (COVID-19) reportedly causes venous thromboembolism (VTE), but the status of this complication in Japan was unclear.Methods and Results:The VTE and COVID-19 in Japan Study is a retrospective, multicenter cohort study enrolling hospitalized patients with COVID-19 who were evaluated with contrast-enhanced computed tomography (CT) examination at 22 centers in Japan between March 2020 and October 2020. Among 1,236 patients with COVID-19, 45 (3.6%) were evaluated with contrast-enhanced CT examination. VTE events occurred in 10 patients (22.2%), and the incidence of VTE in mild, moderate, and severe COVID-19 was 0%, 11.8%, and 40.0%, respectively. COVID-19 patients with VTE showed a higher body weight (81.6 vs. 64.0 kg, P=0.005) and body mass index (26.9 vs. 23.2 kg/m, P=0.04), and a higher proportion had a severe status for COVID-19 compared with those without. There was no significant difference in the proportion of patients alive at discharge between patients with and without VTE (80.0% vs. 88.6%, P=0.48). Among 8 pulmonary embolism (PE) patients, all were low-risk PE.

Conclusions: Among a relatively small number of patients undergoing contrast-enhanced CT examination in Japanese real-world clinical practice, there were no VTE patients among those with mild COVID-19, but the incidence of VTE seemed to be relatively high among severe COVID-19 patients, although all PE events were low-risk without significant effect on mortality risk.
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http://dx.doi.org/10.1253/circj.CJ-21-0169DOI Listing
November 2021

[Patch Repair by Anterolateral Thoracotomy with Partial Sternotomy for Saccular Aortic Arch Aneurysm with Severe Thoracic Deformity:Report of a Case].

Kyobu Geka 2021 Feb;74(2):147-151

Department of Cardiovascular Surgery, Yokosuka Municipal Uwamachi Hospital, Yokosuka, Japan.

An 87-year-old male was referred to our hospital for surgery of saccular aortic arch aneurysm. As he had a history of thoracoplasty on his left side due to pulmonary tuberculosis, his aortic arch adhered to the apex of the left thorax. Total arch replacement(TAR) via median sternotomy was considered difficult, and anterolateral thoracotomy with partial sternotomy (ALPS) was performed. During surgery, we considered TAR difficult even with ALPS approach. Taking account of his age, aneurysmectomy and patch repair were chosen instead of TAR to shorten operation time. Although he suffered from diffuse cerebral infarction, he was discharged without neurological deficit at 39 days after operation.
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February 2021

Solar-Driven Photoelectrochemical Water Oxidation over an n-Type Lead-Titanium Oxyfluoride Anode.

J Am Chem Soc 2019 Oct 17;141(43):17158-17165. Epub 2019 Oct 17.

Department of Chemistry, School of Science , Tokyo Institute of Technology , 2-12-1-NE-2 Ookayama , Meguro-ku, Tokyo 152-8550 , Japan.

Mixed-anion compounds (e.g., oxynitrides and oxysulfides) are potential candidates as photoanodes for visible-light water oxidation, but most of them suffer from oxidative degradation by photogenerated holes, leading to low stability. Here we show an exceptional example of a stable, mixed-anion water-oxidation photoanode that consists of an oxyfluoride, PbTiOF, having a band gap of ca. 2.4 eV. PbTiOF particles, which were coated on a transparent conductive glass (FTO) support and were subject to postdeposition of a TiO overlayer, generated an anodic photocurrent upon band gap photoexcitation of PbTiOF (λ <520 nm) with a rather negative photocurrent onset potential of ca. -0.6 V vs NHE, which was independent of the pH of the electrolyte solution. Stable photoanodic current was observed even without loading a water oxidation promoter such as CoO. Nevertheless, loading CoO onto the TiO/PbTiOF/FTO electrode further improved the anodic photoresponse by a factor of 2-3. Under AM1.5G simulated sunlight (100 mW cm), stable water oxidation to form O was achieved using the optimized PbTiOF photoanode in the presence of an applied potential smaller than 1.23 V, giving a Faradaic efficiency of 93% and almost no sign of deactivation during 4 h of operation. This study presents the first example of photoelectrochemical water splitting driven by visible-light excitation of an oxyfluoride that stably works, even without a water oxidation promoter, which is distinct from ordinary mixed-anion photoanodes that usually require a water oxidation promoter.
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http://dx.doi.org/10.1021/jacs.9b06570DOI Listing
October 2019

[Pseudoaneurysm with Infective Endocarditis Ten Years After the Resection of Pseudoaneurysm Complicated with Myocardial Infarction;Report of a Case].

Kyobu Geka 2019 Oct;72(11):923-927

Department of Cardiovascular Surgery, Yokosuka Municipal Uwamachi Hospital, Yokosuka, Japan.

A 76-year-old female was referred to our hospital for fever and chillness. She was diagnosed with pneumonia and sepsis, and methicillin-resistant Staphylococcus aureus (MRSA)was detected by the sputum culture. Echocardiography showed mobile vegetation and left ventricular pseudoaneurysm at the apex. As she had a history of ventricular pseudoaneurysmectomy 10 years before, we considered the patient had developed infective endocarditis at the surgical site. Surgical treatment was needed because of the rapidly growing pseudoaneurysm despite the use of antibacterial agents. She successfully underwent resection of the pseudoaneurysm and MRSA was also detected in the culture of the previous vascular graft patch. Antibacterial agents were administrated for 6 weeks, and she was discharged at 53 days after operation.
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October 2019

Off-pump coronary artery bypass grafting via left anterior thoracotomy from the 4th costal space in a patient with total laryngectomy and a permanent tracheostoma.

Gen Thorac Cardiovasc Surg 2020 Jun 20;68(6):633-636. Epub 2019 May 20.

Department of Cardiovascular Surgery, Yokosuka Uwamachi Hospital, 2-36 Uwamachi, Yokosuka, Kanagawa, 238-8567, Japan.

Median sternotomy is the standard approach for coronary artery bypass grafting. Herein, we performed off-pump coronary artery bypass grafting via left anterior thoracotomy from the 4th costal space in an unstable angina pectoris patient with total laryngectomy and a permanent tracheostoma. In this patient, median sternotomy had high risks of surgical-site infection and tracheal injury. To avoid these risks, we selected left anterior thoracotomy. Initially, it was difficult to expose the ascending aorta and postdescending branch. With extension of the skin incision to the median area and division of the 5th and 6th ribs and costal arch, we could expose the anastomotic sites, including the ascending aorta and postdescending branch, without median sternotomy conversion. We performed multiple coronary artery bypass graft procedures safely. This approach might be an additional surgical option in patients with total laryngectomy and a permanent tracheostoma.
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http://dx.doi.org/10.1007/s11748-019-01143-1DOI Listing
June 2020

[Combined Thoraco-abdominal Aortic Aneurysm Repair and Coronary Artery Bypass Grafting through a Left Thoracotomy].

Kyobu Geka 2018 Aug;71(8):588-592

Department of Cardiovascular Surgery, Yokosuka General Hospital Uwamachi, Yokosuka, Japan.

Approximately 40% of the patients with aortic aneurysm have coronary artery disease(CAD), which is an important factor contributing to early mortality associated with aneurysm surgery. Combined coronary artery bypass grafting (CABG)and aortic aneurysm repair of the ascending aorta to the aortic arch is often performed through a median sternotomy due to a good surgical exposure. However, treatment strategy of thoraco-abdominal aortic aneurysm(TAAA) combined with CAD is often controversial. We report a successful case of a 69-year-old man who underwent TAAA repair and CABG through a left thoracotomy. Left thoracotomy via the 5th intercostal space with para-rectal incision provides a good surgical exposure of the thoraco-abdominal aorta and the left anterior descending artery(LAD). LAD was revascularized with a saphenous vein graft which was anastomosed to the descending aorta, followed by TAAA repair. The postoperative course was uneventful and the patient was discharged on 13th postoperative day without any complications.
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August 2018

Evaluation of the in vivo radiosensitizing activity of etanidazole using tumor-bearing chick embryo.

J Radiat Res 2011 ;52(2):208-14

Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima, Tokushima, Japan.

Chick embryos have been used as alternative experimental animals in various research fields, including virology, immunology, toxicology, oncology, and embryology. Until now, there have been no in vivo models using chick embryo to evaluate radiosensitizing activity. Here, the in vivo radiosensitizing activity of etanidazole, a well-known hypoxic cell radiosensitizer, was evaluated using tumor-bearing chick embryo. On the basis of tumor growth, drug administration and X-ray irradiation were performed on day 15 chick embryo, with the endpoint being day 18 chick embryo. In day 15 chick embryo, an X-ray irradiation dose of equal or less than 10 Gy did not cause significant tumor growth suppression. Intravenous administration of equal or less than 1.0 mg of etanidazole did not cause tumor growth suppression. Neither doses of equal or less than 8 Gy of irradiation nor 1.0 mg of etanidazole caused fatality of the chick embryo. On the basis of these results, we evaluated the radiosensitizing effect of a combination treatment with 8 Gy of irradiation and 1.0 mg of etanidazole. As noted above, 1.0 mg of etanidazole alone and 8 Gy of irradiation alone did not show tumor growth suppression. In contrast, a combination treatment with 8 Gy of irradiation and 1.0 mg of etanidazole showed 35% of significant tumor growth suppression. Thus, we succeeded in evaluating the in vivo radiosensitizing activity of etanidazole using tumor-bearing chick embryo. These results suggest that the use of tumor-bearing chick embryo may be part of a promising system for evaluating radiosensitizing activity.
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http://dx.doi.org/10.1269/jrr.10122DOI Listing
July 2011

Brain-derived neurotrophic factor regulates AMPA receptor trafficking to post-synaptic densities via IP3R and TRPC calcium signaling.

FEBS Lett 2007 May 25;581(10):2047-54. Epub 2007 Apr 25.

Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.

The change in the number of post-synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamatergic receptors (AMPARs) by neuronal activity is recognized as a molecular basis of synaptic plasticity. Here, we show that Ca(2+) transients evoked by brain-derived neurotrophic factor (BDNF) induce translocation of a subunit of AMPAR, GluR1, but not NMDAR, to the post-synaptic membrane in cultured cortical pyramidal neurons. Among BDNF-induced Ca(2+) transients, that dependent on IP3R was fully required, while store-operated calcium influx through the non-selective cation channel TRPC (transient receptor potential canonical) was partially required for the GluR1 up-regulation, suggesting that spatial and temporal calcium signaling regulate translocation of GluR1 to the polarized membrane domain.
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http://dx.doi.org/10.1016/j.febslet.2007.04.041DOI Listing
May 2007

[Case of bronchial asthma complicated with Takotsubo cardiomyopathy after frequent epinephrine medication].

Nihon Kokyuki Gakkai Zasshi 2006 Oct;44(10):701-5

Second Department of Internal Medicine, Nagasaki University School of Medicine.

A 62-year-old man with non-topic severe persistent asthma and chronic obstructive disease suffered severe asthma exacerbation. Epinephrine was repeatedly injected subcutaneously (0.3mg x 8 times in four hours) in addition to intravenous methylprednisolone for his severe asthma. Despite these treatments, his symptoms steadily deteriorated and thus he was transferred to our hospital. He did not have chest pain or a sensation of compression, while ECG on admission demonstrated ST elevation, loss of R-wave progression, negative T waves and QT interval prolongation, suggesting ischemic heart disease. Nonetheless creatine kinase and its MB isozyme were within normal range and myosin light chain I and troponin T were only mildly elevated. Echocardiography demonstrated apical dyskinesia and hypersystole in the basal region of the heart. Finally this case was diagnosed as Takotsubo cardiomyopathy, probably due to catecholamine-mediated myocardial stunning by overuse of epinephrine for acute severe asthma exacerbation. Abnormal findings of ECG and echocardiography became normal without any specific treatments for the heart.
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October 2006

[A case of anaphlaxis caused by mite-contaminated Okonomi-yaki].

Arerugi 2006 May;55(5):574-7

Second Department of Internal Medicine, Nagasaki University, Nagasaki.

A 21-year-old man, who had suddenly developed dyspnea with sneeze, cough and nasal congestion following supper, was admitted to our hospital because of hypoxemia and hypercapnia. Physical examination revealed wheezing in all lung fields and skin flushing. He took home-made Okonomi-yaki made from flour, which had been opened few months ago, and then had been remained uncooked at room temperature. Skin prick tests showed positive for problem flour and mite, but negative for just opened control flour. Collectively, we gave his diagnosis of anaphylaxis caused by mite-contaminated Okonomi-yaki.
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May 2006

A clinical evaluation of definitive and clinical allergic bronchopulmonary mycosis.

Intern Med 2006 18;45(12):759-62. Epub 2006 Jul 18.

Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto.

Objective: The present study aims to overcome problems associated with the early diagnosis of allergic bronchopulmonary mycosis (ABPM) using the current criteria.

Patients And Methods: Clinical features including radiographic findings from 10 patients with definitive ABPM based on the diagnostic criteria of Rosenberg-Patterson were compared with those from 9 patients with ABPM clinically diagnosed by respiratory allergy specialists.

Results: ABPM should be considered in patients with peripheral blood eosinophilia and pulmonary infiltration and/or central bronchiectasis when serum total IgE is elevated. Complication by bronchial asthma suggested ABPM, but was not essential. The expectoration of sputum containing solid components was a critical factor in patients with a history in ABPM. Evaluation of sputum cultures, serum specific IgE antibodies, skin tests and precipitating antibodies were required to establish a diagnosis, but the positive rate of these tests remained low.

Conclusions: Even when a definitive diagnosis cannot be established, systemic corticosteroid therapy should be initiated for clinically diagnosed ABPM to prevent irreversible pulmonary dysfunction.
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http://dx.doi.org/10.2169/internalmedicine.45.1751DOI Listing
September 2006

Naturally occurring parainfluenza virus 3 infection in adults induces mild exacerbation of asthma associated with increased sputum concentrations of cysteinyl leukotrienes.

Int Arch Allergy Immunol 2005 Nov 7;138(3):267-72. Epub 2005 Oct 7.

Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, Japan.

Background: Viral respiratory tract infections represent the most frequent cause of asthma exacerbation in both children and adults, but the precise mechanism of such exacerbation remains unknown.

Objectives: To determine the critical mediator of naturally occurring parainfluenza virus (PIV) 3-induced mild asthma exacerbations in adults.

Methods: The study subjects were 19 adult asthmatics with mild asthma exacerbation (peak expiratory flow = 60-80% of predicted before bronchodilator use and >80% of predicted after initial bronchodilator treatment). Differential cell counts and concentrations of inflammatory markers including eosinophil cationic protein (ECP), cysteinyl leukotrienes (cysLTs), interleukin (IL)-5, IL-10 and IL-12 were measured in the induced sputum obtained from adults with PIV3- (n = 9) and non-cold-induced (n = 10) exacerbation of asthma during both acute and convalescent phases.

Results: PIV3 infection was confirmed by the presence of viral RNA in nasopharyngeal aspirates. Mild exacerbation of asthma was not associated with significant changes in sputum differential cell counts. Concentrations of sputum ECP and cytokines were comparable between PIV3 and non-cold-induced patients. In contrast, PIV3 infection was associated with a significant increase in sputum cysLTs during the acute phase of mild asthma exacerbation.

Conclusions: Our results identified cysLTs as a critical mediator of PIV3-induced acute asthma exacerbation.
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http://dx.doi.org/10.1159/000088728DOI Listing
November 2005

Functional characterization of Galphao signaling through G protein-regulated inducer of neurite outgrowth 1.

Mol Pharmacol 2005 Mar 7;67(3):695-702. Epub 2004 Dec 7.

Department of Pharmacology (M/C 868), University of Illinois at Chicago, 835 South Wolcott Avenue, Chicago, IL 60612, USA.

G protein-regulated inducer of neurite outgrowth 1 (GRIN1) was initially identified as a binding protein for guanosine 5'-3-O-(thio)triphosphate-bound Galphaz. GRIN1 is specifically expressed in brain and interacts selectively with activated alpha subunits of the Gi subfamily. GRIN1 colocalizes with Galphao at the growth cone of neuronal cells and promotes neurite extension in Neuro2a cells when coexpressed with constitutively active mutant GalphaoQ205L. These results suggest that GRIN1 functions as a downstream target for Galphao. However, GRIN1 does not contain domains that are homologous to known signaling motifs. To understand the mechanisms of Galphao-GRIN1 pathway, we analyzed functional domains of GRIN1 that are involved in binding with Galphao or with its targeting to the plasma membrane. Using pull-down assays with glutathione S-transferase-fused GRIN1 deletion mutants, Galphao binding regions were localized to amino acid residues 716 to 746 and 797 to 827 of GRIN1. The Galphao binding region of GRIN1 did not demonstrate GTPase accelerating activity for Galphao. GRIN1 localized in the cell periphery in Neuro2a cells, and two cysteine residues at C-terminal region of GRIN1 (Cys818 and Cys819) were shown to be critical for its membrane targeting. Coexpression of GRIN1 with GalphaoQ205L or GRIN1Delta(717-827), which lacks Galphao binding region, promoted microspike formation in Swiss 3T3 cells or neurite extension in Neuro2a cells. The dominant-negative mutant of Cdc42 blocked these morphological changes. Coexpression of GRIN1 and GalphaoQ205L stimulated the formation of GTP-bound Cdc42 in Swiss 3T3 cells. These results suggest that the binding of activated Galphao to GRIN1 induces activation of Cdc42, which leads to morphological changes in neuronal cells.
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http://dx.doi.org/10.1124/mol.104.003913DOI Listing
March 2005

Interaction of G protein beta subunit with inward rectifier K(+) channel Kir3.

Mol Pharmacol 2003 Nov;64(5):1085-91

Department of Pharmacology, College of Medicine, University of Illinois at Chicago, 835 S. Wolcott Ave., Chicago, IL 60612, USA.

G protein betagamma subunits bind and activate G protein-coupled inward rectifier K+ (GIRK) channels. This protein-protein interaction is crucial for slow hyperpolarizations of cardiac myocytes and neurons. The crystal structure of Gbeta shows a seven-bladed propeller with four beta strands in each blade. The Gbeta/Galpha interacting surface contains sites for activating GIRK channels. Furthermore, our recent investigation using chimeras between Gbeta1 and yeast beta (STE4) suggested that the outer strands of blades 1 and 2 of Gbeta1 could be an interaction area between Gbeta1 and GIRK. In this study, we made point mutations on suspected residues on these outer strands and investigated their ability to activate GIRK1/GIRK2 channels. Mutations at Thr-86, Thr-87, and Gly-131, all located on the loops between beta-strands, substantially reduced GIRK channel activation, suggesting that these residues are Gbeta/GIRK interaction sites. These mutations did not affect the expression of Gbeta1 or its ability to stimulate PLCbeta2. These residues are surface-accessible and located outside Gbeta/Galpha interaction sites. These results suggest that the residues on the outer surface of blades 1 and 2 are involved in the interaction of Gbetagamma with GIRK channels. Our study suggests a mechanism by which different effectors use different blades to achieve divergence of signaling. We also observed that substitution of alanine for Trp-332 of Gbeta1 impaired the functional interaction of Gbeta1 with GIRK, in agreement with the data on native neuronal GIRK channels. Trp-332 plays a critical role in the interaction of Gbeta1 with Galpha as well as all effectors so far tested.
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http://dx.doi.org/10.1124/mol.64.5.1085DOI Listing
November 2003

Risk factors and treatment of deep sternal wound infection after cardiac operation.

Ann Thorac Cardiovasc Surg 2003 Aug;9(4):226-32

Department of Cardiovascular Surgery, Tsukuba Medical Center Hospital, Ibaraki, Japan.

Objective: Although deep sternal wound infection (DSWI) after cardiac surgery is infrequent, its consequences are serious. The purposes of this study were to define the risk factors, and to establish the best surgical treatment for DSWI.

Methods: Retrospective analysis for 863 patients who underwent cardiac surgery was performed. The patients were divided into the DSWI group (n=17) and the non-infection group (n=846). Preoperative, perioperative, and postoperative variables were compared between the two groups using univariate and multivariate logistic regression analysis. The modality of treatment for DSWI was also analyzed.

Results: The incidence of DSWI was 1.97%. Independent predictors for DSWI were concomitant coronary artery bypass grafting (CABG) with valve or aortic surgery [odds ratio, 4.1; 95% confidence interval, (1.1, 15.1)] and postoperative use of intraaortic balloon pumping [4.4, (1.6, 12.3)]. An independent predictor in isolated CABG patients was emergency operation [10.9, (2.7, 44.7)]. Four of 17 patients died. Methicillin-resistant Staphylococcus aureus (MRSA) was cultured from 10 (58.8%) patients, and all four of the deceased subjects died of its infection. Seventeen patients were treated by debridement, primary closure, and the addition of an omentum or muscle flap if necessary.

Conclusions: Patients in poor perioperative condition are at high risk for the development of this infection. It was difficult to establish the best treatment, owing to the small series of this study. Mortality and morbidity of DSWI due to MRSA was high.
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August 2003

Cerebral embolism in off-pump coronary artery bypass grafting.

Circ J 2002 Aug;66(8):777-8

Department of Cardiovascular Surgery, Tsukuba Medical Center Hospital, Japan.

A 64-year-old woman with a history of cerebral infarction from chronic occlusion of the middle cerebral artery presented with acute myocardial infarction. Double, off-pump coronary artery bypass grafting could not prevent stroke caused by atheroembolism from the ascending aorta. The risk of stroke from atheroembolism should be taken into consideration when planning coronary artery bypass grafting.
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http://dx.doi.org/10.1253/circj.66.777DOI Listing
August 2002

Regulation of GTP-binding protein alpha q (Galpha q) signaling by the ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50).

J Biol Chem 2002 Oct 21;277(43):40751-9. Epub 2002 Aug 21.

Service de Rhumatologie, Faculté de Médecine and Centre de Recherche Clinique-CHUS, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada.

Although ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a PDZ domain-containing protein known to bind to various channels, receptors, cytoskeletal elements, and cytoplasmic proteins, there is still very little evidence for a role of EBP50 in the regulation of receptor signal transduction. In this report, we show that EBP50 inhibits the phospholipase C (PLC)-beta-mediated inositol phosphate production of a Galpha(q)-coupled receptor as well as PLC-beta activation by the constitutively active Galpha(q)-R183C mutant. Coimmunoprecipitation experiments revealed that EBP50 interacts with Galpha(q) and to a greater extent with Galpha(q)-R183C. Agonist stimulation of the thromboxane A(2) receptor (TP receptor) resulted in an increased interaction between EBP50 and Galpha(q), suggesting that EBP50 preferentially interacts with activated Galpha(q). We also demonstrate that EBP50 inhibits Galpha(q) signaling by preventing the interaction between Galpha(q) and the TP receptor and between activated Galpha(q) and PLC-beta1. Investigation of the EBP50 regions involved in Galpha(q) binding indicated that its two PDZ domains are responsible for this interaction. This study constitutes the first demonstration of an interaction between a G protein alpha subunit and another protein through a PDZ domain, with broad implications in the regulation of diverse physiological systems.
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http://dx.doi.org/10.1074/jbc.M207910200DOI Listing
October 2002

A critical interplay between Ca2+ inhibition and activation by Mg2+ of AC5 revealed by mutants and chimeric constructs.

J Biol Chem 2002 Sep 13;277(36):33139-47. Epub 2002 Jun 13.

Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.

Adenylyl cyclase type 5 (AC5) is sensitive to both high and low affinity inhibition by Ca(2+). This property provides a sensitive feedback mechanism of the Ca(2+) entry that is potentiated by cAMP in sources where AC5 is commonly expressed (e.g. myocardium). Remarkably little is known about the molecular mechanism whereby Ca(2+) inhibits AC5. Because previous studies had showed that Ca(2+) antagonized the activation of adenylyl cyclase brought about by Mg(2+), we have now evaluated the Mg(2+)-binding domain in the catalytic site as the potential site of the interaction, using a number of mutations of AC5 with impaired Mg(2+) activation. Mg(2+) activation exerted contrasting effects on the high and low affinity Ca(2+) inhibition. In both wild type and mutants, activation by Mg(2+) decreased the absolute amount of high affinity inhibition without affecting the K(i) value, whereas the K(i) value for low affinity inhibition was decreased. These effects were directly proportional to the sensitivity of the mutants to Mg(2+). Parallel changes were noted in the efficacies of Ca(2+), Sr(2+), and Ba(2+) in the mutant species, suggesting a simple mutation in a shared domain. Strikingly, forskolin, which activates by a mechanism different from Mg(2+), did not modify inhibition by Ca(2+). Deletion of the N terminus and the C1b domain of AC5 and a chimera formed with AC2 confirmed that the catalytic domain alone was responsible for high affinity inhibition. We therefore conclude that both low and high affinity inhibition by Ca(2+) are exerted on different conformations of the Mg(2+)-binding sites in the catalytic domain of AC5.
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http://dx.doi.org/10.1074/jbc.M112373200DOI Listing
September 2002

Cystic tumor of the atrioventricular nodal region.

Jpn J Thorac Cardiovasc Surg 2002 Jan;50(1):37-9

Department of Cardiovascular Surgery, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki 317-0077, Japan.

We report a case of a 66-year-old female who presented exertional dyspnea and palpitation. Echocardiography, transesophageal echocardiography and computed tomography showed a right atrial cystic mass attached to the interatrial septum. The patient underwent successful excision of the mass. The histopathological findings confirmed the lesion as a cystic tumor of the atrioventricular nodal region. This is the third known case of this condition diagnosed antemortem and treated successfully with surgical excision.
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http://dx.doi.org/10.1007/BF02913485DOI Listing
January 2002
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