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2.
Article in English | MEDLINE | ID: mdl-38082640

ABSTRACT

To achieve good treatment outcomes in coil embolization for cerebral aneurysms, it is important to select an appropriate 1st coil for each aneurysm since it serves as a frame to support the subsequent coils to be deployed. However, its selection as appropriate size and length from a wide variety of lineups is not easy, especially for inexperienced neurosurgeons. We developed a machine learning model (MLM) to predict the optimal size and length of the 1st coil by learning information on patients and aneurysms that were previously treated with coil embolization successfully. The accuracy rates of the MLM for the test data were 86.3% and 83.4% in the prediction of size and length, respectively. In addition, the accuracy rates for the 30 cases showed good prediction by the MLM when compared with two different skilled neurosurgeons. Although the accuracy rate of the well-experienced neurosurgeon is similar to MLM, the inexperienced neurosurgeon showed a worse rate and can benefit from the method.Clinical Relevance- The developed MLM has the potential to assist in the selection of the 1st coil for aneurysms. A technically and cost efficient supply chain in the treatment of aneurysms may also be achieved by MLM application.


Subject(s)
Embolization, Therapeutic , Intracranial Aneurysm , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/therapy , Embolization, Therapeutic/adverse effects , Treatment Outcome , Blood Vessel Prosthesis
3.
Langenbecks Arch Surg ; 407(7): 3113-3122, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35906300

ABSTRACT

INTRODUCTION: SyngoDynaPBVNeuro® is a tool to perform cerebral blood volume (CBV) measurements intraoperatively by functional imaging producing CT-like images. Aim of this prospective study was to analyze the clinical relevance and benefit of CBV measurement with regard to neurological complications like cerebral hyperfusion syndrome (CHS). METHODS: Forty-five patients undergoing endarterectomy (CEA) of the internal carotid artery were included; functional imaging with CBV measurement was performed before and after CEA. To evaluate and analyze CBV, six regions of interest (ROI) were identified for all patients with an additional ROI in patients with symptomatic ICA stenosis and previous stroke. The primary endpoint of the study was a perioperative change in CBV measurements. Secondary outcomes were incidence of stroke, TIA, CHS, and perioperative morbidity and mortality. RESULTS: Thirty-day stroke incidence and thirty-day mortality were 0%. Thirty-day morbidity was 6.7%. Two patients from the asymptomatic group suffered from transient neurological symptoms without signs of intracerebral infarction in CT or MR scan, meeting diagnostic criteria for CHS. In 83.3% of ROIs in these patients, an increase of blood volume was detected. Overall, 26.7% patients suffered from unilateral headache as expression of potential CHS. A total of 69.4% of ROIs in patients with postoperative unilateral headache showed an increase when comparing pre- and postoperative CBV measurements. CONCLUSION: The results show that increased CBV measured by functional imaging is a possible surrogate marker of neurological complications like CHS after CEA. By using intraoperative CBV measurement, the risk of CHS can be estimated early and appropriate therapeutic measures can be applied.


Subject(s)
Carotid Stenosis , Endarterectomy, Carotid , Stroke , Humans , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/surgery , Endarterectomy, Carotid/adverse effects , Headache , Prospective Studies , Syndrome
4.
J Neuroradiol ; 48(4): 311-315, 2021 Jun.
Article in English | MEDLINE | ID: mdl-31563590

ABSTRACT

BACKGROUND AND PURPOSE: Precise vessel measurement plays a major role in size selection of stents used for the treatment of intracranial aneurysms and became even more critical after the introduction of flow diverter stents. We assessed agreement between intracranial vessel diameters of aneurysm patients measured on 2D digital subtraction (2D DSA) and 3D volume rendering digital subtraction angiography (3D DSA) images using an automatic windowing algorithm. MATERIALS AND METHODS: Ten patients with intracranial aneurysms were enrolled and 120 measurement points were selected on both 2D and 3D DSA images acquired by a biplane angiographic system. Automatic windowing was applied to the 3D DSA images. Inter-method agreement of vessel measurements on 2D and 3D DSA images was assessed by Bland Altman plots and intraclass correlation coefficients (ICC). Inter- and intra-rater agreement of measurements on 3D DSA images were assessed by ICCs. RESULTS: The mean differences between measurements on 2D and 3D DSA images were 0.14mm for the ICA, and 0.18mm for the ACA and MCA, which is about the size of one 3D DSA image voxel. For ICA measurements, inter-method, inter-rater and intra-rater agreements were good or excellent (consistency and absolute ICC≥0.95). For ACA and MCA measurements, the inter-method, inter-rater and intra-rater agreements were also good or excellent (consistency ICC=0.94, 0.89 and 0.93, absolute ICC=0.83, 0.84 and 0.85 respectively). CONCLUSIONS: Vessel diameters may be measured on 3D DSA images with sufficient reliability for clinical use when applying an automatic windowing algorithm.


Subject(s)
Intracranial Aneurysm , Algorithms , Angiography, Digital Subtraction , Cerebral Angiography , Humans , Imaging, Three-Dimensional , Intracranial Aneurysm/diagnostic imaging , Reproducibility of Results
5.
AJNR Am J Neuroradiol ; 42(2): 306-312, 2021 01.
Article in English | MEDLINE | ID: mdl-33361373

ABSTRACT

BACKGROUND AND PURPOSE: Obtaining information on invisible vasculature distal to the occlusion site helps to deploy a stent retriever safely during mechanical thrombectomy for large-vessel occlusion. It is essential to reduce the amount of contrast used for detecting the vessels distal to the occlusion site because acute ischemic stroke patients tend to have chronic kidney disease and patients with severe chronic kidney disease are at an increased risk of contrast-associated acute kidney injury. We assessed whether vessels distal to the occlusion site during acute ischemic stroke with large-vessel occlusion could be visualized on angiographic images using flat panel detector CT acquired following intra-arterial diluted contrast injection, compared with MRA findings. MATERIALS AND METHODS: Between May 2019 and January 2020, we enrolled 28 consecutive patients with large-vessel occlusions of the anterior circulation eligible for mechanical thrombectomy following MR imaging. The patients underwent CBV imaging using flat panel detector CT with an intra-arterial diluted contrast injection instead of intravenous injection. Flat panel detector CT angiographic images reconstructed from the same dataset were evaluated for image quality, collateral status of the MCA territory, and visualization of the vessels distal to the occlusion site. These findings were compared with MRA findings. RESULTS: Twenty-two patients were retrospectively examined. Flat panel detector CT angiographic image quality in 20 patients (91%) was excellent or good. The distal portion of the occluded vessel segment was visualized in 14 patients (70%), while the proximal portion of the segment adjacent to the occluded vessel in 3 (15%) was visualized. No visualization was observed in only 1 patient (5%) with no collateral supply. Flat panel detector CT angiographic images were shown to evaluate vessels distal to the occlusion site more accurately than MRA. CONCLUSIONS: In acute ischemic stroke with large-vessel occlusion, flat panel detector CT angiographic images could successfully visualize vessels distal to the occlusion site with a small amount of contrast material.


Subject(s)
Cerebral Angiography/methods , Computed Tomography Angiography/methods , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/surgery , Thrombectomy/methods , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Surgery, Computer-Assisted/methods
6.
AJNR Am J Neuroradiol ; 41(2): 286-292, 2020 02.
Article in English | MEDLINE | ID: mdl-32001447

ABSTRACT

BACKGROUND AND PURPOSE: Delayed leukoencephalopathy is a rare complication that occurs after endovascular coiling of cerebral aneurysms. We aimed to describe a clinical picture of delayed leukoencephalopathy and explore potential associations with procedural characteristics. MATERIALS AND METHODS: We considered endovascular coiling procedures for cerebral aneurysms performed between January 2006 and December 2017 in our institution with follow-up MRIs. We used logistic regression models to estimate the ORs of delayed leukoencephalopathy for each procedural characteristic. RESULTS: We reviewed 1754 endovascular coiling procedures of 1594 aneurysms. Sixteen of 1722 (0.9%) procedures demonstrated delayed leukoencephalopathy on follow-up FLAIR MR imaging examinations after a median period of 71.5 days (interquartile range, 30-101 days) in the form of high-signal changes in the white matter at locations remote from the coil mass. Seven patients had headaches or hemiparesis, and 9 patients were asymptomatic. All imaging-associated changes improved subsequently. We found indications suggesting an association between delayed leukoencephalopathy and the number of microcatheters used per procedure (P = .009), along with indications suggesting that these procedures required larger median volumes of contrast medium (225 versus 175 mL, OR = 5.5, P = .008) as well as a longer median fluoroscopy duration (123.6 versus 99.3 minutes, OR = 3.0, P = .06). Our data did not suggest that delayed leukoencephalopathy was associated with the number of coils (P = .57), microguidewires (P = .35), and guiding systems (P = .57). CONCLUSIONS: Delayed leukoencephalopathy after coiling of cerebral aneurysms may have multiple etiologies such as foreign body emboli, contrast-induced encephalopathy, or hypersensitivity reaction to foreign bodies.


Subject(s)
Endovascular Procedures/adverse effects , Endovascular Procedures/methods , Intracranial Aneurysm/surgery , Leukoencephalopathies/etiology , Postoperative Complications/etiology , Adult , Aged , Endovascular Procedures/instrumentation , Female , Humans , Incidence , Leukoencephalopathies/epidemiology , Male , Middle Aged , Postoperative Complications/epidemiology , Stents , Treatment Outcome
7.
Neuropathol Appl Neurobiol ; 46(4): 344-358, 2020 06.
Article in English | MEDLINE | ID: mdl-31600825

ABSTRACT

AIMS: Globular glial tauopathy (GGT) is a new category within the 4-repeat tauopathies that is characterised neuropathologically by tau-positive globular glial inclusions (GGIs), namely, globular oligodendrocytic and astrocytic inclusions (GOIs and GAIs). Occurrence of tau-positive neuronal cytoplasmic inclusions (NCIs) is also a feature. GGT is classified into three pathological subtypes (Types I, II and III). We studied the tau pathology in 6 cases of GGT (Type II, n = 3; Type III, n = 3), with special reference to GAIs and NCIs. METHODS: Neuropathological examinations were conducted, along with immunohistochemistry, morphometry and three-dimensional imaging, and biochemical and genetic analysis of tau. RESULTS: The cortical GAIs in Type II and those in Type III were distinguishable from each other. In the motor cortex, GAIs were much more numerous in Type III than in Type II. Prominent occurrence of perikaryal globular structures was a feature of GAIs in Type III. By contrast, prominent occurrence of radiating process-like structures was a feature of GAIs in Type II. Overall, the GAIs were significantly smaller in Type III than in Type II. NCIs were divisible into three subgroups in terms of shape: diffuse granular, thick cord-like, and round/horseshoe-shaped structures. In all cases, NCIs were a feature of the upper and lower motor neurons. Interestingly, the round/horseshoe-shaped NCIs were observed only in Type III cases. CONCLUSIONS: These findings, which characterised GAIs and NCIs, indicated that Type II and Type III constitute two distinct pathological subtypes, and also further strengthen the concept of GGT as a distinct entity.


Subject(s)
Brain/pathology , Neuroglia/pathology , Neurons/pathology , Tauopathies/pathology , Aged , Aged, 80 and over , Female , Humans , Inclusion Bodies/pathology , Male
8.
Colorectal Dis ; 20(11): 1041-1046, 2018 11.
Article in English | MEDLINE | ID: mdl-29877028

ABSTRACT

AIM: Surgery for colorectal cancer located in the splenic flexure is difficult to perform because of the complex anatomy. Recently, in addition to the middle colic artery and left colic artery (LCA), the accessory middle colic artery (AMCA) has been recognized as a feeding artery for the left-sided colon. This study aimed to evaluate the vascular anatomy of the splenic flexure focusing on the AMCA in a large number of patients. METHOD: A total of 734 patients who underwent CT before surgery for colorectal cancer were enrolled. We retrospectively evaluated the vascular anatomy using both two- and three-dimensional CT angiography. RESULTS: The AMCA existed in 36.4% of the cases (n = 267). In many cases, it originated from the superior mesenteric artery (n = 228, 85.4%). The AMCA had a common trunk with the transverse pancreatic artery in 54 patients (20.2%). The frequency of the presence of the AMCA was associated with the branching pattern of the LCA, and was more frequent when the LCA was absent (P < 0.001). CONCLUSION: The presence of the AMCA is not rare and the AMCA has some branching patterns; therefore, recognizing it preoperatively and intra-operatively is important, being especially careful when the LCA is absent.


Subject(s)
Colon, Transverse/blood supply , Colon/blood supply , Colorectal Neoplasms/diagnostic imaging , Mesenteric Artery, Superior/anatomy & histology , Adult , Aged , Aged, 80 and over , Colon/diagnostic imaging , Colon/surgery , Colon, Transverse/diagnostic imaging , Colorectal Neoplasms/surgery , Computed Tomography Angiography , Female , Humans , Imaging, Three-Dimensional , Male , Mesenteric Artery, Superior/diagnostic imaging , Mesenteric Artery, Superior/surgery , Middle Aged , Retrospective Studies , Young Adult
9.
AJNR Am J Neuroradiol ; 39(3): 524-531, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29371253

ABSTRACT

BACKGROUND AND PURPOSE: Dual-energy CT can distinguish iodine-enhanced tumors from nonossified cartilage and has been investigated for evaluating cartilage invasion in patients with laryngeal and hypopharyngeal squamous cell carcinomas. In this study, we compared the diagnostic accuracy of MR imaging and of a combination of weighted-average and iodine overlay dual-energy CT images in detecting cartilage invasion by laryngeal and hypopharyngeal squamous cell carcinomas, in particular thyroid cartilage invasion. MATERIALS AND METHODS: Fifty-five consecutive patients who underwent 3T MR imaging and 128-slice dual-energy CT for preoperative initial staging of laryngeal or hypopharyngeal squamous cell carcinomas were included. Two blinded observers evaluated laryngeal cartilage invasion on MR imaging and dual-energy CT using a combination of weighted-average and iodine-overlay images. Pathologic findings of surgically resected specimens were used as the reference standard for evaluating sensitivity, specificity, and the areas under the receiver operating characteristic curve of both modalities for cartilage invasion by each type of cartilage and for all cartilages together. Sensitivity and specificity were compared using the McNemar test and generalized linear mixed models. RESULTS: Dual-energy CT showed higher specificity than MR imaging for diagnosing all cartilage together (84% for MR imaging versus 98% for dual-energy CT, P < .004) and for thyroid cartilage (64% versus 100%, P < .001), with a similar average area under the curve (0.94 versus 0.95, P = .70). The sensitivity did not differ significantly for all cartilages together (97% versus 81%, P = .16) and for thyroid cartilage (100% versus 89%, P = .50), though there was a trend toward increased sensitivity with MR imaging. CONCLUSIONS: Dual-energy CT showed higher specificity and acceptable sensitivity in diagnosing laryngeal cartilage invasion compared with MR imaging.


Subject(s)
Hypopharyngeal Neoplasms/diagnostic imaging , Laryngeal Neoplasms/diagnostic imaging , Magnetic Resonance Imaging/methods , Neoplasm Metastasis/diagnostic imaging , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Hypopharyngeal Neoplasms/pathology , Laryngeal Cartilages/diagnostic imaging , Laryngeal Cartilages/pathology , Laryngeal Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis/pathology , ROC Curve , Sensitivity and Specificity , Squamous Cell Carcinoma of Head and Neck/pathology , Thyroid Cartilage/diagnostic imaging , Thyroid Cartilage/pathology
11.
Phys Rev E ; 95(5-1): 053208, 2017 May.
Article in English | MEDLINE | ID: mdl-28618605

ABSTRACT

Time-resolved measurements of the ionization states of warm dense aluminum via K-shell absorption spectroscopy are demonstrated using betatron radiation generated from laser wakefield acceleration as a probe. The warm dense aluminum is generated by irradiating a free-standing nanofoil with a femtosecond optical laser pulse and was heated to an electron temperature of ∼20-25 eV at a close-to-solid mass density. Absorption dips in the transmitted x-ray spectrum due to the Al^{4+} and Al^{5+} ions are clearly seen during the experiments. The measured absorption spectra are compared to simulations with various ionization potential depression models, including the commonly used Stewart-Pyatt model and an alternative modified Ecker-Kröll model. The observed absorption spectra are in approximate agreement with these models, though indicating a slightly higher state of ionization and closer agreement for simulations with the modified Ecker-Kröll model.

12.
Genet Mol Res ; 16(1)2017 Mar 08.
Article in English | MEDLINE | ID: mdl-28290618

ABSTRACT

In vitro studies have shown that multidrug resistance protein 1 (MDR1) has an affinity for cortisol; however, in vivo association studies on the relationship between MDR1 gene polymorphisms and blood cortisol levels have produced inconsistent results. Therefore, we examined the effects of the C3435T polymorphism of the MDR1 gene on blood levels of hypothalamus-pituitary-adrenal (HPA) axis hormones such as cortisol and adrenocorticotropic hormone (ACTH) in healthy subjects. The subjects comprised 30 healthy Japanese males. Ten subjects were recruited for each of the C3435T MDR1 genotypes: C/C, C/T, and T/T. Blood samples were taken at 6:00 pm on two occasions with an interval of 2 weeks. Blood levels of cortisol and ACTH were determined by an electrochemiluminescence immunoassay. There were no significant differences in the blood levels of the HPA axis hormones among the MDR1 genotypes. The present study suggests that the C3435T MDR1 polymorphism does not affect blood levels of HPA axis hormones in healthy Japanese males.


Subject(s)
Hypothalamo-Hypophyseal System/metabolism , Pituitary-Adrenal System/metabolism , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Adrenocorticotropic Hormone/blood , Adult , Alleles , Gene Frequency , Genotype , Healthy Volunteers , Humans , Hydrocortisone/blood , Japan , Male , Polymorphism, Single Nucleotide
13.
Epidemiol Infect ; 145(3): 462-470, 2017 02.
Article in English | MEDLINE | ID: mdl-27788693

ABSTRACT

Climate change, by its influence on the ecology of vectors might affect the occurrence of vector-borne diseases. This study examines the effects of meteorological factors in Japan on the occurrence of scrub typhus, a mite-borne zoonosis caused by Orientia tsutsugamushi. Using negative binomial regression, we analysed the relationships between meteorological factors (including temperature, rainfall, snowfall) and spring-early summer cases of scrub typhus in Yamagata Prefecture, Japan, during 1984-2014. The average temperature in July and August of the previous year, cumulative rainfall in September of the previous year, snowfall throughout the winter, and maximum depth of snow cover in January and February were positively correlated with the number of scrub typhus cases. By contrast, cumulative rainfall in July of the previous year showed a negative relationship to the number of cases. These associations can be explained by the life-cycle of Leptotrombidium pallidum, a predominant vector of spring-early summer cases of scrub typhus in northern Japan. Our findings show that several meteorological factors are useful to estimate the number of scrub typhus cases before the endemic period. They are applicable to establish an early warning system for scrub typhus in northern Japan.


Subject(s)
Disease Vectors , Meteorological Concepts , Orientia tsutsugamushi/isolation & purification , Scrub Typhus/epidemiology , Trombiculidae/growth & development , Animals , Female , Japan/epidemiology , Male , Retrospective Studies
14.
Colorectal Dis ; 18(8): O278-82, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27354363

ABSTRACT

AIM: Ulcerative colitis (UC) is considered to be a disease of continuous mucosal inflammation extending proximally from the rectum. However, appendiceal orifice inflammation (AOI) is a skip lesion with segments of continuous involvement from the rectum. The aim of this study was to examine the clinical characteristics and clinical course, particularly focused on proximal extension, of UC in patients with AOI. METHOD: A retrospective evaluation of patients with UC who underwent total colonoscopy at the Department of Surgical Oncology, The University of Tokyo, from 2004 to 2014. The degree of AOI was graded endoscopically as follows: 0 (no inflammation); 1 (slight oedema); 2 (moderate inflammation); and 3 (marked inflammation). A total of 189 patient records were reviewed retrospectively. The presence of AOI was analysed with regard to the clinical information of each patient, and its association with proximal extension of proctitis or left-sided colitis was evaluated. RESULTS: Of 189 patients with UC who underwent total colonoscopy at our institution, 92 were diagnosed with pancolitis, 50 with left-sided colitis and 47 with proctitis. Endoscopic findings of AOI were observed in 26 patients, including 11 (12.0%) with pancolitis, six (12.0%) with left-sided colitis and nine (19.1%) with proctitis. During follow up, proximal extension of the disease occurred in all nine patients with proctitis AOI. CONCLUSION: AOI is more frequently observed in patients with proctitis. Our results showed correlations between AOI and subsequent proximal extension of mucosal inflammation in patients with proctitis.


Subject(s)
Appendicitis/pathology , Colitis, Ulcerative/pathology , Colon/pathology , Colonoscopy , Proctitis/pathology , Rectum/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Appendix/pathology , Child , Colon, Descending/pathology , Colon, Sigmoid/pathology , Female , Humans , Inflammation , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Young Adult
15.
Mucosal Immunol ; 9(3): 659-68, 2016 05.
Article in English | MEDLINE | ID: mdl-26349656

ABSTRACT

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce cytokines, including tumor necrosis factor-α and interleukins (ILs), in the small intestine via a Toll-like receptor 4 (TLR4)-dependent pathway, leading to intestinal ulceration. Activation of the inflammasome promotes pro-caspase-1 cleavage, leading to pro-IL-1ß maturation. We examined the role of NLRP3 inflammasome in NSAID-induced enteropathy. Small intestinal damage developed 3 h after indomethacin administration, accompanied by increases in IL-1ß and NLRP3 mRNA expression and mature caspase-1 and IL-1ß levels. In vivo blocking of IL-1ß using neutralizing antibodies attenuated indomethacin-induced damage, whereas exogenous IL-1ß aggravated it. NLRP3(-/-) and caspase-1(-/-) mice exhibited resistance to the damage with reduction of mature IL-1ß production. This resistance was abolished by exogenous IL-1ß. TLR4 deficiency prevented intestinal damage and inhibited upregulation of NLRP3 and IL-1ß mRNAs and maturation of pro-caspase-1 and pro-IL-1ß, whereas TLR4 activation by its agonists exerted opposite effects. Apyrase, an adenosine triphosphate (ATP) scavenger, or Brilliant Blue G, a purinergic P2X7 receptor antagonist, inhibited the damage as well as caspase-1 activation and IL-1ß processing, despite there being sufficient amounts of pro-IL-1ß and NLRP3. These results suggest that NLRP3 inflammasome-derived IL-1ß plays a crucial role in NSAID-induced enteropathy and that both TLR4- and P2X7-dependent pathways are required for NLRP3 inflammasome activation.


Subject(s)
Caspase 1/metabolism , Inflammasomes/metabolism , Interleukin-1beta/metabolism , Intestine, Small/immunology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Toll-Like Receptor 4/metabolism , Ulcer/immunology , Animals , Anti-Inflammatory Agents, Non-Steroidal , Caspase 1/genetics , Cells, Cultured , Disease Models, Animal , Humans , Indomethacin , Interleukin-1beta/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Receptors, Purinergic P2X7/metabolism , Signal Transduction , Toll-Like Receptor 4/genetics , Ulcer/chemically induced
16.
Acta Physiol (Oxf) ; 213(2): 472-80, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25069823

ABSTRACT

AIM: Eukaryotic elongation factor 2 kinase (eEF2K), also known as calmodulin (CaM)-dependent protein kinase (CaMK) III, is a unique member of CaMK family protein. We have recently found that expression of eEF2K protein increased in mesenteric artery from spontaneously hypertensive rats. As pathogenesis of hypertension is in part regulated by vascular structural remodelling via proliferation and migration of vascular smooth muscle cells (SMCs), we tested the hypothesis that eEF2K controls SMCs proliferation and migration. METHODSAND RESULTS: In rat mesenteric arterial SMCs, an eEF2K inhibitor, A-484954 (10 µm), significantly inhibited platelet-derived growth factor (PDGF)-BB (10 ng mL(-1) )-induced SMCs proliferation as determined by a cell counting and bromodeoxyuridine incorporation assay. PDGF-BB (10 ng mL(-1) )-induced SMCs migration was significantly inhibited by A-484954 (10 µm) as determined by a Boyden chamber assay. A-484954 (10 µm) significantly inhibited PDGF-BB (10 ng mL(-1) )-induced phosphorylation of eEF2K, extracellular signal-regulated kinase (ERK), Akt, p38 and heat-shock protein (HSP) 27 as determined by Western blotting. It was confirmed that a CaM inhibitor, W-7 (50 µm), inhibited PDGF-BB (10 ng mL(-1) )-induced phosphorylation of eEF2K. In an ex vivo mesenteric arterial ring assay, 10% foetal bovine serum-induced SMCs outgrowth was significantly inhibited by A-484954 (10 µm). CONCLUSION: We for the first time revealed that eEF2K mediates PDGF-BB-induced SMCs proliferation and migration through activating ERK, Akt, p38 and HSP27 signals in a CaM-dependent manner. Our results suggest eEF2K as a novel pharmaceutical target for the prevention of hypertensive cardiovascular diseases.


Subject(s)
Cell Movement/drug effects , Cell Proliferation/drug effects , Elongation Factor 2 Kinase/metabolism , Muscle, Smooth, Vascular/drug effects , Myocytes, Smooth Muscle/drug effects , Animals , Cell Movement/physiology , Cell Proliferation/physiology , Cells, Cultured , Elongation Factor 2 Kinase/antagonists & inhibitors , Extracellular Signal-Regulated MAP Kinases/metabolism , HSP27 Heat-Shock Proteins/metabolism , Heat-Shock Proteins , Hypertension/drug therapy , Male , Mitogen-Activated Protein Kinases/drug effects , Molecular Chaperones , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Platelet-Derived Growth Factor/drug effects , Platelet-Derived Growth Factor/metabolism , Rats, Wistar , p38 Mitogen-Activated Protein Kinases/metabolism
17.
Eur Psychiatry ; 30(2): 291-5, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24768472

ABSTRACT

BACKGROUND: It has been shown that certain personality traits are related to mortality and disease morbidity, but the biological mechanism linking them remains unclear. Telomeres are tandem repeat DNA sequences located at the ends of chromosomes, and shorter telomere length is a predictor of mortality and late-life disease morbidity. Thus, it is possible that personality traits influence telomere length. In the present study, we examined the relationship of leukocyte telomere length with personality traits in healthy subjects. SUBJECTS AND METHODS: The subjects were 209 unrelated healthy Japanese who were recruited from medical students at 4th-5th grade. Assessment of personality traits was performed by the Revised NEO Personality Inventory (NEO-PI-R) and the Temperament and Character Inventory (TCI). Leukocyte relative telomere length was determined by a quantitative real-time PCR method for a ratio of telomere/single copy gene. RESULTS: In the stepwise multiple regression analysis, shorter telomere length was related to lower scores of neuroticism (P<0.01) and conscientiousness (P<0.05) of the NEO-PI-R, and lower scores of harm avoidance (P<0.05) and reward dependence (P<0.05) of the TCI. CONCLUSIONS: The present study suggests that leukocyte telomere length is associated with some personality traits, and this association may be implicated in the relationship between personality traits and mortality.


Subject(s)
Asian People/statistics & numerical data , Leukocytes , Personality , Telomere , Adult , Anxiety Disorders , Character , Cooperative Behavior , Extraversion, Psychological , Female , Healthy Volunteers , Humans , Japan , Male , Mortality , Neuroticism , Personality/genetics , Personality Inventory , Reward , Self Efficacy , Temperament
18.
J Periodontal Res ; 50(2): 265-73, 2015 Apr.
Article in English | MEDLINE | ID: mdl-24966062

ABSTRACT

BACKGROUND AND OBJECTIVE: Beta-tricalcium phosphate (ß-TCP), a bio-absorbable ceramic, facilitates bone conductivity. We constructed a highly porous three-dimensional scaffold, using ß-TCP, for bone tissue engineering and coated it with co-poly lactic acid/glycolic acid (PLGA) to improve the mechanical strength and biological performance. The aim of this study was to examine the effect of implantation of the PLGA/ß-TCP scaffold loaded with fibroblast growth factor-2 (FGF-2) on bone augmentation. MATERIAL AND METHODS: The ß-TCP scaffold was fabricated by the replica method using polyurethane foam, then coated with PLGA. The PLGA/ß-TCP scaffold was characterized by scanning electron miscroscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction, compressive testing, cell culture and a subcutaneous implant test. Subsequently, a bone-forming test was performed using 52 rats. The ß-TCP scaffold, PLGA-coated scaffold, and ß-TCP and PLGA-coated scaffolds loaded with FGF-2, were implanted into rat cranial bone. Histological observations were made at 10 and 35 d postsurgery. RESULTS: SEM and TEM observations showed a thin PLGA layer on the ß-TCP particles after coating. High porosity (> 90%) of the scaffold was exhibited after PLGA coating, and the compressive strength of the PLGA/ß-TCP scaffold was six-fold greater than that of the noncoated scaffold. Good biocompatibility of the PLGA/ß-TCP scaffold was found in the culture and implant tests. Histological samples obtained following implantation of PLGA/ß-TCP scaffold loaded with FGF-2 showed significant bone augmentation. CONCLUSION: The PLGA coating improved the mechanical strength of ß-TCP scaffolds while maintaining high porosity and tissue compatibility. PLGA/ß-TCP scaffolds, in combination with FGF-2, are bioeffective for bone augmentation.


Subject(s)
Biocompatible Materials/chemistry , Calcium Phosphates/chemistry , Fibroblast Growth Factor 2/therapeutic use , Lactic Acid/chemistry , Osteogenesis/drug effects , Polyglycolic Acid/chemistry , Tissue Scaffolds/chemistry , 3T3 Cells , Animals , Fibroblast Growth Factor 2/administration & dosage , Male , Mice , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Osteoblasts/physiology , Osteogenesis/physiology , Polylactic Acid-Polyglycolic Acid Copolymer , Porosity , Rats , Rats, Wistar , Skull/pathology , Skull/surgery , Stress, Mechanical , Subcutaneous Tissue/pathology , Time Factors , Tissue Engineering/methods , X-Ray Diffraction
20.
Neuroscience ; 263: 148-58, 2014 Mar 28.
Article in English | MEDLINE | ID: mdl-24444827

ABSTRACT

Neonatal stroke occurs in approximately 1/4000 live births and results in life-long neurological impairments: e.g., cerebral palsy. Currently, there is no evidence-based specific treatment for neonates with stroke. Several studies have reported the benefits of umbilical cord blood (UCB) cell treatment in rodent models of neonatal brain injury. However, all of the studies examined the effects of administering either the UCB mononuclear cell fraction or UCB-derived mesenchymal stem cells in neonatal rat models. The objective of this study was to examine the effects of human UCB CD34(+) cells (hematopoietic stem cell/endothelial progenitor cells) in a mouse model of neonatal stroke, which we recently developed. On postnatal day 12, immunocompromized (SCID) mice underwent permanent occlusion of the left middle cerebral artery (MCAO). Forty-eight hours after MCAO, human UCB CD34(+) cells (1×10(5)cells) were injected intravenously into the mice. The area in which cerebral blood flow (CBF) was maintained was temporarily larger in the cell-treated group than in the phosphate-buffered saline (PBS)-treated group at 24h after treatment. With cell treatment, the percent loss of ipsilateral hemispheric volume was significantly ameliorated (21.5±1.9%) compared with the PBS group (25.6±5.1%) when assessed at 7weeks after MCAO. The cell-treated group did not exhibit significant differences from the PBS group in either rotarod (238±46s in the sham-surgery group, 175±49s in the PBS group, 203±54s in the cell-treated group) or open-field tests. The intravenous administration of human UCB CD34(+) cells modestly reduced histological ischemic brain damage after neonatal stroke in mice, with a transient augmentation of CBF in the peri-infarct area.


Subject(s)
Antigens, CD34/metabolism , Cord Blood Stem Cell Transplantation , Stroke/therapy , Administration, Intravenous , Animals , Animals, Newborn , Cerebral Cortex/blood supply , Cerebral Cortex/pathology , Disease Models, Animal , Female , Humans , Male , Mice , Rotarod Performance Test
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