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Noriaki Tsukie,
Kaku Nakano,
Tetsuya Matoba,
Seigo Masuda,
Eiko Iwata,
Miho Miyagawa,
Gang Zhao,
Wei Meng, Junji Kishimoto,
Kenji Sunagawa,
Kensuke Egashira
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ABSTRACT: Aim: The use of currently marketed drug-eluting stents presents safety concerns including increased late thrombosis, which is thought to result mainly from delayed endothelial healing effects (impaired re-endothelialization resulting in abnormal inflammation and fibrin deposition). We recently developed a bioabsorbable polymeric nanoparticle (NP)-eluting stent using a novel cationic electrodeposition technology. Statins are known to inhibit the proliferation of vascular smooth muscle cells (VSMC) and to promote vascular healing. We therefore hypothesized that statin-incorporated NP-eluting stents would attenuate in-stent stenosis without delayed endothelial healing effects.Methods: Among six marketed statins, pitavastatin (Pitava) was found to have the most potent effects on VSMC proliferation and endothelial regeneration in vitro. We thus formulated a Pitava-NP-eluting stent (20µg Pitava per stent).Results: In a pig coronary artery model, Pitava-NP-eluting stents attenuated in-stent stenosis as effectively as polymer-coated sirolimus-eluting stents (SES). At SES sites, delayed endothelial healing effects were noted, whereas no such effects were observed in Pitava-NP-eluting stent sites.Conclusion: Pitava-NP-eluting stents attenuated in-stent stenosis as effectively as SES without the delayed endothelial healing effects of SES in a porcine coronary artery model. This nanotechnology platform could be developed into a safer and more effective device in the future.
Journal of atherosclerosis and thrombosis 09/2012; · 2.69 Impact Factor
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ABSTRACT: Object The authors undertook this study to investigate the incidence, cause, and clinical influence of short circuits in patients treated with deep brain stimulation (DBS). Methods After the incidental identification of a short circuit during routine follow-up, the authors initiated a policy at their institution of routinely evaluating both therapeutic impedance and system impendence at every outpatient DBS follow-up visit, irrespective of the presence of symptoms suggesting possible system malfunction. This study represents a report of their findings after 1 year of this policy. Results Implanted DBS leads exhibiting short circuits were identified in 7 patients (8.9% of the patients seen for outpatient follow-up examinations during the 12-month study period). The mean duration from DBS lead implantation to the discovery of the short circuit was 64.7 months. The symptoms revealing short circuits included the wearing off of therapeutic effect, apraxia of eyelid opening, or dysarthria in 6 patients with Parkinson disease (PD), and dystonia deterioration in 1 patient with generalized dystonia. All DBS leads with short circuits had been anchored to the cranium using titanium miniplates. Altering electrode settings resulted in clinical improvement in the 2 PD cases in which patients had specific symptoms of short circuits (2.5%) but not in the other 4 cases. The patient with dystonia underwent repositioning and replacement of a lead because the previous lead was located too anteriorly, but did not experience symptom improvement. Conclusions In contrast to the sudden loss of clinical efficacy of DBS caused by an open circuit, short circuits may arise due to a gradual decrease in impedance, causing the insidious development of neurological symptoms via limited or extended potential fields as well as shortened battery longevity. The incidence of short circuits in DBS may be higher than previously thought, especially in cases in which DBS leads are anchored with miniplates. The circuit impedance of DBS should be routinely checked, even after a long history of DBS therapy, especially in cases of miniplate anchoring.
Journal of Neurosurgery 09/2012; · 2.96 Impact Factor
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ABSTRACT: To determine the age of onset of type 1 diabetes that is most closely related to the subsequent development of a severe eating disorder such as anorexia nervosa (AN) or bulimia nervosa (BN).
Participants were 53 female type 1 diabetes patients with AN or BN referred to our outpatient clinic from the Diabetes Center of Tokyo Women's Medical University. Forty-nine female type 1 diabetes patients who regularly visited the Diabetes Center and had no eating disorder-related problems constituted the 'direct control' group, whereas 941 female patients who for the first time visited the Diabetes Center constituted the 'historical control' group. The kernel function method was used to generate a density estimation of the onset age of each group and the chi-square test was used to compare the distribution.
The control groups had similar density shapes for the onset age of type 1 diabetes, but both differed from the 'eating disorder' group. For onset age 7-18 yr, the density of the 'eating disorder' group was higher than those of the control groups, but for the younger and older onset ages the densities were lower. The 'eating disorder' group developed type 1 diabetes significantly more frequently than the 'historical control' group between 7 and 18 yr of age (χ2 = 9.066, p < 0.011).
The development of type 1 diabetes in preadolescence or adolescence seems to place girls at risk for the subsequent development of AN or BN. Careful attention should be paid to these high-risk patients.
Pediatric Diabetes 06/2011; 12(4 Pt 2):396-401. · 2.16 Impact Factor
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ABSTRACT: GH plays a significant role in the lipid metabolism. In this study, we focused on the JAK2 - signal transducer and activator of the transcription 5 (STAT5) pathway, which transmit the signals from the GH receptor, and selected the STAT5A/B gene as a candidate for the regulation of lipid metabolism in GH deficiency (GHD).
The study population comprised 83 children with idiopathic GHD. The serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and the non-HDL cholesterol (non-HDL-C) levels were monitored before and at 3, 6, 9 and 12 months after starting GH treatment. The height, weight, body mass index, and serum insulin-like growth factor-I (IGF-I) level were also measured before and 12 months after starting the GH treatment. For the genetic analysis of the STAT5A/B gene, five tag SNPs were selected using the tag SNP picker programme on the homepage of the HapMap project. The evaluation of promoter activity of the -44816A/G SNP in the STAT5B gene was performed by a luciferase assay in vitro.
The TC and non-HDL-C levels were gradually decreased during the GH treatment. Five tag SNPs (rs4029774, rs6503691, rs9900213, rs16967637 and rs2272087) were picked up for the STAT5A/B gene, and the genetic study demonstrated that the paediatric GHD patients who were heterozygotes or homozygotes of minor alleles of the analysed SNPs in the same block of the STAT5B gene showed significantly higher serum TC or non-HDL-C levels both before and after GH treatment for 12 months. Most of the SNPs also demonstrated significant differences among genotypes in the decreases in serum TC or non-HDL-C levels during the 12 months of GH treatment. A luciferase assay showed that the -44816A/G SNP (rs4029774) in the STAT5B gene functionally affected the expression level in vitro.
These results indicate that STAT5B may therefore play a role in regulating the cholesterol metabolism in children with GHD.
Clinical Endocrinology 05/2011; 74(5):611-7. · 3.17 Impact Factor
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Daisuke Okamoto,
Kengo Yoshimitsu,
Akihiro Nishie,
Tsuyoshi Tajima,
Yoshiki Asayama,
Kousei Ishigami,
Masakazu Hirakawa,
Yasuhiro Ushijima,
Daisuke Kakihara,
Tomohiro Nakayama,
Yunosuke Nishihara,
Shinichi Aishima,
Akinobu Taketomi, Junji Kishimoto,
Hiroshi Honda
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ABSTRACT: To elucidate the correlation between hypervascular hepatocellular carcinoma (HCC) enhancement patterns on dynamic MR imaging and histological findings.
Surgically proven 46 hypervascular HCCs of forty-one patients were enrolled. For each HCC, the signal intensity in the portal phase (SIPP) was evaluated. In this study, high, iso-, or low intensity in the portal phase was hypothesized as late, moderate, or early washout pattern, respectively. The SIPP of each HCC was correlated to histological grade and architectural subtypes that represent degrees of trabecular structure. For the trabecular HCCs, the thickness of tumor plate was also correlated for indirect estimation of tumor sinusoid.
There was a significant correlation between the SIPP vs. histological grade and also vs. architectural subtypes, namely the degree of trabecular structure. Washout of hypervascular HCC occurred earlier as the histological grade advanced and the histological architecture got closer to pure trabecular HCC. For the trabecular HCCs, the thickness of tumor plate correlated significantly with SIPP or histological grade. Hypervascular HCCs with thicker tumor plates showed worse histological grade and earlier washout pattern.
Histological grade of hypervascular HCC may be predicted using SIPP. The thickness of tumor plate, resultantly the size of sinusoid between tumor plates, can account for the relationship between washout pattern and histological grade in the trabecular HCCs.
European journal of radiology 03/2011; 81(6):1116-21. · 2.65 Impact Factor
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Ling Chen,
Kaku Nakano,
Satoshi Kimura,
Tetsuya Matoba,
Eiko Iwata,
Miho Miyagawa,
Hiroyuki Tsujimoto,
Kazuhiro Nagaoka, Junji Kishimoto,
Kenji Sunagawa,
Kensuke Egashira
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ABSTRACT: Pulmonary artery hypertension (PAH) is an intractable disease of the small PAs in which multiple pathogenic factors are involved. Statins are known to mitigate endothelial injury and inhibit vascular remodeling and inflammation, all of which play crucial roles in the pathogenesis of PAH. We tested the hypothesis that nanoparticle (NP)-mediated delivery of pitavastatin into the lungs can be a novel therapeutic approach for the treatment of PAH. Among the marketed statins, pitavastatin was found to have the most potent effects on proliferation of PA smooth muscle cells in vitro. We formulated pitavastatin-NP and found that pitavastatin-NP was more effective than pitavastatin alone in inhibiting cellular proliferation and inflammation in vitro. In a rat model of monocrotaline-induced PAH, a single intratracheal instillation of NP resulted in the delivery of NP into alveolar macrophages and small PAs for up to 14 days after instillation. Intratracheal treatment with pitavastatin-NP, but not with pitavastatin, attenuated the development of PAH and was associated with a reduction of inflammation and PA remodeling. NP-mediated pitavastatin delivery was more effective than systemic administration of pitavastatin in attenuating the development of PAH. Importantly, treatment with pitavastatin-NP 3 weeks after monocrotaline injection induced regression of PAH and improved survival rate. This mode of NP-mediated pitavastatin delivery into the lungs is effective in attenuating the development of PAH and inducing regression of established PAH, suggesting potential clinical significance for developing a new treatment for PAH.
Hypertension 02/2011; 57(2):343-50. · 6.21 Impact Factor
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ABSTRACT: Sessile serrated adenoma (SSA), also referred to as sessile serrated polyp, has been proposed as a precursor lesion to microsatellite unstable carcinoma. However, the mechanism of stepwise progression from SSA to early invasive carcinoma has been unclear. The purpose of this study was to elucidate the histologic characteristics and possible role of p53, β-catenin, BRAF, KRAS, and PIK3CA in the development and progression of SSA. We analyzed 12 cases of SSA with neoplastic progression (SSAN), including 7 cases of intraepithelial high-grade dysplasia (HGD) and 5 cases of submucosal invasive carcinoma, and compared them with 53 SSAs and 66 hyperplastic polyps (HPs) by immunohistochemistry and gene mutation analysis. Histologically, 75% (9 of 12) of SSANs showed tubular or tubulovillous growth patterns rather than serrated ones in the HGD/intramucosal carcinoma component. All 5 SSANs with invasive carcinoma lost their serrated structure and developed increased extracellular mucin in their submucosal carcinoma component, a consistent feature of mucinous adenocarcinoma. Nuclear accumulations of β-catenin and p53 were observed in 50% (6 of 12) and 41.7% (5 of 12) of SSANs, respectively, and were exclusively present in HGD/carcinoma areas. By contrast, neither nuclear β-catenin nor p53 expressions were seen in HPs or SSAs (P<0.0001). BRAF mutations (V600E) were observed in 45.8% (11 of 24) of HPs, 60.9% (14 of 23) of SSAs, and 63.6% (7 of 11) of SSANs, and were equally found in both SSA and carcinoma/HGD areas of the individual SSANs. KRAS exon 1 mutations were uncommon in all 3 groups (4.2%, 4.4%, and 0%, respectively). No mutations of PIK3CA exon 9 or exon 20 were found in any cases that were examined. These findings suggest that BRAF mutations may be associated with the pathogenesis of SSA, but progression to HGD or early invasive carcinoma may be associated with other factors, such as alterations of p53 and β-catenin. In addition, our histologic observations suggest a possible close association between SSAN and mucinous adenocarcinoma.
The American journal of surgical pathology 02/2011; 35(2):295-304. · 4.06 Impact Factor
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ABSTRACT: Dysadherin is a cancer-associated cell membrane glycoprotein that down-regulates E-cadherin and plays important roles in tumor progression and metastasis. Differentiated-type gastric carcinoma can be classified into 2 histologic subtypes according to the presence of poorly differentiated components: a mixed type (differentiated carcinoma with poorly differentiated components) and a pure type (purely differentiated-type adenocarcinoma). We studied the clinicopathologic features of 318 cases of differentiated-type gastric carcinoma with submucosal invasion and evaluated the immunohistochemical expression of dysadherin and E-cadherin. We also evaluated 46 cases of metastatic lymph nodes. Tumors with combined dysadherin-positive (≥50%) expression and E-cadherin-negative (<50%) expression had significantly higher proportions of the moderately differentiated type, deeper submucosal invasion, positivity of lymphatic permeation, and positivity of lymph node metastasis than tumors with other combinations of dysadherin and E-cadherin expression (P = .0009, P = .0015, P = .0273, and P = .0187, respectively). Moreover, the frequency of dysadherin-positive (≥50%) expression was higher in the mixed type (60.3%) than in the pure type (12.4%) (P < .0001), whereas the frequency of E-cadherin-negative (<50%) expression was higher in the mixed type (84.5%) than in the pure type (50.5%) (P < .0001). The frequency of dysadherin expression in the metastatic lymph nodes (80.4%) was significantly higher than that in the primary tumors (45.7%) (P = .001). Dysadherin-positive (≥50%) expression and E-cadherin-negative (<50%) expression may be correlated with the mixed type. Combined dysadherin-positive (≥50%) expression and E-cadherin-negative (<50%) expression may be valuable information for predicting aggressive tumor behavior.
Human pathology 01/2011; 42(4):558-67. · 3.03 Impact Factor
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ABSTRACT: This study was designed to analyze the subcellular localization of E-cadherin and β-catenin both of which play a critical role in cell-cell adhesion in uterine carcinosarcoma (UCS). We performed an immunohistochemical reaction analysis of the subcellular localization of E-cadherin and β-catenin proteins in 46 cases of UCSs consisting of 28 UCSs with heterologous sarcoma and 18 UCSs with homologous sarcoma and compared their clinicopathological features. In most UCSs, membranous expression of E-cadherin and β-catenin was completely lost in sarcomatous components, but it was preserved in carcinomatous components. Nuclear β-catenin expression was observed significantly more frequently in sarcomatous components (31/46, 67.4%) than in carcinomatous components (22/46, 47.8%; P = 0.0025). In sarcomatous components, nuclear β-catenin expression was found significantly more frequently in heterologous sarcoma (23/28, 82.1%) than in homologous sarcoma (8/18, 44.4%; P = 0.0279). The stage was the only independent prognostic significant factor. These results suggest that reduced membranous expression of E-cadherin and β-catenin may contribute to the biphasic morphology of UCS. Furthermore, although the precise mechanism is unclear, nuclear β-catenin expression in sarcomatous components may also be associated with biphasic morphology and heterologous sarcomatous differentiation.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 11/2010; 458(1):85-94. · 2.49 Impact Factor
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ABSTRACT: Sessile serrated adenoma (SSA) has been proposed as a precursor to microsatellite-unstable colorectal carcinoma. However, histological criteria dictating how to differentiate serrated lesions have not been completely established, and a histological overlap exists between SSA and hyperplastic polyps (HPs), particularly the microvesicular type. In this study, based on a critical review of histology, we aimed to elucidate the potential utility of the mucin phenotype in the identification of SSA. We evaluated mucin core protein expression (MUC2, MUC5AC, and MUC6) by immunohistochemical stain in 65 cases of microvesicular-type HPs, 51 SSAs, and 72 traditional serrated adenomas (TSAs). SSAs had clinicopathological and morphological features distinct from those of HPs and TSAs. MUC6 was more frequently positive in SSAs (39%) than in TSAs (4%) and HPs (19%) (P < 0.001 and P = 0.0107, respectively). Right-sided HPs more frequently expressed MUC6 than did left-sided HPs (60% vs. 4%, respectively; P < 0.0001), but SSAs and TSAs showed no regional differences. These findings suggest that determination of mucin core protein expression is insufficient for differentiating SSAs from other types of serrated polyps, and that microvesicular-type HPs of the right colon and SSAs may belong to the same mucin spectrum.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 10/2010; 457(4):443-9. · 2.49 Impact Factor
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Fumiaki Yoshida,
Yasushi Miyagi, Junji Kishimoto,
Takato Morioka,
Nobuya Murakami,
Kimiaki Hashiguchi,
Kazuhiro Samura,
Nobutaka Sakae,
Ryo Yamasaki,
Minako Kawaguchi,
Tomio Sasaki
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ABSTRACT: Among the neuropsychiatric symptoms in Parkinson's disease (PD) patients, hallucination can result from the disease itself or medical treatment. Hallucination associated with subthalamic nucleus stimulation (STN-DBS) has been reported; however, it is still unclear whether PD patients with a history of hallucination are appropriate candidates for STN-DBS or not.
We investigated the effect of STN-DBS on preexisting hallucination associated with advanced PD.
Eighteen STN-DBS patients were investigated retrospectively. The severity of hallucination was assessed by the thought disorder score on the Unified Parkinson's Disease Rating Scale (UPDRS, part 1-item 2) in the patients' interviews; the score 6 months after the initiation of STN-DBS was compared with the highest score throughout the preoperative history and the score 2 weeks before surgery.
Hoehn-Yahr stage and motor score (UPDRS part 3) were significantly improved following STN-DBS. Six months after the initiation of STN-DBS, the severity of hallucination, assessed by thought disorder score, did not increase, but rather decreased compared with the preoperative level (p < 0.05 by McNemar's test). The daily levodopa equivalent dose was increased in 2 patients without the development of hallucination. On the other hand, anti-parkinsonian drugs were totally withdrawn in 1 patient, but without improvement of hallucination.
Our findings indicate that STN-DBS surgery does not always lead to deterioration of preexisting hallucination in PD. In advanced PD, hallucination involves a multifactorial pathogenesis and a history of hallucination is not a contraindication to STN-DBS surgery.
Stereotactic and Functional Neurosurgery 02/2009; 87(1):45-9. · 1.85 Impact Factor
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Tadamasa Yoshitake,
Katsumasa Nakamura,
Yoshiyuki Shioyama,
Satoshi Nomoto,
Saiji Ohga,
Takashi Toba,
Takehiro Shiinoki,
Shigeo Anai,
Hiromi Terashima, Junji Kishimoto,
Hiroshi Honda
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ABSTRACT: The aim of this study was to present the technical aspects of the breath-hold technique with respiratory monitoring and visual feedback and to evaluate the feasibility of this system in healthy volunteers.
To monitor respiration, the vertical position of the fiducial marker placed on the patient's abdomen was tracked by a machine vision system with a charge-coupled device camera. A monocular head-mounted display was used to provide the patient with visual feedback about the breathing trace. Five healthy male volunteers were enrolled in this study. They held their breath at the end-inspiration and the end-expiration phases. They performed five repetitions of the same type of 15-s breath-holds with and without a head-mounted display, respectively. A standard deviation of five mean positions of the fiducial marker during a 15-s breath-hold in each breath-hold type was used as the reproducibility value of breath-hold.
All five volunteers well tolerated the breath-hold maneuver. For the inspiration breath-hold, the standard deviations with and without visual feedback were 1.74 mm and 0.84 mm, respectively (P = 0.20). For the expiration breath-hold, the standard deviations with and without visual feedback were 0.63 mm and 0.96 mm, respectively (P = 0.025).
Our newly developed system might help the patient achieve improved breath-hold reproducibility.
Radiation Medicine 02/2008; 26(1):50-5.
