研究者紹介システム
| 大﨑 博之 |  |
| オオサキ ヒロユキ | |
| 大学院保健学研究科 保健学専攻 | |
| 准教授 | |
| 保健その他 |
研究者情報
所属
【主配置】
大学院保健学研究科 保健学専攻【配置】
医学部 保健学科
学位
授業科目
- 病理学, 医学部 保健学科, 2022
- 症状マネージメント論, 医学部 保健学科, 2022
- 基礎臨床検査学, 医学部 保健学科, 2022
- 病理組織細胞学, 医学部 保健学科, 2022
- 検査管理総論, 医学部 保健学科, 2022
- 臨床検査概論, 医学部 保健学科, 2022
- 保健学初年次セミナー, 医学部 保健学科, 2022
- グローバルヘルスフィールド演習, 医学部 保健学科, 2022
- 病理学Ⅱ, 医学部 保健学科, 2022
- 病理組織細胞学実習I, 医学部 保健学科, 2022
- 検査情報解析学, 医学部 保健学科, 2022
- 検査情報解析学演習, 医学部 保健学科, 2022
- 病理組織細胞学実習II, 医学部 保健学科, 2022
- 基礎臨床検査学実習, 医学部 保健学科, 2022
- 検査統合実習, 医学部 保健学科, 2022
- 検査統合演習, 医学部 保健学科, 2022
- 分析医科学特講I, 大学院保健学研究科 保健学専攻, 2022
- 分析医科学演習I, 大学院保健学研究科 保健学専攻, 2022
- 保健学研究共通特講Ⅱ, 大学院保健学研究科 保健学専攻, 2022
- 分析医科学特講II, 大学院保健学研究科, 2022
- 分析医科学演習II, 大学院保健学研究科, 2022
- 保健学研究共通特講Ⅵ, 大学院保健学研究科, 2022
ジャンル
コメントテーマ
研究ニュース
研究活動
プロフィール情報
プロフィール
取得資格：臨床検査技師，細胞検査士，国際細胞検査士
研究テーマ：臨床細胞学
研究キーワード
研究分野
委員歴
- 2022年06月 - 現在, 日本臨床検査学教育協議会, 科目別分科会（一般検査）会長
- 2022年04月 - 現在, 泌尿器細胞診カンファレンス, 理事
- 2018年06月 - 現在, 兵庫県臨床検査技師会, 理事（組織部長）
- 2017年05月 - 現在, 日本臨床検査学教育協議会, 国際協力委員会委員（副委員長）
- 2017年04月 - 現在, NPO法人 ラオス保健医療・医学協力協会, 理事
- 2017年04月 - 現在, 日本臨床検査学教育学会, 評議員
- 2009年05月 - 現在, The International Academy of Cytology, Cytotechnologist Fellow, The International Academy of Cytology
- 2009年04月 - 現在, 日本臨床細胞学会, 評議員
- 2021年04月 - 2023年03月, 日本臨床検査学教育協議会近畿中国四国部会, 会長
- 2020年04月 - 2021年03月, 日本臨床検査学教育協議会近畿中国四国部会, 幹事
- 2015年04月 - 2021年03月, 泌尿器細胞診カンファレンス, 幹事
- 2009年04月 - 2015年03月, 日本細胞診断学推進協会, 代議員
- 2009年04月 - 2011年03月, 細胞検査士会, 都道府県代表者委員会委員
- 2006年04月 - 2009年03月, 四国臨床検査技師会, 病理細胞診研究班班長
- 2006年04月 - 2008年03月, 日本臨床衛生検査技師会, 精度管理調査部会ワーキンググループ委員
受賞
2023年 Wiley, Top Cited Article 2021-2022 (Cytopathology)
2020年 小島三郎記念技術賞
2017年 European Congress of Pathology Best Poster Award
2011年 日本臨床細胞学会技師賞（学術）
日本国2010年 サクラ病理技術賞
日本国2009年 日本臨床細胞学会, 最優秀論文賞
日本国2007年 香川大学大学院医学系研究科特待生（学業）
論文
In this brief report, we described some uncommon cytomorphological features of malignant mesothelioma (MM) cells in pleural effusions. The tumor cells exhibited abundant cytoplasmic vacuolization, with presence of single or multiple eccentric nuclei in several cells. In the Giemsa-stained smear, we observed a glossy spherical material in some cells, which tested positive in Sudan III stain. In immunocytochemical analysis, tumor cells were positive for calretinin, podoplanin, epithelial membrane antigen, and methylthioadenosine phosphorylase; tumor cells were negative for BRCA1-associated protein 1, CD68, and desmin. The intracytoplasmic vacuoles were positive for adipophilin expression.
2023年12月, Diagnostic cytopathology, 51 (12), E328-E331, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
Abstract Recent studies have shown that D-allose, a rare sugar, elicits antitumor effects on different types of solid cancers, such as hepatocellular carcinoma, non-small-cell lung cancer, and squamous cell carcinoma of the head and neck. In this study, we examined the effects of D-allose on the proliferation of human glioblastoma (GBM) cell lines (i.e., U251MG and U87MG) in vitro and in vivo and the underlying mechanisms. D-allose treatment inhibited the proliferation of U251MG and U87MG cells in a dose-dependent manner (3–50 mM). However, D-allose treatment did not affect cell cycles or apoptosis in these cells but significantly decreased the cell division frequency in both GBM cell lines. In a subcutaneous U87MG cell xenograft model, intraperitoneal injection of D-allose (100 mg/kg/day) significantly reduced the tumor volume in 28 days. These data indicate that D-allose-induced reduction in cell proliferation is associated with a subsequent decrease in the number of cell divisions, independent of cell-cycle arrest and apoptosis. Thus, D-allose could be an attractive additive to therapeutic strategies for GBM.
Springer Science and Business Media LLC, 2023年11月09日, Scientific Reports, 13 (1)[査読有り]
研究論文（学術雑誌）
In most developed countries, cervical cancer screening and human papillomavirus vaccination have reduced cervical cancer incidence. However, the incidence has been increasing in Japan, possibly because of the low screening rate. Although cervical cancer incidence has increased in people in their 20s, the screening rate among 20-24-year-olds in Japan is only 10.2%, meaning that cervical cancer screening rates should be increased among young Japanese women. We conducted a questionnaire survey among students at health sciences universities to determine their knowledge of cervical cancer, screening rates, and barriers to screening. Students taking specialized medical courses were highly knowledgeable; recognition of the facts that "cervical cancer can be prevented through screening" and that "the risk of cervical cancer increases in one's 20s" was significantly high among those who underwent screening. On the other hand, only 7.5% of students used the free coupons provided for screening. Knowledge of cervical cancer improves screening rates. Therefore, educational programs to raise awareness of the importance of cervical cancer screening among non-medical and health sciences university students and young women in general are required.
2023年09月, Nursing & health sciences, 25 (3), 466 - 473, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
OBJECTIVE: The Paris System for Reporting Urinary Cytology considered the nuclear-to-cytoplasmic (N:C) ratio as the most important cytomorphological feature for detecting high-grade urothelial carcinoma (HGUC) cells. Few quantitative studies have been conducted on other features although quantitative studies on the N:C ratio have been reported. Therefore, this study quantitatively analysed important cytomorphological features in distinguishing benign reactive cells from HGUC cells. METHODS: We analysed 2866 cells from the urine of 52 patients. A digital image analyser was used to quantitatively measure the nuclear area, cell area, N:C ratio, and nuclear roundness for HGUC cells and benign reactive cells. Additionally, the diagnostic value of quantitative cytomorphological criteria in HGUC cells was evaluated by the receiver operating characteristic curve. RESULTS: The area under the curve for the prediction of HGUC cells for all cells and the top five cells was in the following order: nuclear area (0.920 and 0.992, respectively), N:C ratio (0.849 and 0.977), cell area (0.781 and 0.920), and nuclear roundness (0.624 and 0.605). The best cutoff value of the N:C ratio to differentiate HGUC cells from benign reactive cells was 0.438, and using the N:C ratio of 0.702, the positive predictive value obtained was 100%. CONCLUSIONS: Our study indicated that nuclear area is a more important cytomorphological criterion than the N:C ratio for HGUC cell detection. Moreover, extracted data of the top five cells were more valuable than the data of all cells, which can be helpful in the routine practice and future criteria definition in urine cytology.
2023年07月, Cytopathology : official journal of the British Society for Clinical Cytology, 34 (4), 295 - 301, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
This study aimed to investigate whether phosphate contributes to the pathogenesis of chronic kidney disease (CKD) in dolphins. Renal necropsy tissue of an aged captive dolphin was analyzed and in vitro experiments using cultured immortalized dolphin proximal tubular (DolKT-1) cells were performed. An older dolphin in captivity died of myocarditis, but its renal function was within the normal range until shortly before death. In renal necropsy tissue, obvious glomerular and tubulointerstitial changes were not observed except for renal infarction resulting from myocarditis. However, a computed tomography scan showed medullary calcification in reniculi. Micro area X-ray diffractometry and infrared absorption spectrometry showed that the calcified areas were primarily composed of hydroxyapatite. In vitro experiments showed that treatment with both phosphate and calciprotein particles (CPPs) resulted in cell viability loss and lactate dehydrogenase release in DolKT-1 cells. However, treatment with magnesium markedly attenuated this cellular injury induced by phosphate, but not by CPPs. Magnesium dose-dependently decreased CPP formation. These data support the hypothesis that continuous exposure to high phosphate contributes to the progression of CKD in captive-aged dolphins. Our data also suggest that phosphate-induced renal injury is mediated by CPP formation in dolphins, and it is attenuated by magnesium administration.
2023年03月29日, Scientific reports, 13 (1), 5161 - 5161, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
BACKGROUND: Competency is used to channel abilities into successful processes and is employed in the medical field. Globally, several laboratory competencies exist, but the job descriptions of Japanese medical laboratory scientists differ from those of other countries and little evidence-based information on novice medical laboratory scientist competency is available in Japan. This study clarified the competencies of novice medical laboratory scientists based on various expert opinions in Japan. METHODS: The Delphi method was used to achieve an expert consensus on novice medical laboratory scientist competencies. We asked the participants to evaluate the importance of each item using the Likert scale and set 70% as the final consensus rate. RESULTS: We obtained 106/400 (26.5%) and 95/106 (89.6%) responses from participants in rounds 1 and 2, respectively. Their professional experience mean ± standard deviation was 32.4 ± 6.0 years (range: 13-41). The average of each category consensus rate was > 99.1%. Ninety-five expert opinions converged and agreed that the competency comprised 8 categories and 54 items. CONCLUSIONS: The survey results revealed that novice medical laboratory scientists were expected to have relatively higher main laboratory skill competencies in the 'Preparation and analysis' category than in other categories. Nevertheless, competencies in other categories required basic skills. In addition, our competencies contained unique competencies compared with others due to their divergent roles and their environment. Further research is warranted to explore assessment tools by developing a competency scale, thereby helping clarify the differences between ability and correlated factors. The unique competencies scale can help assess the efficacy of educational programmes for Japanese medical laboratory scientists.
2022年12月16日, BMC medical education, 22 (1), 875 - 875, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
BACKGROUND: The nonsteroidal mineralocorticoid receptor blocker esaxerenone is effective in reducing blood pressure (BP). OBJECTIVE: In this study, we investigated esaxerenone-driven sodium homeostasis and its association with changes in BP in Dahl salt-sensitive (DSS) hypertensive rats. METHODS: In the different experimental setups, we evaluated BP by a radiotelemetry system, and sodium homeostasis was determined by an approach of sodium intake (food intake) and excretion (urinary excretion) in DSS rats with a low-salt diet (0.3% NaCl), high-salt diet (HSD, 8% NaCl), HSD plus 0.001% esaxerenone (w/w), and HSD plus 0.05% furosemide. RESULTS: HSD-fed DSS rats showed a dramatic increase in BP with a non-dipper pattern, while esaxerenone treatment, but not furosemide, significantly reduced BP with a dipper pattern. The cumulative sodium excretion in the active period was significantly elevated in esaxerenone- and furosemide-treated rats compared with their HSD-fed counterparts. Sodium content in the skin, skinned carcass, and total body tended to be lower in esaxerenone-treated rats than in their HSD-fed counterparts, while these values were unchanged in furosemide-treated rats. Consistently, sodium balance tended to be reduced in esaxerenone-treated rats during the active period. Histological evaluation showed that esaxerenone, but not furosemide, treatment attenuated glomerulosclerosis, tubulointerstitial fibrosis, and urinary protein excretion induced by high salt loading. CONCLUSIONS: Collectively, these findings suggest that an esaxerenone treatment-induced reduction in BP and renoprotection are associated with body sodium homeostasis in salt-loaded DSS rats.
2022年08月10日, International journal of molecular sciences, 23 (16), 英語, 国際誌[査読有り]
研究論文（学術雑誌）
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly malignant neoplasm. DNA-damaging drugs, such as cisplatin (CDDP) and 5-fluorouracil (5-FU), are most frequently used in preoperative chemotherapy for ESCC. However, the response to preoperative chemotherapy varies among patients. p53, encoded by TP53, participates in apoptotic pathways following chemotherapy with DNA-damaging drugs, and mutation of TP53 contributes to chemoresistance. Organic cation transporter 1 (OCT1) participates in the uptake of CDDP, and its reduced expression is associated with CDDP resistance. The aim of this study was to evaluate the predictive impact of the expression status of p53 and OCT1 in response to preoperative chemotherapy in ESCC. METHODS: We retrospectively assessed 66 ESCC patients who received preoperative chemotherapy with CDDP/5-FU (CF) or docetaxel/CDDP/5-FU (DCF). p53 and OCT1 expression in pretreatment biopsy specimens was immunohistochemically determined and correlated with histological response to preoperative chemotherapy. RESULTS: p53 with wild-type (p53WT-ex) and mutant-type (p53MT-ex) expression patterns was identified in 40.9% and 59.1% of patients, respectively. High expression of OCT1 (OCT1High) was detected in 45.5%, and the remaining 54.5% showed low expression (OCT1Low). In a univariate analysis of the entire cohort, p53MT-ex was significantly correlated with poor response (P = 0.026), whereas OCT1Low showed marginal significance (P = 0.091). In a combined analysis, tumors with either p53MT-ex or OCT1Low showed a significant correlation with poor response compared with tumors with both p53WT-ex and OCT1High (P < 0.001). The sensitivity, specificity, and accuracy of combined p53/OCT1 were 93.9%, 47.1%, and 81.8%, respectively. Multivariate analysis identified p53 (P = 0.017), OCT1 (P = 0.032), and combined p53/OCT1 (P < 0.001) as independent predictors of histological response. When samples were stratified according to chemotherapy regimen in the univariate analysis, combined p53/OCT1 was the only significant factor for poor response in the CF (P = 0.011) and DCF (P = 0.021) groups, whereas p53 showed no statistical significance. CONCLUSIONS: Our results suggest that either p53MT-ex or OCT1Low expression in pretreatment biopsy specimens may be a potential predictor of poor response to preoperative chemotherapy with the CF-based regimens in ESCC, although the specificity needs to be improved.
2022年04月01日, World journal of surgical oncology, 20 (1), 105 - 105, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
INTRODUCTION: This study investigated whether our urinary podocyte detection method using podocalyxin (PDX) and Wilms tumor 1 (WT1) immunoenzyme staining combined with liquid-based cytology can serve as a noninvasive routine laboratory test for glomerular disease. METHODS: The presence of PDX- and WT1-positive cells was investigated in 79 patients with glomerular disease and 51 patients with nonglomerular disease. RESULTS: The frequencies and numbers of PDX- and WT1-positive cells were significantly higher in the glomerular disease group than in the nonglomerular disease group. The best cutoffs for PDX- and WT1-positive cell counts for identifying patients with glomerular disease were 3.5 (sensitivity = 67.1% and specificity = 100%) and 1.2 cells/10 mL (sensitivity = 43.0% and specificity = 100%), respectively. CONCLUSION: Because our urinary podocyte detection method using PDX immunoenzyme staining can be standardized and it detected glomerular disease with high accuracy, it can likely serve as a noninvasive routine laboratory test for various glomerular diseases.
2022年03月29日, Acta cytologica, 66 (5), 434 - 440, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
Gastric carcinoma is one of the most common types of cancer worldwide and a leading cause of cancer-related mortality. Gastric carcinoma is histologically subdivided into differentiated and undifferentiated carcinoma, with the latter including poorly differentiated carcinoma and signet ring cell carcinoma (SRCC). Poorly differentiated carcinoma and SRCC have a worse prognosis compared with differentiated carcinoma. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors and the PPAR-α subtype regulates important cellular functions, including cell proliferation, energy metabolism, oxidative stress, immune responses and cell differentiation. The aim of the present study was to elucidate the associations between clinicopathological factors and PPAR-α expression in patients with gastric carcinoma. The immunohistochemical staining of specimens obtained from 57 patients showed that PPAR-α expression was slightly weaker in undifferentiated carcinoma than in differentiated carcinoma (P<0.01). PPAR-α expression also significantly differed between poorly differentiated carcinoma (both positive and negative: 14/20, 70%) and SRCC (not expressed: 0/7, 0%) (P<0.01). However, PPAR-α expression was not significantly affected by age, lymph node invasion, venous invasion, lymph node metastasis, depth of invasion or stage. Collectively, the present results demonstrated that the downregulated expression of PPAR-α may play a key role in the biological transformation of tumors. Therefore, PPAR-α appears to be an important protein related to histology and may hold promise as a prognostic marker. Further studies with a larger number of subjects are needed to elucidate the relationship between PPAR-α expression and tumor progression and to analyze long-term clinical survival.
2022年02月, Molecular and clinical oncology, 16 (2), 51 - 51, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a well-known nuclear receptor that is activated in the nucleus to regulate several transcription factors. Its expression patterns have been examined in various types of cancer. The present study investigated the expression patterns of PPAR-γ in non-muscle-invasive urothelial carcinoma. The expression rates of PPAR-γ, p53 and Ki-67 were compared to determine whether PPAR-γ may be considered as an immunobiomarker for bladder cancer. The intensity and extent of PPAR-γ expression were evaluated in 79 cases of non-muscle-invasive urothelial carcinoma (30 cases of papillary carcinoma low-grade, 30 cases of high-grade and 19 cases of carcinoma in situ) and 30 non-malignant cases. The nuclear overexpression of PPAR-γ was frequently observed in non-muscle-invasive urothelial carcinoma (63/79 cases) but was rarely detected in non-malignant cases (2/30 cases). The histological proliferation types of non-muscle-invasive urothelial carcinoma revealed that PPAR-γ was more frequently overexpressed in papillary carcinoma (54/60 cases) than in carcinoma in situ (9/19 cases). Immunohistochemical staining demonstrated that PPAR-γ was more useful as an immunobiomarker than p53 or Ki-67 (diagnostic odds ratios; 55.13, 16.82 and 11.13, respectively). In summary, this study demonstrated that the expression patterns of PPAR-γ were associated with histological proliferation type and that PPAR-γ was expressed in the nuclei of papillary carcinoma cells. These findings suggested that immunohistochemical staining for PPAR-γ may be used to comprehensively detect non-muscle-invasive urothelial carcinoma.
2022年02月, Molecular and clinical oncology, 16 (2), 36 - 36, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
AIMS: The number of cancer survivors with cardiovascular disease is increasing. However, the effect of cancer on body fluid regulation remains to be clarified. In this study, we evaluated body osmolyte and water imbalance in rats with hepatocellular carcinoma. MAIN METHODS: Wistar rats were administered diethylnitrosamine, a carcinogenic drug, to establish liver cancer. We analyzed tissue osmolyte and water content, and their associations with aldosterone secretion. KEY FINDINGS: Hepatocellular carcinoma rats had significantly reduced body mass and the amount of total body sodium, potassium, and water. However, these rats had significantly increased relative tissue sodium, potassium, and water content per tissue dry weight. Furthermore, these changes in sodium and water balance in hepatocellular carcinoma rats were significantly associated with increased 24-h urinary aldosterone excretion. Supplementation with 0.25% salt in drinking water improved body weight reduction associated with sodium and water retention in hepatocellular carcinoma rats, which was suppressed by treatment with spironolactone, a mineralocorticoid receptor antagonist. Additionally, the urea-driven water conservation system was activated in hepatocellular carcinoma rats. SIGNIFICANCE: These findings suggest that hepatocellular carcinoma induces body mass loss in parallel with activation of the water conservation system including aldosterone secretion and urea accumulation to retain osmolyte and water. The osmolyte and water retention at the tissue level may be a causative factor for ascites and edema formation in liver failure rats.
2022年01月15日, Life sciences, 289, 120192 - 120192, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
BACKGROUND: p53 immunostaining is routinely used as a surrogate marker for TP53 mutational status. In urine cytology, p53 immunocytochemistry is reportedly useful in detecting urothelial carcinoma cells as well as in improving the detection sensitivity and specificity. However, to the best of our knowledge, p53 expression in repair/reactive renal tubular cells (RRTCs) from urine cytologic specimens has not been assessed to date. METHODS: We evaluated the immunoexpression of p53 and homogentisate 1,2-dioxygenase (HGD) antibody, a renal tubular cells marker, in RRTCs using voided urine and renal biopsy samples from 80 patients who were histologically diagnosed with glomerular disease. RESULTS: Repair/reactive renal tubular cells were detected in 68 (68/80, 85%) samples at a mean count of 141.1 cells per sample (range, 5-4220). Immunocytochemical analysis found p53-positive RRTCs in all the samples (68/68, 100%) with an average p53 positivity rate of RRTCs per sample at 47.7% (range, 3.8%-96.5%). Of the 68 p53-positive RRTC samples, 38 (55.9%) included cells that were HGD positive for cytoplasm. Similarly, renal biopsy analysis revealed p53-positive RRTCs in all the specimens (68/68, 100%). All 68 (100%) cases showed RRTCs that were positive for both p53 and HGD. CONCLUSION: To avoid false positives of p53 immunocytochemistry, cytologists must consider the fact that RRTCs from patients with glomerular disease are positive for p53.
2021年11月16日, Cancer medicine, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
Inappropriate activation of the renin-angiotensin system decreases glucose uptake in peripheral tissues. Chronic angiotensin receptor type 1 (AT1) blockade increases glucose uptake in skeletal muscle, decreases the abundance of large adipocytes, and macrophage infiltration in adipose. However, the contributions of each tissue to the improvement in hyperglycemia in response to AT1 blockade are not known. Therefore, we determined the static and dynamic responses of soleus muscle, liver, and adipose to an acute glucose challenge following the chronic blockade of AT1. We measured adipocyte morphology along with TNF-α expression, F4/80 and CD11c positive cells in adipose and measured insulin receptor (IR) phosphorylation and AKT phosphorylation in soleus muscle, liver, and retroperitoneal fat before (T0), 60 (T60), and 120 (T120) minutes after an acute glucose challenge in the following groups of male rats: LETO (lean control; n = 5/time point), (2) obese OLETF (n = 7-8/time point) and (3) OLETF + ARB (ARB; 10 mg olmesartan/kg/d; n = 7-8/time point). AT1 blockade decreased adipocyte TNF-α expression and F4/80 and CD11c positive cells. In retroperitoneal fat at T60, IR phosphorylation was 155% greater in ARB than in OLETF. Furthermore, in retroperitoneal fat AT1 blockade increased GLUT4 protein expression in ARB compared to OLETF. IR phosphorylation and AKT phosphorylation were not altered in the liver of OLETF, but AT1 blockade decreased hepatic PCK1 and G6PC1 mRNA expressions. Collectively, these results suggest that chronic AT1 blockade improves obesity-associated hyperglycemia in OLETF rats by improving adipocyte function and by decreasing hepatic glucose production via gluconeogenesis.
2021年10月18日, American journal of physiology. Endocrinology and metabolism, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
Although oral cytology using Papanicolaou stain is useful for the early detection of oral premalignant lesions and squamous cell carcinoma (SCC) in people, little work has been conducted on this topic in veterinary medicine. This paper describes the features of oral cytology using Papanicolaou stain and immunocytochemistry on liquid-based cytology slides in a case of oral SCC in an Indo-Pacific bottlenose dolphin (Tursiops aduncus). In this case, dysplastic cells with koilocyte-like changes and SCC cells were identified using the Papanicolaou stain. These cells were positive for p53 using an immunocytochemistry analysis. A cytologic diagnosis of SCC was made. We believe that the early detection of premalignant oral lesions and SCC in dolphins can be significantly improved with cytology using liquid-based cytology, Papanicolaou staining, and immunocytochemistry.
2021年09月, Veterinary clinical pathology, 50 (3), 404 - 409, 英語, 国際誌[査読有り]
Immunocytochemistry (ICC) is an important ancillary technique in clinical cytology for not only identifying and characterizing tumor cells but also gaining prognostic or therapeutic information. Although cell blocks are often prepared for immunocytochemical evaluation of body cavity fluid and fine-needle aspiration specimens, they are not suitable for hypocellular samples. Liquid-based cytology can help prepare additional smears from residual cytological specimens. However, since conventional methods are used for nongynecological specimens in most laboratories, ICC is often limited by the number of cytological smears. Cell transfer methods permit to evaluate several immunocytochemical markers in a single cytological smear. Yet, these methods have some limitations; for example, they are time-consuming (about 3-40 h) and medium membranes with their attached cells are occasionally stretched or torn when peeled off the slides. Therefore, in an attempt to solve these problems, we developed a rapid and reliable cell transfer method using a nylon mesh. Our method requires no special equipment or reagent and can significantly reduce the turnaround time, as compared to previous methods.
2021年09月, Acta cytologica, 65 (5), 424 - 429, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
OBJECTIVE: In The Paris System for Reporting Urinary Cytology (TPS), the important cytomorphological features for diagnosing high-grade urothelial carcinoma (HGUC) are a nuclear-to-cytoplasmic (N:C) ratio exceeding 0.7, hyperchromasia, coarse chromatin, and irregular nuclear borders. However, quantitative cytomorphological assessments of HGUC cells using SurePath slides are rare. Therefore, we evaluated HGUC cells on SurePath slides quantitatively using a digital image analysis system and compared these data with ThinPrep data. METHODS: The same urine samples were divided into two aliquots and used to prepare SurePath and ThinPrep slides. We used ImageJ to measure the N:C ratio, hyperchromasia, and irregular nuclear borders for HGUC cells on SurePath and ThinPrep slides. RESULTS: The total number of analysed HGUC cells on SurePath slides was 981, versus 889 on ThinPrep slides. Hyperchromasia and irregular nuclear borders were significantly more severe on SurePath than on ThinPrep slides. Conversely, the N:C ratio did not differ between the methods. Additionally, HGUC cells with N:C ratios exceeding 0.7 were present on almost all slides for both methods. CONCLUSIONS: Our data indicated the reasonableness of using the N:C ratio as the major criterion for TPS on both SurePath and ThinPrep slides, and an N:C ratio cut-off of 0.7 as suitable for identifying HGUC cells. However, the severity of hyperchromasia and irregular nuclear borders differed between the processing methods.
2021年05月25日, Cytopathology : official journal of the British Society for Clinical Cytology, 32 (5), 654 - 659, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
We investigated the effects of esaxerenone, a novel, nonsteroidal, and selective mineralocorticoid receptor blocker, on cardiac function in Dahl salt-sensitive (DSS) rats. We provided 6-week-old DSS rats a high-salt diet (HSD, 8% NaCl). Following six weeks of HSD feeding (establishment of cardiac hypertrophy), we divided the animals into the following two groups: HSD or HSD + esaxerenone (0.001%, w/w). In survival study, all HSD-fed animals died by 24 weeks of age, whereas the esaxerenone-treated HSD-fed animals showed significantly improved survival. We used the same protocol with a separate set of animals to evaluate the cardiac function by echocardiography after four weeks of treatment. The results showed that HSD-fed animals developed cardiac dysfunction as evidenced by reduced stroke volume, ejection fraction, and cardiac output. Importantly, esaxerenone treatment decreased the worsening of cardiac dysfunction concomitant with a significantly reduced level of systolic blood pressure. In addition, treatment with esaxerenone in HSD-fed DSS rats caused a reduced level of cardiac remodeling as well as fibrosis. Furthermore, inflammation and oxidative stress were significantly reduced. These data indicate that esaxerenone has the potential to mitigate cardiac dysfunction in salt-induced myocardial injury in rats.
2021年02月19日, International journal of molecular sciences, 22 (4), 英語, 国際誌[査読有り]
研究論文（学術雑誌）
The kidneys are the major organs for erythropoietin (EPO) production in adults, and thus, kidney damage results in reduced EPO levels and anemia. Inhibitors of Hypoxia-inducible factor-prolyl hydroxylase domain-containing protein (HIF-PHD) are awaited as new therapeutic options for renal anemia. It can be predicted that most patients who receive HIF-PHD inhibitors have renal dysfunction as a cause of anemia. Therefore, in the present study, we investigated the effects of the HIF-PHD inhibitor molidustat on anemia and renal dysfunction when initiated after the onset of renal anemia. Male C57BL/6J mice received adenine orally to induce nephropathy. After the onset of nephropathy, the mice were treated with either vehicle or molidustat. After 4 weeks of administration, vehicle-treated mice displayed significant anemia, and molidustat ameliorated this anemia. Vehicle-treated mice exhibited reduced creatinine clearance and body weight, increased blood urea nitrogen levels, histopathological changes, immune cell infiltration, and dehydration. Molidustat reversed immune cell infiltration, dehydration, and renal fibrosis without improving renal functional parameters. In conclusion, molidustat treatment initiated after the onset of nephropathy and renal anemia reversed anemia in mice. Molidustat improved some parameters of renal abnormality, but it did not restore renal function.
2020年12月, Journal of pharmacological sciences, 144 (4), 229 - 236, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
(Pro)renin receptor [(P)RR] has a role in various diseases, such as cardiovascular and renal disorders and cancer. Aberrant (P)RR expression is prevalent in pancreatic ductal adenocarcinoma (PDAC) which is the most common pancreatic cancer. Here we show whether aberrant expression of (P)RR directly leads to genomic instability in human pancreatic ductal epithelial (HPDE) cells. (P)RR-expressing HPDE cells show obvious cellular atypia. Whole genome sequencing reveals that aberrant (P)RR expression induces large numbers of point mutations and structural variations at the genome level. A (P)RR-expressing cell population exhibits tumour-forming ability, showing both atypical nuclei characterised by distinctive nuclear bodies and chromosomal abnormalities. (P)RR overexpression upregulates SWItch/Sucrose Non-Fermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (SMARCA5) through a direct molecular interaction, which results in the failure of several genomic stability pathways. These data reveal that aberrant (P)RR expression contributes to the early carcinogenesis of PDAC.
2020年11月27日, Communications biology, 3 (1), 724 - 724, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
Gentisic acid (GA), a metabolite of acetylsalicylic acid (ASA), and homogentisic acid (HGA), which is excreted at high levels in alkaptonuria, are divalent phenolic acids with very similar structures. Urine containing HGA is dark brown in color due to its oxidation. We recently reported a new oxidation method of HGA involving the addition of sodium hydroxide (NaOH) with sodium hypochlorite pentahydrate (NaOCl·5H2O), which is a strong oxidant. In the present study, we attempted to oxidize GA, which has a similar structure to HGA, using our method. We herein observed color changes in GA solution and analyzed the absorption spectra of GA after the addition of NaOH with NaOCl·5H2O. We also examined the oxidation reaction of GA using a liquid chromatography time-of-flight mass spectrometer (LC/TOF-MS). The results obtained indicated that GA solution had a unique absorption spectrum with a peak at approximately 500 nm through an oxidation reaction following the addition of NaOH with NaOCl·5H2O. This spectrophotometric method enables GA to be detected in sample solutions without expensive analytical instruments or a complex method.
2020年, PloS one, 15 (4), e0232263, 英語, 国際誌[査読有り]
Protein kinase N1 (PKN1) knockout (KO) mice spontaneously form germinal centers (GCs) and develop an autoimmune-like disease with age. Here, we investigated the function of PKN1 kinase activity in vivo using aged mice deficient in kinase activity resulting from the introduction of a point mutation (T778A) in the activation loop of the enzyme. PKN1[T778A] mice reached adulthood without external abnormalities; however, the average spleen size and weight of aged PKN1[T778A] mice increased significantly compared to aged wild type (WT) mice. Histologic examination and Southern blot analyses of spleens showed extramedullary hematopoiesis and/or lymphomagenesis in some cases, although without significantly different incidences between PKN1[T778A] and WT mice. Additionally, flow cytometry revealed increased numbers in B220+, CD3+, Gr1+ and CD193+ leukocytes in the spleen of aged PKN1[T778A] mice, whereas the number of lymphocytes, neutrophils, eosinophils, and monocytes was reduced in the peripheral blood, suggesting an advanced impairment of leukocyte trafficking with age. Moreover, aged PKN1[T778A] mice showed no obvious GC formation nor autoimmune-like phenotypes, such as glomerulonephritis or increased anti-dsDNA antibody titer, in peripheral blood. Our results showing phenotypic differences between aged Pkn1-KO and PKN1[T778A] mice may provide insight into the importance of PKN1-specific kinase-independent functions in vivo.
2019年09月27日, Scientific reports, 9 (1), 13977 - 13977, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
OBJECTIVE: Cleaved caspase-3 (CC3), phosphorylated-mixed-lineage kinase domain-like protein (p-MLKL), and microtubule-associated protein-1 light chain-3B (LC3B) have pivotal functions in apoptosis, necroptosis, and autophagy, respectively. In vitro studies have shown that interaction of these proteins are complex and their roles in cancer can be influenced by many factors. However, these findings are not adequately assessed in human tissues. Here, we determined CC3, p-MLKL, and LC3B expression in colorectal cancers (CRCs), and assessed their associations with clinicopathological parameters, and with KRAS and p53 status. METHODS: We immunohistochemically assessed 113 CRC specimens for levels of CC3, p-MLKL, LC3B, and p53. KRAS gene status was analyzed using the Scorpion- amplification refractory mutation system. RESULTS: High levels of CC3 (CC3High) and LC3B (LC3BHigh) were detected in 38% and 35% of the 113 CRCs, respectively, but no or only a few p-MLKL-positive cells were observed in any of the tumors. CC3High was significantly associated with high pT status (P = 0.03), vascular invasion (P = 0.03) and high pStage (P = 0.04) and was marginally associated with lymph node (P = 0.06) and distant metastases (P = 0.06). LC3BHigh was also significantly associated with high pT status (P = 0.02) and lymphatic invasion (P = 0.002), and was marginally associated with nerve plexus invasion (P = 0.06). In combined analysis, compared with CC3Low/LC3BLow tumors, tumors that were either CC3High, LC3BHigh, or both were significantly associated with high pT status (P = 0.0007), lymphatic invasion (P = 0.03), vascular invasion (P = 0.003), distant metastasis (P = 0.04) and high pStage (P = 0.04). LC3BHigh was significantly associated with a mutant-type expression pattern of p53 (P = 0.003). CONCLUSION: To the best of our knowledge, this is the first study to examine the combination of CC3/LC3B and p-MLKL expression in clinical CRC samples and to correlate these expression data with clinicopathological parameters and EGFR and p53 status. Our results suggest that necroptosis is a rare process in CRC, apoptosis and autophagy are upregulated in aggressive CRCs, and p53 mutation may lead to the upregulation of autophagy.
2019年07月, Pathology, research and practice, 215 (7), 152425 - 152425, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
OBJECTIVE: Anaplastic lymphoma kinase (ALK) positive (+) lung cancers are predictive for response to crizotinib and alectinib. There are many cases of lung cancer in which surgery cannot be performed, and such cases require diagnosis by cytological specimen or biopsy. Estimating ALK (+) lung cancer from cytomorphology would allow molecular testing to proceed without the waste of a small amount of specimen. The purpose of this study was to assess whether qualitative and quantitative cytomorphological features are sufficient for distinguishing primary ALK (+) from ALK (-) lung cancer. METHODS: We examined eight qualitative cytomorphological parameters and three quantitative nuclear morphometric parameters in 17 cases of primary ALK (+) lung cancer, diagnosed by fluorescence in situ hybridisation (FISH) using histological specimens, and in 41 cases of ALK (-) lung cancer. Quantitative nuclear morphometric parameters were analysed by a computer-assisted image analysis system. RESULTS: In ALK (+) lung cancer, three qualitative parameters (signet ring cells, nuclear grooves and single type nucleoli) and two quantitative parameters (large nuclear area and irregular nuclear shape) were observed in significantly higher proportions. However, in ALK (-) lung cancer, one qualitative parameter (unclear and multiple type nucleoli) was seen significantly more often. CONCLUSIONS: These results show that the cytomorphological features of signet ring cells, nuclear grooves and nucleoli shape can help to triage a small amount of cytological and biopsy specimens for appropriate molecular testing of primary ALK (+) lung cancer.
2019年05月, Cytopathology : official journal of the British Society for Clinical Cytology, 30 (3), 295 - 300, 英語, 国際誌[査読有り]
Peroxisome proliferator-activated receptor alpha (PPAR-α) belongs to the PPAR family and plays a critical role in inhibiting cell proliferation and tumorigenesis in various tumors. However, the role of PPAR-α in colorectal tumorigenesis is unclear. In the present study, we found that fenofibrate, a PPAR-α agonist, significantly inhibited cell proliferation and induced apoptosis in colorectal carcinoma cells. In addition, PPAR-α was expressed in the nucleus of colorectal carcinoma cells, and the expression of nuclear PPAR-α increased in colorectal carcinoma tissue compared with that of normal epithelium tissue (P<0.01). The correlation between the expression of nuclear PPAR-α and clinicopathological factors was evaluated in human colorectal carcinoma tissues, and the nuclear expression of PPAR-α was significantly higher in well-to-moderately differentiated adenocarcinoma than in mucinous adenocarcinoma (P<0.05). These findings indicate that activation of PPAR-α may be involved in anticancer effects in colorectal carcinomas, and nuclear expression of PPAR-α may be a therapeutic target for colorectal adenocarcinoma treatment.
2019年, PPAR research, 2019, 7486727 - 7486727, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
- 2019年01月, Biotechnic & histochemistry : official publication of the Biological Stain Commission, 94 (1), 60 - 64
[査読有り]
BACKGROUND: Although constitutive activating mutations in the Wnt/β-catenin signalling pathway are important for colorectal cancer development, canonical signalling through Wnt ligands is essential for β-catenin activation. Here, we investigated the role of (pro)renin receptor ((P)RR), a component of the Wnt receptor complex, in the pathogenesis of colorectal cancer. METHODS: (P)RR silencing was performed in human colorectal cancer cells containing constitutive activating mutations in the Wnt/β-catenin pathway. (P)RR overexpression was induced in normal colon epithelial cells. Protein and mRNA levels of pathway components were detected, and Wnt signalling activity was measured using a β-catenin reporter. Cell proliferative activity and apoptosis were evaluated using WST-1 assay and flow cytometry. Xenografts were induced in nude mice. RESULTS: (P)RR expression was greater in colorectal cancer tissues and cells than in normal colorectal samples. Patients with strong (P)RR expression took more proportion in groups with poorly-differentiated, advanced and rapidly-progressing cancers. (P)RR silencing attenuated the pathway in colorectal cancer cells, impaired their proliferation in vitro and vivo. (P)RR overexpression enhanced the pathway and proliferation of normal colon epithelial cells. CONCLUSIONS: Aberrant (P)RR expression promotes colorectal cancer through the Wnt/β-catenin signalling pathway despite constitutive pathway-activating mutations. (P)RR is a potential diagnostic and therapeutic target for colorectal cancer.
2019年01月, British journal of cancer, 120 (2), 229 - 237, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
- Springer Science and Business Media LLC, 2018年07月, Scientific reports, 8 (1), 11364
[査読有り]
研究論文（学術雑誌）
In glomerular disease, podocytes and parietal epithelial cells (PECs) are shed in the urine. Therefore, urinary podocytes and PECs are noninvasive biomarkers of glomerular disease. The purpose of this protocol is to employ immunocytochemistry to detect podocytes and PECs, using the WT1 antibody on liquid-based cytology slides.
2018年05月05日, Bio-protocol, 8 (9), e2827, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
BACKGROUND: It is uncertain whether kidneys from marginal donors are suitable for live kidney transplantation. In deceased donor kidneys, tubular cell senescence affects allograft function. However, the degree of cell senescence in a living donor kidney with marginal factors has not been reported. In this study, we assessed the association of tubular cell senescence with allograft and remnant kidney function by a prospective observational clinical study. METHODS: Thirty-eight living donor kidney transplantations were analyzed prospectively. Tissue sections obtained from preimplantation kidney biopsies were immunostained for p16INK4a to indicate cell senescence. Various kidney biomarkers were analyzed in urine and blood samples. RESULTS: Of the 38 donors, 21 had marginal factors. Severe tubular senescence was found in living donors with overlapping marginal criteria. Tubular senescence in living donor kidneys was significantly related to donor age and lower recipient kidney function at 1 year after transplantation independently of donor age (β = -0.281; p = 0.050) but did not affect remnant kidney function after donation. Pretransplantation donor pre-estimated glomerular filtration rate and hypertension did not show a significant area under the curve (AUC) for prediction of high tubular senescence. High plasma levels of soluble αKlotho were associated with a higher predictive value for low tubular cell senescence with an AUC of 0.78 (95% CI 0.62-0.93; p < 0.01). CONCLUSIONS: The nuclear p16-staining rate in donated kidney tubules is a predictor for allograft kidney function but not donor remnant kidney function. Detection of tubular cell senescence may facilitate selection of appropriate living donor candidates.
2018年, American journal of nephrology, 47 (1), 8 - 17, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
Claudins are members of a large family of transmembrane proteins, which are essential for the formation of tight junctions and have a significant effect on the biological behavior of tumor progression. Previous studies have demonstrated that several claudins show aberrant expression patterns in numerous types of cancer. The present study investigated the expression and localization of claudin-3 and claudin-7 in human colorectal adenocarcinoma cell lines and tissues. The protein expression levels of claudin-3 and claudin-7 were determined using immunocytochemical and immunohistochemical staining. Claudin-3, but not claudin-7, exhibited nuclear localization in the human colorectal adenocarcinoma Caco-2 and SW620 cell lines. Surgically resected colorectal adenocarcinoma tissue specimens were obtained, and the associations between the expression of claudin-3 or claudin-7 and various clinicopathological parameters were analyzed. The membranous expression rates of claudin-3 and claudin-7 were 58.0 and 50.0%, while their nuclear expression rates were 22.0 and 2.0%, respectively. The membranous expression of claudin-3 and claudin-7 was not associated with any clinicopathological factors, whereas the nuclear expression of claudin-3 was associated with histological type and was significantly increased in colorectal mucinous adenocarcinomas compared with that in well-to moderately-differentiated colorectal adenocarcinomas (P< 0.01). However, no associations were observed between the nuclear expression of claudin-7 and any clinicopathological parameter. In conclusion, the nuclear expression of claudin-3 in colorectal mucinous adenocarcinoma may be involved in the biological transformation of tumors. The results from the present study indicated that claudin-3 is an important protein associated with histological type and has potential as a prognostic marker. Although the mechanisms underlying the nuclear localization of claudin-3 in tumorigenesis have not yet been elucidated in detail, the present results indicated the potential of claudin-3 as a histopathological biomarker for colorectal adenocarcinomas.
Spandidos Publications, 2018年01月01日, Oncology Letters, 15 (1), 99 - 108, 英語[査読有り]
研究論文（学術雑誌）
ObjectiveThe purpose of this study was to assess the relationship between urinary WT1-positive cells (podocytes and active parietal epithelial cells) and WT1-positive cells in renal biopsy to investigate whether urinary WT1-positive cells are useful for detection of crescent formation. MethodsFifty-two patients with kidney disease were investigated (15 cases with crescentic lesions and 37 cases with non-crescentic lesions) for immunoenzyme staining using anti-WT1 antibody for urine cytology and renal biopsy. Numbers of WT1-positive cells in urine and renal biopsy were counted. ResultsThere was no correlation between urinary WT1-positive cells and WT1-positive cells in renal biopsy. However, the number of urinary WT1-positive cells in patients with crescentic lesions was significantly higher than in patients with non-crescentic lesions. In addition, the best cut-off value to detect patients with crescentic lesions using urinary was 5 cells/10-mL (area under the concentration-time curve=0.735). ConclusionsThe results of our study suggest urinary WT1-positive cells can be used to detect patients with crescent formation using 5 cells/10-mL cutoff value. WT1-positive glomerular podocytes and parietal epithelial cells may be shed into urine in active glomerular disease. This study, investigating the relationship between WT1-positive cells in urine and in the renal biopsy found no correlation; however, the results do suggest that, using a cutoff value of 5 cells/10mL, WT1 positive urinary cells can be used to detect patients with crescent formation.
WILEY, 2017年12月, CYTOPATHOLOGY, 28 (6), 524 - 530, 英語[査読有り]
研究論文（学術雑誌）
Knock-in mice lacking PKN1 kinase activity were generated by introducing a T778A point mutation in the catalytic domain. PKN1[T778A] mutant mice developed to adulthood without apparent external abnormalities, but exhibited lower T and B lymphocyte counts in the peripheral blood than those of wild-type (WT) mice. T and B cell development proceeded in an apparently normal fashion in bone marrow and thymus of PKN1[T778A] mice, however, the number of T and B cell counts were significantly higher in the lymph nodes and spleen of mutant mice in those of WT mice. After transfusion into WT recipients, EGFP-labelled PKN1[T778A] donor lymphocytes were significantly less abundant in the peripheral circulation and more abundant in the spleen and lymph nodes of recipient mice compared with EGFP-labelled WT donor lymphocytes, likely reflecting lymphocyte sequestration in the spleen and lymph nodes in a cell-autonomous fashion. PKN1[T778A] lymphocytes showed significantly lower chemotaxis towards chemokines and sphingosine 1-phosphate (S1P) than WT cells in vitro. The biggest migration defect was observed in response to S1P, which is essential for lymphocyte egress from secondary lymphoid organs. These results reveal a novel role of PKN1 in lymphocyte migration and localization.
NATURE PUBLISHING GROUP, 2017年08月, SCIENTIFIC REPORTS, 7 (1), 7663, 英語[査読有り]
研究論文（学術雑誌）
ObjectivesDamage and detachment of podocytes and loss into the urine have been implicated in the progression of kidney diseases. The purpose of this study was to investigate the potential role of urine cytology based on SurePath combined with immunoenzyme staining using Wilms' tumour 1 (WT1) antibody as a podocyte marker in the discrimination of normality and non-renal urinary tract disease from kidney disease. MethodsSixty-six patients with kidney disease, 45 patients with lower urinary tract disease and 30 healthy volunteers were examined. Urine cytology slides were prepared using the SurePath method and immunoenzyme stained with WT1 antibody, and the number of WT1-positive cells was counted. ResultsIn kidney disease, WT1-positive cells were found in 33 (50%) of 66 samples. No WT1-positive cells were found in 45 patients with lower urinary tract disease or in 30 healthy volunteers. The positive rates for WT1 varied with disease type, but not significantly: immunoglobulin A (IgA) nephropathy, (14/23); membranous glomerulonephritis, (4/10); Henoch-Schonlein purpura nephritis, (3/5); diabetic glomerulopathy, (5/5); minor glomerular abnormality/minimal change nephrotic syndrome (0/4). ConclusionsThe results suggest that WT1 immunoenzyme staining of urine cytology can be used to detect some types of kidney disease. Immunoenzyme staining for WT1 on Surepath (TM) processed urine cytology samples showed WT1 positive podocytes in 50% of the patients with kidney disease studied. There was no positive staining in urine from those with lower urinary tract disease or healthy volunteers. WT1 staining, which is cytoplasmic in these Surepath preparations, could be a low cost, easy to perform method for the detection of some types of kidney disease.
Wiley, 2016年02月, Cytopathology, 27 (1), 43 - 49, 英語[査読有り]
研究論文（学術雑誌）
Claudins are members of a large family of transmembrane proteins, which are essential in the formation of tight junctions and have previously been associated with the process of tumor progression. Studies have reported the aberrant expression of claudin-1 and claudin-4 in numerous types of cancer. The present study aimed to investigate the expression of claudin-1 and claudin-4 in gastric adenocarcinoma tissue. Surgically resected gastric adenocarcinoma tissue specimens were obtained from 94 patients. Protein expression levels of claudin-1 and claudin-4 were determined using immunohistochemical staining; the association between claudin-1 or claudin-4 expression and various clinicopathological parameters were then analyzed. In gastric adenocarcinoma specimens, the expression rates of claudin-1 and claudin-4 were 43.6 and 87.2%, respectively. Claudin-1 expression demonstrated a significant correlation with histological type (P<0.01) and was significantly higher in well- to moderately-differentiated gastric adenocarcinomas compared with poorly-differentiated tumors. However, no correlation was observed between claudin-4 expression in adenocarcinoma and clinicopathological parameters. In conclusion, downregulation of claudin-1 expression in poorly-differentiated gastric adenocarcinoma may be involved in the biological transformation of tumors. The present findings suggested that claudin-1 may be an important protein associated with histological type and therefore may have potential for use as a prognostic marker for gastric adenocarcinoma. Further studies are required to elucidate the precise mechanism of claudin expression and its involvement in tumor progression.
SPANDIDOS PUBL LTD, 2015年07月, ONCOLOGY LETTERS, 10 (1), 93 - 98, 英語[査読有り]
研究論文（学術雑誌）
In this study, a fixation protocol using a 10% neutral buffered formalin (FA) solution and another protocol using a methanol (MeOH) solution were compared for detection of ion channels, K(v)1.5, K(v)4.2, Ca(v)1.2, K(ir)6.2, Na(v)1.5 and Na(v)1.1 in rat myocytes by immunolabelling. K(v)1.5 and K(v)4.2 at intercalated discs and Ca(v)1.2 at transverse tubules were not detected by FA but were detected by MeOH. K(ir)6.2 at transverse tubules and Na(v)1.5 at sarcolemma were detected by FA but not by MeOH. It is suggested that both FA and MeOH fixation protocols should be used for the detection of cardiac ion channels by immunolabelling.
VIA MEDICA, 2015年05月, FOLIA MORPHOLOGICA, 74 (2), 258 - 261, 英語[査読有り]
研究論文（学術雑誌）
- WILEY-BLACKWELL, 2014年09月, DIAGNOSTIC CYTOPATHOLOGY, 42 (9), 823 - 826, 英語
[査読有り]
Aims: Kidney cells in patients with diabetic nephropathy are reported to be senescent. However, the mechanisms that regulate cellular senescence in the diabetic kidney are still unknown. In the present study, we evaluated the contribution of high glucose to renal cell senescence in streptozotocin (STZ)-induced diabetic mice. Methods: Non-diabetic and streptozotocin (STZ, 10 mg kg(-1) day(-1) for 7 days, i.p.)-induced type 1 diabetic C57BL/6 J mice and cultured human proximal tubular cells were used in this study. Results: Hyperglycemia dramatically increased the renal expression of p21 but not other CDK inhibitors such as p16 and p27 at 4 weeks after STZ injection. These changes were accompanied by an increase in senescence-associated beta-galactosidase staining in tubular epithelial cells. Administration of insulin at doses that maintained normoglycemia or mild hypoglycemia suppressed the changes induced by STZ. Insulin did not affect the senescent markers in non-diabetic mice. Exposure of cultured human proximal tubular cells to 25 mmol/L, but not 8 mmol/L, glucose medium increased the expression of senescence markers, which was suppressed by knock-down of p21 or sodium glucose cotransporter (SGLT) 2. Conclusions: These results suggest that hyperglycemia causes tubular senescence via a SGLT2- and p21-dependent pathway in the type 1 diabetic kidney. (c) 2014 Elsevier Inc. All rights reserved.
ELSEVIER SCIENCE INC, 2014年09月, JOURNAL OF DIABETES AND ITS COMPLICATIONS, 28 (5), 604 - 611, 英語[査読有り]
研究論文（学術雑誌）
Blood-rich gynecologic specimens can be problematic in the processing of liquid-based cytology. However, little is known about the influence of erythrocytes and protein on urine specimens. In addition, the SurePath (TM) system has two preservatives for non-gynecologic specimens. In this study, we compared the epithelial cell counts and cytomorphology obtained from CytoRich (TM) (CR) Red and CR Blue. A total of 98 voided urine samples were processed using both CR Red and CR Blue. We made an assessment of the epithelial cell counts, fixation, and staining quality, and backgrounds of both slides. Urine protein and urine erythrocyte counts were analyzed, and those data were compared with the epithelial cell counts in CR Red and CR Blue slides. Overall, epithelial cell counts were equivalent for both CR Red and CR Blue slides. However, in high-level proteinuria cases, the CR Red slides showed higher epithelial cell counts than the CR Blue slides. On the other hand, in microscopic hematuria cases, the CR Blue slides showed higher epithelial cell counts than the CR Red slides. We have found both CR Red and CR Blue to be available for urine cytology. However, it is important to note that CR Blue is inferior to CR Red in epithelial cell recovery rates in cases of high-level proteinuria. Diagn. Cytopathol. 2014;42:423-427. (c) 2013 Wiley Periodicals, Inc.
WILEY-BLACKWELL, 2014年05月, Diagnostic cytopathology, 42 (5), 423 - 427, 英語[査読有り]
研究論文（学術雑誌）
The cyclin-dependent kinase inhibitor p21 plays important roles in chronic renal disorders; however, its roles in response to acute renal stress are unclear. Here we evaluated p21 in acute kidney injury and ischemic preconditioning using wildtype and p21 knockout mice that underwent renal ischemia followed by reperfusion. The decline in renal function and histological changes were worse in the knockout than in wild-type mice. Ischemia/reperfusion increased p21 expression in the kidney of wild-type mice compared with sham surgery, suggesting p21 may confer tolerance to ischemia/reperfusion injury. We next tested whether p21 is associated with the protective effect of ischemic preconditioning, an established method to reduce ischemia/reperfusion injury. Ischemic preconditioning attenuated ischemia/reperfusion injury in wild-type but not p21-knockout mice. This preconditioning decreased the number of proliferating tubular cells before but increased them at 24 h after ischemia/reperfusion in the kidneys of wild-type mice. In p21-knockout mice, ischemic preconditioning did not change the number of proliferating cells before but decreased them after ischemia/reperfusion. Ischemic preconditioning increased renal p21 expression and the number of cells in the G1 phase of the cell cycle before ischemia/reperfusion compared with sham surgery. Thus, renal p21 is essential for the beneficial effects of renal ischemic preconditioning. Transient cell cycle arrest induced by ischemic preconditioning by a p21-dependent pathway seems to be important for subsequent tubular cell proliferation after ischemia/reperfusion.
NATURE PUBLISHING GROUP, 2014年04月, KIDNEY INTERNATIONAL, 85 (4), 871 - 879, 英語[査読有り]
研究論文（学術雑誌）
Objective: The removal of blood components is necessary to improve the quality of the liquid-based cytology (LBC) preparations. In ThinPrep® (TP) samples a cell suspension in a methanol-based fixative undergoes a vacuum filtration method, whereas in SurePath™ (SP) samples a cell suspension in an ethanol-based fixative is processed through a density gradient centrifugation system prior to gravity deposition of the specimen onto a glass slide. We compared the cyto-architectural features for the cytologic diagnosis of endometrial adenocarcinoma using parallel TP and SP preparations in a previous publication. Study Design: We performed our study on LM8 cells (a cultured osteosarcoma cell line). LM8 cells at a concentration of 1.25 × 10 3 cell/cm2 were seeded on a 35-mm plate in culture medium, which contained 10% fetal bovine serum (FBS), 100 units/ml penicillin, and 100 μ/ml streptomycin in Dulbecco's modified Eagle's medium (DMEM), and aliquots of the cell suspension obtained in this way were compared after the addition of a hemolytic agent, i.e. Cytolyt® (CyL). LBC preparations were then obtained on cell suspensions treated with CyL after different time intervals of hemolysis. Results: Treatment with CyL did not alter the cellularity of the preparation, but reduction of the nuclear area and a tendency towards nuclear chromatin condensation with a subsequent higher brightness were found. Because CyL is a 25% methanol-buffered solution, its alcoholic concentration is low it was our impression that, while its fixative effect was weak, its hemolytic effect was high. Water influx or efflux through the cell membrane is controlled by osmotic pressure changes induced by the buffer solution in the CyL solution. While CyL was not shown to alter the cell shape, nuclear shrinkage was thought to be probably due to the increasing cell dehydration caused by longer exposure intervals to methanol. Conclusion: This study has allowed us to make significant observations on the hemolytic properties of CyL, and on its combined effects with PreservCyt on the cytomorphology of cells suspensions. © 2013 S. Karger AG, Basel.
S. Karger AG, 2014年, Acta cytologica, 58 (1), 76 - 82, 英語[査読有り]
研究論文（学術雑誌）
- 2014年, Open Journal of Pathology, 4, 206 - 212, 英語
[査読有り]
研究論文（学術雑誌）
It is well known that "condensed cluster of stromal cells (CCSC)" and "metaplastic clumps with irregular protrusion (MCIP)" in endometrial glandular and stromal breakdown (EGBD) cases may simulate "clumps of cancer cells (CCC)" in endometrioid adenocarcinoma grade 1 (G1), leading to difficulty in cytological interpretation. The aim of this study was undertaken to clarify the cytological immunoreactivity of nuclear findings about CCSC and MCIP which may be recognized in EGBD cases by using p53 protein and cyclin A in liquid-based cytologic (LBC) preparations. The material consists of cytologic smears of 20 cases of EGBD and 20 cases of G1 for which histopathological diagnosis was obtained by endometrial curettage at the JA Suzuka General Hospital. The evaluation of immunoreactivity was performed by using the intensity of nuclear staining and the nuclear labeling index (N-LI). The intensity of nuclear staining was scored as negative (0), weak (1), moderate (2), or strong (3). The N-LI was scored as less than 10% (0), from 10 to 25% (1), from 26 to 50% (2), or greater than 50% (3). The final score was calculated of the addition of both partial scores. Results are as follows: As for the p53 protein immunoreactivity, CCC (2.4 +/- 1.4) was a significantly higher value in comparison with CCSC (0) and MCIP (0.8 +/- 0.4), respectively. As for the cyclin A immunoreactivity, CCC (2.8 +/- 1.1) was a significantly higher value in comparison with CCSC (0) and MCIP (0.6 +/- 0.5), respectively. CCSC and MCIP in EGBD are misunderstood as cellular atypia and structural atypia on occasion; but, as for results of the immunoreactivity scores of p53 protein and cyclin A in our study, it seemed that those biochemical characters proved that the biological activity level was low (or degenerative). The results of the current study demonstrated that the cytological immunoreactivity of nuclear findings by p53 and cyclin A appear to be more useful for the LBC assessment of endometrial lesions, especially for the discrimination of EGBD and G1. Diagn. Cytopathol. 2013;41:303-307. (C) 2011 Wiley Periodicals, Inc.
WILEY-BLACKWELL, 2013年04月, DIAGNOSTIC CYTOPATHOLOGY, 41 (4), 303 - 307, 英語[査読有り]
研究論文（学術雑誌）
The aim of this study was to assess the utility of liquid-based cytologic preparation (LP) compared with conventional preparation (CP) for the assessment of nuclear findings in endometrial glandular and stromal breakdown (EGBD) which may be misdiagnosed as carcinoma in EGBD cases. The material consists of cytologic smears including 20 cases of proliferative endometrium (PE), 20 cases of EGBD, and 20 cases of endometrioid adenocarcinoma grade1 (G1) for which histopathological diagnosis was obtained by endometrial curettage at the JA Suzuka General Hospital. Nuclear findings were examined in PE cells, EGBD-stromal cells, EGBD-metaplastic cells, and G1 cells, respectively. It was examined about the following items; (1) nuclear shape; (2) A long/minor axis ratio in cell nuclei; (3) an area of cell nuclei; (4) overlapping nuclei. Results are as follows: (1) nuclear shape; as for the reniform shape of EGBD-stromal cells and spindle shape of EGBD-metaplastic cells, the ratio of the LP method was a higher value than the CP method. (2) The long axis and area of cell nuclei; LP in all groups was a recognizable tendency for nuclear shrinkage. (3) The long/minor axis ratio in cell nuclei; only EGBD-metaplastic cells recognize a significant difference between CP and LP. (4) Overlapping nuclei; LP was a higher value in comparison with CP in the other groups except PE cells, and the degree of overlapping nuclei was enhanced about three times. Therefore, although a cell of LP has a shrinking tendency, (1) it is excellent that LP preserves a characteristic of nuclear shape than CP; (2) a cellular characteristic becomes clearer, because three-dimensional architecture of LP is preserved of than CP. As for the standard preparation method for endometrial cytology samples, we considered that a concrete introduction of the LP method poses no problems. Diagn. Cytopathol. 2013. (c) 2011 Wiley Periodicals, Inc
WILEY-BLACKWELL, 2013年02月, DIAGNOSTIC CYTOPATHOLOGY, 41 (2), 120 - 125, 英語[査読有り]
研究論文（学術雑誌）
Objective: To assess whether the morphology of urine erythrocytes can be an effective tool for distinguishing glomerular disease from lower urinary tract disease in SurePath (TM) liquid-based cytology (SP-LBC). Methods: We examined four morphological parameters of erythrocytes: (1) irregular erythrocytes (of all types including fragmented forms) comprising greater than or equal to 20% of erythrocytes; (2) uniform erythrocytes (>80%); (3) doughnut or target-like shaped (D/T) erythrocytes (=1%); and (4) acanthocytes (=1%) in glomerular disease (n = 32) and lower urinary tract disease (n = 20) with SP-LBC slides in cases that had also been assessed by fresh urine sediment examination. Results: Sensitivity of D/T erythrocytes and acanthocytes (dysmorphic erythrocytes) for glomerular disease were 100% and 87.5%, respectively, with urine sediment examination, and 81.3% and 46.9%, respectively, in SP-LBC slides. Specificity was 100% for D/T erythrocytes and acanthocytes using either procedure. While irregular erythrocytes were specific for glomerular disease using urine sediment examination, they were seen in 70% of those with lower urinary tract disease using SP-LBC slides as a result of the deformation of erythrocytes by the fixative. Conclusions: Although the sensitivity of D/T erythrocytes and acanthocytes for glomerular disease was lower in SP-LBC slides than fresh urine sediment examination, their specificity was equally high. Therefore, urine erythrocyte morphology is useful in the detection of glomerular disease with the SP-LBC slides. However, morphological features apart from D/T erythrocytes and acanthocytes are not useful in SP-LBC slides.
WILEY-BLACKWELL, 2013年02月, Cytopathology, 24 (1), 52 - 57, 英語[査読有り]
研究論文（学術雑誌）
We compared the cytoarchitectural features used for the cytologic diagnosis of endometrial adenocarcinoma (EC) using ThinPrep® (TPS = ThinPrep Sample) and BD SurePath™ (SPS = SurePath Sample) preparations. In 20 patients, a direct endometrial sample using the Uterobrush was obtained. Nineteen cases of EA and one case of carcinosarcoma were studied. TPS and SPS were performed according to the manufacturer's recommendations. Moreover, after the TPS preparation, the residual material was also used to prepare an SPS sample (TP-SPS = ThinPrep-Surepath sample). The following points were investigated in both preparations: (1) number of cell clumps SPS had a significantly higher (20.9) than TPS (1.7) and TP-SPS (10.3) (2) long axis of clumps SPS had a significantly higher (215.4) than TPS (146.0) (3) rate of cell clumps with longer axes than 200 μm SPS had a significantly higher (36.7) than TPS (15.2) and TP-SPS (24.2). TP-SPS showed higher values than TPS (4) nuclear area TPS had a significant higher (61.2) than SPS (40.8) and TP-SPS (38.6) (5) degree of overlapping nuclei SPS (3.4) had a significantly higher number of overlapping nuclei than TPS (0.7) and TP-SPS (2.1) (6) nuclear chromatin pattern no significant differences for the nuclear chromatin pattern were found in the three different methods. The poor performance of TPS versus SPS and TP-SPS was explained with the heavy blood contamination of the samples, and the absence of adhesive coating in the slides is used for TPS. Further investigation of technical differences in liquid-based cytology methodologies is needed. © 2013 Wiley Periodicals, Inc.
2013年, Diagnostic Cytopathology, 41 (8), 673 - 681, 英語[査読有り]
研究論文（学術雑誌）
This study was to clarify the nuclear features of condensed clusters of stromal cells (EGBD-stromal cells) and metaplastic clumps with irregular protrusions (EGBD-metaplastic cells) which may be recognized in endometrial glandular and stromal breakdown (EGBD) cases in liquid-based cytologic (LBC) preparations of endometrial brushings. The material consists of cytologic smears of 20 cases of proliferative endometrium (PE), 20 cases of EGBD, and 20 cases of endometrioid adenocarcinoma grade 1 (G1) for which histopathological diagnosis was obtained by endometrial curettage. Nuclear findings were examined in PE cells, EGBD-stromal cells, EGBD-metaplastic cells, and G1 cells, respectively. It was examined about the following items: (1) Nuclear shape; (2) A long/minor axis ratio in cell nuclei; (3) An area of cell nuclei; (4) Overlapping nuclei; (5) The distribution pattern of nuclei within cell clusters. The following observations were made: (1) In PE cells, round-oval nuclei appeared to predominate, overlapping nuclei were not observed, and a slightly abnormal distribution pattern of nuclei was recorded; (2) In EGBD-stromal cells, reniform nuclei were characteristically observed, nuclei had small size and a generally elongated appearance, overlapping nuclei were recognized, and a remarkable abnormal distribution pattern of nuclei was found; (3) In EGBD-metaplastic cells, spindle nuclei were a characteristic feature, nuclei were larger in size and had a bipolar appearance, overlapping nuclei with moderately abnormal distribution pattern of nuclei were identified; (4) In G1 cells round-oval nuclei predominated, overlapping nuclei with moderately abnormal distribution pattern of nuclei were found. The study demonstrates that the analysis of selected nuclear findings appears to be very useful in the cytopathological assessment of endometrial lesions in LBC samples, especially for the discrimination of EGBD and G1. Diagn. Cytopathol. 2012. (c) 2012 Wiley Periodicals, Inc.
WILEY-BLACKWELL, 2012年12月, DIAGNOSTIC CYTOPATHOLOGY, 40 (12), 1077 - 1082, 英語[査読有り]
研究論文（学術雑誌）
BACKGROUND Studies were performed to determine if early treatment with an angiotensin II (Ang II) receptor blocker (ARB), olmesartan, prevents the onset of microalbuminuria by attenuating glomerular podocyte injury in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with type 2 diabetes mellitus. METHODS OLETF rats were treated with either a vehicle, olmesartan (10 mg/kg/day) or a combination of nonspecific vasodilators (hydralazine 15 mg/kg/day, hydrochlorothiazide 6 mg/kg/day, and reserpine 0.3 mg/kg/day; HHR) from the age of 7-25 weeks. RESULTS OLETF rats were hypertensive and had microalbuminuria from 9 weeks of age. At 15 weeks, OLETF rats had higher Ang II levels in the kidney, larger glomerular desmin-staining areas (an index of podocyte injury), and lower gene expression of nephrin in juxtamedullary glomeruli, than nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. At 25 weeks, OLETF rats showed overt albuminuria, and higher levels of Ang II in the kidney and larger glomerular desmin-staining areas in superficial and juxtamedullary glomeruli compared to LETO rats. Reductions in mRNA levels of nephrin were also observed in superficial and juxtamedullary glomeruli. Although olmesartan did not affect glucose metabolism, it decreased blood pressure and prevented the renal changes in OLETF rats. HHR treatment also reduced blood pressure, but did not affect the renal parameters. CONCLUSIONS This study demonstrated that podocyte injury occurs in juxtamedullary glomeruli prior to superficial glomeruli in type 2 diabetic rats with microalbuminuria. Early treatment with an ARB may prevent the onset of albuminuria through its protective effects on juxtamedullary glomerular podocytes.
NATURE PUBLISHING GROUP, 2012年05月, AMERICAN JOURNAL OF HYPERTENSION, 25 (5), 604 - 611, 英語[査読有り]
研究論文（学術雑誌）
This study was undertaken to clarify the origin of the chromophilic substance that stained in light green [light green body (LGB)] was observed in the condensed cluster of stromal cells and in the background of endometrial glandular and stromal breakdown cases. The material consists of cytologic smears of endometrial glandular and stromal breakdown (EGBD) from 58 samples in which a histopathological diagnosis was subsequently obtained by endometrial curettage. The following parameters were examined. (1) The occurrence and number of a LGB. As for the "condensed cluster of stromal cells," "condensed cluster of stromal cells including LGB" and "LBG in background," it was observed with all fields on one slide per case. When it was observed more than one in a preparation, the occurrence was determined and the number was also calculated. (2) Immunostaining of paraffin-embedded tissue sections and cytologic preparations. 1. The occurrence of "condensed cluster of stromal cells," "condensed cluster of stromal cells including LGB" and "LGB in background" was 100%, 44.8% and 91.4%, respec-tively. The number of "condensed cluster of stromal cells," "condensed cluster of stromal cells including LGB" and "LGB in background" was 21.2, 2.0 and 4.0, respectively. 2. When histological sections from paraffin-embedded tissue were tested by immunocytochemistry, "LGB" stained weakly or negative for fibrinogen, whereas it stained positively for CD31 and factor VIII. In addition, it stained positively for CD42b. 3. When cytologic preparation was tested by immunocytochemistry, "LGB" stained positively for CD31, factor VIII and CD42b. However, as for the fibrinogen, quantitative and qualitative evaluation of the immunocytochemical stain was not feasible due to extensive nonspecific reaction in the whole preparation. The "LGB" in EGBD cases proved to be a thrombus mostly made up by platelets, and it seemed that the recognition of the LGB showed to be a useful cytomorphological criterion for an always more accurate diagnosis of EGBD cases. Diagn. Cytopathol. 2012; 40: 204-209. (C) 2010 Wiley Periodicals, Inc.
WILEY-BLACKWELL, 2012年03月, DIAGNOSTIC CYTOPATHOLOGY, 40 (3), 204 - 209, 英語[査読有り]
研究論文（学術雑誌）
A case of endometriosis of the sigmoid colon on imprint cytology from an intraoperative biopsy is discussed. Cytologic specimens showed sheets or tubular epithelial clusters and stromal fragments. The epithelial cell nuclei were small and round to ovoid with finely granular chromatin and inconspicuous nucleoli. The background showed a few scattered spindle-type stromal cells without pigment-laden histiocytes. A definitive diagnosis of endometriosis can be based on cytology, provided that the cytologic findings are interpreted in the appropriate clinical context. Diagn. Cytopathol. 2012. (c) 2011 Wiley Periodicals, Inc.
WILEY-BLACKWELL, 2012年02月, DIAGNOSTIC CYTOPATHOLOGY, 40 (2), 159 - 162, 英語[査読有り]
研究論文（学術雑誌）
Recent studies demonstrated a possible role of aldosterone in mediating cell senescence. Thus, the aim of this study was to investigate whether aldosterone induces cell senescence in the kidney and whether aldosterone-induced renal senescence affects the development of renal injury. Aldosterone infusion (0.75 mu g/h) into rats for 5 weeks caused hypertension and increased urinary excretion rates of proteins and N-acetyl-beta-D-glucosaminidase. Aldosterone induced senescence-like changes in the kidney, exhibited by increased expression of the senescence-associated beta-galactosidase, overexpression of p53 and cyclin-dependent kinase inhibitor (p21), and decreased expression of SIRT1. These changes were abolished by eplerenone (100 mg/kg/d), a mineralocorticoid receptor (MR) antagonist, but unaffected by hydralazine (80 mg/liter in drinking water). Furthermore, aldosterone induced similar changes in senescence-associated beta-galactosidase, p21, and SIRT1 expression in cultured human proximal tubular cells, which were normalized by an antioxidant, N-acetyl L-cysteine, or gene silencing of MR. Aldosterone significantly delayed wound healing and reduced the number of proliferating human proximal tubular cells, while gene silencing of p21 diminished the effects, suggesting impaired recovery from tubular damage. These findings indicate that aldosterone induces renal senescence in proximal tubular cells via the MR and p21-dependent pathway, which may be involved in aldosterone-induced renal injury. (Endocrinology 152: 680-688, 2011)
ENDOCRINE SOC, 2011年02月, ENDOCRINOLOGY, 152 (2), 680 - 688, 英語[査読有り]
研究論文（学術雑誌）
Value of computer-assisted quantitative nuclear morphometry for differentiation of reactive renal tubular cells from low-grade urothelial carcinoma Objective: To assess whether computer-assisted quantitative morphological parameters can be an effective tool for objectively distinguishing reactive renal tubular cells from low-grade urothelial carcinoma cells (LG-UCs) in voided urine. Methods: Nuclear morphometry was performed by a computer-assisted image analyser system on Papanicolaou-stained cytological specimens. The circumference of reactive renal tubular cells (n = 40) or LG-UC (n = 20) nuclei were manually traced, and the following nuclear morphometric parameters were analysed: (i) area, (ii) perimeter, (iii) roundness factor, (iv) maximum length, and (v) linear factor. For each nuclear measurement, we calculated the maximum, minimum, mean and standard deviation. Results: The mean nuclear area and nuclear perimeter were higher in reactive renal tubular cells compared to the LG-UCs. The mean of roundness and linear factors (reflecting a tendency for the nuclear outline to be regular and oval, respectively) were higher in LG-UCs compared with reactive renal tubular cells. Among nuclear areas, the nuclear perimeter, roundness factors and maximum length did not show any significant differences between reactive renal tubular cells and LG-UCs. On the other hand, the linear factor showed a mean higher value among LG-UCs than reactive renal tubular cells (P = 0.023). Conclusions: Of five quantitative nuclear morphological parameters, only linear factor was statistically significant in differentiating reactive renal tubular cells in renal disease from LG-UCs.
WILEY-BLACKWELL, 2010年10月, CYTOPATHOLOGY, 21 (5), 334 - 338, 英語[査読有り]
研究論文（学術雑誌）
Can cytological features differentiate reactive renal tubular cells from low-grade urothelial carcinoma cells? Objective: To compare the cytomorphological and immunocytochemical features of reactive renal tubular cells and low-grade urothelial carcinoma cells (LG-UCs). Methods: We examined 15 cytological parameters in 38 cases with reactive renal tubular cells in renal disease and 20 cases of LG-UCs from bladder cancer that had been diagnosed by histological examination. Voided urine cytological parameters evaluated were as follows: (i) maximum cell numbers of clusters, (ii) cannibalism, (iii) rosette-like arrangement, (iv) hobnail-shaped cells, (v) vacuolated cytoplasm, (vi) intracytoplasmic haemosiderin, (vii) irregular nuclear contours, (viii) chromatin pattern, (ix) prominent nucleoli, (x) cast encasement, (xi) casts, (xii) dysmorphic erythrocytes, (xiii) isomorphic erythrocytes, (xiv) necrosis, and (xv) vimentin reactivity. The above parameters were determined using Mann-Whitney U-test and chi-square test, with differences considered significant at P < 0.05. Results: In reactive renal tubular cells, low to moderate cell numbers of clusters (fewer than 50 cells), rosette-like arrangement, hobnail-shaped cells, vacuolated cytoplasm, intracytoplasmic haemosiderin, euchromatin pattern, prominent nucleoli, dysmorphic erythrocytes and vimentin reactivity were present in significantly higher proportions compared with those in LG-UCs. In LG-UCs, high cell numbers of clusters (50 cells or more), cannibalism, heterochromatin pattern, isomorphic erythrocytes and necrosis were seen in significantly higher proportions. No significant differences were observed in irregular nuclear contours, cast encasement or casts. Conclusions: Based on results of the present study, maximum cell numbers of clusters, cannibalism, rosette-like arrangement, hobnail-shaped cells, vacuolated cytoplasm, intracytoplasmic haemosiderin, chromatin pattern, prominent nucleoli, dysmorphic erythrocytes, isomorphic erythrocytes, necrosis, and vimentin reactivity were capable of distinguishing reactive renal tubular cells from LG-UCs.
WILEY-BLACKWELL, 2010年10月, CYTOPATHOLOGY, 21 (5), 326 - 333, 英語[査読有り]
研究論文（学術雑誌）
- WILEY-LISS, 2010年09月, DIAGNOSTIC CYTOPATHOLOGY, 38 (9), 702 - 704, 英語
[査読有り]
- Cilnidipine suppresses podocyte injury and proteinuria in metabolic syndrome rats: possible involvement of N-type calcium channel in podocyte.
OBJECTIVES: Clinical studies have indicated the beneficial effect of an L/N-type calcium channel blocker (CCB), cilnidipine, on the progression of proteinuria in hypertensive patients compared with an L-type CCB, amlodipine. In the present study, we examined the effects of cilnidipine and amlodipine on the renal injury in spontaneously hypertensive rat/ND mcr-cp (SHR/ND) and their underlying mechanism. METHODS AND RESULTS: SHR/ND were treated with vehicle (nU10), cilnidipine [33 mg/kg per day, orally (p.o.); nU11] or amlodipine (20 mg/kg per day, p.o.; nU9) for 20 weeks. SHR/ND developed proteinuria in an age-dependent manner. Cilnidipine suppressed the proteinuria greater than amlodipine did. The immunohistochemical analysis showed that N-type calcium channel and Wilm's tumor factor, a marker of podocyte, were co-expressed. SHR/ND had significantly greater desmin staining, an indicator of podocyte injury, with lower podocin and nephrin expression in the glomeruli than Wistar-Kyoto rat or SHR. Cilnidipine significantly prevented the increase in desmin staining and restored the glomerular podocin and nephrin expression compared with amlodipine. Cilnidipine also prevented the increase in renal angiotensin II content, the expression and membrane translocation of NADPH oxidase subunits and dihydroethidium staining in SHR/ND. In contrast, amlodipine failed to change these renal parameters. CONCLUSION: These data suggest that cilnidipine suppressed the development of proteinuria greater than amlodipine possibly through inhibiting N-type calcium channel-dependent podocyte injury in SHR/ND.
2010年05月, Journal of hypertension, 28 (5), 1034 - 43, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
Objectives Clinical studies have indicated the beneficial effect of an L/N-type calcium channel blocker (CCB), cilnidipine, on the progression of proteinuria in hypertensive patients compared with an L-type CCB, amlodipine. In the present study, we examined the effects of cilnidipine and amlodipine on the renal injury in spontaneously hypertensive rat/ND mcr-cp (SHR/ND) and their underlying mechanism. Methods and results SHR/ND were treated with vehicle (n=10), cilnidipine [33 mg/kg per day, orally (p.o.); n=11] or amlodipine (20 mg/kg per day, p.o.; n=9) for 20 weeks. SHR/ND developed proteinuria in an age-dependent manner. Cilnidipine suppressed the proteinuria greater than amlodipine did. The immunohistochemical analysis showed that N-type calcium channel and Wilm's tumor factor, a marker of podocyte, were co-expressed. SHR/ND had significantly greater desmin staining, an indicator of podocyte injury, with lower podocin and nephrin expression in the glomeruli than Wistar-Kyoto rat or SHR. Cilnidipine significantly prevented the increase in desmin staining and restored the glomerular podocin and nephrin expression compared with amlodipine. Cilnidipine also prevented the increase in renal angiotensin II content, the expression and membrane translocation of NADPH oxidase subunits and dihydroethidium staining in SHR/ND. In contrast, amlodipine failed to change these renal parameters. Conclusion These data suggest that cilnidipine suppressed the development of proteinuria greater than amlodipine possibly through inhibiting N-type calcium channel-dependent podocyte injury in SHR/ND. J Hypertens 28:1034-1043 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
LIPPINCOTT WILLIAMS & WILKINS, 2010年05月, JOURNAL OF HYPERTENSION, 28 (5), 1034 - 1043, 英語[査読有り]
研究論文（学術雑誌）
Carcinoma of the collecting ducts of Bellini (CCDB) is a rare histological type of renal cell carcinoma. This article describes the cytological features of CCDB in voided urine, confirmed on the basis of the histopathology and immunohistochemistry. The CCDB cells occurred singly in loose aggregates and in small clusters, occasionally in a rosette-like structure. There were various types of cancer cells, including round to oval, spindle, and tadpole-like cells. The nuclei usually showed coarse chromatin, inconspicuous nucleoli, and lacy to vacuolated cytoplasm. CCDB of the kidney is a rare cytodiagnostic challenge in voided urine cytology alone. When the cytological diagnosis is considered, it is necessary to perform immunocytochemistry and correlate the clinical history and imaging studies. Diagn. Cytopathol. 2009;37:670-679. (C) 2009 Wiley-Liss, Inc.
WILEY-LISS, 2009年09月, DIAGNOSTIC CYTOPATHOLOGY, 37 (9), 676 - 679, 英語[査読有り]
研究論文（学術雑誌）
Objective: Cannibalism of one cell by another in voided urine cytology has been considered a cytological feature for differentiating urothelial carcinoma (UC) from benign lesions. Recently, however, we observed cannibalism in voided urine obtained from patients with renal glomerular disease (RGD). The purpose of this study was to determine the cytomorphological and immunocytochemical characteristics of cannibalism in voided urine from RGD. Methods: Seventy cytology specimens of voided urine were examined and the findings were compared with the histological findings. In addition, we compared the cytomorphological and immunocytochemical differences in cannibalism found in RGD and cases of UC selected as showing cannabilism. Results: Cannibalism in voided urine was found in three (5.5%) of 55 RGD cases. The finding was measured as (1+) < 5 cells, (2+) 5-20 cells, and (3+) > 20 cells and was (1+) in all three RGD cases, compared with 6.7%, 60% and 33.3% respectively in 15 UC cases. Differences in low cellularity cases (1+) and moderate to high cellularity cases (2+ or 3+) were statistically significant between RGD (3 and 0) and UC (1 and 14) (P=0.005). The maximum diameter of cannibalized cells in RGD was 24.3-33.0 mu m (mean 29.8 mu m) versus 18.0-30.4 mu m (mean 23.3 mu m) in UC (P=0.004). Necrosis and isomorphic erythrocytes were absent in RGD, but were found in 46.7% and 86.7%, respectively, of UC cases (P=0.245 and P=0.012). Dysmorphic erythrocytes were identified in all three cases with RGD and 13.3% of UC (P=0.012). Vimentin reactivity was found in all cases with cannibalism in RGD, but never in UC (P=0.001). Conclusions: Our results demonstrated that cannibalism in voided urine is present not only in UC but also in RGD. Furthermore, we showed that cellularity of cannibalism, vimentin reactivity and background differed significantly and can be used for differential diagnosis between the two groups.
WILEY-BLACKWELL PUBLISHING, INC, 2009年08月, CYTOPATHOLOGY, 20 (4), 224 - 230, 英語[査読有り]
研究論文（学術雑誌）
- Association of Metastin/a G-protein-coupled Receptor Signaling and Down Syndrome Critical Region 1 in Epithelial Ovarian Cancer
It has been revealed that metastin/a G-protein-coupled receptor (AXOR12) signaling enhances the expression of Down syndrome critical region 1 (DSCR1), known to be duplicated in Down syndrome, and suppresses tumor metastasis in in vitro study. The aim of this study was to evaluate whether gene expression of metastin/AXOR12 signaling system is correlated with that of DSCR1 and consequently affect prognosis of patients with epithelial ovarian cancer. Patients and Methods: The expression levels of metastin, AXOR12, DSCR1 isoform 1 (DSCR1-1), DSCR1 isoform 4 (DSCR1-4), calcineurin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression were analyzed by real-time quantitative reverse transcription-polymerase chain reaction in 102 epithelial ovarian cancer surgical specimens. Results: Patients were dichotomized into two groups having low and high expressions by using the median value as the cut-off. A good agreement was noticed between metastin and AXOR12 gene expression levels (kappa coefficient; 0.73), however, the gene expression of metastin/AXOR12 signaling system was not significantly correlated with that of DSCR1-4. BIN, univariate Cox regression analysis, the prognosis of the patients with low metastin and low AXOR12 gene expression was significantly worse than that of those with high metastin and high AXOR12 gene expression, respectively, (p=0.04 and 0.018). Combination of metastin and AXOR12 gene expression also had significant impact on patient prognosis (p=0.045). The DSCR1-1, DSCR1-4 and calcineurin gene expressions did not significand.N, affect the prognosis. Conclusion: The precise mechanism of metastin/AXOR12 signaling for suppression of the invasive phenotype in vivo, especially in epithelial ovarian cancer, is still uncertain. Genes such as DSCR1 that are duplicated in Down syndrome might not play an important role in tumorigenesis of epithelial ovarian cancer.
INT INST ANTICANCER RESEARCH, 2009年02月, ANTICANCER RESEARCH, 29 (2), 617 - 623, 英語[査読有り]
研究論文（学術雑誌）
- WILEY-BLACKWELL, 2008年12月, CYTOPATHOLOGY, 19 (6), 389 - 393, 英語
[査読有り]
研究論文（学術雑誌）
Objective To investigate the morphologic characteristics and immuno-cytochemical reaction to vimentin of the reactive renal tubular cells (RRTCs) in renal glomerular disease. Study Design We prospectively evaluated the urine cytology of renal glomerular disease in 40 patients who underwent renal biopy. The cytology and renal biopsy specimens were analyzed for vimentin immunostaining. Results A total of 40 urine samples from the 40 patients were cytologically analyzed, and RRTCs were found in 25 samples (25 of 40, 62.5%). These RRTCs showed clear or vacuolated cytoplasm., intracytoplasmic pigmented granules (hemosiderin or lipofuscin) and large nuclei with round to irregular nuclear contours and prominent nucleoli. These cells were seen singly and in acinar clusters. Occasionally RRTCs were embedded in a cast (RRTC cast). Immunocyto chemical study revealed RRTCs to be positive for vimentin (25 of 25, 100%). Conclusion Frequently observed characteristic cytomorphologic features of RRTCs included RRTC cast, acinar cluster, vacuolated cytoplasm and intracytoplasmic pigmented granules. A diagnosis of RRTCs can be suggested based on these cytomorphologic features. However, a definitive diagnosis will require immunocytochemical confirmation for vimentin.
SCI PRINTERS & PUBL INC, 2008年05月, ACTA CYTOLOGICA, 52 (3), 297 - 303, 英語[査読有り]
研究論文（学術雑誌）
In view of a cytoprotective effect of elastase inhibitor on chemokine-mediated tissue injury, we examined the neuroprotective effect of ONO-5046, a specific inhibitor of neutrophil elastase, in rats with spinal cord injury. Standardized spinal cord compression markedly increased cytokine-induced neutrophil chemo-attractant (CINC)-1 mRNA and protein. Their increases correlated with neurologic severity of injured rats. Immunohistochemically, CINC-1 protein was detected sequentially in vascular endothelial cells at 4 h, in perivascular neutrophils at 8 h, and in neutrophils infiltrating into cord substance at 12 h. Pretreatment with ONO-5046 (50 mg/kg) markedly ameliorated motor disturbance in injured rats, and reduced CINC-1 protein and mRNA expression. ONO-5046 also significantly reduced the increase of neutrophil accumulation or infiltration estimated by myeloperoxidase activity, and the extent of vascular permeability by Evans blue extravasation in the injured cord segment in comparison to control animals receiving vehicle. These results suggest that CINC-1 contributed to inflammation in rat spinal cord injury and ONO-5046 attenuated neurologic damage partly by blocking CINC-1 production of the chemoattractant, preventing neutrophil activation and vascular endothelial cell injury.
BLACKWELL SCIENCE LTD, 2001年09月, JOURNAL OF NEUROCHEMISTRY, 78 (5), 1064 - 1072, 英語[査読有り]
研究論文（学術雑誌）
MISC
- (株)医学書院, 2022年03月, 検査と技術, 50 (3), 296 - 318, 日本語
[招待有り]
＜文献概要＞はじめに 症例報告(case report)は,原著論文などに比べ過小評価される傾向にある.これは,実験や数十例以上の症例が必要な原著論文と異なり,1〜数例の症例があれば執筆できること,海外学術誌の多くが症例報告を掲載しなくなったこと注などが原因と考える.しかし,希少症例や例外的な所見を呈した症例などから得られた教訓・知見を論文にして,情報を発信することは臨床的に重要な意味をもつ.そもそも,原著論文と症例報告は役割が違うものであり,比較する対象ではない.症例報告は,医療現場で働く臨床検査技師が初めて書く論文のスタイルとして最適と考える.その理由として,日々の業務のなかでまれな症例や例外的な所見を呈した症例などに遭遇することは少なくないこと,特別な機材や試薬がなくとも執筆できることなどがある.ただし,希少症例といってもある程度はすでに症例報告として論文にされている場合が多い.自身が経験した症例が既報の症例報告の内容と同じであれば,論文にすることは困難である.いずれにしろ症例報告においても論文とするからには,なんらかの教訓や新たな知見が必要となる.
(株)医学書院, 2020年09月, 検査と技術, 48 (9), 976 - 979, 日本語[招待有り]
- (株)医学書院, 2020年09月, 検査と技術, 48 (9), 1022 - 1023, 日本語
[招待有り]
＜文献概要＞はじめに 尿沈渣と尿細胞診は,ともに尿を遠心沈殿して得られた沈渣成分を顕微鏡で観察する検査である.そのため,尿中に癌細胞があれば,尿沈渣と尿細胞診の両方に癌細胞が出現する.しかし,時に同一患者の尿沈渣と尿細胞診で結果が異なることがある.特に,今回の質問のように,"尿沈渣で陽性,尿細胞診で陰性"という判定となった場合には,(1)尿を採取するタイミングや方法が異なっている,(2)尿細胞診標本を細胞回収率の低い方法で作製している,以上の2つが原因である可能性が高い.本稿では,最初に"異型細胞"という言葉について確認した後に,今回の質問のような尿沈渣と尿細胞診で検査結果に違いがある場合の主な原因とその対策について私見を述べる.
(株)医学書院, 2020年05月, 検査と技術, 48 (5), 538 - 541, 日本語[招待有り]
- (公財)政策医療振興財団, 2019年11月, 医療の広場, 59 (11), 19 - 21, 日本語尿中ポドサイトによるIgA腎症の早期発見と病態評価 尿細胞診を用いた免疫細胞化学的検討
[招待有り]
- 兵庫県臨床検査技師会西播地区における災害支援への取組み
筆頭著者は、熊本地震の災害支援のために日本臨床衛生検査技師会が実施した深部静脈血栓症(deep vein thrombosis;DVT)検診に参加する機会を得た。それにより、災害支援としてのDVT検診の重要性のみならず、災害支援に対する事前準備の必要性を実感した。そこで我々は、災害支援に対する事前準備として「西播地区DVT検診実施可能者名簿」の作成を企画し、様々な方々の協力のもとに完成させた。今後は兵庫結全域の臨床検査技師を対象とした名簿作成や他組織との連携についても検討していく予定である。(著者抄録)
(一社)日本臨床衛生検査技師会, 2019年10月, 医学検査, 68 (4), 724 - 727, 日本語[査読有り]
- (一社)日本腎臓学会, 2019年08月30日, 日本腎臓学会誌, 61 (6), 916 - 916, 日本語腎結石を有するツチクジラの一症例
- Laboratory Practice 病理 尿細胞診におけるvimentin陽性細胞
＜文献概要＞はじめに 尿細胞診は,腎盂・尿管・膀胱の粘膜上皮に発生する腫瘍の発見,すなわち尿中の癌細胞の検出を主目的としている.一方で,尿細管上皮細胞など腎実質由来の細胞は,その形態や意義に関する知見に乏しかったこともあり,尿細胞診において軽視されてきた.筆者らは約20年前から,尿細胞診標本に出現する尿細管上皮細胞の細胞学的特徴の検討を行ってきた.その過程で,糸球体腎炎などの患者の尿中に再生異型を伴う尿細管上皮細胞(反応性尿細管上皮細胞)が出現すること,その形態が癌細胞に類似するため誤陽性の原因となっていることを見い出した(図1).さらに,その後の検討で,反応性尿細管上皮細胞と尿路上皮癌細胞の形態学的・免疫細胞化学的な鑑別点を解明してきた.特に免疫細胞化学において,反応性尿細管上皮細胞がvimentin陽性を示すことを発見し,vimentin陰性の尿路上皮癌細胞との鑑別に極めて有用であることを明らかにした.近年,学会などにおいて反応性尿細管上皮細胞とvimentinの反応性について発表されることも多くなり,その認識の広がりを実感している.しかし一方で,"vimentinは尿細管上皮細胞のマーカーである"などの誤解も生じている.本稿では,尿中に出現する各種上皮細胞と尿路上皮癌細胞におけるvimentinの反応性について解説する.
(株)医学書院, 2019年08月, 検査と技術, 47 (8), 927 - 931, 日本語[査読有り]
- (株)医学書院, 2018年04月, 検査と技術, 46 (4), 480 - 485, 日本語研究のすゝめ〜Bedside to Bench, Bench to Bedside〜(第5回) 臨床現場から教育現場へ 地方の中小規模病院でも研究はできる!
[招待有り]
- 日本組織細胞化学会, 2017年07月, 組織細胞化学, 2017, 67 - 80, 日本語酵素抗体法 基礎から実践まで
[招待有り]
尿細胞診は、尿路系悪性腫瘍のスクリーニングや経過観察に欠かすことのできない検査であるが、他領域の細胞診に比べ誤陽性の比率が高いという問題がある。特に、尿路結石患者の尿中に出現する反応性尿路上皮細胞は、形態学的に尿路上皮癌細胞に類似するため、誤陽性の原因となっている。そこで今回は、反応性尿路上皮細胞と尿路上皮癌細胞を客観的に鑑別することを目的として、vimentinを用いた免疫細胞化学的検討を行った。反応性尿路上皮細胞群18症例、尿路上皮癌細胞群17症例、正常尿路上皮細胞群21症例を対象とした。上記症例にvimentinを用いた免疫細胞化学を行い、1)各群における症例別のvimentin陽性率、2)各群における全細胞集団別のvimentin陽性率、3)反応性尿路上皮細胞群における結石の存在部位とvimentin陽性率の3項目について比較検討を行った。症例別と全細胞集団別のvimentin陽性率においては、反応性尿路上皮細胞群が尿路上皮癌細胞群・正常尿路上皮細胞群よりも有意に高い結果を示した。結石の存在部位とvimentin陽性率では、腎盂の方が尿管よりも有意に高いvimentin陽性率を呈した。今回の検討で、尿路結石症例に出現する反応性尿路上皮細胞のvimentin陽性率は、尿路上皮癌細胞よりも有意に高いことが明らかになった。以上よりvimentinを用いた免疫細胞化学は両者の客観的な鑑別に有用である。(著者抄録)
(一社)日本臨床衛生検査技師会, 2017年01月, 医学検査, 66 (1), 1 - 7, 日本語- 反応性尿路上皮細胞と尿路上皮癌細胞の鑑別におけるvimentinの有用性について
尿細胞診は、尿路系悪性腫瘍のスクリーニングや経過観察に欠かすことのできない検査であるが、他領域の細胞診に比べ誤陽性の比率が高いという問題がある。特に、尿路結石患者の尿中に出現する反応性尿路上皮細胞は、形態学的に尿路上皮癌細胞に類似するため、誤陽性の原因となっている。そこで今回は、反応性尿路上皮細胞と尿路上皮癌細胞を客観的に鑑別することを目的として、vimentinを用いた免疫細胞化学的検討を行った。反応性尿路上皮細胞群18症例、尿路上皮癌細胞群17症例、正常尿路上皮細胞群21症例を対象とした。上記症例にvimentinを用いた免疫細胞化学を行い、1)各群における症例別のvimentin陽性率、2)各群における全細胞集団別のvimentin陽性率、3)反応性尿路上皮細胞群における結石の存在部位とvimentin陽性率の3項目について比較検討を行った。症例別と全細胞集団別のvimentin陽性率においては、反応性尿路上皮細胞群が尿路上皮癌細胞群・正常尿路上皮細胞群よりも有意に高い結果を示した。結石の存在部位とvimentin陽性率では、腎盂の方が尿管よりも有意に高いvimentin陽性率を呈した。今回の検討で、尿路結石症例に出現する反応性尿路上皮細胞のvimentin陽性率は、尿路上皮癌細胞よりも有意に高いことが明らかになった。以上よりvimentinを用いた免疫細胞化学は両者の客観的な鑑別に有用である。(著者抄録)
(一社)日本臨床衛生検査技師会, 2017年01月, 医学検査, 66 (1), 1 - 7, 日本語[査読有り]
- (一社)日本臨床衛生検査技師会, 2015年11月, 医学検査, 64 (6), 743 - 748, 日本語尿細胞診におけるBDサイトリッチ法と従来法の比較検討 特に集細胞率について
[査読有り]
- 大分県臨床細胞学会, 2015年02月, 大分県臨床細胞学会誌, 25, 1 - 5, 日本語尿細胞診における尿細管上皮細胞の細胞学的特徴について
[招待有り]
- (一社)日本臨床衛生検査技師会, 2014年07月, 医学検査, 63 (4), 428 - 433, 日本語長期透析患者の尿中に腫瘍細胞を認めた後天性嚢胞性腎疾患関連腎細胞癌の1例
[査読有り]
- 2014年, 腎とフリーラジカル, 12, 95 - 99急性腎障害および腎虚血プレコンディショ二ングにおけるｐ21の腎保護効果
[招待有り]
- (一社)高知県臨床検査技師会, 2014年01月, こうち, 43 (2), 118 - 121, 日本語小規模施設における尿沈渣疑問症例コンサルテーションシステムの検討
[査読有り]
- 糸球体腎炎患者の尿中に出現する各種細胞の出現状況による病態推定 Liquid-based cytologyを用いた形態学的・免疫細胞化学的検討
SurePath法で作製した尿細胞診標本に、WT-1を用いた酵素抗体法を実施し、尿中WT-1陽性細胞と各種腎炎の関連について検討した。腎生検を施行した32例を対象とした。尿細胞診標本においてWT-1陽性細胞が1個以上出現していたのは12例であった。WT-1陽性細胞が出現したのは、IgA腎症(36%)、紫斑病性腎炎(100%)、糖尿病性腎症(75%)、アルポート症候群(100%)のみであった。腎生検時の血清クレアチニン値は平均1.49±1.51mg/dLであった。尿中WT-1陽性細胞数と尿蛋白とは有意な相関を認めた。細胞性半月体形成症例で尿中にWT-1陽性細胞が出現する率が高く、尿中WT-1陽性細胞は細胞性半月体形成の予測因子であった。尿中WT-1陽性細胞による細胞性半月体形戒の予測は感度58.3%、特異度95.0%で、AUCはO.83と中等度の正確性をもって予測可能と考えられた。
(公財)日本腎臓財団, 2013年11月, 腎臓, 36 (2), 134 - 139, 日本語[招待有り]
- (一社)日本腎臓学会, 2013年04月, 日本腎臓学会誌, 55 (3), 310 - 310, 日本語腎虚血プレコンディショニングにおけるp21の抗酸化酵素群を介した腎保護効果
- 体腔液における消化器腺癌のEGFRとp53の発現
上皮成長因子受容体(EGFR)とp53の免疫細胞化学を用い、消化器腺癌と反応性中皮細胞の体腔液細胞診での発現について検討し、発現と臨床病理学的な相関について検討した。EGFR抗体による免疫細胞化学の結果は反応性中皮44例ではスコア0である陰性35例、スコア1+が8例、2+が1例の計9例であった。腺癌32例では陰性11例、陽性はスコア1+が7例、2+が6例、3+が8例の計21例であった。EGFR抗体による腺癌および反応性中皮に対する感度は65.6%、特異度は79.5%であった。p53抗体による免疫細胞化学の結果は反応性中皮44例では陰性13例、スコア1+が11例、2+が11例、3+が9例の計31例であった。腺癌32例では陰性16例、陽性はスコア1+が3例、2+が3例、3+が10例の計16例であった。p53抗体による腺癌および反応性中皮に対する感度は50.0%、特異度は29.5%であった。
香川県臨床細胞学会, 2013年03月, 香川臨床細胞雑誌, 25 (1), 18 - 22, 日本語[査読有り]
- (一社)愛媛県臨床検査技師会, 2013年03月, 愛媛県臨床検査技師会誌, 32, 107 - 109, 日本語尿中に多数の尿細管上皮細胞が出現した小児ネフローゼ症候群の1例 尿細胞診における尿細管上皮細胞の経時的出現動態変化について
[査読有り]
- 医歯薬出版(株), 2011年03月, Medical Technology, 別冊 (最新染色法のすべて), 257 - 258, 日本語【最新染色法のすべて】病理検査 細胞診染色 性クロマチン(Xクロマチン)染色
[招待有り]
- 日本臨床細胞学会香川県支部, 2008年, 香川臨床細胞雑誌, 20 (1), 48 - 52, 英語Case report: Asymptomatic dissecting aneurysm of the celiac artery
[査読有り]
- 2008年, Kagawa jounal of clinical cytology, 20 (1), 19 - 21Asymptomatic dissecting aneurysm of the celiac artery
[査読有り]
- 2008年, Kagawa jounal of clinical cytology, 20 (1), 48 - 52The quantitive mRNA detection of podoplanin in body cavity fluids
[査読有り]
- 香川県臨床細胞学会, 2008年, 香川臨床細胞雑誌, 20 (1), 31 - 34, 日本語糸球体腎炎患者尿中に出現する反応性尿細管上皮細胞の形態学的・免疫細胞化学的特徴
[査読有り]
- 特定非営利活動法人 日本臨床細胞学会, 2008年, 日本臨床細胞学会雑誌, 47 (3), 196 - 199, 日本語シェーグレン症候群に合併した乳腺のアミロイド腫瘤
[査読有り]
- 医歯薬出版(株), 2000年05月, Medical Technology, 別冊 (尿沈渣検査症例アトラス), 200 - 201, 日本語【尿沈渣検査症例アトラス】尿沈渣で発見しえた大腸癌の膀胱内浸潤症例
[招待有り]
書籍等出版物
- 共著, 日本組織細胞化学会, 2017年08月, 日本語組織細胞化学2017
学術書
- 分担執筆, 篠原出版新社, 2016年04月液状化検体細胞診断マニュアル
- 分担執筆, 篠原出版新社, 2014年05月細胞診断マニュアル
- 分担執筆, 医学書院, 2012年06月, ISBN: 9784260015547顕微鏡検査ハンドブック
- 分担執筆, 医歯薬出版, 2011年06月, ISBN: 9784263223277病理検査学実習書
- 分担執筆, 医学書院, 2010年06月, ISBN: 9784260009416アトラス 細胞診と病理診断
講演・口頭発表等
- 日本臨床細胞学会雑誌, 2020年05月, 日本語, (公社)日本臨床細胞学会原発推定に苦慮した転移性脊椎腫瘍の一例
- 日本病理学会会誌, 2020年03月, 日本語, (一社)日本病理学会術後補助化学療法施行肺腺癌におけるATOX1の発現と患者予後との関連
- 日本病理学会会誌, 2020年03月, 日本語, (一社)日本病理学会非小細胞肺癌におけるCaveolin-1及びTks5発現の臨床病理学的意義
- 日本内分泌学会雑誌, 2020年02月, 日本語, (一社)日本内分泌学会Modulistatは腎炎モデルマウスにおいて貧血を改善する
- 日本臨床細胞学会雑誌, 2019年10月, 日本語, (公社)日本臨床細胞学会細胞検査士・研究活動教育への試み 大学院修士課程における細胞検査士養成、修士課程での研究教育
- 日本腎臓学会誌, 2019年08月, 日本語, (一社)日本腎臓学会腎結石を有するツチクジラの一症例
- 日本臨床細胞学会雑誌, 2019年05月, 日本語, (公社)日本臨床細胞学会尿中WT1陽性細胞(ポドサイト)と各種糸球体腎炎・半月体形成の関連について
- 日本医学検査学会抄録集, 2019年05月, 日本語, (一社)日本臨床衛生検査技師会兵庫県臨床検査技師会西播地区における災害支援への取組み
- 日本病理学会会誌, 2019年04月, 日本語, (一社)日本病理学会大腸癌肝転移巣におけるcleaved caspase-3(CC3)陽性血管 患者予後との関連
- 第57回日本臨床細胞学会秋期大会, 2018年11月, 日本語, 日本臨床細胞学会, 横浜, 国内会議腎実質由来細胞（尿細管上皮細胞・ポドサイト）における免疫細胞化学の有用性とpitfall
[招待有り]
シンポジウム・ワークショップパネル（指名）
- 第57回日本臨床細胞学会秋期大会, 2018年11月, 日本語, 横浜, 国内会議ALK陽性原発性肺癌の定性的および定量的細胞形態評価
ポスター発表
- 日本臨床細胞学会雑誌, 2018年10月, 日本語, (公社)日本臨床細胞学会泌尿器細胞診における免疫細胞化学の有用性と注意点 腎実質由来細胞(尿細管上皮細胞・ポドサイト)における免疫細胞化学の有用性とpitfall
- 第59回日本臨床細胞学会総会春期大会, 2018年06月, 日本語, 国内会議尿中ポドサイトは糸球体腎炎や半月体形成の非侵襲性バイオマーカーである
[招待有り]
シンポジウム・ワークショップパネル（指名）
- 第59回日本臨床細胞学会総会春期大会, 2018年06月, 日本語, 国内会議尿中ポドカリキシン陽性細胞は半月体形成のバイオマーカーとなり得るか
口頭発表（一般）
- 第107回日本病理学会総会, 2018年06月, 日本語, 国内会議大腸癌肝転移巣におけるアポトーシス・マーカーの発現：患者予後との関連
ポスター発表
- 第107回日本病理学会総会, 2018年06月, 日本語, 国内会議大腸癌肝転移巣におけるthymidine kinase 1（TK1）陽性血管と予後との関連性
ポスター発表
- 日本病理学会会誌, 2018年04月, 日本語, (一社)日本病理学会大腸癌肝転移巣におけるアポトーシス・マーカーの発現 患者予後との関連
- 日本臨床細胞学会雑誌, 2018年04月, 日本語, (公社)日本臨床細胞学会泌尿器細胞診における新技術と診断における問題点 尿中ポドサイトは糸球体腎炎や半月体形成の非侵襲性バイオマーカーである
- 日本分子生物学会/日本生化学会 2017年度生命科学系学会合同年次大会, 2017年12月, 日本語, 国内会議PKN1はリンパ球の細胞運動・トラフィッキングを制御する
ポスター発表
- 29th European Congress of Pathology, 2017年09月Urinay WT1 positive cells as a non-invasive biomarker of crescent formation.
- 日本高血圧学会臨床高血圧フォーラムプログラム・抄録集, 2017年05月, 日本語, (NPO)日本高血圧学会ドナー腎における尿細管老化度がレシピエント移植腎機能を規定する
- 日本臨床細胞学会雑誌, 2017年04月, 日本語, (公社)日本臨床細胞学会細胞検査士の教育と研究 ステップアップを目指して 地方の中小規模施設の細胞検査士でも研究実施と学位取得は可能である
- 第106回日本病理学会総会, 2017年04月, 日本語, 東京, 国内会議腫瘍新生血管同定のためのthymidine kinase 1/CD31二重免疫染色
ポスター発表
- 日本病理学会会誌, 2017年03月, 英語, (一社)日本病理学会大腸癌におけるclaudin-1の発現と臨床病理学的因子との相関(Reduced expression of claudin-1 in colorectal carcinoma is correlated with poor prognosis)
- 日本病理学会会誌, 2017年03月, 日本語, (一社)日本病理学会腫瘍新生血管同定のためのthymidine kinase 1/CD31二重免疫染色
- 日本臨床細胞学会中国四国連合会会報, 2015年07月, 日本語, 日本臨床細胞学会-中国四国連合会尿中WT-1陽性細胞は腎疾患のバイオマーカーとなり得るか?
- 日本臨床細胞学会中国四国連合会会報, 2015年07月, 日本語, 日本臨床細胞学会-中国四国連合会LBCの細胞像 従来法との比較、処理法による比較 尿細胞診におけるBDサイトリッチTM法と従来法の比較検討
- 38th European Congress of Cytology. Geneva, Switzerland, 2014年, 英語, 国際会議Urinary WT1-positive cells can detect some kinds of kidney disease
ポスター発表
- 38th European Congress of Cytology. Geneva, Switzerland, 2014年, 英語, 国際会議Case report of acquired cystic disease-associated renal cell carcinoma in voided urine.
ポスター発表
- 日本臨床細胞学会近畿連合会会誌, 2012年09月, 日本語, 日本臨床細胞学会-近畿連合会腎疾患の尿細胞診 特に反応性尿細管上皮細胞とLiquid-based cytologyについて
- The 37th European Congress of Cytology. Dubrovnik, Croatia, 2012年, 英語, 国際会議Diagnostic value of urine erythrocytes morphology in SurePath liquid-based cytology
- he 37th European Congress of Cytology. Dubrovnik, Croatia, 2012年, 英語, 国際会議Diagnostic value of urine erythrocytes morphology in SurePath liquid-based cytology
ポスター発表
- The 35th European Congress of Cytology. Lisbon, Portugal, 2009年, 英語, 国際会議Cytomorphology of reactive renal tubular cells in glomerular disease
[招待有り]
シンポジウム・ワークショップパネル（指名）
- The 35th European Congress of Cytology, 2009年, 英語, 国際会議Cytomorphology of reactive renal tubular cells in glomerular disease
[招待有り]
シンポジウム・ワークショップパネル（指名）
- 香川臨床細胞雑誌, 2008年03月, 日本語, 香川県臨床細胞学会胆・膵疾患の細胞診の諸問題 膵病変における術中穿刺吸引細胞診の有用性
- 香川臨床細胞雑誌, 2008年03月, 日本語, 香川県臨床細胞学会胆・膵疾患の細胞診の諸問題 胆汁細胞診疑陽性例の細胞診学的検討
- 香川臨床細胞雑誌, 2008年03月, 日本語, 香川県臨床細胞学会胆・膵疾患の細胞診の諸問題 四国細胞病理センターにおける胆汁細胞診の検討
- 香川臨床細胞雑誌, 2008年03月, 日本語, 香川県臨床細胞学会糸球体腎炎患者尿中に出現する反応性尿細管上皮細胞(RRTCs)について
- The 27th International Congress of The International Academy of Pathology. Athens, Greece., 2008年, 英語, 国際会議Presence of cell cannibalism itself does not rule out renal glomerular disease: cytologic-histologic correlation study
ポスター発表
- The 27th International Congress of the International Academy of Pathology, 2008年, 英語, 国際会議Presence of cell cannibalism itself does not rule out renal glomerular disease: cytologic-histologic correlation study
ポスター発表
- 中国四国医学検査学会抄録集, 2007年10月, 日本語, 中四国支部医学検査学会糸球体腎炎患者尿中に出現する反応性尿細管上皮細胞の細胞学的特徴
- 中国四国医学検査学会抄録集, 2007年10月, 日本語, 中四国支部医学検査学会尿細胞診における各種検体処理方法の比較
- 中国四国医学検査学会抄録集, 2007年10月, 日本語, 中四国支部医学検査学会尿路の異形成と上皮内癌の鑑別は可能か?尿路平坦病変鑑別におけるCK20、Ki-67、p53の有効性について
- 中国四国医学検査学会抄録集, 2007年10月, 日本語, 中四国支部医学検査学会血尿から腎・尿路疾患へのアプローチ 病理・細胞診からのアプローチ
- The 16th International Congress of Cytology. Vancouver, BC, Canada., 2007年, 英語, 国際会議Cytomorphologic and immunocytochemical characteristics of reactive renal tubular cells in renal glomerular disease
ポスター発表
- The 6th Japan-Korea Joint Meeting for Diagnostic Cytopathology. Pusan, South Korea., 2007年, 英語, 国際会議Cytologic features and vimentin expression of reactive renal tubular cells in renal glomerular disease
ポスター発表
- The 6th Japan-South Korea Workshop in Diagnostic Cytopathology, 2007年, 英語, 国際会議Cytologic features and vimentin expression of reactive renal tubular cells in renal glomerular disease
ポスター発表
- The 16th International Congress of Cytology, 2007年, 英語, 国際会議Cytomorphologic and immunocytochemical characteristics of reactive renal tubular cells in renal glomerular disease
ポスター発表
- 日本臨床細胞学会近畿連合会会誌, 2005年08月, 日本語, 日本臨床細胞学会-近畿連合会尿細胞診で軽視されてきた所見 特に円柱・赤血球・尿細管上皮細胞について
所属学協会
共同研究・競争的資金等の研究課題
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2022年04月 - 2026年03月, 研究代表者IgA 腎症の新たな非侵襲的検査法の開発 －腎生検と透析を回避するために－
- 日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 香川大学, 2022年04月 - 2026年03月, 研究分担者老化・加齢性疾患の予防に向けた「夏眠様反応」制御メカニズム解明のための基盤研究
- 公益財団法人 政策医療振興財団, 令和５年度 研究助成金, 神戸大学大学院 保健学研究科, 2023年06月 - 2024年05月, 研究分担者体腔液細胞診検体を用いた肺癌 PD-L1 発現の評価
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 香川大学, 2021年04月01日 - 2024年03月31日移植腎老化に着目した移植腎予後予測モデル構築に関する前向き観察研究
- （公財）平和中島財団, 2023年度 国際学術研究助成, 2023年04月 - 2024年03月, 研究代表者新たな診断技術を用いたラオスの悪性中皮腫の実態解明 ーアスベスト禁止法の成立のためにー
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2020年04月01日 - 2023年03月31日SLCトランスポーターの免疫組織化学染色による食道癌術前化学療法の効果予測
- 日本学術振興会, 科学研究費助成事業 挑戦的研究(萌芽), 挑戦的研究(萌芽), 香川大学, 2020年07月30日 - 2022年03月31日健康長寿をもたらす夏眠反応同定とその制御
- 日本臨床細胞学会, 班研究課題研究助成, 2020年04月 - 2022年03月, 研究代表者尿中ポドサイトによる糸球体腎炎の各種判定基準の確立
- （公財）政策医療振興財団, 平成30年度研究助成金, 2018年03月 - 2019年04月, 研究代表者尿中ポドサイトによるIgA腎症の早期発見と病態評価
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2016年04月01日 - 2019年03月31日VEGF依存性腫瘍血管の同定と大腸癌ベバシズマブ療法の効果予測
大腸癌組織のTK1陽性血管率（TK1-PVR；TK1/CD31二重免疫染色を利用）とKi67-PVRは正常組織よりも有意に高かったが、正常組織のTK1-PVRはKi67-PVRより有意に低かった。術前化学療法（NAC）後の大腸癌肝転移において、低血管密度群の全生存期間（OS）は有意に延長しており、低TK1-PVR群に死亡例はなかった。一方、腫瘍細胞におけるCC3やCCK18の高発現群、高CC3-PVR群のOSは有意に短縮していた。TK1/CD31二重免疫染色は腫瘍血管の同定に有用であること、NAC後の腫瘍血管やアポトーシスの解析により大腸癌肝転移患者の予後を予測できる可能性が示唆された。
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 香川大学, 2015年04月01日 - 2018年03月31日非侵襲的バイオマーカーによる腎移植後再発性腎炎の発症・活動性予測法の確立
新規バイオマーカー糖鎖異常IgA1による腎移植後IgA沈着症・腎症の非侵襲的診断・病態解明・予後予測・治療効果判定を目的に前向きコホート研究を行った。血清糖鎖異常IgA1、抗糖鎖異常IgA1-IgG、糖鎖異常IgA1-IgG免疫複合体ともにIgA沈着の有無で有意差は認めなかった。1年目にはIgA沈着症を認めるものの3年後には消失した症例では1年時の免疫複合体濃度は低い傾向にあり、糖鎖異常IgA1-IgG免疫複合体定量はIgA沈着症の予後予測に有用である可能性が示唆された。また、尿細管老化が移植腎機能に与える影響に関しても検討を行った。
- 文部科学省, 科学研究費補助金(基盤研究(C)), 2015年04月 - 2018年03月
競争的資金
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 愛媛県立医療技術大学, 2012年04月 - 2017年03月２０歳代女性のセクシャリティを育む子宮頸がん検診受診行動啓発プログラムの開発
本研究は、20歳代女性の子宮頸がんに対する心理・社会的特徴を明らかにし、子宮頸がん予防冊子配布型啓発による効果を検証するものである。 子宮頸がん検診に対する思いは、「検診不安」、「リプロダクティブヘルス意識」、「検診煩わしさ」が抽出され、「リプロダクティブヘルス意識」が高い者は、子宮頸がん予防の理解と行動がとれることが明らかになった。そこで、リプロダクティブヘルス、セクシャリティ向上に着目した子宮頸がん予防パンフレットを作成し配布した。対象者の背景に即した内容の啓発媒体は、子宮頸がん予防の意識を向上させる効果が示された。
- （公財）日本腎臓財団, 若手研究者助成, 2012年06月 - 2013年05月, 研究代表者糸球体腎炎患者の尿中に出現する各種細胞の出現状況による病態推定 －Liquid-based cytology を用いた形態学的・免疫細胞化学的検討－
競争的資金