Differential Expression of Vascular Endothelial Growth Factor (VEGF) and VEGF Receptors in the Sequence of Hyperplastic Polyp, Serrated Adenoma and Adenocarcinoma of Colorectum

AIM: The aim of this study was to investigate the role for vascular endothelial growth factor (VEGF) and its receptors, VEGFR-1 and -2, in the hyperplastic polyp (HP)- serrated adenoma (SA)-adenocarcinoma (AC) sequence of the colorectum.Methods: Thirty-six HPs, 33 SAs and 7 ACs (which contained HP and/or SA) were immunohistochemically examined for the expression of VEGF, VEGFR-1, and VEGFR-2.Results: VEGF protein was expressed in the cytoplasm of SA and AC tumor cells, and VEGFR-1 and VEGFR-2 were expressed both in the cytoplasm and on the membrane of these tumors, while there was faint or no expression of VEGF, VEGFR-1 and VEGFR-2 in HPs. Immunohistochemical staining revealed that 8.3% (3 of 36) HPs, 87.9% (29 of 33) SAs and 100% (7 of 7) ACs were positive for VEGF; 2.8% (1 of 36) HPs, 97.0% (32 of 33) SAs and 100% (7 of 7) ACs were positive for VEGFR-1; 16.7% (6 of 36) HPs, 100% (33 of 33) SAs and 100% (7 of 7) ACs were positive for VEGFR-2. The expression of VEGF, VEGFR-1 or VEGFR-2 was statistically correlated with the sequence of HP, SA and AC (P < 0.0001, respectively) Conclusion: Our results suggest that the VEGF pathway may play an important role in the HP-SA-AC sequence

Expression and Significance of Angiopoietin-1, 2 and Tie-2 Receptor in Human Extrahepatic Bile Duct Carcinoma: Correlation with Clinicopathological Factors

Extrahepatic bile duct cancer is a high mortal malignancy. Angiopoietin (Ang) and its receptor Tie, which are known to contribute to angiogenesis, have recently been reported to participate in the proliferation and differentiation of malignant tumor cells. The aim of this study is to investigate the expression and the significance of Ang-1, 2 and Tie-2 in extrahepatic bile duct carcinoma cells. We used immunohistochemistry to study 119 cases of surgically resected human extrahepatic bile duct carcinoma, and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) to confirm the expression of Ang-1, 2 and Tie-2 mRNA. Among these 119 cases, 52 (43.7%), 50 (42.0%) and 89 (74.8%) cases showed positive staining for Ang-1, 2 and Tie-2, respectively, in bile duct carcinoma cells. In 38 cases of normal mucosa, 6 (15.8%), 10 (26.3%) and 9 (23.7%) cases were positive for Ang-1, 2 and Tie-2, respectively. The positivity for Ang-1 and Tie-2 in normal mucosa was significantly different from all carcinomas (p<0.01 and p<0.001, respectively). We found no significant correlation between Ang-1 and Ang-2 expression and other clinicopathological factors such as histological differentiation, grade of tumor invasion or survival rate after surgery. In contrast, Tie-2 expression correlated significantly with degree of desmoplasia, cancer stage and survival of patients. RT-PCR analyses of five surgically resected tumor samples and three human bile duct cancer cell lines all showed positive expression of Ang-1, 2 and Tie-2 mRNAs. High expressions of Ang-1, 2 and Tie-2 in human extrahepatic bile duct carcinoma cells suggested that Ang-Tie system may be involved in the progression of human bile duct cancer

LNGFR+THY-1+VCAM-1hi+ cells reveal functionally distinct subpopulations in mesenchymal stem cells

Human mesenchymal stem cells (hMSCs), which conventionally are isolated based on their adherence to plastic, are heterogeneous and have poor growth and differentiation, limiting our ability to investigate their intrinsic characteristics. We report an improved prospective clonal isolation technique and reveal that the combination of three cell-surface markers (LNGFR, THY-1, and VCAM-1) allows for the selection of highly enriched clonogenic cells (one out of three isolated cells). Clonal characterization of LNGFR(+)THY-1(+) cells demonstrated cellular heterogeneity among the clones. Rapidly expanding clones (RECs) exhibited robust multilineage differentiation and self-renewal potency, whereas the other clones tended to acquire cellular senescence via P16INK4a and exhibited frequent genomic errors. Furthermore, RECs exhibited unique expression of VCAM-1 and higher cellular motility compared with the other clones. The combination marker LNGFR(+)THY-1(+)VCAM-1(hi+) (LTV) can be used selectively to isolate the most potent and genetically stable MSCs

Histological Remission during Corticosteroid Therapy of Overlapping Nonalcoholic Steatohepatitis and Autoimmune Hepatitis: Case Report and Literature Review

Concurrence of nonalcoholic steatohepatitis (NASH) with autoimmune hepatitis (AIH) is a rare condition that is challenging to diagnosis, due to the relatively high prevalence of autoantibodies in NASH. It is also difficult to determine the most effective treatment as corticosteroids are likely to worsen NASH despite being effective in the treatment of AIH. In this case report, we present a female diagnosed with NASH-AIH overlap with accompanying diabetes mellitus, who successfully achieved normalization of serum alanine aminotransferase levels following prednisolone therapy and weight loss. A follow-up liver biopsy performed 40 months after the initial diagnosis showed only minimal inflammatory infiltrates in the portal area without any NASH histology. Resolution of NASH, in conjunction with a reduction in hepatic fibrosis, might suggest that prednisolone itself does not aggravate steatohepatitis, but rather prevents disease progression. Appropriate immunosuppressive treatment may therefore be an important component of the optimum therapy for NASH-AIH overlap

Current status and problems of elderly drivers in our outpatient clinic

　当院では平成29年３月12日の道路交通法改正を踏まえて平成29年４月より，もの忘れ外来とは別に「運転免許外来」を新設し，時間をかけた丁寧な診療と告知，指導，運転免許返納後の生活確保・支援ができるよう，多職種で受診者に対応している．平成31年４月までの運転免許外来受診者は31人で，平均年齢80.07±3.91歳．第一分類該当者19人，交通違反での紹介３人で，その他は自発的な受診であった．10例は既に事故を起こし，６例は既に抗認知症薬を内服していた . 受診者のほとんどが，通院，買い物，農作業など運転中止後の生活が困るとの理由から，運転継続を希望した．神経心理検査では，MMSE-J 22.32/30±3.87, Kohs IQ 66.42±11.87, DASC-21 29.53±7.07, CDR 0.58±0.19と比較的認知機能低下が軽度な者が多かった．頭部 MRI では20例に陳旧性脳梗塞や脳挫傷，12例に脳萎縮を認め，123I-IMP 脳血流 SPECT では14例にアルツハイマー病を示唆する脳血流低下を認めた．診断後，全例に運転免許返納を推奨したが，自発的に運転中止に至った例は９例のみであった．かかりつけ医による診断書作成が普及し自主返納事例も増加したためか，当院の受診者数ならびに運転免許取り消し処分となる事例は外来開設当初の予想より少なかった．認知機能低下は認めるものの明らかな認知症に至っていない MCI 症例については，診断書提出後も運転継続している事例が多かった．運転継続希望者に丁寧に現制度の意義を説明し，移動手段の確保や生活支援について地域で相談できる体制作りが必要である．　Following the revision of the Road Traffic Act, which obligates elderly drivers to undergo cognitive screening tests at license renewal, we established a new outpatient memory clinic specializing in issues surrounding elderly drivers’ driver licenses. In this new outpatient clinic, we provide guidance and information about supporting resources for life after returning their driver’s licenses and the usual medical care and education. In the past two years, 31 patients, with an average age of 80.1±3.9 years, visited this clinic. Among these, 19 were referred to our clinic because of impaired cognition by screening test (the first classification), three were referred us for traffic violations and the others visited voluntarily. Among these 31 patients, ten had already experienced car accidents and six had already been prescribed cholinesterase inhibitors. Neuropsychological examination revealed mildly impaired cognitive function including MMSE-J 22.3±3.9, Kohs IQ 66.4±11.9, DASC-21 29.5±7.1 and CDR 0.58 ±0.19. Brain MRI revealed significant brain atrophy in 20 patients and brain contusions in 12. 123I-IMP SPECT showed decreased cerebral blood flow in 14 patients. Although driving is necessary for most patients to maintain activities of daily living and quality of life, we recommended all to stop driving based on the revised Road Traffic Act, which restricts driving by people with dementia. However, only nine patients suspended their driving and returned their licenses voluntarily; most MCI patients continued driving even after diagnosis. More effort is necessary to persuade patients of the significance of the current system, as is a social system that offers alternative means of transportation and supports patients in their lives in their local community

二歳児クラスでの集団遊びの発生過程における保育者の介入 : 「追いかけ遊び」におけるパターン化されたふりの生成

本稿では、二歳児クラスのごっこ的「追いかけ遊び」の発生過程における保育者の介入について、魅力的な遊びパターンの創出と伝染という視点から分析した。ごっこ的「追いかけ遊び」の基本パターンは、「怖いものの名前を呼んで想像世界を立ち上げる」「追いかける-逃げる」であった。保育者はこの基本パターンを創出し、子どもたちはこれで繰り返し遊び、自分のものにし、新しいパターンに作りなおしていった。この過程で子どもたちは遊びをリードし、他児の行動をルールにもとづいて調整し始めた。In this article, the generation processes of group play "Pretending to Chase" in the Two-year-olds Class and the intervention provided by the caregiver in these processes were explored from the point of generation and contagion of interesting play patterns. The basic pattern of "Pretending to Chase" was structured with "calling the names of scary things: the creation of an imaginary world" and pretending to "run after-run away." At first, the caregiver generated a fantasy play pattern. Next, the children played repeatedly with this pattern, and appropriated and recreated it. In these processes, the children began to lead the play and to regulate others\u27 behaviors following the rule

Apical membrane localization of glycogen synthase kinase 3beta protein in normal colon epithelium and aberrant distribution in colorectal cancer.

Glycogen synthase kinase 3beta (GSK-3beta) was subsequently shown to function in a wide range of cellular processes. GSK-3beta is a multifunctional serine/threonine kinase which performs a role in several signaling pathways including Wnt signal transduction. Recently, the activity of membrane-localized GSK-3beta has been shown to be crucial for initiation of Wnt cascade. In our study, the membrane localization of GSK-3beta was found on the apical membrane of normal epithelium, where co-localized and directly bound with MUC1. In colorectal cancer, depolarized cells showed the aberrant distribution of GSK-3beta on the cellular membrane with beta-catenin nuclear accumulation. The aberrant distribution of the membrane-localized GSK-3beta may contribute to the development of colorectal cancer

Differential Expression of Vascular Endothelial Growth Factor (VEGF) and VEGF Receptors in the Sequence of Hyperplastic Polyp, Serrated Adenoma and Adenocarcinoma of Colorectum

AIM: The aim of this study was to investigate the role for vascular endothelial growth factor (VEGF) and its receptors, VEGFR-1 and -2, in the hyperplastic polyp (HP)- serrated adenoma (SA)-adenocarcinoma (AC) sequence of the colorectum.Methods: Thirty-six HPs, 33 SAs and 7 ACs (which contained HP and/or SA) were immunohistochemically examined for the expression of VEGF, VEGFR-1, and VEGFR-2.Results: VEGF protein was expressed in the cytoplasm of SA and AC tumor cells, and VEGFR-1 and VEGFR-2 were expressed both in the cytoplasm and on the membrane of these tumors, while there was faint or no expression of VEGF, VEGFR-1 and VEGFR-2 in HPs. Immunohistochemical staining revealed that 8.3% (3 of 36) HPs, 87.9% (29 of 33) SAs and 100% (7 of 7) ACs were positive for VEGF; 2.8% (1 of 36) HPs, 97.0% (32 of 33) SAs and 100% (7 of 7) ACs were positive for VEGFR-1; 16.7% (6 of 36) HPs, 100% (33 of 33) SAs and 100% (7 of 7) ACs were positive for VEGFR-2. The expression of VEGF, VEGFR-1 or VEGFR-2 was statistically correlated with the sequence of HP, SA and AC (P < 0.0001, respectively) Conclusion: Our results suggest that the VEGF pathway may play an important role in the HP-SA-AC sequence