1.An Adenoid Cystic Carcinoma Cell Line Possessing High Metastatic Activity has High NF-κB Activation in Response to TNF-α
Katsuhiro Seki ; Kotaro Ishii ; Tsuyoshi Sugiura ; Miho Takahashi ; Yoshiko Inoue ; Kanemitsu Shirasuna
Oral Science International 2005;2(1):36-44
Adenoid cystic carcinoma (AdCC) is characterized by frequent recurrence and distant metastasis. Although lung metastasis in AdCC is very common, the mechanism by which this occurs is uncertain. When five AdCC cell lines (ACCS, ACCT, ACCH, Acc-3, and Acc-M) were screened for metastatic ability by injecting tumor cells into nude mice via the tail vein, lung metastases were found in mice injected with Acc-M (15/16 mice) but not in mice injected with any of the other four cell lines (0/10 mice with each line). To determine why Acc-M metastasizes to the lung but the others do not, we examined the biological characteristics of Acc-M and compared them with those of the other lines.Nuclear factor-κB (NF-κB) may play a key role in malignant tumor behaviors such as invasion and metastasis. Thus, we examined these cell lines for response to tumor necrosis factor (TNF-α), one of the typical stimulators of NF-κB. Although treatment with TNF-α stimulated matrix metalloprotease 9 (MMP-9) expression in all cell lines, the response to TNF-α varied between cell lines; the greatest stimulation was observed in Acc-M. Acc-M expressed higher levels of TNF receptors (both TNF-R1 and TNF-R2) than did the other AdCC lines. Judging from inhibitor-κBα degradation and nuclear translocation and DNA binding by NF-κB, the degree of activation of NF-κB in response to TNF-α in Acc-M cell lines was very high compared to the other lines. Moreover, the ability of Acc-M cells to adhere to endothelial cells, which was greater than that of the other cell lines, was further enhanced by pretreatment with TNF-α. Acc-M cells also expressed higher levels of sialyl Lewisx than did the other AdCC cell lines. These findings suggest that lung metastasis is mediated by tumor-endothelial cell interaction, which is probably associated with the NF-κB activation pathway. Further experiments are required to identify the molecules that mediate both lung metastasis and NF-κB activation.
2.Expression of Urokinase-type Plasminogen Activator (uPA), uPA Receptor, and Plasminogen Activator Inhibitor-1 in Oral Squamous Cell Carcinoma
Yoshiko Inoue ; Tsuyoshi Sugiura ; Ryousuke Matsuki ; Kotaro Ishii ; Katsuhiro Seki ; Kanemitsu Shirasuna
Oral Science International 2007;4(1):38-44
We investigated whether the expression levels of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1) correlate with clinicopathological features of oral squamous cell carcinoma (SCC). We immunohistochemically examined the expression levels of uPA, uPAR, and PAI-1 in 160 biopsy specimens of oral SCC. Positive stainings for uPA, uPAR, and PAI-1 were observed mainly in SCC cells, and their intensity and number of positive cells were related to lymph node involvement (p < 0.001, p < 0.001, and p < 0.001, respectively). The expression levels of uPA and uPAR were also related to the pattern of invasion (p < 0.05 and p < 0.001, respectively), while both were associated with tumor size (p < 0.05). Moreover, a poor survival rate was related to the expression of uPAR (p < 0.01) and PAI-1 (p < 0.05). These findings suggest that the uPA system may regulate the invasion and metastasis of oral SCC cells.
3.Neuroimmune interactions and kidney disease
Sho HASEGAWA ; Tsuyoshi INOUE ; Reiko INAGI
Kidney Research and Clinical Practice 2019;38(3):282-294
The autonomic nervous system plays critical roles in maintaining homeostasis in humans, directly regulating inflammation by altering the activity of the immune system. The cholinergic anti-inflammatory pathway is a well-studied neuroimmune interaction involving the vagus nerve. CD4-positive T cells expressing β2 adrenergic receptors and macrophages expressing the alpha 7 subunit of the nicotinic acetylcholine receptor in the spleen receive neurotransmitters such as norepinephrine and acetylcholine and are key mediators of the cholinergic anti-inflammatory pathway. Recent studies have demonstrated that vagus nerve stimulation, ultrasound, and restraint stress elicit protective effects against renal ischemia-reperfusion injury. These protective effects are induced primarily via activation of the cholinergic anti-inflammatory pathway. In addition to these immunological roles, nervous systems are directly related to homeostasis of renal physiology. Whole-kidney three-dimensional visualization using the tissue clearing technique CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) has illustrated that renal sympathetic nerves are primarily distributed around arteries in the kidneys and denervated after ischemia-reperfusion injury. In contrast, artificial renal sympathetic denervation has a protective effect against kidney disease progression in murine models. Further studies are needed to elucidate how neural networks are involved in progression of kidney disease.
Acetylcholine
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Arteries
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Autonomic Nervous System
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Cholinergic Neurons
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Homeostasis
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Humans
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Immune System
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Inflammation
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Kidney Diseases
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Kidney
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Macrophages
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Nervous System
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Neurotransmitter Agents
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Norepinephrine
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Optogenetics
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Physiology
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Receptors, Adrenergic
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Receptors, Nicotinic
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Reperfusion Injury
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Spleen
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Sympathectomy
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Sympathetic Nervous System
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T-Lymphocytes
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Ultrasonography
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Vagus Nerve
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Vagus Nerve Stimulation
4.An Observational Study of Google Reviews and Ratings of Medical Institutions
Kazushi TAKEHISA ; Masaya HONDA ; Ryutaro HIBI ; Tsuyoshi SUGIMARU ; Tomoya HIGUCHI ; Tomoko MATSUI ; Machiko INOUE ; Giichiro OISO
An Official Journal of the Japan Primary Care Association 2023;46(1):2-11
Introduction: Patients often refer to information on the Internet when selecting a medical institution, and some patients provide feedback on their experiences. In this study, we analyzed the content of patients' evaluations of medical institutions on Google.Methods: This study evaluated Google reviews and ratings of medical institutions in Shizuoka Prefecture. We coded the reviews with 12 items according to their content, and further categorized them into "positive," "negative," "unclassifiable," and "no description." We used modified Poisson regression analysis to investigate the relationship between ratings and assessment items.Results: Our sample consisted of 2,044 medical institutions. The number of reviews included in the analysis was 13,769. Reviews frequently commented on "doctor's behaviors," and positive comments about doctor's behaviors were significantly associated with high ratings (B: 0.76, 95%CI: 0.70 to 0.82), whereas negative comments were associated with low ratings (−4.65, −5.24 to −4.06).Conclusion: Within the reviews on Google, doctors' behavior had an impact on the ratings of medical institutions.
5.Three cases of hypersensitivity pneumonitis caused by inhalation of spores of "Cortinus Shiitake (Lentinus edodes)" and results of an epidemiological survey on Shiitake-growers.
Tsuyoshi IMURA ; Akiyoshi BANDO ; Yasuo WADA ; Yasushi FUKUSHIMA ; Ryozo HAYAI ; Hajime MATSUURA ; Hiroyuki INOUE ; Tetsuo KAGEYAMA ; Yoshio TAKEDA ; Teruyoshi ICHIHARA ; Kazunori KATO
Journal of the Japanese Association of Rural Medicine 1986;35(1):45-54
Three patients with hypersensitivity pneumonitis caused by inhalation of spores of Cortinus shiitake (Lentinus edodes) cultivated in vinyl houses were observed. These three patients developed the disease after harvesting shiitake for several hours in closed frame houses with a heater in the autum and winter. The frames were full of spores of shiitake and the patients suffered from a discordant feeling, systemic weakness, a feeling of cold, fever (over 38 C), a feeling of airway occlusion, a slight cough and sputum. These symptoms disappeared during rest the next day.
Case 1 was examined by the inhalation provocation test with a suspension of shiitake spores and spore-allergen. This test caused several clinical symptoms (fever, airway occlusion and various symptomatic feelings), leucocytosis, decrease of PaO2 a positive reaction of CRP and X-ray findings (appearance of interstitial pneumonitis shadows).
The 3 patients were considered to be suffering from allergic hypersensitivity pneumonitis due to inhalation of spores of Cortinus shiitake, because of their work, the development of symptoms after work in specific occupational conditions, a positive reaction to precipitating antibody against spore-allergen of shiitake, negative reactions to precipitation antibodies to 11 molds-allergens, various abnormal values in immunological tests and a positive reaction in a provocation test in one case.
In a survey of 45 shiitake-grower, it was found that 6 (13.3%) suffered from respiratory disease. No difference was found in the incidence of intracutaneous reactions to spore-allergen or allergen of dried shiitake in non-farm workers. Among 31 growers of shiitake a precipitation antibody to spore-allergen was observed only in these three patients. These results indicate that an allergic disposition is very important for development of hypersensitivity pneumonitis.
6.Swallowing‑related muscle inflammation and fibrosis induced by a single dose of radiation exposure in mice
Shuntaro SOEJIMA ; Chia‑Hsien WU ; Haruna MATSUSE ; Mariko TERAKADO ; Shinji OKANO ; Tsuyoshi INOUE ; Yoshihiko KUMAI
Laboratory Animal Research 2024;40(2):150-158
Background:
Although radiotherapy is commonly used to treat head and neck cancer, it may lead to radiation-asso‑ ciated dysphagia (RAD). There are various causes of RAD, however, the mechanism has not yet been fully identified.Currently, the only effective treatment for RAD is rehabilitation. Additionally, there are few available animal models of RAD, necessitating the development of new models to establish and evaluate RAD treatments. We hypothesize that radiation-induced neck muscle fibrosis could be one of the causes of RAD due to impairment of laryngeal eleva‑ tion. Therefore, in this study, we focused on the changes in inflammation and fibrosis of the strap muscles (Sternohy‑ oid, Sternothyroid, and Thyrohyoid muscles) after a single-dose irradiation. This research aims to provide a reference animal model for future studies on RAD.
Results:
Compared to control mice, those treated with 72-Gy, but not 24-Gy, irradiation had significantly increased tumor necrosis factor-α (TNF-α) (p < 0.01) and α-smooth muscle actin (αSMA) (p < 0.05) expression at 10 days and sig‑ nificantly increased expression levels of motif chemokine ligand-2 (CCL2), α-SMA, tumor growth factor-β1 (TGF-β1), type1 collagen, and interleukin-1β (IL-1β) (p < 0.05) in the muscles at 1 month by real-time PCR analysis. The results of immunohistochemistry showed that the deposition of type 1 collagen gradually increased in extracellular space after radiation exposure, and the positive area was significantly increased at 3 months compared to non-irradiated control.
Conclusions
A single dose of 72-Gy irradiation induced significant inflammation and fibrosis in the strap muscles of mice at 1 month, with immunohistochemical changes becoming evident at 3 months. This cervical irradiationinduced fibrosis model holds potential for establishing an animal model for RAD in future studies.
7.A Novel, Fully Covered Laser-Cut Nitinol Stent with Antimigration Properties for Nonresectable Distal Malignant Biliary Obstruction: A Multicenter Feasibility Study.
Hiroyuki ISAYAMA ; Kazumichi KAWAKUBO ; Yousuke NAKAI ; Kouta INOUE ; Chimyon GON ; Saburo MATSUBARA ; Hirofumi KOGURE ; Yukiko ITO ; Takeshi TSUJINO ; Suguru MIZUNO ; Tsuyoshi HAMADA ; Rie UCHINO ; Koji MIYABAYASHI ; Keisuke YAMAMOTO ; Takashi SASAKI ; Natsuyo YAMAMOTO ; Kenji HIRANO ; Naoki SASAHIRA ; Minoru TADA ; Kazuhiko KOIKE
Gut and Liver 2013;7(6):725-730
BACKGROUND/AIMS: Stent migration occurs frequently, but the prevention of complications resulting from covered self-expandable metal stents (C-SEMSs) remains unresolved. We prospectively assessed a newly developed C-SEMS, a modified covered Zeo stent (m-CZS), in terms of its antimigration effect. METHODS: Between February 2010 and January 2011, an m-CZS was inserted into 42 patients (31 initial drainage cases and 11 reintervention cases) at a tertiary referral center and three affiliated hospitals. The laser-cut stent was flared for 1.5 cm at both ends, with a 1 cm raised bank located 1 cm in from each flared end. The main outcome of this study was the rate of stent migration, and secondary outcomes were the rate of recurrent biliary obstruction (RBO), the time to RBO, the frequencies of complications, and overall survival. RESULTS: Of the 31 patients with initial drainage, stent migration occurred in four (12.9%, 95% confidence interval, 5.1% to 29.0%), with a mean time of 131 days. RBO occurred in 18 (58%), with a median time to RBO of 107 days. Following previous C-SEMS migration, seven of 10 patients (70%) did not experience m-CZS migration until death. CONCLUSIONS: m-CZSs with antimigration properties effectively, although not completely, prevented stent migration after stent insertion.
Aged
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Aged, 80 and over
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Alloys
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Carcinoma/*complications
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Cholestasis/etiology/*therapy
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Digestive System Neoplasms/*complications
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Drainage
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Equipment Design
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Feasibility Studies
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Female
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Humans
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Kaplan-Meier Estimate
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Lymphatic Metastasis
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Male
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Middle Aged
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*Prosthesis Failure
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Recurrence
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Reoperation
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*Stents/adverse effects
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Time Factors
8.Hooks at the Upper Instrumented Vertebra Can Adjust Postoperative Shoulder Balance in Patients with Adolescent Idiopathic Scoliosis: 5 Years or More of Follow-up
Shingo KUROYA ; Tsutomu AKAZAWA ; Toshiaki KOTANI ; Tsuyoshi SAKUMA ; Shohei MINAMI ; Yoshiaki TORII ; Tasuku UMEHARA ; Masahiro IINUMA ; Kenichi MURAKAMI ; Sumihisa ORITA ; Kazuhide INAGE ; Yawara EGUCHI ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Junichi NAKAMURA ; Gen INOUE ; Masayuki MIYAGI ; Wataru SAITO ; Seiji OHTORI ; Hisateru NIKI
Asian Spine Journal 2019;13(5):793-800
STUDY DESIGN: A retrospective cohort study. PURPOSE: This study aims to investigate postoperative shoulder imbalance (PSI) ≥5 years postoperatively in patients who underwent posterior spinal fusion using hooks at the upper instrumented vertebra (UIV) for Lenke type 1 adolescent idiopathic scoliosis (AIS). OVERVIEW OF LITERATURE: Studies have reported PSI due to excessive correction of the main thoracic curve. METHODS: We examined 56 patients with AIS who underwent a posterior spinal fusion with hooks at the UIV from 2004 to 2010. Of these, we enrolled 14 patients who underwent surgery, at least, 5 years ago. X-rays and Scoliosis Research Society-22 (SRS-22) questionnaire were administered. To evaluate the shoulder balance, T1 vertebral tilt angle (T1 tilt), clavicle angle, and radiographic shoulder height (RSH) were measured. PSI was considered as the absolute value of the postoperative RSH being ≥20 mm. Based on radiographs obtained immediately postoperatively, we divided patients into two groups as follows: the balanced group (absolute value of RSH <20 mm) and imbalanced group (absolute value of RSH ≥20 mm). RESULTS: The frequency of PSI was 28.6% immediately postoperatively, 0% 2 years postoperatively, and 7.1% at the last follow-up. In the balanced group, PSI did not occur even at 2 years postoperatively or at the last follow-up. In the imbalanced group, PSI was improved in all patients 2 years postoperatively and all patients, except one patient, at the last follow-up. No significant differences were noted in the frequency of distal adding-on at 2 years postoperatively or the last follow-up between the balanced group and the imbalanced group. We observed moderate negative correlations between the absolute value of T1 tilt and the SRS-22 pain and satisfaction at the last follow-up. CONCLUSIONS: Hooks at the UIV could adjust the shoulder balance to avoid long-term PSI in patients with AIS.