Toshitaka Nakagawa

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Long-Term Chronic Toxicity and Mesothelial Cell Reactions Induced by Potassium Octatitanate Fibers (TISMO) in the Left Thoracic Cavity in A/J Female Mice

International Journal of Toxicology (2015)

Masanao Yokohira Nozomi Hashimoto Toshitaka Nakagawa Yuko Nakano Keiko Yamakawa

The present study was conducted to examine the chronic effects of potassium octatitanate fibers (trade name TISMO; chemical formula K 2 O·6TiO 2 ) on the mouse lung and thoracic cavity. This method of infusion was employed to examine the direct effects of the fibers to the pleura. In the present study, 52- and 65-week experiments were employed to examine the long-term chronic effects after infusion of fiber-shaped TISMO into the thoracic cavities of A/J mice. Following this infusion, TISMO fibers were observed in the alveoli, indicating penetration through the visceral pleura. The additional histopathological detection of TISMO fibers in the liver, spleen, kidneys, ovary, heart, bone marrow, and brain of TISMO-infused mice indicated migration of the fibers out from the thoracic cavity. Atypical mesothelial cells with severe pleural proliferation were observed, but malignant mesotheliomas were not detected. This study demonstrated that intrathoracic infusion of TISMO fiber did not cause malignant mesothelioma but did cause severe chronic inflammation and proliferation of pleural mesothelial cells.

Thoracic cavity

Mesothelium

Pleural cavity

Chronic toxicity

Intratracheal instillation

Abdominal cavity

10.1177/1091581815587744

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Citations (5)

Presence of FXYD6 in the endolymphatic sac epithelia

Neuroscience Letters (2012)

Takenori Miyashita Kosuke Akiyama Ryuhei Inamoto Ai Matsubara Toshitaka Nakagawa

Endolymph

Endolymphatic sac

Immunolabeling

10.1016/j.neulet.2012.02.005

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Citations (9)

Strict angiotensin blockade prevents the augmentation of intrarenal angiotensin II and podocyte abnormalities in type 2 diabetic rats with microalbuminuria

Journal of Hypertension (2008)

Akira Nishiyama Toshitaka Nakagawa Hiroyuki Kobori Yukiko Nagai Noriyuki Okada

Objectives Beneficial effects of angiotensin II type 1 receptor blockers have been indicated for patients with diabetic nephropathy. We investigated the effects of an angiotensin II type 1 receptor blocker, telmisartan, on intrarenal angiotensin II levels and the progression of albuminuria or glomerular injury in type 2 diabetic Otsuka Long–Evans Tokushima Fatty rats with microalbuminuria. Methods and Results Otsuka Long–Evans Tokushima Fatty rats were randomly treated with telmisartan (10 mg/kg/day, orally), hydralazine (25 mg/kg/day in drinking water) or vehicle from the initiation of albuminuria (13 weeks old). At this age, Otsuka Long–Evans Tokushima Fatty rats showed low but detectable albuminuria (1.0 ± 0.1 mg/day) and higher systolic blood pressure, postprandial blood glucose and kidney angiotensin II levels than age-matched nondiabetic Long–Evans Tokushima Otsuka rats. At 35 weeks of age, vehicle-treated Otsuka Long–Evans Tokushima Fatty rats did not show apparent glomerular injury or tubulointerstitial fibrosis but did exhibit severe albuminuria (72.6 ± 5.9 mg/day) and accumulation of cytoplasmic granules containing albumin in podocytes. Otsuka Long–Evans Tokushima Fatty rats also showed higher systolic blood pressure, postprandial blood glucose, collagen gene expression, desmin staining (a marker of podocyte injury) and angiotensin II levels than Long–Evans Tokushima Otsuka rats. Treatment with telmisartan did not affect postprandial blood glucose but decreased systolic blood pressure, collagen gene expression, desmin staining and angiotensin II levels. Telmisartan also prevented the development of albuminuria (0.6 ± 0.1 mg/day at 35 weeks old) and accumulation of cytoplasmic granules. Hydralazine treatment resulted in a similar reduction in systolic blood pressure and partially attenuated the albuminuria (35.4 ± 1.8 mg/day at 35 weeks old) but did not affect the other parameters. Conclusion The present results suggest the contribution of augmented intrarenal angiotensin II levels to the initiation and progression of albuminuria as well as podocyte abnormalities in type 2 diabetic rats. Angiotensin II blockade may inhibit the transition from microalbuminuria to overt nephropathy through prevention of intrarenal angiotensin II augmentation, independently of changes in blood pressure and glucose levels.

Albuminuria

Telmisartan

Microalbuminuria

10.1097/hjh.0b013e3283060efa

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Citations (45)

(プロ)レニン受容体との相互作用のためのプロレニンの“ハンドル”領域の基本的なアミノ酸残基の重要な役割

Hypertension (2009)

Fumihiko Suzuki Tadashi Inagami Akiko Ichihara Toshitaka Nakagawa Yasumichi Arai

Source

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Citations (0)

Histomorphometry of ectopic mineralization using undecalcified frozen bone sections

Microscopy Research and Technique (2018)

Ryuji Fujihara Yoichi Chiba Toshitaka Nakagawa Ryuta Murakami Koichí Matsumoto

To investigate the correlation between mineral formation and enhanced expressions of some proteins using undecalcified frozen bone sections. Histological studies have revealed that some proteins, such as BMP2, BMPR1A, and Connexin 43, are expressed in and around sites of ectopic ossification. However, the relationship between the expressed proteins considered to be associated with the ossification and mineral formation in vivo is not clear. Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1)-mutant spinal hyperostotic TWY mice and ICR mice as controls were euthanized after calcein labeling, and undecalcified frozen sections were obtained from the middle thoracic spine. Intervertebral disc areas were examined histologically and by measuring calcein-labeled areas and areas showing immunoreactivity for BMP2, BMPR1A, and Connexin 43. Calcein-labeled areas, indicating mineralization in the ectopic mineralization sites, were significantly larger in the mutant mice than in controls. The expression of Connexin 43 was elevated in the annulus fibrosus. Increases in the calcein-labeled areas was not correlated with increases in the areas showing immunoreactivity for Connexin 43 in the annulus fibrosus. There was no statistical correlation between enhanced immunohistochemical expression and elevated calcein-labeled areas. By applying the morphometrical analysis method using undecalcified frozen sections to ENPP1-mutant mice, quantitative evaluation of the mineralization and proteins expressed in the surrounding area in the same animal became possible.

Calcein

Intervertebral Disc

10.1002/jemt.23140

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Citations (4)

The expression of LDL receptor in vessels with blood–brain barrier impairment in a stroke-prone hypertensive model

Histochemistry and Cell Biology (2010)

Masaki Ueno Bin Wu Toshitaka Nakagawa Yukiko Nagai Masayuki Onodera

LRP1

RAGE

10.1007/s00418-010-0705-y

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Citations (14)

168 Effect of topical FK506 on the number of epidermal Langerhans cells

Journal of Dermatological Science (1995)

Kazuhisa Nakashima Toshitaka Nakagawa Yoshitaka Manabe Takashi TAKAIWA

10.1016/0923-1811(95)93881-z

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Citations (1)

The expression of matrix metalloproteinase-13 is increased in vessels with blood–brain barrier impairment in a stroke-prone hypertensive model

Hypertension Research (2009)

Masaki Ueno Bin Wu Akira Nishiyama Chenglong Huang Naohisa Hosomi

Immunostaining

Stroke

10.1038/hr.2009.26

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Citations (27)

Monopolar Spindle Induced by Isoamericanol A Suppresses Human Breast Cancer Cell (MCF-7) Growth

Asian Journal of Cell Biology (2018)

Ayako Katagi Li Sui Kazuyo Kamitori Toshisada Suzuki T. Katayama

Background and Objective: The neolignan isoamericanol A was purified from the organic layer of the MeOH extract of the waste residue of the Jatropha curcas L. (Jatropha) seed.The previous work revealed that isoamericanol A can induce G2/M arrest on MCF-7.The aim of the present study was to evaluate the selective effect of isoamericanol A on the human breast cancer cell line (MCF-7), as well as to clarify the point at which isoamericanol A exhibited anti-cancer activity on MCF-7 at M phase.Materials and Methods: The normal human breast cell line (MCF-10A) and the human breast cancer cell line (MCF-7) were subjected to isoamericanol A treatment for 3 days for cell growth inhibition assay.DNA microarray analysis was performed to reveal the expressional difference on MCF-7 with or without 3-day isoamericanol A treatment.Also, the effect of short term isoamericanol A treatment was studied by flow cytometry analysis, as well as immunofluorescent staining using Aurora B, "-tubulin and the chromosome.Results: In this experiment, both MCF-10A and MCF-7 were treated with isoamericanol A to measure the relative degrees of inhibition.Though inhibiting both cell lines, isoamericanol A effected 25.9±6.14%(n = 4, p<0.05) more growth inhibition on MCF-7 than it did on MCF-10A.Microarray analysis showed isoamericanol A resulted in numerous expressional changes in cell division related genes pertaining to spindle formation.The immunofluorescent staining showed that brief isoamericanol A treatment is capable of inducing cell growth inhibition specifically by disrupting regular spindle formation during M phase.Flow cytometry analysis showed brief isoamericanol A treatment induced G2/M arrest.Conclusion: Isoamericanol A inhibits human breast cancer cell proliferation more than it does normal human breast cells.Moreover, this study revealed that isoamericanol A treatment can induce G2/M cell cycle arrest due to monopolar spindle formation during cell division.

MCF-7

10.3923/ajcb.2019.1.6

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Citations (2)

3.P.175 CD36 is expressed in atherosclerotic lesion and its expression is upregulated by oxidized LDL

Atherosclerosis (1997)

Satoshi Nozaki Shunichi Yamashita Toshitaka Nakagawa Atsuyuki Nakata Motohiro Nishida

CD36

Expression (computer science)

10.1016/s0021-9150(97)89250-7

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Citations (0)