-
[show abstract]
[hide abstract]
ABSTRACT: Germinal center/lymphoid follicle area ratio and CD3/CD20-positive area ratio were calculated for the spleen, submandibular and mesenteric lymph nodes, and Peyer's patches in cynomolgus monkeys treated orally with cyclosporin A (CsA), an immunosuppressant which blocks Ca(2+)/NFAT signaling. A difference in hypocellularity between lymphoid organs was observed after CsA administration in a dose-dependent manner. Regarding drug efficacy, the highest susceptibility to CsA tended to be shown in the Peyer's patches, and susceptibility then descended in the order of the spleen, mesenteric lymph nodes, and submandibular lymph nodes. It was shown in the present study that decreases in germinal center area and CD3-positive area were sensitive indicators of the efficacy of CsA for lymphoid organs and tissue in cynomolgus monkeys.
Journal of Veterinary Medical Science 06/2012; · 0.85 Impact Factor
-
Chika Hirowatari,
Rinya Kodama,
Yuji Sasaki,
Yohei Tanigawa,
Junko Fujishima,
Tsuyoshi Yoshikawa,
Kaori Yabuuchi,
Yuki Kuwamura,
Kimiaki Hirakawa,
Yasuhiro Kamimura, Hiroshi Maeda
[show abstract]
[hide abstract]
ABSTRACT: Porencephaly was observed in a female cynomolgus monkey (Macaca fascicularis) aged 5 years and 7 months. The cerebral hemisphere exhibited diffuse brownish excavation with partial defects of the full thickness of the hemispheric wall, and it constituted open channels between the lateral ventricular system and arachnoid space. In addition, the bilateral occipital lobe was slightly atrophied. Histopathologically, fibrous gliosis was spread out around the excavation area and its periphery. In the roof tissue over the cavity, small round cells were arranged in the laminae. They seemed to be neural or glial precursor cells because they were positive for Musashi 1 and negative for NeuN and GFAP. In the area of fibrous gliosis, hemosiderin or lipofuscin were deposited in the macrophages, and activated astroglias were observed extensively around the excavation area.
Journal of Toxicologic Pathology 03/2012; 25(1):45-9. · 0.48 Impact Factor
-
Rinya Kodama,
Takanobu Okazaki,
Tamio Sato,
Shuichiro Iwashige,
Yohei Tanigawa,
Junko Fujishima,
Akiko Moriyama,
Nobuyoshi Yamashita,
Yuji Sasaki,
Tsuyoshi Yoshikawa,
Yasuhiro Kamimura, Hiroshi Maeda
[show abstract]
[hide abstract]
ABSTRACT: We investigated chronological changes in immunohistochemical phenotyping in the thymus and spleen in Crl:CD rats up to the age of about one year. In the thymus, T cells increased markedly from 3 to 4 weeks of age. Proliferating cells also increased markedly at these points. B cells tended towards an increase with age. In the spleen, white pulp increased until 9 weeks of age and remained fairly stable thereafter. In the periarteriolar lymphoid sheath and marginal zone, T cells gradually increased until 9 weeks of age and became almost flat thereafter. In the lymph follicle, T cells increased with age. B cells tended towards an increase with age in all areas of the spleen. It was concluded that development of the thymus was most marked from 3 to 4 weeks of age and that both the thymus and spleen had matured by 9 weeks of age.
Journal of Toxicologic Pathology 03/2012; 25(1):55-61. · 0.48 Impact Factor
-
Tsuyoshi Yoshikawa,
Akiko Moriyama,
Rinya Kodama,
Yuji Sasaki,
Tatsumi Sunagawa,
Takanobu Okazaki,
Asami Urashima,
Yoshiro Nishida,
Akihiro Arima,
Ayumi Inoue,
Takayuki Negishi,
Yasuhiro Yoshikawa,
Toshio Ihara, Hiroshi Maeda
[show abstract]
[hide abstract]
ABSTRACT: To evaluate morphologic alterations in the thyroid gland in the second generation in cynomolgus monkeys, pregnant dams were exposed to high doses of thiamazole. In Experiment A, dams received thiamazole intragastrically via a nasogastric catheter from gestation day (GD) 50 to GD 150 or on the day before delivery. Initially, the dose level was 20 mg/kg/day (10 mg/kg twice daily); however, the dose level was subsequently decreased to 5 mg/kg/day (2.5 mg/kg twice daily), since deteriorated general conditions were observed in two dams. Six out of seven neonates died on the day of birth. The cause of neonatal death was tracheal compression and suffocation from goiter. The transplacental exposure to thiamazole affected the fetal thyroid glands and induced goiter in all neonates. The surviving neonate was necropsied 767 days after discontinuation of thiamazole exposure and showed reversibility of the induced changes. In Experiment B, dams were intragastrically administered thiamazole at 5 mg/kg/day (2.5 mg/kg twice daily) for treatment periods from GDs 51 to 70, 71 to 90, 91 to 110, 111 to 130 and 131 to 150. All fetuses showed enlarged thyroid glands but were viable. Histopathologically, hypertrophy and/or hyperplastic appearance of the follicular epithelium of the thyroid gland was observed at the end of each treatment period. The most active appearance of the follicular epithelium, consisting of crowded pedunculated structure, was demonstrated at end of the treatment period from GD 131 to 150. This is the first report on the morphology of fetal and neonatal goiter in the cynomolgus monkey.
Journal of Toxicologic Pathology 12/2011; 24(4):215-22. · 0.48 Impact Factor
-
Akiko Moriyama,
Junko Fujishima,
Tomohiro Furukawa,
Tsuyoshi Yoshikawa,
Rinya Kodama,
Yuji Sasaki,
Takaharu Nagaoka,
Yasuhiro Kamimura, Hiroshi Maeda,
Takuya Hirai,
Ryoji Yamaguchi
[show abstract]
[hide abstract]
ABSTRACT: To clarify the morphological characteristics of the cynomolgus monkey immune system, we analyzed quantitative data on their lymphoid organs. Spleens, major lymph nodes and Peyer's patches were sampled from cynomolgus monkeys, and the lymphoid follicle and germinal center areas and percentages of CD3- and CD20-positive areas were calculated. All the organs analyzed showed large interindividual variations in the sizes of lymphoid follicles and germinal centers. Lymphoid follicle in the spleen, submandibular lymph nodes and Peyer's patches showed no marked difference in size. Germinal center size in the mesenteric lymph nodes and Peyer's patches were significantly smaller than those in the spleen. Areas containing T cells were largest in the lymph nodes, while those containing B cells were largest in the spleen and Peyer's patches. The mean size of the splenic lymphoid follicle in cynomolgus monkeys is larger than that in rats and similar to that in humans. Based on the large individual variation and the characteristics of lymphoid organs, it is important to use cynomolgus monkeys in standard toxicity studies. Taking advantage of the characteristics of each species enables reliable evaluation of the immunologic system in standard toxicity studies.
Journal of Veterinary Medical Science 07/2011; 73(11):1459-64. · 0.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Two cases of spontaneous focal hepatic hyperplasia were observed in young female cynomolgus macaques (Macaca fascicularis). Grossly, a single raised nodule was observed in the left hepatic lobe. Histopathologically, the nodule compressed surrounding normal tissue; however, the hepatic cords within the nodule continued to those in the nor mal area except in part. Extensive fibrosis and absence of a normal hepatic triad were observed in the nodule. Thin fibrous septa radiating from the dense central stellate scarring and distended vessels were apparent in one animal. Hepatocytes in the nodule lacked cellular atypia, showed frequent PAS-positive eosinophilic inclusions in the cytoplasm and showed higher positive ratios for PCNA. The present cases resembled focal nodular hyperplasia reported in humans and a chimpanzee.
Journal of Toxicologic Pathology 06/2011; 24(2):125-9. · 0.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Severe bilateral cataract was found in a 7 year-old naïve female cynomolgus monkey (Macaca fascicularis) 3 months before necropsy. During macroscopic examination, severe opacity and thinning of the lens were observed in both eyes. Histopathology revealed that the lens nuclei and majority of cortex lens fibers had disappeared and become excavated, while the lens fibers in the subcapsular area were swollen and distorted. Other observations included atrophy and vacuolation in the lens epithelial cells and proliferation of spindle cells and collagen fiber beneath the anterior capsule of the right eye. Immunohistochemical staining of these spindle cells revealed the presence of vimentin, cytokeratin and α-smooth muscle actin (α-SMA), which were considered to be derived from lens epithelial cells. This is a rare case of spontaneous, bilateral, hypermature cataract in a cynomolgus monkey.
Journal of Toxicologic Pathology 03/2011; 24(1):69-73. · 0.48 Impact Factor
-
Rinya Kodama,
Xiuying Yang,
Tomoaki Araki,
Masato Sato,
Shuichiro Iwashige,
Yohei Tanigawa,
Mie Uchimura,
Keisuke Ishimaru,
Yuji Sasaki,
Yasuhiro Kamimura, Hiroshi Maeda
[show abstract]
[hide abstract]
ABSTRACT: In a seven-year-old male cynomolgus monkey, erythema of the upper eyelid and forehead and corneal opacity, edema and conical protrusion in the eye were observed. At necropsy, ophthalmological and serological examinations revealed binocular corneal opacity and conical protrusion and a high IgE level, respectively. Thinning of the epithelium and stroma of the cornea were noted histopathologically. At the center of the corneal epithelium, the number of epithelial cells was reduced, their cytoplasm was poorer and the basal cells were flatter than at the periphery. Bowman's membrane was folded with partial loss or breakage. Collagen fibers were compacted or disarranged, and the keratocytes were increased in the stroma, with focal pyknosis or loss of the endothelium and folding of Descemet's membrane. Electron microscopical examination revealed atrophy of the corneal epithelial basal cells. This is the first report of a case of keratoconus in a cynomolgus monkey.
Journal of Toxicologic Pathology 03/2010; 23(1):53-8. · 0.48 Impact Factor
-
Hirofumi Minomo,
Yusuke Torikai,
Tomohiro Furukawa,
Hiroshi Uchino,
Hidetomi Kadokura,
Kazuhiro Nakama, Hiroshi Maeda,
Takeshi Kamenosono,
Takayuki Sukamoto,
Koichiro Fukuzaki,
Ryoichi Nagata
[show abstract]
[hide abstract]
ABSTRACT: Recently, troponin T (TnT) and troponin I (TnI) have been reported as suitable biomarkers of myocardial injury for pre-clinical toxicity studies. The purpose of the present study was to investigate the characteristics of troponins as myocardial damage biomarkers in cynomolgus monkeys. Initially, tissue distribution of biomarkers was investigated in nine organs (including the heart, liver, and kidneys) collected from naive cynomolgus monkeys. The results showed that TnT and TnI were distributed specifically in the heart, and were not detected in other tissues. Secondly, changes in blood biomarker levels and histopathological changes in cardiac tissue were investigated following myocardial injury induced by concomitant administration of isoproterenol (ISO) and vasopressin (VASO). Compared with pre-dosing, TnT and TnI were markedly increased in the ISO + VASO groups, in which severe histopathological changes including necrosis and vacuolation of muscle fibers were observed. In order to investigate the relationship of biomarker levels with the severity of myocardial injury, Spearman's correlation coefficient was calculated between C(max) and AUC and necrosis and vacuolation scores in the heart. A high correlation between necrosis and vacuolation in the heart and TnT and TnI levels was noted. These results suggest that TnT and TnI possess high sensitivity and specificity for myocardial injury in cynomolgus monkeys, and are useful biomarkers for detection of drug-induced myocardial injury in cynomolgus monkeys.
The Journal of Toxicological Sciences 12/2009; 34(6):589-601. · 1.52 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study investigated structural alterations and the immunohistochemical expression of androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PgR) in the mammary glands from surgically postmenopausal cynomolgus monkeys (Macaca fascicularis). Fourteen animals were divided into 2 groups. Seven animals underwent an ovariectomy (OVX), and the other 7 animals underwent a sham operation (sham). The in-life phase of study was 78 weeks. Atrophy in the mammary glands of OVX monkeys was similar to early postmenopausal atrophy of the human breast. The proportion of AR-positive cells in the OVX group was significantly higher than in the sham group, but the proportion of ER and PgR-positive cells was significantly lower. These results suggest that use of a primate model for hormone receptor expression has potential applications in basic human endocrinology, particularly in research in hormone receptor expression in mammary glands (both normal and neoplastic).
Veterinary Pathology 02/2009; 46(3):526-30. · 1.95 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A solid mass arising from the mammary gland was found in a 7-year-old female cynomolgus monkey. Histologically, the mass consisted of 2 components: spindle-shaped or ovoid sarcomatous cells and squamous epithelial cells. Metastatic nodules noted in the lung, liver and the gallbladder had the same histological features as the mammary mass. Immunohistochemistry revealed that the sarcomatous cells were positive for alpha-smooth muscle actin (alpha-SMA), vimentin, calponin, S-100 protein, epithelial membranous antigen (EMA), cytokeratin (large spectrum) and cytokeratin 14 (CK 14) in the cytoplasm, and p53, erbB-2 and progesterone receptor in the nuclei, but negative for desmin and estrogen receptor. The squamous epithelial cells were positive for EMA, cytokeratin (large spectrum) and CK 14, but negative for the rest. Both sarcomatous and squamous epithelial components were negative for glial fibrillary acidic protein (GFAP). Based on histological and immunohistochemical features, the present case was diagnosed as a malignant myoepithelioma with a squamous epithelial component in the mammary gland with distant metastases.
Toxicologic Pathology 31(5):549-53. · 1.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Spontaneous mammary tumors were seen in seven of the 12 breeding female rats aged 2 years. All mammary tumors were diagnosed as mammary dysplasia (MD). Bone mineral contents (BMC) and bone mineral density (BMD) of their lumbar vertebrae and femur were determined using dual energy X-ray absorptiometry (DXA). In rats with MD, body weight (BW), BMD of the lumbar vertebrae and BMC of the femur were significantly higher than in the rats without MD. Although corpus luteum (CL) and follicles were seen in the ovaries of all animals, the number of CL in rats with MD was significantly lower than the rats without MD. It was suggested that high BMD, BW and decreased CL promoted mammary tumors.
In vivo (Athens, Greece) 21(4):583-6. · 1.17 Impact Factor
