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41.
Y Kanai Y Nakai N Nakajima S Tanayama 《Xenobiotica; the fate of foreign compounds in biological systems》1979,9(1):33-50
1. [14C]Ethyltetrazolylchromone ([14C]ETC) was promptly absorbed from the rat small intestine by the portal route. 2. The maximum plasma concn. of unchanged drug after oral administration (10 mg/kg) was highest in dogs (456 microgram/ml), followed by monkeys (287 microgram/ml), guinea-pigs (146 microgram/ml) and rats (55 microgram/ml), and lowest in rabbits (09 microgram/ml). The half-life of the drug in plasma varied with the species, ranging from 13 to 133 h. The drug was highly bound to plasma protein. In dogs and rats, the plasma 14C was predominantly the unchanged drug, whereas in guinea-pigs, rabbits and monkeys it was mainly metabolites. 3. At 10 min after oral administration of the drug to rats there was a wide distribution of the 14C in the tissues. At this time, the 14C concn. were the highest in stomach, followed by kidney, liver, plasma, heart and lung, and lowest in brain. 4. Almost all administered 14C was eliminated from the body in 72 h. The major route of excretion was via the urine except with guinea-pigs, in which animal the 14C was almost equally divided between urine and faeces. 5. only trace amounts of the unchanged drug were found in urine and bile. The major urinary metabolites were as follows: I (1-hydroxyethyl ETC), II (acetyl ETC), III (IIIa, 2-hydroxyethyl ETC) and IV (1,2-dihydroxyethyl ETC) in rats, I and VI (5-carboxymethylsalicylic acid) in guinea-pigs, I, III (IIIb, carboxymethyl ETC) and VII (ETC-N-1-glucuronide) in rabbits, I and VII in dogs, and I and IV in monkeys. 相似文献
42.
Developmental changes in multispecific organic anion transporter 1 expression in the rat kidney 总被引:5,自引:0,他引:5
Nakajima N Sekine T Cha SH Tojo A Hosoyamada M Kanai Y Yan K Awa S Endou H 《Kidney international》2000,57(4):1608-1616
BACKGROUND: The cDNA of the multispecific organic anion transporter 1 (OAT1) responsible for the tubular secretion of organic anions was recently isolated. In the current study, we investigated the developmental changes in OAT1 expression in the rat kidney. METHODS: Ontogenic expression of rat OAT1 was investigated by Northern blot, in situ hybridization, Western blot, and immunohistochemical analysis. In addition, para-aminohippurate (PAH) accumulation was measured using fetal, neonatal, and adult rat kidney slices. RESULTS: In Northern blot analysis, OAT1 was detected as early as on embryonic day 18 in the fetal kidney. The expression level of OAT1 mRNA increased remarkably just after birth (postnatal day 0). In situ hybridization revealed OAT1 expression on embryonic day 19. In both the fetal and neonatal kidneys, OAT1 mRNA was localized in a relatively deep region in the cortex. Western blot analysis detected OAT1 protein on embryonic day 20, and the expression level increased after birth. Immunohistochemical analysis did not reveal OAT1 staining in the fetal kidneys. A faint signal of OAT1 protein was detected on postnatal day 0; thereafter, the expression level increased. In the functional study using kidney slices, low but definite probenecid-sensitive PAH accumulation was noted in fetal rat kidney on embryonic day 20. After birth, probenecid-sensitive PAH uptake was increased. CONCLUSIONS: The present study consistently demonstrates the remarkable increase of OAT1 expression after birth, and the immature excretory capacity of the proximal tubules of the neonatal kidney can be attributed, at least in part, to the low expression level of OAT1. 相似文献
43.
Tsubosa Y; Fukutomi T; Tsuda H; Kanai Y; Akashi-Tanaka S; Nanasawa T; Linuma G; Ushio K 《Japanese journal of clinical oncology》1998,28(1):42-46
We report a case of invasive breast cancer in a 62-year-old female patient
with Cowden's disease. A left modified radical mastectomy was performed and
histopathology of the tumor showed invasive ductal carcinoma, histological
grade 3, without lymph node metastasis. The patient had a past history of
endometrial cancer at 55 but did not have a family history of malignant
disease. Goiter was palpable but aspiration cytology revealed no
malignancy. There were several papillomas on the oral mucosa and multiple
papillomatous lesions on the right femur. Barium X-ray and endoscopic
examination revealed multiple, small, hyperplastic polypoid lesions on the
esophagus, stomach and rectum. Histopathology of the biopsy specimens from
the esophagus and stomach showed acanthotic squamous epithelium and
foveolar hyperplastic polyps. The patient was followed up closely to
monitor the thyroid lesions and polyposis of the digestive tract. A total
of 12 breast cancer patients who also had Cowden's disease have been
reported in Japan and these cases are reviewed in this report.
相似文献
44.
Fujii K; Fukutomi T; Tsuda H; Akashi-Tanaka S; Nanasawa T; Kanai Y; Muramatsu Y 《Japanese journal of clinical oncology》1998,28(1):47-49
A 44-year-old woman presented with a right huge axillary mass. Both
mammography and ultrasonography revealed a primary cancer of 2.8 cm maximum
diameter in the right breast and metastases in the axillary lymph nodes,
both being confirmed by aspiration cytology as ductal carcinoma. Right
standard radical mastectomy with level III axillary lymph node dissection
was carried out. Pathologically, the tumor was diagnosed as ductal
carcinoma in situ with microinvasion (DCISM), histologic grade 3. The area
of stromal invasion measured 1 mm at its widest point. Sixteen of the 17
resected axillary lymph nodes contained metastases, including six level III
lymph nodes. Immunohistochemical studies of the tumor revealed
overexpression of p53 protein, but not that of c-erbB-2 protein. The
frequency of lymph node metastases from DCISM is reported to be very low.
Therefore, the present case with extensive involvement of level III lymph
nodes was unusual.
相似文献
45.
N Kikuchi M Kanai N Kita Y Mitsuhashi I Konishi 《International journal of gynaecology and obstetrics》2006,94(1):62-66
Buerger's disease is an inflammatory occlusive vascular disorder involving small- and medium-sized arteries in the distal extremities and is usually complicated with thrombophlebitis. Since Buerger's disease develops most frequently in men who smoke, pregnancy complicated with this disease is extremely rare. Only three pregnancies have been reported previously. All cases indicate that Buerger's disease worsens during pregnancy. However, anti-coagulant therapy appeared to be effective in this case. Accordingly, careful observation is mandatory in pregnancies complicated with Buerger's disease. 相似文献
46.
Matsuo H Tsukada S Nakata T Chairoungdua A Kim DK Cha SH Inatomi J Yorifuji H Fukuda J Endou H Kanai Y 《Neuroreport》2000,11(16):3507-3511
Amino acid transport system L has been proposed to be one of the major nutrient transport systems at the blood-brain barrier. Using immunohistochemical analyses, a system L transporter LAT1 was shown to be expressed in the brain capillary endothelial cells in rats. Because LAT1 was coexpressed with 4F2 heavy chain which brings LAT1 to the plasma membrane, LAT1 is proposed to be functional in the plasma membrane of brain capillary endothelial cells. Both LAT1 and 4F2hc immunoreactivities were detected in a double line appearance surrounding endothelial cell nuclei, suggesting both proteins are present in the luminal and abluminal membranes. LAT1 is, thus, a blood-brain barrier system L transporter responsible for the permeation of aromatic or branched-chain amino acids and amino acid-related drugs such as L-DOPA. 相似文献
47.
Inoue K Saito M Kanai T Kawata T Shigematsu N Uno T Isobe K Liu CH Ito H 《The American journal of Chinese medicine》2008,36(3):625-634
The honeybee product propolis and its extracts are known to have biological effects such as antibiotic, anti-viral, anti-inflammatory and anti-tumor activities. This study was designed to investigate whether water-soluble propolis (WSP) inhibits tumor growth. The tumor cell line used was mouse sarcoma 180 (S-180), and its growth was determined in vitro and in vivo with exposure to different concentrations of WSP. The effects of WSP on tumor cells in vitro were evaluated by measuring the intracellular uptake of 3H-thymidine. 3H-thymidine uptake was inhibited in accordance with the concentration of WSP. The minimum concentration of WSP necessary for 3H-thymidine uptake inhibition was 1.0 microg/ml and uptake was suppressed to 88% of the level in non-treated cells at this concentration. In an experiment using tumor-bearing mice, oral administration of WSP was begun 24 hours after transplantation of S-180 cells. WSP was administered to the mice 5 times, every other day for 10 days. The doses were 320 mg/kg (10 mg/mouse) or 960 mg/kg (30 mg/mouse) of body weight. All mice were sacrificed 10 days after transplantation, and tumor growth was evaluated. The orally administered WSP significantly inhibited the growth of transplanted tumors (p < 0.05). Furthermore, histological findings revealed a significant reduction in mitotic cells and tumor invasion of the muscular tissue at both dose-levels of WSP. 相似文献
48.
49.
Preheparin serum lipoprotein lipase mass is negatively related to coronary atherosclerosis 总被引:4,自引:0,他引:4
Hitsumoto T Ohsawa H Uchi T Noike H Kanai M Yoshinuma M Miyashita Y Watanabe H Shirai K 《Atherosclerosis》2000,153(2):391-396
In preheparin serum, there exists lipoprotein lipase (LPL) mass with little activity. The clinical significance of this preheparin serum LPL mass (preheparin LPL mass) is unclear. We studied the levels of preheparin LPL mass in patients with coronary atherosclerosis, comparing the results with those in healthy men. We also evaluated the correlation between preheparin LPL mass and the severity of coronary atherosclerosis by comparing with other risk factors such as age, smoking, family history, hypertension, hyperuricemia, diabetes mellitus, total cholesterol, triglyceride, high density lipoprotein-cholesterol and body mass index. The subjects, 70 men presenting with symptoms of coronary artery disease, underwent coronary angiographic examination. Significant narrowness was defined as > or = 75%. Control group comprised 77 men who had annual health checks and showed no abnormal findings. Preheparin LPL mass in the stenosis group was lower than normal coronary group and also than the control group. Multivariate analysis showed that preheparin LPL mass had the highest t-value (-2.53) for the number of lesions among the risk factors listed above. These results suggest that low preheparin LPL mass may be deeply involved in the progression of coronary atherosclerosis. 相似文献
50.
Overexpression of interleukin-6 aggravates viral myocarditis: impaired increase in tumor necrosis factor-alpha 总被引:10,自引:0,他引:10
Tanaka T Kanda T McManus BM Kanai H Akiyama H Sekiguchi K Yokoyama T Kurabayashi M 《Journal of molecular and cellular cardiology》2001,33(9):1627-1635
The process of inflammation and immune response is regulated by proinflammatory cytokines. Interleukin-6 (IL-6), one of the proinflammatory cytokines, plays a potentially critical role in viral-induced myocarditis. Our previous work demonstrates that exogenous IL-6 administration, given at the time of encephalomyocarditis virus (EMCV) inoculation in C3H/HeJ mice, has a protective effect on myocardium and improves survival rates. In the present study, we examined whether overexpression of IL-6 modified viral myocarditis. On day 3 and 10 after inoculation with EMCV, the ratio of heart weight to body weight and myocardial injury were significantly increased in IL-6 transgenic mice (IL-6TG). On day 3, a reduction of viral clearance was shown by the presence of elevated viral titers and viral replication in the heart of IL-6TG. The concentrations of serum tumor necrosis factor- alpha (TNF alpha) were dramatically increased in wild-type mice on day 1, in contrast, this change was not observed in IL-6TG. Treatment with recombinant human TNF (2 microg) significantly improved viral clearance in the IL-6TG hearts. Thus, overexpression of IL-6 promotes myocardial injury by interrupting both the cytokine network and viral clearance. These experiments suggest the possibility that IL-6 is one of the factors that accelerates tissue damage, including myocardial injury, in the viral myocarditis. 相似文献