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Peroxisome proliferator-activated receptor delta (PPARdelta), a novel target site for drug discovery in metabolic syndrome. 总被引:5,自引:0,他引:5
Sadao Takahashi Toshiya Tanaka Tatsuhiko Kodama Juro Sakai 《Pharmacological research》2006,53(6):501-507
The development of new treatments for metabolic syndrome is urgent project for decreasing the prevalence of coronary heart disease and diabetes mellitus in the advanced countries. Peroxisome proliferator-activated receptor (PPAR)alpha and gamma agonists have shed light on the treatment of hypertriglyceridemia and type 2 diabetes mellitus, respectively. Among PPARs, analysis of the PPARdelta functions is lagging behind because specific PPARdelta agonists have not been developed. The appearance of new PPARdelta agonists is brightening the prospects for elucidating the physiological role of PPARdelta. PPARdelta is a new target for the treatment of metabolic syndrome. In particular, the fact that fatty acid oxidation and energy dissipation in skeletal muscle and adipose tissue by PPARdelta agonists lead to improved lipid profile, reduced adiposity and insulin sensitivity is a breakthrough. It seems that treatment of PPARdelta agonists operate similarly to the caloric restriction and prolonged exercise. We suggest that the physiological role of PPARdelta may be an indicator for switching from glucose metabolism to fatty acid metabolism. To receive new benefits of PPARdelta agonists against metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue, we need to unveil more details on the functions of PPARdelta itself and its agonists in the future. 相似文献
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4.
Toshiya Takemura Masazumi Watanabe Keigo Takagi Susumu Tanaka Shinsuke Aida 《Surgery today》1995,25(7):651-653
We present herein the rare case of a young man who was found to have a solitary tumor in the right upper lobe of his lung by a routine chest X-ray. The tumor was removed by thoracoscopic surgery, and pathological examinations confirmed the diagnosis of a primary lymphangioma of the lung. A brief review of the available literature on this extremely rare type of benign tumor follows the case report. 相似文献
5.
K. Terayama Syuji Toda Nobuhisa Yonemitsu Norimasa Koike Hajime Sugihara 《Virchows Archiv : an international journal of pathology》1997,431(4):291-295
We describe a rare case of papillary carcinoma with extensive proliferation of stromal cells. The stromal cells were immunocytochemically
positive for vimentin, α-smooth muscle actin and desmin, but negative for cytokeratin, epithelial membrane antigen, S-100,
thyroglobulin and CD34. These results and the ultrastructure of the stromal cells, which exhibited the characteristics of
both fibroblasts and smooth muscle cells, indicated an origin from myofibroblasts. We conclude that myofibroblastic proliferation
may contribute to the stromal response in the slow growth of the papillary carcinoma.
Received: 29 August 1996 / 26 May 1997 相似文献
6.
Kaname Ishii Yuichi Hayashida Katsuhiro Yoshimoto Hidehiro Tajima Uichiro Fuchisaki Toshiya Takeda Toru Kamata Hirotoshi Miyamori Masahiro Kanno 《Nihon Shokakibyo Gakkai zasshi》2006,103(8):931-935
We report a case of granulocyte-colony stimulating factor producing gastric cancer with multiple liver metastases. A 68-year-old woman who complained of epigastralgia visited our hospital. Upper gastrointestinal endoscopic examination revealed a type-2 gastric cancer. The laboratory data at admission indicated leukocytosis (35,900/microl) and a high level of serum granulocyte-colony stimulating factor (61 pg/mg). Granulocyte-colony stimulating factor producing gastric cancer was diagnosed by immunohistochemistry of biopsy specimen. Since we detected multiple liver metastases, chemotherapy was performed. Granulocyte-colony stimulating factor-producing gastric cancer is relatively rare and we summarize previous reports. 相似文献
7.
Selective necrosis in hamster pancreatic tumours using photodynamic therapy with phthalocyanine photosensitization. 总被引:3,自引:0,他引:3
P T Chatlani P J Nuutinen N Toda H Barr A J MacRobert J Bedwell S G Bown 《The British journal of surgery》1992,79(8):786-790
Photodynamic therapy (PDT) is often thought to be able to effect selective tumour necrosis. This therapeutic selectivity, based on transient differences in tumour: normal tissue photosensitizer concentration ratios, is rarely useful clinically in extracranial tumours, although PDT itself may be of value by virtue of the nature of the damage produced and healing of normal tissue by regeneration. This report describes the effects of PDT on normal pancreas and chemically induced pancreatic cancers in the hamster, where a different mechanism of selective necrosis may be seen. Photosensitizer distribution in normal and neoplastic pancreas was studied by chemical extraction and fluorescence microscopy. Correlation of distribution studies with necrosis produced by PDT shows that the photodynamic dose (product of tissue concentration of sensitizer and light dose) threshold for damage is seven times as high for normal pancreas as for pancreatic cancer. Tumour necrosis extended to the point where tumour was invading normal areas without damaging the normal tissue. In rat colonic cancer, photodynamic dose thresholds in tumour and normal tissue are similar and so such marked selectivity of necrosis is not possible. The reason for this selectivity in the pancreas is not clear, but recent evidence has suggested a difference in response to PDT between normal and neoplastic pancreatic cell lines and the presence of a singlet oxygen scavenger in normal pancreas is postulated. Furthermore, the present fluorescence microscopy studies suggest that tumour stroma contains the highest level of photosensitizer and thus receives the highest photodynamic dose during PDT. These results suggest a possible role for PDT in treating small pancreatic tumours or as an adjuvant to other techniques, such as surgery, that reduce the main bulk of tumours localized to the pancreas. 相似文献
8.
AIMS: Differential diagnosis of allergic conjunctivitis or dry eye is sometimes very difficult to diagnose by symptoms and clinical examination alone, especially in older patients. It was hypothesised that clinically allergic patients who were serum antigen specific IgE negative were candidates for dry eye. METHODS: Sixty patients were studied prospectively who were clinically diagnosed with allergic conjunctivitis by their itchy sensation and papilla formation of conjunctiva. They consisted of 30 serum antigen specific IgE positive and 30 IgE negative patients, with no significant differences in age. Dry eye examination and serum total IgE were performed on these two groups. RESULTS: No significant differences were seen between the two groups with regard to age (p = 0.76) and sex ratio. The antibody negative group had lower Schirmer's test scores (p = 0.002), lower tear clearance (p = 0.0001), lower tear function index (p = 0.0001), and lower serum total IgE (p = 0.04) than the antibody positive group. CONCLUSION: This study suggests that the evaluation of serum antigen specific IgE and tear dynamics are important for the differential diagnosis of patients with allergic conjunctivitis and dry eye. Clinically diagnosed allergic conjunctivitis with negative serum antigen specific and total IgE can be one form of dry eye. 相似文献
9.
Abstract Nitric oxide (NO) plays an important physiological role in regulating gastrointestinal motility. Involvement of endogenous NO was evaluated in the response to non-adrenergic, non-cholinergic (NANC) nerve stimulation of the dog sphincter muscle of Oddi. Transmural electrical stimulation (TES), nicotine (10?5M) and K+ (10 mM) produced only a relaxation in the sphincter muscle strips contracted with substance P, which was not potentiated by atropine. The TES-induced relaxation was abolished by tetrodotoxin (3 times 10?7 M) and oxyhaemoglobin (1.6 times 10?5 M), but not affected by atropine (10?7 M), propranolol (10?7 M), phentolamine (10?7 M), indomethacin (10?6 M), chole-cystokinin (CCK, 10?8 M) and vasoactive intestinal polypeptide (VIP, 10?8 M). The relaxation was also abolished by treatment with NG-nitro-L-arginine (L-NA, 10?5 M), an NO synthase inhibitor. Nicotine produced a transient relaxation, which was abolished by tetrodotoxin, hexamethonium (10?5 M) and L-NA, but not affected by atropine and NG-nitro-D-arginine (D-NA, 10?5 M). The addition of K+ elicited a transient relaxation, which was abolished by tetrodotoxin and L-NA. The inhibitory effects of L-NA were antagonized by L-arginine (10?3 M). The presence of neurons containing nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was histochemically demonstrated in the sphincter of Oddi. These findings may indicate that TES, nicotine and K+ liberate NO from NANC inhibitory nerve which is involved in the relaxation of the dog sphincter of Oddi. The muscular tone does not seem to be regulated by cholinergic nerves under the experimental conditions used. 相似文献
10.
Toshiya Inada M.D. Fumiko Minagawa B.A. Satoru Iwashita M.D. Tatsuji Tokui M.D. 《Psychiatry and clinical neurosciences》1994,48(4):729-735
Abstract: In order to examine the characteristics of potential difficult-to-manage psychiatric cases, seven potential subgroups were extracted from the criminal offenders who were sent to the division of psychiatric diagnosis, Tokyo District Public Prosecutors Office for Pre-Prosecution Psychiatric Justice (PPPJ). The following criteria were used to select the potential subgroups: offenders who had experienced compulsory discharge from a mental hospital, those who had experienced Involuntary Admission to the mental hospital by the Prefectural Governor at least twice, those who had experienced admission to mental hospitals on more than 5 occasions, those who had been put on PPPJ previously for other criminal matters at least 3 times, those who had previously attempted suicide, and those who had committed homicide or arson. From the results of this study, it could be concluded that at least two types of "difficult-to-manage" psychiatric cases exist in the criminal offenders. 相似文献