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41.
42.
Okada Y Sahara T Mitsubayashi H Ohgiya S Nagashima T 《Artificial intelligence in medicine》2005,35(1-2):171-183
BACKGROUND AND MOTIVATION: DNA microarray technology has made it possible to determine the expression levels of thousands of genes in parallel under multiple experimental conditions. Genome-wide analyses using DNA microarrays make a great contribution to the exploration of the dynamic state of genetic networks, and further lead to the development of new disease diagnosis technologies. An important step in the analysis of gene expression data is to classify genes with similar expression patterns into the same groups. To this end, hierarchical clustering algorithms have been widely used. Major advantages of hierarchical clustering algorithms are that investigators do not need to specify the number of clusters in advance and results are presented visually in the form of a dendrogram. However, since traditional hierarchical clustering methods simply provide results on the statistical characteristics of expression data, biological interpretations of the resulting clusters are not easy, and it requires laborious tasks to unveil hidden biological processes regulated by members in the clusters. Therefore, it has been a very difficult routine for experts. OBJECTIVE: Here, we propose a novel algorithm in which cluster boundaries are determined by referring to functional annotations stored in genome databases. MATERIALS AND METHODS: The algorithm first performs hierarchical clustering of gene expression profiles. Then, the cluster boundaries are determined by the Variance Inflation Factor among the Gene Function Vectors, which represents distributions of gene functions in each cluster. Our algorithm automatically specifies a cutoff that leads to functionally independent agglomerations of genes on the dendrogram derived from similarities among gene expression patterns. Finally, each cluster is annotated according to dominant gene functions within the respective cluster. RESULTS AND CONCLUSIONS: In this paper, we apply our algorithm to two gene expression datasets related to cell cycle and cold stress response in budding yeast Saccharomyces cerevisiae. As a result, we show that the algorithm enables us to recognize cluster boundaries characterizing fundamental biological processes such as the Early G1, Late G1, S, G2 and M phases in cell cycles, and also provides novel annotation information that has not been obtained by traditional hierarchical clustering methods. In addition, using formal cluster validity indices, high validity of our algorithm is verified by the comparison through other popular clustering algorithms, K-means, self-organizing map and AutoClass. 相似文献
43.
Wada Takehiko Ishimoto Takuji Nakaya Izaya Kawaguchi Takehiko Sofue Tadashi Shimizu Sayaka Kurita Noriaki Sasaki Sho Nishiwaki Hiroki Koizumi Masahiro Saito Shoji Nishibori Nobuhiro Oe Yuji Yoshida Mai Miyaoka Yoshitaka Akiyama Shin’ichi Itano Yuya Okazaki Masaki Ozeki Takaya Ichikawa Daisuke Oguchi Hideyo Kohsaka Satoshi Kosaka Shiho Kataoka Yuki Shima Hideaki Shirai Sayuri Sugiyama Kazuhiro Suzuki Tomo Son Daisuke Tanaka Tomomi Nango Eishu Niihata Kakuya Nishijima Yoko Nozu Kandai Hasegawa Midori Miyata Rei Yazawa Masahiko Yamamoto Yoshihiro Yamamoto Ryohei Shibagaki Yugo Furuichi Kengo Okada Hirokazu Narita Ichiei 《Clinical and experimental nephrology》2021,25(12):1277-1285
Clinical and Experimental Nephrology - 相似文献
44.
Shun Kaneko Masayuki Kurosaki Toshie Mashiba Hiroyuki Marusawa Masahiko Kondo Yuji Kojima Yasushi Uchida Hideki Fujii Takehiro Akahane Hitoshi Yagisawa Atsunori Kusakabe Haruhiko Kobashi Takehiko Abe Hideo Yoshida Chikara Ogawa Koichiro Furuta Nobuharu Tamaki Keiji Tsuji Tomomichi Matsushita Namiki Izumi the Japanese Red Cross Liver Study Group 《Journal of medical virology》2023,95(1):e28210
Nucleos(t)ide analogs (NAs) cannot completely suppress the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to identify the risk factors for HCC development in naïve CHB patients treated with current NA. Patients receiving NA (n = 905) were recruited retrospectively from the 17 hospitals of the Japanese Red Cross Liver Study Group. All treatment-naïve patients had been receiving current NA continuously for more than 1 year until the end of the follow-up. We analyzed the accuracy of predictive risk score using the area under receiver operating characteristic curve. The albumin–bilirubin (ALBI) score was significantly improved by NA therapy (−0.171 ± 0.396; p < 0.001 at Week 48). A total of 72 (8.0%) patients developed HCC over a median follow-up of 6.2 (1.03–15.7) years. An independent predictive factor of HCC development was older age, cirrhosis, lower platelet counts at baseline and ALBI score, and alpha-fetoprotein (AFP) at 1 year after NA therapy according to multivariate analysis. The accuracy was assessed using the PAGE-B, mPAGE-B, aMAP, APA-B, and REAL-B scores that included these factors. Discrimination was generally acceptable for these models. aMAP and REAL-B demonstrated high discrimination with 0.866/0.862 and 0.833/0.859 for 3- and 5-year prediction from the status of 1 year after NA therapy, respectively. Baseline age and platelet count, as well as ALBI and AFP one year after NA, were useful for stratifying carcinogenesis risk. The aMAP and REAL-B scores were validated with high accuracy in Japanese CHB patients. 相似文献
45.
Wei-dong Zhang Masataka Nagao Takehiko Takatori Kimiharu Iwadate Yoshiyuki Itakura Yoshihiro Yamada Hirotaro Iwase Tsuneaki Oono 《International journal of legal medicine》1995,107(4):174-178
This paper investigates the immunohistochemical dynamics of leukotoxin (9,10-epoxy-12-octadecenoic acid, LTx) in the lungs of rats exposed to hyperoxia with or without paraquat. The rats were treated with 100% oxygen or ambient air for 24. 48, 72 and 96 h in the presence or absence of a low or high dose paraquat (1,1-di-methyl-4,4-bipyridinium, PQ) injection. Immunostaining for LTx demonstrated positive reactions in the neutrophils that showed a progressive increase in intensity of staining with time in all groups exposed to 100% oxygen and in the group with high dose PQ, but the positive findings were weak in the group injected with low dose PQ only. We found the positive immunostaining reaction not only in neutrophils but also in alveolar macrophages. This indicates that LTx is produced by alveolar macrophages as well as by neutrophils depending on the treatment period under hyperoxic conditions, suggesting that LTx is an important chemical mediator in pulmonary diseases. 相似文献
46.
Glucocorticoid-induced osteoporosis has been reported to be caused by enhanced bone resorption and suppressed bone formation.
To clarify whether administration of vitamin K, which enhances bone formation, prevents prednisolone-induced loss of bone
mineral density (BMD), a randomized, prospective, controlled study was conducted on 20 patients with chronic glomerulonephritis
scheduled for treatment with prednisolone. All patients were initially treated with 0.8 mg/kg body weight/day of prednisolone
(maximum of 40 mg) for 4 weeks, tapering to 20 mg/day over approximately 6 weeks. Ten patients received prednisolone alone
(Group 1), and the other 10 patients received prednisolone plus 15 mg of menatetrenone, vitamin K, three times per day (Group
2). BMD of the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) and biochemical markers of bone metabolism
in blood and urine were evaluated before and 10 weeks after administration of prednisolone alone or with menatetrenone. In
Group 1, treatment with prednisolone significantly reduced BMD of the lumbar spine from 1.14 ± 0.12 to 1.10 ± 0.11 g/cm2 (P= 0.0029). Serum intact osteocalcin and procollagen type I C-peptide (PICP) concentrations, biochemical markers of bone formation,
were markedly reduced. A biochemical marker of bone resorption, urinary excretion of deoxypyridinoline, was significantly
reduced. In Group 2, prednisolone-induced reduction of BMD was prevented by menatetrenone administration (1.09 ± 0.09 to 1.07
± 0.07 g/cm2, P= 0.153). Menatetrenone prevented reduction of PICP concentration by prednisolone but not in serum intact osteocalcin concentration
and urinary excretion of deoxypyridinoline. Thus, treatment with prednisolone resulted in loss of BMD of the lumbar spine
associated with suppression of both bone formation and bone resorption. Menatetrenone is a useful agent in preventing prednisolone-induced
loss of BMD.
Received: 7 July 1998 / Accepted: 13 August 1999 相似文献
47.
Toshihiko Iizasa Hao Chang Makoto Suzuki Mizuto Otsuji Sana Yokoi Masako Chiyo Shinichiro Motohashi Kazuhiro Yasufuku Yasuo Sekine Akira Iyoda Kiyoshi Shibuya Kenzo Hiroshima Takehiko Fujisawa 《Clinical cancer research》2004,10(16):5361-5366
PURPOSE: The aim of this study was to determine whether collagen XVIII expression is correlated with circulating serum endostatin and whether this has any prognostic value in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Serum endostatin levels were measured quantitatively by a competitive enzyme immunoassay, and collagen XVIII expression in tumor tissue was investigated with an immunohistochemical method in a series of 94 patients who underwent surgery for NSCLC. RESULTS: Sixty cases (63.8%) had positive immunohistochemical staining with anticollagen XVIII polyclonal antibodies, including strongly positive staining in 11 (11.7%) cases. The mean (+/- SD) serum endostatin level was 41.6 +/- 34.4 ng/ml in the patient group and 16.3 +/- 10.3 ng/ml in the control group (P < 0.0001). The 11 cases who were strongly collagen XVIII-positive had significantly higher serum endostatin levels than the cases who were negative or weakly positive (P = 0.0297). The 5-year survival rates of negative, weakly positive, and strongly positive patients were 77.8%, 56.9%, and 43.8%, respectively. The cases with strongly positive collagen XVIII expression had a significantly poorer outcome than cases with negative expression (P = 0.0027). A multivariate analysis with Cox proportional hazards model for disease-specific survival revealed that expression of collagen XVIII (strongly positive versus negative; weakly positive versus negative), tumor classification, and regional lymph node classification were independent prognostic factors. CONCLUSIONS: Our results suggest that expression of collagen XVIII in tumor tissue is strongly associated with a poorer outcome in NSCLC and correlates with elevated levels of circulating serum endostatin. 相似文献
48.
Inaba H Miyaji K Kaneko Y Ohtsuka T Ezure M Tambara K Takamoto S Omata S 《Artificial organs》2000,24(10):808-815
In clinical settings, no method has been established to examine the fatigue of a latissimus dorsi muscle (LDM) preconditioned for cardiomyoplasty. We examined the feasibility of measuring muscle stiffness (tactile stiffness) to evaluate muscle fatigue in situ using our tactile sensor. We stimulated canine LDM with burst pacing and monitored both stiffness and tension to determine their relationship. In both dissected LDM and LDM in situ, the decrements of these parameters during burst pacing were compared between preconditioned and unconditioned LDM. In measurement in situ, the sensor probe was placed on the LDM through a small incision. Strong statistical correlation was shown between stiffness and tension (r = 0.935). In decrements of stiffness in situ, there were statistically significant differences between preconditioned and unconditioned LDM. Our tactile sensor system can provide an efficient method for evaluating fatigue of muscles in situ without measuring muscle tension. 相似文献
49.
Therapeutic targeting of the survivin pathway in cancer: initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis. 总被引:36,自引:0,他引:36
Olivier P Blanc-Brude Mehdi Mesri Nathan R Wall Janet Plescia Takehiko Dohi Dario C Altieri 《Clinical cancer research》2003,9(7):2683-2692
PURPOSE: Molecular antagonists of the inhibitor of apoptosis protein survivin have shown promise as novel anticancer strategies for triggering tumor cell apoptosis, dysregulating mitotic progression, and inhibiting tumor growth in preclinical models. However, how survivin couples to the cell death machinery has remained elusive, and the relevant cellular targets of survivin antagonists have not been completely elucidated. Experimental Design: Human umbilical vein and dermal microvascular endothelial cells were infected with replication-deficient adenoviruses encoding survivin (pAd-Survivin), green fluorescent protein (pAd-GFP), or a phosphorylation-defective survivin Thr(34)-->Ala (pAd-T34A) dominant negative mutant. The effect of wild-type or mutant survivin was investigated on capillary network stability, endothelial cell viability, and caspase activation in vitro and on kinetics of tumor growth and development of angiogenesis in a breast cancer xenograft model in vivo. The cell death pathway initiated by survivin targeting was mapped with respect to cytochrome c release, changes in mitochondrial transmembrane potential, and apoptosome requirements using mouse embryonic fibroblasts deficient in Apaf-1 or caspase-9. RESULTS: Adenoviral transduction of endothelial cells with pAd-Survivin inhibited growth factor deprivation- or ceramide-induced apoptosis, reduced caspase-3 and -7 generation, and stabilized three-dimensional capillary networks in vitro. Conversely, expression of pAd-T34A caused apoptosis in umbilical vein and dermal microvascular endothelial cells and resulted in caspase-3 activity. Cell death induced by survivin targeting exhibited the hallmarks of mitochondrial-dependent apoptosis with release of cytochrome c and loss of mitochondrial transmembrane potential and was suppressed in Apaf-1 or caspase-9 knockout mouse embryonic fibroblasts. When injected in human breast cancer xenografts, pAd-T34A inhibited growth of established tumors and triggered tumor cell apoptosis in vivo. This was associated with a approximately 60% reduction in tumor-derived blood vessels by quantitative morphometry of CD31-stained tumor areas, and appearance of endothelial cell apoptosis by internucleosomal DNA fragmentation in vivo. CONCLUSIONS: Survivin functions as a novel upstream regulator of mitochondrial-dependent apoptosis, and molecular targeting of this pathway results in anticancer activity via a dual mechanism of induction of tumor cell apoptosis and suppression of angiogenesis. 相似文献
50.
Four tropical PSP toxins-producing dinoflagellates, Alexandrium minutum, Alexandrium tamiyavanichii, Alexandrium tamarense and Alexandrium peruvianum from Malaysian waters were studied to investigate the influences of salinity on growth and toxin production. Experiments were conducted on constant temperature 25 degrees C, 140 microE mol m(-2) s(-1) and under 14:10 light:dark photo-cycle with salinity ranged from 2 to 30 psu. The PSP-toxin congeners, GTX 1-6, STX, dcSTX, NEO and C1-C2 were analysed by high performance liquid chromatography. Salinity tolerance of the four species in decreasing order is A. minutum>A. peruvianum>A. tamarense>A. tamiyavanichii. Specific growth rates and maximum densities varied among these species with A. minutum recorded as the highest, 0.5 day(-1) and 6 x 10(4) cells L(-1). Toxin content decreased with elevated salinities in A. minutum, the highest toxin content was about 12 fmole cell(-1) at 5 psu. In A. tamiyavanichii, toxin content peaked at optimal growth salinity (20 and 25 psu). Toxin content of A. tamarense, somehow peaked at sub-optimal growth salinity (15 and 30 psu). Results of this study implied that salinity fluctuation not only influenced the growth physiology but also toxin production of these species. 相似文献