Search PubMed⌕ Search

Biomedical subjects

Satoshi Ando

Publications and source records attributed to Satoshi Ando.

18 recordsLinked to original sources
PubMed2007

Synergistic association of mitochondrial uncoupling protein (UCP) genes with schizophrenia.

Many studies suggest that mitochondrial dysfunction is involved in the pathophysiology of schizophrenia. We performed a case-control study using tag SNPs in the mitochondrial uncoupling protein genes, UCP2, UCP4, and BMCP1/UCP5, to investigate their association with schizophrenia. These neuronal UCPs are expressed in various brain tissues and may exert a neuroprotective effect against increased oxidative stress. We found modest associations between schizophrenia and the four tag SNPs, rs660339 (odds ratio (OR) = 1.330; P = 0.0043) and rs649446 (OR = 0.739; P = 0.0069) in UCP2, and rs10807344 (OR = 0.622; P = 0.0029) and rs2270450 (OR = 0.704; P = 0.0043) in UCP4, all of which were statistically significant even after correcting for multiple comparisons. Moreover, we found a statistically significant synergistic interaction between UCP2 and UCP4 by using the multifactor dimensionality reduction (MDR) method. The synergistic interaction was also confirmed by the logistic regression analysis, where the maximal OR was obtained when the risk alleles at rs660339 and rs10807344 were simultaneously homozygous. Individuals possessing homozygous risk alleles at these two loci have a 7.6-fold risk of developing schizophrenia compared with those of minimal OR. Our findings suggest that UCP2 and UCP4 have a modest but important involvement in the genetic etiology of schizophrenia. This is the first report of the association between schizophrenia and neuronal UCPs.

Alleles↗
PubMed2006

Completion and toxicity of induction chemotherapy for metastatic testicular cancer: an updated evaluation of Japanese patients.

BACKGROUND: Combination of bleomycin, etoposide and cisplatin (BEP) remains the standard chemotherapy for testicular cancer. Since the development of BEP in the 1980s, there has been a considerable advance in supportive therapies, such as granulocyte colony-stimulating-factor and 5-HT3 antagonists. Therefore, we re-evaluated the completion and toxicity of BEP combined with modern supportive care. METHODS: The medical records of all 42 testicular cancer patients who received induction chemotherapy at Tsukuba University Hospital were reviewed. Toxicities during the induction chemotherapy were graded according to the Japanese CTCAE v3.0. RESULTS: Dose reduction was needed in only three patients. The subsequent chemotherapy was started at the planned 3 week interval or within 3 days of postponement in 89% of the treatment cycles. The average relative dose intensity (RDI) of bleomycin was 0.95, while that for etoposide and cisplatin was 0.97. There was no death due to toxicity. The most frequent toxicity was leukopenia (grade 3 in 44% and grade 4 in 55%). Post-chemotherapy diffusion capacity was significantly decreased in 30% of patients. Two patients developed bleomycin-induced pneumonitis, but recovered successfully. Sixteen patients received second line or salvage chemotherapy after BEP, subsequently. The overall 5 year cause-specific survival rate was 85%. CONCLUSION: BEP with high RDIs is acceptable if combined with modern supportive care, with acceptable toxicity profile in most patients.

Adolescent↗
PubMed2006

Neutropenic colitis during standard dose combination chemotherapy with nedaplatin and irinotecan for testicular cancer.

A 54-year-old man received combination chemotherapy with nedaplatin and irinotecan as salvage chemotherapy for refractory non-seminomatous testicular cancer. The patient developed abdominal pain and high fever on Day 21 after the initiation of chemotherapy. Computed tomography revealed thickening of the terminal ileum wall and paralytic ileus. The patient recovered with intensive supportive management including broad-spectrum antibiotics, bowel rest with gastric intubation and intravenous gamma-globulin. Neutropenic colitis has been thought to be a serious gastrointestinal complication associated with chemotherapy for hematological malignancy. The mortality rate is as high as 21-48% according to a recent review. The present case indicates that the neutropenic colitis can occur under neutropenic conditions induced by the standard-dose chemotherapy for solid cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Splenogonadal fusion: case report and review of published works.

Splenogonadal fusion is a rare congenital anomaly. We report herein a case of splenogonadal fusion associated with contra lateral testicular aplasia, and review the etiology, pathogenesis and management of this rare disease. As far as we know, this is the first reported case of splenogonadal fusion associated with testicular aplasia.

Abnormalities, Multiple↗
PubMed2006

[Renal cell carcinoma with bilateral adrenal and small intestinal metastases: a case report].

A 69-year-old man who had a complaint of melena and hematemesis was referred to our hospital for further evaluation and treatment of renal masses, bilateral adrenal swelling and a tumor in the small intestine. The abdominal CT scan demonstrated two tumors sized 45 mm and 15 mm in diameter, located in the center and lower pole of the left kidney. Bilateral adrenal swelling and a small intestinal tumor with invagination were also observed. We diagnosed left renal cell carcinomas with bilateral adrenal metastases or hyperplasia, and a primary or metastatic small intestinal tumor. He received left radical nephrectomy, right adrenalectomy, and small intestinal resection. Pathological diagnosis was renal cell carcinoma, granular cell carcinoma, G2>G3>G1, INFalpha, v (+), pT1a, pM1, Stage IV. Bilateral adrenal swelling and small intestinal tumor were metastases from the renal cell carcinoma After operation, we administered interferon-alpha and steroid replacement. He died after 27-month follow-up period because of renal cell carcinoma. Renal cell carcinoma with simultaneous metastases to bilateral adrenal glands and the small intestine is extremely rare.

Adrenal Gland Neoplasms↗
PubMed2006

[Bilateral uretero-common iliac arterial fistula with long term uretelal stent: a case report].

A 37-year-old man underwent Miles' operation and adjuvant irradiation therapy for rectum cancer in 1999. The patient suffered from bilateral ureteral stricture after the previous therapies. Bilateral double-J ureteral stents were inserted and exchanged at regular intervals. Four years after the start of ureteral stenting, he complicated with gross hematuria and dysuria. When the right double-J stent was exchanged, massive bleeding from external opening of urethra was observed. Retrograde pyelography showed right uretero-iliac arterial fistula. Since endovascular treatment with covered stents had failed, we performed right common iliac artery embolization and femoral-femoral artery bypass. Two days after the operation, gross hematuria developed again. When the left ureteral stent was exchanged, active bleeding from the external meatus of urethra was revealed. Angiography showed extravasation from left common iliac artery. We diagnosed left uretero-iliac arterial fistula. Although we tried endovascular treatment with covered stent that was made of artificial vessel graft and metallic stent, thromboembolism was occurred in the covered stent. Finally, right axillo-femoral artery bypass was indicated. The last treatment achieved long-term good control of uretero-arterial fistula. The present case shows that uretero-arterial fistula is a serious complication of long-term ureteral stenting, especially in the case of post pelvic surgery and irradiation.

Adult↗
PubMed2005

Whole genome association study of rheumatoid arthritis using 27 039 microsatellites.

A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.

Arthritis, Rheumatoid↗
PubMed2005

Optimization of liver biopsy RNA sampling and use of reference RNA for cDNA microarray analysis.

In this study, we used the rat liver as a model system to optimize the conditions for extracting RNA from liver biopsies for use in cDNA microarrays. We found that a 5-mm biopsy with a 16-gauge needle and storage in RNA later at 4 degrees C were optimal conditions for RNA extraction. The most important factor for the quantity and quality of RNA extraction was the sample diameter. Using the optimized sampling conditions and a cDNA microarray, we compared the expression of genes in the normal and the fibrotic tissues of the LEC rat liver, a model of liver tumorigenesis, with SD rat liver RNA as a reference. We found 29 genes that were up-regulated and 33 genes that were down-regulated in the fibrotic part of the liver. Furthermore, with the help of the reference RNA, we were able to classify the expression profiles into five groups without complex mathematical analyses; without the reference RNA, the genes could be classified into only two groups. Finally, we found that osteopontin was expressed at a very high level in the fibrotic portion of the LEC rat liver. This cDNA microarray result was validated by immunohistochemistry, which showed an elevated expression of osteopontin in the region of cholangiocarcinoma and a lack of expression in normal tissues. With optimized conditions, we should be able to apply the microarray system for routine practice.

Animals↗
PubMed2005

Functional anatomy of the basal ganglia in X-linked recessive dystonia-parkinsonism.

Dystonia is a neurological syndrome characterized by sustained muscle contractions that produce repetitive twisting movements or abnormal postures. X-linked recessive dystonia parkinsonism (XDP; DYT3; Lubag) is an adult-onset disorder that manifests severe and progressive dystonia with a high frequency of generalization. In search for the anatomical basis for dystonia, we performed postmortem analyses of the functional anatomy of the basal ganglia based on the striatal compartments (ie, the striosomes and the matrix compartment) in XDP. Here, we provide anatomopathological evidence that, in the XDP neostriatum, the matrix compartment is relatively spared in a unique fashion, whereas the striosomes are severely depleted. We also document that there is a differential loss of striatal neuron subclasses in XDP. In view of the three-pathway basal ganglia model, we postulate that the disproportionate involvement of neostriatal compartments and their efferent projections may underlie the manifestation of dystonia in patients with XDP. This study is the first to our knowledge to show specific basal ganglia pathology that could explain the genesis of dystonia in human heredodegenerative movement disorders, suggesting that dystonia may result from an imbalance in the activity between the striosomal and matrix-based pathways.

Adult↗
PubMed2005

Pretreatment prediction of interferon-alfa efficacy in chronic hepatitis C patients.

BACKGROUND & AIMS: Interferon has been used widely to treat patients with chronic hepatitis C infections. Prediction of interferon efficacy before treatment has been performed mainly by using viral information, such as viral load and genotype. This information has allowed the successful prediction of sustained responders (SR) and non-SRs, which includes transient responders (TR) and nonresponders (NR). In the current study we examined whether liver messenger RNA expression profiles also can be used to predict interferon efficacy. METHODS: RNA was isolated from 69 liver biopsy samples from patients receiving interferon monotherapy and was analyzed on a complementary DNA microarray. Of these 69 samples, 31 were used to develop an algorithm for predicting interferon efficacy, and 38 were used to validate the precision of the algorithm. We also applied our methodology to the prediction of the efficacy of interferon/ribavirin combination therapy using an additional 56 biopsy samples. RESULTS: Our microarray analysis combined with the algorithm was 94% successful at predicting SR/TR and NR patients. A validation study confirmed that this algorithm can predict interferon efficacy with 95% accuracy and a P value of less than .00001. Similarly, we obtained a 93% prediction efficacy and a P value of less than .0001 for patients receiving combination therapy. CONCLUSIONS: By using only host data from the complementary DNA microarray we are able to successfully predict SR/TR and NR patients for interferon therapy. Therefore, this technique can help determine the appropriate treatment for hepatitis C patients.

Adult↗
PubMed2005

AICAR, an AMPK activator, has protective effects on alcohol-induced fatty liver in rats.

BACKGROUND: Previous work with metformin has shown that this antidiabetic agent improves nonalcoholic fatty liver in ob/ob mice. AMP-activated protein kinase (AMPK) is one of the major cellular regulators of lipid and glucose metabolism, and reportedly mediates the beneficial metabolic effects of metformin. In this study, we examined the effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), an AMPK activator, on an experimental model of ethanol-induced hepatic steatosis. METHODS: Rats were randomly divided into three groups: (A) rats fed ethanol-containing liquid diet for six weeks; (B) rats pair-fed ethanol-containing liquid diet for six weeks, during the last three weeks of which they were subcutaneously injected with 0.5 mg AICAR/g body weight per day; (C) rats pair-fed isocaloric liquid diet without ethanol for six weeks. At the end of the six-week period, the animals were sacrificed. Serum and liver specimens were analyzed using biochemical and histologic methods, as well as real-time PCR. RESULTS: Chronic ethanol feeding resulted in fatty liver both histologically and biochemically, whereas AICAR administration attenuated the degree of change in the liver. AICAR also decreased the hepatic sterol regulatory factor binding protein-1c (SREBP-1c) and reduced fatty acid synthase (FAS) expression; these changes led to reduced triglyceride synthesis in rat livers. Furthermore, detection of 4-hydroxy-2-nonenal (4-HNE)-protein adducts showed that the AICAR treatment also decreased the products of lipid peroxidation. CONCLUSION: In this preclinical rat model, AICAR, an AMPK activator, appears to protect the liver from fatty changes associated with chronic alcohol use. As such, AICAR may have a role in the treatment and prevention of alcohol-induced fatty liver.

AMP-Activated Protein Kinases↗
PubMed2005

Molecular dissection and anatomical basis of dystonia: X-linked recessive dystonia-parkinsonism (DYT3).

Pathological findings in dystonia have been unclear. X-linked recessive dystonia-parkinsonism (XDP, DYT3), endemic in the Panay island, the Philippines, is characterized by the clinical onset with dystonia followed by parkinsonism. It provides a unique opportunity to explore the anatomical basis of dystonia, because it has discernible pathological changes even at its early phase of dystonia. After extensive searches for the anatomical basis in XDP, we found selective loss of striosomal neurons in the striatum in dystonic patients' brain. Because striosomal neurons inhibit nigrostriatal dopaminergic neurons via GABAergic innervation, the striosomal lesion could account for dopamine excess in the striatum, which in turn causes a hyperkinetic state or dystonia. We also identified the causative gene as one of the general transcription factor genes, TAF1. XDP has certain similarities to Huntington disease not only in pathological and clinical findings, but also the molecular mechanism, which disturbs expression of genes essential for striatal neurons, such as DRD2. Therapeutic intervention may become possible through pharmacological measures that affect gene expression.

Chromosomes, Human, X↗
PubMed2005

Method of duplicating film using the CR system: evaluation of detectability in a simulated nodule.

PURPOSE: Since film processors used for screen-film systems have been decreasing recently, it is becoming difficult to develop duplicating film (Dup film) used conventionally. The purpose of this study was to evaluate the usefulness of the method of duplicating film using a computed radiography (CR) system. MATERIALS AND METHODS: The process of duplicating film using CR is 1) to eliminate energy accumulated on the imaging plate (IP) using white light, 2) to accumulate energy on the whole surface, and 3) to place the original film in piles. 4) After an exposure of white light, duplicated films can be obtained by CR system. In order to evaluate the reproducibiliy of our system, duplicated films were read by experienced observers and receiver operating characteristic (ROC) analysis was carried out. Observers read 50 images with a simulated nodule and 50 images without a simulated nodule. RESULTS: The average Az values were 0.94 for the original films, 0.91 for films duplicated using Dup film, and 0.90 for films duplicated using the CR system. When the two-tailed paired-T test was performed for each result, there were no statistically significant differences at p<0.05. CONCLUSION: The detectability of a simulated nodule for films duplicated using the CR system did not differ from the detectability of films duplicated using Dup film. This method may be a reasonable substitute for the conventional duplication system.

Copying Processes↗
PubMed2004

A low-density cDNA microarray with a unique reference RNA: pattern recognition analysis for IFN efficacy prediction to HCV as a model.

We have designed and established a low-density (295 genes) cDNA microarray for the prediction of IFN efficacy in hepatitis C patients. To obtain a precise and consistent microarray data, we collected a data set from three spots for each gene (mRNA) and using three different scanning conditions. We also established an artificial reference RNA representing pseudo-inflammatory conditions from established hepatocyte cell lines supplemented with synthetic RNAs to 48 inflammatory genes. We also developed a novel algorithm that replaces the standard hierarchical-clustering method and allows handling of the large data set with ease. This algorithm utilizes a standard space database (SSDB) as a key scale to calculate the Mahalanobis distance (MD) from the center of gravity in the SSDB. We further utilized sMD (divided by parameter k: MD/k) to reduce MD number as a predictive value. The efficacy prediction of conventional IFN mono-therapy was 100% for non-responder (NR) vs. transient responder (TR)/sustained responder (SR) (P < 0.0005). Finally, we show that this method is acceptable for clinical application.

Algorithms↗
PubMed2004

Leptin deficiency enhances sensitivity of rats to alcoholic steatohepatitis through suppression of metallothionein.

Oxidative stress is stated to be a central mechanism of hepatocellular injury in alcohol-induced liver injury. Recent reports have shown that Kupffer cell dysfunction in the leptin-deficient state contributes partly to the increased sensitivity to endotoxin liver injury. Here we report that leptin also plays a key role in the development of alcoholic liver injury and that leptin signaling in hepatocytes is involved in cellular mechanisms that mediate ethanol-induced oxidative stress. We found that chronic ethanol feeding in leptin receptor-deficient Zucker (fa/fa) rats for 6 wk resulted in a much more severe liver injury and augmented accumulation of hepatic lipid peroxidation compared with control littermates. The hepatic induction of stress-response and antioxidant proteins, such as metallothionein (MT)-1 and -2, was significantly suppressed in fa/fa rats after chronic ethanol feeding. Zinc concentration in liver was also decreased in fa/fa rats, compared with control littermates. In primary cultured hepatocytes from fa/fa rats, incubation with ethanol significantly suppressed MT-1 and -2 expressions. Addition of leptin to leptin-deficient ob/ob mouse primary hepatocytes led to an increase in MT-1 and -2 mRNA levels and a decrease in oxidative stress after incubation with ethanol. In conclusion, leptin deficiency enhances sensitivity of rats to alcohol-induced steatohepatitis through hepatocyte-specific interaction of MT-1 and -2 and resultant exaggeration of oxidative stress in hepatocytes. These findings suggest that leptin resistance in hepatocytes is an important mechanism of alcohol-induced liver injury.

Animals↗
PubMed2002

CENP-A, -B, and -C chromatin complex that contains the I-type alpha-satellite array constitutes the prekinetochore in HeLa cells.

CENP-A is a component of centromeric chromatin and defines active centromere regions by forming centromere-specific nucleosomes. We have isolated centromeric chromatin containing the CENP-A nucleosome, CENP-B, and CENP-C from HeLa cells using anti-CENP-A and/or anti-CENP-C antibodies and shown that the CENP-A/B/C complex is predominantly formed on alpha-satellite DNA that contains the CENP-B box (alphaI-type array). Mapping of hypersensitive sites for micrococcal nuclease (MNase) digestion indicated that CENP-A nucleosomes were phased on the alphaI-type array as a result of interactions between CENP-B and CENP-B boxes, implying a repetitive configuration for the CENP-B/CENP-A nucleosome complex. Molecular mass analysis by glycerol gradient sedimentation showed that MNase digestion released a CENP-A/B/C chromatin complex of three to four nucleosomes into the soluble fraction, suggesting that CENP-C is a component of the repetitive CENP-B/CENP-A nucleosome complex. Quantitative analysis by immunodepletion of CENP-A nucleosomes showed that most of the CENP-C and approximately half the CENP-B took part in formation of the CENP-A/B/C chromatin complex. A kinetic study of the solubilization of CENPs showed that MNase digestion first released the CENP-A/B/C chromatin complex into the soluble fraction, and later removed CENP-B and CENP-C from the complex. This result suggests that CENP-A nucleosomes form a complex with CENP-B and CENP-C through interaction with DNA. On the basis of these results, we propose that the CENP-A/B/C chromatin complex is selectively formed on the I-type alpha-satellite array and constitutes the prekinetochore in HeLa cells.

Antibodies↗
PubMedDate not supplied

Study of arsenic trioxide-induced vascular shutdown and enhancement with radiation in solid tumor.

PURPOSE: Arsenic trioxide (ATO) has been reported to be an effective chemotherapeutic agent for acute promyelocytic leukemia (APL), and, recently, anti-tumor effect has been demonstrated in solid tumors. However, little is known about the mechanism of action of the ATO effect on solid tumor. We investigated the anti-vascular effect of ATO and the potential of combining ATO with radiation therapy. MATERIALS AND METHODS: We studied the anti-vascular effect of ATO and radiosensitization of squamous cell carcinoma (SCC) VII murine tumors of C3H mice. The anti-vascular effect was examined using magnetic resonance imaging(MRI), and radiosensitivity was studied by clonogenic assay and tumor growth delay. Histopathological changes of the tumors after various treatments were also observed with hematoxylin and eosin (H&E) staining. RESULTS: Necrosis and blood flow changes in the central region of tumors in the hind limbs of the animals were observed on T2-weighted imaging after an i.p. injection of 8 mg/kg of ATO alone. ATO exposure followed by radiation decreased the clonogenic survival of SCC VII cells compared with either treatment alone. Tumor growth delay after 10-20 Gy of radiation alone was increased slightly compared with control tumors, but the combination of ATO injection 2 hours before exposure to 20 Gy of radiation significantly prolonged tumor growth delay by almost 20 days. CONCLUSION: The results suggest that ATO and radiation can enhance the radiosensitivity of solid tumor.

Animals↗