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Biomedical subjects

Satoshi Ikeda

Publications and source records attributed to Satoshi Ikeda.

At least 37 records · Page 2Linked to original sources

Chest pain and ST segment depression caused by expansion of gastric tube used for esophageal reconstruction.

We describe a 76-year-old man in whom a gastric tube was used for esophageal reconstruction via the anterior mediastinum after esophagectomy for esophageal cancer. Stenosis of the tube resulted in fluid accumulation, which directly compressed the heart and caused angina-like chest pain associated with ST-segment depression in lead V(2-3) on the electrocardiogram (ECG). Coronary angiography revealed no stenosis. Drainage of the fluid in the gastric tube resulted in immediate relief of symptoms and normalization of ECG. Angina-like chest pain associated with ST segment changes were caused by expansion of the gastric tube and compression of the heart.

Aged↗

Alterations and correlations of the components in the Wnt signaling pathway and its target genes in breast cancer.

Both cyclin D1 and c-myc are key molecules in breast cancer carcinogenesis, and their transcriptional level and stability are regulated through several signaling pathways, including the Wnt signaling pathway. We performed immunohistochemical and mutational analyses of Wnt signaling components to investigate the association of Wnt signaling alterations with breast cancer carcinogenesis using 49 surgically resected primary breast cancer samples. Positive staining of cyclin D1 and c-myc was observed in 55.1% and 30.6% of the 49 breast cancer samples, respectively. Aberrant cytoplasmic expression of beta-catenin, which indicates the existence of alterations in the Wnt signaling pathway, was observed in 38.8% of breast cancer samples, though no mutation was found in the beta-catenin and Axin 1 genes. Reduced expression of APC was observed in 34.7% of samples. Statistical analysis revealed strong correlations between overexpression of beta-catenin and that of cyclin D1 and c-myc (p=0.0001 and 0.0117, respectively). Furthermore, overexpression of beta-catenin was significantly correlated with reduced expression of APC (p=0.0127). Wnt signaling alterations were frequently observed in breast cancer from the results of beta-catenin immunohistochemistry, although no mutation in the components of the Wnt signaling pathway was found in the present study. Based on the statistical analyses, we speculated that reduced expression of APC leads to overexpression of beta-catenin, and aberrant expression of cyclin D1 and c-myc mainly depends on alterations in the Wnt signaling pathway in breast cancer.

Adenomatous Polyposis Coli Protein↗

Immunohistochemical detection of telomerase reverse transcriptase (TERT) protein in benign and malignant tumor cells of the breast.

Telomerase activity is associated with immortality and is expressed in various malignant tumors. Telomerase reverse transcriptase (TERT) is a human telomerase catalytic subunit and is strongly correlated with telomerase activity. In this study, the expression of TERT was investigated by immunocytochemistry to determine whether it is a useful marker for differential diagnosis in benign or malignant breast tumors. We examined imprint smears prepared from 63 surgically resected breast lesions, and 27 cases of secretion or aspiration cytology smears had been routinely diagnosed. Eighteen of the 63 cases were examined for TERT mRNA and the correlation with expression of TERT protein was investigated. Expression of TERT protein was correlated with expression of TERT mRNA by in situ hybridization (p=0.044), suggesting that telomerase activity might be expressed with morphologic factors. In imprint smears and routine cytology smears, TERT-positive cases significantly tended to be malignant cases (p=0.014, p=0.033 respectively). Especially, in malignant imprint smear cases, positive expression of TERT was significantly correlated with lymph node metastasis (p=0.022). In conclusion, the expression of TERT protein might be a useful marker for differential diagnosis in malignant and benign breast tumors. In malignant cases, it could be a useful indicator for the assessment of potential of lymph node metastasis [corrected].

Biomarkers, Tumor↗

Immunohistochemical and mutational analyses of Wnt signaling components and target genes in intrahepatic cholangiocarcinomas.

The mechanisms of carcinogenesis in intrahepatic cholangiocarcinoma (ICC) are not well characterized although alterations in several oncogenes and onco-suppressor genes have been reported to occur in ICC. In the present study, we focused on alterations in the Wnt signaling components and target genes by analyzing 24 surgically resected samples of ICC. Immunohistochemical analysis of beta-catenin showed positive staining in cytoplasm and/or nucleus in 58.3% of the samples, indicating the presence of alterations in the Wnt signaling pathway in these samples. In sequencing analyses, mutations in the beta-catenin, adenomatous polyposis coli and Axin 1 genes were observed in 8.3, 12.5 and 41.7%, respectively, of the 24 ICC samples; however, the functional significance of these mutated genes is controversial. Furthermore, cyclin D1, c-myc and urinary-type plasminogen activator receptor, which are the downstream target genes in the Wnt signaling pathway, were overexpressed in 41.7, 41.7 and 58.3%, respectively, of the 24 ICC samples. The overexpression of cyclin D1 was statistically correlated with that of beta-catenin. Based on these results, we speculated that the Wnt signaling pathway plays an important role in carcinogenesis in ICC through overexpression of its target genes, particularly cyclin D1.

Aged↗

The usefulness of immunostaining in washed cell cytological smears for differential diagnosis of B cell type malignant lymphoma.

We investigated the usefulness of immunostaining on washed cell cytological smears for the differential diagnosis of B-cell type malignant lymphoma. Twenty-eight cases with possible malignant lymphoma were examined. The tissues were squashed in a test tube of isotonic saline. The cell suspensions were then washed to remove non-specific soluble immmunoglobulin, and were smeared. Immunocytochemical staining for IgG, IgA, IgM, kappa and lambda was performed on the smears. As seen in the results, all cases of B cell lymphoma have a positive rate of 20% or over for kappa or lambda, and a kappa/lambda ratio of over 4.5 or a ratio of over 2.0 lambda/kappa, in the washed cell smears. Thus, it is possible to distinguish B cell lymphoma from the others by means of the results use as cut off scores. In addition, the rapid staining protocol in the present study was able to provide the results within 15 min. Therefore, it might be the most suitable method for the detection of immunoglobulin monoclonality in general laboratories.

Diagnosis, Differential↗

Antiapoptotic activity of Akt is down-regulated by Ca2+ in myocardiac H9c2 cells. Evidence of Ca(2+)-dependent regulation of protein phosphatase 2Ac.

Cell survival signaling of the Akt/protein kinase B pathway was influenced by a change in the cytoplasmic free calcium concentration ([Ca2+]i) for over 2 h via the regulation of a Ser/Thr phosphatase, protein phosphatase 2Ac (PP2Ac), in rat myocardiac H9c2 cells. Akt was down-regulated when [Ca2+]i was elevated by thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, but was up-regulated when it was suppressed by 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester (BAPTA-AM), a cell permeable Ca2+ chelator. The inactivation of Akt was well correlated with the susceptibility to oxidant-induced apoptosis in H9c2 cells. To investigate the mechanism of the Ca(2+)-dependent regulation of Akt via the regulation of PP2A, we examined the transcriptional regulation of PP2Acalpha in H9c2 cells with Ca2+ modulators. Transcription of the PP2Acalpha gene was increased by thapsigargin but decreased by BAPTA-AM. The promoter activity was examined and the cAMP response element (CRE) was found responsible for the Ca(2+)-dependent regulation of PP2Acalpha. Furthermore, phosphorylation of CRE-binding protein increased with thapsigargin but decreased with BAPTA-AM. A long term change of [Ca2+]i regulates PP2Acalpha gene transcription via CRE, resulting in a change in the activation status of Akt leading to an altered susceptibility to apoptosis.

Animals↗

Evaluation of venous thromboembolism and coagulation-fibrinolysis markers in Japanese patients with inflammatory bowel disease.

BACKGROUND: Arterial or venous thromboembolism is rarely encountered clinically as an extradigestive tract complication in inflammatory bowel disease (IBD). However, it is one of the important prognostic factors for IBD patients. The present study was designed to evaluate the relationship between pulmonary embolism (PE) and deep vein thrombosis (DVT) with coagulation-fibrinolysis markers in patients with active IBD. METHODS: In 47 consecutive cases hospitalized due to active IBD [26 with Crohn's disease (CD) and 21 with ulcerative colitis (UC)], we evaluated the disease severity, blood tests, pulmonary ventilation-perfusion scan (V/Q scan), and magnetic resonance venography (MRV) or conventional venography. RESULTS: PE was diagnosed by V/Q scan in 5 (2 with CD and 3 with UC; 10.6%). DVT was diagnosed in 5 (2 with CD and 3 with UC; 10.6%). Of the 47 patients, 8 (17.0%) had venous thromboembolism (either PE or DVT), and 2 of them (4.3%) had both conditions. In UC patients, the thrombosis group was in more severe stages based on endoscopic grading than the nonthrombosis group. In all patients, the thrombosis group were older (50.3 +/- 14.3 years) than the nonthrombosis group (29.2 +/- 11.7 years). Furthermore, the thrombosis group had higher thrombin-antithrombin III complex (13.1 +/- 17.7 ng/ml) and d-dimer (964 +/- 1402 ng/ml) values than the nonthrombosis group (5.3 +/- 5.5 ng/ml, P=0.0245, and 207 +/- 192 ng/ml, P=0.0016, respectively). There were no significant differences in leukocyte and platelet counts, C-reactive protein, and fibrinogen between the two groups. CONCLUSIONS: A high incidence of venous thromboembolism was suggested in Japanese patients with active IBD. We should be careful with thrombosis in treatment of IBD patients, especially those who are of older age and in more severe stages.

Adult↗

Allochronic overlapping malignancies after renal transplantation in a patient with p53 gene mutation: report of a case.

We report a rare case of the development of various tumors over a 16-year period after renal transplantation. A 56-year-old woman underwent renal transplantation using a US kidney. Immunosuppressive treatment consisted of a triple regimen of methylprednisolone, azathioprine, and mizoribine. Left breast cancer was diagnosed 9 years after the renal transplantation, then colon cancers and meningeal epidermal meningioma were diagnosed, 10 years and 12 years post-transplant, respectively. During the investigations for the breast and colon cancers, a p53 gene mutation was detected. A deterioration of renal function was found 16 years after the transplant and graft biopsy confirmed chronic rejection. We suggest that the effects of the immunosuppressive drugs combined with the p53 gene abnormality accelerated tumor development in this patient.

Azathioprine↗

Regulation of mineral-to-matrix ratio of lumbar trabecular bone in ovariectomized rats treated with risedronate in combination with or without vitamin K2.

The relationship between bone turnover and bone tissue and material properties was examined in ovariectomized (OVX) rats treated with risedronate in combination with or without vitamin K2. Seventy female rats, 18 weeks of age, were assigned to 7 groups (n=10): sham-operated + vehicle control; OVX + vehicle control; OVX + risedronate 0.1, 0.5, or 2.5 mg/kg/day po; OVX + vitamin K2 approximately 30 mg/kg/day po; OVX + vitamin K2 (approximately 30 mg/kg/day) and risedronate (0.5 mg/kg/day). Treatments were given daily for 9 months. To assess bone turnover, we measured serum osteocalcin and urinary deoxypyridinoline at 0, 3, and 9 months. To assess vertebral and femoral tissue and material properties, bone mass, bone mineral density (BMD by DXA), trabecular bone structure (vertebra: 3D-microCT), cortical bone structure (femur: histomorphometry), biomechanical properties, and mineral properties (mineral-to-matrix and carbonate-to-phosphate ratios by Fourier transform infrared microspectroscopy) were measured ex vivo at 9 months. Ovariectomy increased bone turnover and induced significant loss of bone mass/density, structure, mineral properties (mineral-to-matrix ratio), and strength. Risedronate produced dose-dependent inhibition of the ovariectomy-induced increase in turnover and loss of bone mass/density, structure, mineral-to-matrix ratio, and strength, with a lowest effective dose of 0.1-0.5 mg/kg/day. High-dose risedronate (2.5 mg/kg/day) did not induce increases in any parameter above that of sham control. Vitamin K2 had no effects. In the OVX groups, urinary deoxypyridinoline at 3 and 9 months correlated significantly with vertebral BMD, trabecular bone volume, ultimate load, stiffness, and mineral-to-matrix ratio, and with femoral BMD, cortical area, and ultimate load. These results support the concept that changes in bone tissue and material properties can result directly from changes in bone turnover. Different effects among different drugs on material properties, including mineral-to-matrix ratio, may reflect differences in the relative rate and magnitude of osteoclastic bone resorption and osteoblastic primary bone mineralization.

Absorptiometry, Photon↗

Human parathyroid hormone (1-34) increases mass and structure of the cortical shell, with resultant increase in lumbar bone strength, in ovariectomized rats.

Estrogen deficiency causes reduction of bone mass and abnormal bone microarchitecture, consequently reducing bone strength. Human parathyroid hormone (hPTH) (1-34) increases bone mass and strength. To clarify the factors that determine the recovery of bone strength in the lumbar vertebrae of ovariectomized rats by intermittent hPTH administration, we analyzed the relationship between skeletal measurements and bone strength. Human PTH (1-34) administration resulted in recovery of cortical bone mineral content (BMC) and cortical bone area to sham the levels, but in resulted in a less pronounced recovery of trabecular BMC and no increase in the total cross-sectional area of the vertebral body. Of the three-dimensional (3D) trabecular bone parameters, hPTH (1-34) increased trabecular thickness (Tb.Th). The cortical shell area of L4, determined by histomorphometry, was also increased. In hPTH-treated rats, the only determinant of the compressive load of L5 was the cortical shell BMC, in the early recovery period (days 42-84). Our data suggest that increased cortical bone mass contributes more than trabecular bone mass and structure to the recovery of bone strength in response to hPTH therapy in the rat lumbar vertebral body after ovariectomy.

Animals↗

The use of a hydrophilic-coated catheter during transradial cardiac catheterization is associated with a low incidence of radial artery spasm.

BACKGROUND: Radial artery spasm (RAS) is a common complication of transradial approach (TRA) to percutaneous coronary angiography (CAG) and coronary intervention. Lower friction resistance between catheter and RA wall may reduce RAS upon insertion, manipulation, and withdrawal of the catheter. The aim of this study was to investigate whether the use of a hydrophilic-coated (HC) catheter, which has lower friction coefficient, could reduce the incidence of RAS compared with a non-hydrophilic-coated (NHC) catheter. METHODS: A total 250 patients attempted diagnostic CAG using 5-French catheters via the TRA between September 2000 and April 2002. Two hundred thirty-four (93.6%) patients who achieved successful coronary cannulation were selected for the study. NHC catheters were used in 149 patients (63.7%), and HC catheters were used in 85 patients (36.3%). We compared the incidence of RAS between NHC and HC catheters. RESULTS: RAS occurred in 17 (7%) patients totally. RAS was less likely to occur in HC group (one patient, 1%) than in the NHC group (16 patients, 11%, P = 0.007). CONCLUSIONS: We conclude that the use of HC catheters can reduce RAS upon insertion, manipulation, and withdrawal of the catheter compared with NHC catheters.

Angioplasty, Balloon, Coronary↗

Expression of IAP family proteins in esophageal cancer.

Members of the inhibitor of apoptosis protein (IAP) family, including survivin, have been reported to be expressed in many tumors. However, their expression in esophageal cancer has not been clarified completely. We investigated the expression of mRNA for IAP family proteins in samples from esophageal cancers and their adjacent normal mucosa tissues by real-time quantitative RT-PCR. The survivin expression in esophageal cancer was significantly higher than that in normal mucosa (P < 0.05). Other IAP family proteins including cIAP1, cIAP2, NAIP and XIAP tended to show stronger expression in cancer tissue than normal mucosa, although the differences were not significant. As to the histological type of tumor, poorly differentiated squamous cell carcinomas exhibited significantly higher level of expression than well-differentiated carcinomas (P < 0.05). The proportion of apoptotic cells of cancer tissue inversely correlated with the intensity of survivin expression (P < 0.05). Immunohistochemical staining demonstrated cytoplasmic as well as nuclear expression of survivin in esophageal cancer, and further, in situ hybridization analysis demonstrated cytoplasmic expression of mRNA for survivin. The results suggest that the expression of IAP family proteins, especially survivin, may be associated with the biological character of esophageal cancer, such as apoptosis.

Aged↗

Induction of myogenin messenger ribonucleic acid in rat skeletal muscle after 1 hour of passive repetitive stretching.

OBJECTIVE: To investigate the effect of repetitive passive stretch of living rat muscle on myogenin messenger ribonucleic acid (mRNA) expression. DESIGN: Case-controlled study. SETTING: University laboratory. ANIMALS: Seventeen female 8-week-old Wistar rats. INTERVENTIONS: Repetitive stretch (15 times/min) was performed manually on gastrocnemius muscle of anesthetized rats for 15, 30, and 60 minutes. MAIN OUTCOME MEASURES: Total RNA was extracted, after the animals were killed, from the gastrocnemius muscle, and Northern blotting was performed using oligonucleotide complementary to myogenin. RESULTS: Repetitive stretch to gastrocnemius muscles of anesthetized rats for 1 hour induced a 21.5% increase in the expression of myogenin mRNA. CONCLUSIONS: Repetitive passive stretch of the rat skeletal muscle for 60 minutes induced the expression of myogenic transcription factor myogenin mRNA. These findings suggest the clinical utility of passive repetitive stretch to maintain muscle strength in patients who are unconscious or paralyzed.

Animals↗

Immunohistochemical and sequencing analyses of the Wnt signaling components in Japanese anaplastic thyroid cancers.

We investigated the status of the components and target genes of the Wnt signaling pathway in Japanese anaplastic thyroid cancers (ATCs) in the present study. Nuclear and cytoplasmic positive staining of beta-catenin, which might indicate the existence of alterations in the Wnt signaling pathway, were found in 40.9% and 63.6% of the 22 ATC samples, respectively. The beta-catenin, adenomatous polyposis coli (APC) and Axin 1 gene mutations were observed in 4.5%, 9.0%, and 81.8% of the 22 ATC samples, respectively. Overexpression of cyclin D1 and c-myc, which are the target genes of the Wnt signaling pathway, was observed in 27.3% and 59.1% of the ATC samples, respectively. There was no significant correlation between nuclear or cytoplasmic positive staining of beta-catenin and nuclear positive staining of cyclin D1 or c-myc. Taken together, the results of beta-catenin immunohistochemistry suggest that alterations in the Wnt signaling pathway are associated with carcinogenesis of ATC, but the frequency of beta-catenin gene mutation in our series is lower than that previously reported. Furthermore, cyclin D1 and c-myc frequently accumulated in ATC, independently of dysfunction in the Wnt signaling pathway.

Adenoma↗

Role of follicular dendritic cells in the early HIV-1 infection: in vitro model without specific antibody.

About 90% of HIV-1 RNA in the lymph nodes is reported to localize in follicular dendritic cellsnetwork (FDC-NW) as early as several days after infection and as much as that in the late stage. But the mechanism remains to be fully understood. To elucidate the role of follicular dendritic cells (FDC) in the early stage of HIV-1 infection, FDC-like cell strains (FDCLC) were established and they were characterized in the co-culture system with T cells for their effect on HIV-1 trapping and replication in p24 immunoassay, immunohistochemistry as well as confocal and electronmicroscopy. Established FDCLC were positive for CNA-42, S-100alpha and intercellular desmosome-like junctions. L-SIGN and DC-SIGN were also detected in FDCLC. Alu-HIV-1 PCR analysis showed no HIV-1 integration in FDCLC. FDCLC trapped HIV-1 and transferred them to uninfected MOLT-4 T cells (MOLT-4) efficiently in the absence of specific antibody. FDCLC also accelerated HIV-1 replication in HIV-1-pre-exposed MOLT-4. These unique FDCLC effects were explained, at least partly, by the fact that FDCLC up-regulated CD4 expression in MOLT-4 and helped T cells escape from apoptosis in the co-culture. These data suggest that FDC/FDCLC engage not only in trapping but also in active expansion of HIV-1 in the absence of specific antibody.

Cells, Cultured↗

Expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin antigen in pancreatic tumors.

Alterations in the expression of mucin family members play an important role as well as alterations in oncogenes and onco-suppressor genes in carcinogenesis and progression of pancreatic cancer. We analyzed the expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin antigen (SIMA) in pancreatic tumors. MUC1 expression was observed in almost all samples, whereas MUC2 expression was not. MUC5AC expression was observed in 73.9% of the cancerous regions, 48.7% of the dysplastic regions and 72.0% of the hyperplastic regions but not in the normal pancreatic duct. SIMA expression was observed in 45.7% of cancerous regions, 17.9% of the dysplastic regions and 8.0% of the hyperplastic regions. Furthermore, stromal expression of MUC1, MUC5AC and SIMA was observed in 37.0%, 60.9% and 26.1% of the cancerous regions, respectively. Stromal expression of these mucins was not observed in the hyperplastic regions and normal pancreatic duct and was observed in only two dysplastic regions. The survival of pancreatic cancer patients with stromal expression of MUC1 or SIMA was worse than that of other patients (P=0.04). In conclusion, the localization of mucin expression, especially stromal expression of MUC1 or SIMA, might be a prognostic factor for patients with pancreatic cancer.

Adult↗

Immunohistochemical analysis and mutational analyses of beta-catenin, Axin family and APC genes in hepatocellular carcinomas.

Several lines of evidence show that the development of hepatocellular carcinoma (HCC) requires an accumulation of genetic alterations. However, molecular mechanism in HCC carcinogenesis remains unsolved. A total of 89 HCC samples were analyzed in this study to determine how alterations in the Wnt signaling pathway associate with the carcinogenesis of HCC. beta-catenin immunohistochemistry showed positive nuclear staining in 24 (27.0%) of the 89 HCC samples, indicating the existence of alterations in the Wnt signaling pathway in those 24 HCC samples. Mutations in the beta-catenin, Axin1 and Axin2 genes were detected in 10 (41.7%), 13 (54.2%) and 9 (37.5%) of the 24 beta-catenin-positive samples, respectively, but no mutation was detected in the APC gene. In conclusion, in addition to mutations in the beta-catenin gene, mutations in the Axin1 and Axin2 genes may alter the Wnt signaling pathway, resulting in accumulation of beta-catenin.

Adenomatous Polyposis Coli Protein↗