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Biomedical subjects

Satoshi Ikeda

Publications and source records attributed to Satoshi Ikeda.

At least 55 records · Page 3Linked to original sources
PubMed2003

Immunohistochemical and mutational analyses of beta-catenin, Ki-ras, and p53 in two subtypes of colorectal mucinous carcinoma.

PURPOSE: The adenoma-carcinoma sequence theory is accepted in carcinogenesis of colorectal carcinoma. To elucidate the nature and genetic alterations in colorectal mucinous carcinoma (MC), we analyzed clinical and pathological characteristics of colorectal MC and nonmucinous carcinoma (NMC), and, furthermore, we compared the prognoses and the statuses of the Wnt signaling pathway, Ki-ras, and p53 in these two subtypes. EXPERIMENTAL DESIGN: Samples of colorectal MC obtained by surgical resections from 41 patients during the period from 1980 to 1999 were classified into fixed (FIX) type and floating (FLO) type (22 and 19 cases, respectively). The statuses of the Wnt signaling pathway and p53 protein were estimated by immunohistochemistry of beta-catenin and p53 proteins, respectively. The mutations in the Ki-ras gene were examined by direct sequencing. RESULTS: The prognosis of colorectal MC was poorer than that of NMC at both stage II and stage III (P = 0.0037 and <0.0001, respectively). The survival rate of patients with the FLO type of MC was lower than that of patients with the FIX type (P = 0.021). Although the results of immunohistochemistry of beta-catenin and mutational analysis of the Ki-ras gene in the two subtypes were not significantly different; the rate of positive nuclear staining of p53 was lower in the FLO type than in the FIX type (P = 0.04). CONCLUSIONS: Colorectal MC, particularly the FLO type, has a more aggressive nature than does colorectal NMC. The FLO type of colorectal MC may develop through different mechanisms from those through which NMC and the FIX type develop.

Adenocarcinoma, Mucinous↗
PubMed2003

Oxidative modulation of NF-kappaB signaling by oxidized low-density lipoprotein.

Oxidized low-density lipoprotein (oxLDL) modifies macrophage inflammatory responses in the pathogenesis of atherosclerosis. In the present study, we focused on gamma-glutamylcysteine synthetase (gamma-GCS), a rate limiting enzyme of glutathione synthesis, and examined whether inflammatory stimulation of gamma-GCS gene in macrophages by lipopolysaccharide (LPS) is modified when the cells were exposed to oxLDL. We found that the nuclear factor-kappaB (NF-kappaB)-mediated induction of gamma-GCS by LPS (100 ng/ml) was suppressed by a 48-h pre-treatment with oxLDL (50 micro/ml), and this was due to a decrease in the DNA-binding activity of NF-kappaB. Furthermore, pre-treatment with oxLDL caused a carbonylation of NF-kappaB subunit p65. With alpha-tocopherol, the oxLDL-induced carbonylation of proteins decreased with a restoration of DNA-binding activity of NF-kappaB. Together, these indicate that oxidative modification of NF-kappaB suppresses LPS-induced expression of gamma-GCS gene in ox-LDL-treated cells, suggesting an implication of oxLDL-induced modulation of NF-kappaB signaling with atherosclerosis.

Animals↗
PubMed2003

Bone structure and mineralization demonstrated using synchrotron radiation computed tomography (SR-CT) in animal models: preliminary findings.

We investigated the ability of synchrotron radiation computed tomography (SR-CT) to demonstrate trabecular microstructure, detail of trabecular surfaces, and mineralization of bones. Eight rat vertebrae, six rat tibiae, and eight minipig vertebrae were scanned using SR-CT at the synchrotron radiation facility Super Photon ring-8GeV (SPring-8). Images obtained using conventional micro-CT, scanning electron microscopy (SEM), and contact microradiography (CMR) were compared with the SR-CT images. SR-CT showed high image quality without visible partial volume effect. Three-dimensional SR-CT revealed shallow concavities in the bone surface, which were considered to correspond to osteoclastic resorption areas, as well as the connectivity, anisotropy, and shape (rod- or platelike) of trabeculae. Two-dimensional SR-CT showed different density along the surface of the trabecular bone, indicating the degree of bone mineralization. In conclusion, SR-CT seems to be a useful tool for delineating trabecular surfaces, evaluating bone mineralization, and revealing precise trabecular structure.

Animals↗
PubMed2003

Effects of 1,25(OH)2D3 on turnover, mineralization, and strength of bone in growing rats with liver cirrhosis induced by administration of carbon tetrachloride.

To clarify the effects of 1 alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on bone growth, strength, and turnover in growing rats with liver cirrhosis induced by carbon tetrachloride (CCl(4)) injection, groups of 4-week-old male Wistar rats (n = 10, each) were injected intraperitoneally with CCl(4) twice weekly for 7 weeks. One group was treated with the vehicle alone (Group 1). Three CCl(4)-injected groups were orally administered 1,25(OH)(2)D(3) at doses of 0, 0.05, and 0.1 micro g/kg, respectively (Groups 2, 3, and 4). At the end, serum levels of 1,25(OH)(2)D(3), IGF-I, and osteocalcin were reduced in Group 2 compared to Group 1, and the corresponding values in Group 4 were larger than those in Group 2. Urinary deoxypyridinoline levels increased in Group 2 compared to Group 1, and did not significantly differ in Groups 2-4. The values for bone sizes, mineral content (BMC) in the lumbar vertebra and femur, and ultimate bending load in the femur were reduced in Group 2 compared to Group 1, and lumbar BMC in Group 3 and bone sizes in Group 4 were larger than those in Group 2. The values for lumbar trabecular bone volume in Group 2 were reduced compared to Group 1, and the corresponding values in Group 4 were larger than those in Group 2. Bone formation rates, reduced in Group 2 compared to Group 1, did not differ in Groups 2-4. Parameters for trabecular osteoclasts did not differ among all groups. In the proximal tibia, the value of activation frequency (Ac.f) in Group 2 significantly decreased compared to Group 1. Ac.f values in Groups 3 and 4 were larger than that in Group 2. These data demonstrated that retardation of bone growth in CCl(4)-injected rats was associated with reduced serum 1,25(OH)(2)D(3) and IGF-I levels. The trabecular bone in the rats exhibited low turnover osteopenia. 1,25(OH)(2)D(3) administration partially prevented the growth disturbance, but did not substantially affect bone turnover. Factors other than 1,25(OH)(2)D(3) and IGF-I appeared to be critical in the low turnover osteopenia evident in liver cirrhosis.

Animals↗
PubMed2003

Reductions in bone turnover, mineral, and structure associated with mechanical properties of lumbar vertebra and femur in glucocorticoid-treated growing minipigs.

The present study was designed to determine the effects of glucocorticoid (GC) on bone turnover, minerals, structure, and bone mechanical properties in minipigs. Six 8-month-old Göttingen minipigs were subcutaneously injected with prednisolone (PN, 0.5 mg/kg body wt (BW)/day, 5 days/week for 26 weeks (Group GC)), 6 were treated with vehicle alone (Group VC), and 4 were sacrificed at start of the study for baseline controls (Group BC). The increase in BW was similar in all groups. PN significantly reduced serum osteocalcin and urinary type-1 collagen N-telopeptide levels at 13 weeks and thereafter, compared with baseline and control, and also reduced serum bone specific alkaline phosphatase levels relative to baseline. At 26 weeks, the longitudinal axis of the lumbar bone and length of femur were smaller in Group GC than Group VC. The total cross-sectional area of femur, but not the lumbar bone, in Group GC was significantly different from Group VC. BMD of the femur, but not L2, measured by DXA, was lower in Group GC than in Groups BC and VC. The cortical shell structure measured by 2D-micro-CT deteriorated and age-dependent increases in trabecular bone structure 3D micro-CT were reduced by PN. PN also caused deterioration of the cortical structure of the mid-femur. In L2 and femur, PN significantly reduced the ultimate load and maximum absorption energy of the femur and L2 compared with Group VC. The structural modulus in Group GC was lower than in Group BC. Regression analyses revealed that bone minerals, bone structure, and chemical markers correlated with mechanical properties of L2 and mid-femur. Our results indicate that PN reduced systemic bone formation and resorption and suppressed the age-dependent increases in bone minerals, structure, and mechanical properties of L2 and mid-femur. Reduced bone turnover seemed to be associated with a reduction in mechanical properties. The growing minipig could be a suitable model of GCs-induced osteoporosis in humans.

Animals↗
PubMed2003

Correlation between the expression of telomerase reverse transcriptase and proliferative activity in breast cancer cells using an immunocytochemical restaining method.

Telomerase activity is thought to contribute to the immortality of cancers. Recently, some investigators described a correlation between the activity of telomerase and the proliferative activity of cancer cells. The aim of this study was to evaluate the correlation between the expression of telomerase-associated protein and proliferative activity. Telomerase reverse transcriptase (TERT) is one of the proteins that correlates with telomerase activity. We investigated TERT protein and its mRNA, and examined the correlation between the TERT protein and Ki-67, which reflects proliferative activity with immunostaining, and its mRNA, which correlates with telomerase activity, using in situ hybridization. Imprint smears from 17 invasive ductal adenocarcinomas were investigated. In most cases positive for TERT mRNA, the percentage of TERT protein-positive cells was also high and was closely related to mRNA (P = 0.024). The positive rates of TERT for the cases with lymph node metastasis were significantly higher than those for the cases without metastasis (P = 0.046). The positivity of TERT protein also correlated significantly with the Ki-67-positive rate (r = 0.82). As the proliferation activity increased, the number of cells positive for both proteins also increased (r = 0.89). In conclusion, it was suggested that the expression of TERT protein is associated with the expression of Ki-67, and is concerned with maintenance of the high proliferative activity in cancer cells with aggressive proliferation.

Adult↗
PubMed2003

Repetitive stretch induces c-fos and myogenin mRNA within several hours in skeletal muscle removed from rats.

OBJECTIVE: To investigate what effect repetitive stretch has on gene transcription in muscle tissues removed from rats. DESIGN: Case-control study. SETTING: University laboratory. ANIMALS: Eight female 8-week-old Wistar rats. INTERVENTIONS: Rat anterior tibial and soleus muscles were removed and repetitively stretched about 20% of the muscle length by using the Magnus method in Krebs-Ringer solution. Stretch-relax cycles 15 times per minute were continued for 2 hours in 1 group and 4 hours in another group. Contralateral muscles removed from the same rat were incubated without stretch as the control. MAIN OUTCOME MEASURES: After repetitive stretch, total ribonucleic acid (RNA) was extracted from the muscles and Northern blotting was carried out using c-fos and myogenin oligonucleotide as probes. RESULTS: Repetitive stretch during 2 hours significantly increased the expression of c-fos messenger RNA (mRNA) in both the tibialis anterior and soleus muscles. Increased expression of myogenin mRNA in both muscles was observed with repetitive stretch for 4 hours. Because of the initial increase of immediate early gene c-fos mRNA and the subsequent increase of myogenic transcription factor myogenin mRNA, it appears that repetitive muscle stretch induces sequential progression of gene transcription toward muscle hypertrophy. CONCLUSIONS: Mechanical repetitive stretch for a few hours would be one of the stimulating factors for muscle growth and should be available for muscle training in clinical rehabilitation.

Animals↗
PubMed2003

Relationship between ECG findings and pulmonary artery pressure in patients with acute massive pulmonary thromboembolism.

Pulmonary thromboembolism (PTE) is associated with various electrocardiogram (ECG) abnormalities, but the utility of evaluating the severity of PTE based on ECG abnormalities alone has not been investigated in Japanese patients previously. The purpose of this study was to examine the relationship between ECG abnormalities and the mean pulmonary artery pressure (MPAP) in patients with acute massive PTE (AMPTE). ECG examination of 21 patients, who were diagnosed with AMPTE by pulmonary arteriography, found that S(1)Q(3)T (3) was the most frequently observed abnormality (in 67% of the patients), followed by negative T (62%), clockwise rotation (57%), and ST elevation (48%). When these patients were divided into 2 groups based on the level of MPAP, 8 of the 11 ECG findings, which were associated with PTE in a previous report, were more frequently observed in Group H (MPAP >/=40 mmHg) than in Group L (MPAP <40 mmHg). MPAP correlated significantly with the total number of ECG abnormalities (r=0.82, p<0.001). In particular, at least 5 ECG abnormalities were noted in patients with MPAP >/=45 mmHg. These results suggested that the total number of ECG abnormalities in patients with AMPTE can be used to evaluate the severity of APTE, including PAP level.

Acute Disease↗
PubMed2003

Role of autonomic nervous dysfunction in electrocardio-graphic abnormalities and cardiac injury in patients with acute subarachnoid hemorrhage.

Electrocardiographic abnormalities, cardiac injury, and autonomic nervous function were investigated in patients with acute-phase subarachnoid hemorrhage (SAH) (42 patients with SAH related to ruptured aneurysm and 42 control subjects). Electrocardiogram and Holter electrocardiogram for spectral analysis of heart rate variability (HRV) were recorded. Concentrations of cardiogenic enzymes (ie, creatine kinase-myocardial fraction [CK-MB], myosin light chain I, and troponin T), plasma concentrations of catecholamine (ie, noradrenaline, adrenaline, 3-methoxy-4-hydroxy-phenylethylene glycol [MHPG]) and HRV were compared in the acute and chronic phase of SAH, and with the values in the controls subjects. As previously reported, patients with acute SAH exhibited electrocardiographic (ECG) abnormalities and increased concentrations of both cardiogenic enzymes and plasma catecholamines, suggesting that acceleration of sympathetic activity is involved. However, HRV analysis showed enhanced parasympathetic activity, probably associated with increased intracranial pressure after the onset of SAH, which may be explained by accentuated antagonism, negative feedback of noradrenaline to the center, and reduction of sympathetic activity after reaching a peak level. The results suggest that not only sympathetic activity but also vagal activity is enhanced during the acute phase of SAH, thus contributing to the ECG abnormalities and the onset of cardiac injury.

Acute Disease↗
PubMed2003

[New evaluation for osteoporosis using calcaneal computed radiographs].

Quantitative analysis of bone mass is a method mainly used for the diagnosis of osteoporosis. However, there are cases of osteoporosis that cannot be diagnosed by this method alone. This study was performed to develop a new quantitative method for the evaluation of osteoporosis using texture analysis and geometric feature analysis of trabecular bone on lateral calcaneal computed radiographs. Thirty-seven cases including 11 normal and 26 abnormal lateral calcaneal radiographs were examined. The patients' ages ranged from 24 to 89 years (average age, 58.3 years). The root mean square (RMS) variation and first moment of power spectrum of trabecular bone patterns were determined as quantitative measures for texture analysis. In addition, the total area and total length of trabecular bone were obtained from geometric feature analysis. The RMS variations in pixel values, total area, and total length of trabecular bone were decreased as bone atrophy progressed. These three quantitative measures corresponded well to radiologists' subjective evaluations of bone atrophy. Moreover, our results indicated that these three quantitative measures had strong correlations with bone mineral density of the femoral neck. Therefore, we consider the computerized method with texture analysis and geometric feature analysis of lateral calcaneal radiographs to be very useful for radiologists in evaluating osteoporosis.

Adult↗
PubMed2003

[Frequency of apoptotic cells and BAX positive cells in the lymph nodes of colorectal cancer patients with metastasis and micrometastasis].

It is regarded that the presence of micrometastatic(isolated) cancer cells is a forerunner of metastasis. We classified advanced colorectal cancers into 3 groups such as metastasis group in which distinct metastasis was identified in lymph nodes by HE stain, micrometastasis group which was negative for metastasis by HE stain but positive for micrometastasis by immunostain using antibody for cytokeratin, and non-metastasis group which was negative for both stains. We investigated proliferative activity of cells and frequency of apoptotic cells in the lymph nodes from each group. The frequency of apoptotic cells in the metastasis group was significantly lower than the other groups (p < 0.02), and correlated with expression of BAX protein. In conclusion, frequencies of apoptotic cells and BAX positive cells in the nodes of metastasis group were significantly lower than micrometastasis group. And it was suggested that those changes were correlated with inflow of isolated cancer cells and formation of metastatic foci in the lymph nodes, and may reflected the difference of immunological activity against cancer cells.

Apoptosis↗
PubMed2003

[Haemostatic molecular markers].

Because a significant number of the deaths caused by acute (massive) pulmonary thromboembolism occur within the hours after the onset of symptoms, its early diagnosis is very important. The gold standard diagnostic tests for venous thromboembolism (VTE), contrast venography and pulmonary angiography, respectively, are invasive, expensive, not readily available, and labor intensive. A diagnostic tool for VTE is needed that is noninvasive and highly accurate, allowing immediate treatment decisions to be made in most cases. D-dimer, a one of haemostatic molecular markers, is specific cross linked fibrin derivatives. This is the most promising blood test for VTE screening. Although elevated concentrations of D-dimers are sensitive for the presence of VTE, they are not specific. They therefore cannot be used to make a positive diagnosis of VTE.

Acute Disease↗
PubMed2003

Pulmonary granulomas caused experimentally in mice by a recombinant trigger-factor protein of Propionibacterium acnes.

Etiology of sarcoidosis remains unknown. A trigger factor from Propionibacterium acnes causes a cellular immune response in some sarcoid patients but not in nonsarcoid subjects. We examined whether experimentally induced hypersensitivity to the trigger factor gives rise to granulomas. Female C57BL/6 mice primed intravenously with P. acnes or not were sensitized with recombinant-protein RP35, a fragment of P. acnes trigger factor, and complete Freund's adjuvant. In controls, RP35 was replaced with P. acnes or one of two control proteins. In primed and unprimed mice, pulmonary granulomas were found in some of the mice sensitized with RP35 or P. acnes but in no control-protein-sensitized mice. Detection of pulmonary granulomas (25-57%) did not differ significantly between mice sensitized with RP35 or P. acnes, primed or not. No difference in popliteal lymph-node-cell reactivity and serum antibodies to these two antigens was found between mice with and without pulmonary granulomas. P. acnes was cultured from the lungs of 8 (33%) of 24 untreated mice. The recombinant trigger-factor protein of P. acnes caused pulmonary granulomas in primed and unprimed mice sensitized with the protein and adjuvant. Sarcoid granulomas may form during hypersensitivity to antigens of P. acnes indigenous to the affected organ.

Animals↗
PubMed2002

Nepsilon-(Carboxymethyl)lysine induces gamma-glutamylcysteine synthetase in RAW264.7 cells.

Advanced glycation end products (AGEs) play an important role in the development of angiopathy in diabetes mellitus and atherosclerosis. Here, we show that adducts of N(epsilon)-(carboxymethyl)lysine (CML), a major AGE, and bovine serum albumin (CML-BSA) stimulated gamma-glutamylcysteine synthetase (gamma-GCS), which is a key enzyme of glutathione (GSH) synthesis, in RAW264.7 mouse macrophage-like cells. CML-BSA stimulated the expression of gamma-GCS heavy subunit (h) time- and dose-dependently and concomitantly increased GSH levels. CML-BSA also stimulated DNA-binding activity of activator protein-1 (AP-1) within 3h, but the stimulatory effect decreased in 5h, and nuclear factor-kappaB (NF-kappaB) with a peak activity at 1h and the stimulatory effect diminished in 3h. Studies of luciferase activity of the gamma-GCSh promoter showed that deletion and mutagenesis of the AP-1-site abolished CML-BSA-induced up-regulation, while that of NF-kappaB-site did not affect CML-BSA-induced activity. CML-BSA also stimulated the activity of protein kinase C, Ras/Raf-1, and MEK/ERK1/2. Inhibition of ERK1/2 abolished CML-BSA-stimulated AP-1 DNA-binding activity and gamma-GCSh mRNA expression. Our results suggest that induction of gamma-GCS by CML adducts seems to increase the defense potential of cells against oxidative stress produced during glycation processes.

Animals↗
PubMed2002

Frequent alterations in the Wnt signaling pathway in colorectal cancer with microsatellite instability.

It is generally accepted that both dysfunction of the Wnt signaling pathway, including mutations in the adenomatous polyposis coli (APC) and beta-catenin genes, and genetic instability play important roles in colorectal carcinogenesis. However, alteration of the components in the Wnt signaling pathway in colorectal cancer (CRC) with microsatellite instability (MSI) has not been elucidated. In order to assess the status of the Wnt signaling components in CRC with MSI, mutational analyses of the beta-catenin, APC, Axin 1, and T cell factor 4 (TCF4) genes were performed. Three of 33 samples had mutations in exon 3 of the beta-catenin gene and two in the APC gene. Eight mutations in seven samples were detected by single-strand conformation polymorphism and subsequent direct sequence analysis of the entire coding region of the Axin 1 gene. Furthermore, TCF4, which is one of the transcriptional factors in the Wnt signaling pathway and has a mononucleotide repeat sequence (a nine- adenine repeat, (A)9) in its C-terminal region, was mutated in 13 of the 33 samples. Thus, alteration in the Wnt signaling pathway is frequently observed in CRC with MSI, including hereditary nonpolyposis colorectal cancer, as well as in familial adenomatous polyposis and sporadic CRC without MSI.

Adenomatous Polyposis Coli Protein↗
PubMed2002

In situ localization of Propionibacterium acnes DNA in lymph nodes from sarcoidosis patients by signal amplification with catalysed reporter deposition.

Sarcoidosis is a systemic granulomatous disease of unknown aetiology. Many genomes of Propionibacterium acnes and P. granulosum have been detected in lymph nodes from patients with sarcoidosis. In situ localization of propionibacterial genomes in sarcoid lymph nodes may help to establish an aetiological link between sarcoidosis and these indigenous bacteria. Formalin-fixed and paraffin-embedded biopsy samples of lymph nodes from nine patients with sarcoidosis, nine patients with tuberculosis, and nine patients with non-specific lymphadenitis as controls were examined by quantitative real-time PCR (QPCR) for P. acnes and by in situ hybridization (ISH) that used catalysed reporter deposition (CARD) for signal amplification with digoxigenin-labelled oligonucleotide probes that complemented 16S rRNA of P. acnes. The signals per 250 micro m(2) of tissue sections were counted from inside and outside the granulomas of sarcoidosis and tuberculosis and from control lymph nodes. The number of genomes by QPCR was examined for correlation with the mean signal count by ISH with CARD. In sarcoid samples, one or several signals were detected in the cytoplasm of some epithelioid cells in granulomas and of many mononuclear cells around granulomas. The mean signal counts were higher (p < 0.001) in granulomatous areas than in other areas of sarcoid lymph nodes. Even in their non-granulomatous areas, counts were higher than in granulomatous areas (p = 0.0023) and non-granulomatous areas (p < 0.001) of tuberculous lymph nodes and control lymph nodes (p = 0.0071). Correlation between the results by QPCR and ISH with CARD was significant (r = 0.86, p < 0.001). The accumulation of P. acnes genomes in and around sarcoid granulomas suggests that this indigenous bacterium may be related to the cause of granulomatous inflammation in sarcoidosis.

Animals↗
PubMed2002

Diethylstilbestrol attenuates antioxidant activities in testis from male mice.

It has been reported that acute exposure to diethylstilbestrol (DES) induces apoptosis in the testis, and antioxidants play a role in preventing DES-induced tissue damage. In this study, the effect of chronic exposure to DES on the antioxidants was examined in the testis and liver. Eight-week old male ICR mice were treated subcutaneously with various doses of DES for 20 days. Morphologically apparent apoptotic changes, 4-hydroxy-2-nonenal-positive cells and TUNEL-positive DNA-fragmentation, were demonstrated in the testis, but were minimal in the liver. Activities of antioxidants such as glutathione (GSH) peroxidase and GSH S-transferase decreased in both the liver and testis. The activity of Mn-superoxide dismutase (SOD) decreased in the liver but increased in the testis. The activity of Cu, Zn-SOD decreased in the liver but was unchanged in the testis. On Western and Northern blots, gamma-glutamylcysteine synthetase (gamma-GCS), a rate limiting enzyme of GSH synthesis, was increased in the liver dependent on the dose of DES. However, the expression of gamma-GCS was reduced in the testis. Since quinones, metabolites of DES, generate reactive oxygen species, which damage DNA, antioxidants are important to prevent the damage. The data suggest that antioxidant activities are impaired by DES, and the levels of GSH are related to DES-induced apoptosis in the testis.

Animals↗