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Biomedical subjects

T Toyama

Publications and source records attributed to T Toyama.

At least 73 records · Page 4Linked to original sources
PubMed1999

[Usefulness of 18F-FDG PET for diagnosis of cardiac sarcoidosis].

Cardiac sarcoidosis, the main cause of death among patients with sarcoidosis, frequently becomes clinically apparent when the disease is far advanced. To evaluate the usefulness of the 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting cardiac sarcoidosis, 18F-FDG PET was performed in 16 patients with sarcoidosis (13 female, 63 +/- 12 yrs), compared with scintigraphic findings of 99mTc-MIBI and 67Ga. Ten of 16 patients were considered to have cardiac complications on clinical grounds with tissue confirmation such as positive endomyocardial biopsy, severe ventricular arrhythmia, more than second degree atrioventricular block, and echocardiographically proven ventricular dysfunction. Among these patients with cardiac complications, abnormal myocardial uptake of FDG were observed in all (100%), which confirms significantly higher frequency compared to 67Ga scintigraphy (50%) (abnormality of 99mTc-MIBI SPECT were observed in 80%). Although abnormal FDG accumulations were observed in region with decreased uptake of 99mTc-MIBI in many cases, localization of regional abnormality of each tracer was frequently independent. This discrepancy may reflect inflammatory and degenerative process of myocardium in cardiac sarcoidosis. 18F-FDG PET is thought to be a useful noninvasive method in detecting cardiac involvement of sarcoidosis and may provide a useful information on the activity of the disease.

Adult↗
PubMed1999

[The characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy].

We evaluated the characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy (LVH). Myocardial imaging with 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) was performed in 28 patients with hypertrophic cardiomyopathy (HCM), 15 patients with hypertensive heart disease (HHD), 13 patients with aortic stenosis (AS) and 8 normal controls (NC). The patients with HCM consisted of 13 patients of asymmetric septal hypertrophy (ASH), 7 patients of diffuse hypertrophy (Diffuse-HCM) and 8 patients of apical hypertrophy (APH). Planar and SPECT images of BMIPP were acquired 15 minutes and 4 hours after tracer injection. Resting 201Tl SPECT images and echocardiography were also performed on other days. We calculated heart/mediastinum count ratio and washout rate of BMIPP by using planar image. In patients with LVH, the incidence of reduced BMIPP uptake was more frequent than that of reduced 201Tl uptake. In delayed images, more than 60% of patients with LVH reduced BMIPP uptake, especially remarkable for patients with ASH and APH. The washout rate of all cardiac hypertrophic disorders was tended to be higher than that of normal subjects. Reduced BMIPP uptake was frequently found in septal portion of anterior and inferior wall in patients with ASH, in inferior wall in patients with Diffuse-HCM and HHD, in apex in patients with APH and AS. These results suggest that BMIPP scintigraphy can differentiate three types of cardiac hypertrophy.

Aged↗
PubMed1999

[Effect of exercise therapy on oxygen consumption in patients with chronic heart failure].

The effect of exercise training on delta Vo2/delta WR was studied in 12 patients(11 men, one woman, mean age 62 +/- 9 yr)with chronic heart failure(old myocardial infarction, dilated cardiomyopathy, patients after coronary arterial bypass graft surgery and patients after aortic valve replacement). Cardiopulmonary exercise testing was performed to decide the exercise tolerance and assess the delta Vo2/delta WR. Patients underwent physical training at the anaerobic threshold for 3 months. Cardiopulmonary exercise testing was performed after the second week and after the third month. The anaerobic threshold increased at the third month compared with before exercise testing and the second week(p < 0.05, respectively) (before exercise testing: 13.6 +/- 2.0 ml/min/kg, the second week: 14.7 +/- 2.5 ml/min/kg, the third month: 16.2 +/- 2.1 ml/min/kg). The delta Vo2/delta WR increased at the second week compared with before exercise testing(before exercise testing: 8.9 +/- 1.9 ml/min/W, the second week: 10.6 +/- 1.9 ml/min/W, p < 0.05), but significantly decreased at the third month compared with the second week(the third month: 9.4 +/- 1.7 ml/min/W, p < 0.05). Serial increase of the anaerobic threshold and the peak Vo2/heart rate suggests that the exercise tolerance and cardiac function of the patients improved significantly. The increase of the delta Vo2/delta WR after the first 2 weeks seemed to depend on the luxury blood supply to both working and non-working muscles. The decrease of delta Vo2/delta WR at the third month may be due to the redistribution of the blood flow to the working muscles.

Chronic Disease↗
PubMed1998

Involvement of growth factor receptor-bound protein-2 in rat hepatocyte growth.

Growth factor receptor-bound protein-2 (GRB-2) is a protein linking receptor tyrosine kinase and Sos (Son of Sevenless gene; Ras GDP/GTP exchange protein), leading to activation of the Ras-mitogen-activated protein kinase (MAPK) cascade. So far, it remains unclear how GRB-2 plays a role in signal transduction pathways evoked by hepatotrophic factors. This study was attempted to evaluate the involvement of GRB-2 in signalling in rat hepatocyte growth. Using rat cultured hepatocytes stimulated by hepatotrophic factors and regenerating livers after partial hepatectomy (PH) we examined GRB-2-mediated linkage of hepatotrophic factor receptors to signal transducing molecules such as Sos or dynamin-II by immunoprecipitation and western blot analysis. In primary cultured hepatocytes stimulated with hepatocyte growth factor (HGF) or epidermal growth factor (EGF), GRB-2 linked HGF receptor or EGF receptor, respectively, to Sos which activated the mitogen-activated protein kinase (MAPK) cascade. In contrast, in primary cultured hepatocytes stimulated with insulin, GRB-2 linked insulin receptor substrate-1 (IRS-1) to dynamin-II as well as Sos. In the early phase after PH, GRB-2 activated the Ras-MAPK cascade by linking HGF receptor, IRS-1, or EGF receptor to Sos. In the late phase after PH, a complex of IRS-1-GRB-2 associated with dynamin-II, indicating that GRB-2 may transduce signals from IRS-1 to dynamin-II. We conclude that GRB-2 may play a role in transmitting signals from hepatotrophic factors to not only MAPK but also to other signalling pathways in hepatocyte growth.

Adaptor Proteins, Signal Transducing↗
PubMed1998

[Prognostic significance of loss of heterozygosity in breast cancer].

Loss of heterozygosity (LOH) was analyzed in 113 cases of sporadic breast cancer using 35 microsatellite markers on 20 chromosomes. LOH was frequently seen in 17p (44%), 16q (31%), 17q (29%) and 13q (23%). Individual patients were scored according to the incidence of LOH at the above four chromosomal markers; with no LOH as 1, with one or two LOH as 2, and with three of four LOH as 3. A high LOH score was well associated with high histological grade (p = 0.019) and a significantly poor prognosis (p = 0.0035). These data suggest that accumulation of LOH occurs at a later stage of breast cancer progression, and that the LOH score may be a useful prognostic marker of breast cancer.

Breast Neoplasms↗
PubMed1997

The Clinical Value of Microsatellite Instability and a Loss in Heterozygosity in Sporadic Breast Cancers.

We analyzed loss of heterozygosity (LOH) and microsatellite instability (MI) in 108 cases of sporadic breast cancers using 22 microsatellite markers on 12 chromosomes. LOH was frequently seen in 1p(13%), 6p(18%), 8p(11%), 11p(18%), 13q(21%),16q(31%), 17p(44%) and 17q(29%). Individual patients were scored according to the degree of LOH at the above eight chromosomal markers. Patients with no LOH were scored as 1, patients with one to three LOH were scored as 2, and patients with four or more LOH were scored as 3. A high LOH score correlated with a high histological grade (p=0.019) and a poor prognosis (p=0.0035). Eleven(10.2%) of 108 patients with breast cancer showed MI, with 6 cases showing MI at a single locus and 5 at multiple loci. Of the 11 MI-positive patients only one had lymph node involvement(p=0.015), none had histological grade 3 disease, and MI-positive patients tended to have a better prognosis than MI-negative ones. These data suggest that MI may be an early event in mammary tumorigenesis, and that LOH occurs at a later stage. The LOH score may be a useful prognostic marker of operable breast cancer.

Journal Article↗
PubMed1997

Clinical significance of bcl-2 gene expression in human breast cancer tissues.

The expression of estrogen receptor (ER) and bcl-2 (Bcl-2), an apoptosis protective oncogene, in normal and cancerous breast duct epithelia was immunohistochemically examined in fresh frozen tumor tissues from 142 Japanese breast cancer patients. The clinico-pathological characteristics and the disease free survival of the patients were analyzed. The expression of both the proteins was also observed in intraductal components of breast cancer. Although less than 1% of normal duct epithelia expressed ER, Bcl-2 was diffusely expressed. The expression of both these proteins in breast cancer significantly correlated with each other. Their expression significantly correlated negatively with tumor size but not with lymph node status. The papillo-tubular sub-type of invasive ductal carcinoma expressed Bcl-2 significantly more frequently than the solid-tubular sub-type. Patients with Bcl-2 expressing tumors survived without recurrence significantly more than those with tumors exhibiting reduced expression. Papillary-cribriform type intraductal components expressed both those proteins more often than the solid-comedo type.

Adult↗
PubMed1997

Simultaneous quantitative analyses of c-erbB-2 protein, epidermal growth factor receptor, cathepsin D, and hormone receptors in breast cancer.

The overexpression of c-erbB-2 protein (ErbB2), epidermal growth factor receptor (EGFR), and/or cathepsin D (CD) in breast cancer is known to be a poor prognostic factor. Eighty frozen breast cancer specimens obtained at the initial operation were examined for ErbB2, EGFR, and CD by immunohistochemical assay (ICA) and enzyme immunoassay (EIA). Estrogen and progesterone receptors (ER and PgR) were measured simultaneously by EIA. The mean values +/- 1SD for ErbB2, EGFR and CD were 141 +/- 400 U/mg membrane protein (range: 0-3385), 4.88 +/- 4.33 fmol/mg membrane protein (range: 0-21.1), and 47.1 +/- 32.8 pmol/mg cytosol protein (range: 4.7-182), respectively. The percentage of specimens positive for ErbB2, EGFR, and CD was 12.5, 38.8, and 35%, when the tentative cutoff value were used as 200 U/mg protein, 5 fmol/mg protein, and 50 pmol/mg protein, respectively. These E1A results were correlated with ICA, EGFR and ER were negatively correlated. Although the prognostic value of ErbB2 and EGFR was superior to hormone receptors, ErbB2 and EGFR were interior as predictors compared with lymph node involvement and tumor size. Quantitation of ErbB2, EGFR, and CD can be performed readily using the same specimen in which hormone receptors are measured.

Adult↗
PubMed1997

[The usefulness of 18F-FDG SPECT imaging in evaluating myocardial viability].

UNLABELLED: We compared myocardial viability evaluated by 18F-deoxyglucose (FDG) SPECT in 14 old myocardial infarction patients with that evaluated by 201TI SPECT and 123I-beta-methyl-iodophenyl pentadecanoic acid SPECT as imaging of fatty acid metabolism. FDG-SPECT was performed after oral administration of glucose. From each SPECT image which was divided into 7 segments, the degree of accumulation of each radioisotope (RI) was visually classified into four grades of defect score (ranging from 0 as normal to 3 as severe defect). The % uptake in the same area was also quantitatively calculated. RESULTS: The degree of accumulation of myocardial Rl relative to regional wall motion. FDG is the most wide for a range of accumulation of Rl of infarct area. Also, at FDG, in the area of wall motion had done a disorder, the degree of accumulation was higher than other two methods. In the infarcted area, the degree of accumulation on FDG-SPECT in the area of decreased wall motion was greater than that on the other two procedures. These results suggest that FDG-SPECT is useful for evaluating myocardial viability.

Aged↗
PubMed1997

[Usefulness of 201Tl/123I-BMIPP myocardial SPECT to evaluate myocardial viability and area at risk in acute myocardial infarction--comparison with 201Tl/99mTc-PYP dual SPECT].

To evaluate the area at risk and the myocardial viability of acute myocardial infarction (AMI), we compared rest 123I-beta-methyl iodophenyl pentadecanoic acid (123I-BMIPP) and 201Tl myocardial SPECT with 201Tl/99mTc-PYP dual SPECT (D-SPECT) in 65 patients (mean age 64 +/- 11 years) with AMI. D-SPECT was performed in 3 to 5 days, 123I-BMIPP myocardial SPECT in 5 to 7 days, and left ventriculography on 1 month after onset of AMI. Furthermore, 201Tl/123I-BMIPP myocardial SPECT and left ventriculography were performed on 4 months after onset of AMI. The area which showed the reduced 123I-BMIPP uptake was larger than that showed the accumulation of 99mTc-PYP. The improvement of regional wall motion on 4 months after onset of AMI tended to be more closely correlated with the existence of discrepancy zone between 201Tl and 123I-BMIPP uptake than that of overlap zone between 201Tl and 99mTc-PYP uptake in acute period. We conclude that 201Tl/123I-BMIPP myocardial SPECT is more useful to evaluate the area at risk and myocardial viability of AMI than D-SPECT.

Aged↗
PubMed1996

Low Frequency Loss of Heterozygosity in the BRCA1 Region in Japanese Sporadic Breast Cancer.

To investigate the possible involvement of the BRCA1 gene in Japanese sporadic breast cancer we have analyzed loss of heterozygosity (LOH) at the BRCA1 region (17q12-q22) in 101 sporadic breast cancers using 5 microsatellite markers, such as D17S250, D17S846, D17S855, D17S579, and NME1. The frequency of LOH in each markers was 14.9%(11/74), 11.9 %(8/67),14.3%(12/84),5.3%(4/75), and13.3%(9/68),respectively. The incidence of LOH in at least one of 5 markers was 23.8%(24/101). The LOH at the BRCA1 region did not significantly correlate with clinicopathologic factors. Despite using a microdissection method, the LOH frequency in our series was relatively lower than other reports, especially in Western countries. We suggest that the BRCA1 gene might play only a limited role as a tumor suppressor gene in the majority of Japanese sporadic breast cancers.

Journal Article↗
PubMed1996

Microsatellite instability in in situ and invasive sporadic breast cancers of Japanese women.

We studied the timing of microsatellite instability (referred to as replication error; RER) presentation during human breast carcinogenesis using tissue microdissected from both in situ and invasive breast cancers of Japanese women. We analyzed 100 breast cancer specimens for RER at nine genomic loci on seven chromosomes. Eight of the 100 cases (8%) were RER-positive at one or more chromosomal loci. Additionally; we obtained genomic DNA from two of four RER-positive patients with an intraductal component, both of which showed microsatellite instability in in situ foci. This finding indicates that microsatellite instability may be an early event during human breast carcinogenesis.

Breast Neoplasms↗
PubMed1996

Microsatellite instability in sporadic human breast cancers.

Human breast-cancer specimens from 100 patients were analyzed for microsatellite instability (referred to as replication error; RER) at 12 genomic loci on 7 chromosomes, and results were correlated with clinicopathologic characteristics. In 42 of 100 breast-cancer patients, we investigated whether RER was associated with the amplification of oncogenes and/or suppression of tumor-suppressor genes. Of the 100 patients, 8 (8%) were RER-positive at one or more chromosomal loci. The majority of RER-positive patients had early-stage disease with ER-positive tumors, suggesting that RER occurs early in breast tumorigenesis. However, no significant correlation was observed between RER and oncogenes or tumor-suppressor genes. Thus, the mechanism of RER in sporadic human breast cancer may be independent of the multi-step carcinogenesis caused by the alterations of oncogenes and tumor-suppressor genes.

Breast Neoplasms↗
PubMed1996

Flow Cytometric Assay of c-erbB-2 Protein in Fine Needle Aspirates of Fresh and Frozen Human Breast Cancer Tissues.

Using FCM (flow cytometry), we analyzed the ErbB-2 (c-erbB-2 protein) status of 61 breast cancer tissue samples obtained by FNAB (fine-needle aspiration biopsy). The number of cancer cells collected by FNAB from fresh samples was 1.7+/-0.7 x10&sup5;, 2.5 +/-0.6 x10&sup5;, and 4.0+/- 0.8x10 &sup5;, by single, double and triple aspirations, respectively. A mean of 3.0+/-0.6 x10&sup5;cells was collected on three aspirations from frozen samples. The number of cells collected on three aspirations was sufficient for the measurement of ErbB-2. Cells with higher ErbB-2 levels than those of normal human lymphocytes were designated ErbB-2 positive cells. The mean overall for ErbB-2 positive cell rates was 20.5 +/- 27.9 % (mean+/-SD). The rates were 27.9 +/- 31.6 % in patients with recurrence and 15.9 +/- 24.4% in patients without recurrence. When the cut-off value was set at 20% of the positive cell rate (P =0.008, generalized Wilcoxon test), patients with ErbB-2 negative tumors showed highly significantly longer survival without recurrence (P=0.008, generalized Wilcoxontest) and better overall survival rates (P=0.013) than patients with ErbB-2 positive tumors. Among 61 specimens, 16 (26.2%) scored positive for ErbB-2 by FCM. These finding indicated that the analysis of ErbB-2 status using FCM of samples obtained by FNAB should be useful for preoperatively evaluating the prognosis of patients with breast cancer.

Journal Article↗
PubMed1996

Noncoding RNA for CR20, a cytokinin-repressed gene of cucumber.

The CR20 gene was identified as a cytokinin-repressed gene in excised cotyledons of cucumber. We determined the sequences of some CR20 cDNAs with different structures and sequenced genomic clones for CR20. This gene consisted of three exons, and there were at least three types of transcript, which seemed to be generated by alternative splicing of the second intron. None of the CR20 transcripts included a long open reading frame (ORF). We isolated a cDNA of Arabidopsis thaliana with cucumber CR20 cDNA as a probe. This cDNA for a gene designated AtCR20-1 also lacked a long ORF. A region of 180 nucleotides was conserved in the CR20 RNA of cucumber and the AtCR20-1 RNA of Arabidopsis, although the homology was relatively low when the entire sequences were compared. Each conserved region consisted of seven elements, and seems to form stable secondary structure. These suggest that CR20 RNA may function as an RNA that is not translated into a protein.

Alternative Splicing↗
PubMed1996

Clinical significance of CD45RO expression on peripheral blood mononuclear cells in HTLV-I-infected individuals.

The phenotype of peripheral blood mononuclear cells (PBMC) was examined in 13 healthy volunteers, 26 HTLV-I carriers, and 58 ATL patients (22 smouldering, five chronic, 24 acute, and seven lymphoma type). The percentage of CD4+, CD25+, CD28+ and CD45RO+ cells in the PBMC of the chronic and acute type patients was significantly higher than that of the volunteers, whereas the percentage of CD8+ and CD45RA+ cells in these patients was significantly low. The histogram for CD45RO fluorescence intensity (FI) revealed two patterns: pattern A consisted of CD45RO+ cells with high FI (CD45ROhigh) and intermediate FI (CD45ROint). Pattern B consisted exclusively of CD45ROhigh. Pattern A was evident in all volunteers. The percentage of subjects showing pattern B was increased in an order that reflected disease progression. In the patients with pattern A, the CD45ROint cells were CD4+ and CD8-, and the FI of CD2, CD3, and Fas within the CD45ROint cells appeared to be lower than that within the CD45ROhigh cells. The acute type patients with pattern A had a significantly longer survival curve than that of these patients with pattern B. These results suggest that the presence of CD45ROint cells may be related to protection against disease progression in HTLV-I-infected individuals.

Acute Disease↗
PubMed1996

Changes in serum fibrogenesis markers during interferon therapy for chronic hepatitis type C.

We serially measured the levels of serum N-terminal peptide of type III procollagen (PIIINP), the 7S domain of type IV collagen (IV-7S), and hyaluronate (HA) before (0 month), at the end (6 months), and 24 weeks after the end of interferon therapy (12 months) in patients with chronic hepatitis type C to estimate the effects of interferon alfa (IFN-alpha) on serum levels of hepatic fibrogenesis markers. One hundred twenty-one patients with chronic hepatitis type C received intramuscular injection of 6 million U of natural IFN-alpha for 24 weeks. Patients were divided into three groups: sustained complete response (CR-S), complete response with rebound (CR-R), and nonresponse (NR). Serum PIIINP, IV-7S, and HA levels were significantly decreased and reached normal levels at 12 months in CR-S; only IV-7S levels were significantly decreased at 12 months in CR-R, whereas these levels remained abnormally high in the NR. These results suggest that IFN-alpha therapy could lower the levels of serum hepatic fibrogenesis markers along with improvements in hepatic inflammation.

Adult↗