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Biomedical subjects

T Toyama

Publications and source records attributed to T Toyama.

At least 19 recordsLinked to original sources
PubMed1999

Cardiac sympathetic activity estimated by 123I-MIBG myocardial imaging in patients with dilated cardiomyopathy after beta-blocker or angiotensin-converting enzyme inhibitor therapy.

UNLABELLED: Impaired cardiac sympathetic activity can be evaluated by 123I-metaiodobenzylguanidine (MIBG) imaging. METHODS: We studied the significance of MIBG imaging for 24 patients (age 58+/-12 y) with dilated cardiomyopathy (DCM). We compared 12 patients (group A) treated with metoprolol (dose from 30-60 mg/d) with 12 patients treated with angiotensin-converting enzyme (ACE) inhibitors. Patients were studied before treatment, after 5 mo of treatment (only in group A) and after 1 y of treatment. Cardiac MIBG uptake was assessed as the heart-to-mediastinum activity ratio (H/M) and total defect score (TDS) from anterior planar and SPECT MIBG images, which were acquired in 4 h after tracer injection. New York Heart Association (NYHA) class and left ventricular ejection fraction (LVEF) calculated by echocardiography were also assessed. RESULTS: TDS decreased in both groups (in group A, from 30+/-7 through 23+/-9 to 18+/-10; P < 0.01, in group B, from 30+/-6 to 24+/-8; P < 0.01) and H/M was increased in both groups (in group A, from 1.87+/-0.31 through 2.03+/-0.28 to 2.14+/-0.29; P < 0.01, in group B, from 1.82+/-0.28 to 1.94+/-0.26; P < 0.05). But TDS and H/M were more improved in group A than in group B (P < 0.05). LVEF was significantly increased in only group A (from 38+/-6 through 43+/-8 to 49%+/-9%; P < 0.01). NYHA improved in both groups (in group A, from mean 2.5 through 2.1 to 1.8; P < 0.01, in group B, from mean 2.6 to 2.1; P < 0.05) but was more improved in group A than in group B (P < 0.05). CONCLUSION: Cardiac function, symptom and cardiac sympathetic activity evaluated by MIBG images improved after the beta-blocker therapy more than with the treatment that used ACE inhibitors.

3-Iodobenzylguanidine↗
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

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

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

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↗
PubMed1996

The level of mRNA transcribed from psaL, which encodes a subunit of photosystem I, is increased by cytokinin in darkness in etiolated cotyledons of cucumber.

A cDNA clone for an mRNA whose level increased within 2 h of the start of treatment with N6-benzyladenine in etiolated cotyledons of cucumber was isolated by differential hybridization. The cDNA was homologous to psaL, which encodes subunit XI (PSI-L) of photosystem I. The accumulation of psaL mRNA was specifically induced by cytokinins or light.

Amino Acid Sequence↗
PubMed1996

Evaluation of cardiac sympathetic nervous function by 123I-metaiodobenzylguanidine scintigraphy in insulin-treated non-insulin dependent diabetics with hypoglycemia unawareness.

The association between the lack of adrenergic symptoms during hypoglycemia and myocardial 123I-metaiodobenzylguanidine (MIBG) accumulation was investigated in 12 insulin-treated non-insulin-dependent diabetes mellitus (NIDDM) patients who had no evidence of heart disease. These patients were divided into 2 groups according to the presence (group A) or absence (group B) of adrenergic symptoms during hypoglycemia. Autonomic function tests revealed significantly severe autonomic dysfunction in group B compared to that in group A. Insulin infusion test indicated no significant difference in the catecholamine response between the two groups. 123I-MIBG scintigraphy showed that the heart/mediastinum ratio of MIBG uptake was significantly lower, and scintigraphic defect was greater in group B than in group A. There were no significant differences in the washout rate between the two groups. These results suggested that the lack of adrenergic symptoms during hypoglycemia may be associated with cardiac sympathetic nervous dysfunction in insulin-treated NIDDM patients, and this dysfunction is mainly due to cardiac sympathetic denervation.

3-Iodobenzylguanidine↗
PubMed1996

[Molecular analysis of the estrogen receptor (ER) gene in association with ER negativity in breast cancer].

DNA from ninety-eight primary breast cancer biopsies has been examined for loss of heterozygosity (LOH). Thirteen of seventy-two informative cases (18.1%) were positive for LOH, which correlated with age at operation but not with ER status. This result suggests that LOH of the ER gene does not have an important role in the lack of ER function in breast cancer tissues. Thirteen breast cancers with ER negative/progesterone receptor (PgR) positive were screened for mutation analysis of the ER gene using single strand conformational polymorphism (SSCP). We found 2 polymorphisms in codon 10 (C to G) codon 325 (C to T), although neither germline nor somatic mutation was detected. Since the sequence variant of codon 325 tends to be more frequently seen in ER negative/PgR negative breast cancer patients than non-cancer control patients, it is suggested that this polymorphism was related to negativity and function of ER in breast cancer tissues.

Breast Neoplasms↗
PubMed1996

[The regional wall motion and the myocardial fatty acid metabolism at hibernating myocardium].

To evaluate the regional wall motion and the myocardial fatty acid metabolism at hibernating myocardium after revascularization (PTCA or CABG), we performed dual SPECT with 201Tl and 123I-beta-methyliodophenyl-pentadecanoic acid (BMIPP), and left ventriculography (LVG) in 34 patients with coronary artery disease before and 3 to 4 months after revascularization. In the SPECT, regional tracer uptake was estimated qualitatively (visual) and quantitatively (% uptake). Regional wall motion was estimated qualitatively (visual) and quantitatively (shortening fraction). At the 78 hibernating areas, the improvement of regional wall motion was more significantly (p < 0.05) correlated with that of regional tracer uptake of 123I-BMIPP (r = 0.63) than 201Tl (r = 0.39), and also correlated with the improvement of the difference between 201Tl and 123I-BMIPP regional uptake (r = 0.36). These results suggest that the improvement of wall motion at hibernating myocardium is more significantly correlated with the improvement of 123I-BMIPP than 201Tl uptake after revascularization.

Adult↗