Search PubMed⌕ Search

Biomedical subjects

E Tahara

Publications and source records attributed to E Tahara.

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

Allele frequency of D17S855 microsatellite locus in Japanese people.

Allele frequency of D17S855 microsatellite locus, an intragenic polymorphic cytosine-adenine repeat located in the BRCA1 gene, was analyzed in 456 normal tissues of Japanese adults. The frequency of D17S855 microsatellite polymorphism was 77.9% (335/456). The size of D17S855 PCR fragments ranged from 137 to 157 bp. The most frequent allele was 151 bp (29.9%) followed by 149-bp (19.3%), 145-bp (17.5%), and 147-bp (17.0%) fragments. The observed allele distribution of this microsatellite was similar to that of Southern Swedes, while it was quite different from that of European Caucasian specimens deposited in the Genome Database.

Adult↗
PubMed1999

Inhibitory mechanisms of glycoprotein fraction derived from Miscanthus sinensis for the immediate phase response of an IgE-mediated cutaneous reaction.

We investigated the inhibitory effect of the glycoprotein fraction (fraction 2) extracted from Miscanthus sinensi ANDERSSON (M. sinensis) on biphasic cutaneous reactions in mice passively sensitized with IgE. Biphasic skin reactions with peak responses at 1 (IPR, immediate phase reaction) and 24 h (LPR, late phase reaction) were caused by passive sensitization with an anti-dinitrophenol IgE monoclonal antibody (anti-DNP IgE mAb) followed by an epicutaneous challenge of 0.1% dinitrofluorobenzene (DNFB) in 100% ethanol. Intraperitoneal injection of fraction 2 before the DNFB challenge significantly inhibited the biphasic ear swelling response in passively sensitized mice in a dose-dependent manner (1-30 mg/kg). We also found that fraction 2 was effective at inhibiting the vascular permeability in mouse ear induced by an injection of compound 48/80, histamine or serotonin. In addition, fraction 2 inhibited scratching behavior as well as ear edema observed within 2 h after DNFB challenge. Marked inhibition was observed in both passively sensitized and non-sensitized mice. The locomotor activity of mice was also reduced by the administration of fraction 2 as well as by diphenhydramine. These results suggest that the inhibitory effect of glycoprotein fraction 2 of M. sinensis on an IgE-mediated allergic inflammatory reaction is due to the protection of mediator-induced vascular permeability and that in addition to the inhibition of an inflammatory reaction, a sedative action is responsible for the inhibition of allergy-induced scratching responses.

Acute-Phase Reaction↗
PubMed1999

Allele frequency of D1S191 microsatellite locus in Japanese people.

The allele frequency of D1S191 microsatellite locus was analyzed in 398 normal tissues of Japanese adults. The frequency of D1S191 microsatellite polymorphism was 90.2% (359/398). The size of D1S191 PCR fragments ranged from 147 bp to 169 bp. The most frequent allele in the Japanese subjects was 161 bp (34.1%) followed by 159 bp (27.9%), 163 bp (17.7%), and 157 bp (12.4%) fragments. The observed allelic distribution of this microsatellite in the Japanese subjects was similar to that of European Caucasians deposited in the Genome Database.

Adult↗
PubMed1999

Quantitative reevaluation of telomerase activity in cancerous and noncancerous gastrointestinal tissues.

Telomerase activity has been examined extensively in a variety of human cancerous and noncancerous tissues. However, it was sometimes difficult to measure telomerase activity quantitatively with the methods used and in the tissues examined. We examined telomerase activity quantitatively in gastrointestinal tissues by using the hybridization protection assay combined with the telomeric repeat amplification protocol (TRAP) to assess the diagnostic utility of measuring telomerase activity and to determine the relationship between telomerase activity and human telomerase reverse transcriptase (hTERT) expression. We report here that (i) polymerase chain reaction (PCR) inhibitors in the tissue extracts used for the telomerase assay were practically nullified by using tissue extract at 0.1 microg of protein/assay; (ii) RNase activity in tissue extracts should be blocked with 0.5 U of RNase inhibitor/microg tissue protein for the quantitative telomerase assay; (iii) no inhibitors of telomerase were found in tissue extracts other than RNase and PCR inhibitors (iv) higher telomerase activity in cancerous tissue than in noncancerous tissue from the same patients was observed in both gastric and colorectal tissues, but the telomerase activity varied from low to high levels in cancerous tissues, and it was not practical to set a general cut-off level for cancer diagnosis; (v) hTERT was expressed in both cancerous and noncancerous tissues, and (vi) the telomerase activity levels were generally lower than expected from the hTERT expression levels, suggesting posttranscriptional regulation of expression of telomerase activity.

Adenocarcinoma↗
PubMed1999

Abnormalities in the expression of cell cycle-related proteins in tumors of the small bowel.

Tumors of the small bowel are quite rare for unknown reasons, although they resemble colorectal tumors in many respects. The purpose of this study was to determine whether abnormalities in the expression of several cell cycle control genes are of importance in small bowel tumorigenesis by comparing a series of samples of normal mucosa, adenomatous polyps, and adenocarcinomas. The levels of cyclin D1, cyclin E, p16, p21, p27, and p53 proteins were determined by immunohistochemistry in samples of normal small bowel (n = 16), small bowel adenomas (n = 20), and small bowel adenocarcinomas (n = 24). Normal small bowel mucosa expressed p27 protein, but not the other cell cycle-related proteins. About 20% of the tumors displayed a decrease in the expression of this protein. The most frequent alteration in the tumors was an increase in the p16 protein. Increased expression of p53 was associated with tumor progression because it was overexpressed in 45% of the adenomas and 65% of the adenocarcinomas (P<0.05). Advanced age and increased detection of cyclin D1 and p53 were associated with a decreased 3-year survival (P<0.05). Cell cycle abnormalities are early and important events in the multistep process of small bowel tumorigenesis, thus resembling colorectal carcinogenesis. As in colon cancer, deregulated expression of G1 proteins may perturb cell cycle control in benign adenomas of the small bowel and thereby enhance tumor progression. Increased expression of cell cycle inhibitors in tumors may serve as a defense mechanism for tumor progression.

Adenocarcinoma↗
PubMed1999

Microsatellite instabilities in gastric cancer patients with multiple primary cancers.

To answer whether microsatellite instability (MSI) can serve as a molecular marker for the risk-assessment of the development of multiple cancers, 26 tumors from 10 gastric cancer cases with multiple primary cancers were investigated. Six out of 10 cases revealed MSI in one or more cancer DNA. Significant statistical association was observed between MSI positive gastric cancer and cancer multiplicity (chi2 test, P<0.05). The complicated primary tumors in MSI-positive cases arose in colorectum, urogenital tract and ovary, which mimicked the tumor spectrum of hereditary non-polyposis colorectal cancer (HNPCC). On the other hand, most of the multiple cancers in MSI negative group were found synchronously and limited to the digestive organs. These observations suggest that MSI test on gastric cancer may be considered as a good marker for the assessment of multiple cancer development especially in the sites where tumors of HNPCC usually develop.

Aged↗
PubMed1999

Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma.

We examined the expression level of several genes that regulate distinct steps of metastasis in formalin-fixed, paraffin-embedded, archival specimens of primary human pancreatic carcinomas from patients undergoing curative surgery. The expression of epidermal growth factor receptor, E-cadherin, type IV collagenase [matrix metalloproteinase (MMP) 2 and MMP-9), basic fibroblast growth factor, vascular endothelial growth factor/vascular permeability factor, and interleukin 8 was examined by a colorimetric in situ mRNA hybridization technique. Down-regulation of E-cadherin and up-regulation of type IV collagenase (MMP-9 and MMP-2) at the periphery of the neoplasms (P = 0.0167, 0.0102, and 0.0349, respectively) had significant prognostic value. The ratio of type IV collagenase expression (mean of the expression of MMP-2 and MMP-9) to E-cadherin expression (MMP:E-cadherin ratio) at the periphery of the tumors was significantly higher in patients with recurrent disease (4.7 +/- 2.1) than in patients who were disease free (2.3 +/- 1.7; P = 0.0008). Death from pancreatic cancer was significantly associated with a high MMP:E-cadherin ratio (>3.0) by overall survival analysis (P < 0.0002), whereas a low MMP:E-cadherin ratio (<3.0) was found in seven of eight patients alive 28-64 months after surgery. Multivariate analysis of overall survival showed that the MMP:E-cadherin ratio was a significant independent prognostic factor, whereas stage, nodal metastasis, and histological type were not. These data show that multiparametric analysis for several metastasis-related genes may allow physicians to assess the metastatic potential and hence predict the clinical outcome of individual patients with resectable pancreatic carcinoma.

Adenocarcinoma↗
PubMed1998

Reduced expression of cyclin-dependent kinase inhibitor p27Kip1 is an indicator of malignant behavior in oral squamous cell carcinoma.

BACKGROUND: Reduced expression of the cyclin-dependent kinase inhibitor p27Kip1 has been reported to correlate with poor survival in cohorts of breast and colorectal carcinoma patients. Posttranslational ubiquitin-mediated proteasomal proteolysis is related to p27Kip1 protein levels. However, to the authors' knowledge, no previous study has examined the expression of p27Kip1 in oral squamous cell carcinoma (OSCC). METHODS: To examine the expression of p27Kip1 and its clinicopathologic roles in OSCC, the authors studied the expression of p27Kip1 protein by immunohistochemistry in deparaffinized tissue sections of 20 normal oral mucosa specimens, 22 epithelial dysplasia specimens, and 70 OSCCs, and analyzed its correlation with clinicopathologic parameters. They also studied the expression of p27Kip1 mRNA and protein in six OSCC cell lines by Northern blot and Western blot analysis. To examine the mechanism of reduced expression of p27Kip1, OSCC cell lines were treated with the proteasome inhibitor LLnV. RESULTS: All the normal oral mucosa specimens and 73% (16 of 22) of the oral epithelial dysplasia specimens expressed p27Kip1 at high levels, whereas 87% of the OSCCs (61 of 70) showed reduced expression of p27Kip1. Furthermore, the levels of expression of this protein were significantly lower in carcinomas with metastasis than those without metastasis. Although OSCC cell lines expressed p27Kip1 mRNA at various levels, most of them expressed p27Kip1 protein at lower or undetectable levels. LLnV induced the expression of p27Kip1 protein in HSC2 cells, in which p27Kip1 protein was originally undetectable. CONCLUSIONS: These findings suggest that 1) reduced expression of p27Kip1 may correlate with the development and progression of OSCC and can be an indicator of malignant behavior of this neoplasm, and 2) increased proteasome-mediated degradation may play an important role in the reduction of p27Kip1 protein expression.

Adult↗
PubMed1998

Slowly progressive L-DOPA nonresponsive pure akinesia due to nigropallidal degeneration: a clinicopathological case study.

We report an autopsy case of a 51-year old man who showed slowly progressive pure akinesia: freezing phenomenon and festination during 21 years of illness without tremor, rigidity, upward gaze palsy, bradykinesia and dementia, which were not responded to L-DOPA clinically. Neuropathological findings revealed the circumscribed regions in the substantia nigra and middle portion of the internal globus pallidus (GPi), without neurofibrillary tangles, neuropil threads, and glial fibrillary tangles. So this case was clearly distinguished with progressive nuclear palsy and pallidonigroluisian atrophy. It was first reported to describe that L-DOPA nonresponsive pure akinesia can arise from nigopallidal atrophy.

Disease Progression↗
PubMed1998

Co-expression of osteopontin and CD44v9 in gastric cancer.

We have examined the expression of osteopontin (OPN) in 40 human primary gastric carcinoma tissues, 5 metastatic foci (lymph nodes) and corresponding normal mucosas. Twenty-nine of 40 primary tumors (72.5%) and 3 of 5 lymph node metastases (60%) overexpressed OPN mRNA in comparison with those of the corresponding normal mucosa. The incidence as well as relative expression level of OPN mRNA was higher in well differentiated gastric cancers than poorly differentiated ones. Moreover, increased OPN mRNA expression in primary tumor specimens was observed along with the advancement of the clinico-pathological stage. Using in situ hybridization (ISH) analysis, not only inflammatory cells in tumor stroma but also tumor cells showed positive signals for OPN mRNA. By immunohistochemistry, co-immunoreaction of OPN and CD44v9 in tumor cells obviously correlated with the degree of lymphatic vessel invasion or long distant lymph node metastases in poorly differentiated gastric cancer. Interestingly, strong co-immunoreaction of OPN and CD44v9 of tumor cells was concommitant with cluster formation in the lymphatic vessels. Our results suggest that overexpression of OPN correlated with the progression of human gastric carcinoma. Especially in CD44-bearing poorly differentiated gastric cancer, interaction between OPN and CD44 may parallel lymphogenous metastasis.

Adult↗
PubMed1998

Multilineage hematopoietic recovery by a single injection of pegylated recombinant human megakaryocyte growth and development factor in myelosuppressed mice.

Previous studies have shown that daily multiple administration of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) markedly stimulates thrombopoiesis and effectively ameliorates thrombocytopenia, and in most cases anemia and neutropenia, in myelosuppressed animals. In this study, we evaluated the effects of a single intravenous injection of PEG-rHuMGDF on hematopoietic recovery after sublethal total-body irradiation in mice. A single injection of PEG-rHuMGDF (1 to 640 microg/kg) 1 hour after irradiation accelerated platelet, red blood cell (RBC), and white blood cell (WBC) recovery in a dose-dependent fashion. In the bone marrow of vehicle-treated mice, megakaryocytic, erythroid, and myeloid progenitors, as well as day 12 colony-forming unit-spleen (CFU-S), were dramatically decreased much earlier than the nadirs of peripheral blood cells, whereas megakaryocytes were modestly decreased. Treatment with PEG-rHuMGDF (80 microg/kg, an optimal dose) 1 hour after irradiation resulted in more rapid recovery of these four hematopoietic progenitors and also significantly facilitated megakaryocyte recovery. In addition, the same PEG-rHuMGDF administration schedule expanded bone marrow cells capable of rescuing lethally irradiated recipient mice. As the interval between irradiation and PEG-rHuMGDF treatment was longer, its effects on hematopoietic recovery were attenuated. In contrast to the effects of PEG-rHuMGDF, a single injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 1 hour after irradiation exclusively accelerated WBC recovery, but only to a similar extent as PEG-rHuMGDF (80 microg/kg) treatment even when rhG-CSF doses were escalated to 1,000 microg/kg. This appeared related to different pharmacokinetics of these two factors after a single injection in irradiated mice. The concentrations of PEG-rHuMGDF after injection persisted in the plasma for a longer time compared with rhG-CSF. These results indicate that a single injection of PEG-rHuMGDF at an early time after irradiation is able to effectively improve thrombocytopenia, anemia, and leukopenia with concomitant accelerated recovery of both primitive and committed hematopoietic progenitors in irradiated mice. Our data also show that compared with the rhG-CSF shown to exert multilineage effects on hematopoiesis, PEG-rHuMGDF has more wide-ranging effects on peripheral blood cell recovery.

Animals↗
PubMed1998

Frequent p53 gene mutations in serrated adenomas of the colorectum.

Serrated adenoma has been recently proposed as a distinct histological lesion of the colorectum. This study examined p53 immunoreactivity, mutations of exons 5-8 of the p53 gene, codon 12 of the Ki-ras gene by PCR-SSCP analyses, and microsatellite instability in 19 serrated adenomas, ten adenocarcinomas in/with serrated adenomas, 23 hyperplastic nodules, four hyperplastic polyps and 29 tubular adenomas of the colorectum. Eleven of 11 (100 per cent) serrated adenomas had p53 immunoreactivity and all six (100 per cent) adenocacinomas in/with serrated adenomas exhibited moderate to severe p53 immunoreactivity. It was confirmed that 9 of 19 (47 per cent) serrated adenomas and 5 of 10 (50 per cent) adenocarcinomas in/with serrated adenomas harboured p53 gene mutations. On the other hand, no p53 gene mutation was detected in the other colorectal lesions. Meanwhile, 11 (58 per cent) serrated adenomas and six (60 per cent) adenocarcinomas in/with serrated adenomas had Ki-ras gene mutations, as also did 9 of 23 (39 per cent) hyperplastic nodules, 3 of 4 (75 per cent) hyperplastic polyps, and 12 of 29 (41 per cent) tubular adenomas. Microsatellite instability was detected in one (5 per cent) serrated adenoma and one (10 per cent) adenocarcinoma in a serrated adenoma. The other lesions did not show microsatellite instability. Serrated adenomas had significantly frequent p53 gene mutations compared with hyperplastic lesions or tubular adenomas (p < 0.005). On the other hand, they did not exhibit significant differences in mutations of the Ki-ras gene or in microsatellite instability. Genetic changes were then examined in small parts of serrated adenomas, such as the upper or lower parts of crypts, to determine the extent of gene mutations by using a microdissection technique. Exon 15 of the APC gene and the DCC gene, in addition to the p53 and Ki-ras genes and microsatellite instability, were analysed. Identical mutations of the p53 gene were found in both invasive adenocarcinomas and adjacent serrated adenomas by direct sequencing, suggesting single clonal origins for those lesions. Mutations of the APC gene and microsatellite instability were heterogeneous in some lesions. No loss of heterozygosity (LOH) of the DCC gene was found. These findings suggest that mutations of the p53 gene are the most characteristic genetic alterations in serrated adenomas, as a relatively early event in a multistep carcinogenic pathway of this type of colorectal lesion, that might be distinct from the ordinary adenoma-carcinoma sequence or from carcinogenesis via mutations of mismatch repair genes.

Adenocarcinoma↗
PubMed1998

Molecular mechanism of human stomach carcinogenesis implicated in Helicobacter pylori infection.

Genetic and epigenetic alterations in oncogenes, tumor suppressor genes, cell adhesion molecules, telomere and telomerase activity as well as genetic instability at several microsatellite foci are responsible for multistep process of human stomach carcinogenesis. The scenario of these alterations found in gastric cancer differs depending on the two histological types, indicating that different genetic pathways exist for well differentiated or intestinal type and poorly differentiated or diffuse type gastric cancers, even though both types of gastric cancer may arise from epithelial "stem cells" which express human telomerase reverse transcriptase (hTRT) and telomerase activity. Infection with Helicobacter pylori, which evidently causes the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS), may be a strong trigger for "stem cell" hyperplasia in intestinal metaplasia, followed by telomere reduction and increase telomerase activity as well as hTRT overexpression. They may precede DNA replication error, DNA hypermethylation, CD44 abnormal transcript and p53 mutations, all of which occur in at least 30% of intestinal metaplasia as early events of multistep pathogenesis of well differentiated type gastric cancer.

DNA, Neoplasm↗
PubMed1998

Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas.

Telomerase is a specialized type of reverse transcriptase which catalyzes the synthesis and extension of telomeric DNA (for review, see ref.1). This enzyme is highly active in most cancer cells, but is inactive in most somatic cells. This striking observation led to the suggestion that telomerase might be important for the continued growth or progression of cancer cells. However, little is known about the molecular mechanism of telomerase activation in cancer cells. Human telomerase reverse transcriptase (hTRT) has recently been identified as a putative human telomerase catalytic subunit. We transfected the gene encoding hTRT into telomerase-negative human normal fibroblast cells and demonstrated that expression of wild-type hTRT induces telomerase activity, whereas hTRT mutants containing mutations in regions conserved among other reverse transcriptases did not. Hepatocellular carcinoma (20 samples) and non-cancerous liver tissues (19 samples) were examined for telomerase activity and expression of hTRT, the human telomerase RNA component (hTR; encoded by TERC) and the human telomerase-associated protein (hTLP1; encoded by TEP1). A significant correlation between hTRT expression and telomerase activity was observed. These results indicate that the hTRT protein is the catalytic subunit of human telomerase, and that it plays a key role in the activation of telomerase in cancer cells.

Amino Acid Sequence↗
PubMed1998

Microsatellite instability associated with primary head and neck cancers and secondary esophageal cancers.

BACKGROUND: It is common that patients with head and neck cancers have secondary malignant neoplasm of esophageal cancer. METHODS: To know the genetic background of the development of these secondary cancers, we performed microsatellite assay at six loci and immunohistochemical analysis on head and neck cancers of eight patients with esophageal cancer and on those of 19 patients without esophageal cancer. RESULTS: Replication error (RER) at more than two loci was observed in two (25%) of eight double cancer patients, whereas it was not observed in the patients without the secondary cancer. Immunohistochemically, overexpression of cyclin D1 was detected in two (25%) of eight double cancer cases and in two (11%) of 19 non-double cancer cases, respectively, the incidence showing a higher tendency in the former. CONCLUSIONS: The results suggest that microsatellite instability may be implicated in the development of head and neck double cancers and that RER (+) phenotype may serve as a biomarker to predict the development of secondary esophageal cancer in patients with head and neck cancer.

Adult↗