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Biomedical subjects

R Ueda

Publications and source records attributed to R Ueda.

At least 73 records · Page 4Linked to original sources
PubMed2000

Effects of sesquiterpenoids from "Oriental incenses" on acetic acid-induced writhing and D2 and 5-HT2A receptors in rat brain.

Six sesquiterpenoids, namely jinkoh-eremol, agarospirol, alpha- and beta-santalols, dehydrocostus lactone and costunolide, isolated from oriental incenses inhibited acetic acid-induced writhing in mice. The incidence of writhing produced by jinkoh-eremol, alpha-santalol and costunolide were revealed by administration of naloxone (mu-, kappa- and delta-antagonists). Inhibitory activities of alpha-santalol on opioid receptors were shown only by the delta antagonist, but not by the mu- and kappa-antagonists. The delta2-antagonist, but not the delta-antagonist, inhibited the activity of alpha santalol. The mechanism of inhibitory activity on the opioid receptor by alpha-santalol was different from that of morphine. Alpha-santalol was shown to be the most potent of the six as an antagonist of dopamine D2 and serotonine 5-HT2A receptor binding. The effect of alpha-santalol, was the same as that of chlorpromazine as an antipsychotic agent, although alpha-santalol was less potent than chlorpromazine.

Acetic Acid↗
PubMed2000

Neuronal distribution and subcellular localization of HCNP-like immunoreactivity in rat small intestine.

A novel peptide, hippocampal cholinergic neurostimulating peptide (HCNP), originally purified from young rat hippocampus, affects the development of specific cholinergic neurons of the central nervous system in vitro. In this study, HCNP-like-immunoreactive nerve processes and nerve cell bodies were identified by electron microscopic immunocytochemistry in the rat small intestine. Labeled nerve processes were numerous in the circular muscle layer and around the submucosal blood vessels. In the submucosal and myenteric plexuses, some HCNP-like-immunopositive nerve cell bodies and nerve fibers were present. The reaction product was deposited on the membranes of various subcellular organelles, including the rough endoplasmic reticulum, Golgi saccules, ovoid electron-lucent synaptic vesicles in axon terminals associated with submucosal and myenteric plexuses, and the outer membranes of a few mitochondria. The synaptic vesicles of HCNP-like positive terminals were 60-85 nm in diameter. The present data provide immunocytochemical evidence that HCNP-like-positive nerve cell bodies and nerve fibers are present in the submucosal and myenteric plexuses of the rat small intestine. An immunohistochemical light microscopic study using mirror-image sections revealed that in both the submucosal and myenteric ganglia, almost all choline acetyltransferase (ChAT)-immunoreactive neurons were also immunoreactive for HCNP. These observations suggest (i) that HCNP proper and/or HCNP precursor protein is a membrane-associated protein with a widespread subcellular distribution, (ii) that HCNP precursor protein may be biosynthesized within neurons localized in the rat enteric nervous system, and (iii) that HCNP proper and/or HCNP precursor protein are probably stored in axon terminals.

Animals↗
PubMed2000

In vivo treatment of mutant FLT3-transformed murine leukemia with a tyrosine kinase inhibitor.

Somatic mutation of the FLT3 gene, in which the juxtamembrane domain has an internal tandem duplication, is found in 20% of human acute myeloid leukemias and causes constitutive tyrosine phosphorylation of the products. In this study, we observed that the transfection of mutant FLT3 gene into an IL3-dependent murine cell line, 32D, abrogated the IL3-dependency. Subcutaneous injection of the transformed 32D cells caused leukemia in addition to subcutaneous tumors in C3H/HeJ mice. To develop a FLT3-targeted therapy, we examined tyrosine kinase inhibitors for in vitro growth suppression of the transformed 32D cells. A tyrosine kinase inhibitor, herbimycin A, remarkably inhibited the growth of the transformed 32D cells at 0.1 microM, at which concentration it was ineffective in parental 32D cells. Herbimycin A suppressed the constitutive tyrosine phosphorylation of the mutant FLT3 but not the phosphorylation of the ligand-stimulated wild-type FLT3. In mice transplanted with the transformed 32D cells, the administration of herbimycin A prolonged the latency of disease or completely prevented leukemia, depending on the number of cells inoculated and schedule of drug administration. These results suggest that mutant FLT3 is a promising target for tyrosine kinase inhibitors in the treatment of leukemia.

Animals↗
PubMed2000

MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies.

MUM1/IRF4 is a myeloma-associated oncogene transcriptionally activated as a result of t(6;14)(p25,q32) chromosomal translocation and by virtue of its juxtaposition to the immunoglobulin heavy chain gene (IgH) locus. When this oncogene becomes non-functional, no activated B/T lymphocytes and Ig secreting plasma cells are observed, suggesting that MUM1/IRF4 is crucial for lymphoid development. Its expression was analyzed in both reactive lymphoid and lymphoma tissues by means of an immunohistochemical technique using specific goat antiserum against MUM1/IRF4. This analysis detected a 50 kDa MUM1 product whose localization was restricted to the nuclei of the lymphocytes. The MUM1+ cells in reactive lymph nodes were found to consist of plasma cells and a small fraction (approximately 7.9%) of B cells harboring CD20+CD38+, which were located in the light zone of the germinal center. MUM1 expression in peripheral blood B/T lymphocytes was upregulated by mitogenic stimuli, suggesting that MUM1 positivity represents the activated state of the B/T cells. In B cell non-Hodgkin's lymphoma (NHL), MUM1 expression was observed in 73.2% (30/41) of diffuse large B cell lymphoma (DLBCL), 20% (1/5) of marginal zone lymphoma (MZL) and 43% (3/7) of small lymphocytic lymphoma (SLL) cases, whereas it was not seen in any cases of mantle cell lymphoma (MCL) or follicle center lymphoma (FCL). Also, MUM1 was stained at high intensity in various types of T cell lymphomas including adult T cell leukemia/lymphoma (ATL/L) and anaplastic large cell lymphoma (ALCL) and in the majority of Hodgkin's diseases. Our results suggest that a major proportion of lymphomas comprise either physiologically or aberrantly activated neoplastic lymphocytes expressing the MUM1 protein.

B-Lymphocytes↗
PubMed2000

Quantitative expression of erythropoietin receptor (EPO-R) on acute leukaemia cells: relationships between the amount of EPO-R and CD phenotypes, in vitro proliferative response, the amount of other cytokine receptors and clinical prognosis. Japan Adult Leukaemia Study Group.

Expression of erythropoietin (EPO) receptor (EPO-R) was analysed in leukaemia cells from 150 patients with acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL). EPO-R was expressed in 81 (60%) out of 136 AML, and in vitro treatment with EPO led to proliferation of leukaemia cells in 13 (16%) out of 81 AML examined. EPO-R expression and in vitro response to EPO were observed in all subtypes of AML according to the French-American-British (FAB) classification. All eight patients with FAB-M6 expressed EPO-R, and one out of four showed an in vitro response to EPO. Although there was no significant correlation (r = 0.2522) between the amount of EPO-R and the in vitro response to EPO, all of the AML patients who showed in vitro response expressed EPO-R. Stem cell factor significantly enhanced both EPO-R expression and in vitro response to EPO. Interleukin-3 tended to increase in vitro response to EPO. CD phenotypes, the amount of granulocyte colony-stimulating factor (G-CSF) receptors and the amount of TPO receptors had no significant relationship with the amount of EPO-R. Patients with both EPO-R expression and in vitro response to EPO had shorter duration of complete remission than those without EPO-R (P = 0.0053). EPO-R was expressed in four (29%) out of 14 ALL, and none out of five ALL showed in vitro response to EPO.

Acute Disease↗
PubMed2000

In vitro hyperprocessing of Drosophila tRNAs by the catalytic RNA of RNase P the cloverleaf structure of tRNA is not always stable?

We have previously reported that the catalytic RNA subunit of RNase P of Escherichia coli (M1 RNA) cleaves Drosophila initiator methionine tRNA (tRNA(Met)i) within the mature tRNA sequence to produce specific fragments. This cleavage was dependent on the occurrence of an altered conformation of the tRNA substrate. We call this further cleavage hyperprocessing. In the present paper, to search for another tRNA that can be hyperprocessed in vitro, we used total mature tRNAs from Drosophila as substrates for the in vitro M1 RNA reaction. We found that some tRNAs can be hyperprocessed by M1 RNA and that two such tRNAs are an alanine tRNA and a histidine tRNA. Using mutant substrates of these tRNAs, we also show that the hyperprocessing by M1 RNA is dependent on the occurrence of altered conformations of these tRNAs. The altered conformations were very similar to that of tRNA(Met)i. We show here that M1 RNA can be used as a powerful tool to detect the alternative conformation of tRNAs. The relationship between these hyperprocessing reactions and stability of the tRNA structure will also be discussed.

Alanine↗
PubMed2000

Genetic instability and aberrant DNA methylation in chronic hepatitis and cirrhosis--A comprehensive study of loss of heterozygosity and microsatellite instability at 39 loci and DNA hypermethylation on 8 CpG islands in microdissected specimens from patients with hepatocellular carcinoma.

A study was conducted to examine the significance of genetic instability and aberrant DNA methylation during hepatocarcinogenesis. Genomic DNA was extracted from 196 microdissected specimens of noncancerous liver tissue that showed no marked histologic findings or findings compatible with chronic hepatitis or cirrhosis, and 80 corresponding microdissected specimens of hepatocellular carcinoma (HCC) from 40 patients. Loss of heterozygosity (LOH) and microsatellite instability (MSI) were examined by polymerase chain reaction (PCR) using 39 microsatellite markers, and DNA methylation status on 8 CpG islands was examined by bisulfite-PCR. In noncancerous liver tissues, LOH, MSI, and DNA hypermethylation were found in 15 (38%), 6 (15%), and 33 (83%) of 40 cases, respectively. The incidence of DNA hypermethylation in histologically normal liver was similar to that in chronic hepatitis and cirrhosis, although neither LOH nor MSI was found in histologically normal liver. In cancerous tissues, LOH, MSI, and DNA hypermethylation were found in 39 (98%), 8 (20%), and 40 (100%) of 40 cases, respectively. CpG islands of the p16 gene and methylated in tumor 1, 2, 12, and 31 clones were frequently methylated in cancerous tissues, although neither the thrombospondin-1 nor the human Mut L homologue (hMLH1) gene was methylated. Absence of silencing of the hMLH1 gene by DNA hypermethylation is consistent with the low incidence of MSI in HCCs. The results of this study indicate that LOH and aberrant DNA methylation contribute to hepatocarcinogenesis; DNA hypermethylation in particular, which precedes or may even cause LOH, is as an early event during hepatocarcinogenesis.

Adult↗
PubMed2000

Lack of association with interleukin 1 receptor antagonist and interleukin-1beta gene polymorphisms in sarcoidosis patients.

Interleukin-1beta (IL-1beta) and its endogenous antagonist, the interleukin-1 receptor antagonist (IL-1ra), play important roles in immune responses. In sarcoidosis, IL-1beta is reported to be increased whereas IL-1ra is decreased. It has recently been shown that polymorphisms in the IL-1ra and IL-1beta genes may account for variation in the two proteins. These polymorphisms are also reported to be associated with several autoimmune diseases. Since this might be expected to affect sarcoidosis, an investigation of 108 sarcoidosis patients and 113 healthy control subjects was performed. The IL-1ra genotype was determined using the polymerase chain reaction (PCR), and the IL-1beta genotype by PCR restriction fragment length polymorphism. We found no significant differences in IL-ra and IL-1beta genotypes between sarcoidosis patients and healthy controls. Furthermore, there was no association between the IL-1beta genotype and the roentgenographic stage, disappearance of chest X-ray shadows or organ involvement. In conclusion, there is no bias in the IL-1ra and IL-1beta genotype in Japanese sarcoidosis patients.

Female↗
PubMed2000

Long-term effect of antihypertensive therapy with calcium antagonist or angiotensin converting enzyme inhibitor on serum nitrite/nitrate levels in human essential hypertension.

Endothelial function is impaired in hypertension. In the present study the effects of long-term antihypertensive therapy on endothelial production of nitric oxide (NO) were investigated. Fifteen untreated mild to moderate essential hypertensive patients and 13 normotensive subjects were enrolled in this study. Blood pressure, heart rate, lipid profiles, cyclic guanosine 3', 5'-monophosphate (cGMP) and nitrite/nitrate (NOx), which are stable metabolites of NO, were measured. The hypertensive patients were treated with a calcium antagonist, benidipine (CAS 91559-74-5) (Ca group: n = 8) or an angiotensin converting enzyme inhibitor, trandolapril (CAS 87679-37-6) (ACEI group: n = 7) and 12 weeks after the treatment the same examinations were performed. NOx and cGMP levels in hypertensive patients were significantly lower than those in normotensive subjects (32.3 +/- 4.1 versus 49.0 +/- 6.5 mumol/l and 2.16 +/- 0.39 versus 3.39 +/- 0.42 pmol/ml, respectively). Both antihypertensive agents decreased the elevated blood pressure (mean blood pressure; 120 +/- 3 to 99 +/- 3 mmHg in Ca group and 117 +/- 4 to 104 +/- 4 mmHg in ACEI group) and normalized the decreased NOx and cGMP levels (29.1 +/- 6.2 to 46.2 +/- 8.6 mumol/l and 1.96 +/- 0.37 to 3.20 +/- 0.71 pmol/ml in Ca group, 36.0 +/- 5.3 to 54.7 +/- 6.9 mumol/l and 2.45 +/- 0.52 to 2.87 +/- 0.43 pmol/ml in ACEI group, respectively). Either benidipine or trandolapril improves the endothelial function and increases the impaired basal release of NO in hypertension. This suggests the beneficial effects of the drugs on protection against the vascular complications in hypertension.

Adult↗
PubMed2000

Lack of association between TTV viral load and aminotransferase levels in patients with hepatitis C or non-B-C.

TT virus (TTV) is a newly identified un-enveloped single-stranded DNA virus. Although TTV was initially thought to be a new hepatitis virus, it is still unclear whether it causes hepatitis. To clarify the natural history and pathogenesis of TTV infection, serial serum samples from patients with chronic hepatitis were analysed. TTV DNA was quantified by real-time detection polymerase chain reaction assay (RTD-PCR), which was adapted for TTV. Five patients with chronic hepatitis, 4 with hepatitis C and 1 with non-B-C, were studied. The study period ranged from 9 to 50 months. In 3 patients there were frequent increases in TTV DNA titres, but no concomitant elevation of the aminotransferase (ALT) levels. In 2 patients who were treated with interferon, the changes in TTV titres were not synchronized with those of the ALT levels. Thus, in cases of chronic hepatitis, no correlation was observed between the serum TTV DNA titres and the ALT levels.

Adult↗
PubMed2000

Apoptotic cytotoxic effects of a histone deacetylase inhibitor, FK228, on malignant lymphoid cells.

Histone deacetylases are promising targets for cancer treatment. Here we studied the in vitro effects of a potent histone deacetylase inhibitor, FK228 (formerly FR901228), on human leukemia / lymphoma cells and cell lines compared with normal hematopoietic cells. In a lymphoma cell line, Raji, a nanomolar concentration of FK228 induced G1 arrest and / or apoptotic cell death, depending on the concentration and exposure time. Growth of lymphoid cell lines including Raji (N = 13) was inhibited by 50% (IC(50)) after 2-day treatment at concentrations of 0.83 to 1.87 ng / ml. Viability of clinical samples from patients with acute lymphoblastic leukemia was decreased by 50% at 0.78 +/- 0.46 ng / ml, whereas the IC(50) values for normal mononuclear cells from peripheral blood and bone marrow were 2.3 +/- 0.96 and 7.8 +/- 1.0 ng / ml, respectively. The IC(50) values for normal progenitor cells were 3.1, 4.4 and 7.8 ng / ml for BFU-E, CFU-GM and CFU-Mix, respectively. Expression levels of HDAC-1 and HDAC-3 proteins, which varied among cell lines, but were stable during the treatment with FK228, did not correlate with the sensitivity to FK288. This novel agent might be useful in the treatment of lymphoid malignancies, because the above concentrations are clinically achievable in vivo according to a recent clinical study.

Anti-Bacterial Agents↗
PubMed2000

Development of a TT virus DNA quantification system using real-time detection PCR.

Although TT virus (TTV) was isolated from a cryptogenic posttransfusion hepatitis patient, its pathogenic role remains unclear. It has been reported that the majority of the healthy population is infected with TTV. To elucidate the differences between TTV infection in patients with liver diseases and TTV infection in the healthy population, a quantification system was developed. TTV DNA was quantified by a real-time detection PCR (RTD-PCR) assay on an ABI Prism 7700 sequence detector. With this system, TTV DNA was quantified in 78 hepatitis C virus (HCV)-infected patients (63 with elevated serum alanine aminotransferase [ALT] levels and 15 with normal ALT levels) and in 70 voluntary blood donors (BDs). The quantification range was 2.08 to 7.35 log copies/ml. The intra-assay and interassay coefficients of variation were 0.37 to 6.33% and 0.60 to 7.07%, respectively. The mean serum TTV DNA levels in the HCV-infected patients with both elevated and normal ALT levels and BDs were 3.69 +/- 0.89, 3.45 +/- 0.76, and 3.45 +/- 0.67 log copies/ml, respectively. Comparison of the serum TTV DNA levels among the HCV-infected patients revealed that they were not related to the serum ALT and HCV core protein levels or to the histopathological score on liver biopsy. This study showed that (i) the RTD-PCR assay for the detection of TTV was accurate and had a high degree of sensitivity, (ii) the mean serum TTV DNA level was similar among HCV-infected patients, irrespective of their ALT level, and also among BDs, and (iii) a high serum TTV DNA level does not affect the serum ALT and HCV levels or liver damage in HCV-infected patients.

Blood Donors↗
PubMed2000

Human herpesvirus 8 is not associated with sarcoidosis in Japanese patients.

STUDY OBJECTIVES: The etiology of sarcoidosis remains unknown, but recently it was reported that human herpesvirus 8 (HHV-8) may be detected in sarcoid tissue in a high proportion of patients. This study was performed to determine whether HHV-8 is implicated in sarcoidosis in Japan. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from 100 patients with sarcoidosis and 100 healthy donors living in central Japan. Additionally, 19 samples of sarcoid tissue, 10 of tuberculous tissue, and 10 of lung cancers were examined. DNA was extracted from PBMC or tissue samples, and a hemi-nested polymerase chain reaction assay was performed for HHV-8 detection. RESULTS: In the PBMC study, the detection rates for HHV-8 in patients with sarcoidosis and in normal donors were 2% and 1%, respectively, the difference not being significant (p>0.99). In the tissue study, HHV-8 was detected in 10.5% of sarcoid and in 15% of nonsarcoid tissues, again not a significant difference (p>0.99). CONCLUSIONS: From these results, we conclude that HHV-8 is not implicated in sarcoidosis in Japanese patients.

Antibodies, Viral↗
PubMed2000

Lack of integrated TT virus (TTV) genomes in cellular DNA in infected human hematopoietic cells.

TT virus (TTV) isolated from the serum of a patient with posttransfusion hepatitis has been characterized as a member of the Circoviridae, a family of small DNA viruses with single-stranded circular genomes. TTV appeared to infect not only the serum and liver, but also the peripheral blood mononuclear cells (PBMC). We investigated the prevalence of TTV DNA in human hematopoietic cells, based on 84 mononuclear cell samples obtained from the bone marrow or lymph nodes of patients with hematopoietic malignancies including leukemia, malignant lymphoma and aplastic anemia. Forty-nine (58.3%) out of the 84 samples were positive for TTV DNA with polymerase chain reaction analysis, which was almost similar to the frequency found in the patients' serum. Southern blot analyses using a 3.2-kb fragment derived from the TTV DNA, however, showed no evidence supporting the fact that the TTV genomes are integrated into the human hematopoietic cell genomes, thus suggesting their existence as episomal forms.

Blotting, Southern↗
PubMed2000

[Chemotherapy based on EBM in the field of hematological malignancies].

In the field of hematology/oncology, there are reasonable number of chemotherapy-related reports with level 1 evidences based on the analysis of the evidence based medicine (EBM). Following reasons may be pointed out; the first is that the history of chemotherapy has been initiated in the field of in hematology/oncology so it has more than 50 years' experience. The second is that leukemia and lymphoma are very chemosensitive diseases to compare with solid tumor, so the ultimate goal of their therapy is increase of the cure rate. The third is hematologists with high specialty only can manage such serious patients. Thus they have proposed plenty well-designed and well-organized clinical protocols and have performed some of them in this field. We have learned several recommended therapy of some hematological malignancies with level 1 evidences. It is not so easy, however, to treat all patients according to the best recommended therapy for Japanese patients, because of some limitations of using Japanese health insurance. This is very crucial problem for the patients. We should settle the issue from the scientific and social aspects as soon as possible.

Clinical Trials as Topic↗
PubMed2000

Therapy-related leukemia and myelodysplastic syndrome: a large-scale Japanese study of clinical and cytogenetic features as well as prognostic factors.

It is known that alkylating agents and topoisomerase II inhibitors can cause distinct forms of therapy-related leukemia and myelodysplastic syndrome (TRL/MDS). Although several reports have been made on each of these agents separately, no study has yet been conducted to evaluate the effect of these two types of agents in the same population. In a nationwide, large-scale population study, the clinical and cytogenetic features as well as the prognostic factors in 256 patients with TRL/MDS were assessed. Median age was 61 years, and the median period of latency from primary malignancies was 47.9 months. The latency period was significantly shorter in patients undergoing chemotherapy, especially that of topoisomerase II inhibitors, for primary cancer. The morphological diagnosis of TRL/MDS was acute myeloid leukemia in 59% and MDS in 41% of patients. Chromosome abnormalities that frequently involved chromosomes 5, 7 or 11 were documented in 77% of the 189 patients examined. MLL gene rearrangements were detected in 11 of 58 subjects and were correlated with a borderline significance (P = 0.072) with topoisomerase II inhibitor administration. Overall median survival was only 9.7 months. Survival was similar in cases with or without MLL gene rearrangement. Multivariate analysis identified chromosome 5 abnormalities, hypoproteinemia, poor therapy outcomes for primary cancer, C-reactive protein, and thrombocytopenia as being significantly poor prognostic factors (P < 0.05). This large-population study provided a comprehensive update of TRL/MDS status in Japan, identified significant prognostic factors, and enabled the clinical significance of MLL gene rearrangement to be assessed.

Adult↗