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Biomedical subjects

T Ueda

Publications and source records attributed to T Ueda.

At least 973 records · Page 54Linked to original sources
PubMed1991

Antitumor activity of 2'-deoxy-2'-methylidenecytidine, a new 2'-deoxycytidine derivative.

The antitumor activity of 2'-deoxy-2'-methylidenecytidine (DMDC), an inhibitor of DNA synthesis, was examined and compared with that of 1-beta-D-arabinofuranosylcytosine (ara-C) against various murine tumors and human tumor xenografts. Against P388 murine leukemia, repeated treatments of DMDC were more effective than its single administration. Interestingly, DMDC was effective against colon 26 murine carcinoma, M5076 murine reticulum cell sarcoma, LX-1 human lung cancer xenograft, and SK-Mel-28 human melanoma xenograft, which are less sensitive or refractory to ara-C, while DMDC was not more potent against murine leukemias P388 and L1210 than ara-C. The in vitro cytotoxic effects of DMDC and ara-C against L1210 leukemia cells were prevented dose dependently by deoxycytidine, suggesting that DMDC, like ara-C, may require phosphorylation by deoxycytidine kinase for antitumor activity. DMDC was effective against human and murine experimental tumor models, especially nonleukemic tumors refractory to ara-C, suggesting that DMDC will be a promising agent for the treatment of cancer.

Animals↗
PubMed1991

Phosphorothioate-containing RNAs show mRNA activity in the prokaryotic translation systems in vitro.

Phosphorothioate-containing RNAs were generated by transcription of coliphage T7 DNA using the Sp diastereomers of ribonucleoside 5'-O-(1-thiotriphosphates) and T7 RNA polymerase. RNAs in which a single nucleotide was substituted by the corresponding nucleoside phosphorothioate functioned as mRNA in the cell-free translation systems prepared from Escherichia coli and from an extreme thermophilic bacterium, Thermus thermophilus. This substitution increased the efficiency of protein synthesis by stabilizing the mRNAs in these systems. As the proportion of substituted nucleotides was increased, their mRNA activity was decreased accordingly. As judged from the analysis by SDS-polyacrylamide gel-electrophoresis, the proteins synthesized using phosphorothioate-containing mRNAs as template were identical to those obtained with unsubstituted mRNAs. However, larger proteins which were barely detectable when unsubstituted mRNA was used were well represented when phosphorothioate-RNA was used instead. The advantages in using the phosphorothioate-mRNAs in the in vitro translation systems are discussed.

Cell-Free System↗
PubMed1991

Purification and characterization from rat liver cytosol of a GDP dissociation inhibitor (GDI) for liver 24K G, a ras p21-like GTP-binding protein, with properties similar to those of smg p25A GDI.

A regulatory protein for a liver GTP-binding protein (G protein) with a molecular weight value of 24,000 (24K G), which we have recently purified, was purified to near-homogeneity from rat liver cytosol and characterized. This regulatory protein, designated here as GDP dissociation inhibitor for 24K G (24K G GDI), inhibited the dissociation of GDP from and the subsequent binding of GTP to 24K G. 24K G GDI was inactive for other ras p21/ras p21-like small G proteins including c-Ha-ras p21, rhoB p20, smg p21B, and smg p25A. 24K G was, however, recognized by bovine brain smg p25A GDI which regulated the GDP/GTP exchange reaction of smg p25A. By analyses of sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE), immunoblotting with anti-smg p25A GDI antibody, two-dimensional PAGE, and C4 column chromatography, 24K G GDI showed physical properties very similar to those of smg p25A GDI. The peptide map and the partial amino acid sequences of 24K G GDI were not identical with those of smg p25A GDI. Among the 83 residues, 2 amino acids were different between rat liver 24K G GDI and bovine brain smg p25A GDI. These results indicate that there is a specific regulatory protein for 24K G, 24K G GDI, in rat liver cytosol and that 24K G GDI has close similarity to smg p25A GDI.

Amino Acid Sequence↗
PubMed1991

Calcium-dependent release of accumulated glutamate from synaptic vesicles within permeabilized nerve terminals.

We have studied glutamate release from synaptic vesicles in permeabilized synaptosomes, which were preloaded with [3H]glutamate in an ATP-dependent manner. The release was found to be calcium-dependent and to require a heat-labile cytosolic macromolecule factor for maximum activity. Maximal release occurred at 5 microM free Ca2+ and within 5 min. Of the other divalent cations tested, only barium stimulated release of vesicular glutamate. The release was inhibited by N-ethylmaleimide. These results are characteristic of exocytotic release of monoamines and peptides observed in endocrine systems, and constitute direct evidence for the notion that calcium-dependent release of glutamate originates from the vesicular pool.

Adenosine Triphosphate↗
PubMed1991

Replication of a geminivirus derived shuttle vector in maize endosperm cells.

A maize (Zea mays L.) endosperm cell culture has been shown to efficiently replicate DNA sequences derived from wheat dwarf virus (WDV), a monopartite monocot geminivirus. To analyze sequences necessary for viral replication and to verify their application for a plant gene expression vector, we have developed a 3.7 kilobase pairs Escherichia coli--plant cell shuttle vector, pWI-11. The p15A origin of replication, functional in E. coli, was introduced into the viral sequences. We have replaced the coding region of the coat protein gene by that of bacterial neomycin phosphotransferase II (NPT II) gene. The resulting NPT II gene fusion can serve as a selectable marker in both plant and E. coli systems. Into a unique cloning site in this pWI-11 vector, we introduced a gene fusion carrying the bacterial beta-glucuronidase (GUS) coding region under control of the cauliflower mosaic virus 35S (CaMV35S) gene promoter and terminator. By transferring these viral sequences into protoplasts derived from maize endosperm cell cultures, we have demonstrated that the plasmid pWI-11 can replicate in maize endosperm cells, that the GUS reporter gene introduced into pWI-11 can be expressed at high level in the transformed cells, and that the replicating viral DNA can be rescued from endosperm cells by transforming E. coli in the presence of kanamycin. The level of GUS gene expression increased progressively in transformed endosperm cells during a prolonged culture period, coinciding with replication of the viral sequences in these cells.

Blotting, Southern↗
PubMed1991

Atypical lymphocytes with a multilobated nucleus from a patient with tsutsugamushi disease (scrub typhus) in Japan.

A case of tsutsugamushi disease (scrub typhus) with atypical lymphocytes with a multilobated nucleus is reported. Although this type of atypical lymphocyte has been reported in patients with viral infections such as adult T-cell leukemia, infectious mononucleosis, human immunodeficiency virus (HIV) infection, this is the first reported case of atypical lymphocyte with a multilobated nucleus in a patient with rickettsial infection. This type of atypical lymphocyte seems to exist in a broad spectrum of infectious diseases.

Cell Nucleus↗
PubMed1991

Validity of heart rate and ratings of perceived exertion as indices of exercise intensity in a group of children while swimming.

The purpose of this study was to investigate the validity of heart rate (fc) and ratings of perceived exertion (RPE) as indices of exercise intensity in a group of children while swimming. Six healthy male swimmers, aged 10-12, swam tethered using the breast-stroke in a flume. The resistance started at 1.0 kg and increased in 1.0 kg steps up to the point of their exhaustion. The subjects swam for 5 min during each period, with a rest of 10-20 min until they had returned to their resting fc level. The last exercise intensity was with the maximal mass the subjects could support for 2 min. The last min of oxygen consumption (VO2) and 30 s of fc were measured during each exercise period. The subjects gave their RPE assessment at the end of exercise. The individual relationships between fc and VO2, and percentage maximal oxygen consumption (%VO2max) were linear with a high correlation r = 0.962-0.996 and r = 0.962-0.996, respectively. Therefore, it was concluded that fc was valid as an index of the exercise intensity of children while swimming. Compared to the results found in adults using a similar protocol, the children's fc were 8.3-26.9 beats.min-1 higher than those of the adults at the given %VO2max. The present study showed two different patterns in the relationship between VO2 and RPE in individuals. In two subjects the RPE increased linearly with VO2 while in the other four subjects the increase was discontinuous. If fc and RPE were to be applied to the setting and evaluation of exercise intensity during swimming, it would seem that fc would be a more useful guide than RPE for some children.

Body Height↗
PubMed1991

Adenylate cyclase induces intracellular Ca2+ increase in single human epidermal keratinocytes of the epidermal sheet as measured by digital imaging microscopy using Fura 2-AM.

Intracellular Ca2+ ([Ca2+]i) is thought to act as a second messenger of transmembrane signalling systems. However, no measurement of [Ca2+]i has been made in intact epidermal keratinocytes. We have developed a method for measuring [Ca2+]i in human keratinocytes from pure epidermal sheet by the application of digital imaging fluorescence microscopy with the use of Fura 2-AM. Normal human pure epidermal sheets were obtained by dispase treatment. Epinephrine and salbutamol induced transient [Ca2+]i increases. Propranolol, a beta-antagonist, inhibited this response, while prazosin and yohimbine (alpha 1- and alpha 2-antagonists, respectively) did not affect the response. Histamine and adenosine, also receptor agonists of the epidermal adenylate cyclase system, induced a similar [Ca2+]i increase, as did forskolin, a direct activator of adenylate cyclase. These data coincide with those previously presented for cultured human epidermal keratinocytes, and reveal that adenylate cyclase activation induces an increase of [Ca2+]i in intact epidermal cells. This technique enables the kinetics of [Ca2+]i in various skin disorders to be investigated.

Adenosine↗
PubMed1991

Therapeutic efficacy of interferon on HCV-RNA in chronic hepatitis C.

The efficacy of interferon therapy for chronic hepatitis C were evaluated by the changes of serum RNA of the hepatitis C virus (HCV) by the polymerase chain reaction. Before the treatment, HCV-RNA was detected in all of the 17 patients. 5 patients given IFN for 4 weeks, 12 cases given IFN by the 2 weeks/on 2 weeks off schedule (4 cases given 4 cycles and 8 given 6 cycles). Immediately after the treatment ended, the HCV-RNA was not detected in 12 (71%) cases. Five cases were persistently positive for HCV-RNA and showed continuously abnormal level of ALT. In 7 of 12 cases who became negative for HCV-RNA just after the treatment ended, HCV-RNA was detected again at first and 12th month after therapy. The ALT level were continuously abnormal in 4 of these 7 cases during and after the treatment, and became normal transiently in the other 3. In the 5 cases who became persistently negative (at least 1 year), ALT level decreased to normal or near-normal during follow up for more than one year. According to our results, we classified the therapeutic efficacy of IFN therapy for chronic hepatitis C. Type I response is complete response. In this type, HCV-RNA became negative persistently and ALT became normal or near-normal for at least 12 months after therapy. Type II is partial response. In this type, HCV-RNA became negative transiently and ALT level was transiently normal or poor. Type III is ineffective. In this type, HCV-RNA did not become negative and the effect for ALT was poor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Hypereosinophilic syndrome appearing as a focal defect on liver scan.

The case reported here is of a 34-year-old man diagnosed as having hypereosinophilic syndrome. Blood tests showed a large increase in the number of eosinophils and a slight increase in aspartate aminotransferase and alkaline phosphatase. In scintigraphy of the liver with Tc-99m-phytate and with Ga-67-citrate, a focal defect was found in the outer part of the right lobe of the liver. Abdominal computed tomography showed a low density lesion in the same area. Histological inspection of the biopsy specimen showed heavy periportal infiltration with eosinophils. The results suggested that the focal defect seen in liver scintigraphy arose from a circulatory disturbance arising from infiltration by eosinophils.

Adult↗
PubMed1991

2-Chlorodeoxyadenosine inhibits the repair of DNA double-strand breaks and does not inhibit the repair of DNA single-strand breaks in X-irradiated Chinese hamster V79 cells.

The exposure of log-phase Chinese hamster V79 cells to 2-chlorodeoxyadenosine (CdA) for 3 h after X irradiation enhanced the lethal effects of X-rays in a concentration-dependent manner. The enhancement of the killing efficiency of X-rays by CdA was mainly observed in the reduction of quasi-threshold doses (Dq) of the dose-response curves. When the ability of CdA to inhibit the repair of X-ray-induced double- and single-strand breaks (dsb and ssb) of DNA was investigated by neutral- and alkaline-filter elution techniques, respectively, it was observed that 90% of dsb were rejoined in the absence of CdA within 30 min after X irradiation and 15-40% of dsb rejoining was suppressed by co-incubation of the cells with 5-10 microM of CdA for 3 h after X irradiation, whereas almost 100% of ssb were rejoined within 15 min regardless of the presence or absence of CdA. From these results it was concluded that CdA interfered exclusively with the repair of DNA dsb in X-irradiated Chinese hamster V79 cells and thereby increased the lethality of X-rays.

2-Chloroadenosine↗
PubMed1991

Prognostic factors and value of adjunctive nephrectomy in patients with stage IV renal cell carcinoma.

We reviewed 57 cases of Stage IV renal cell carcinoma to clarify the factors influencing prognosis and to evaluate the value of nephrectomy. Cumulative survival from the initial diagnosis was analyzed with respect to the patients' age, sex, side of primary tumor, initial performance status (PS), site of metastasis, and nephrectomy. Overall survival for the patients was 51 percent at one year, 22 percent at three years, and 11 percent at five years. Age, sex, and side of primary tumor had no influence on survival. Improved survival was correlated with good PS, metastases limited to single organ, and removal of the primary tumor. With regard to histopathologic features in nephrectomized patients, low grade and stage were correlated with longer survival. These factors should be considered in the analysis of results of future clinical trials of metastatic renal cell carcinoma.

Aged↗
PubMed1991

Pharmacological studies of retinol palmitate and its clinical effect in patients with acute non-lymphocytic leukemia.

The pharmacokinetics of retinol palmitate were studied, and a therapeutic trial was performed in patients with ANLL. In the pharmacokinetics study, retinol was the only metabolite that was detected in plasma, and the peak concentration was 332 micrograms/dl (about 1.2 x 10(-5) M) 2.1 h after administration of retinol palmitate. Five patients with ANLL (4 with ANLL-M3 and one with ANLL-M2) were treated with retinol palmitate. In all patients with ANLL-M3, bone marrow suspension culture studies revealed that retinol induced both morphological and functional differentiation of immature leukemic cells. During the course of the treatment with retinol palmitate, morphological differentiation of bone marrow immature leukemic cells was observed in all patients with ANLL-M3 within 3-4 days after initiation of the therapy. In three of the four patients who underwent conventional chemotherapy, the sequential treatment with retinol palmitate resulted in a complete remission: controlling residual bone marrow leukemic cells. None of the patients showed any signs of aggravation of DIC in the coagulation parameters. These findings suggest the possibility that retinol palmitate functions as salvage therapy by inducing maturation and slowing proliferation, there by clearing out the residual leukemic cells following conventional chemotherapy.

Adult↗
PubMed1991

Dephosphorylation of specific proteins in HL-60 cells by 1 alpha, 25-dihydroxyvitamin D3: possible involvement of cAMP-dependent protein kinase.

Changes of phosphoprotein patterns in HL-60 cells were studied during short exposures to 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3]. One hundred nanometers 1,25(OH)2D3 dephosphorylated at least three proteins in 6 h: phosphoproteins with molecular weights of 82 kD (pp82), 33 kD (pp33), and 31 kD (pp31). Phosphorylation of pp33 and pp31 was also suppressed by 1 mM dbcAMP, and dephosphorylation of the two protein by 1,25(OH)2D3 was inhibited by 8 microM H-8, an inhibitor of cAMP-dependent protein kinase (PKA). Furthermore, 8 microM H-8 inhibited dephosphorylation of the two proteins when it was added with 1,25(OH)2D3. On the other hand, 10 nM TPA gave no significant change to these two phosphoproteins. These results suggest the possibility that PKA is involved in the early stages of 1,25(OH)2D3-induced HL-60 cell differentiation through specific protein dephosphorylation.

Bucladesine↗