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J Uchida

Publications and source records attributed to J Uchida.

At least 73 records · Page 4Linked to original sources
PubMed1992

[Significance of measuring 5-fluorouracil incorporated into RNA of tumor tissue as a parameter for the antitumor activity of 5-fluorouracil and its analogs].

A sensitive method for determination of incorporation of non-radiolabeled 5-fluorouracil (FUra) into RNA (F-RNA) of tumor tissue samples was established and was shown to be applicable to clinical materials. RNA fractions containing incorporated FUra were extracted from perchloric acid precipitates of tissue sonicates by KOH hydrolysis. FUra in RNA fractions was released by HCl hydrolysis at 100 degrees C and its levels were determined by GC-MS. The sensitivity of this method was 100 fold higher than that of HPLC method. F-RNA levels were dose dependent and correlated well with antitumor efficacy of the drugs. F-RNA levels in FUra resistant murine tumors were significantly lower than that in parent tumors despite of the lack of difference in FUra concentrations in tumor tissue. Based on these results, it is suggested that measurement of F-RNA levels together with the determination of FUra concentration and the inhibition rate of thymidylate synthase should be considered as a good parameters of the evaluation of antitumor efficacy of FUra and its analogs both in experimental and clinical settings.

Administration, Oral↗
PubMed1992

[Effect of exercise on rats with renal injury].

Effect of exercise on rats with renal injury was studied. Nephritis was induced in rats by injection of anti-GBM antibody followed by ligation of a branch of the left renal artery after nephrectomy of the right kidney. Moderate daily treadmill exercise was forced on these experimental rats for ten weeks. Sedentary nephritic rats that received the same treatment described above served as controls. The sedentary nephritic rats suffered progressively increasing proteinuria during the time course of the experiment, whereas the nephritic rats with daily treadmill exercise experienced less proteinuria. Mild proteinuria was induced by daily treadmill exercise forced on non-nephritic rats that had received only nephrectomy of the right kidney, but no NTS injection. Light microscopy and immunofluorescence microscopy revealed severe glomerular injury in the sedentary nephritic rats, however, less glomerular injury was seen in nephritic rats with treadmill exercise. Serum cholesterol level was higher in the sedentary rats than in the rats with daily treadmill exercise. The results suggest that daily exercise by nephritic rats will not aggravate renal injury.

Animals↗
PubMed1991

Antitumor activity of FTC-092, a masked 5-trifluoromethyl-2'-deoxyuridine derivative.

1-(3-O-Benzyl-2-deoxy-beta-D-ribofuranosyl)-5-trifluoromethyl-2,4(1H,3)- pyrimidinedione (FTC-092), a fluorinated pyrimidine derivative, appeared to be effective against various transplantable tumors in mice following oral administration, and its activity was superior to that of several other antitumor fluorinated pyrimidines. The ED50 value for FTC-092 the dose effective in achieving 50% inhibition of tumor growth against the solid form of sarcoma 180 was 13.3 mg/kg daily, whereas those for 5-trifluoromethyl-2'-deoxyuridine (CF3dUrd), the parent compound of FTC-092, for 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur, FT), the prodrug of 5-fluorouracil (FUra), and for FUra were 64.1, 122, and 28 mg/kg daily, respectively. The therapeutic indices (LD10/ED50) of FTC-092, CF3dUrd, FT, and FUra were 4.39, 1.7, 1.35, and 1.65, respectively. FTC-092 itself is not an active agent. After it has been absorbed from the gastrointestinal tract, FTC-092 undergoes a gradual biotransformation, mainly via the action of liver microsomes, releasing CF3dUrd over a long period. The levels of CF3dUrd in the stomach and small intestine of mice after the oral administration of FTC-092 were undetectable, whereas those following the administration of CF3dUrd at the same dose were high for a period of several hours. In contrast, the CF3dUrd level generated in plasma after the administration of FTC-092 remained at a high level for a longer period than did that observed on the administration of CF3dUrd. The low levels of CF3dUrd measured in stomach and small-intestine tissues and the maintenance of CF3dUrd in blood over long periods after the administration of FTC-092 are features that favor the possible clinical application of FTC-092.

Administration, Oral↗
PubMed1991

[Combination chemotherapy with orally administered UFT and leucovorin (LV)].

We evaluated the efficacy of the combination therapy of UFT with Leucovorin (LV) against mouse colon adenocarcinomas and human colon adenocarcinoma. In vitro studies, it was shown that LV potentiated the cytotoxicity of FUra against 7 out of 9 cell lines used in this experiment. In vivo studies, the antitumor activity of UFT against mice bearing colon 38 adenocarcinoma was increased following administration of LV either before, after or at the time of treatment with UFT. Further studies were performed on the combination effect of UFT and LV against mouse colon 26 adenocarcinoma and human colon adenocarcinoma KM20C. Consequently, the combined treatment of UFT with LV was more effective than UFT alone against two cell lines. Our studies suggest that combination chemotherapy of UFT with LV is a promising approach for the treatment of a human colon cancer in clinical practice.

Adenocarcinoma↗
PubMed1990

[Relationship between antitumor activity and the inhibition of thymidylate synthase after oral administration of UFT in nude mice bearing human tumor].

We studied the relationship between antitumor efficacy of UFT, which is a most widely used drug among fluorinated pyrimidines recently, and its effect on the content and the inhibition rate of thymidylate synthase (TS) in 15 human tumor xenografts derived from stomach, colon, breast and pancreatic cancer patients. There was a linear relationship between the content of TS and tumor mass doubling time (MDT). It may be shown that TS content reflects the growth rate of tumor cells. It should be stressed that tumor growth inhibition rate (TGIR), induced by UFT, correlated well with the inhibition of TS (TSI), particularly in the stomach and breast cancer. These results demonstrate that the measurement of inhibition rate of TS is important for the prediction and evaluation of clinical efficacy of UFT.

Administration, Oral↗
PubMed1989

Attachment of tumor cells to endothelial monolayers: detection of surface molecules involved in cell-cell binding.

Trypsinization of P815 mastocytoma cells interferes with their ability to bind to endothelial monolayers in vitro, suggesting the involvement of proteins in cell-cell binding. Binding is also dependent upon divalent cations. Incubation of tumor cells with tunicamycin, which blocks protein glycosylation, or the monosaccharide N-acetyl-D-glucosamine could also inhibit binding. In addition, antibodies prepared against whole P815 cells had the ability to interfere with tumor cell binding. The protein fragments released from P815 cells by trypsin interfered with the binding of fresh P815 cells to endothelium. Moreover, those fragments as well as CHAPS extracts of tumor cell membranes were able to neutralize the inhibitory effect of an anti-P815 antibody on tumor cell-endothelial cell binding. These observations, taken together, strongly suggest the presence of adhesion molecules on the tumor cell. The anti-P815 antibody preparation could also inhibit endothelial binding of an unrelated tumor. Ehrlich ascites (EA). In addition, membrane preparations of EA could neutralize the antibody's effect on intact P815, and membrane preparations of P815 could neutralize the antibody's effect on EA. These observations suggest that there are common epitopes on these tumor cells and raise the possibility that a variety of tumors may share common mechanisms for attachment to endothelium. This, in turn, raises the possibility that monospecific antibodies against such epitopes might be useful agents for interfering with metastasis in vivo.

Animals↗
PubMed1988

A hydrophobic protein, chargerin II, purified from rat liver mitochondria is encoded in the unidentified reading frame A6L of mitochondrial DNA.

Previous studies showed that a hydrophobic protein called chargerin II may have a key role in energy transduction of oxidative phosphorylation, since antibody against chargerin II labeled with monoazide ethidium inhibited ATP synthesis, ATP-Pi exchange, and reversed electron flow from succinate to NAD coupled with succinate oxidation by O2. In the present work, unlabeled chargerin II was purified from intact rat liver mitochondria by high performance liquid chromatography. The purified preparation of chargerin II, which was a single protein as judged by polyacrylamide gel electrophoresis and Western blotting, was digested with lysylendopeptidase. The digest was separated on a reverse-phase column into five peptides, which all cross-reacted with the antibody against chargerin II, indicating that they were fragments of chargerin II. The sequences of two of these peptides (a total of 12 amino acids) were determined and found to be highly homologous with the sequence of the carboxyl-terminal peptide of the putative polypeptide encoded by the unidentified reading frame A6L (URFA6L) of mammalian mitochondrial DNA. The amino acid compositions of the purified preparation of chargerin II were in good accord with those of the putative product of the URFA6L. Thus, we concluded that chargerin II is encoded by the URFA6L. This is the first demonstration that the URFA6L product was identified in rat liver mitochondria and purified from the membranes.

Amino Acid Sequence↗
PubMed1988

Electron microscopic study of microfold cells (M cells) in normal and inflamed human appendix.

Electron microscopic observation was made on microfold cells (M cells) in the covering epithelium of the lymphoid follicle (dome epithelium) of the intestine. Materials consisted of ten human appendices, five of those were inflamed and obtained from children with acute appendicitis. The remainder was not inflamed macroscopically, and there was one human Peyer's patch for control. The results indicate that in the human appendix, the elevated surface type of M cells named by protruding apical cytoplasm to the lumen was more conspicuous than the depressed surface type. The latter type was named by shorter irregular microvilli than those of neighboring cells, and was present dominantly in human Peyer's patch. M cells with enfolded lymphocytes consisted of the stumpy type and the slim type in the whole shape. M cells in the inflamed appendix showed their apical cytoplasm swelling like a balloon and microfolds disappearing, and seemed vulnerable to inflammation. It is considered that the M cell surface structure changes not only in accordance with enfolded lymphocytes and the uptake of antigenic materials, but also according to the organ in which M cells are present and whether inflammation is present or not.

Acute Disease↗
PubMed1988

[The significance of measuring inhibition of thymidylate synthase activity as a parameter for antitumor activity of 5-fluorouracil derivatives].

We investigated the relationships between antitumor activity and the inhibition of Thymidylate Synthase (TS) activity after oral administration of 5-fluorouracil (FUra) and its derivatives, FT, UFT, HC-FU, PH-FU and 5'-DFUR, using mainly Sarcoma 180 as an experimental tumor model. The inhibition of TS activity in the tumor, after oral administration of these drugs to Sarcoma 180 bearing mice, reached the plateau phase shortly after drug administration. The inhibition of TS activity remained at the same level for over 24 hours and was dose dependent. UFT and FT showed a very high correlation between the inhibition of TS activity and their antitumor activity. However, such a correlation was not found for other FUra derivatives despite their high TS inhibiting values. The relationship between the tumor growth inhibition (TGI) and the TS inhibition (TSI) of these drugs, presented as a ratio of ED50 of TGI to ED50 of TSI in case of UFT and FT, was shown to be 0.81 and 1.18, respectively (i.e., nearly 1.00). However, the above ratio for FUra and HCFU was shown to be 2.49 and 3.88, respectively. These findings demonstrate that it is necessary to take into account other mechanisms besides TS inhibition of some fluorinated pyrimidines to explain their total antitumor activity.

Animals↗
PubMed1987

Immunochemical study of role of chargerin II, a product of URFA6L of mitochondrial DNA in energy transduction of rat liver mitochondria.

Antibody against chargerin II [product of the unidentified reading frame A6L (URFA6L) of mitochondrial DNA] inhibited the ATP-Pi exchange reaction and reversed electron flow from succinate to NAD in mitoplasts (inner membrane plus matrix). The antibody against chargerin II caused greater inhibition on incubation with mitoplasts in the energized than the nonenergized state, suggesting that redox reactions are coupled with a conformational change of chargerin II. The present findings showed that chargerin II, the URFA6L product, may have a key role in energy transduction of mitochondrial oxidative phosphorylation.

Adenosine Triphosphate↗
PubMed1987

SLE-like and sicca symptoms in late component (C9) complement deficiency.

Hereditary deficiencies in early and late complement components are well known to predispose to SLE-like syndromes or recurrent infection. Hitherto reported C9 deficient cases have usually been healthy subjects, however, and it is not considered that C9 deficiency is associated with any specific disease. We describe a completely C9 deficient patient with possible Sjögren's syndrome and discuss the relationship.

Autoimmune Diseases↗
PubMed1987

Acute changes in C3a and C5a in an anaphylactoid reaction in hemodialysis patients.

Blood sample were collected from both the arterial and venous lines of the patients undergoing hemodialysis using cuprophan membrane at several time intervals. Radioimmunoassay was then applied to measure the C3a and C5a levels. C3a levels from the arterial lines of patients undergoing uneventful hemodialysis were 463.2 +/- 51.3 ng/ml (mean +/- S.D.), 1112.9 +/- 109.9, 956.0 +/- 72.1, and 721.2 +/- 49.6 at 0, 15, 120 and 360 min, respectively. C5a levels did not change significantly during uneventful hemodialysis. C3a and C5a levels were significantly higher in the blood from the venous lines than those from the arterial lines, a finding indicating that complement activation via alternative pathway takes place in the dialyzer. C3a and C5a levels were markedly elevated in patients with anaphylactoid reaction. Reuses of dialyzers on the patients having a history of an anaphylactoid reaction during hemodialysis suppressed not only the rise of C3a levels, but also the recurrence of the reaction. From these findings, it is concluded that rises of C3a and C5a in the arterial lines of patients are causally related to the induction of anaphylactoid reaction during hemodialysis.

Anaphylaxis↗
PubMed1985

Purified hydrophobic proteins, chargerins, are essential for energy transduction in oxidative phosphorylation.

Studies on anisotropic inhibitors, a unique type of inhibitor of energy transduction in oxidative phosphorylation, suggested that redox reactions generate two kinds of negative charges on the outer surface of mitochondrial inner membranes, on redox complexes and on F0, and that the inhibitors inhibit energy transduction by binding to these negative charges. Recent experiments on photoaffinity labeling of mitochondria with monoazide ethidium, which is an anisotropic inhibitor, showed that the inhibitor specifically binds to a hydrophobic protein of the membranes. In the present work the mitochondrial components labeled with monoazide ethidium were further purified and two kinds of hydrophobic proteins (apparent molecular masses, 8 and 13 kDa) were found to be specifically labeled with the inhibitor. These proteins were named chargerin I and II, respectively. Redox reactions greatly increased the molar ratio of ethidium bound to chargerin I and II in mitochondria, reflecting a conformational change of the chargerins coupled with the redox reactions. It was also shown that antibody against chargerin II specifically inhibited ATP synthesis in mitoplasts (inner membranes plus matrix) prepared from rat liver mitochondria. Thus, the present findings show that chargerins have an essential role in energy transduction in oxidative phosphorylation in rat liver mitochondria, in good accord with the conformational coupling model of the H+ pumps and ATP synthesis.

Affinity Labels↗