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T Tsuruoka

Publications and source records attributed to T Tsuruoka.

At least 37 records · Page 2Linked to original sources

[Sex and age distribution of patients with macroamylasemia found in the daily isoenzyme analysis].

We studied distributions of sex and age for 102 patients with macroamylasemia found in routine isoenzyme analysis. This study was based on a questionnaire to promote understanding of the clinical significance of macroamylase. More than half of the physicians received our report evaluated the information on macroamylase in the questionnaire. Macroamylasemia found in this study consisted of IgA type immunoglobulin in 92% and mostly had high activities in the serum. The back-ground of these patients with macroamylasemia were 10 cases of hepato-biliary disease, 9 cases of diabetes mellitus, 8 cases of autoimmune disease and so on. The frequency of macroamylasemia in males was double than in females and age distribution was not significant in statistic analysis.

Adolescent↗

[Markedly decreased uptake with 123I-MIBG myocardial scintigraphy in a case with vasospastic angina].

A 68-year-old female whose myocardial sympathetic function was severely damaged with multi-vessel vasospastic angina is presented. She had no signs of autonomic dysfunction or diabetes mellitus. Myocardial imaging with 123I-MIBG showed extremely diminished uptake, but 201TlCl and 123I-BMIPP SPECT images were almost normal. Coronary arteriography revealed no significant atherosclerotic stenosis, multivessel spasm was observed by provocation test using acetylcholine. The extremely diminished uptake of 123I-MIBG was slightly increased in response to medication and the subsequent improvement of the patient's condition. Markedly decreased uptake with 123I-MIBG myocardial scintigraphy was considered to be due to multi-vessel spastic angina. We believe that this method of imaging study is useful for evaluating the healing stage of myocardial sympathetic dysfunction.

3-Iodobenzylguanidine↗

PF1092A, B and C, new nonsteroidal progesterone receptor ligands produced by Penicillium oblatum. I. Taxonomy of producing strain, fermentation, isolation and biological activities.

Three new nonsteroidal progesterone receptor ligands, PF1092A, B and C, have been isolated from Penicillium oblatum. They were purified from the solid cultures of rice media using ethyl acetate extraction, silica gel and Sephadex LH-20 column chromatographies, and crystallization. All three ligands competitively inhibited [3H]-progesterone binding to porcine uteri cytosol preparations with IC50 of 3.0 x 10 nM (PF1092A), 2.2 x 10(2) nM (PF1092B) and 2.2 x 10(3) nM (PF1092C).

Animals↗

PF1092A, B and C, new nonsteroidal progesterone receptor ligands produced by Penicillium oblatum. II. Physico-chemical properties and structure elucidation.

The structures of PF1092A (1), B (2) and C (3), new nonsteroidal progesterone receptor ligands produced by Penicillium oblatum, were elucidated by spectroscopic analyses. These compounds possess an eremophilane-type sesquiterpene carbon skeleton and differ only in that 1 and 2 are different monoacetates of 3. The absolute configurations of 1-3 were determined by single crystal X-ray diffraction analysis of the 4-bromobenzoyl ester of PF1092A and by measuring the optical rotations of the acetylation products of these compounds.

Furans↗

Inhibition of mouse tumor metastasis with nojirimycin-related compounds.

The antimetastatic activity of ten compounds structurally related to nojirimycin A was examined using a pulmonary metastatic model of mouse B16 melanoma. Nojirimycin B, deoxynojirimycin, D-gluco-delta-lactam, CP3068 and CP3069 are structural analogues of nojirimycin A, and showed potent or moderate antimetastatic activities. Nojirimycin A, nojirimycin B, deoxynojirimycin and D-gluco-delta-lactam showed potent or moderate inhibitory activities against alpha-glucosidase, beta-glucosidase and beta-mannosidase, but CP3068 and CP3069 in which the structures were related to D-gluco-delta-lactam showed no inhibitory activities. CP3041, CP3042, CP3043, CP3045 and CP3048 are analogues of sodium D-glucaro-delta-lactam (ND2001), a carboxy derivative of nojirimycin A, and showed potent or moderate antimetastatic activities. But no analogue was superior to ND2001 concerning with antimetastatic and anti-beta-glucuronidase activities. CP3041 and CP3042 showed potent and moderate inhibitory activities against beta-glucuronidase, respectively, but CP3043, CP3045 and CP3048 showed little or no activities.

1-Deoxynojirimycin↗

[Usefulness of 123I-BMIPP myocardial scintigraphy for evaluation of the left ventricular function in patients with chronic heart failure].

We examined the relationship between free fatty acid metabolism using 123I beta-methyl-iodophenyl-pentadecanoic acid (BMIPP) and cardiac function in patients with chronic heart failure (CHF). Cardiac free fatty acid metabolism was evaluated by the heart to mediastinum ratio (H/M), the heart to lung ratio (H/Lu), the heart to liver ratio (H/Li) and the myocardial uptake ratio (MUR) obtained from the planar imaging. Cardiac function was evaluated by the percent of fractional shortening (%FS) and the amount of left ventricular mass (LV mass) calculated with echocardiography. The study included 34 male and 14 female subjects of CHF with mean age of 61 +/- 9 years; dilated cardiomyopathy (DCM): n = 17, ischemic heart disease (IHD): n = 16, valvular disease: n = 5, hypertrophic cardiomyopathy: n = 4, hypertension: n = 4, amyloidosis: n = 2. The correlations between indices of BMIPP uptake and those of echocardiography were as follows: H/M vs. %FS (r = 0.67, p < 0.01), H/Lu vs. %FS (r = 0.49, p < 0.01), H/Li vs. %FS (r = 0.12, p = 0.42), MUR vs. %FS (r = 0.03, p = 0.86) and MUR/LV mass vs. %FS (r = 0.59, p < 0.01). The correlation coefficient between H/M and MUR/LV mass in patients with IHD was higher than that in patients with DCM. In conclusion, BMIPP, in particular, is a useful tool for evaluating cardiac function in patients with CHF.

Aged↗

[Isolation and characterization of isogenic transductants related with the resistance from in vitro fosfomycin resistant strains].

The mutation sites in FR182 and FR190, which were selected as fosfomycin (FOM) resistant mutants in vitro from an Escherichia coli (E. coli) K-12 derivative, were found to be close to the 52 min. and the 85 min., respectively, on linkage map of E. coli K-12. Therefore, the site of mutation in FR182 appears to be ptsI and that in FR190 to be cyaA based on the physiological and biochemical characteristics. We isolated isogenic transductants from the FOM resistant strains (from FR182, resistant strain AMG3 and sensitive strain AMG4, and from FR190, resistant strain AMI5 and sensitive strain AMI6) by transducing the genes of the resistant strains into recipients that were deficient in alkaline phosphatase. Under anaerobic conditions, MICs in the isogenic transductants were all decreased and the resistant transductants showed similar FOM sensitivities to the respective sensitive transductants. The FOM resistant strains were clearly lysed by much lower concentrations of FOM in the presence of cyclic adenosine-3',5'-monophosphate (cAMP) or glucose 6-phosphate (G6P) than in their absence, but the extent of lysis was more pronounced when both cAMP and G6P were present together, resembling the lysis of sensitive strains in same condition.

Alkaline Phosphatase↗

Inhibition of pulmonary metastases and tumor cell invasion in experimental tumors by sodium D-glucaro-delta-lactam (ND2001).

Sodium D-glucaro-delta-lactam (ND2001) inhibited spontaneous pulmonary metastases of the highly metastatic B16 melanoma variant with a maximal inhibition rate of 99.5%, and 6 of 7 animals remained metastasis-free. Likewise, ND2001 inhibited the spontaneous pulmonary metastases of both Lewis lung carcinoma (3LL) with a rate of 98.0% (3 of 5 animals remaining metastasis-free) and rat KDH-8 liver carcinoma with a rate of 82.5% (3 of 7 animals remaining metastasis-free), although it was unable to inhibit the metastases of mouse BMT-11 fibrosarcoma and rat SST-2 breast carcinoma. Pretreatment with ND2001 in vitro inhibited the pulmonary metastases of the B16 variant and 3LL cells, which indicates direct action upon the cancer cells. When the invasive activity of cancer cells was measured by the Boyden chamber method, the number of invading B16 variant or 3LL cells was reduced with maximal inhibition rates of 93.0% or 89.9%, respectively, but pretreatment with ND2001 failed to reduce the invasive activity of BMT-11 or SST-2 cells. ND2001 showed neither cytocidal nor antitumor activity. These results suggest that ND2001 inhibited pulmonary metastases at the invasive step into the basement membrane by directly changing some property of the tumor cells.

Animals↗

Inhibition of tumor cell haptotaxis by sodium D-glucaro-delta-lactam (ND2001).

We used the Boyden chamber system to investigate the mechanism by which the antimetastatic agent sodium D-glucaro-delta-lactam (ND2001) inhibits tumor cell invasion, and by establishing what ND2001 did not achieve, we were able to pinpoint the areas in which it was successful as an inhibitor. ND2001 did not inhibit cell adhesion of a highly metastatic B16 melanoma variant (the B16 variant) to the reconstituted basal membrane Matrigel, nor did it affect the production or activity of basal membrane-degrading type i.v. collagenase, but, in the Boyden chamber, ND2001 inhibited cell migration of the B16 variant toward a chemoattractant, laminin, on the lower surface of a Matrigel-free filter set (haptotaxis). Lewis lung carcinoma (3LL) cells that had been treated with ND2001 also exhibited hardly any haptotaxis, although the cells showed no alteration in behavior during cell adhesion to Matrigel. Since ND2001 did succeed in inhibiting the pulmonary metastases of the B16 variant and 3LL, we infer that inhibition of the metastases by ND2001 in these tumors is likely to be due to the inhibition of haptotactic migration.

Adenocarcinoma↗

[Lytic action of cefminox against slowly growing bacteria].

Lytic action of cefminox (CMNX) against slowly growing Escherichia coli (E. coli) K-12 JE1011 was compared with that of the related cephamycin cefmetazole (CMZ) or ampicillin (ABPC). The growth rate in doubling time was 30 min. at 37 degrees C. Minimal concentrations of CMNX, CMZ and ABPC showing clear lysis were 0.39, 3.13 and 12.5 micrograms/ml, respectively, under these conditions. When E. coli was cultured at 12 degrees C, the doubling time was 720 and 816 min. which were 24 and 27.2 fold as slow as those at 37 degrees C, respectively. In 12 degrees C culture, the minimal concentrations showing clear lysis were 0.78 (2 fold at 37 degrees C), 25 (8 fold) and 100 micrograms/ml and higher (8 fold or more) with CMNX, CMZ and ABPC, respectively. Therefore, it appeared that the lytic activity of CMNX was not significantly affected by bacterial growth rate and was demonstrated effectively against slowly growing bacteria at a low concentration. We determined release activity of cell wall peptidoglycan fragments by 5 beta-lactam antibiotics in addition to the above-mentioned 3 antibiotics. The results showed that the release activity was not proportional to the MIC and that of CMNX was the strongest among those antibiotics. The rapid and strong bactericidal action of CMNX against bacteria at the early stationary phase was suggested to result from the characteristic lytic action against slowly growing bacteria.

Ampicillin↗

[Active transport of fosfomycin into cells of Escherichia coli, multidrug-resistant Pseudomonas aeruginosa and Staphylococcus aureus].

We examined effect of fosfomycin (FOM) on growth of Escherichia coli (E. coli) NIHJ JC-2, multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa) PFS80 and Staphylococcus aureus (S. aureus) Smith. FOM inhibited the growth of these organisms at 0.1 approximately 0.5, 10 approximately 50 or 5 approximately 50 micrograms ml, respectively. In E. coli, FOM clearly lyzed the cells at 0.5 microgram/ml. These 3 bacteria incorporated radiolabeled FOM proportionately to incubation time. Intracellular concentration of FOM was estimated by considering the water content of E. coli cells. The ratio of intracellular to extracellular concentrations of FOM was larger than 1 after 5 approximately 10 min. incubation with FOM and reached about 7 after 40 min. FOM was incorporated actively into P. aeruginosa over extracellular concentration after 40-min. incubation on the basis of the above-mentioned water content. It was suggested that FOM was incorporated actively into various bacterial cells, and inhibited efficiently cell wall peptidoglycan synthesis, thus inhibited bacterial growth or lyzed the bacterial cells.

Anti-Bacterial Agents↗

Totally synthetic analogues of siastatin B. III. Trifluoroacetamide analogues having inhibitory activity for tumor metastasis.

A trifluoroacetamide analogue of siastatin B, (3S,4S,5R,6R)-6-(trifluoroacetamido)-4,5-dihydroxy-3-piperidine carboxylic acid has been chemically synthesized. This compound, as well as the previously synthesized analogue, (3R,4R,5R,6R)-6-(trifluoroacetamido)-3,4,5-trihydroxy-3-piperid inecarboxylic acid, showed marked inhibitory activity against beta-glucuronidase and significant inhibition of experimental pulmonary metastasis of the highly metastatic melanoma B16.

Acetamides↗

Selection of a mutant cell line based on differential expression of glycosphingolipid, utilizing anti-lactosylceramide antibody and complement.

A mouse mammary carcinoma mutant cell line showing a characteristic alteration of glycosphingolipid (GSL) composition, but with unchanged protein glycosylation pattern, was isolated. Parent cell line FM3A/F28-7 is characterized by the predominance of lactosylceramide (LacCer) and virtual absence of more complex GSLs. Mutant cell line FUA169 was isolated after treatment of F28-7 cells with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine and incubation with anti-LacCer monoclonal antibody T5A7 and complement. FUA169 cells were characterized by a dramatic reduction in LacCer and by the presence of a major ganglioside identified as GM3. They also showed high activity of CMP-sialic acid:LacCer 2,3-sialosyltransferase, whereas F28-7 cells had no detectable activity of this enzyme. In contrast to the difference in GSL pattern, F28-7 and FUA169 showed identical protein glycosylation patterns, as evidenced by "Western blotting" with various lectins and surface labeling with galactose oxidase/NaB3H4 and periodate/NaB3H4. Thus, FUA169 is identified as a glycosylation mutant with regard to GM3 expression and will be useful for studies of the functional role of GM3. Growth of FUA169 cells, relative to F28-7 cells, showed greater temperature sensitivity and greater inhibitability based on restriction of growth factors, particularly insulin.

Animals↗

Regulatory role of GM3 ganglioside in alpha 5 beta 1 integrin receptor for fibronectin-mediated adhesion of FUA169 cells.

Mouse mammary carcinoma mutant cell line FUA169, characterized by high GM3 ganglioside content, was established from parent cell line FM3A/F28-7, which has high lactosyl ceramide (LacCer) content but no GM3. FUA169 displays no changes in protein glycosylation, and is a typical glycolipid mutant differing from its parent in that it contains high quantities of GM3 and GlcCer, but no LacCer (see accompanying paper; Tsuruoka, T., Tsuji, T., Nojiri, H., Holmes, E. H., Hakomori, S. (1993) J. Biol. Chem. 268, 2211-2216). In contrast to parent F28-7 cells, FUA169 cells showed clear adhesion to fibronectin (FN). Several lines of evidence indicate that adhesion of FUA169 cells to FN requires the presence of GM3, which supports the function of integrin receptor. (i) Both FUA169 and F28-7 cells express the same quantity of FN integrin receptor, which consists of alpha 5 beta 1 (sensitive to RGDS peptide) and alpha 4 beta 1 (sensitive to CS1 peptide). However, adhesion to FN-coated plates, regardless of type of FN, was much higher for FUA169 than for F28-7 cells. (ii) F28-7 cells, which normally lack GM3 and adhere only weakly to FN, acquired GM3 during incubation in GM3-containing medium, and subsequently adhered strongly to FN. (iii) Cholesterol-lecithin liposomes (cholesterol was 14C-labeled) incorporating alpha 5 beta 1 receptor isolated from human placenta showed clear adhesion to FN-coated plates, and this adhesion was completely inhibited by RGDS peptide and by anti-beta 1 mAb ZH1. When liposomes included a moderate quantity of GM3 (0.22-0.44 micrograms (0.2-0.4 nmol)/55 micrograms of phosphatidylcholine, 33 micrograms of cholesterol, 5 micrograms of alpha 5 beta 1 in liposome), adhesion was enhanced significantly. In contrast, adhesion was greatly reduced below control level for alpha 5 beta 1 liposomes containing a higher quantity (2.2 micrograms; > 2 nM) of GM3. Adhesion to FN was also inhibited, but never enhanced, for alpha 5 beta 1 liposomes with similar composition but containing 0.4 nmol (or other quantities) of LacCer or GlcCer instead of GM3. These findings suggest that the greater adhesion to FN by FUA169 cells, relative to parent F28-7 cells, is due to functional support by GM3 of alpha 5 beta 1 integrin receptor.

Animals↗

Regulatory role of GM3 ganglioside in integrin function, as evidenced by its effect on function of alpha 5 beta 1-liposomes: a preliminary note.

Mouse mammary carcinoma mutant cell line FUA169, characterized by high GM3 ganglioside content, was established from parent cell line FM3A/F28-7, which has high LacCer content but no GM3. Although both cell lines showed the same quantity and quality of integrin receptors, FUA169 showed much stronger adhesion to fibronectin (FN)-coated plates than did F28-7. Liposomes containing phosphatidylcholine, cholesterol, alpha 5 beta 1, and a moderate amount of GM3 showed greatly enhanced adhesion to FN-coated plates, but adhesion of similar liposomes containing a large amount of GM3, or no GM3, was much lower. Our results suggest that GM3 regulates integrin receptor function essential for cell adhesion to FN.

Animals↗

Inhibitory effect of novel 1-deoxynojirimycin derivatives on HIV-1 replication.

The effect of 11 derivatives of 1-deoxynojirimycin (DNM) on the replication of HIV-1 was studied. Compared with DNM, seven of them showed remarkable inhibition of HIV-1-induced syncytium formation at significantly low concentrations which were not cytotoxic. Two derivatives were found to markedly reduce the infectious virus yields from cell lines chronically infected with HIV. Analysis of HIV-1 envelope glycoproteins showed that the derivatives induced modification of the processing of not only gp120/160 but also the transmembrane glycoprotein gp41. The modification of the processing of the transmembrane glycoprotein gp41 might play an important role in the inhibition of virus replication at a step after the binding of gp120 to CD4. The enhanced anti-HIV activity of DNM derivatives reported here could increase the possibility of non-toxic therapeutic intervention in HIV infections.

1-Deoxynojirimycin↗