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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 1,135 records · Page 63Linked to original sources

[Application of the nucleolar organizer regions to urinary cytology and its computer-assisted image analysis].

Quantification of argyrophilic nucleolar organizer regions (AgNORs) stained by the silver colloid method in urinary exfoliative cells from 36 benign urological diseases and 33 transitional cell carcinomas (TCC) of the urinary bladder was carried out. Also, AgNORs of these cells were measured by means of the computer-assisted image analysis system. There was a significant correlation between AgNORs numbers of cells from voided or wash-out smears and those from touch smears (p less than 0.01). The mean AgNOR numbers per nucleus showed a stepwise increase from non-infected benign urological diseases (mean +/- SD: 3.33 +/- 0.60) through infected urological diseases (3.88 +/- 0.58), grade 1 of TCC (5.23 +/- 1.39) and grade 2 of TCC (6.34 +/- 0.86), to grade 3 of TCC (8.09 +/- 1.19). The maximum number of AgNORs in each group indicated almost the same results. The estimation of the distribution of the maximum AgNOR number might be of great value for rapid and reliable detection of bladder cancers. Moreover, the computer-assisted image analysis of AgNORs could offer an objective index for the cytological assessment of urinary bladder diseases including TCC.

Analysis of Variance↗

[Endourological re-establishment by transluminal puncture for a complete obliteration of traumatic urethral disruption].

We performed transluminal re-canalization by needle puncture under fluoro-endoscopic control on a total of ten patients (membranous urethra, 8; bulbous urethra, 2) with complete obliteration after traumatic urethral disruption. The re-canalized tract was created by balloon dilation, internal urethrotomy or endoscopic resection of the scar tissue. The patient age ranged from 10 to 57 years (mean age; 37.9 +/- 15.3 years). A transluminal puncture was attempted in three patients by transperineal-transurethral approach and in seven by transurethral approach. In one of them, who sustained a complete membranous disruption 5 weeks ago, transluminal puncture failed because of the movable proximal urethra. The remaining nine patients voided without difficulty for the mean follow-up period of 18.1 +/- 14.3 months (range: 2-46). Three patients had mild stress urinary incontinence. A transluminal puncture is less invasive, safe and reliable for re-establishment of the true proximal part of the disrupted urethra. It can be recommended as a useful technique for endo-urological re-establishment for a completely obliterated urethra. Although this endoscopic re-establishment requires urethral sounding or internal urethrotomy for 6 months postoperatively, it may be an alternative to conventional surgical repair.

Adolescent↗

Antitumor spectrum of deoxyspergualin and its lack of cross-resistance to other antitumor agents.

Antitumor activities of 15-deoxyspergualin (NKT-01), an analogue of spergualin (SGL), were examined in cultured tumor cells, transplantable murine tumors, and human tumor xenografts in nude mice. NKT-01 exhibited strong antitumor activity specifically against leukemias both in vitro and in vivo. Moreover, it also showed activity against AH66F hepatoma, M5076 fibrosarcoma and MH134 hepatoma. However, antitumor activity of NKT-01 against other non-leukemic tumors was marginal. Effective dose range of NKT-01 in sensitive tumors was so wide that the largest chemotherapeutic indexes were produced by NKT-01 in P388 and L1210 leukemias among 15 antitumor agents examined. The efficacy of NKT-01 against doxorubicin- and cytosine arabinoside-resistant P388 leukemias was comparable to that against parental sensitive P388 leukemia. NKT-01 also retained activity against other p388 leukemia sublines resistant to cisplatin, 5-fluorouracil or nimustine, although the effect was slightly decreased. In addition, in the in vitro and in vivo experiments using NKT-01-resistant P388 and SGL-resistant L1210(IMC) leukemias, no cross-resistance was observed. Moreover, collateral sensitivity was observed especially to alkylating agents in animal study.

Animals↗

Anthracycline metabolites from Streptomyces violaceus A262. I. Isolation of antibiotic-blocked mutants from Streptomyces violaceus A262.

Five mutant (or variant) strains producing new anthracycline antibiotics were derived from Streptomyces violaceus A262 by mutagenesis treatment. Strain SE1-625 showed a limited production of three known beta-rhodomycinone diglycosides while the parent strain produced numerous unidentified beta-rhodomycinone glycosides. Strain SU2-730 was an antibiotic-blocked mutant which produced only epsilon-rhodomycinone glycosides (named epelmycins). Strains SC-7 and SE2-2385 were variants which produced alpha-citromycinone glycosides (named yellamycins) and beta-isorhodomycinone glycosides (named obelmycins), respectively. Strain SE2-2385-A1 produced alpha 2-rhodomycinone glycosides (named alldimycins). Glycosidation-less mutants which accumulated only aglycone were also obtained. Isolation of these mutants or variants and preliminary identification of their anthracycline products are described.

Anthracyclines↗

Anthracycline metabolites from Streptomyces violaceus A262. II. New anthracycline epelmycins produced by a blocked mutant strain SU2-730.

New anthracycline antibiotics, identified as epsilon-rhodomycinone glycosides, were isolated from the culture broth of a blocked mutant of beta-rhodomycin-producing Streptomyces violaceus A262. They were designated as epelmycins A, B, C, D and E, and assayed for their in vitro cytotoxicities against murine leukemic L1210 cell culture and the antimicrobial activities in comparison with known anthracycline antibiotics.

Animals↗

Anthracycline metabolites from Streptomyces violaceus A262. III. New anthracycline obelmycins produced by a variant strain SE2-2385.

New anthracycline antibiotics, designated as obelmycins A, D, E, F and G, were isolated from the culture broth of a variant strain of beta-rhodomycin-producing Streptomyces violaceus A262, identified as beta-isorhodomycinone glycosides and gamma-isorhodomycinone glycosides and assayed for their in vitro cytotoxicities against murine leukemic L1210 cell culture and the antimicrobial activities in comparison with some known anthracyclines.

Animals↗

Antifungal and antiviral activities of benanomicins and their analogues.

In vitro activities of benanomicins and their analogues against human immunodeficiency virus and fungi including Candida, Cryptococcus and Aspergillus, were examined. The free carboxyl group and at least one sugar moiety in the benanomicins were essential for their activities. Benanomicin A was most active and had low toxicity, and was selected as the best candidate for chemotherapy.

Animals↗

Isolation of new minor benanomicins.

Four minor benanomicins, dexylosylbenanomicins A and B, 2'-demethylbenanomicin A and 7-methoxybenanomicinone have been isolated from the culture filtrate of Actinomadura sp. MH193-16F4. Their structures were confirmed by spectral analyses. Dexylosylbenanomicins A and B were derived chemically from benanomicins A and B, respectively.

Anthracyclines↗

The nature of in vivo cell-killing of deoxyspergualin, and its implication in combination with other antitumor agents.

The mode of in vivo cell-killing by 15-deoxyspergualin (NKT-01) was assessed by measuring change of whole body radioactivity of mice inoculated with 125I-iododeoxyuridine-labeled P388 leukemia cells. Although NKT-01 showed strong life prolonging effect on P388 leukemia-bearing mice, significant excretion of 125I was not observed within 4 days after the start of treatment with NKT-01. Thereafter, the remaining 125I was reduced gradually and reached about half of control level on day 7. Colony forming ability in soft agar media of peritoneal tumor cells taken after completion of 5-day treatment with NKT-01 was markedly reduced to less than 3%. These results suggested that life prolongation of NKT-01 was produced both by a cytostatic effect, which lasts for an extraordinarily long period, and by a subsequent cytotoxic effect. Cell cycle distribution analysis using flow cytometry showed the cytostatic action of NKT-01 caused G0/G1 arrest of the tumor cells. Therefore, the drug-sensitive cycling population of the tumor cells was reduced, and combination with other antitumor agents was antagonistic, if they were administered simultaneously or consecutively with NKT-01. In contrast, if the other drugs such as cyclophosphamide, cisplatin and cytosine arabinoside, were administered prior to NKT-01, a synergistic combination effect was obtained. This synergism might be due to prolongation of the period of cell cycle perturbation caused by other drugs (such as G2 arrest by cisplatin) by the cytostatic effect of NKT-01. Although the precise mechanisms of the cytostatic action of NKT-01 remain unclear, it might play an important role in the combination with other antitumor drugs.

Animals↗

Inhibition of pinocytosis by hygrolidin family antibiotics: possible correlation with their selective effects on oncogene-expressed cells.

A fermentation broth of Streptomyces sp. SIPI-A4-0044 inhibited in vitro growth of src or ras oncogene-expressed (onc+) cells more strongly than that of oncogene-unexpressed (onc-) counterparts. The active components were isolated and identified as hygrolidin family antibiotics (HGL). In mixed cultures consisting of onc+ and onc- cells, at an appropriate ratio, HGL showed selective toxicity to focus like structures of onc+ cells, leaving monolayer areas of onc- cells little damaged. HGL rapidly inhibited pinocytosis, or the influx of neutral red into the cells, at concentrations partially inhibitory to the cell growth. In contrast, HGL only slightly inhibited the influx of 2-deoxyglucose, nucleosides and leucine and the syntheses of DNA, RNA and protein even at high concentrations. Upon prolonged exposure to sublethal concentrations of HGL, onc- cells but not onc+ cells recovered pinocytotic activity and resumed growth.

Animals↗

Dioxamycin, a new benz[a]anthraquinone antibiotic.

A new antibiotic, dioxamycin (1) was isolated from the culture broth of the strain MH406-SF1, which was closely related to Streptomyces xantholiticus. This antibiotic was purified by countercurrent chromatography, column chromatography and preparative HPLC. The molecular formula of 1 was determined to be C38H40O15 by HRFAB-MS. The structure was determined by spectral analysis of 2D NMR; 1H-1H COSY, 13C-1H COSY, long range 13C-1H COSY (HMBC) and NOESY. The antibiotic is active in vitro against Gram-positive bacteria and some tumor cells. Dioxamycin is a benz[a]anthraquinone antibiotic related to capoamycin.

Anthraquinones↗