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Biomedical subjects

H Tone

Publications and source records attributed to H Tone.

At least 19 recordsLinked to original sources
PubMed1995

Effects of pirarubicin in comparison with epirubicin and doxorubicin on the contractile function in rat isolated cardiac muscles.

1. We have examined the effects of pirarubicin (THP), compared with epirubicin (EPI) and doxorubicin (DXR), on the contractile function in papillary muscles isolated from rats. 2. In in vivo experiments, in which the rat was treated once a week for 4 weeks with DXR (total dose 10 mg/kg) and thereafter once a week for 4 weeks with THP, EPI or DXR (total dose 10 mg/kg), a positive instead of negative force-frequency relationship was observed in the muscles treated with EPI and DXR, but not with THP, and an increase in contractile response to extracellular Ca2+ was observed more markedly in the muscles treated with DXR than in those treated with EPI and THP. 3. In in vitro experiments, in which the muscle preparations were incubated with the drugs at 100 or 200 microM for 2 hr, EPI and DXR caused a negative inotropic effect and a prolongation of tension duration, while THP caused a slight positive inotropic effect and a slight prolongation of tension duration. 4. Furthermore, a decrease in the potentiated postrest contraction was observed more markedly in the muscles incubated with EPI and DXR at 200 microM than in those with THP. 5. These results suggest that both EPI and DXR show a cardiotoxicity by impairing the function of cardiac sarcoplasmic reticulum, and that the switching of the treatment from DXR to THP produces less impairing effects.

Animals↗
PubMed1995

Characterization of Pseudomonas paucimobilis FP2001 which forms flagella depending upon the presence of rhamnose in liquid medium.

A bacterial strain FP2001 isolated from the exudate of land reclaimed for municipal waste was identified as Pseudomonas paucimobilis. Cells of strain FP2001 were mobile by means of polar monotrichous flagellum, only when rhamnose was added as a carbon source in the liquid medium. The replacement of rhamnose by arabinose, galactose, glucose or xylose did not lead to the formation of flagella.

Bacteriological Techniques↗
PubMed1995

Induction of unresponsiveness of antigen-specific T lymphocytes by oral administration of cedar pollen extract in mice.

T lymphocyte unresponsiveness, induced in mice by a single gastric intubation of 0.2 ml cedar pollen extract (CPE, containing 4 micrograms protein/ml)/mouse daily for 3 to 28 consecutive days, was evaluated by the absence of a proliferative response of popliteal lymph node (PLN) T lymphocytes to CPE in vitro. T lymphocyte unresponsiveness increased with the period of gastric intubation of CPE and reached more than 80% of the control on day 28. The unresponsiveness to CPE was antigen-specific and T lymphocyte-mediated. In vitro CPE-specific T lymphocyte proliferation was significantly suppressed by intestinal intraepithelial lymphocytes (IELs) and hepatic mononuclear cells (MNCs), but not by spleen cells or PLN T lymphocytes from mice fed CPE for 28 days. The effector activity of IELs and MNCs was obviously antigen-specific. These results suggest that lymphocytes in the intestine and liver of mice fed CPE would be involved in the induction and maintenance of CPE-specific T lymphocyte unresponsiveness.

Animals↗
PubMed1995

[Vasodilating effects of NY-008 in ring preparation of rat aorta].

Vasodilating effects of NY-008 were compared to those of verapamil in isolated rat aorta. NY-008 at the dose of 3 x 10(-5) M relaxed 10-70 mM potassium chloride (KCl)-induced contraction. NY-008 relaxed preparations precontracted with 60 mM KCl concentration-dependently with an IC50 of (6.17 +/- 1.75) x 10(-6) M, and those precontracted with norepinephrine (NE) (10(-6) M) concentration-dependently, maximally by 90.0 +/- 2.86%, with an IC50 of (2.06 +/- 0.38) x 10(-5) M. At 10(-8)-3 x 10(-6) M, verapamil relaxed preparations precontracted with NE (10(-6) M) concentration-dependently, maximally by 55.9 +/- 5.56%. At 3 x 10(-5) M and 10(-4) M, NY-008 relaxed (10(-6) M)-induced phasic contractions in a Ca(2+)-free 1 mM EGTA-containing buffer, by 22.4 +/- 3.69% and 35.4 +/- 5.74%, respectively. In contrast, 3 x 10(-7) M verapamil did not. NY-008 concentration-dependently decreased the maximal responses to calcium chloride (CaCl2) in 60 mM KCl-depolarized preparations, and it shifted the ED50 values of CaCl2 to the right, whereas verapamil shifted the ED50 values of CaCl2 to the right without decreasing the maximal responses to CaCl2. At 10(-5)-3 x 10(-4) M, NY-008 concentration-dependently relaxed preparations precontracted with prostaglandin F2 alpha (10(-5) M) in a Ca(2+)-free, 0.5 mM EGTA-containing buffer, whereas 10(-7)-10(-5) M verapamil did not. These results suggest that NY-008 antagonized Ca2+ and decreased the Ca(2+)-sensitivity of contractile elements or inhibited contractile proteins in rat aorta.

Animals↗
PubMed1995

Antitumor effects of pirarubicin and epirubicin in combination with doxifluridine and cisplatin against mouse P388 leukemia.

In vivo antitumor activity of pirarubicin (THP) and epirubucin (EPI) in combination with doxifluridine (5'-DFUR) and cisplatin (CDDP) were examined using mouse P388 leukemia. THP (1.25-7.5 mg/kg) or EPI (1.25-15 mg/kg) was given intravenously on day 1, and then 5'-DFUR (125 or 250 mg/kg/day) and CDDP (4 mg/kg) were given orally on days 1-4 and intravenously on day 5 after tumor inoculation, respectively. Both THP and EPI enhanced the antitumor of a combination of 5'-DFUR and CDDP. The enhancement by THP was additive or synergistic, while that by EPI was additive. Cured animals were observed in the combination of THP with the two drugs, but not in that of EPI. Thus, in combination with 5'-DFUR and CDDP, THP was more effective against P388 leukemia than was EPI. The combination therapy using THP, 5'-DFUR and CDDP may be a novel chemotherapeutic approach to a variable type of tumors in clinical trials.

Animals↗
PubMed1994

Studies on thermophile products. IX. Isofatty acid-containing phosphatidylglycerol that enhances the induction of concanavalin A-activated suppressor T cells.

A new enhancer of the induction of concanavalin A (Con A)-activated suppressor T (Ts) cells has been demonstrated in the ethanolysate of Bacillus stearothermophilus UBT8038. It was purified by successive silica gel column chromatographies and identified as phosphatidylglycerol with C14:0-C18:0 isofatty acids (Fr. 7-C). Mouse splenocytes activated with Con A and Fr. 7-C (0.01-1 microgram/ml) in vitro significantly suppressed the proliferative response of syngenic splenocytes by mitogen stimulation in a dose-dependent manner, compared to those stimulated by Con A alone. The immunosuppressive response enhanced by Fr. 7-C disappeared when the cell populations of Thy-1.2 or CD8 positive lymphocytes were depleted. The result strongly suggests that Fr. 7-C is an immunosuppressive substance which enhances the induction of Con A-activated CD8 positive Ts cells.

Animals↗
PubMed1994

Studies on thermophile products. X. Further biological properties of isofatty acid-containing phosphatidylglycerol that enhances the induction of suppressor T cells.

Isofatty acid-containing phosphatidylglycerol (Fr. 7-C), isolated from Bacillus stearothermophilus UBT8038, enhances the induction of concanavalin A (Con A)-activated suppressor T (Ts) cells in a dose dependent manner (0.01-1 microgram/ml). Its further biological properties on mouse mixed lymphocyte reaction (MLR) has been demonstrated. Fr. 7-C (0.01-1 microgram/ml) suppressed the MLR at 4 d in a dose-dependent manner when added at the start of splenocyte cultivation. Moreover, Fr. 7-C was effective in preventing the generation of cytotoxic T lymphocytes after the MLR. On the other hand, this fraction significantly enhanced the induction of Ts cells in the MLR carried out in any of the antigen-specific, antigen-nonspecific and major histocompatibility complex antigen-nonrestricted fashions. Fr. 7-C increased prostaglandin E2 (PGE2) release approximately 2-fold in the culture supernatant of Con A-activated splenocytes, and PGE2 release decreased dose-dependently when cultured with indomethacin. The inhibitory effect by Fr. 7-C on the MLR was abrogated by the addition of indomethacin. The enhancement by Fr. 7-C on Ts cell induction was blocked by indomethacin in a dose dependent manner. These results strongly suggest that Fr. 7-C suppresses the MLR via the enhancement of antigen-nonspecific Ts cell induction mediated at least partly by PGE2.

Animals↗
PubMed1994

Studies on thermophile products. VII. Effect of 1,3-di-14-methylpentadecanoyl glycerol and its related isofatty acids on T cell proliferation in vitro.

It has been found that Bacillus stearothermophilus UK563-derived immunosuppressant fraction (Fr. 5-B) consists of 1,3-diacylglycerols with saturated iso- and anteiso-type fatty acids (C14:0-C18:0) as major components. The compound, 1,3-di-14-methylpentadecanoyl glycerol (1,3-diiso C16:0 G), was synthesized and its effect on T cell proliferation was investigated together with its related isofatty acids. While 1,3-diiso C16:0 G, iso C16:0, iso C17:0, iso C17:0 methyl ester (OMe) and anteiso C17:0 OMe suppressed the mixed lymphocyte reaction (MLR) of C57BL/6 against BALB/c mice, iso C15:0, 1,3-acylglycerols with normal C16:0, C16:1 and C18:0 did not, suggesting that the presence of isofatty acids with a certain length may be essential for the suppression of MLR. 1,3-Diiso C16:0 G and iso C16:0 strongly inhibited the autologous MLR of mesenteric lymph node cells against self-antigen presenting cells in MRL/MpJ-lpr/lpr (MRL/lpr) mice, but had no effect on concavalin A-induced T cell proliferation.

Animals↗
PubMed1994

Synthesis of doxorubicin-cyclodextrin conjugates.

Doxorubicin-gamma-cyclodextrin conjugates have been synthesized by the coupling of 14-bromodaunomycin with mono half-ester compounds linked to a 6-hydroxyl group of gamma-cyclodextrin. Release of drug from the conjugates in saline phosphate buffer solution and in vitro antitumor activity against L1210 leukemia cells were also investigated.

Animals↗
PubMed1994

Effects of cytogenin, a novel anti-arthritic agent, on type II collagen-induced arthritis in DBA/1J mice and adjuvant arthritis in Lewis rats.

The anti-arthritic effects of cytogenin (8-hydroxy-3-hydroxymethyl-6- methoxyisocoumarin) on type II collagen-induced arthritis in DBA/1J mice and adjuvant arthritis in Lewis rats were examined. Prophylactic treatment with cytogenin (30, 100 mg/kg) had a potent inhibitory effect on type II collagen-induced arthritis. Prophylactic or therapeutic treatment with cytogenin (10, 30 and 100 mg/kg) also had a potent inhibitory effect on adjuvant arthritis. In contrast to nonsteroidal anti-inflammatory drugs (NSAIDs), cytogenin (10, 30 and 100 mg/kg) had neither an anti-inflammatory effect on carrageenan-induced paw oedema in rats nor an analgesic effect on acetic acid-induced writhing in mice. These results suggest that the mode of the anti-arthritic action of cytogenin is different from that of NSAIDs and that cytogenin may become a useful drug for the treatment of rheumatoid arthritis.

Animals↗
PubMed1994

Comparison of cardiotoxicity of pirarubicin, epirubicin and doxorubicin in the rat.

The authors have examined the cardiotoxic actions of pirarubicin (THP), compared with epirubicin (EPI) and doxorubicin (DXR), on the electrocardiogram (ECG) and myocardial structure in rats. The rats were treated once a week for four weeks with DXR (total dose 10 mg/kg), and then further treated (post-treated) once a week for four weeks with THP, EPI or DXR (total dose 5 and 10 mg/kg). In the ECG study, a prolongation of QaT interval (interval from the upstroke of R wave to the apex of T wave) and a flattening of T wave were observed more severely in the rats post-treated with EPI and DXR than in those treated with THP. Also, a prolongation of QRS duration was observed more prominently in those treated with DXR than with THP and EPI. Histopathologically, a vacuolization and swelling of myocardial cells and an infiltration of mononuclear cells were observed more severely in the rats post-treated with EPI and DXR than in those treated with THP. Furthermore, a meandering of myofibril was observed in those treated with EPI and DXR, but not with THP. These results suggest that the cardiotoxic actions of THP are weaker than those of EPI and DXR and that the replacement of DXR with THP leads to more successful cancer chemotherapy with less cardiotoxicity.

Animals↗
PubMed1994

Experimental combination chemotherapy of pirarubicin with various antitumor drugs against P388 murine leukemia.

We have examined the therapeutic effects of combination therapy of pirarubicin ((2"R)-4'-O-tetrahydropyranyladriamycin, THP) with various antitumor agents against P388 murine leukemia. THP showed a high antitumor activity in combination with various antitumor drugs, especially with cyclophosphamide (CPM), cisplatin (CDDP), mitomycin C (MMC), enocitabine (BHAC), vindesine (VDS) or methotrexate (MTX). The effects of combination therapy depended on the order of administration of THP and combined drugs. THP-preceding treatment gave more synergistic effects in combination with 5-fluorouracil (5-FU) or MTX. THP-preceding or simultaneous treatment with etoposide (ETP) indicated the higher synergistic activity than ETP-preceding one. Moreover, THP showed much higher synergistic effects in any order of the combination with CPM, CDDP, MMC, BHAC, VDS or MTX. These results suggest that THP possesses a therapeutic usefulness clinically in combination with various antitumor drugs, if the selection of drugs combined with THP and the order of administration are suitable.

Animals↗
PubMed1993

Cloning and nucleotide sequences of two genes involved in the 4''-O-acylation of macrolide antibiotics from Streptomyces thermotolerans.

A DNA fragment responsible for the 4''-O-acylation of macrolide antibiotics was cloned from a mutant strain of the carbomycin producer Streptomyces thermotolerans. The gene encoding the macrolide 4''-O-acyltransferase was within a 2.7-kb region of the cloned fragment (15-kb). Streptomyces lividans carrying the region converted exogenously added tylosin to 4''-O-acyltylosins. Nucleotide sequencing of the region showed two open reading frames (ORFs). Expression assay using deleted plasmids showed that both ORFs were essential for optimal expression of the acyltransferase activity. One of them (acyB1) was identical with carE reported previously as a gene encoding 4''-mycarosyl isovaleryl-CoA transferase. The other (acyB2) was assumed to encode a novel regulatory protein that could active acyB1 expression. acyB1 and acyB2 were highly conserved among streptomycetes with macrolide 4''-O-acyl transferase activity.

Acylation↗