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T Okumoto

Publications and source records attributed to T Okumoto.

At least 37 records · Page 2Linked to original sources
PubMed1996

An application of nitrogen microwave-induced plasma mass spectrometry to isotope dilution analysis of selenium in marine organisms.

Nitrogen microwave-induced plasma mass spectrometry was studied for its applicability to the isotope dilution analysis of selenium in biological samples. Spectroscopic interference by calcium, which is present in high concentrations in biological samples, was investigated. No detectable background spectrum was observed for the major selenium isotopes of 78Se and 80Se. No detectable interferences by sodium, potassium, calcium and phosphorus on the isotope ratio 80Se/78Se were observed up to concentration of 200 mg/ml. The method was applied to the analysis of selenium in biological reference materials of marine organisms. The results showed good agreement between the certified and found values.

Animals↗
PubMed1994

Increased capillary density due to atrophy of ischaemic soleus muscle of the rat.

This investigation was undertaken to determine whether a severe limitation of blood supply by external iliac artery ligation can change the number and density of capillaries in rat soleus muscle. The external iliac artery in one hindlimb was ligated for 2, 7 or 28 days, and the other, sham-operated, hindlimb was used as a control. Muscle blood flow in the ischaemic soleus muscle at 2, 7 and 28 days after external iliac artery ligation was significantly decreased compared with the control. The muscle fibre area and the ratio of the fibre area to body mass in the ischaemic soleus muscle at 28 days after the external iliac artery ligation were significantly reduced in the ischaemic soleus muscle, but no change in the number of capillaries per fibre was observed. Capillary density per millimetres squared at 28 days and the ratios of the number of capillaries around type I fibres to the fibre area at 7 and 28 days were significantly increased in the ischaemic soleus muscle (P < 0.05). These results suggested that long-term severe limitation of blood flow in the soleus muscle by ligation of the external iliac artery could have induced the increase in capillary density, as a result of atrophy of muscle fibres rather than capillary growth.

Animals↗
PubMed1994

Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite.

A potent immunosuppressive activity was found in the culture broth of the fungus Isaria sinclairii (ATCC 24400). The metabolite, ISP-I ((2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2- hydroxymethyl-14-oxoeicos-6-enoic acid, myriocin = thermozymocidin) suppressed the proliferation of lymphocytes in mouse allogeneic mixed lymphocyte reaction, but had no effect on the growth of human tumor cell lines. It also suppressed the appearance of plaque-forming cells in response to sheep red blood cells and the generation of allo-reactive cytotoxic T lymphocytes in mice after intraperitoneal or oral administration. The metabolite was 10- to 100-fold more potent than cyclosporin A as an immunosuppressive agent of the immune response in vitro and in vivo, and appears to be a candidate for clinical application as a powerful immunosuppressant.

Animals↗
PubMed1994

Fungal metabolites. Part 12. Potent immunosuppressant, 14-deoxomyriocin, (2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-hydroxymethyleicos-6-enoic acid and structure-activity relationships of myriocin derivatives.

In order to investigate the structure-activity relationships, fourteen derivatives of myriocin ((2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-hydroxymethyl-14-oxoeicos- 6-enoic acid) were prepared and examined for immunosuppressive activity on mouse allogeneic mixed lymphocyte reaction in vitro. Among them, 14-deoxomyriocin ((2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2- hydroxymethyleicos-6-enoic acid) was the most potent. It also suppressed the generation of allo-reactive cytotoxic T lymphocytes in mice upon intraperitoneal administration, with a potency 10-fold greater than that of myriocin.

Animals↗
PubMed1994

Fungal metabolites. Part 14. Novel potent immunosuppressants, mycestericins, produced by Mycelia sterilia.

Mycestericins A, B, C, D and E were isolated from the culture broth of Mycelia sterilia ATCC 20349 along with thermozymocidin (= myriocin). Their structures were elucidated on the basis of spectroscopic studies and chemical evidence. The acetate of mycestericin C was identical with the acetate of 6,7-dihydromyriocin. Mycestericins suppressed the proliferation of lymphocytes in the mouse allogeneic mixed lymphocyte reaction, with a potency similar to that of myriocin.

Animals↗
PubMed1993

Inhibition of leukocyte adhesion to endothelial cells of human umbilical vein by Y-24180, an antagonist of platelet-activating factor.

Effect of Y-24180 (4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H- thieno [3,2-f][1, 2, 4]triazolo[4,3-a][1,4]diazepine), an antagonist of platelet-activating factor (PAF), on adhesion of leukocytes to endothelial cells of human umbilical vein was examined. Y-24180 inhibited the adhesion of guinea-pig peritoneal exudate cells activated by leukotriene B4 to endothelial cells in a concentration-dependent manner. WEB2086, another PAF antagonist, did not show the inhibitory effect. Inhibition by Y-24180 was not influenced by addition of PAF. Y-24180 had no effect on the expression of intercellular adhesion molecule-1 or endothelial-leukocyte adhesion molecule-1 on endothelial cells activated with interleukin-1 beta, while it suppressed the expression of CD18 antigen on human peripheral blood polymorphonuclear cells activated with leukotrien B4, inhibiting their adhesion to endothelial cells activated with interleukin-1 beta. In oxazolone-induced ear edema in mice, which involves delayed-type hypersensitivity with infiltration by inflammatory cells, Y-24180 dose-dependently inhibited the increase in ear weights, but WEB2086 did not. These results indicate that Y-24180 inhibits not only the actions of PAF but also the adhesion of leukocytes by suppressing the expression of CD18 antigen, inducing the inhibition of infiltration by inflammatory cells.

Animals↗
PubMed1991

Stimulation of biosynthesis of nerve growth factor by acidic fibroblast growth factor in cultured mouse astrocytes.

Bovine acidic and basic fibroblast growth factors (aFGF and bFGF) dose-dependently stimulated the release of nerve growth factor (NGF) in a culture medium of mouse astrocytes. The NGF concentration in the medium started to increase compared to that of the control cultures 4 h later and was further sustained for 24 h when aFGF was contained. The content of NGF mRNA in the astrocytes treated with aFGF peaked at eightfold over the control level after 4 h. The astrocytes did not proliferate until after 72 h when treated with FGFs under the conditions employed. These results indicate that aFGF stimulates the biosynthesis of NGF in cultured astrocytes without promoting cell proliferation.

Animals↗
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

Genesis of breast cancer in Japanese: a possible relationship between sex hormone binding globulin (SHBG) and serum lipid components.

We investigated changes in the amount of sex hormone binding globulin (SHBG) and the percentage of free estradiol (% FE2) during normal menstrual cycles in the sera of 8 young Japanese controls, and also the relation between the lipid components of serum and the serum level of SHBG in 250 normal Japanese controls aged 18-77 years. The amount of SHBG measured by IRMA was significantly higher in the luteal phase than in the follicular phase, whereas the % FE2 values remained constant throughout the menstrual cycle in 8 healthy young controls. These results suggest that the estrogen status in serum is constantly controlled by SHBG. The amount of SHBG was significantly correlated with the serum level of triglycerides (TG) in 250 normal Japanese controls. From these results, we postulate that the decrease in serum SHBG, probably caused by increased level of serum TG, leads to elevation of % FE2 and later to a status with a high risk of breast cancer.

Adult↗
PubMed1991

Inhibition by cyclo-oxygenase inhibitors of interleukin-6 production by human peripheral blood mononuclear cells.

The effects of cyclo-oxygenase inhibitors on interleukin-6 (IL-6) production by human peripheral blood mononuclear cells were examined. Indomethacin and Y-9223, a novel cyclo-oxygenase inhibitor, inhibited the increases in the IL-6 level in the culture medium of both mitogen-stimulated adherent cells and non-adherent cells fractionated from mononuclear cells. Northern blotting showed that the mitogen-induced increase in the expression of IL-6 mRNA was inhibited by indomethacin and Y-9223, indicating that these agents inhibit IL-6 biosynthesis. Aspirin, ibuprofen, and phenylbutazone also inhibited IL-6 production by adherent cells stimulated with lipopolysaccharide (LPS). There was, however, no direct relationship between inhibition of IL-6 and prostaglandin E2 (PGE2) production by these agents. The addition of PGE2 corresponding to the amount produced by adherent cells stimulated with LPS slightly increased IL-6 production by unstimulated adherent cells, but to a lower level than that reached with LPS. An anti-PGE2 antibody partially blocked IL-6 production by adherent cells stimulated with LPS. These results suggest that, in addition to the inhibition of PGE2 production, other mediators including cyclooxygenase products or other action mechanisms are involved in the inhibition of IL-6 production by these drugs.

Benzopyrans↗
PubMed1990

Purification and characterization of two forms of cytochrome P-450 with omega-hydroxylase activities toward prostaglandin A and fatty acids from rabbit liver microsomes.

Two forms of cytochrome P-450 (P-450), designated as P-450LPGA omega 1 and P-450LPGA omega 2, have been purified to specific contents of 17.9 and 11.1 nmol P-450/mg protein, respectively, from liver microsomes of rabbits treated with di(2-ethylhexyl)phthalate (DEHP), a peroxisomal proliferator. The purified P-450LPGA omega 1 and P-450LPGA omega 2 were found to have apparent molecular weights of 52,500 and 53,000, respectively. They showed absorption maxima at 451 and 450 nm in the carbon monoxide-difference spectra for their reduced forms, respectively. The two P-450s both efficiently catalyzed the omega-hydroxylation of prostaglandins A1 (PGA1) and A2 (PGA2), as well as the omega- and (omega-1)-hydroxylation of fatty acids such as laurate, myristate, and palmitate. In a reconstituted system, various metal ions such as Na+ and Mg2+ stimulated these reactions. The P-450s exhibited no detectable activity toward several xenobiotics tested. The two P-450s showed different peptide map patterns following limited proteolysis with Staphylococcus aureus V8 protease or papain. The NH2-terminal amino acid sequences (ALNPTRLPGSLSGLLQVAGL and ALSLTRLPGSFSGFLQAxGLLGLLL) of P-450LPGA omega 1 and P-450LPGA omega 2 were identical at 18/20 and 19/24 positions with that of the lung prostaglandin omega-hydroxylase from pregnant rabbits, respectively. An antibody against P-450LPGA omega 2 recognized a 52,000-53,000 molecular weight protein(s) in rabbit liver microsomes. The intensity of the immunoblot was significantly increased in liver microsomes from rabbits treated with DEHP, but not with phenobarbital or 3-methylcholanthrene.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

[Genesis and clinical significance of an apical diastolic rumble in patients with mitral Björk-Shiley valve: a Doppler echocardiographic study].

The genesis and clinical significance of an apical diastolic rumble after replacement with mitral Björk-Shiley prosthesis were studied in 20 patients by left ventricular (LV) inflow dynamics using Doppler echocardiography. 1. The rumble was audible in 17 of the 20 patients (85%). In all but one patient, its intensity was less than Levine 2/6. Duration of the rumble ranged from 248 to 544 (mean 377) msec. There was no case of prosthetic valve dysfunction. Duration of the slow filling wave (SF interval) of the apexcardiogram in 19 cases ranged from 150 to 541 (mean 317) msec, and it correlated significantly with the duration of the rumble (r = 0.95) in 15 cases. 2. In 20 patients, peak velocity of the LV inflow obtained from continuous wave Doppler echocardiograms ranged from 1.17 to 1.89 (mean 1.56) m/sec, and pressure half time (PHT) ranged from 82 to 233 (mean 134) msec. In 19 patients, the SF interval correlated significantly with PHT (r = 0.87), but not with peak inflow velocity. 3. Peak inflow velocity was significantly slower in cases without a rumble than in cases with a rumble. PHT and the SF interval tended to be shorter in the former than in the latter. 4. There was no significant difference in the SF interval, peak inflow velocity and PHT between eight patients with smaller valve sizes (less than or equal to 25 mm) and 12 with larger valve sizes (greater than or equal to 27 mm). 5. There was no obvious relation between the direction of the main LV inflow jet as assessed by Doppler color flow mapping and the presence of the rumble in 19 patients. 6. In 19 patients, the SF interval correlated significantly with left atrial dimension (r = 0.47), but it did not correlate with LV end-diastolic dimension, fractional shortening of the LV, and the peak lengthening rate of LV internal dimension. 7. Three patients with both the rumble and SF lasting 500 msec had prolonged PHT longer than 190 msec. One of these three had congestive heart failure and suspected prosthetic mitral valve stenosis. From these results, we concluded that an apical diastolic rumble after replacement with mitral Björk-Shiley valve is mainly due to the increase in resistance and velocity of the LV inflow, and that both durations of the rumble and the SF intervals as well as PHT of the Doppler echocardiogram are useful in detecting stenosis of prosthetic mitral valves.

Adult↗
PubMed1990

[Relationship between regurgitant flow dynamics and cardiac physical in tricuspid regurgitation: a phono-, mechano- and Doppler echocardiographic study].

To evaluate the relationships between regurgitant flow dynamics of tricuspid regurgitation (TR) and cardiac physical signs, and to clarify the role of atrial function on central venous flow, we investigated physical signs by cardiac auscultation and palpation of the liver. In addition, phonocardiography, jugular venous and hepatic pulse tracings and Doppler echocardiographic recordings were performed. The subjects, 109 patients with Doppler-detected TR, were categorized as an SR group of 42 with sinus rhythm, an Af group of 63 with atrial fibrillation and four with sinus arrest. Thirty-five patients underwent open heart surgery before six months or more. Results were as follows: 1. In the Af group, the maximum systolic flow velocity data in the superior vena cava (SVC) and hepatic vein (HV) correlated well with the maximum tricuspid regurgitant signal area on the color Doppler echocardiogram, and systolic backward flow from the heart was more evident in the HV than in the SVC. In the SR group, however, no correlation was observed between the maximum systolic flow velocity and the TR signal area, and systolic backward flow was not evident even in cases with severe TR. 2. After open heart surgery, systolic flow velocities in the SVC and HV were significantly decreased in the SR group compared to the Af group. 3. There was close correlation between the presence of hepatomegaly and systolic backward flow towards the liver. Hepatomegaly was more marked in the Af group than in the SR group. 4. Jugular venous and hepatic pulse data correlated well with the flow velocity data in the SVC and HV and with the TR signal area. 5. Intensity of the tricuspid regurgitant murmur as estimated by the Levine's classification correlated relatively well with the systolic pressure gradient between the right ventricle and right atrium as calculated by the modified Bernoulli equation, but did not correlate with the TR signal area. From these results, we conclude that the intensity of the tricuspid regurgitant murmur and the jugular venous or hepatic pulse patterns are useful for evaluating tricuspid regurgitant dynamics, when they are applied clinically with precise recognition of their significance and limitations, and that sinus rhythm or atrial fibrillation is also an important factor.

Atrial Fibrillation↗
PubMed1989

Relationship between the levels of serum thyroid hormones or estrogen status and the risk of breast cancer genesis in Japanese women.

For the purpose of investigating a possible correlation between the genesis of breast cancer and the levels of serum thyroid hormones or the estrogen status, which is one of the potential risk factors for breast cancer in Japanese women, we measured the percentage of free estradiol (E2) and the amounts of sex hormone-binding globulin (SHBG) and thyroid hormones in serum samples from Japanese patients with breast cancer (N = 39) and normal controls (N = 36). The patients were found to have significantly higher free E2 and significantly lower SHBG than controls. Moreover, the serum levels of free triiodothyronine (FT3) and free thyroxine (FT4) were lower in the patients than in controls, while the serum levels of TSH and TBG in the patients were not significantly different from those in controls. The percentage of free E2 in serum was not significantly correlated with the level of any one of FT3, FT4, TSH, and TBG either in the patients or in controls regardless of menstrual status. These results suggest the possibility that the reduction in the serum FT3 and FT4 levels, which is independent of changes in the serum level of free E2, may be one of the risk factors for breast cancer in Japanese women.

Adult↗
PubMed1989

Stimulation of phagocytic activity of leukocytes and macrophages by traxanox sodium in mice and rats.

Phagocytosis of yeast particles by mouse peritoneal macrophages or rat peritoneal polymorphonuclear leukocytes was enhanced by traxanox sodium in vitro. Traxanox sodium (30 and 100 mg/kg, p.o.) enhanced phagocytosis of yeast particles by leukocytes and macrophages in vivo or ex vivo. On the other hand, prednisolone, isoproterenol and theophylline inhibited phagocytosis by leukocytes and macrophages under the same conditions. Traxanox sodium (30 mg/kg, p.o.) prevented the suppression of phagocytosis by the above drugs. Combined with theophylline, isoproterenol synergistically inhibited phagocytosis by leukocytes in vivo. Traxanox sodium (100 mg/kg, p.o.) administered alone had no influence on carbon clearance in normal mice. However, traxanox sodium (1-30 mg/kg, p.o.) prevented the suppression of carbon clearance by the treatment with carrageenan, but not by the treatment with ethyl palmitate. These results suggest that traxanox sodium stimulates the phagocytic activity of leukocytes or macrophages and prevents the drug-induced suppression of the phagocytic activity of these cells.

Animals↗