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Biomedical subjects

T Masuda

Publications and source records attributed to T Masuda.

At least 379 records · Page 21Linked to original sources

IC101, extracellular matrix antagonist produced by Streptomyces sp. MJ202-72F3. Production, isolation, structure determination and biological activity.

In our search for inhibitors of cell adhesion to components of extracellular matrix (ECM), fibronectin, laminin and collagen type IV, we succeeded in finding a novel cyclic hexadepsipeptide antibiotic, named IC101, which was isolated from cultured mycelium of Streptomyces albulus MJ202-72F3. It was purified by centrifugal partition chromatography, preparative reverse phase HPLC and Sephadex LH-20 and was obtained as a white powder. IC101 strongly inhibited cell adhesion to ECM components, suppressed immune responses in vitro and in vivo, and exhibited antimicrobial activity on Gram-positive bacteria.

Animals↗

Effect of conagenin in tumor bearing mice. Antitumor activity, generation of effector cells and cytokine production.

Antitumor effects and function of T cells in tumor bearing mice given conagenin (CNG), a low molecular immunomodulator, were investigated. The administration of CNG, once a week for 4 weeks, was the most effective schedule in inhibiting growth of IMC carcinoma, a syngeneic tumor. In this regimen, cytotoxic T lymphocytes and natural killer activities in spleens of CNG treated mice were maintained at higher levels than those of non-treated mice. Lymphokine production by splenic T cells was also enhanced in cultures, whereas monokine production by macrophages, which was increased in accordance with tumor growth, was reduced by CNG administration. The antitumor effect of CNG was not observed in mice given anti-asialo GM1 serum and in athymic mice. Results shown in this report suggest that CNG exerts its antitumor effects through activation of T cells and enhancement of generation of antitumor effector cells.

Adjuvants, Immunologic↗

Delaminomycins, novel nonpeptide extracellular matrix receptor antagonist and a new class of potent immunomodulator. I. Taxonomy, fermentation, isolation and biological activity.

In order to develop a new class of immunomodulator we have searched for a low molecular weight inhibitors of cell adhesion to components of extracellular matrix (ECM), fibronectin (FN), laminin (LM) and collagen type IV (CL), and succeeded to find a group of novel antibiotics, named delaminomycins. Delaminomycins were isolated from the mycelium and cultured broth of Streptomyces albulus MJ202-72F3. It was purified by use of centrifugal partition chromatography (CPC), preparative reverse phase HPLC and Sephadex LH-20 and was obtained as a white powder. Delaminomycins with inhibitory activity for cell adhesion to ECM components suppressed immune responses in vitro and in vivo and exhibited antimicrobial activity on Gram-positive bacteria.

Adjuvants, Immunologic↗

[The left ventricular force-length relationship in patients with heart failure].

A new contractility index (Ec) is proposed based on the slope of the left ventricular (LV) end-systolic force-length relationship. The Ec values of normal human hearts are relatively constant. The present study investigated the Ec values of 16 cases of heart failure in 11 patients with old myocardial infarction and 5 with dilated cardiomyopathy in NYHA functional class 1 to 3. The LV end-systolic pressure (Pes) and dimension (Des) were estimated simultaneously by intraarterial cannulation and LV echocardiography. The LV pressure decreased from 111 +/- 17 to 90 +/- 14 mmHg after intravenous infusion of nitroglycerin. The LV Fes-Des relationship was found to be nearly linear and the slope (Ec) and extrapolated dimension intercepts (Do) were obtained as 60 +/- 22 g/cm and 2.7 +/- 1.2 cm, respectively. The values of Ec and Do were both proportional to the baseline Des value. Our model predicts that the Ec value reflects intracellular peak Ca2+ concentrations ([Ca2+]) of the myocardium and/or myosin ATPase activity. The present results suggest that the working myocardium of a failing heart increases [Ca2+] and/or myosin ATPase activity to compensate for depressed LV pump function due to myocardial damage.

Adult↗

Quantitative measurement of hemosiderin deposition in tissue sections of the liver by image analysis.

Hemosiderin has been quantitated in tissue sections by image analysis employing Perls' Berlin blue reaction. A linear correlation was observed between the mean optical density of the tissue section measured with a commercial image analyzer and the iron concentration measured with an atomic absorption spectrophotometer. The correlation coefficient of .945 (P < .001) indicated that a linear correlation existed between these measurements. Thus, the hemosiderin volume in tissue sections can be measured quantitatively by image analysis.

Hemosiderin↗

[The etiology of sudden cardiopulmonary arrest in subarachnoid hemorrhage].

Sudden death due to subarachnoid hemorrhage (SAH) is not uncommon. However, the mechanism remains unclear. In this paper, sixty-eight consecutive patients with sudden death in SAH (DOA group) were studied to clarify the etiology of sudden cardiopulmonary arrest (CPA) in SAH. SAH was confirmed by CT scan and/or by autopsy. These patients accounted for 10% of the total intrinsic DOA patients in that period. Clinical symptoms, CT scan and autopsy findings concerning the DOA group were carefully evaluated and compared to those of patients with SAH of WFNS Grade V (V group). The DOA group accounted for 10% of all SAH patients. Average time interval from the onset of SAH to the recognition of CPA was 21.2 minutes. In 30% of cases, the time interval was within 15 minutes. Pulmonary edema was recognized as being significantly higher in the DOA group than in the V group (P < 0.01). In CT finding, the number of patients who were classified into S type (mainly subarachnoid clot only) was significantly higher in the DOA group than in the V group (P < 0.01). The CT Score and MAX. CT NO. in the DOA group were significantly lower than in the V group (P < 0.01 and P < 0.0001, respectively), suggesting that the intensity of subarachnoid hemorrhage was not severe in the DOA group. Postmortem histological examination of the myocardium was carried out on 6 cases of the DOA group. A contraction band necrosis in the myocardium which did not correspond to the coronary perfusion area was found in all 6 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Accumulation of protoporphyrin IX in light-sensitive mutants of Escherichia coli.

The accumulation of protoporphyrin IX (Proto IX) in light-sensitive mutants of Escherichia coli was detected by spectrofluorimetry. Fluorescence emission and excitation spectra were recorded from extracts of bacterial cells. Proto IX clearly accumulated in cells with mutations in the visA (hemH) gene but not in the wild-type strain CA274 or in visA mutants that had been rendered light-resistant by introduction of the wild-type visA+ gene. Accumulation of Proto IX was also not observed in cells with a mutation in the visB gene. These results confirm the hypothesis that the sensitivity of the visA mutants to light is caused by the abnormal accumulation of Proto IX, a substrate of ferrochelatase, as the result of a genetic defect in the gene for ferrochelatase.

Escherichia coli↗

Association of patency of the infarct-related coronary artery with plasma levels of plasminogen activator inhibitor activity in acute myocardial infarction.

To examine the fibrinolytic capacity in patients with acute myocardial infarction (AMI), baseline levels of plasma plasminogen activator inhibitor (PAI) activity and tissue-type plasminogen activator (t-PA) antigen were measured in 47 patients with Q-wave AMI who underwent emergent coronary angiography 3.0 +/- 0.2 hours after the symptom onset. They received intracoronary injection of urokinase if their infarct-related arteries were occluded. They were classified into 3 groups according to the patency of the infarct-related artery before and after thrombolytic therapy: the patent group (13 patients), the recanalized group (23 patients) and the occluded group (11 patients). The mean level of plasma PAI activity (IU/ml) was higher in patients with AMI as a whole than in the control group (12.8 +/- 1.6 vs 5.4 +/- 0.5, p less than 0.01). The level was lower in the patent group (3.0 +/- 1.1) and higher in the recanalized (18.6 +/- 2.2) and occluded (10.8 +/- 2.5) groups than in the control group (each p less than 0.01). The level was lower in the occluded than in the recanalized group (p less than 0.01) and 62% of the patients in the occluded group had levels within range of the control group. The mean level of plasma t-PA antigen (ng/ml) was higher in patients with AMI as a whole than in the control group (10.3 +/- 0.8 vs 5.8 +/- 0.3, p less than 0.01). There was no difference in the level among the 3 groups with AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cooperative function of rho GDS and rho GDI to regulate rho p21 activation in smooth muscle.

The GDP/GTP exchange reaction of rho p21, a member of ras p21-related small GTP-binding protein superfamily, is regulated by two stimulatory GDP/GTP exchange proteins (GEPs), named smg GDS and rho GDS, and by one inhibitory GEP, named rho GDI. In bovine aortic smooth muscle, rho GDS and rho GDI were major GEPs for rho p21, and the rho GDI activity on the GDP/GTP exchange reaction of rho p21 was stronger than the rho GDS activity in their simultaneous presence. Moreover, in the crude cytosol, the GDP-bound form of rho p21 was complexed with rho GDI but not with rho GDS. These results, together with our recent finding that rho p21 is involved in the vasoconstrictor-induced Ca2+ sensitization of smooth muscle contraction, suggest that there is some mechanism to release the inhibitory action of rho GDI and to make rho p21 sensitive to the stimulatory action of rho GDS, eventually leading to the rho p21 activation, in the signaling pathways of the vasoconstrictor receptors in smooth muscle.

Animals↗

Purification and characterization of luciferases from fireflies, Luciola cruciata and Luciola lateralis.

Luciferases of Luciola cruciata and Luciola lateralis, LcL and LlL, were purified to homogeneity by ammonium sulfate precipitation, gel-filtration column chromatography, and hydroxyapatite HPLC. The molecular masses of the enzymes determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were both 62 kDa, almost identical to that of Photinus pyralis (PpL). LcL was found to be similar to PpL in thermal stability, pH stability, and the wavelength of maximum light intensity. LlL was superior to LcL and PpL in thermal and pH stability, and the reaction catalyzed by LlL emits green light with a peak intensity at 552 nm, which is 10 nm shorter in wavelength than those of PpL and LcL.

Animals↗

Plasma platelet-derived growth factor levels in coronary circulation in unstable angina pectoris.

To examine whether plasma platelet-derived growth factor (PDGF) levels are elevated in the coronary circulation of patients with unstable angina, the plasma PDGF levels in the coronary sinus and aortic root were simultaneously examined in 14 patients with unstable angina, 15 with stable exertional angina, and 15 control subjects. The mean plasma PDGF level (pg/ml) in the coronary sinus was significantly higher (p less than 0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (502.1 +/- 98.7 vs 301.3 +/- 62.5, and 312.7 +/- 62.6). However, there were no significant differences in mean plasma PDGF levels in the aortic root among the 3 groups. It is concluded that PDGF release is increased in the coronary circulation in patients with unstable angina.

Aged↗

Prognostic assessment of superficial squamous cell carcinoma of the esophagus using karyometric analysis and nucleolar organizer regions.

To investigate prognostic values for squamous cell carcinoma, we measured nuclear area (NA), nuclear shape factor (NSF), DNA content and mean number of nucleolar organizer regions (NOR), using formalin-fixed, paraffin-embedded tissue sections from 39 patients with superficial squamous cell carcinoma of the esophagus. NA and DNA content were significantly higher in patients with lymph node metastasis than in those without metastasis. NA and the NOR number were also significantly higher in patients with recurrence than in those surviving for more than 3 years without recurrence. To determine the optimal combination of these parameters for prognostic assessment, we used a stepwise discriminant analysis to obtain two linear discriminant functions. One (f = 0.331 x NA + 6.64 x NSF + 9.85) gave an accuracy of 87.2% in predicting lymph node metastasis, and the other (f = -0.071 x NA - 2.34 x NOR + 13.0) yielded an overall accuracy of 88.9% in classifying patients into two groups with a better and worse prognosis. These results suggest that karyometric analysis and determination of the NOR number are useful for the prediction of disease outcome in patients with superficial squamous cell carcinoma of the esophagus.

Aged↗

Interleukin-8 is constitutively and commonly produced by various human carcinoma cell lines.

We examined the production of interleukin-8 and interleukin-6 by 30 human carcinoma cell lines. Serum levels of interleukin-8 were measured in 14 patients with hepatocellular carcinoma by enzyme-linked immunosorbent assay and Northern blotting. Furthermore, serum interleukin-8 was also investigated in a nude mouse bearing a tumor of the HuH7 hepatoma cell line producing interleukin-8. Of the 30 cell lines, 29 (96.7%) constitutively produced interleukin-8, and 19 of the 29 (65.5%) were high producers (> 1 ng/ml culture supernatant). Among the high producers, 4 cell lines released both interleukin-8 and interleukin-6. Interleukin-6 was constitutively produced by 17 of the 30 (56.7%) cell lines, 4 of which (23.5%) were high producers (> 1 ng/ml). By Northern blot analysis, mRNAs of interleukin-8 and interleukin-6 were detected in producing cell lines. Of 14 patients with hepatocellular carcinoma 4 (28.5%) showed increased levels of serum interleukin-8. Furthermore, inoculation of the HuH7 hepatoma cell line which produced the highest amount of interleukin-8 into a nude mouse resulted in tumor production accompanied by an elevated level of human interleukin-8 (646 pg/ml) in the peripheral blood. Thus, interleukin-8 is constitutively and commonly produced by various carcinoma cell lines. The production of interleukin-8 by carcinoma cells may be related to the elevation of serum interleukin-8 in patients with hepatocellular carcinoma. Finally, these cell lines may be valuable for studying the relationship between interleukin-8 and cancer.

Animals↗

Plasma plasminogen activator inhibitor activity and tissue plasminogen activator levels in patients with unstable angina and those with coronary spastic angina.

Plasminogen activator inhibitor (PAI) activity and tissue plasminogen activator (TPA) antigen were measured in venous samples in 14 patients with unstable angina consisting of eight patients with organic stenosed coronary arteries and six patients with coronary spastic angina (unstable angina group); in 14 patients with stable exertional angina (stable exertional angina group); and in 14 patients with chest pain syndrome (chest pain syndrome group). The plasma levels of PAI activity were higher (p less than 0.01) in the unstable angina group than in the stable exertional angina group and the chest pain syndrome group (12.3 +/- 1.0 versus 5.1 +/- 0.7 and 4.8 +/- 0.6 IU/ml). The plasma levels of TPA antigen were also higher (p less than 0.05) in the unstable angina group than in the stable exertional angina group and the chest pain syndrome group (10.2 +/- 1.3 versus 6.5 +/- 0.8 and 6.0 +/- 0.7 ng/ml). There were no significant differences in PAI activity and TPA antigen levels between the stable exertional angina group and the chest pain syndrome group. Furthermore, both PAI activity and TPA antigen levels in the unstable angina group decreased to the levels in the stable exertional angina group and the chest pain syndrome group after treatment (p less than 0.01). In conclusion, the increased plasma PAI activity in patients with unstable angina and in those with coronary spastic angina indicates that the fibrinolytic system is impaired in these patients.

Angina, Unstable↗

Activation of extrathymic T cells in the liver and reciprocal inactivation of intrathymic T cells by bacterial stimulation.

We recently demonstrated that the liver might be a major site of extrathymic T cell differentiation, including both alpha beta and gamma delta T cells. This extrathymic pathway in the liver, which has a relatively minor role in normal young mice, is activated in mice under bacterial stimulation. In the present study, we investigated how the extrathymic and intrathymic T cell differentiations were mutually related in mice injected intravenously with 10(8) heat-killed Escherichia coli. Three days after stimulation, extrathymic T cells in the liver were observed to be prominently activated in terms of increases in the total number of cells yielded, spontaneous cell proliferation in in vitro culture, and intermediate alpha beta TCR cells. Intermediate alpha beta TCR cells were extrathymic T cells uniquely seen in the liver. However, at the same time intrathymic T cells were profoundly inactivated, showing decreases in the number of thymocytes (more than 90% atrophy), spontaneous cell proliferation, and dull TCR cells with double positive CD4+8+ phenotype. With time, these responses were reversed and normal states were regained. These results suggested that extrathymic and intrathymic T cells are always activated or inactivated in the opposite direction, and that the liver and the thymus are dynamic immune organs. It raises the possibility that the extrathymic T cell differentiation in the liver and the intrathymic T cell differentiation may be reciprocally regulated by certain factors.

Animals↗

Radical-mediated modification of deoxyguanine and deoxyribose by luteoskyrin and related anthraquinones.

When cultured Reuber hepatoma H4-II-E and fibroblast Balb/3T3 cells were exposed to various concentrations of 5 derivatives of anthraquinones, luteoskyrin, a bis-anthraquinoid hepatocarcinogenic mycotoxin, exhibited the highest cytotoxicity to these cell lines. The content of 8-hydroxydeoxyguanine residues in the DNA of H4-II-E cells was dose- and time-dependently increased by luteoskyrin. The tumorigenic anthraquinones such as rugulosin and danthron also slightly elevated the level of this modified DNA base, while no such modification was observed with chrysophanol and emodin. Detailed experiments with luteoskyrin have demonstrated the formation of 8-hydroxydeoxyguanine and the degradation of deoxyribose into thiobarbituric acid-reactive products in the presence of ascorbic acid. These findings suggest the possible involvement of anthraquinone-derived hydroxy radicals for the modification of DNA base and deoxyribose.

3T3 Cells↗

Growth potential of endometrial cancers assessed by a Ki-67 Ag/DNA dual-color flow-cytometric assay.

Ki-67 is a monoclonal antibody directed against a nuclear antigen present only in proliferating cells. To assess the growth potential of uterine endometrial cancer, the population of cells in proliferating cycle (%PC) was examined with Ki-67, using flow cytometry. The %PC of 27.18 +/- 12.00% in 22 endometrial cancers was significantly higher than the 14.5 +/- 5.94% found in 28 normal endometrial tissues. In premenopausal endometrial tissue, the %PC in the proliferatory phase was significantly higher than the %PC found in the secretory phase. In endometrial cancers, an increase of %PC was found in cases with deep myometrial invasion, and the %PC was elevated in groups containing histologically poorly differentiated types when compared to groups of well-differentiated and moderately differentiated types. Sorted cells reactive with Ki-67 antibody were large and had a high nuclear/cytoplasmic ratio. On the bases of these results, it was concluded that a Ki-67 Ag/DNA dual-color assay would be useful to examine the growth fraction in endometrial carcinoma and that an increased growth fraction was related to deep myometrial invasion or poorly differentiated types.

Adenocarcinoma↗