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Biomedical subjects

Y Kotake

Publications and source records attributed to Y Kotake.

At least 91 records · Page 5Linked to original sources

Corticotropin-releasing hormone enhances the superoxide anion production of rabbit peritoneal macrophages stimulated with N-formyl-methionyl-leucyl-phenylalanine.

Effects of corticotropin-releasing hormone (CRH) on the superoxide anion (O2-) production in macrophages (M phi s) were investigated. CRH by itself failed to induce the O2- production of rabbit peritoneal M phi s elicited with thioglycollate medium. However, M phi s preincubated with CRH showed significant enhancement of O2- production following stimulation with a chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), at CRH concentrations from 10(-10) to 10(-7) M. Maximal enhancement of O2- production was obtained with 10 min preincubation with CRH for FMLP stimulation. CRH had no effect on O2- production when stimulated with phorbol 12-myristate 13-acetate. Neither corticotropin nor beta-endorphin augmented the O2- production induced with FMLP. These results indicate that CRH has priming effects on FMLP-induced O2- production of rabbit peritoneal M phi s, although the underlying mechanism remains to be clarified.

Adrenocorticotropic Hormone↗

Nitric oxide does not contribute to superoxide-mediated sulfhydryl oxidation in human polymorphonuclear leukocytes.

Recent findings have suggested that nitric oxide (NO) reacts with superoxide anion (O2-) to form a potential oxidant, peroxynitrite anion, which then decays to hydroxyl radical and nitrogen dioxide. In order to ascertain this hypothesis in human polymorphonuclear leukocytes (PMNs) which release both NO and O2-, we studied oxidation of L-cysteine (CYS) and bovine serum albumin (BSA) by PMNs and cell-free O2(-)-generating system of hypoxanthine (HX)-xanthine oxidase (XO) reaction. Oxidation of CYS by HX-XO was equally inhibited by superoxide dismutase (SOD) and catalase (CAT), and that of BSA by HX-XO was inhibited weakly by SOD and strongly by CAT. PMNs stimulated with phorbol 12-myristate 13-acetate increased the oxidation rates of CYS and BSA, and they were inhibited by SOD and CAT almost in a similar way to those by HX-XO. The NO synthase inhibitor, NG-monomethyl-L-arginine (NMMA), was confirmed to have an inhibitory effect on the inhibition of platelet aggregation by PMNs, and L-arginine (ARG) reversed this effect. However, pretreatment of PMNs with either of NMMA, or ARG, or both did not change the oxidation rates of CYS and BSA. We could not confirm the hypothesis at least in human PMNs that interaction of NO with O2- forms powerful oxidants to sulfhydryls of CYS and BSA. These results suggest that oxidation of sulfhydryls of CYS and BSA by PMNs is primarily dependent on reactive oxygen species, and is not modified by NO production.

Adult↗

Determination of the rate of superoxide generation from biological systems by spin trapping: use of rapid oxygen depletion to measure the decay rate of spin adducts.

A method was developed to measure the superoxide generation rate from biological systems using the spin trapping method. Kinetic treatment of the decay rate of the superoxide adduct of 5,5-dimethylpyrroline N-oxide (DMPO) revealed that the EPR signal intensity of the system is proportional to the superoxide generation rate. Rapid depletion of oxygen in the sample was utilized to terminate superoxide generation so that the decay rate of the DMPO superoxide adduct (DMPO-OOH) could be determined. For this decay measurement, a controlled atmosphere EPR cavity was developed and was used with an open-air sample cell. Superoxide generation rates determined with this method for stimulated neutrophils and for the hypoxanthine-xanthine oxidase system were comparable to those obtained with the cytochrome c reduction method. This method is specifically applicable to the system in which dissolved oxygen supplied from the gas phase is utilized as a source of superoxide.

Cyclic N-Oxides↗

[Lung resection for lung carcinoma with idiopathic interstitial pneumonia].

Of 12 patients who underwent lung resections for lung cancer with idiopathic interstitial pneumonia (IIP), eight patients survived and four patients died due to acute exacerbation of IIP after the operation. The preoperative values for percent forced vital capacity, predicted postoperative percent vital capacity, percent one-second forced expiratory volume index and serum level of C-reactive protein were significantly different between the group of patients who survived and that of having died. Three days after the operation, the percentage of lymphocytes among leukocytes and serum level of lactate dehydrogenase in the two groups were both significantly different. These findings showed that the operative strategy for patients with lung cancer and IIP needs specifically careful consideration for operative procedure, and preoperative serum levels of C-reactive protein and postoperative lactate dehydrogenase and the percentage of lymphocytes in leukocytes would be useful in evaluation of the severity of IIP.

Adenocarcinoma↗

Preoperative histologic diagnosis of chest wall invasion by lung cancer using ultrasonically guided biopsy.

Before operation, we evaluated the usefulness of ultrasonically guided needle biopsy to detect histologically invasion of the chest wall by tumor in patients with lung cancer. Ultrasonically guided needle biopsy, computed tomography, and ultrasonography were done in 29 patients with lung cancer. In all of them, chest wall invasion was histologically confirmed by thoracotomy. As for the diagnosis of chest wall invasion, sensitivity, specificity, and accuracy of ultrasonically guided needle biopsy diagnosis were 61.5%, 100%, and 82.8%, respectively; for diagnosis by computed tomographic scan these figures were 69.2%, 75.0%, and 72.4%, respectively; and for diagnosis by ultrasonography they were 76.9%, 68.8%, and 72.4%, respectively. We had no false-positive cases in the ultrasonically guided needle biopsy assessment and no fatal complications or implantation metastases. Our results indicate that ultrasonically guided needle biopsy is safe and useful for preoperative histologic diagnosis of chest wall invasion in cases in which combined chest wall resection is being considered in patients with lung cancer.

Aged↗

Thyrotropin-releasing hormone enhances the superoxide anion production of rabbit peritoneal macrophages stimulated with N-formyl-methionyl-leucyl-phenylalanine and opsonized zymosan.

Effects of thyrotropin-releasing hormone (TRH) on the superoxide anion (O2-) production, which is essential for effective microbicidal and cytotoxic activity in macrophages (M phi s), were investigated. TRH by itself failed to induce the O2- production of rabbit peritoneal M phi s elicited with thioglycollate medium. However, M phi s preincubated with TRH showed the significant enhancements of O2- production following stimulation with the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), at TRH concentrations from 10(-7) to 10(-4) M with a peak enhancement at 10(-5) M. O2- generations of M phi s stimulated with opsonized zymosan (OZ) were also enhanced at TRH concentrations from 10(-10) to 10(-5) M with a peak enhancement at 10(-7) M. Maximal enhancements of O2- production were obtained with 10 min preincubation with TRH both for FMLP and OZ stimulations. TRH had no effect on O2- production when stimulated with phorbol 12-myristate 13-acetate. Thyrotropin did not augment the O2- production induced with either FMLP or OZ. These results indicate that TRH has the priming effect on FMLP- and OZ-induced O2- production of rabbit peritoneal M phi s, although the mechanism remains to be clarified.

Amino Acid Sequence↗

Spin trapping of superoxide radicals following stimulation of neutrophils with fMLP is temperature dependent.

Oxygen radical formation by human neutrophils stimulated with a chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (fMLP), was studied through the use of spin trapping and superoxide dismutase-inhibitable reduction of oxidized cytochrome c. Both methods provided comparable data on temperature-dependent kinetics of superoxide radical formation, but hydroxyl radicals were also detected in spin-trapping experiments. When superoxide generation was monitored at 37 degrees C, the respiratory burst lasted only a few minutes. If the neutrophils were stimulated at 37 degrees C, but superoxide measurements were done at room temperature, the respiratory burst was again transient. However, neutrophils persistently generated superoxide when both stimulation and subsequent measurements were performed at room temperature. In the presence of the actin polymerization inhibitor, cytochalasin B, superoxide generation was persistent, even when measurements were conducted at 37 degrees C. A possible explanation for these observations is that the fMLP receptor complexes quickly aggregate and are internalized at physiological temperature, but not at room temperature. Very little superoxide was formed if cells were kept at a temperature of 4 degrees C for 1 h prior to fMLP addition, which is consistent with decreased expression of the fMLP receptor at cold temperatures.

Cytochalasin B↗

Spin trapping of superoxide from glass adherent polymorphonuclear leukocytes induced by N-formylmethionyl-leucyl-phenylalanine.

Dahinden et al. reported that N-formylmethionyl-leucyl-phenylalanine (fMLP)-induced superoxide release from polymorphonuclear leukocytes (PMNs) lasted more than 60 min when the cells were allowed to attach to a petri dish before induction. In contrast, it lasted only for 2.5 min when cells were in suspension (J. Clin. Invest. 72: 113-121, 1983). In spite of this report, the effect of cell adhesion has been ignored in most spin trapping studies of superoxide release from PMNs. This study shows that most PMNs in a quartz flat electron paramagnetic resonance (EPR) cuvette which was placed horizontally adhered to the wall within 3 min. In contrast, if the cuvette was placed vertically, only 20-30% of the cells became adherent in 30 min. We performed spin trapping studies using 5,5-dimethylpyrroline-N-oxide (DMPO) as a spin trap, and monitored the effect of cell adhesion on superoxide generation. When spin trapping was conducted on PMNs in suspension, the EPR signal of superoxide adduct (DMPO-OOH) was undetectable after stimulation with fMLP. However, PMNs which were allowed to adhere to the cuvette after stimulation generated superoxide for hours. Moreover, when PMNs were allowed to adhere prior to the stimulation, the magnitude of superoxide release was augmented three-to fourfold. Unlike fMLP, phorbol myristate acetate (PMA), which has been most commonly used in spin trapping studies, induced superoxide release which was not influenced by cell adhesion. We emphasize the importance of specifying the cell-adhesion-state in spin trapping studies.

Cell Adhesion↗

[In vitro effects of anesthetics on hydrogen peroxide generating system of the thyroid gland].

Effects of anesthetics on thyroidal hydrogen peroxide generating system was studied using porcine thyroid follicles. This system is indispensable in thyroid hormone synthesis and seems also to play an important role in regulation of thyroid hormone release. The results indicated that H2O2 generation was controlled by Ca2+ ion mobilization and protein kinase-C linked signal transduction system. It was also demonstrated that thiopental, halothane, and enflurane had inhibitory effects on H2O2 generation system in thyroid follicle cells, and 50% inhibitory concentrations (IC50) of each anesthetic drug were 60 microM, 2.5% and 4.0%, respectively. Other anesthetic agents, such as local anesthetics and major tranquilizers did not show any inhibitory effects on porcine thyroid peroxidase activity as well as on the regulation of thyroid hormone release. Other than inhaled anesthetic agents, thiopental only is thought to have an antithyroid effects in clinical situation.

Anesthetics↗

Stabilities of hydroxyl radical spin adducts of PBN-type spin traps.

The stability of the hydroxyl spin adduct of nine different PBN-type spin traps has been examined in phosphate buffer solutions of various pH. The hydroxyl adduct is produced by short illumination of hydrogen peroxide with UV light in the presence of spin trap and the decay of its EPR signal followed. The stability measured by the half life of the first-order decay is strongly dependent on the pH of the solution and the structure of the aromatic ring used in the trap. All hydroxyl adducts are more stable in acidic media. tert-Butyl hydroaminoxyl is detected as a degradation product of the hydroxyl adduct from all spin traps.

Cyclic N-Oxides↗

[Thymic carcinoid tumor--report of 3 operative cases].

Three cases of thymic carcinoid were surgically treated in our hospital. All 3 cases belonged to stage IVb (Masaoka's classification) because of anterior lymph nodes metastasis. A 44-year-old male patient died of multiple metastasis of bone and liver in 94 months after the operation. A 45-year-old female patient who had undergone operation 4 years ago, was re-operated on for recurrent carcinoid tumor but complete resection of the tumor could not be performed because of the tumorous invasion to superior vena cava, pericardium and costal bone. After the operation she has been treated by radiotherapy and any re-growth of the tumor has never been detected for 1 year. Another 50-year-old male patient who had been operated and treated by chemo-radiotherapy for thymic carcinoid before 50 months was diagnosed as recurrent tumor at left interpectoral lymph node. Radiotherapy is now preparing for this patient. 160 cases of thymic carcinoid reports in Japan were reviewed. 37 cases were stage IVb and 36 cases had supraclavicular or mediastinal lymph nodes metastasis. Those cases which had been underwent complete resection followed by radiotherapy seemed to have better prognosis. We conclude that patients of thymic carcinoid should be treated with complete resection including supraclavicular and mediastinal lymph nodes dissection, followed by radiotherapy.

Adult↗

[Intra-bullous ventilation of giant bulla: does slow ventilation space on multi-breath nitrogen washout test mean that giant bulla is present?].

Intra-bullous ventilation and uneven ventilation in patients with giant bulla were studied by the multi-breath nitrogen washout and 133Xe washout tests. Fourteen patients underwent the nitrogen washout test before and after bullectomy; 2 of them also underwent the 133Xe washout test before surgery. After bullectomy, pulmonary nitrogen clearance delay and alveolar dilution rate (ADR) of slow ventilation space improved significantly (p less than 0.01) from 202.5% to 51.5%, and from 0.98 to 0.95, respectively. The dilution rate of 133Xe in the bullous region, based on the 133Xe clearance curve, showed the same values as the nitrogen washout test. Therefore, we considered that bullous ventilation could be estimated by the ADR of the nitrogen washout test and that uneven ventilation resulted from the ADR difference between the giant bulla and the nonbullous lung. When the nonbullous lung region was emphysematous, however, it was impossible to estimate the intra-bullous ventilation from the nitrogen washout test.

Adolescent↗

Intraoperative pleural lavage cytology in lung cancer patients.

Cytology of intraoperative pleural lavage was examined in 164 lung cancer patients who underwent pulmonary resections. None of the patients had any pleural effusion or dissemination. Cytology was performed three times: (1) at thoracotomy, (2) immediately after resection, and (3) after washing the pleural cavity with 5,000 mL of physiological saline solution just before closure of the chest wall. Twenty-three patients (14%) had more than one positive cytological finding. The frequency of positive cytological findings was significantly correlated with pathological T classification, pleural status, and pathological stage. The positive lavage group had a significantly higher recurrence rate than the negative lavage group in patients with stage I or stage II cancer. Four patients in the positive lavage group (17.4%) had recurrence in pleura or pericardium whereas only 1 patient in the negative lavage group (0.7%) had a recurrence in pericardium. The positive cytological finding of pleural lavage has more important meaning as a prognostic factor in stage I and stage II and indicates a greater possibility of recurrence in pleura or pericardium, but further examinations to evaluate the viability of detected malignant cells are required so that the positive cytological findings of pleural lavage can be regarded as subclinical pleural dissemination.

Adenocarcinoma↗

Spin-trapping studies of hepatic free radicals formed following the acute administration of ethanol to rats: in vivo detection of 1-hydroxyethyl radicals with PBN.

The generation of free radicals in rat liver following the acute oral administration of ethanol was studied with the spin-trapping method, using a deuterated derivative of phenyl-N-tert-butylnitrone (PBN-d14) as the spin-trapping agent. After administration of ethanol and PBN-d14 to rats, organic extracts of the liver were prepared and subjected to ESR spectroscopy. In the case of ethanol-treated rats, the ESR spectra indicated that mixtures of radicals had been trapped, while spectra from control rats were essentially negative. The predominant spin adduct detected after ethanol treatment is proposed to be from a carbon-centered, primary alkyl radical, based on gamma-hydrogen hyperfine splitting patterns observed with PBN-d14. Oxygen-centered radicals also contributed to the ESR spectra. Liver extracts also contained low concentrations of the 1-hydroxyethyl radical spin adduct, which was indicated by weak spectral lines corresponding to those of the 1-13C-ethanol adduct. These data confirm previous suggestions that ethanol is metabolized to a free radical metabolite in rat liver. In addition, some information on types of lipid radicals generated during alcohol intoxication has been obtained.

Alcoholic Intoxication↗

Catechol oxidation by peroxidase-positive astrocytes in primary culture: an electron spin resonance study.

In rodents, chronic estrogenization has been shown to induce degeneration of dendrites and myelin figures in the hypothalamic arcuate nucleus adjacent to peroxidase-positive astrocyte processes. Because in this brain region estradiol is metabolized to 2-hydroxyestradiol (catecholestrogen), we hypothesized that the latter may be oxidized by the astrocytic peroxidase activity to cytotoxic ortho-semiquinones as occurs in peripheral tissues. Cysteamine induces nonenzymatic peroxidase activity in cultured astroglia identical to that observed in vivo. Using electron spin resonance, we demonstrate robust peroxidase-catalyzed oxidation of 2-hydroxyestradiol and dopamine by cysteamine-pretreated astrocyte cultures relative to untreated controls. These results implicate the peroxidase-positive astrocytes in the pathogenesis of estradiol-related hypothalamic damage, parkinsonism, and other free-radical-related neurologic disorders.

3,3'-Diaminobenzidine↗

[Multihospital randomized study on pre- and post-operative adjuvant chemotherapy for colorectal cancer (Part 2)].

Prior to surgery, 400 mg/day of UFT was administered for seven days to 86 patients with colorectal cancer. After surgery, the survival rate and side effects of the MMC only group (group A) and the MMC + UFT group (group B) were investigated. The two year survival rate for all cases was 79.8% for group B as opposed to 67.1% for group A. The two year survival rate for cases of histological curative resection were 80.0% for group A and 91.4% for group B, but the difference was not significant. There were few side effects in either group, and a significant difference in the incidence was not observed. Based on the above, MMC combined with UFT, as adjunctive chemotherapy for colorectal cancer, is considered to be a safe and effective treatment.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of benign pulmonary metastasis from ovarian immature teratoma].

A thirty one-year-old female underwent resection for pulmonary metastatic tumor from immature ovarian teratoma (G-II). Resected specimens from the lung revealed no malignant findings in the cystic teratoma (G-0). We speculated this finding might be due to retroconversion of ovarian immature teratoma. Retroconversion of ovarian immature teratoma is rarely reported and no report was found which dealt with pulmonary metastatic lesion histologically.

Adult↗