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Biomedical subjects

N Hara

Publications and source records attributed to N Hara.

At least 253 records · Page 14Linked to original sources

IL-10 inhibits prostaglandin E2 production by lipopolysaccharide-stimulated monocytes.

Since IL-10 has recently been shown to exhibit pleiotropic effects on human monocytes, it was of interest to determine the effect of this cytokine on prostaglandin E2 (PGE2) production by monocytes. Recombinant IL-10 (rIL-10) did not significantly affect PGE2 production by lipopolysaccharide (LPS)-unstimulated monocytes, but efficiently inhibited PGE2 production by LPS-stimulated monocytes. The inhibition by rIL-10 was achieved in a dose-dependent manner. Recombinant IL-4 also inhibited PGE2 production at the same degree as rIL-10. Viral IL-10 inhibited PGE2 production by monocytes in a similar fashion as did human rIL-10. Endogenously produced IL-10 was also shown to inhibit PGE2 production by LPS-stimulated monocytes. Kinetic studies showed that the inhibition by rIL-10 on PGE2 production was observed at least 3 h after LPS stimulation. Taken together, these results indicate that IL-10 may play an important role in modulating immunological responses via down-regulation of PGE2 production by monocytes.

Cells, Cultured↗

Contribution of Ad4BP, a steroidogenic cell-specific transcription factor, to regulation of the human CYP11A and bovine CYP11B genes through their distal promoters.

We analyzed the upstream regions of the human CYP11A and bovine CYP11B genes, and identified a distal promoter in each gene. The distal promoters are located at -1.8 to -1.5 kb in the upstream region of the CYP11A gene and -1.5 to -1.1 kb in the upstream region of the CYP11B gene. Transient transfection of CAT plasmid carrying each of the two distal promoters indicated that the regions had a transcriptional activating function and that the function was stimulated by cAMP. The basal and cAMP-stimulated transcriptional activities were detected only in steroidogenic cells. On structural analyses of the regions, we identified two Ad4 sites and a cAMP responsive element in the distal promoter of CYP11A, and two Ad4 sites and one NF-IL6 binding site in the distal promoter of CYP11B. The presence of an Ad4 site in common suggests its major contribution of the transcriptional activation. We also investigated the functional interactions between the distal promoters and basal promoters of both genes. Interestingly, the two distal promoters showed different requirements as to the basal promoter.

Animals↗

Presence of C5a-potentiating activity in the plasma of a patient with Kimura's disease.

To determine whether the response to the active complement fragment C5a in polymorphonuclear leukocytes (PMN) obtained from a patient with Kimura's disease is similar to that in normal subjects, we evaluated superoxide anion (O2-) generation after stimulation with C5a. The patient's PMN produced more O2- than did those from healthy controls after stimulation with human C5a in vitro. The response returned to normal with the improvement in clinical indicators after initiation of steroid administration. We conducted the following experiments with the plasma of this patient during the active disease stage to establish the presence of a humoral factor that potentiated the C5a-response of PMN. Incubation of PMN from normal controls having the same blood type as the patient at 37 degrees C for 2 h with the patient's plasma at the active disease stage revealed that the cells generated abundant O2- after stimulation with C5a. Incubation of normal PMN with the patient's plasma during the inactive disease stage showed no potentiated response to C5a. This activity was lost after incubation at 56 degrees C for 30 min. Coincubation of PMN with methylprednisolone up to 100 micrograms/ml did not suppress this activity. Although the plasma concentration of C5a at the active stage was mildly elevated (13 ng/ml), it was below the limit of detection (< 10 ng/ml) at the inactive stage. These results suggest the presence of a heat-labile, humoral factor in the patient's plasma that upregulated the response of PMN to C5a and that was not suppressed by in vitro treatment with a steroid. This factor may influence the acute inflammatory reaction in this disorder.

Angiolymphoid Hyperplasia with Eosinophilia↗

Contraction and depolarization induced by fetal bovine serum in airway smooth muscle.

We investigated the effects of fetal bovine serum (FBS) on the resting membrane potential and muscle tone of canine airway smooth muscles using tension recording and microelectrode methods. At concentrations > 0.1%, FBS induced a sustained increase in muscle tone. At concentrations > 1%, FBS depolarized the resting membrane potential of dog trachea in a dose-dependent manner. When FBS was dialyzed, it failed to induce a sustained increase in muscle tone or to depolarize the membrane, indicating that FBS contained factor(s) that induced contraction of dog airway smooth muscles. When FBS was dialyzed against distilled water, the outer solution which was freeze dried and then reconstituted (> 1% in original vol) induced a sustained increase in muscle tone, indicating that FBS contained dialyzable factor(s) that increased muscle tone and depolarized the resting membrane potential of dog airway smooth muscles. Methysergide (10(-6) M) or cyproheptadine (10(-6) M), nonspecific antagonists to serotonin receptors, 5-hydroxytryptamines (5-HT1 and 5-HT2), markedly reduced the FBS-induced increase in the muscle tone to approximately 20% of the original value but did not abolish the response. On the other hand, methysergide (10(-6) M) completely suppressed the increase in the muscle tone evoked by peak fractions obtained by application of the dialysate of FBS or 5-HT to a C18 reverse-phase column, indicating the peak fractions contained only 5-HT. These observations indicate that FBS contained 5-HT and an unknown factor(s) responsible for increase in the muscle tone of the airway smooth muscle induced by FBS.

Animals↗

Case of cough syncope with seizure.

A rare case of cough syncope accompanied by seizure is presented. Interseizure electroencephalogram revealed in this 55-year-old man spikes and sharp waves over the bilateral temporal regions. Bronchodilators and antiepileptic medication effectively controlled cough syncope and seizure in this patient.

Bronchial Provocation Tests↗

Specific induction of LTC4 synthase by retinoic acid in rat basophilic leukemia-1 cells.

Overnight (10-16 h) incubation of retinoic acid (RA), a derivative of vitamin A, specifically induced LTC4 synthase activity (5 to 10-fold), but not LTA4 hydrolase activity in the lysate of rat basophilic leukemia-1 (RBL-1) cells. A time course study revealed that the increase of LTC4 synthase activity was time dependent and that the peak value was obtained after a 24-hour incubation with RA. The induction of enzyme activity was specifically localized to the microsomal fraction. Glutathione (GSH) S-transferase activity measured by using the same cell lysate as an enzyme source and 1-chloro-2,4-dinitrobenzene (DNCB) as a substrate was not influenced by RA treatment, indicating that the induction by RA is specific for membrane-bound LTC4 synthase. The induction of LTC4 synthase may be an important regulatory mechanism of peptide-LT synthesis in allergy and inflammatory diseases.

Animals↗

Effects of epithelial cell supernatant on membrane potential and contraction of dog airway smooth muscles.

We investigated the effects of cultured epithelial cells and supernatants on resting membrane potential and excitatory neuroeffector transmission in smooth muscle cells of dog trachea and bronchioles. The mean resting membrane potential of the mucosa-free tracheal smooth muscle cells was -59.5 +/- 1.5 mV (+/- SD). Application of cultured epithelial cells (> 2.5 x 10(5) cells/ml) hyperpolarized the membrane, resulting in a potential of -64.5 +/- 1.7 mV. The supernatant of the cultured epithelial cells also increased the resting membrane potential of the mucosa-free tracheal smooth muscle cells by 4 to 9 mV. These hyperpolarizing actions were not modified by indomethacin (10(-5) M), l-NG-nitroarginine (10(-5) M), or oxyhemoglobin (10(-5) M), but were inhibited by glibenclamide (10(-6) M). The supernatants of the cultured epithelial cells completely or partially suppressed the contractile response of epithelium-denuded bronchioles to electrical field stimulations and suppressed the amplitude of excitatory junction potentials of the trachealis evoked by electrical field stimulations. Indomethacin prevented the inhibitory effect of supernatants on the amplitude of twitch contractions and excitatory junction potentials and markedly suppressed supernatant-associated inhibition of the excitatory neuroeffector transmission. Furthermore, indomethacin with AA861, a lipoxygenase inhibitor, completely suppressed this effect. Our findings suggest that cultured airway epithelial cells spontaneously release at least two factors. One factor selectively modulates the resting membrane potential, and the other inhibits the excitatory neuroeffector transmission.

Animals↗

Inhibition by dexamethasone of retinoic acid-induced enhancement of leukotriene C4 synthesis in rat basophilic leukemia-1 cells.

We investigated inhibitory actions of dexamethasone (DEX) on retinoic acid (RA)-induced enhancement of leukotriene C4 (LTC4) synthesis in rat basophilic leukemia-1 (RBL-1) cells. Cultured cells were preincubated with RA for 16 h with or without DEX, and generation of LTC4 was measured by high performance liquid chromatography in cell-free and intact cell systems. RA (0.1 microgram/ml) significantly potentiated calcium ionophore-stimulated production of LTC4 synthesis. DEX inhibited the RA-induced enhancement of LTC4 synthesis by up to approximately 95% in intact cells when stimulated with calcium ionophore. RA-induced LTC4 synthase activity, which was determined by enzyme assay, was also inhibited by DEX by 65% in a cell-free system. This discrepancy of inhibition between the intact and cell-free systems was due to a partial inhibition of phospholipase A2 activity by DEX in the intact cells. These results indicate that the production of LTC4 is predominantly regulated at a level of LTC4 synthase. The induction of new LTC4 synthase activity by RA and inhibition of the RA-induced activity by DEX are important regulatory mechanisms of LTC4 synthesis.

Animals↗

Cellular fatty acid composition of Erysipelothrix rhusiopathiae and Erysipelothrix tonsillarum.

The cellular fatty acid compositions in 6 strains of Erysipelothrix rhusiopathiae and 7 strains of Erysipelothrix tonsillarum were determined by gas chromatography. Fatty acids, ranging from C10 to C18, were detected in the test strains. The fatty acid profile was characterized by very high percentages of 18:1 (cis-9) (cis-9-octadecenoic acid; 72.4 to 82.1%) and 16:1 (hexadecenoic acid; 8.7 to 13.7%). The profiles of the E. rhusiopathiae and E. tonsillarum strains resembled each other, indicating that discrimination between E. rhusiopathiae and E. tonsillarum from qualitative or quantitative fatty acid differences is difficult.

Animals↗

Association of thrombosis-inducing activity (TIA) with fatal hypercoagulable complications in patients with lung cancer.

We previously reported that thrombosis-inducing activity (TIA) is present in plasma from patients with advanced lung cancer. Of 73 patients with non-small cell lung cancer, stages IIIb and IV, 41 (56 percent) had such activity in plasma. The median survival time was significantly shorter in the TIA-positive vs the TIA-negative group. When 34 of those 73 patients who had died at Kyushu University Hospital were evaluated for the incidence of disseminated intravascular coagulation (DIC) and adult respiratory distress syndrome (ARDS), they were significantly higher in the TIA positive group (p < 0.05). The DIC occurred in 7 of 20 patients positive for TIA and 5 died of ARDS. In contrast, in the 14 TIA-negative subjects, only 1 patients experienced DIC and none died of ARDS. Peripheral platelet counts, which had been rather elevated on the day of hospital admission, were below normal within 1 week of death in 40 percent of the 20 patients who were positive for TIA. These observations suggest that TIA may be responsible at least in part for the increased activity of the coagulation system and the high incidence of DIC and ARDS in patients with advanced lung cancer.

Animals↗

Multiple pulmonary nodules manifested in a patient with NK cell granular lymphocyte proliferative disorder.

An 18-year-old man was admitted to our hospital with high temperature and dyspnea. A chest radiograph revealed the presence of multiple round nodules compatible with a metastatic lung cancer. The peripheral white blood cell count was 22,000/mm3 and more than 85 percent were atypical large lymphocytes with azurophilic granules. He was diagnosed as having natural killer (NK)-cell granular lymphocyte proliferative disorder (NK-GLPD) as the lymphocytes were positive with CD56, a cell surface marker characteristic for NK cells. The major pathologic finding of the tissue collected from the pulmonary nodules by transbronchial lung biopsy was infiltration of mostly large granular lymphocytes.

Adolescent↗

[A chronic case of summer type hypersensitivity pneumonitis].

A 59-year-old woman complaining of progressive dyspnea on exertion was admitted to our hospital in August 1992. In 1983 she had experienced exertional dyspnea from August to November, then improved spontaneously. In August 1984, she was admitted to our hospital due to the recurrence of the symptom. She was diagnosed as summer type hypersensitivity pneumonitis based on the following findings, 1) detection of non-caseous granuloma by transbronchial lung biopsy, 2) detection of precipitating antibody to Trichosporon cutaneum in the serum, 3) induction of the symptom by provocation test with the fungi, 4) isolation of the fungi from her house. In spite of moving from her house after discharge, she continued to visit her former house once a week to clean it. During the period, fibrotic changes on the chest roentgenogram were slowly progressive. In August 1992, ten years after the onset, she was re-admitted to our hospital with a complaint of exacerbated dyspnea on exertion. Open lung biopsy revealed granulomatous lesions with fibrotic changes, which was compatible with chronic type hypersensitivity pneumonitis. This patient was diagnosed as a chronic case of summer type hypersensitivity pneumonitis because of the clinical course and findings of open lung biopsy as well as laboratory data at the first admission. We consider that this case offer various information in considering the mechanism of chronic progress of summer type hypersensitivity pneumonitis.

Alveolitis, Extrinsic Allergic↗

[Percutaneous intracavitary treatment of pulmonary aspergilloma-clinical efficacy and prognosis].

We have performed percutaneous intracavitary treatment with anti-fungal reagents in 8 patients with pulmonary aspergilloma (6 males and 2 female) over the past decade. Ages ranged from 43 to 84 years old. All of the patients had underlying lung diseases, seven having old pulmonary tuberculosis and one pneumoconiosis. Five patients had a history of hemoptysis or hemosputum. Amphotericin B (AMPH) was injected daily in 5 patients, Fulconazol (FCZ) in 2 patients, and both in the remaining patient. For AMPH, maximal dose, total dose, and treatment duration were 20 to 50 mg, 285 to 1560 mg, and one to 7.5 months, respectively, and for FCZ, 20 to 30 mg, 450 to 1600 mg, 3 weeks to 4 months, respectively. At the end of treatment, fungus balls disappeared in 2 patients, decreased in size in 3 patients and were unchanged in 3 patients. After follow up periods of 7 months through 6.5 years, 5 of 6 patients remained in roentogenologically better condition than before treatment, and 3 of 5 patients with episodes of hemoptysis or hemosputum have not since had airway bleeding. The prognosis of the other two patients are unknown, since they died of other diseases before this survey. One patient had aspergillus empyema 7 months after treatment. There were no serious side effects or complications directly related to treatment. It was suggested that continuous percutaneous intracavitary treatment with anti-fungal reagents is safe and effective for inoperable patients with aspergilloma.

Adult↗

Local recurrence after complete resection for non-small-cell carcinoma of the lung. Significance of local control by radiation treatment.

Of 471 patients undergoing a complete resection for non-small-cell carcinoma of the lung between 1972 and 1989, 40 patients (8.5%) had local recurrences without extrathoracic distant metastasis. Excluding 8 patients who had malignant pleural effusion, we selected 32 patients (24 with hilar-mediastinal lymph node, 6 with bronchial stump, and 2 with chest wall recurrence) from the 40 patients and assessed the significance of local control by radiotherapy. The median length of survival after disease recurrence for these 32 patients was 19 months. Of 29 patients given radiation treatment, 16 who responded to the treatment survived significantly longer than nonresponders (median survival time 27 months versus 6 months, p < 0.01). Univariate analyses of survival after recurrences in relation to various factors revealed that sex and disease-free intervals were significant prognostic factors (p < 0.05) other than the effect of radiotherapy. A multivariate analysis showed that the effect of radiotherapy was the predominant prognostic factor. From these results, we conclude that local control with radiation is beneficial in patients with solely locally recurrent tumors in terms of improved survival.

Adult↗

Triggering of degranulation in mast cells by exogenous type II phospholipase A2.

We have previously shown the possibility that endogenous type II phospholipase A2 (PLA2) might participate in degranulation in mast cells (MC) (Murakami, M., et al. 1992. Eur. J. Biochem. 209:257). Now we have examined whether or not exogenously added type II PLA2 triggers MC degranulation. When rat peritoneal connective tissue MC (CTMC) were exposed to purified rat type II PLA2 at concentrations of more than 10 micrograms/ml, significant release of histamine was observed, whereas PGD2 was not generated under the same conditions. Mouse peritoneal CTMC as well as bone marrow-derived immature MC also responded to PLA2. Preincubation of CTMC with tyrosine kinase inhibitors, genistein, and herbimycin A, but not with pertussis toxin, resulted in abolition of the sensitivity to PLA2. The ability of type II PLA2 to induce histamine release was inhibited by an antibody or chemicals, both of which blocked the catalytic activity of type II PLA2. Heparin or an antibody recognizing the heparin-binding domain of type II PLA2 also suppressed the MC-degranulating activity, probably due to inhibition of binding of PLA2 to the cells. The interaction between heparan sulfate on cell surface and the heparin-binding domain of type II PLA2 may be important for the induction of exocytosis. The catalytic domain of the enzyme is also crucially important for the degranulation induction. Furthermore, we found that nerve growth factor, one of the potent regulators of MC function, significantly potentiated type II PLA2-induced histamine release from rat CTMC. These results suggest the possible role of extracellular type II PLA2 in activation of CTMC primed with nerve growth factor at inflamed sites.

Animals↗

Treatment and prognosis of primary thymic carcinoma.

From 1972 to 1990, we treated eight cases of thymic carcinoma (6 squamous cell and 2 small cell carcinomas). According to the classification by Masaoka et al., they consisted of one stage I, four stage III, one stage IVa, and two stage IVb. A complete resection of the primary tumour could be done in only three patients; the others had diagnostic biopsy and then radiation treatment. Four of five patients had a prolonged regression of the primary tumors after irradiation at 40-61.2 Gy. Six patients suffered from extrathoracic metastases. All patients received systemic chemotherapy with different regimens to counter either metastatic or locally recurrent lesions. Only two patients (with a regimen including cyclophosphamide, doxorubicin, and vincristine) obtained a partial response. The median survival of the eight patients was 70 months after surgical operation. The identification of an effective drug combination may thus improve the long-term prognosis of thymic carcinoma since radiotherapy is able to control primary lesions, even in the case of unresectable advanced disease.

Adult↗