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Biomedical subjects

N Hara

Publications and source records attributed to N Hara.

At least 217 records · Page 12Linked to original sources
PubMed1996

[Interstitial pneumonia treated with intermittent cyclophosphamide pulse therapy].

A 52-year-old woman was admitted to the hospital because of polyarthralgia and dry coughing. A chest X-ray film showed bilateral diffuse reticulo-nodular shadows. A specimen obtained by transbronchial lung biopsy revealed alveolar septal thickening and infiltration by mononuclear cells. Interstitial pneumonia associated with rheumatoid arthritis was diagnosed. Interstitial pneumonia relapsed soon after the first pulse of corticosteroid therapy. Cyclophosphamide pulse therapy was given in addition to a second pulse of corticosteroid therapy; 700 mg of cyclophosphamide (500 mg/m2) was administered intravenously every month and the dose of steroids was gradually reduced. Cyclophosphamide pulse therapy was repeated three times and the dose of oral corticosteroids was reduced from 60 mg to 35 mg. There was no bone marrow suppression or hemorrhagic cystitis after the cyclophosphamide pulses. Eventually, corticosteroid therapy was stopped with no clinical deterioration. This case suggests that intermittent cyclophosphamide pulse therapy can be effective for treatment of interstitial pneumonia unresponsive to corticosteroids.

Arthritis, Rheumatoid↗
PubMed1996

[Clinical usefulness of helical computed tomography in evaluating chronic obstructive pulmonary diseases].

To assess the usefulness of healical computed tomography (CT) in evaluating pathophysiological abnormalities in chronic obstructive pulmonary disease, we compared the results of helical CT with those of pulmonary-function tests in 46 subjects with pulmonary emphysema. We obtained 3-D images of emphysematous lung tissue by choosing voxels with values less than -930 HU because the mean CT score in 10 normal subjects was -869 +/- 29 HU. For each patient the total lung volume (TLV) was computed from the 3-D image of the entire lung with CT score less than -600 HU, and the volume of emphysematous lung tissue (ELV) was computed from the lung with CT score less than -930 HU. TLV measured on inspiration correlated significantly with TLC (r = 0.601, p < 0.001), and TLV measured on expiration correlated significantly with RV (r = 0.836, p < 0.0001). The difference between inspiratory TLV and expiratory TLV correlated significantly with VC (r = 0.781, p < 0.001). ELV both on inspiration and on expiration correlated significantly with FEV1/FVC (p < 0.001) and with RV (p < 0.01, p < 0.001, respectively). These results suggest that the volume data obtained by helical CT reflect functional abnormalities of the lung. In addition to volume data, the distribution of abnormal lung tissue is easily assessed by helical CT. We conclude that helical CT is useful in evaluating pathophysiological abnormalities in chronic obstructive pulmonary disease.

Humans↗
PubMed1995

Detection of arginine-ADP-ribosylated protein using recombinant ADP-ribosylarginine hydrolase.

We made use of ADP-ribosylarginine hydrolase to detect arginine-ADP- ribosylated proteins. The hydrolase was expressed in Escherichia coli as a protein fused with glutathione S-transferase (GST). The fusion protein GST-ADP-ribosylarginine hydrolase catalyzed the hydrolysis of alpha-ADP-ribosylarginine to produce ADP-ribose and arginine. Casein ADP-ribosylated with [32P]NAD and chicken heterophil arginine-specific ADP-ribosyltransferase served as a substrate for the recombinant ADP-ribosylarginine hydrolase and the released ADP-ribose was determined. Protein ADP-ribosylated by cholera toxin could serve as substrate of the hydrolase but protein ADP-ribosylated by pertussis toxin, diphtheria toxin, or C(3) enzyme of Clostridium botulinum could not. The hydrolase did not release the radioactivity incorporated into isolated rat liver nuclei incubated with [(32)P]NAD or in bovine brain cytosol incubated with [(32)P]ADP-ribose. In homogenate of mouse heart which contained arginine-specific ADP-ribosyltransferase, labeling of a 55-kDa protein by incubation with [(32)P]NAD was removed by ADP-ribosylarginine hydrolase treatment; hence, the specific hydrolysis of ADP-ribose-arginine bond by GST-ADP-ribosylarginine hydrolase can be used to detect the arginine-ADP-ribosylated proteins in crude preparations. Arginine--ADP-ribosylated proteins in crude preparations. Arginine-ADP-ribosylated proteins in mouse spleen lymphocytes were identified using this method.

Adenosine Diphosphate Ribose↗
PubMed1995

Biological activities of Annona glabra.

On a preliminary screening, substantial antimicrobial, antifungal and moderate insecticidal, sporicidal and cytotoxic activities were observed for the hexane extract of the stem bark of Amona glabra L. Chromatographic fractionation of this extract led to the isolation of kaur-16-en-19-oic acid in a large amount as the main constituent, which was found to be largely responsible for the biological activities possessed by the crude extract.

Anthelmintics↗
PubMed1995

A phase II trial of oral tegafur and uracil plus cisplatin in patients with inoperable nonsmall cell lung cancer.

BACKGROUND: The combination of uracil and tegafur in a 4:1 molar concentration (UFT) has a greater antitumor activity than 5-fluorouracil (5-FU) and tegafur. Because the combination of 5-FU and cisplatin has been proven to have a synergistic antitumor effect in many experimental and clinical studies, a Phase II study was conducted using the combination of UFT and cisplatin in patients with inoperable nonsmall cell lung cancer. METHODS: Thirty-one patients with measurable disease were entered into the study; all were evaluable for toxicity and response. Their median age was 61 years (range, 36-75 years). There were 13 patients with Stage III and 17 with Stage IV disease. Twenty-two (71%) patients had received no prior treatment. UFT (400 mg/m2) was administered orally on days 1 through 21 and cisplatin (80 mg/m2) was injected intravenously on day 8. This treatment was repeated every 4 weeks. RESULTS: The median number of treatment cycles was two (range, 1-4 cycles). There were 11 partial responses (35%; 95% confidence interval, 19%-52%). The median response time was 6 months (range, 3-13 months). The median survival time was 11 months (range, 4-27+ months) for Stage III and 8 months (range, 2-22 months) for Stage IV. This chemotherapy regimen was well tolerated. The hematologic toxicities, such as leukopenia and thrombocytopenia of grades 3 and 4, occurred in only 2 of 31 (6%) patients. Nonhematologic toxicities of grades 3 or 4 were not observed. CONCLUSIONS: Oral UFT plus cisplatin administration demonstrated an activity comparable with that of other combinations based on cisplatin and an extremely low incidence of side effects. These observations suggest that this chemotherapy regimen is worthy of further investigation in a multi-institutional trial to determine the antitumor effect and the quality of life of patients.

Administration, Oral↗
PubMed1995

An inhibitor of cyclic AMP-dependent protein kinase enhances the superoxide production of human neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine.

Intact human neutrophils produced superoxide (O2-) by the stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP) even when the extracellular Ca2+ was absent (0.56 +/- 0.13 nmol/min per 10(6) cells). The production by fMLP was enhanced more than twice in the presence of the extracellular Ca2+. Moreover, the O2- production by fMLP in the presence of extracellular Ca2+ was enhanced nearly three times by the treatment of cells with H-89, an inhibitor of cyclic AMP-dependent protein kinase (PKA). The enhancement was not observed when the extracellular Ca2+ was depleted from the reaction mixture. In addition, H-89 did not enhance fMLP-induced O2- production of electropermeabilized neutrophils in which the intracellular Ca2+ concentration was fixed to about 100 nM. These observations suggest that not only Ca2+ influx but the inhibition of PKA is necessary for the maximum O2- production by fMLP and that the O2- production is partially suppressed by the activation of PKA induced by fMLP.

Bucladesine↗
PubMed1995

Nitric oxide induces an increased Na+ conductance in identified neurons of Aplysia.

The ionic mechanism of the effects of micropressure ejections of hydroxylamine (HOA) and sodium nitroprusside (SNP), nitric oxide (NO) generators, on the membrane of identified neurons (R9-R12) of Aplysia kurodai was investigated with conventional voltage-clamp, micropressure ejection, and ion-substitution techniques. Micropressure ejection of HOA and SNP onto the neurons caused a marked depolarization in the unclamped neurons. Clamping the same neurons at their resting potential level (-60 mV) and reejecting HOA and SNP with the same dose produced a slow inward current (Ii(HOA) and Ii(SNP), 3-7 nA in amplitude, 15-60 s in duration) associated with an increase in input membrane conductance. Bath-applied hemoglobin (50 microM), a nitric oxide scavenger, almost completely blocked Ii(HOA) and Ii(SNP), and 3-isobutyl-1-methylxanthine (IBMX, 50 microM) prolonged and enhanced both Ii(HOA) and Ii(SNP). An intracellular injection of cyclic guanosine 3',5'-monophosphate (cGMP) into the same neurons produced a slow inward current (Ii(cGMP)) which resembled the responses to HOA and SNP, and this current was enhanced in IBMX. Bath-applied methylene blue (10 microM), an inhibitor of guanylate cyclase, significantly reduced Ii(HOA) and Ii(SNP). The inward currents induced by HOA, SNP and cGMP were sensitive to changes in the external Na+ concentration. These results suggest that extracellular NO can induce a slow inward current associated with an increase in Na+ conductance, mediated by an increase in intracellular cGMP.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Ozone exposure suppresses epithelium-dependent relaxation in feline airway.

We examined the effect of exposure to ozone on the epithelium-dependent relaxation (EpDR) of bronchioles evoked by electrical field stimulation (EFS) in a feline model with hyperresponsive airways induced by exposure to ozone. Airway responsiveness was assessed by measuring the increases in total pulmonary resistance (RL) produced by aerosolized acetylcholine (ACh) in vivo. Airway responsiveness was also measured in vitro in dissected bronchiolar ring preparations. Exposure to ozone (3 ppm, 2h) significantly increased the airway responsiveness in vivo. The concentration of ACh required increasing RL to 200% of the baseline value, decreased from 1.97 mg/ml (GSEM 1.94) to 0.12 mg/ml (GSEM 1.77, p < 0.01) after exposure to ozone. EFS evoked atropine-, guanethidine-, and tetrodotoxin-resistant relaxations in the control bronchiolar rings precontracted by 5-hydroxytryptamine. Such relaxation was significantly suppressed by the mechanical denudation of epithelium, confirming that it was epithelium dependent. The amplitude of the EpDR was significantly suppressed in the animals exposed to ozone. These results suggest that EpDR is present in cats, and that its inhibition may contribute to the development of airway hyperresponsiveness.

Acetylcholine↗
PubMed1995

Hederagenin glycosides from Pometia eximia.

Seven new saponins, all glycosides of hederagenin (3 beta,23- dihydroxyolean-12-en-28-oic acid), were isolated from the stem of Pometia eximia along with hederagenin and two known saponins. Their structures were established as 28-O-beta-D-apiosyl(1-->2)-beta-D-glucopyranosyl-, 3-O-alpha-L- arabinofuranosyl(1-->3)[alpha-L-rhamnopyranosyl (1-->2)]-beta-D- xylopyranosyl-, 3-O-beta-D-apiosyl(1-->3)[alpha-L-rhamnopyranosyl-(1-->2)-beta-D- glucopyranosyl-, 3-O-alpha-L-arabinofuranosyl(1-->3)[alpha-L-rhamnopyranosyl- (1-->2)]-beta-L-arabinopyranosyl-, 3-O-beta-D-xylopyranosyl(1-->3)[alpha-L- rhamnopyranosyl(1-->2)]-alpha-L-arabinopyranosyl-, 3-O-beta-D-xylopyranosyl-(1-->3)[alpha-L-rhamnopyranosyl(1-->2)]-beta-D- glucopyranosyl-, 3-O-beta-D-galactopyranosyl(1-->3)[alpha-L-rhamnopyranosyl(1-->2)]-beta- D- glucopyranosyl-hederagenins.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Effect of BAY u3405, a thromboxane A2 receptor antagonist, on neuro-effector transmission in canine tracheal tissue.

Thromboxane A2 (TXA2) is reported to potentiate vagal nerve neuro-effector transmission in airway smooth muscle tissue. We investigated the effects of BAY u3405 (3(R)-[[4-fluorophenyl)sulfonyl]amino]-1,2,3,4,-tetrahydro-9H-carbazole - 9-propanoic acid), a potent and selective TXA2 receptor antagonist, on the increase in vagal nerve neuro-effector transmission induced by a TXA2 mimetic, U-46619, in the canine trachea. We measured the contractions of canine tracheal smooth muscle evoked by electrical field stimulation (EFS) and by acetylcholine (ACh) in the presence and absence of a subthreshold dose of U-46619 (the highest dose that did not induce any smooth muscle contraction). We then examined whether BAY u3405 inhibited the effect of U-46619 on tracheal smooth muscle. The following results were obtained: (i) subthreshold doses of U-46619 (10(-10) M and 10(-9) M) significantly increased the amplitude of the contractions evoked by EFS; (ii) by contrast, U-46619 had no effect on the contractile response of smooth muscle to exogenously applied ACh; (iii) the contraction evoked by EFS was completely abolished by the application of atropine (10(-6) M) or tetrodotoxin (10(-7) M), indicating that EFS caused the smooth muscle contraction through the release of ACh from vagal nerve terminals; and (iv) pretreatment with BAY u3405 (10(-6) M) abolished the excitatory action of U-46619 on the amplitude of twitch contraction evoked by EFS in the trachea. These results indicate that U-46619, at low concentrations, has a prejunctional action stimulating neuro-effector transmission, presumably increasing ACh release from vagal nerve terminals through TXA2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Case report: the first report of idiopathic hypereosinophilic syndrome involved with lung and middle ear.

It has been reported that various organs are involved in idiopathic hypereosinophilic syndrome. Frequently, the heart, lung, skin, and nervous system are involved. Involvement of the middle ear, however, has not yet been reported. In this article, the authors describe the first case of hypereosinophilic syndrome involving the lung and middle ear. A 39-year-old woman had a 4-month history of low grade fever, non-productive cough, and a feeling of fullness and hearing loss in both ears. Peripheral blood cell count showed eosinophilia. Bilateral tympanic cavities were obstructed with granulation tissue, and she was diagnosed as obliterative otitis media. The granulation tissue consisted of foamy histiocytes and eosinophils. Chest X-ray film and computed tomography showed patchy infiltrative shadow in the lung. Histologic examination of the open lung biopsied specimen showed alveolar spaces infiltrated by eosinophils. After treatment with 30 mg oral prednisolone daily, there was a rapid improvement in her clinical condition. Based on the clinical course and the histologic findings of this case, obliterative otitis media may be caused by eosinophilic infiltration and eosinophilic pneumonia.

Adult↗
PubMed1995

Histochemical demonstration of interleukin-2 in decidua cells of patients with preeclampsia.

PROBLEM: The objective of this study was to gain insight into the immunological aspects of preeclampsia. METHOD: The presence of interleukin-2 (IL-2) protein in the decidua was examined in five preeclamptic patients and seven normal pregnant women employing the immunohistochemistry. RESULTS: The decidua cells were strongly stained for IL-2 in four out of five preeclamptic patients, while only very weak, if any, staining was observed in all the uncomplicated pregnant women. CONCLUSIONS: IL-2 was clearly present in decidua cells in the preeclamptic setting, suggesting the possible involvement of immune-activation in the phathophysiology of preeclampsia.

Adult↗
PubMed1995

Evaluation of nested polymerase chain reaction for detecting mycobacterial DNA in pleural fluid.

A protocol based on the polymerase chain reaction (PCR) is the most sensitive method for detecting mycobacteria in clinical samples. However, few studies have assessed the usefulness of this method in the diagnosis of tuberculous effusion. We developed a highly sensitive and specific nested PCR method, that amplifies the bovine tuberculous MPB70 gene and the mycobacterial 16S rRNA gene for use in detecting Mycobacterium tuberculosis (M. tuberculosis) and mycobacteria, respectively, in clinical samples. We determined the sensitivity of this method for detecting mycobacteria in samples containing known amounts of mycobacterial DNA and in DNA extracted from pleural effusions obtained from 10 patients with pulmonary tuberculosis in whom standard microbiological techniques had detected mycobacteria in sputum but not in pleural effusion. The nested PCR method for the bovine tuberculous MPB70 gene and the mycobacterial 16S RNA gene was able to detect M. tuberculosis and mycobacterial genomes only if there were at least 2 copies per sample. Positive results for M. tuberculosis and the mycobacterial genomes were obtained by nested PCR in 2 of 10 and in 3 of 10 samples of pleural fluid, respectively but no mycobacteria were detected in malignant effusions obtained from 9 patients with lung cancer. The nested PCR method represents a rapid means for detecting mycobacteria in some pleural effusions previously found to be negative by culture. We speculate that the reaction of the host against mycobacteria is more important than the mycobacteria themselves in the pathogenesis of pleural effusion in which mycobacteria are not detected.

Base Sequence↗
PubMed1995

Inhibition by erythromycin of superoxide anion production by human polymorphonuclear leukocytes through the action of cyclic AMP-dependent protein kinase.

The long-term low-dose administration of erythromycin is effective in treating chronic inflammatory diseases of the lower respiratory tract. The aim of this study was to clarify the mechanism for this therapeutic effect of erythromycin. We measured its effect on the production of superoxide anion (O2-) by polymorphonuclear leukocytes (PMN) that was induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) or by phorbol myristate acetate (PMA). 25 microM erythromycin inhibited fMLP-induced O2- production by about 50%, but not PMA-induced O2- production. Moreover, this inhibition was overcome by adding an inhibitor of cyclic AMP-dependent protein kinase (PKA), H-89. The fMLP-induced O2- production was also inhibited by isoproterenol, a beta-adrenergic agonist, and by dibutyryl cyclic AMP, a cell membrane permeating analogue of cyclic AMP. The inhibition was also overcome by the addition of H-89. Therefore, the effect of erythromycin seemed to be, in part, mediated through the activation of PKA. The inhibition by erythromycin of O2- generation by PMN may contribute to the beneficial effect of this drug in treating chronic respiratory diseases.

Adrenergic beta-Agonists↗
PubMed1995

An important role of tachykinins in ozone-induced airway hyperresponsiveness.

We investigated the role of tachykinins in ozone-induced airway hyperresponsiveness (AHR) in guinea pigs. Airway responsiveness was assessed by determining the provocative concentration (PC200) of a histamine aerosol. Ozone exposure (3.0 ppm for 2 h) caused significant AHR. For vehicle-pretreated animals, the geometric mean pre- and post-ozone PC200 values were 0.87 mg/ml (GSEM 1.33) and 0.11 mg/ml (GSEM 1.17), respectively. Tachykinin depletion by capsaicin (50 mg/kg) prevented this AHR, whereas it did not alter pre-ozone airway responsiveness. The PC200 was 0.36 mg/kg (GSEM 1.64) before ozone and 0.24 mg/kg (GSEM 1.72) after ozone for this group. Ozone also caused a significant increase in neutrophils in bronchoalveolar lavage fluid (BALF) compared with BALF from a normal control group (1.71 +/- 0.69 versus 0.07 +/- 0.02 x 10(5)/ml, respectively). Capsaicin pretreatment attenuated this neutrophil influx (0.23 +/- 0.16 x 10(5)/ml). Morphometric assessment revealed edema of the bronchiolar wall after ozone exposure, which was not observed in the capsaicin group. BAL and morphometry revealed that the degree of ozone-induced epithelial desquamation was similar in both groups. These results suggest that tachykinins may be responsible for ozone-induced AHR, possibly via neurogenic inflammation.

Animals↗
PubMed1995

Chronic bronchobronchiolitis obliterans associated with Stevens-Johnson syndrome.

We report a case of bronchobronchiolitis obliterans associated with Stevens-Johnson syndrome diagnosed using bronchography and bronchoscopy in a 25-year-old man with dyspnea. Eighteen months prior to admission, the diagnosis of Stevens-Johnson syndrome due to anticonvulsant therapy was made at another hospital. On admission, the patient was wheezing and had overinflation of the lungs, with marked obstructive pulmonary dysfunction. Ventilation and perfusion scintigrams revealed multiple ventilation and perfusion defects but not mismatch. Bronchography revealed central bronchiectasis and obstruction of the peripheral bronchi. Occlusion of the fifth right basal bronchus was observed with fiberoptic bronchoscopy. Bronchography and bronchoscopy provide useful information for the diagnosis of this disease.

Adult↗
PubMed1995

Effects of inhibitors of ouabain-sensitive Na+, K(+)-ATPase and Li+ ions on the neuromuscular transmission of the frog.

The effect of blockade of ouabain-sensitive alpha 2 and alpha 3 (neural type) isozymes of Na+, K(+)-ATPase was investigated on frog neuromuscular preparations by recording the frequency augmentation-potentiation (FAP) of the endplate potential, an electrophysiological and neuropharmacological technique to analyze the drug actions on the release process of the readily releasable transmitter quanta. Erythrosin B, which was thought to selectively inhibit the neural type Na+, K(+)-ATPase, pivoted the log-linear FAP relation counterclockwise without altering the intercept on the ordinate. Chlormadinone had a similar action. An increase in the concentration of extracellular K+ ions pivoted the FAP relation clockwise with a concomitant upward shift of the intercept on the ordinate, and low K+ Ringer's solution produced an inverse effect. In contrast, Li+ ions shifted the FAP relation upwards dose-dependently leaving its slope unchanged. Cinnarizine, a blocker for inositol-1,4,5-trisphosphate-induced Ca2+ release, and 5,5'-dimethyl-1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid, a specific intracellular Ca2+ chelator, significantly antagonized the potentiating action of Li+. The ouabain-sensitive neural type Na+, K(+)-ATPase isozyme, which is abundant in neural tissues, seems to play an important role in stimulation frequency-dependent modulation of the quantal transmitter release such as FAP.

Adrenal Cortex Hormones↗