Biomedical subjects

H Kanazawa

Publications and source records attributed to H Kanazawa.

At least 73 records · Page 4Linked to original sources

PubMed1999

Plasma endothelin-1 level in chronic obstructive pulmonary disease: relationship with natriuretic peptide.

BACKGROUND AND OBJECTIVE: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by the vascular endothelium. The purpose of this study was to elucidate the pathophysiological role of ET-1 in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD). METHOD: We measured plasma ET-1 levels during right heart catheterization both at rest and during exercise on room air and while breathing oxygen in patients with COPD. In addition, we simultaneously measured plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). RESULTS: Plasma ET-1 levels at rest were significantly higher in 21 patients with COPD than in 16 control subjects (p < 0.001). For COPD patients, there was no correlation between the plasma ET-1 level and pulmonary arterial pressure or pulmonary vascular resistance at rest. On the other hand, there was a significant negative correlation between plasma ET-1 level and mixed venous oxygen tension (r = -0. 503, p < 0.05). Also, the plasma ET-1 level was positively correlated with those of ANP (r = 0.540, p < 0.05) and BNP (r = 0. 533, p < 0.05) at baseline. Oxygen administration significantly decreased plasma ET-1 levels at rest (p < 0.05). Plasma ET-1 levels did not change significantly with exercise despite the progression of pulmonary hypertension and hypoxemia. In contrast, plasma ANP and BNP levels both increased markedly with exercise (p < 0.01). CONCLUSION: We conclude that in patients with COPD, the plasma ET-1 level is not affected by acute progression of pulmonary hypertension and hypoxemia during exercise, and persistent hypoxemia may be associated with an increase in the plasma ET-1 level. In addition, our findings suggest that ANP and BNP may modulate the pulmonary vascular tone by interacting with ET-1 in these patients.

Aged↗

PubMed1999

Guinea pig airway hyperresponsiveness induced by blockade of the angiotensin II type 1 receptor. Role for endogenous nitric oxide.

Losartan is the first angiotensin II type 1 (AT1) receptor antagonist to become available for the treatment of hypertension. However, recent reports have revealed several cases of losartan-induced bronchoconstriction. We investigated to determine the mechanism of losartan-induced bronchoconstriction, considering in particular the involvement of endogenous nitric oxide (NO). In this study, we examined the effects of losartan on airway obstruction and endogenous NO production using anesthetized guinea pigs and cultured airway epithelial cells. Five minutes after administration of angiotensin II (Ang II), the bronchoconstriction induced by acetylcholine was not changed. In contrast, Ang II in the presence of losartan caused a significant increase in the acetylcholine responsiveness. Pretreatment with L-N omega-nitroarginine-methylester (L-NAME) potentiated acetylcholine-induced bronchoconstriction 5 min after administration of Ang II, and L-arginine reversed this action of L-NAME on the acetylcholine responsiveness. Moreover, Ang II administration increased NO concentration in expired air (12.5 +/- 1.5 ppb for saline, 40 +/- 5 ppb for Ang II, p < 0.01), and losartan significantly inhibited Ang II-stimulated NO release (20 +/- 3.5 ppb) from guinea pig airway. In cultured airway epithelial cells, Ang II also increased NO release (160 +/- 25 nM), and the effect of this Ang II-induced NO release was significantly inhibited by pretreatment with losartan (25 +/- 8 nM, p < 0.01). These findings suggest that losartan-induced bronchoconstriction may result from inhibition of endogenous NO release in the airway.

Acetylcholine↗

PubMed1999

Inhibition of bronchoprotective effects of beta2-adrenoceptor agonists by peroxynitrite in guinea pig airways.

Peroxynitrite plays an important role in the pathogenesis of inflammatory diseases, including those affecting the lung. In inflamed airways, simultaneous cellular production of superoxide anion (.O2-) and nitric oxide (NO) may occur, potentially resulting in continuous formation of peroxynitrite. However, because peroxynitrite has a short half-life, its in vivo physiologic effects in the airways may not be sufficiently evaluated with a single administration. Accordingly, this study was designed to use 3-morpholinosydnonimine (SIN-1), a compound that releases peroxynitrite, to determine whether peroxynitrite could alter airway beta2-adrenoceptor (beta2-AR) function in anesthetized guinea pigs. Though SIN-1(10(-)7 M) alone had no effect on pulmonary resistance, pretreatment with SIN-1 significantly attenuated isoprenaline- and salbutamol-induced bronchoprotection against acetylcholine. Pretreatment with SIN-1 also attenuated forskolin-induced bronchoprotection. S-Nitroso-N-acetylpenicillamine (SNAP), a potent NO donor, did not have the same effect as SIN-1. N-Acetylcysteine and glutathione each significantly reversed the inhibitory effect of SIN-1 on isoprenaline-induced bronchoprotection in a dose-dependent manner. These striking findings suggested that peroxynitrite, but not NO, is an important mediator of alteration of beta2-AR function in airway smooth muscle. Additionally, the action of peroxynitrite seems to be directed either at adenylate cyclase activity or at effects downstream of such activity.

Acetylcholine↗

PubMed1999

Imaging of living cultured cells of an epithelial nature by atomic force microscopy.

The present paper describes the applicability of atomic force microscopy (AFM) to the observation of living cultured cells of an epithelial nature (human esophageal squamous cell carcinoma cells, or C7 subclone of KESC2 cells) in a culture medium. For this purpose, we made a fluid chamber system which allows a constant-speed perfusion of fluid at a regulated temperature in the chamber. Using this system, AFM images of living cells were successfully obtained for over one hour at time intervals of 2-4 min during continuous perfusion of the fresh culture medium. A series of these AFM images proved useful for examining the movements of cellular processes in relation to subcellular cytoskeletal elements. Time-lapse movie records produced by sequential AFM images further verify the reality of the cellular dynamics.

Carcinoma, Squamous Cell↗

PubMed1999

The existence of Merkel cells in the lingual connective tissue of the Surinam caiman, Caiman crocodilus crocodilus (order Crocodilia).

The tongue of the Surinam caiman (a reptilian species) was studied by light microscopy including immunohistochemistry for protein gene product 9.5 (PGP 9.5), and transmission electron microscopy. The connective tissue immediately under taste buds housed a cluster of cells immunoreactive for PGP 9.5. These cells synapsed on nerves, and their cytoplasm contained characteristic granules of 90 nm in the mean diameter, glycogen particles, and bundles of intermediate filaments. In light of these ultrastructural features, they were identified as Merkel cells. The Merkel cells were also surrounded by Schwann cells. These findings indicate that the present Merkel cell-neurite-Schwann cell complex is comparable to the avian Merkel corpuscle. On the basis of the granule localization in the cytoplasm, the caiman Merkel cell was presumed to be involved in not only mechanoreception but also endocrine or paracrine functions.

Alligators and Crocodiles↗

PubMed1999

[Clinical investigation of 15 patients with pulmonary cryptococcosis--clinical comparison of HTLV-I carriers and non-carriers].

We investigated 15 pulmonary cryptococcosis patients. The group had a mean age of 51.7 years, and 6 (40%) of the patients were women. Cryptococcosis was primary in 13 patients and secondary in 2 (diabetes mellitus and smoldering adult T-cell leukemia). Eight patients were asymptomatic and 9 patients were detected by medical examinations. Dry cough was the most common symptoms. On chest radiographs, 5 patients showed solitary nodules, 4 patients showed infiltrative shadows, and 4 patients showed multiple nodules. The right lower lobe was the predominant location of solitary nodules, and the left upper and middle lung fields were the predominant locations of infiltrative shadows. Transbronchial lung biopsy was the method of diagnosis for 9 patients, and open lung biopsy for the others. Eleven patients were treated with fluconazole, and the mean treatment period was 7 months. Four patients underwent, resection procedures only, and experienced no recurrence. Five patients were positive for HTLV-I (one had smoldering ATL) and 5 were negative. Eighty percent of the HTLV-I positive patients had some symptoms and 80% of the HTLV-I negative patients were asymptomatic. HTLV-I positive patients showed various pulmonary shadows and 80% of the HTLV-I negative patients showed solitary nodules. The pulmonary lesions in HTLV-I positive patients were more extensive than those in HTLV-I negative patients (p < 0.05). We postulate the possible existence of subtle immunological abnormalities, including abnormalities of cellular immunity, in HTLV-I carriers.

Aged↗

PubMed1999

[Combination of 5'-DFUR and MMC for recurrent rectal cancer with pulmonary metastasis].

We report a 68-year-old man with rectal cancer and recurrent pulmonary metastasis treated with concomitant 5'-DFUR + MMC, which resulted in an extreme reduction of the lesion. The initial pulmonary metastases were treated by pneumonectomy, but 32 months later the patient again showed a pulmonary metastasis. Thus, from July 1997, he was treated with 5'-DFUR (800 mg/day) + MMC (4 mg/2 weeks). After 3 months of therapy, the chest CT examination showed an extreme reduction of the pulmonary lesion, and at 5 months the lesion was even smaller. Presently, after 7 months of therapy, the lesion remains stable. His CEA level is 1.0-2.6 ng/ml. After 4 months of treatment he had mild anorexia, which was alleviated by reducing the 5'-DFUR to 600 mg/day. No other adverse reaction was observed; the therapy was safely conducted on an outpatient basis.

Adenocarcinoma↗

PubMed1998

Reconstitution of F1-ATPase activity from Escherichia coli subunits alpha, beta and subunit gamma tagged with six histidine residues at the C-terminus.

An engineered gamma subunit of Escherichia coli F1-ATPase with extra 14 and 20 amino acid residues at the N- and C-termini (His-tag gamma), respectively, was overproduced in E. coli and purified. Six histidines are included in the C-terminal extension. The reconstituted F1 containing alpha, beta, and His-tagged gamma exhibited sixty percent of the wild-type ATPase activity. The reconstituted alphabeta His-tag gamma complex was subjected to affinity chromatography with nickel-nitrilotriacetic acid (Ni-NTA) agarose resin. ATPase activity was eluted specifically with imidazole. These results implied that the tag sequence protruded to the surface of the complex and did not seriously impair the activity. The reconstituted alphabeta His-tag gamma complex, even after its binding to the resin, exhibited ATPase activity suggesting that the gamma subunit, when fixed to a solid phase, may rotate the alphabeta complex. This system may provide a new approach for analysis of the rotation mechanisms in F1-ATPase.

Bacterial Proteins↗

PubMed1998

Determination of sedatives and anesthetics in plasma by liquid chromatography-mass spectrometry with a desalting system.

Though liquid chromatography-mass spectrometry (LC-MS) is a powerful tool for analysis of drugs and their metabolites, it does not allow the use of a non-volatile buffer such as phosphate buffer. We used a column-switching desalting system in combination with atmospheric pressure chemical ionization LC-MS for analysis of sedatives and anaesthetics. The drugs examined were flumazenil, butorphanol, midazolam, lorazepam, phenobarbital and flunitrazepam. The separation was carried out on a reversed-phase column using acetonitrile-0.1 M phosphate buffer as a mobile phase. The mass spectra are almost the same as those obtained by direct analysis and the molecular ions were clearly observed. In the analysis, phosphate buffer was completely removed with the trapping column and did not interfere with ionization of the drugs in MS. The chiral separation of lorazepam was achieved on a chiral column with UV, optical rotatory detection and MS. This method is sufficiently sensitive and accurate for the pharmacokinetic studies of these drugs in biological samples.

Anesthetics↗

PubMed1998

Effects of transjugular intrahepatic portosystemic shunt (TIPS) on esophageal motor function and gastroesophageal reflux.

The effects of transjugular intrahepatic portosystemic shunt (TIPS) placement on esophageal motor function and gastroesophageal reflux were investigated in patients with esophageal varices. In six men with esophageal varices, esophageal manometry and upper gastrointestinal endoscopy were performed before and 15-20 days after TIPS placement. Intraesophageal pH monitoring was performed in the four patients with severe esophageal varices (defined as the largest sized varices) following TIPS placement. Findings were compared with those in six healthy men (controls) who underwent esophageal manometry and intraesophageal pH monitoring. The esophageal varices resolved or were reduced after TIPS placement. Resting lower esophageal sphincter (LES) pressures were similar in the study group before and after TIPS placement and in the control subjects. The incidence and progression of esophageal contractions were similar in the study group before and after TIPS placement and in the control subjects. At 3 cm above the LES, the amplitude of esophageal contraction after TIPS placement was significantly higher than that before TIPS placement. At 3 and 8 cm above the LES, the amplitude of esophageal contraction in the control subjects was significantly higher than that in the study group before and after TIPS placement. Esophageal acid exposure time after TIPS placement was similar to that in the controls. TIPS placement is a useful treatment that improves esophageal motor function without the occurrence of pathologic gastroesophageal reflux.

Esophageal and Gastric Varices↗

PubMed1998

Inhibitory action of spinorphin, an endogenous regulator of enkephalin-degrading enzymes, on carrageenan-induced polymorphonuclear neutrophil accumulation in mouse air-pouches.

Whether spinorphin, an endogenous regulator of enkephalin-degrading enzymes, plays a role in an anti-inflammatory action was examined, using a mouse air-pouch assay as a model of acute inflammation. Repeated intravenous administration (6 times) of spinorphin every hour significantly suppressed carrageenan-induced polymorphonuclear neutrophil (PMN) accumulation, an indicator of inflammation (3.21+/-0.95 x 10[6] cells vs 8.92+/-0.96 x 10[6] cells, 10mg/kg spinorphin-treated vs saline-treated group, n=5, P<0.01) at 6 hr. The combination of spinorphin and leuhistin (2 mg/kg, i.v.), a specific inhibitor of aminopeptidase N (APN), markedly suppressed the PMN accumulation induced by carrageenan (1.11+/-0.17 x 10[6] cells, 88% inhibition compared to the saline-treated group, n=5, P<0.01). This inhibition was less than, but comparable to that of dexamethasone (30 mg/kg/one shot, i. v.), a representative anti-inflammatory drug. These results indicate that spinorphin may be an endogenous anti-inflammatory regulator, its inhibitory activity being modulated by APN.

Aminopeptidases↗

PubMed1998

CYFRA 21-1, a cytokeratin subunit 19 fragment, in bronchoalveolar lavage fluid from patients with interstitial lung disease.

1. It has been suggested that CYFRA21-1, a cytokeratin subunit 19 fragment, is potentially useful for diagnosis and monitoring of lung carcinoma. However, serum levels of CYFRA21-1 are also increased in a high proportion of patients with interstitial lung disease. In this study we measured CYFRA21-1 levels in bronchoalveolar lavage fluid from 10 normal subjects, 18 patients with idiopathic pulmonary fibrosis and 14 patients with sarcoidosis, and determined whether any relationship exists between CYFRA21-1 levels in bronchoalveolar lavage fluid and clinical parameters. 2. CYFRA21-1 levels in bronchoalveolar lavage fluid were significantly higher in patients with sarcoidosis (mean value 8.3 ng/ml, P < 0.01) and idiopathic pulmonary fibrosis (42.5 ng/ml, P < 0.005) than in normal controls (1.0 ng/ml). Moreover, higher CYFRA21-1 levels in bronchoalveolar lavage fluid were found in sarcoidosis patients in radiological stage 2 or 3 than in those in stage 1. In patients with idiopathic pulmonary fibrosis, there was a significant correlation between CYFRA21-1 levels, and percentage of inflammatory cells in bronchoalveolar lavage fluid (r = 0.56, P < 0.05) and the magnitude of the alveolar--arterial oxygen pressure difference [P(A-a)O2] gradient (r = 0.66, P < 0.01). 3. Serial bronchoalveolar lavage samples were obtained from six patients with clinically active pneumonitis after they had undergone systemic corticosteroid therapy. CYFRA21-1 levels were significantly lower after these patients exhibited clinical improvement (P < 0.05). 4. These findings suggest that the level of CYFRA21-1 in bronchoalveolar lavage fluid is a useful marker for the clinical diagnosis of pneumonitis, and is also adequate for the evaluation of disease activity, especially over the course of treatment.

Adrenal Cortex Hormones↗

PubMed1998

Increased production of endogenous nitric oxide in patients with bronchial asthma and chronic obstructive pulmonary disease.

BACKGROUND: Nitric oxide (NO) plays an important role as an inflammatory mediator in the airways. Though direct measurement of endogenous NO has been difficult in humans, we have recently found that measurement of NO derivatives in induced sputum may be useful for assessing airway inflammation in asthmatic patients. OBJECTIVE: This study was designed to determine the direct in vivo evidence of increased production of endogenous NO in patients with bronchial asthma and chronic obstructive pulmonary disease (COPD). METHODS: We have investigated simultaneous assessment of NO using two non-invasive methods, such as NO level in exhaled air and induced sputum, in these patients. We determined the concentration of stable end-products of NO (nitrite plus nitrate) in induced sputum and exhaled NO concentration using a chemiluminescence analyser in 10 normal controls, 10 asthmatic patients and 11 patients with COPD, and evaluated whether endogenous NO levels correlate with percentage of neutrophils and interleukin-8 (IL-8) level in induced sputum in patients with COPD. RESULTS: We found significantly higher concentrations of exhaled NO in patients with bronchial asthma (25.1 [5.1] p.p.b.) than in patients with COPD (12.1 [1.9] p.p.b.) and normal controls (5.2 [1.4] p.p.b.). However, higher concentrations of NO derivatives in induced sputum were found in patients with bronchial asthma (1190 [106] micromol/L) and COPD (950 [105] micromol/L) than in normal controls (514 [30] micromol/L). In patients with asthma, but not in those with COPD, concentrations of NO derivatives in induced sputum were significantly correlated with concentrations of exhaled NO (r = 0.64, P < 0.05). Moreover, in patients with COPD, concentrations of NO derivatives in induced sputum were significantly correlated with percentage of neutrophils (r = 0.71, P < 0.05) and IL-8 level (r = 0.80, P < 0.01). CONCLUSION: We conclude the increased production of endogenous NO in patients with asthma and COPD, and that NO derivatives in induced sputum are more valuable than exhaled NO in assessing airway inflammation in patients with COPD.

Adult↗

PubMed1998

Severity of exercise-induced bronchoconstriction is related to airway eosinophilic inflammation in patients with asthma.

Exercise-induced bronchoconstriction (EIB) is widely prevalent in asthmatic patients. Eosinophilic airway inflammation is considered to be a major factor in the pathogenesis of asthma. However, the effects of eosinophilic airway inflammation on EIB have been elucidated insufficiently. To examine the relationship between the severity of EIB and eosinophilic inflammation, sputum induction and exercise challenge were performed in 21 asthmatic patients. Significantly higher percentages of eosinophils and levels of eosinophil cationic protein (ECP) were found in induced sputum in EIB-positive asthmatics (median (range), eosinophils: 23.5 (11.0-61.0)%; ECP: 1,475 (74.8-17,701) ng x mL(-1)) than in EIB-negative asthmatics (eosinophils: 6.0 (1.0-41.5)% (p=0.006); ECP: 270.6 (10.8-7,700) ng x mL(-1) (p=0.049)). There was a significant correlation between the severity of EIB and the sputum eosinophil percentage (r=0.59, p=0.009) and the level of ECP (r=0.47, p=0.037). The area under the curve of the forced expiratory volume in one second for 30 min after exercise correlated with the percentage of eosinophils (r=0.60, p=0.008) and the level of ECP (r=0.45, p=0.04). There was no correlation between airway responsiveness to methacholine on the one hand and EIB, sputum eosinophils or ECP on the other. In conclusion, these results provide evidence that the severity of bronchoconstriction evoked by exercise is more closely related to eosinophilic airway inflammation than airway hyperresponsiveness to methacholine in asthmatic patients.

Adolescent↗

PubMed1998

Subthreshold concentration of endothelin-1-enhanced, capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs.

An increasing number of studies have been performed to address a possible role for endothelin-1 (ET-1) as a significant mediator in asthma. However, the effects of subthreshold concentrations of ET-1, which cannot elicit bronchial smooth muscle contraction itself, in asthma has yet to be determined. This study determined these effects of ET-1 on capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs. Aerosolized ET-1 administered at doses of 10(-9) M and higher induced a dose-dependent increase in pulmonary resistance, but ET-1 at 10(-10) M did not have any bronchoconstrictive effect. However, this subthreshold concentration of ET-1 potentiated capsaicin-induced bronchoconstriction. In addition, the potentiation of capsaicin-induced bronchoconstriction by this subthreshold concentration of ET-1 was completely abolished by BQ788 (ET(B) receptor antagonist), but not BQ123 (ET(A) receptor antagonists). Immunoreactive substance P (SP) levels in bronchoalveolar lavage fluid after capsaicin administration were significantly higher than those after solvent administration. However, ET-1 alone did not significantly stimulate immunoreactive SP release and ET-1 (10(-10) M) did not potentiate capsaicin-induced immunoreactive SP release. In contrast, ET-1 (10(-10) M) potentiated exogenous neurokinin A- and SP-induced bronchoconstriction. These findings suggest that a subthreshold concentration of endothelin-1 does not potentiate the tachykinin release induced by capsaicin but the airway smooth muscle contraction through endothelin-B receptors.

Aerosols↗

PubMed1998

pH-dependent growth retardation of Escherichia coli caused by overproduction of Na+/H+ antiporter.

The overproduction of Na+/H+ antiporter NhaA in Escherichia coli caused growth retardation. Quantities and the activity of the antiporter were studied for their causative roles in terms of this retardation. We constructed a series of nhaA-expression plasmids differing in their transcriptional and translational efficiencies. Low-level nhaA expression complemented the defect of an nhaA mutant and allowed the mutant to survive on a high-NaCl or high-LiCl medium. However, when the production of NhaA was strongly induced by the combination of a stronger promoter, an efficient translational initiation signal and a high copy number plasmid, the growth of the cells carrying the plasmid was severely retarded. This growth retardation correlated well with the amount of NhaA protein produced from the plasmids. Surprisingly, the growth retardation caused by overproduction of NhaA was enhanced more extensively at an alkaline pH than at a neutral pH, in which the antiporter activity was stimulated. However, these retardations were also observed for mutant NhaA antiporters without the activity. These results indicated that the growth retardation was due to an overproduction of the antiporter rather than its increased antiporter activity, and also affected by a pH-dependent change in NhaA, possibly its structural change.

Cell Division↗

PubMed1998

An autopsy case of peripheral neuroepithelioma in posterior mediastinum with p53 point mutation.

An 18-year old male was admitted to our hospital complaining of back pain. His chest computed tomography showed a tumor in the posterior mediastinum. Open biopsy was performed, and a diagnosis of peripheral neuroepithelioma was made. No genetic abnormalities were detected in the DNA obtained from the biopsy specimen. He received chemotherapy and radiation several times. These treatment regimens were effective, but he relapsed 14 months later and died of respiratory failure due to tumor growth. Autopsy examination revealed a large tumor which occupied almost the entire right thoracic cavity, but there was no evidence of metastasis to other organs. Chromosomal translocation t(14;17) (q24;p12.2) and point mutation of exon 5 of the p53 gene were detected.

Adolescent↗

PubMed1998

Clinical implication of protein levels of IL-5 in induced sputum in asthmatic patients.

To determine whether protein levels of interleukin-5 (IL-5) in induced sputum reflect the degree of eosinophilic inflammation, we evaluated the role of IL-5 on clinical characteristics in stable asthmatic patients. IL-5 level, differential eosinophil count, and level of eosinophil cationic protein (ECP) in induced sputum were all significantly higher for asthmatics than for normal controls. Both eosinophil counts and ECP levels in induced sputum were inversely correlated with the degree of airflow limitation (FEV1/FVC). In addition, patients with measurable IL-5 in sputum had significantly more eosinophils, higher levels of ECP in sputum, and lower FEV1 (percent predicted) than did patients with levels of IL-5 beneath the limit of detection. However, we found no significant difference in IL-5 levels between atopic and nonatopic asthmatics. IL-5 level in induced sputum is a good indicator of eosinophilic inflammation in atopic and nonatopic asthmatic patients.

Adult↗