Peripheral chemoreceptor activity on exercise-induced hyperpnea in human.
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Biomedical subjects
Publications and source records attributed to Hitoshi Nakano.
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To determine if doxapram stimulates the carotid body through the same mechanism as hypoxia, we compared the effects of doxapram and hypoxia on isolated-perfused carotid bodies in rabbits. Doxapram stimulated the carotid body in a dose-dependent manner. In Ca(2+)-free solution, neither doxapram nor hypoxia stimulated the carotid body. Although, doxapram had an additive effect on the carotid body chemosensory response to hypercapnia, a synergistic effect was not observed. Also, we investigated the various K(+) channel activators on the response to doxapram and hypoxia: pinacidil and levcromakalim as ATP-sensitive K(+) channel activators; NS-1619 as a Ca(2+)-sensitive K(+) channel activator; and halothane as a TASK-like background K(+) channel activator. The hypoxic response was partially reduced by halothane only, while pinacidil, levcromakalim and NS-1619 had no effect. Interestingly, the effect of doxapram was partially inhibited by NS-1619. Neither pinacidil nor levcromakalim affected the stimulatory effect of doxapram. We conclude that doxapram stimulates the carotid body via a different mechanism than hypoxic chemotransduction.
OBJECTIVES: The goal of our study was to determine whether altered adenosinergic mechanisms contribute to the depressed ventilatory response observed in obese Zucker rats. RESEARCH METHODS AND PROCEDURES: Eight lean and eight obese Zucker rats were studied at 7 to 8 weeks of age. Ventilation (V(E)) during room air, during 5-minute hypercapnic (7% CO(2), balance O(2)), and during 30-minute sustained hypoxic (10% O(2)) exposures were sequentially measured by the barometric method on three separate occasions after the randomized blinded administration of equal volumes of either saline (control), 8-(p-sulfophenyl)-theophylline (8-PST, 7 mg/kg, peripheral adenosine antagonist), or aminophylline (AMPH, 15 mg/kg, peripheral and central adenosine antagonist). RESULTS: During room air and hypercapnic exposures, AMPH (but not 8-PST) significantly (p < 0.05) increased V(E) in both lean and obese rats. During acute (2 minute) hypoxic exposure, 8-PST (but not AMPH) significantly depressed V(E) in lean rats. In contrast, AMPH (but not 8-PST) selectively increased V(E) in obese rats. During sustained (10 to 30 minutes) hypoxic exposure, neither AMPH nor 8-PST administration altered V(E) in lean rats. In contrast, AMPH (but not 8-PST) selectively increased V(E) during the late response in obese rats. DISCUSSION: Our findings indicate that obese rats possess altered adenosinergic modulation of ventilatory responses to acute and sustained hypoxia in two opposite ways. We conclude that the reduced hypoxic ventilatory response observed in obese Zucker rats is attributed to depressed adenosinergic peripheral excitatory mechanisms and to enhanced adenosinergic central depression mechanisms, both of which contribute to the blunted ventilatory response in obesity.
Exposure to cold is known as a potential exacerbating factor in asthmatics. However, few studies have investigated severity of symptoms during daily life in winter for asthmatics living in northern Hokkaido, the coldest region in Japan. We sent questionnaires to 126 asthmatics living in northern Hokkaido, and obtained answers from 116 patients (52 males, 64 females). Breathing difficulties during cold-air exposure were reported by 62.1% of patients. Furthermore, 19.6% of patients had experienced the need for bronchodilators following cold-air-induced attacks. Limitations to daily life in winter caused by exacerbated asthmatic symptoms were recognized by 48.3% of patients. Asthmatic exacerbation was experienced by 30% of patients in summer (May to August), compared to >35% in winter (September to April). No significant differences in results were noted between atopic and non-atopic patients. Improvements in respiratory symptoms during winter are thus necessary for better quality of life in asthmatics living in cold districts.
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Severe pulmonary hypertension is one of the fetal complications in various connective tissue diseases. We report a case of severe pulmonary hypertension associated with primary Sjögren's syndrome. In a lung biopsy specimen, there were findings of intimal and medial hypertrophy with narrowing vessel lumina and plexiform lesions. Moreover, deposits of immunoglobulin M, immunoglobulin A and complement protein C1q were found in the pulmonary arterial walls. Although pulmonary hypertension was refractory to oral prostacyclin, steroid therapy improved the clinical and hemodynamic conditions. In the present case, the immunological etiology may be related to the mechanisms of pulmonary hypertension associated with Sjögren's syndrome.
PURPOSE: To investigate the epidemiologic relationship between hepatitis C virus (HCV) infection and cataract. SETTING: Yoshida Eye Clinic, Fukuoka, Japan. METHODS: This study included 492 patients with age-related cataract and 2624 controls who had a municipal mass health screening. All subjects were 60 years or older and inhabitants of Chikugo City (population 45000), Fukuoka, Japan. Each subject was serologically tested for HCV using the third-generation enzyme immunoassay. Seropositivity was compared in subgroups consisting of patients by decade; that is 60 to 69 years of age, 70 to 79 years of age, and 80 to 90 years of age. RESULTS: The prevalence of HCV in the cataract group and health-screening (control) group was 18.3% and 7.1%, respectively, in the 60- to -69 year subgroup; 17.8% and 6.6%, respectively, in the 70- to 79-year subgroup; and 15.1% and 3.7%, respectively, in the 80- to 90-year subgroup. In each subgroup, the prevalence of HCV was significantly higher in the cataract group than in the control group (P <.01, chi-square test). In the cataract group, the HCV seropositive and seronegative groups did not differ significantly in the prevalence of hepatitis B virus (P =.548, Fisher exact probability test). CONCLUSIONS: Patients with age-related cataract had significantly higher seropositivity for HCV than an age-matched general population. This suggests that HCV infection may play a role in the development and/or progression of cataract.
To investigate the hypothesis that the impaired respiratory drive noted in morbid obesity was attributable to altered dopaminergic mechanisms acting on peripheral and/or central chemoreflex sensitivity, seven obese and seven lean Zucker rats were studied at 11 wk of age. Ventilation (VE) was measured by the barometric technique during hyperoxic (100% O(2)), normoxic (21% O(2)), hypoxic (10% O(2)), and hypercapnic (7% CO(2)) exposures after the administration of vehicle (control), haloperidol [Hal, 1 mg/kg, a central and peripheral dopamine (Da) receptor antagonist], or domperidone (Dom, 0.5 mg/kg, a peripheral Da receptor antagonist). In both lean and obese rats, Hal increased tidal volume and decreased respiratory frequency during hyperoxia or normoxia, resulting in an unchanged VE. In contrast, Dom did not affect tidal volume, frequency, or VE during hyperoxia or normoxia. During hypoxia, however, VE significantly increased from 1,132 +/- 136 to 1,348 +/- 98 ml. kg(-1). min(-1) (P < 0.01) after the administration of Dom in obese rats, whereas no change was observed in lean rats. Hal significantly decreased VE during hypoxia compared with control in lean but not obese rats. In both lean and obese rats, Hal decreased VE in response to hypercapnia, whereas Dom had no effect. Our major findings suggest that peripheral chemosensitivity to hypoxia in obese Zucker rats is reduced as a result of an increased dopaminergic receptor modulation in the carotid body.
The effects of ambient O(2) tension on epithelial metabolism and nitric oxide (NO) production (VNO) in the nasal airway were examined in nine healthy volunteers. Nasal VNO, O(2) consumption (VO(2)), and CO(2) production (VCO(2)) were measured during normoxia followed by gradual hypoxia from 21 to 0% O(2) concentration. Nasal VO(2), VCO(2), and respiratory quotient during normoxia were determined to be 1.19 +/- 0.04 ml/min, 1.60 +/- 0.04 ml/min, and 1.35 +/- 0.04, respectively. Hypoxia exposure to the nasal cavity significantly decreased both VCO(2) and VNO [VCO(2): 1.60 +/- 0.04 to 0.96 +/- 0.03 ml/min (P < 0.01), VNO: 530 +/- 15 to 336 +/- 9 nl/min (P < 0.01)]. VNO was reduced commensurately with gradual decline in O(2) tension, and the apparent K(m) value for O(2) was determined to be 23.0 microM. These results indicate that the nasal epithelial cells exchange O(2) and CO(2) with ambient air in the course of their metabolism and that nasal epithelial cells can synthesize NO by using ambient O(2) as a substrate. We conclude that air-borne O(2) diffuses into the epithelium where it may be utilized for either cell metabolism or NO synthesis.
Pulmonary sarcoidosis in association with dermatomyositis has rarely been reported. A 52-year-old woman was admitted for evaluation of a previously unrecognized bilateral hilar lymphadenopathy on a chest radiogram in August 1995. She had been receiving oral corticosteroids for dermatomyositis, which was confirmed by the typical skin rash and the myogenic changes on an electromyogram in 1977. She had no respiratory symptoms at the time of admission. Chest computed tomography showed hilar and mediastinal lymphadenopathy with reticular shadows in the peripheral lung parenchyma. A 67gallium-citrate scintigram apparently revealed accumulation in bilateral hilums. The tuberculin skin reaction was negative. Flowcytometry of bronchoalveolar lavage fluid indicated a CD4/CD8 ratio of 5.37. Thoracoscopic biopsy specimens sampled from the mediastinal lymph nodes and the lung demonstrated non-caseating granulomas. A definitive diagnosis of pulmonary sarcoidosis was made from these findings. The chest radiographic findings were spontaneously resolved after three years with no increase in the dosage of oral corticosteroids. It is well known that an abnormal immune response playa an important role in development of dermatomyositis and sarcoidosis. This case suggested close associations in both diseases.
A 58-year-old man, a dairy farmer, was admitted to Engaru Kosei Hospital because of cough, fever and dyspnea following repeated exposure to moldy silage in a silo. Chest radiography showed ground-glass opacity and tiny nodules in both lung fields. Arterial blood gas analysis showed severe hypoxia (PaO2, 30.8 torr). The patient was referred to Asahikawa Medical College Hospital for a diagnostic evaluation. At the time of admission, his symptoms were slightly resolved and the lung density on the chest radiograph was decreased. Pulmonary function tests revealed restrictive ventilatory impairment with a reduction in diffusing capacity. Bronchoscopic examination revealed mild lymphocytosis in the bronchoalveolar lavage fluid (BALF). Neither bacteria nor fungi were cultured from the BALF. Transbronchial lung biopsy specimens showed alveolitis with lymphocyte infiltration. The symptoms and signs disappeared spontaneously without any specific treatment, such as corticosteroids or antibiotics. A provocation test consisting of silage handling elicited recurrence of his symptoms, a decrease in diffusing capacity, and hypoxia. A definitive diagnosis of hypersensitivity pneumonitis (HP) was made from these findings. Samplings from the silage revealed a gross growth of the yeast Saccharomyces cerevisiae. A serum-precipitating antibody gave a positive reaction for an extract of S. cerevisiae. These results suggested that repetitive exposure to S. cerevisiae had led to sensitization through the patient's occupational environment, resulting in the development of HP.