Biomedical subjects

M Munakata

Publications and source records attributed to M Munakata.

At least 73 records · Page 4Linked to original sources

PubMed1998

Serum and bronchoalveolar fluid KL-6 levels in patients with pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a disease characterized by the filling of alveolar spaces with periodic acid-Schiff-positive proteinaceous material and by the hypertrophy of type II pneumocytes in the alveolar interstitium. To examine if KL-6, a mucinlike glycoprotein, is useful for the diagnosis of PAP and the estimation of its activity, serum KL-6 levels in patients with PAP were measured by an enzyme-linked immunosorbent assay and compared with those of patients with other lung diseases. Furthermore, to estimate the origin of KL-6 in some patients, measurements of KL-6 levels in bronchoalveolar lavage (BAL) fluid and immunohistochemical staining of the lung tissues with a monoclonal antibody to KL-6 antigen were performed. Serum KL-6 levels in patients with PAP were extremely high and were significantly higher than those in patients with interstitial lung diseases in which elevation of serum KL-6 has been recognized. BAL-fluid KL-6 levels in patients with PAP were higher than serum levels. Both serum and BAL-fluid KL-6 levels in patients with PAP correlated well with the disease activity. Immunohistochemically, positive staining was observed in proliferating type II pneumocytes. These results suggest the usefulness of KL-6 measurement in the diagnosis and estimation of disease activity of PAP.

Antibodies, Monoclonal↗

PubMed1997

Effects of benzodiazepine receptor agonists in neurones acutely dissociated from the rat neostriatum.

To understand the properties of benzodiazepine receptor in the neostriatum, we examined the potentiating effects of diazepam, triazolam and brotizolam on the GABA(A) receptor-mediated Cl- current in dissociated rat neostriatal neurones using the nystatin-perforated patch recording configuration. Neurones were classified into large and small neurones, on their somatic size. In the large neurones, which are putative cholinergic interneurones, all the benzodiazepine receptor agonists recognized a single effective site. However, in the small neurones, which are mostly considered to be projecting neurones, the effect of brotizolam was best described when two effective sites were assumed. Therefore, the properties of benzodiazepine receptor differed among large and small neurones while at least two kinds of functional binding sites were also found to exist in small neurones.

Animals↗

PubMed1997

Circadian blood pressure rhythm in patients with higher and lower spinal cord injury: simultaneous evaluation of autonomic nervous activity and physical activity.

OBJECTIVE: To examine the relationships among the circadian rhythms of blood pressure, autonomic nervous function, and physical activity of patients with varying levels of spinal cord injury. DESIGN AND METHODS: We studied 19 patients with spinal cord injury [10 tetraplegic patients with cervical cord injury (C4-C7), and nine paraplegic patients with thoracic cord injury (Th6-Th12)] compared with 16 control subjects. A new multibiomedical recorder was used to measure blood pressure (every 30 min), cardiac vagal activity (hourly frequency of R-R50), and physical activity (integrated acceleration/min) for 24 h under hospital conditions. Systemic sympathetic nervous activity and sympathoadrenal functioning were assessed by examination of hormone levels in the blood. RESULTS: Daytime and night-time values were compared; the variations in systolic and diastolic blood pressures and heart rate were slight in members of the tetraplegia group, but almost normal differences were observed in members of the paraplegia group. The circadian profile of cardiac vagal activity was normal for both patient groups, suggesting that an alteration in the sympathetic nervous rhythm had occurred in the tetraplegic patients. The plasma norepinephrine level was lower in members of the tetraplegia group than it was in members of the control group (P< 0.001), but was normal in members of the paraplegia group. The plasma level of epinephrine was lower in members of the tetraplegia (P< 0.05) and the paraplegia (P < 0.1) groups than it was in members of the control group. Daytime physical activity of members of both groups of patients was lower than that of subjects in the control group (P< 0.001 for both). CONCLUSION: The central sympathoexcitatory pathway to the upper thoracic cord plays a critical role in the maintenance of normal circadian blood pressure rhythm in humans. Motor nerve functioning and sympathoadrenal secretion are not essential to this regulation.

Adolescent↗

PubMed1997

Genetic factors in lung disease: atopy and bronchial asthma.

Atopy defined as high IgE responsiveness has now been subject to genetic studies at the molecular level owing to the development of a great number of DNA markers over the human genome. Either by linkage analysis or by association study strong candidate genes of atopy have been proposed to be located on chromosome 11q13 and 5q31 where high-affinity IgE Fc receptor beta subunit and allergy-associated cytokines, respectively, have been mapped. Meanwhile, we found a novel association between one of alleles of D11S97, an anonymous DNA marker on 11q13, and high total serum IgE in a large number of Japanese general population and atopic family members. However, failure to replicate linkage or association studies by different investigators suggest polygenic nature of atopy. In addition to the genes regulating IgE synthesis, the requirement of local (pulmonary) genetic factors in the development of bronchial asthma have been speculated. Linkage analysis suggested possible existence of gene(s) regulating susceptibility and/or clinical characteristics of bronchial asthma also on chromosome 5q. One of the candidate is beta 2-adrenergic receptor gene polymorphism. Mutated gene transfection studies suggested functional significance of some polymorphisms and clinical evaluations have revealed their contribution to airway responsiveness and severity of asthma.

Asthma↗

PubMed1997

Genetic factors in lung disease. Part II: Lung cancer and angiotensin converting enzyme gene.

The recent progress in molecular biology has led to the elucidation of pathogenesis of lung cancer. The development of a lung cancer requires multiple genetic changes, consisting of the activation of oncogenes, including the K-ras and myc genes, and of inactivation of tumour suppressor genes, including the Rb, p53 and CDKN2 genes. Knowing the specific genes undergoing such changes should be useful as biomarkers for the early detection of cells destined to become malignant. Moreover, such genetic changes could be targets of newly designed drugs and gene-based therapy. Although the angiotensin I-converting enzyme was originally discovered in equine plasma, it has been recognized in various organs and cells other than vascular endothelial cells. This enzyme is also known to have wide substrate specificity to many peptides. The definite roles of angiotensin converting enzyme (ACE) in the respiratory system are largely unknown. Recent progress in molecular biology of the ACE, however, gives us a good chance to look over the significance of ACE in respiratory diseases as well as cardiovascular disorders. In this review, we show the recent advances in the basic studies of the ACE and refer to its clinical application.

Gene Expression Regulation, Neoplastic↗

PubMed1997

Pulmonary dysanapsis, methacholine airway responsiveness and sensitization to airborne antigen.

Whether the disproportional growth of airways relative to lung parenchyma (dysanapsis) has any relationship to the development of non-specific bronchial hyperresponsiveness and atopy was investigated in 45 family members of the patients with atopic asthma. As indices of pulmonary dysanapsis, forced expiratory flow25-75/forced vital capacity (FEF25-75/FVC) and the tracheal cross sectional area divided by the forced expiratory volume (X-SA/FVC) were examined. As an index of non-specific airway responsiveness, the cumulative dose of inhaled methacholine needed to induce 35% reduction of respiratory conductance (PD35) was determined by continuous respiratory resistance measurement. For examination of atopy, skin prick tests were conducted, and total serum IgE and IgE specific to common inhaled antigens were measured. FEF25-75/FVC showed no significant correlation to FVC but showed a significant correlation to log(PD35). When the analysis was done in the subjects whose FEV1/FVC was more than 0.8, FEF25-75/FVC showed a significant negative correlation to FVC but lost its correlation to log(PD35). X-SA/FVC showed a significant negative correlation to FVC but had no significant correlation to log(PD35). These relations were conserved when the analysis was done in subjects without airway obstruction. In addition, FEV1/FVC had a significant correlation to log(PD35) and FEF25-75/FVC. However, subjects who had a positive IgE(MAST) had a significantly smaller X-SA/FVC than those with a negative IgE(MAST) (0.60 +/- 0.14[SD] and 0.72 +/- 0.18, respectively, P < 0.02). These results suggest that although pulmonary dysanapsis does not have a significant relation to airway responsiveness to inhaled methacholine, it may be associated with sensitization to airborne antigens.

Adolescent↗

PubMed1997

Association of progressive systemic sclerosis with pulmonary sarcoidosis. Just a chance occurrence?

A 46-year-old Japanese woman has been followed up for 3 years due to interstitial pneumonia associated with progressive systemic sclerosis (PSS). During this follow-up period, chest roentgenogram revealed additional diffuse nodular shadows. She was diagnosed as having pulmonary sarcoidosis, which was confirmed by the presence of epitheloid granulomas within the alveolar septa. She was successfully treated with corticosteroids and recovered almost completely without worsening pulmonary abnormalities caused by her PSS. The independent clinical courses of these two diseases in the present case suggest that the complication of PSS and sarcoidosis in this patient may be coincidental.

Adrenal Cortex Hormones↗

PubMed1997

Vasodepressor effects of exercise are accompanied by reduced circulating ouabainlike immunoreactivity and normalization of nitric oxide synthesis.

Our object was to evaluate the effects of regular mild exercise on blood pressure and on circulating level of ouabainlike factors (OLF) and of nitrate anion, an endproduct of nitric oxide (NO) in humans. We measured plasma ouabainlike immunoreactivity (OLI) and nitrate ions (NO3.) before and after mild exercise for 3 months' duration in 16 patients with essential hypertension, diabetes mellitus, obesity, or hyperlipidemia. Plasma OLI was measured using an amplified ELISA system with anti-ouabain antibody and biotinyl-tyramide. Serum NO3. was measured with high-performance liquid chromatography (HPLC) with an anion-exchange column. With the reverse phase HPLC system with an octa decylsilyl silicagel column, the elution volume of plasma OLI of a healthy volunteer matched that of authentic ouabain in a gradient elution system of acetonitrile/H2O. Plasma OLI levels decreased significantly by about 34% after mild exercise, and NO3. levels tended to be within the reference interval in normal volunteers. Body weight, diastolic and systolic blood pressure, serum triglyceride and acetylcholine esterase (a marker of the fatty liver) were significantly decreased (p < 0.01) after 3 months of regular mild exercise. The plasma OLI level was significantly correlated with plasma NO3., there was a trend toward a correlation with diastolic blood pressure (p = 0.06) before and after regular exercise. Regular mild exercise led to a decrease in plasma levels of OLI, and acetylcholine esterase activity and blood pressure in adult patients. Results suggest that changes in OLF production contribute to the blood pressure regulation seen in patients who exercise regularly.

Adult↗

PubMed1997

[Effects of corticosteroid pulse treatment on outcomes in acute exacerbations of idiopathic interstitial pneumonia].

We studied the relationship between the effectiveness of corticosteroid pulse treatment, clinical characteristics and outcomes in 17 patients with acute exacerbatin of idiopathic interstitial pneumonia. Acute exacerbation was defined as a decrease in PaO2 by more than 10 Torr, worsening of chest-radiographic findings, and deterioration of symptoms within 1 month. Effects of corticosteroid pulse treatment were judged 2 weeks and 3 months after the end of treatment. The change in AaD2 was computed and was used to determine whether the treatment had been effective, temporarily effective, or ineffective. The effects at three months were difficult to predict on the basis of those at two weeks. The treatment was often effective in patients who had not previously received steroids and in those with mild disease. Those in whom the treatment was effective at three months lived longer after the exacerbation than did those in whom it was ineffective, but the average lengths of survival through the whole clinical course were not significantly different among the three groups. We suggest that corticosteroid pulse treatment is effective in acute exacerbatins of idiopathic interstitial pneumonia and that effectiveness should be evaluated three months after treatment.

Acute Disease↗

PubMed1997

[Pulmonary infiltration with eosinophilia due to rabbit-fur antigen: diagnosis by allergen inhalation test].

We report the case of a 48-year-old man with asthma and pulmonary eosinophilia. He presented with coughing, dyspnea, and wheezing that began 6 months after he began keeping a rabbit in his house. He was referred to our department for further examination of pulmonary infiltrative shadows. An inhalation test with rabbit-fur antigen induced both immediate and late asthmatic responses. In addition, infiltrative shadows appeared in the right segments 2, 8, and 9 on chest CT films after the antigen inhalation. Examination of fluid obtained by bronchoalveolar lavage from the right S9 showed an increase in the fraction of eosinophils. Examination of a specimen obtained by transbronchial lung biopsy from those segments revealed infiltration of inflammatory cells into the alveolar septa and alveolar spaces, which was consistent with eosinophilic pneumonia. Our diagnosis was asthma and pulmonary eosinophilia due to rabbit-fur antigen.

Allergens↗

PubMed1997

[Preoperative evaluation of the right ventricular function using the pulsed Doppler echocardiogram in the patients scheduled for the elective pulmonary resection].

Preoperative evaluation of the both right ventricular (RV) systolic and diastolic function using the pulsed Doppler echocardiogram were examined for 46 patients scheduled for the pulmonary resection of the pulmonary tumorous lesions. The parameters which included the RV inflow pattern at the tricuspid orifice and the RV ejection flow pattern at the RV outflow tract were obtained by the pulsed Doppler echocardiogram. Following results were obtained. 1) The RV afterload shown by the parameters of the acceleration time (AT, time beginning of RV ejection to peak velocity) were higher in the aged patients, the low FEV 1% populations, and the patients having the deteriorated left ventricular contraction. 2) The RV diastolic dysfunction were present preoperatively in aged patients over the 60 years old. This phenomenon was characterized by a high degree of atrial contraction and an increased ratio of the peak velocity in atrial contraction phase to that in early rapid filling phase (A/E). When we evaluate the RV inflow and ejection Doppler flow patterns after the major lung resection, these findings must be considerable thing.

Adolescent↗

PubMed1997

[Measurement of plaque volume using three-dimensional intravascular ultrasound: in vitro study].

The usefulness of three-dimensional echocardiography using intravascular ultrasound (3D-IVUS) for the measurement of plaque volume was evaluated by comparing plaque volume derived from 3D-IVUS with that directly measured in 10 autopsied iliac or femoral plaque models (5-15 mm long). Using IVUS (3.5 F, 30 MHz), sequential cross-sectional images for three-dimensional datasets were acquired with a motorized catheter pullback device connected to the three-dimensional reconstruction system. Three-dimensional reconstruction was performed from the sum of the two-dimensional cross-sectional views. Plaque volumes were calculated using a summation of disks algorithm based on the reconstructed multiple short-axis cross-sections from the three-dimensional data. Three-dimensional IVUS demonstrated a good correlation with direct measurement of plaque volume (y = 0.71x + 0.001, r = 0.80, SEE = 0.003 ml), so is useful for the measurement of plaque volumes in the experimental models.

Arteriosclerosis↗

PubMed1996

Nitrooxy alkyl apovincaminate modulates GABA(A) receptor in rat neocortical neurones.

We investigated the effects of VA-045 ((+)-eburnamenine-14 carboxylic acid (2-nitroxyethyl) ester) on GABA(A) receptor-mediated Cl- currents in dissociated rat cerebral cortical neurones, using a nystatin-perforated patch recording configuration. At a holding potential of - 40mV, the external application of GABA evoked an inward Cl- current with an EC50 value of 5.6 x 10(-6)M. VA-045 increased the GABA response at GABA concentrations below 3.0 x 10(-6)M. The GABA response showed a time dependent decay consisting of fast and slow components and VA-045 significantly accelerated both components. The site of action for VA-045 was considered to be different from that for benzodiazepines or barbiturates.

Animals↗

PubMed1996

Mechanisms of epidermal growth factor-induced contraction of guinea pig airways.

We investigated the functional effects of epidermal growth factor (EGF) on guinea pig airways in vitro. EGF (3 ng/ml to 1 microgram/ml) induced a concentration-dependent contraction in epithelium-denuded strips. The average maximal contraction was 0.64 +/- 0.1 g (mean +/- S.E., for n = 27), which was 72.0 +/- 9.5% of the 100 mM KCl-induced contraction. The EC50 was 12.3 +/- 1.6 ng/ml. The presence of the epithelium significantly suppressed the EGF-induced contraction (P < 0.01). EGF-induced contraction was abolished by cyclooxygenase inhibitors (indomethacin and ibuprofen) and a 5-lipoxygenase inhibitor, 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benz oqu inone (AA-861). It was also inhibited by a leukotriene-receptor antagonist, 8-[p-(4-phenylbutyloxy)benzoyl]amino-2-(tetrazol-5-yl)-4-oxo -4H-1-benzopyran hemihydrate (ONO-1078) but not affected by a thromboxane A2-synthetase inhibitor, (E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid (OKY-046) or a thromboxane A2-receptor antagonist, 9,11-epithio-11,12-methano-thromboxane A2 (ONO-3708). A phospholipase A2 inhibitor (mepacrine) inhibited the EGF-induced contraction but a diacylglycerol-lipase inhibitor, 1,6-di-(O-(carbamoyl)cyclohexanone oxime)hexane (U-57908) and a phospholipase D inhibitor (wortmannin) did not affect it. A tyrosine kinase inhibitor (genistein) abolished it. Measurement of prostanoids showed that EGF (300 ng/ml) did not increase the prostaglandin F2 alpha level in either epithelium-intact or epithelium-denuded strips. In epithelium-intact strips, EGF significantly increased the prostaglandin E2 concentration (P < 0.01). These results suggest that EGF causes contraction of guinea pig airway smooth muscle by activating tyrosine kinase followed by phospholipase A2 activation, and that arachidonic acid metabolites, especially leukotrienes, may have important roles in this contraction.

Animals↗

PubMed1996

Pulmonary fibrosis in a carpenter with long-lasting exposure to fiberglass.

A 56-year-old male carpenter had a history of glass fiber inhalation for 41 years without any protective device. His chest radiograph showed small nodular opacities in lower lung fields and multiple cystic lesions and low attenuation areas in upper lung fields. Light and polarizing microscopic examinations of his transbronchial lung biopsy specimen revealed mild interstitial fibrosis and mononuclear cell infiltration in alveolar walls without birefringent substances. However, widespread depositions of small glass fibers (< 2.5 microns in length and 0.3 micron in diameter) were detected by analytical electron microscopy, which suggested their possible contribution to the development of his pulmonary fibrosis.

Glass↗

PubMed1996

Seasonal variation in blood pressure in normotensive women studied by home measurements.

1. The factors influencing the seasonal variation in blood pressure measured at home in normotensive women were examined. 2. Sixteen female subjects (56.3 +/- 7.9 years old, mean +/- SD) measured their blood pressure and pulse rate at home each morning for more than 20 times per month for at least 1.5 years. Blood pressure and body weight were also determined in the office once or twice a month in that period. Monthly means of outdoor and indoor temperatures and daytime length were obtained from the Meteorological Observatory. The single cosinor method was used to evaluate circannual rhythm. 3. We observed a biphasic seasonal variation in self-recorded blood pressure measured at home, environmental temperature and daytime length but found no apparent seasonal variation in body weight and blood pressure measured in the office. The lowest levels of systolic and diastolic blood pressure measured at home were observed in July. The longest daytime length was recorded in June, while the highest outdoor temperature and indoor temperature were recorded in August, indicating that the longest daytime length preceded and the highest environmental temperature lagged behind the lowest level of blood pressure. The shortest daytime length is in December. The lowest outdoor and indoor temperature were observed in January, while the highest levels of self-recorded systolic blood pressure and diastolic blood pressure were in January and December, respectively. Half-amplitudes of self-recorded systolic and diastolic blood pressure were 2.6 +/- 1.0 mmHg and 2.0 +/- 0.8 mmHg, respectively. 4. These findings indicate the importance of a seasonal effect, i.e. daytime length and the environmental temperature, on the blood pressure of individuals.

Adult↗

PubMed1996

Interleukin-1 beta decreases sensitivity of guinea-pig airway to potassium chloride and isoproterenol by an epithelium-dependent mechanism.

Airway inflammation may cause alteration of airway responses in chronic airway diseases, such as bronchial asthma. The objective of this study was to examine whether interleukin-1beta (IL-1beta) [corrected], one of the pro-inflammatory cytokines, has a direct effect on airway functions. The effects of IL-1beta on carbachol, KCl and isoproterenol (ISO) responses of isolated guinea-pig tracheal strips were examined by measuring isometric tension in tissue bath. Responses of tracheal strips with or without epithelium to each agonist were compared before and after incubation with IL-1beta (25 ng or 250 ng/mL). Both 1 h and 5 h incubation of the strips with 250 ng/mL IL-1beta significantly decreased the sensitivity not only to KCl (P < 0.05; P < 0.01, respectively), but also to ISO (both P < 0.05) without affecting maximum contraction or relaxation. Response to carbachol was not affected by IL-1beta. Epithelial denudation abolished the effects of IL-1beta on KCl and ISO responses. Indomethacin (2 micromol/L) [corrected] reversed the effects of IL-1beta both on KCl and on ISO. These results suggest that IL-1 beta decreases the sensitivity of airway strips to KCl and ISO, possibly by stimulating prostaglandin production from the airway epithelium [corrected].

Animals↗

PubMed1996

Heterogeneous distribution of benzodiazepine receptors among rat neostriatal neurones.

1. The effects of benzodiazepine receptor (BZR) agonist were investigated in dissociated rat neostriatal neurones by a conventional whole-cell patch recording configuration at room temperature. 2. The dissociated neurones, with a longest somatic diameter of larger than 25 microns, were classified as 'large neurones', while those having soma measuring less than 15 microns were described as 'small neurones'. Large neurones were intensely positive for acetylcholinesterase staining, whereas the small ones were not. 3. CL218,872 enhanced the GABA response in both the large and small neurones with similar EC50S. However, the potentiation efficacy of CL218,872 in large neurones was larger than that of small ones. 4. Zolpidem also potentiated the GABA response in both neuronal populations with similar EC50S. This compound also enhanced the GABA response more strongly in large neurones than in small ones. 5. Zopiclone exerted a prominent potentiation in large neurones, although no difference was seen in the EC50S in the large and small neurones. 6. It was concluded that the BZR in large neurones had a different pharmacological property from that in small ones and that the BZR agonists showed a prominent difference, not in EC50, but in the potentiation efficacy between these neuronal populations.

Animals↗