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Biomedical subjects

M Mishima

Publications and source records attributed to M Mishima.

At least 91 records · Page 5Linked to original sources
PubMed1996

A single Drosophila melanogaster myosin light chain kinase gene produces multiple isoforms whose activities are differently regulated.

BACKGROUND: Myosin light chain kinase (MLCK) specifically phosphorylates the myosin regulatory light chain in a calcium/calmodulin (Ca2+/CaM)-dependent manner in animal cells. The roles of MLCK are not fully understood, particularly in nonmuscle cells. Therefore, we cloned and characterized a Drosophila MLCK gene as the first step in a genetic analysis of this process. RESULTS: Four transcripts are produced from this gene. These transcripts encode at least three isoforms (isoform-I, -II and -III), which share a kinase domain, a fibronectin type III motif and an immunoglobulin C2 motif. However, regulatory regions differ between isoform-I/II and -III due to the alternative splicing of the exon encoding a CaM-binding domain. As a result, isoform-I and -II are Ca2+/CaM-dependent forms, whereas isoform-III is a Ca2+/CaM-independent form. Northern blotting and in situ hybridization showed that the expressions of these isoforms are distinctly regulated in stage- and tissue-dependent manners. Isoform-I seems to be expressed ubiquitously, while isoform-III is expressed predominantly in muscle tissues. In contrast to these isoforms, isoform-II is specific to late pupa and adult. CONCLUSION: In Drosophila, a single MLCK gene produces multiple isoforms whose regulatory regions and expression patterns are different. These differences suggest various cellular functions of MLCK in Drosophila.

Amino Acid Sequence↗
PubMed1996

Cell cycle-dependent phosphorylation of smooth muscle myosin light chain in sea urchin egg extracts.

We studied enzymatic activities in sea urchin egg extracts that phosphorylate myosin regulatory light chain (MRLC) from chicken gizzard smooth muscle. The activity in the presence of EGTA showed cell cycle-dependent changes similar to that of histone H1 kinase, namely, it peaked shortly before cleavage, while that in the presence of Ca2+ ions did not show significant change during division cycle. Phosphopeptide mapping revealed that both the sites phosphorylatable by smooth muscle myosin light chain kinase (MLCK sites) and the sites phosphorylatable by protein kinase C (PKC sites) were phosphorylated in the presence or absence of Ca2+ ions. By analyses using an inhibitor of cdc2 kinase, butyrolactone-I, and ion exchange column chromatography, at least three kinases were detected as kinases that phosphorylate MRLC in vitro. These kinases phosphorylated distinct sites on MRLC. The first one, which phosphorylated the PKC sites, was identified as cdc2 kinase. The second one phosphorylated the MLCK sites in the absence of Ca2+ ions. The third one phosphorylated unknown sites. Possible implication of these activities in regulation of cytokinesis is discussed.

4-Butyrolactone↗
PubMed1996

Dose response study of ipratropium bromide aerosol on maximum exercise performance in stable patients with chronic obstructive pulmonary disease.

BACKGROUND: Although the bronchodilating effect of inhaled anticholinergics has been established in patients with chronic obstructive pulmonary disease (COPD), their effects on exercise capacity are still controversial. Previous studies have suggested that the standard dosage hardly affects exercise tolerance, whereas higher doses might elicit an improvement. The aim of the present study was to determine the dose of ipratropium bromide aerosol that improves exercise performance using progressive cycle ergometry in patients with stable COPD. METHODS: Twenty men with stable COPD of mean (SD) age 69.2 (4.6) years and forced expiratory volume in one second (FEV1) 1.00 (0.37) 1 were studied in a randomised double blind manner. Each patient received ipratropium bromide in doses of 240 micrograms, 160 micrograms, 80 micrograms, 40 micrograms, and placebo from a metered dose inhaler (MDI) with an InspirEase spacer on five separate days. Spirometric parameters were assessed before and at 30, 60, 90, and 120 minutes after each inhalation, and pulse rate and blood pressure were also measured immediately before each spirometric measurement. Symptom limited progressive (20 watts/min) cycle ergometer exercise tests were performed 90 minutes after each inhalation. RESULTS: Ipratropium bromide in doses of 160 micrograms and 240 micrograms produced a greater increase in FEV1 than 40 micrograms or 80 micrograms ipratropium bromide at all time points. Doses of 160 micrograms and 240 micrograms ipratropium bromide also produced greater increases in maximal work load and maximal oxygen consumption than placebo, whereas 40 micrograms and 80 micrograms ipratropium bromide did not. There was a weak correlation between the change in FEV1 and the change in maximal work load (r = 0.45). No differences were found in pulse rate or blood pressure between the treatment and placebo groups, and no side effects were noted throughout the study. CONCLUSIONS: A dose of at least four times the standard dose of ipratropium bromide from an MDI with a spacer device was necessary to improve maximal cycle exercise capacity in patients with stable COPD. Although the data from cycle ergometry cannot be directly applied to exercise performed during day to day activities, it is conceivable that the recommended doses of ipratropium bromide do not elicit the optimal clinical benefits.

Aerosols↗
PubMed1996

Assessment of local lung impedance by the alveolar capsule oscillator in dogs: a model analysis.

The alveolar capsule oscillator technique has shown that the response of the lung periphery to intravenous histamine injection in dogs is extremely inhomogeneous both in terms of local peripheral airway resistance (RA) and local peripheral elastance (EA) (M. Mishima, Z Balassy, and J. H. T. Bates. J. Appl. Physiol. 77: 2140-2148, 1994). To assess the physical extent of the local lung region identified by this technique, we performed computer simulations using an asymmetrical branching model of the canine lung proposed by K. Horsfield, W. Kemp, and S. Philips (J. Appl. Physiol. 52: 21-26, 1982). The acoustic impedance of the model from 26 to 200 Hz as seen from the alveolar capsule oscillator was calculated. RA and EA were estimated from the simulated acoustic impedance between 26 and 200 Hz and were found to be 492 hPa.s.l-1 and 156,300 hPa/l, respectively. These values are similar to those found experimentally in previous studies. By simulating data using the model in various stages of completeness, we determined that approximately 50% of RA is determined by the acinus to which the alveolar capsule is attached, whereas the remainder is determined by airways < or = 1 mm diameter that converge on this acinus. By contrast, EA was determined almost entirely (95%) by the acinus directly under the capsule. Inhomogeneous peripheral airway constriction altered RA severalfold but did not affect EA by >5%. This suggests that the previously observed changes induced in EA by bronchial challenge reflect real changes in intrinsic tissue elastance rather than merely regional mechanical inhomogeneities.

Airway Resistance↗
PubMed1996

Inhibitory effect of an intellectual task on breathing after voluntary hyperventilation.

We investigated the effects of an intellectual task on posthyperventilation (PHV) breathing by using a video game. Eight normal subjects were placed in a supine positions. The game task by itself led to increase ventilation compared with the control tasks via an increase in the average inspiratory flow rate (P < 0.01) and the respiratory frequency (P < 0.001). After hypocapnic voluntary hyperventilation (VHV), the task led to a decrease in the 1-min PHV breathing level compared with the control tasks after VHV [after VHV, first 60 s average minute ventilation while watching television and while playing a video game are 5.54 +/- 2.91 (SD) and 2.05 +/- 1.40 l/min, respectively; P < 0.01]. Only one subject showed PHV apnea for at least 10 s during the control protocol, whereas seven of the same eight subjects showed PHV apnea while performing the task. After isocapnic VHV, the task still led to a decrease in PHV breathing compared with the control tasks. However, this decrease was smaller than in the hypocapnic studies and was only significant during the first 15 s of recovery. These results suggest that increased activity in the higher centers of the central nervous system has an inhibitory effect on PHV breathing at a time when the effects of short-term potentiation after VHV, hypocapnia, and perhaps other mechanisms would be expected to be acting on breathing.

Adult↗
PubMed1996

Effects of NCPAP therapy on fibrinogen levels in obstructive sleep apnea syndrome.

In patients with obstructive sleep apnea syndrome (OSAS), the blood coagulation system may contribute to an increased risk of cardiovascular events, which occur most frequently in the morning. Nasal continuous positive airway pressure (NCPAP) treatment can improve the mortality of patients with OSAS. We measured the plasma fibrinogen concentration, which is an independent risk factor for cardiovascular events, in the afternoon (3:30 P.M.) and the next morning upon awakening (8:30 A.M.) in 11 patients with OSAS (apnea and hypopnea index > 20) before and after NCPAP therapy. We also measured the hematocrit, the C-reactive protein, and the total plasma protein at the same time. The plasma fibrinogen and hematocrit levels in the morning (298 +/- 16 mg/dl and 48.5 +/- 1.5%, mean +/- SEM) were significantly higher than on the previous afternoon (275 +/- 14 mg/dl and 46.6 +/- 1.3%) (fibrinogen, p < 0.02; hematocrit, p < 0.005). The whole blood viscosity (WBV) at a shear rate of 208 inverse seconds, which can be predicted based on the hematocrit and total plasma protein, was also significantly higher in the morning (4.98 +/- 0.20/s) than in the afternoon (4.73 +/- 0.17/s) (p < 0.005). These increases in the plasma fibrinogen concentration and the WBV in the morning disappeared after NCPAP treatment. The attenuation of morning increases in the plasma fibrinogen concentration and WBV induced by NCPAP treatment may contribute to an overall improvement in the mortality from cardiovascular events in patients with OSAS.

Adult↗
PubMed1996

Physiologic factors that determine the health-related quality of life in patients with COPD.

STUDY OBJECTIVE: To determine the physiologic factors that influence the health-related quality of life (HRQL) in patients with stable COPD and to identify the factors that most influence HRQL. METHODS: The Nottingham Health Profile (NHP) was used as a general HRQL measure and the Chronic Respiratory Disease Questionnaire (CRQ) was used as a disease-specific HRQL measure to investigate 132 patients with stable COPD, and measurements of HRQL were compared with physiologic measures. RESULTS: Vital capacity, FEV1, the ratio of the FEV1 to the FVC, diffusion capacity for carbon monoxide, diffusion capacity corrected for alveolar volume, lifetime cigarette consumption expressed as pack-years, and age were weakly correlated with several dimensions of both the NHP and the CRQ. Factor analysis reduced these variables to three factors. Two factors mainly referring to airflow limitation and diffusing capacity were weakly correlated with several dimensions of both the NHP and the CRQ. Logistic regression analysis identified 4 independent predictors of HRQL: airflow limitation (odds ratio [OR] = 0.59 to 0.69), diffusing capacity (OR = 0.75 to 0.82), pack-years (OR = 1.20 to 1.23), and age (OR = 2.13). The CRQ was more sensitive to impairment of HRQL than the NHP. CONCLUSIONS: The HRQL of patients with stable COPD is partly determined by airflow limitation, diffusing capacity, pack-years, and age. However, these factors could not predict the whole spectrum of HRQL, and the contribution of these factors to HRQL was limited. Therefore, HRQL should be measured directly in addition to physiologic measures.

Aged↗
PubMed1996

Relationship between dyspnea in daily life and psycho-physiologic state in patients with chronic obstructive pulmonary disease during long-term domiciliary oxygen therapy.

We examined the relationships among dyspnea ratings in daily life, the physiologic state, and anxiety and depression of fifty-two patients with chronic obstructive disease (COPD) during long-term domiciliary oxygen therapy (LTOT). Clinical ratings of dyspnea were assessed by the visual-analog scale (VAS) during eight types of basic behavior in indoor daily life. Analysis of the physiologic state included forced expiratory volume in 1 second (FEV1.0), and arterial blood gas (PaO2, PaCO2) at rest while breathing room air. The hospital anxiety and depression (HAD) scale, which consists of 14 questions, was used to assess the degree of anxiety (HAD-A) and depression (HAD-D). The mean age of the patients was 69.5 +/- 10.8 year (SD), and the duration of LTOT was 944 +/- 739 days. The mean values were 0.77 +/- 0.45 L for FEV1.0, 57.7 +/- 7.4 Torr for PaO2, and 47.4 +/- 8.1 Torr for PaCO2. FEV1.0 was correlated with PaCO2(r = -0.548, p < 0.0001), but it was not correlated with PaO2. High correlation was noted between HAD-A and HAD-D (r = 0.693, P < 0.0001), whereas correlation was not noted between HAD and the physiologic state. VAS was significantly correlated with FEV1.0 (r = 0.320, p < 0.05), as well as with HAD-A (r = 0.358, p < 0.01) and HAD-D (r = 0.444, p < 0.01). Dyspnea ratings were found to be influenced by anxiety and the depression state, and also by the degree of flow limitation in patients with COPD during LTOT. In contrast, the physiologic state scarcely influenced the anxiety and depression state. Thus, psychotherapy may play an important role in the reduction of dyspnea sensation, which is an important determinant of quality of life.

Activities of Daily Living↗
PubMed1996

Partial deficiency of phosphoglycerate mutase with diabetic polyneuropathy: the first Japanese patient.

We report here findings in a 51-year-old Japanese man with non-insulin-dependent diabetes mellitus who complained of exercise-induced cramps. Muscle biopsy showed scattered regenerating fibers, small angular fibers and increased PAS positive particles. Electron microscopic examination revealed an abnormal accumulation of glycogen particles in subsarcolenmmal areas and between myofibrils while chemical studies showed an increased glycogen concentration and decreased phosphoglycerate mutase (PGAM), 46.9% of the normal mean value. Thus, partial PGAM deficiency, insulin resistance and mild diabetic sensory-motor polyneuropathy can induce severe cramps.

Biopsy↗
PubMed1996

Validity of a random noise oscillation and body box system for the measurement of the respiratory impedance of small animals.

The accuracy and validity of a body box system which was developed for the measurement of airway and chest wall impedance in small animals such as canines was evaluated. Input impedance was calibrated using a resistance tube and the mouth flow sensing system was designed to be as symmetrical as possible such that the minimal common mode rejection ratio (CMRR) from 10 to 40 Hz was greater than 60 dB. The validity of this system using the resistance tube and inertant models indicated that the average error ratio for the input impedance and for the flow transfer function between the mouth and chest flow was within 3 and 0.5%, respectively. The location of the box pressure port near to the oscillatory flow inlet was shown to potentially give rise to errors in the measurement of the flow transfer factor due to the direct effects of the inflow. A distance of 60 cm was adopted in the present system, which proved to be sufficient to avoid this effect. It was concluded that the body box system which is described for small animals in the present study is appropriate for obtaining separate and accurate airway and tissue impedance data.

Airway Resistance↗
PubMed1996

Chest flow during the initial inspiratory phase (V0.1) in pulmonary diseased patients.

We measured the chest flow 0.1 s after the onset of the inspiratory phase (V0.1) in patients with chronic pulmonary emphysema (CPE: n = 5), interstitial pneumonitis (IP: n = 5) and normal subjects (Nor: n = 5). The subjects sat in a body box and breathed air from outside of the body box. V0.1 was measured during rest and during maximal breathing (V0.1-rest, V0.1-max) and then these results were compared with P0.1 (P0.1 rest, P0.1-max) values. V0.1-rest was not significantly different between the three groups (Nor: 0.25 +/- 0.10, CPE: 0.27 +/- 0.06, IP: 0.26 +/- 0.06, l/s), whereas the P0.1-rest in IP patients was significantly greater than in normal subjects (Nor: 1.98 +/- 0.61, CPE: 3.00 +/- 0.80, IP: 3.60 +/- 0.68 hPa; P < 0.05 compared with normal). The V0.1-max in CPE and IP patients was significantly lower than in normal subjects (Nor: 3.66 +/- 1.16, CPE: 0.82 +/- 0.25, IP: 1.02 +/- 0.21 l/s, P < 0.05 compared with normal subjects (Nor: 3.66 +/- 1.16, CPE: 0.82 +/- 0.25, IP: 1.02 +/- 0.21 l/s, P < 0.05 compared with normal), whereas P0.1-max in IP patients was not significantly different with in normal subjects (Nor: 33.2 +/- 10.2, CPE: 9.8 +/- 3.7, IP: 19.5 +/- 3.4 hPa, P < 0.05 compared with normal, P < 0.05 compared with CPE). A simulation of the influence of the mechanical properties of the respiratory system on V0.1 and P0.1 using the Runge-Kutta method suggested that V0.1 was negatively affected by airway resistance but positively affected by chest wall and lung compliance. In contrast, the influence of respiratory mechanics on P0.1 was much less than on the V0.1, except for highly decreased lung compliance. In CPE patients, it was suspected that mechanical disorders might not simply be the determining factors of V0.1-max, but that limitations of the neuro-muscular drive due to chest wall deformity may also play a definitive role in the smaller V0.1-max. In contrast, it may be inferred that IP patients had to exert greater inspiratory effort as compared with the other two groups in order to maintain a similar V0.1-rest because of the increased airway resistance and decreased tissue compliance; thus these abnormal mechanical properties suppress the increase in the V0.1-max. It may be concluded that V0.1 is a good index of chest wall acceleration, which is determined by both the neuro-muscular drive and the mechanics of the respiratory system.

Aged↗
PubMed1996

[Temporary use of chest negative pressure ventilation to facilitate closure of a tracheal stoma before domiciliary nasal intermittent positive pressure ventilation].

A 67-year-old patient with pulmonary tuberculosis sequela had undergone a tracheostomy. The patient was receiving nasal intermittent positive pressure ventilation and the stoma failed to close. Temporary use of chest negative pressure ventilation facilitated closure of the stoma and probably shortened the patient's hospital stay. Nasal intermittent positive pressure ventilation at home was begun safely and effectively.

Aged↗
PubMed1995

New design of N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) lung imaging in the patient with lung cancer.

N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) was injected intravenously into primary non small cell lung carcinoma patients (n = 17). The average pixel count ratios of the cancerous area to the whole lung was measured in the initial and delayed images. In the initial image, this ratio was less than 1.0 for the entire group of patients, and was thought to reflect decreased blood flow in the cancerous tissues. The rate of counts within a ROI in the delayed image to counts in the same ROI in the initial image was also calculated and called the remain rate. The remain rate (delayed count/initial count) was significantly higher in the cancerous area than in the whole lung (0.65 +/- 0.30, median 0.62, 0.38 +/- 0.05, median 0.38, p < 0.01). This observation was thought to be due to a relative decrease in the blood flow and the accumulation of IMP, which forms pools within the alveolar spaces of the cancerous areas. The image prepared with the remain rate revealed a hot image in the cancerous regions, even when this was not apparent in the delayed image. The remain rate image may therefore be useful in the identification of cancerous areas in lung tissue if it is used in comparison with the initial image.

Adult↗
PubMed1995

Production of minor lymphocyte stimulatory-1a antigens from T cell subsets.

T cell subsets that produce minor lymphocyte stimulatory (Mls) antigens were analyzed using mixed lymphocyte reaction (MLR) in vitro or clonal elimination assay in vivo. When lymph node T cells from B10.BR(Mls-1b) mice were stimulated with various T cell subsets from AKR (Mls-1a) mice in the presence of B10.BR antigen presenting cells (APC), proportions of Mls-1a reactive T cell blasts (V beta 6+, V beta 8.1+) increased. The stimulatory potency of CD8+ T cells was higher than that of CD4+ T cells. Furthermore, among either CD8+ or CD4+ T cell subset, CD44+ T cells appeared to produce larger amounts of Mls-1a antigens than CD44- T cells. More marked difference was demonstrated, when stimulator AKR T cells were being activated by immobilized anti-T cell antigen receptor (TCR) antibody during MLR. Thus, AKR T cells appeared to produce large amounts of Mls-1a antigens on appropriate stimulations. These findings were confirmed by the semiquantitative analysis of mRNA levels of MTV-7 in the AKR T cell subsets. When CD8+CD44+ T cells from (AKR x B10.BR)F1 mice were injected intravenously into [B10.BR-->B10.BR] syngeneic bone marrow (BM) chimeras 1 week after BM reconstitution and proportions of V beta 6+ T cells were quantitated 7 weeks later, significant clonal elimination of V beta 6+ T cells was induced among both thymocyte population and lymph node T cell population in a dose-dependent manner of the inoculated F1 T cells. Inoculation of CD8+CD44-F1 T cells eliminated V beta 6+ T cells less efficiently from lymph node T cells and inoculation of CD4+F1 T cells induced no significant clonal elimination of the V beta 6+ T cells. The present findings demonstrate clearly that CD8+CD44+ T cells represent the cells producing large amounts of Mls-1a antigens and inducing clonal elimination of V beta 6+ T cells in vivo.

Animals↗
PubMed1995

Measuring the mechanical properties of the lung in vivo with spatial resolution at the acinar level.

The alveolar capsule technique involves measuring subpleural alveolar pressure in the chamber of a plastic capsule glued to the perforated lung surface. However, measurements of alveolar pressure alone do not permit one to say whether the inhomogeneities that develop are due to changes in local lung resistance, elastance, or both. We have developed an extension of the alveolar capsule technique in which small broad-band oscillations in flow are applied through the capsule. At low oscillation frequencies the imposed flows travel all the way through the airway system, so the associated alveolar pressures then reflect the resistance of the pathway from a small local alveolar region out to the tracheal opening. At high frequencies flows propagate only a very short distance into the lung whereupon the dynamic relationship between flow and alveolar pressure gives a measure of local lung elastance. In this paper we show that considerations of canine lung anatomy suggest that the elastic and resistive quantities provided by the capsule oscillator technique pertain to a lung region of the order of a single acinus with its associated terminal bronchioles. This represents a greatly improved spatial resolution of lung mechanics over that which was possible before the development of the alveolar capsule oscillator technique.

Air Pressure↗
PubMed1995

Changes in regional lung impedance after intravenous histamine bolus in dogs: effects of lung volume.

We measured the effect of lung volume on the time course of regional lung input impedance (ZA) after bolus intravenous administration of 2 mg of histamine in seven open-chest dogs using alveolar capsule oscillators. ZA (24-200 Hz) was obtained during apnea at constant lung volume every 2 s for 80 s at lung inflation pressures of 0.1, 0.2, 0.3, 0.5, 0.7, and 1.0 kPa. Local airway resistance (RA) and elastance of the local lung region were calculated by fitting a four-parameter model to the measured ZA. Total lung resistance and lung elastance were also calculated from tracheal pressure and flow measured during mechanical ventilation (0.3 Hz) just before and after each set of ZA measurements. We found the histamine-induced changes in both lung resistance and lung elastance to decrease with increasing lung volume. RA also showed a large negative dependency on lung volume, and the variation between different RA measurements became markedly increased as lung volume decreased. In contrast, local airway elastance was essentially unaffected by lung volume. These results support the idea that parenchymal tethering of the very distal airways impedes their narrowing during bronchoconstriction. They also indicate that reduced parenchymal tethering causes airway narrowing to become markedly more inhomogeneous.

Airway Resistance↗
PubMed1995

Promotion of rectal absorption of sodium ampicillin by disodium glycyrrhetinic acid 3 beta-O-monohemiphthalate in rats.

The promotional effect on rectal absorption of sodium ampicillin (ABPC) by the glycyrrhetinic acid derivative disodium glycyrrhetinic acid 3 beta-O-monohemiphthalate (GA MHPh) was studied in rats and compared with those of sodium caprate (CAP) and sodium glycocholate (GLY). Duration of the promotive effect of GA MHPh was also studied. Rectal absorption of ABPC was significantly enhanced by addition of GA MHPh at an optimum concentration of about 1.5%. The plasma maximum concentration of ABPC was 78.71 micrograms/ml 10 min after its rectal administration at 100 mg/kg with 1.5% GA MHPh. The bioavailability of ABPC with and without 1.5% GA MHPh was 82.12% and 3.92%, respectively. Thus, absorption of ABPC in the presence of 1.5% GA MHPh was about 21 times that of ABPC alone. GA MHPh was more effective as an absorption promoter than either CAP or GLY. Its promoting action on the mucosal membrane was apparent immediately, reached a maximum at 5 min and remained for at least 20 min after rectal administration of the solution. It is therefore suggested that GA MHPh is a very useful promoter absorption of the hydrophilic drug ABPC when administered rectally.

Ampicillin↗