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Biomedical subjects

T Takishima

Publications and source records attributed to T Takishima.

At least 37 records · Page 2Linked to original sources

Submental stimulation and supraglottic resistance during mouth breathing.

We studied submental stimulation on supraglottic resistance (Rsg) in 5 normals and 6 patients with obstructive sleep apnea. We then examined the most effective sites of stimulation in the submental regions, and the relationships between Rsg and stimulation frequency and voltage in the supine position. Inspiratory and expiratory Rsg's were obtained as the slope of the linear portion of the pressure-flow relation determined at zero flow. Before stimulation, inspiratory and expiratory Rsg's were 0.76 +/- 0.06 (means +/- SE) and 0.61 +/- 0.02 cmH2O.L-1.sec, respectively, in normals, and 1.04 +/- 0.20 and 0.92 +/- 0.29 cmH2O.L-1.sec, respectively, in patients. Stimulation in the proximal half submental region with surface electrodes 1 cm apart decreased inspiratory and expiratory Rsg's in patients, and inspiratory Rsg in normals. Inspiratory Rsg measured in this submental region showed a stimulation frequency-and voltage-dependency in both groups, but expiratory Rsg did not. These findings suggest that submental stimulation in the proximal half region widens the supraglottic airway during mouth breathing and probably involves the upper airway muscles.

Adult↗

Potential role of interleukin-1 in allergen-induced late asthmatic reactions in guinea pigs: suppressive effect of interleukin-1 receptor antagonist on late asthmatic reaction.

Interleukin (IL)-1 is a pluripotential proinflammatory cytokine and is thought to be involved in the pathogenesis of bronchial asthma and late asthmatic reactions (LARs). To determine whether IL-1 plays a role in LAR, guinea pigs sensitized with Ascaris antigen were used. We evaluated IL-1 production by immunostaining with anti-IL-1 beta antibody and elucidated the action of IL-1 in LAR with recombinant IL-1 receptor antagonist. Immunostaining revealed that IL-1 beta-like immunoreactivity-positive cells increased in the airway walls and in bronchoalveolar lavage fluid after the antigen challenge. IL-1 receptor antagonist protein pretreatment reduced the generation of LAR in terms of pulmonary resistance. IL-1 receptor antagonist protein pretreatment did not change cellular components but reduced the percentage of hypodense eosinophils in bronchoalveolar lavage fluid. We also studied the direct effect of recombinant human IL-1 beta on pulmonary resistance and eosinophil activity measured as released eosinophil peroxidase activity. Recombinant human IL-1 beta did not change pulmonary resistance but primed eosinophils to release eosinophil peroxidase activity in response to platelet activating factor. Therefore these results suggest that IL-1 was produced in sensitized pulmonary tissue of guinea pigs by allergen exposure and played a role in the generation of LAR, at least partially by modulating the activation of eosinophils.

Animals↗

Localization of histamine N-methyltransferase messenger RNA in human nasal mucosa.

BACKGROUND: Histamine is metabolized mainly by histamine N-methyltransferase (HMT) to N tau-methylhistamine in human nasal mucosa. Human HMT cDNA has been cloned and expressed in COS cells. The purpose of this study was to determine the localization of HMT METHODS: The fragment (nucleotide residues 430-1055) of human HMT cDNA was subcloned in a Bluescript vector (Stratagene, La Jolla, Calif.), and HMT sense anti-sense RNA probes were made with T7 and T3 RNA polymerases. In situ hybridization with digoxigenin-labeled RNA probes was performed on surgical specimens of human nasal turbinates. RESULTS: HMT mRNA was localized in cells in the epithelium and submucosa, and densely in endothelial cells of vessels. No HMT mRNA was identified in the submucosal glands. The presence of HMT mRNA was confirmed by Northern blot analysis, and HMT activities were also detected in nasal mucosa. CONCLUSION: Our study indicates that endothelium expresses HMT mRNA, whereas cells in the epithelium and submucosa, which remain unidentified, are an additional source of HMT mRNA.

Blotting, Northern↗

Large-volume intraoperative peritoneal lavage with an assistant device for treatment of peritonitis caused by blunt traumatic rupture of the small bowel.

The benefits of large-volume intraoperative peritoneal lavage (IOPL), with an assistant lavage device, were evaluated retrospectively in 114 patients with peritonitis caused by blunt traumatic rupture of the small bowel. Postoperative complications caused by infection were a major problem after rupture of the small bowel (46 of 114, 39.4%). Both prolongation of the interval between injury and laparotomy and rupture of the lower part of the small bowel were risk factors for postoperative complications caused by infection. Large-volume IOPL (25.2 +/- 2.1 L) with an assistant lavage device reduced the rate of complications caused by infection from 30 of 58 (51.8%) to 15 of 56 (26.8%). The volume used for IOPL was closely related to the occurrence of postoperative complications resulting from infection. No complications from infection occurred in patients who received lavage with of 28.3 +/- 2.7 L of saline, whereas complications occurred in those patients treated with a smaller volume of lavage fluid (18.0 +/- 2.5 L). Large-volume IOPL should be considered in patients with blunt rupture of the small bowel who are at risk for infection, and the assistant device for IOPL may be useful for such treatment.

Adolescent↗

Hypoglossal nerve stimulation affects the pressure-volume behavior of the upper airway.

To determine the effects of electrical hypoglossal nerve and submental stimulation on upper airway collapsibility, we examined the pressure-volume (P-V) relationships during bilateral supramaximal stimulation of the distal cut hypoglossal nerve ends over a range of frequencies from zero to 100 Hz in the sealed upper airway of 10 anesthetized supine dogs. Animals were artificially ventilated with 50% O2 and maintained under relative hyperoxia and hypocapnia during the study to eliminate the ventilatory drive output. Sealed upper airway pressures were obtained during random injections of different volumes of air from zero to 50 ml with and without hypoglossal nerve stimulation, and the upper airway P-V curves were obtained. The characteristics of the P-V curves were as follows: (1) the upper airway compliance defined as the slope of the regression of P-V curves fell from 4.07 +/- 0.33 ml/cm H2O without stimulation to 3.02 +/- 0.30 ml/cm H2O with stimulation at 50 Hz and plateaued at frequencies greater than 50 Hz, and (2) the volume at a given pressure during stimulation was larger than that without stimulation. The effects of submental stimulation on upper airway collapsibility were similar to those of hypoglossal nerve stimulation. These results suggest that the increase of upper airway muscle tone by hypoglossal nerve or submental stimulation stiffens the upper airway and that increases in muscle tone expand the upper airway.

Animals↗

TNF-alpha mRNA expression in diaphragm muscle after endotoxin administration.

We studied gene expression and production of TNF-alpha in the diaphragm tissue and changes of muscle contractile properties after endotoxin injection (Escherichia coli, 20 mg/kg) in 88 rats. We assessed the muscle contractile properties by force-frequency curves and twitch kinetics using dissected diaphragm muscle strips. The peak tensions of force-frequency curves decreased from control values (2.15 +/- 0.2 kg/cm2) up to 4 h (0.81 +/- 0.17, p < 0.001), and then increased at 6 h (1.36 +/- 0.19, p < 0.05) after endotoxin injection. The cytotoxic activity on L929 cells in arterial blood samples maximally increased at 2 h (p < 0.001), then decreased to 6 h (p < 0.05). TNF-alpha mRNA in diaphragm tissue was detected by Northern blot method at 1 and 1.5 h, and the immunolocalization of TNF-alpha was evaluated at 2 and 4 h by immunohistochemistry in the muscle tissues. Furthermore, preinjection with anti-m TNF-alpha antibody prevented the decrement of force-frequency curves after endotoxin injection of 10 microliters/kg. From this evidence that TNF-alpha gene expression and production occurred in the diaphragm tissue, but anti-m TNF-alpha antibody preinjection prevented the deterioration of diaphragm muscle contractile properties, we suggest that TNF-alpha may act on muscle cells extracellularly.

Analysis of Variance↗

Increased regional systolic myocardial stiffness of the left ventricle during coronary artery occlusion in a dog: analysis of the finite element model.

(1) We measured the instantaneous systolic transfer function of an isolated canine left ventricle (LV) before and after the ligation of the left anterior descending coronary artery (LAD). The instantaneous transfer function before the ligation of the LAD showed a resonance curve whose peak frequency was 30 to 70 Hz. On the other hand, the transfer function 40 min after the ligation of the LAD showed a divided peak in the resonance curve. (2) We constructed a finite element model of a thick-walled spherical shell with a non-uniform structure. In this model, the myocardial elasticity and viscosity of the ischemic region are different from those of non-ischemic regions. One can calculate the theoretical transfer function using modal analysis and also estimate the elasticity and the viscous coefficient of both non-ischemic and ischemic myocardium by fitting the theoretical transfer function to the experimental one. (3) The estimated elasticity of the ischemic myocardium was three to five times larger than that of the non-ischemic myocardium. The estimated viscous coefficient of the ischemic myocardium was about half that of the non-ischemic myocardium. These results showed that ischemia alters the viscoelastic properties of the myocardium during systole as well as during diastole.

Animals↗

Significance of the right ventricular free wall in dogs with and without pulmonary constriction.

To evaluate the role of the right ventricular (RV) free wall in cardiac function, RV and left ventricular (LV) wall segment lengths were measured by ultrasonic crystals in 10 open chest dogs with the pericardium preserved. Right coronary artery (RCA) was perfused separately by own blood and the flow was reduced stepwise until active shortening (delta L) of the RV segment disappeared or RCA flow became zero (Ischemia). The experiment was repeated with and without pulmonary stenosis (PS). At Ischemia, RV and LV systolic pressures decreased. RV end-diastolic length increased and RV delta L decreased. LV end-diastolic length and LV delta L were reduced. LV stroke volume concurrently fell. These changes became more prominent with PS. The critical level of RCA flow, at which RV delta L began to change, was higher with PS (5.27 +/- 2.85 ml/min, mean +/- S.D.) than without PS (1.44 +/- 1.16, p < 0.01). Based on the relationships between RV delta L and percent changes in RV developed pressure and stroke volume, the degree of the decreases in RV developed pressure and stroke volume at RV delta L of zero were estimated to be about 20%. These results indicate that the RV free wall partly contributes to maintaining the RV function, especially during RV pressure overload.

Animals↗

[The reliability and the significance of serum amylase levels in the diagnosis of the pancreatic injury].

To clarify the diagnostic reliability and significance of serum amylase levels (SAL) in the patients with pancreatic injury (PI), we reviewed 67 PIs. The elapsed time between injury and arrival of the hospital (ETAI) in the patients with normal SAL (1.3 +/- 0.2 hours, mean +/- SE) was significantly shorter than those with hyperamylasemia (5.8 +/- 0.9 hours). SAL on arrival significantly correlated to ETAI in the patients with type I (contusion) and type III injury (ductal injury). Among 45 patients who had arrived over 3 hours after injury, none showed normal SAL. Regardless of severity of PIs, one third of the patients showed normal SAL on arrival within 3 hours after injury. Among 23 patients treated conservatively, SAL in 14 patients (60.9%) normalized within 48 hours after injury, and these patients had no complications related to PIs. Three of remaining 9, who had prolonged hyperamylasemia over 48 hours, had pancreatic ductal branch injury or pseudocysts. This frequency was significantly different compared to that in the patients whose SAL normalized within 48 hours after injury. In conclusion, SAL is unreliable and insignificant to diagnose PIs within 3 hours after injury. Not to overlook the PIs serologically, it is important to determine SAL over 3 hours after injury especially in the patients having stable vital signs and to whom PIs are strongly suspected clinically.

Adolescent↗

[The role of emergent endoscopic retrograde pancreatography (ERP): its usefulness in the diagnosis of pancreatic injury].

To determine the therapeutic modalities for pancreatic injury (PI), it is important for the pancreatic ductal injury (DI) to be present or not. We performed ERPs in 36 patients who had positive findings in physical examinations, serum amylase levels and CT within about 13 hours after injury to diagnose the DIs early after injury and to avoid negative laparotomy. In 33 successful ERP patients (intraoperatively in 3), 22 had PIs (14 DIs) and 11 had non-PIs. Of 14 patients with DIs, 12 with main DIs and one with branch injury were treated surgically. Another patient with branch injury, who was treated conservatively, died of the complications of PI. Nineteen patients without DIs, including 8 PIs, were treated conservatively or operated for the associated abdominal injuries, who had no complications on PIs in the hospital days. Three unsuccessful ERP patients, having PIs, were also operated upon. Among 15 patients, including these 3 patients and 12 treated surgically during the era before introducing ERPs, 2 (13.3%) negative laparotomies were noted. Among 16 patients, who underwent both of ERP and operation, no negative laparotomies were noted. No complications of ERPs occurred. In conclusion, ERP is a reliable modality to detect DIs and to determine the therapeutic modalities for PIs.

Adolescent↗

Effects of chronic right ventricular pressure overload on myocardial glucose and free fatty acid metabolism in the conscious rat.

OBJECTIVE: The aim was to investigate the effects of chronic right ventricular pressure overload on myocardial glucose and free fatty acid metabolism in the right ventricular free wall, ventricular septum, and left ventricular free wall. METHODS: Using a glucose analogue, 14C-2-deoxyglucose (14C-DG), and a fatty acid analogue, 14C-beta methylheptadecanoic acid (14C-BMHDA), quantitative autoradiography was performed in conscious rats with 4 week pulmonary artery constriction. RESULTS: In rats with chronic pulmonary artery constriction, right ventricular peak systolic pressure and right ventricular weight to body weight ratio increased by 88% and 127%, respectively, compared with sham operated rats (P < 0.01 for each). In the right ventricular free wall, 14C-DG deposition increased but 14C-BMHDA accumulation did not differ in the chronic pulmonary artery constricted rats compared with sham operated rats [212(SEM 27), n = 6 v 101(15) nCi.g-1, n = 4, P < 0.01, and 406(40), n = 6, v 333(48) nCi.g-1, n = 4, NS, respectively]. In sham operated rats, 14C-DG and 14C-BMHDA deposition did not differ between the ventricular septum and the left ventricular free wall. In contrast, 14C-DG and 14C-BMHDA accumulations were lower in the ventricular septum compared with the left ventricular free wall wall in chronic pulmonary artery constricted rats. Myocardial blood flow assessed by 14C-iodoantipyrine was homogeneously distributed throughout both ventricles. CONCLUSIONS: Chronic right ventricular pressure overload increases myocardial glucose uptake and/or its phosphorylation in the right ventricular free wall, and alters the regional profiles of substrate use in the ventricular septum and left ventricular free wall despite the homogeneous blood flow distribution. The results of the acute right ventricular pressure overload study, in which only right ventricular 14C-BMHDA deposition was increased compared with controls, suggest that the findings obtained from chronic pulmonary artery constricted rats cannot be explained by increased right ventricular pressure alone.

Animals↗

[Portable home monitoring system in screening for sleep-disordered breathing].

Screening for sleep-disordered breathing is often done in an interview and with a questionnaire. This method is indirect and it appears to underestimate the prevalence of sleep apnea syndrome. Recently, several devices such as the Medilog and Vitalog portable monitoring systems were developed. However, these devices are difficult for patients to operate by themselves, because they include EEG monitoring or measurement of chest and abdominal movement. Therefore, we developed a portable monitoring system that is easier to operate. This system can be used to assess three variables: oronasal airflow, tracheal sound, and electrical activity of the heart. It stores the time of the onset of apnea, apnea duration, and R-R intervals with a built-in microcomputer. Apnea episodes, total apnea time, mean apnea time, and R-R interval are analyzed with a host computer. The sensitivity an specificity of this system are 92.5% and 87.5%, respectively, with an apnea index (AI) of less than 10 episodes/h. Using this device, we found that the prevalence of sleep apnea syndrome among Japanese industrial workers who had an AI of more than 10 episodes was 7.5%. Moreover, from 1984 to 1994 we used this device to monitor 1019 outpatients who complained of sleep disturbances such as snoring, abnormal breathing during sleep, and excessive daytime sleepiness, and found sleep apnea (AI > or = 10) in about 50% of these patients. This monitoring system is useful for screening of outpatients with sleep apnea and for epidemiological studies of sleep apnea. However, it may be necessary to include a non-invasive system for monitoring oxygen saturation in the portable sleep monitor, to detect hypoventilation during sleep.

Adolescent↗

In vivo release of glutamate in nucleus tractus solitarii of the rat during hypoxia.

1. An attempt has been made to test the hypothesis that, in the caudal part of nucleus tractus solitarii (NTS) where carotid sinus nerve (CSN) afferents project, L-glutamate (Glut) modulates the hypoxic ventilatory response. 2. Unanaesthetized, peripherally chemodenervated (carotid body denervated; CBD) and sham-operated, freely moving rats were used. During peripheral chemoreceptor stimulation by hypoxia (10% O2 for 30 min) or doxapram (Dox) infusion (2 mg kg-1 (30 min)-1), ventilation was recorded and successively, under the same conditions, the extracellular Glut concentration ([Glut]o) in the caudal NTS was measured by in vivo microdialysis. [Glut]o was also measured during hyperoxic hypercapnia (10% CO2-30% O2 for 30 min). 3. Furthermore, the effects on ventilation of exogenous Glut, the NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 or the ionotropic receptor antagonist kynurenate microinjected into the caudal NTS were investigated in sham-operated rats. 4. In sham-operated rats, both ventilation and [Glut]o in NTS were increased during peripheral chemoreceptor stimulation. On the other hand, no increases in either ventilation or Glut release were observed in CBD rats. In spite of ventilatory augmentation during hypercapnia, no response of [Glut]o to hypercapnia was observed in either group. 5. Local Glut application into NTS increased ventilation. Pretreatment with MK-801 or kynurenate reduced the hypoxic ventilatory response. This reduction in ventilation was mainly due to the decrease in tidal volume. 6. These results suggest that hypoxia induced the release of Glut in NTS and that this effect was mediated by arterial chemosensory input.

Animals↗

Chemosensitivity and perception of dyspnea in patients with a history of near-fatal asthma.

BACKGROUND: Many deaths from attacks of asthma may be preventable. However, the difficulty in preventing fatal attacks is that not all the pathophysiologic risk factors have been identified. METHODS: To examine whether dyspnea and chemosensitivity to hypoxia and hypercapnia are factors in fatal asthma attacks, we studied 11 patients with asthma who had had near-fatal attacks, 11 patients with asthma who had not had near-fatal attacks, and 16 normal subjects. Their respiratory responses to hypoxia and hypercapnia, determined by the standard rebreathing technique while the patients were in remission, were assessed in terms of the slopes of ventilation and airway occlusion pressure as a function of the percentage of arterial oxygen saturation and end-tidal carbon dioxide tension, respectively. The perception of dyspnea was scored on the Borg scale during breathing through inspiratory resistances ranging from 0 to 30.9 cm of water per liter per second. RESULTS: The mean (+/- SD) hypoxic ventilatory response (0.14 +/- 0.12 liter per minute per percent of arterial oxygen saturation) and airway occlusion pressure (0.05 +/- 0.05 cm of water per percent of arterial oxygen saturation) were significantly lower in the patients with near-fatal asthma than in the normal subjects (0.60 +/- 0.35, P < 0.001, and 0.16 +/- 0.08, P < 0.001, respectively) and the patients with asthma who had not had near-fatal attacks (0.46 +/- 0.29, P = 0.003, and 0.15 +/- 0.09, P = 0.004). The Borg score was also significantly lower in the patients with near-fatal asthma than in the normal subjects, and their lower hypoxic response was coupled with a blunted perception of dyspnea. CONCLUSIONS: Reduced chemosensitivity to hypoxia and blunted perception of dyspnea may predispose patients to fatal asthma attacks.

Adult↗

HMT regulates histamine-induced Cl- secretion across the canine tracheal epithelium.

Although histamine N-methyltransferase (HMT), the primary enzyme responsible for the inactivation of histamine, has been shown to exist in the airway epithelium, it is still unknown whether this enzyme regulates ion transport across the airway epithelium. Using an Ussing chamber, we examined the effect of a HMT inhibitor, SKF 91488, on potential difference (PD) and short circuit current (SCC) in epithelial membranes from the posterior portion of canine trachea. SKF 91488 itself did not significantly alter PD or SCC values. Pretreatment with SKF 91488 significantly augmented PD and SCC induced by histamine. Amiloride did not significantly alter the augmentation by SKF 91488 in histamine-induced PD and SCC rises. These findings indicate that HMT regulates Cl- secretion across airway epithelium.

Amiloride↗

Tachykinins induce a [Ca2+]i rise in the acinar cells of feline tracheal submucosal gland.

The intracellular Ca2+ concentration ([Ca2+]i) of acinar cells of isolated submucosal glands from trachea was measured using a fluorescent dye, Fura-2. Neurokinin A (NK-A) produced a sustained rise in [Ca2+]i in a dose-dependent manner, reaching a response of 500 to 600% of the prior baseline value at 10(-6) or 10(-5) M, and the NK-A evoked [Ca2+]i was significantly higher than that by substance P (SP) at similar concentrations. NK-B did not induce significant increases in [Ca2+]i. In a Ca(2+)-free solution, NK-A produced a transient rise in [Ca2+]i, which returned to the baseline within 3 min. Mucus glycoprotein (MGP) secretion, estimated by measuring trichloroacetic-acid (TCA) precipitable glycoconjugates, was stimulated by NK-A or SP. These findings indicate that tachykinins produce a rise in [Ca2+]i by both entry from the extracellular solution and release from intracellular storage, probably by NK-2 receptor stimulation, and stimulate MGP secretion from airway submucosal glands.

Animals↗

CGRP induces [Ca2+]i rise and glycoconjugate secretion in feline tracheal submucosal gland.

Submucosal glands were isolated from feline trachea. The intracellular Ca2+ concentration ([Ca2+]i) of the acinar cells of isolated glands was measured using the fluorescent dye Fura-2. Calcitonin gene-related peptide (CGRP) at 10(-8) to 10(-5) M produced a significant and sustained rise in the [Ca2+]i of isolated glands, reaching a maximal response of 127% of the prior baseline level but did not alter the intracellular adenosine 3', 5'-cyclic monophosphate ([cAMP]i). In a Ca(2+)-free solution, CGRP produced no significant alteration in [Ca++]i. Glycoconjugate secretion from isolated glands was stimulated by CGRP in a dose dependent fashion, reaching a maximal response of 167% of control at 10(-6) M but was without effect in tracheal explants. Further, CGRP did not produce any significant increase in glycoconjugate secretion in the Ca(2+)-free medium. These findings indicate that CGRP stimulates glycoconjugate secretion from airway submucosal glands by inducing Ca2+ influx from the extracellular solution.

Animals↗

Magnesium regulates ion transport across canine tracheal epithelium.

We examined the effect of Mg2+ on potential difference (PD) and short circuit current (SCC) of the posterior epithelial membrane of canine trachea using an Ussing chamber. After the exchange to a Mg(2+)-free solution, PD and SCC rapidly increased, reaching maximal values within 3 min, followed by a gradual return towards the baseline over 60 min. In a Ca(2+)-free solution, Mg2+ removal did not alter PD and SCC values. Increased Mg2+ in the solution produced significant gradual decreases in PD and SCC. The decreases in PD and SCC were reversed by the addition of excessive Ca2+ to the solution. Mg2+ removal did not alter significantly isoproterenol-induced increases in PD and SCC values, while increased Mg2+ significantly reduced the increases. These findings indicate that extracellular Mg2+ is an important determinant in ion transport across the airway epithelium, probably through antagonistic actions of Mg2+ and Ca2+.

Amiloride↗