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Biomedical subjects

M Mohri

Publications and source records attributed to M Mohri.

At least 55 records · Page 3Linked to original sources
PubMed1999

Coronary microvascular disease in humans.

Myocardial perfusion abnormalities occur in the absence of epicardial coronary artery disease in patients with a wide spectrum of cardiovascular disorders including microvascular angina, hypertension and left ventricular hypertrophy, coronary atherosclerosis, hypercholesterolemia, and non-ischemic left ventricular dysfunction. These patients have limited coronary microvascular dilator reserve which occasionally is associated with evidence of myocardial ischemia. Primary microvascular hyperconstriction (spasm) is also proposed to cause myocardial ischemia in a subset of patients with rest angina. There is ample evidence suggesting that endothelial dysfunction contributes to microvascular dysfunction, but the precise mechanism of endothelial dysfunction is not known. Nitric oxide is one of the key molecules which control microvascular tone and therefore coronary blood flow, and its decreased availability appears to be involved under certain conditions. This hypothesis has attracted considerable interest as a new therapeutic strategy for these patients having coronary microvascular derangements caused by divergent cardiovascular diseases.

Angina Pectoris↗
PubMed1999

Changes in c-Fos expression induced by noxious stimulation in the trigeminal spinal nucleus caudalis and C1 spinal neurons of rats after hyperbaric exposure.

The present study aims to test the hypothesis that hyperbaric exposure inhibits nociceptive processing in the trigeminal spinal nucleus caudalis and C1 spinal neurons. We investigated the c-Fos-like immunoreactivity of the brainstem and upper cervical spinal cord (C1 region) following an injection of mustard oil (15 microliters of 20%) into the nasal mucosa of pentobarbital anesthetized rats after exposure to hyperbaric (2-atmospheres, 1 h) and normobaric pressures. After the hyperbaric exposure, the mean number of Fos-immunoreactive neurons in the ipsilateral laminae I-II and III-IV of the trigeminal spinal nucleus caudalis were significantly lower than those in the normobaric condition. Similarly, the mean number of c-Fos positive neurons in the superficial layer (I-II) of the ipsilateral C1 segment were significantly reduced as compared with that in the normobaric condition. When treated with the vehicle alone, no significant difference was detected in the numbers of c-Fos positive neurons in the trigeminal spinal nucleus caudalis and C1 regions between hyperbaric and normobaric conditions. These results suggest that hyperbaric exposure may attenuate nociceptive signals from the area innervated by the trigeminal nerves at the level of both the trigeminal spinal nucleus caudalis and C1 dorsal horn.

Animals↗
PubMed1999

Evaluation of cutaneous insensible water loss during hyperbaric exposure in humans.

BACKGROUND: Water evaporation diminishes in high pressure environment, however it is unknown whether insensible water dissipation from the human skin falls as a function of the increased environmental pressure. We designed the present study to measure cutaneous insensible water loss at various pressures during exposure to a simulated saturation dive. METHODS: Four healthy male volunteers were exposed to eight different pressures between 1 and 18.4 atmospheres absolute (atm abs). Resting insensible water loss from the skin was measured as change in the body weight and corrected for the weight of the respiratory CO2 - O2 gas exchange and the respiratory water dissipation. RESULTS: We made an equation for the relationship between cutaneous insensible water loss and environmental pressure as: w = 14.5 X p(-0.48), where, w is cutaneous insensible water loss in g x m(-2) x h(-1), and P is the environmental pressure in atm abs. The average cutaneous insensible water loss (15.3 g x m(-2) x h(-1)) at normal atmosphere decreased (p < 0.01) to 4.2 g x m(-2) x h(-1) (reduced by 73%) during a saturation dive to 18.4 atm abs. CONCLUSION: The amount of insensible water loss estimated from the equation was comparable to that of reported observations.

Adult↗
PubMed1999

The inhibitory effect of recombinant human soluble thrombomodulin on initiation and extension of coagulation--a comparison with other anticoagulants.

Recombinant human soluble thrombomodulin (rhsTM) was compared with various anticoagulants for in vitro anticoagulant effects on thrombin generation, clotting time, and thromboelastography. rhsTM as well as APC reduced the level of the peak of the thrombin generation curve, but we did not observe any time-delay to reach the peak. This effect of rhsTM was diminished in PC-deficient plasma and was closely associated with the inhibitory effect on prothrombinase and factor Va. On the other hand, hirudin and argatroban delayed the time to reach the level of the peak, without reducing it. rhsTM and other anticoagulants except for activated protein C (APC) were found to have concentration-dependent anticoagulant activity by conventional clotting tests. However, the concentration of rhsTM for clotting time was slightly affected by anti-protein C antibody. Moreover, the concentration of rhsTM required to inhibit thrombin activity directly was 50 times higher than that needed to inhibit thrombin generation. The effect of rhsTM on clot development was compared with that of other anticoagulants by thromboelastography; rhsTM reduced the growth of the clot but had little effect on the time to activate clotting, while the other anticoagulants had the opposite effect. This effect of rhsTM was completely abolished by the addition of anti-protein C or anti-protein S antibody. These findings suggest that rhsTM attenuates blood clotting by reducing the level of generated thrombin through protein C activation and subsequent factor Va inactivation and prothrombinase inhibition.

Anticoagulants↗
PubMed1998

Lethality of high linear energy transfer cosmic radiation to Escherichia coli DNA repair-deficient mutants during the 'SL-J/FMPT' space experiment.

We investigated the lethal and mutagenic effects of high linear energy transfer cosmic radiation on 11 strains of Escherichia coli, including DNA repair-deficient mutants, using the Radiation Monitoring Container and Dosimeter in the space shuttle 'Endeavour' as part of the 'SL-J/FMPT' space experiment, the 'Fuwatto '92' project. After the return to earth of the shuttle, we evaluated survival and mutations of samples in space and matched controls. The surviving fractions were determined by means of colony count on broth agar plates, and the mutation frequencies were estimated by appearance of arg' revertants on minimal agar plates. The average of the total equivalent dose rate during this space flight was 0.202 mSv/day as measured by the plastic radiation detectors and the thermoluminescent dosimeters in the Radiation Monitoring Container and Dosimeter. The combined action of DNA polymerase and 3'-->5' exonuclease activities was found to make the greatest contribution to the repair of cosmic radiation-induced DNA damage, 5'-->3' exonuclease and recombination repair enzyme activities made a moderate contribution, whereas UV endonuclease activity was not involved in this DNA repair process.

Colony Count, Microbial↗
PubMed1998

Angina pectoris caused by coronary microvascular spasm.

BACKGROUND: Microvascular angina can occur during exercise and at rest. Reduced vasodilator capacity of the coronary microvessels is implicated as a cause of angina during exercise, but the mechanism of angina at rest is not known. Our aim was to test the hypothesis that primary hyperconstriction (spasm) of coronary microvessels causes myocardial ischaemia at rest. METHODS: Acetylcholine induces coronary artery spasm in patients with variant angina. We tested the effects of intracoronary acetylcholine at graded doses in 117 consecutive patients with chest pain (at rest, during exertion, or both) and no flow-limiting (>50%) organic stenosis in the large epicardial coronary arteries. We also assessed the metabolism of myocardial lactate during acetylcholine administration in 36 of the patients by measurement of lactate in paired blood samples from the coronary artery and coronary sinus vein. FINDINGS: Of the 117 patients, 63 (54%) had large-artery spasm, 29 (25%) had microvascular spasm, and 25 (21%) had atypical chest pain. The 29 patients with microvascular spasm developed angina-like chest pain, ischaemic electrocardiogram (ECG) changes, or both spontaneously (two patients) or after administration of acetylcholine (27 patients) without spasm of the large epicardial coronary arteries. Testing of paired samples of arterial and coronary sinus venous blood showed that lactate was produced during angina attack in nine of 11 patients with microvascular spasm. There was more women (p<0.01) and fewer coronary risk factors (p<0.01) in patients with microvascular spasm than in those with large-artery spasm. INTERPRETATION: Coronary microvascular spasm and resultant myocardial ischaemia may be the cause of chest pain in a subgroup of patients with microvascular angina.

Acetylcholine↗
PubMed1998

[Successful repair of critical aortic stenosis with coarctation on the first day of life].

Successful open aortic valvotomy and end-to-end anastomosis were performed to the patient with critical aortic stenosis and CoA on the first day of life. A fetus was diagnosed as aortic stenosis and coarctation by fetal echocardiography at 29 weeks of gestation. The mother was transferred to our hospital at the onset of labor and delivered vaginally at 40 weeks of gestation. Soon after the birth, the newborn, birth weight 2630 gram, female, underwent echocardiography by pediatric cardiologists which demonstrated the aortic orifice of 5.1 mm in diameter and thickened cusps with poor mobility. Transaortic pressure gradient measured by Doppler echocardiography was 111 mmHg and the left ventricular wall motion was hyperdynamic without any signs of endocardial fibroelastosis. Prostaglandin E1 administration was started to maintain systemic circulation and the hemodynamic status has been stable before surgery. On her first day of life, the operation was performed using cardiopulmonary bypass with moderate hypothermia. Isolated cerebral and myocardial perfusion technique was applied during the repair of coarctation of the aorta. The open aortic valvotomy with resection of myoxomatous nodules on leaflet edges effectively released pressure gradient across the aortic valve without regurgitation. Post-operative course was uneventful and she discharged at 28th day after surgery. We conclude early diagnosis including fetal echocardiography and early repair would lead the better surgical outcome to the neonates with critical aortic stenosis.

Alprostadil↗
PubMed1998

Tumor necrosis factor-alpha is expressed by monocytes/macrophages following cardiac microembolization and is antagonized by cyclosporine.

The time course of expression of TNF-alpha in myocardial wound healing following ischemic injury was investigated in the porcine heart. Microembolization was used to induce focal ischemia and necrosis in hearts of 39 adult pigs. The animals were sacrificed after 3, 6, 12, 24 h, 3 and 7 days, and after 4 weeks, and the myocardial tissue was studied by immunofluorescence using specific antibodies. TNF-alpha containing cells were identified as monocytes/macrophages by double staining with a muramidase antibody. Monocytes/macrophages were the only source of TNF-alpha. Microembolization caused multiple necrotic foci with loss of myocytes in the left ventricular myocardium. These foci contained numerous monocytes/macrophages and showed an inflammatory reaction typical of wound healing followed by replacement with scar tissue. The number of TNF-alpha positive cells increased after 24 h, peaked between 3-7 days and slowly decreased thereafter. Expression of TNF-alpha in monocytes/macrophages was significantly reduced after pretreatment of pigs with cyclosporine or dexamethasone. It is concluded that 1.) in myocardial tissue monocytes/macrophages are the only cell type expressing TNF-alpha, 2.) TNF-alpha is involved in wound healing after ischemia, and 3.) synthesis of TNF-alpha and inflammatory angiogenesis can be inhibited be treatment with either cyclosporine or dexamethasone.

Animals↗
PubMed1998

Changes in sleep patterns during He-O2 saturation dives.

During simulated hyperbaric saturation diving experiments of He-O2 mixture at the depths of 150, 180 and 230 m the standard polysomnography of four divers, as well as their subjective feelings of fatigue, were recorded for 268 nights. In all three diving conditions, during the bottom period and the decompression period, wakes after sleep onset and Stage 1 sleep increased while Stage 4 sleep decreased. In deeper diving conditions stage 4 sleep tended to decrease and subjective feelings of fatigue increased. When the results are considered it can be assumed that the deeper the diving depths, the increased sleep disturbances and fatigue. However, it is believed that a fundamental sleep pattern will be maintained.

Adult↗
PubMed1998

Dynamics of subneoglottic lumen in tracheoesophageal phonation.

The patient who employs tracheoesophageal (TE) phonation uses expiratory air passing through the TE fistula to vibrate the mucosa of the neoglottis located in the hypopharynx. To clarify the dynamics of the subneoglottic lumen during phonation, we performed fiberoptic endoscopy and fluoroscopy in 13 TE speakers. During phonation, fiberoptic endoscopy showed concentric closure of the esophagus with ballooning of the subneoglottic lumen, followed by opening of the esophagus during inspiration. Fluoroscopy revealed a dilated subneoglottic lumen and a closure of the esophagus at the bottom of the lumen during phonation. These findings provide evidence for a mechanism to protect against the influx of air deep into the esophagus during TE phonation. We conclude that during TE phonation, a closed airway is established from the lung to the neoglottis that enables the TE speaker to use expiratory air effectively for phonation.

Aged↗
PubMed1998

Infarct Size Reduction by Ischemic Preconditioning Is a Monophasic, Short-Lived Phenomenon in Anesthetized Pigs.

BACKGROUND: Controversy exists concerning the duration of infarct size reduction with ischemic preconditioning in different species. In the present study, we (a) evaluated the time course of protection with preconditioning and (b) sought to determine whether late protection (the "second window") after 24 hours is manifest in the open-chest pig model. METHODS AND RESULTS: Six groups of pentobarbital-anesthetized pigs underwent 1 hour of left anterior descending coronary artery occlusion and 2 hours of reperfusion. Group 1 served as control, and pigs in group 2 received two 10-minute episodes of preconditioning ischemia followed by 30 minutes of reperfusion before the sustained 1-hour occlusion. In groups 3-6, the period of intervening reperfusion between the preconditioning stimulus and the index ischemia was extended to 60, 90, and 300 minutes and 24 hours, respectively. The area at risk was determined by fluorescein dye injection, and infarct size was measured by incubation in p-nitrobluetetrazolium and expressed as percent of the risk area. Infarct size in preconditioned pigs (group 2) was significantly reduced compared with controls (25.6 +/- 3.9% v 71.3 +/- 5.9%, P <.001). Extension of the intervening reperfusion to 60, 90, and 300 minutes and 24 hours resulted in infarct sizes of 64.5 +/- 5.5%, 67.2 +/- 8%, 62.6 +/- 6.1%, and 75.3 +/- 7%, respectively (P = NS v control). CONCLUSIONS: The infarct size-limiting effects of ischemic preconditioning last less than 1 hour in the pig model. Moreover, in contrast to other species, a late protection at 24 hours after the preconditioning stimulus was not detected. These results indicate that precondition-induced reduction of infarct size is monophasic in anesthetized pigs.

Journal Article↗
PubMed1998

Renal function in hyperbaric environment.

During mixed gas saturation diving (to 3-49.5 ATA) daily urine flow increases by about 500 ml/day, with no changes in fluid intake and glomerular filtration rate. The diuresis is accompanied by a significant decrease in urine osmolality and increase in excretion of such solutes as urea, K+, Na+, Ca2+ and inorganic phosphate (Pi). The fall in urine osmolality is mainly due to a reduction of free water reabsorption which is associated with a suppression of insensible water loss and the attendant inhibition of antidiuretic hormone (ADH) system. The increase in urea excretion may be associated with a reduction of urea reabsorption at the collecting duct as a consequence of ADH suppression. The rise in K+ excretion is due to a facilitated K+ secretion at the distal tubule as a result of increased aldosterone, urine flow and excretion of impermeable anions such as Pi. The activation of aldosterone system is partly attributed to a transient dehydration induced by early hyperbaric diuresis. The increase in Na+ excretion in the face of enhanced aldosterone secretion indicates that the Na+ transport in the proximal tubule is markedly inhibited (by unknown mechanism). The Pi excretion increases with no changes in plasma level of parathyroid hormone (PTH), thus it may be due to an inhibition of Na(+)-Pi cotransport in the proximal tubule. The increase in Ca2+ excretion may be secondary to the inhibition of Na+ transport at the proximal tubule. Precise information on the proximal tubular Na+ transport is important to understand the mechanisms of impaired solute transport under hyperbaric conditions.

Diuresis↗
PubMed1998

Psychological and physiological changes during isolation and confinement: I. Group dynamics and member interaction.

The isolated and confined environment of a laboratory setting was used as one of the analogous environments of long-term manned spaceflight. This setting has more advantages than the natural one in that the behavioral variables can be easily controlled. Thus, a hyperbaric chamber was used in this experiment. The subjects were five men from 22- to 26-years old who had never met before the experiment. Over a total 5-day isolation and confinement period as well as 2-day pre- and post-isolation periods, the subjects were given different kinds of physiological and psychological tasks. During these periods their behavior and communications were recorded in order to observe when the formation of a group begins and how it forms and functions. The formation of a sub-group of three men was observed on the third day of isolation, showing strong reciprocal connections among these subjects who developed bonds that were quite stable. It is, however, not known how this sub-group functioned within the large group, since the experimental period was possibly too short.

Adaptation, Physiological↗
PubMed1998

In vitro anticoagulant properties of a minimum functional fragment of human thrombomodulin and in vivo demonstration of its benefit as an anticoagulant in extracorporeal circulation using a monkey model.

Recently, we demonstrated that the last three consecutive epidermal growth factor-like structures of human thrombomodulin form the minimum functional fragment for protein C activating activity. In this study, the recombinant minimum functional fragment of human thrombomodulin (E456) had similar activities for protein C activation and clotting time compared to the recombinant extracellular domains of human thrombomodulin (rhsTM) previously described. E456 had a shorter half-life (6-9 min) in animals, compared to rhsTM (5 h). To evaluate whether or not E456 is a suitable anticoagulant for extracorporeal circulation, the effects of E456 were investigated in the extracorporeal circulation model in monkeys. The effect of E456 at a dose of 0.03 mg/kg plus 0.113 mg/kg/h on circuit pressure was as potent as that of low molecular weight heparin, Fragmin, at a dose of 30 IU/kg plus 15 IU/kg/h. E456, however, also more effectively suppressed an increase of thrombin-antithrombin III complex than Fragmin. Also the APTT quickly returned to the pre-treatment level following E456, but did not when using Fragmin. Moreover, E456 had no influence on the plasma free fatty acid levels, while Fragmin significantly increased them. Thus, E456 appears to have anticoagulant properties which make it more suitable anticoagulant in extracorporeal circulation than Fragmin.

Animals↗
PubMed1998

[Lung abscess in a patient with Good's syndrome and pure red cell aplasia].

A 56-year-old man with pure red cell aplasia (PRCA), hypogammaglobulinemia and mediastinal tumor was admitted to our hospital with of dyspnea, high fever and general fatigue. Chest X-ray showed a large cavity with a niveau in the left lung. Biopsy of the mediastinal tumor revealed an epithelial cell-type thymoma. Lung abscess with Good's syndrome and PRCA was diagnosed. Antibiotics was administered, and percutaneous catheter drainage of the lung abscess was performed. He recovered and was discharged. Hypogammaglobulinemia in the case may have resulted from reduced production of gammaglobulin associated with a quantitative B-cell defect.

Agammaglobulinemia↗
PubMed1998

Assessment of cardiac autonomic nervous activities during heliox exposure at 24 atm abs.

BACKGROUND: This experiment was designed to examine the involvement of the autonomic nervous system in the production of hyperbaric bradycardia. METHODS: Four male divers were exposed to a He-O2 (heliox) environment at 24 atmosphere absolute (atm abs) for 7 d. The heart rate (HR) and respiratory rate were recorded at rest in the morning (0700 h) and at night (2230 h) on 1 d during a 5-d predive control, 2 d during a 7-d saturation dive at 24 atm abs, 2 d during decompression, and on 1 d during a 4-d postdive period. Cardiac sympathetic and parasympathetic activities were estimated by using a spectral analysis of the variability of R-R intervals. RESULTS: The morning HR did not fluctuate throughout the experimental days. The night time HR decreased (p < 0.05) by 11.8% on the first day at 24 atm abs compared with that of the predive control. The bradycardia diminished gradually and returned to the predive level with continued exposure at 24 atm abs. The high-frequency power of the cardiac variability, an index of cardiac parasympathetic activity, increased (p < 0.05) only in the first night at 24 atm abs, whereas the low-frequency power and a ratio of low- to high-frequency power, an index of cardiac sympathetic activity, were unchanged. CONCLUSIONS: The present results suggest that an increased parasympathetic activity rather than a decrease in the sympathetic activity is responsible for the bradycardia on exposure to heliox dry saturation dive at 24 atm abs. The mechanism of the gradual disappearance of the bradycardia is unknown, but perhaps it may be related to the development of cardiovascular deconditioning.

Adult↗