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Biomedical subjects

M Mohri

Publications and source records attributed to M Mohri.

At least 19 recordsLinked to original sources

Adrenomedullin receptors in rat cerebral microvessels.

To characterize the sites of action of adrenomedullin (AM) in the cerebral microvasculature, we studied the effect of AM on cyclic AMP (cAMP) level as well as expression of AM and its receptor in the rat cerebral microvessels. The microvessels were prepared from rat cerebral cortex by albumin flotation and glass bead filtration technique. AM and calcitonin gene-related peptide (CGRP) increased cAMP level in the microvessels in a concentration-dependent manner. The effect of AM was more than 100 times more potent than that of CGRP. The accumulation of cAMP by AM was inhibited by AM[22-52], an AM receptor antagonist, but not by CGRP[8-37], a CGRP receptor antagonist, suggesting that AM increased cAMP accumulation by acting on receptors specific to AM. [125I]AM binding to the microvessels was displaced by AM and less potently by AM[22-52]. The displacing potencies of CGRP and CGRP[8-37] were very weak. mRNAs for AM as well as calcitonin-receptor-like receptor and receptor-activity-modifying protein 2 which form a receptor specific to AM, were highly expressed in the microvessels. These results provide biochemical and pharmacological evidence that AM is produced in and acts on the cerebral microvessels in an autocrine/paracrine manner and is involved in regulation of cerebral microcirculation.

Adrenomedullin↗

alpha(1)-Adrenergic receptor subtypes in rat cerebral microvessels.

To identify alpha(1)-adrenergic receptor subtypes involved in the regulation of cerebral microcirculation, we studied alpha(1)-adrenergic receptor subtypes expressed in the rat cerebral microvessels. The microvessels were prepared from rat cerebral cortex by albumin flotation and glass bead filtration techniques. [(125)I]HEAT binding to the cerebral microvessels was displaced by low concentrations of 5-methylurapidil, a selective antagonist for alpha(1A)-receptors, and modified Scatchard analysis of the data revealed that half of alpha(1)-receptors is alpha(1A)-subtype, and that alpha(1B)- and/or alpha(1D)-receptors are also present. The K(i) value of the high-affinity component for 5-methylurapidil was 3.90+/-1.08 nM, which is comparable with the value obtained in the rat cerebral cortex (2.17+/-0.88 nM). Reverse transcription and polymerase chain reaction experiments showed that mRNAs of alpha(1A)- and alpha(1B)-receptors, but not alpha(1D)-receptors, were expressed in the cerebral microvessels. These results suggest that alpha(1)-receptors involved in the regulation of cerebral microvessel function are alpha(1A)- and alpha(1B)-receptor subtypes.

Adrenergic alpha-Antagonists↗

Job strain, Type A behavior pattern, and the prevalence of coronary atherosclerosis in Japanese working men.

OBJECTIVE: To examine the relation of type A behavior pattern and job strain to angiographically documented coronary stenosis. METHODS: Subjects were 197 male Japanese patients with a full-time job. A questionnaire-based interview elicited psychosocial and other factors. Type A behavior pattern was measured by 12 questions, and job strain by the method of Karasek. Significant coronary stenosis was defined when a 75% or greater luminal narrowing occurred at one or more major coronary arteries or when a 50% or greater narrowing occurred at the left main artery. Logistic regression analysis was used to calculate odds ratio (OR) and 95% confidence interval (CI) with adjustment for traditional coronary risk factors and job type. RESULTS: Type A behavior pattern was related to a statistically non-significant lower prevalence of the coronary stenosis especially in the absence of job strain (adjusted OR 0.6, 95% CI 0.3-1.2). Job strain was non-significantly associated with a modestly increased prevalence of coronary stenosis (OR 1.7, 95% CI 0.6-5.2). CONCLUSION: These findings suggest that both the behavioral pattern and psychosocial work environment may be related to coronary artery stenosis.

Adult↗

Relation between green tea consumption and the severity of coronary atherosclerosis among Japanese men and women.

PURPOSE: To examine the relation between green tea consumption and arteriographically determined coronary atherosclerosis. METHODS: Study subjects were 512 patients (302 men and 210 women) aged 30 years or older who underwent coronary arteriography for the first time at four hospitals in Fukuoka City or one hospital in an adjacent city between September 1996 and August 1997. Lifestyle characteristics including green tea consumption were ascertained before arteriography by a questionnaire supported with interview. RESULTS: 117 men (38.7%) and 50 women (23.8%) had significant stenosis of one or more coronary arteries. Green tea consumption tended to be inversely associated with coronary atherosclerosis in men, but not in women. An evident, protective association between green tea and coronary atherosclerosis was observed in a subgroup of 262 men excluding those under dietary or drug treatment for diabetes mellitus. In this subgroup, after adjustment for traditional coronary risk factors and coffee, odds ratios of significant stenosis for consumption of 2-3 cups and 4 or more cups per day were 0.5 (95% confidence interval 0.2-1.2) and 0.4 (0.2-0.9), respectively, as compared with a consumption of one cup per day or less. CONCLUSIONS: The results indicate that green tea may be protective against coronary atherosclerosis at least in men.

Adult↗

Intracoronary enalaprilat improves metabolic coronary vasodilation in patients with idiopathic dilated cardiomyopathy.

Coronary flow reserve is reduced in patients with idiopathic dilated cardiomyopathy (DCM). We examined acute effects of intracoronary enalaprilat on metabolic coronary vasodilation during pacing tachycardia in patients. Coronary blood flow (Doppler guidewire) and diameter (quantitative angiography) were measured in seven patients with DCM and seven control subjects. In the DCM group, tachypacing increased coronary blood flow by 37 +/- 22% from the baseline before enalaprilat and by 65 +/- 22% (p < 0.01 vs. before treatment) after enalaprilat (0.5 microg/kg/min for 5 min, i.c.) at comparable double product. Pacing-induced dilation of the epicardial coronary artery also was greater after enalaprilat (p < 0.05). Effects of enalaprilat on coronary blood flow and diameter during pacing tachycardia were abolished by pretreatment with intracoronary administration of the nitric oxide (NO) synthesis inhibitor, N(G)-monomethyl-L-arginine. These beneficial effects of enalaprilat on large and small coronary vasodilation were not observed in control patients. Thus, intracoronary enalaprilat acutely augmented dilator responses of the large and small coronary arteries to pacing tachycardia in patients with DCM, and NO appeared to play an important role in mediating the effects of enalaprilat. These favorable effects of enalaprilat on the coronary circulation may be of clinical significance in patients with heart failure due to nonischemic DCM. Further long-term studies of the effects of angiotensin-converting enzyme inhibition on coronary vasodilation will be needed in this population.

Aged↗

Saccharomyces cerevisiae sigma 1278b has novel genes of the N-acetyltransferase gene superfamily required for L-proline analogue resistance.

We discovered on the chromosome of Saccharomyces cerevisiae Sigma 1278b novel genes involved in L-proline analogue L-azetidine-2-carboxylic acid resistance which are not present in the standard laboratory strains. The 5.4 kb-DNA fragment was cloned from the genomic library of the L-azetidine-2-carboxylic acid-resistant mutant derived from a cross between S. cerevisiae strains S288C and Sigma 1278b. The nucleotide sequence of a 4.5-kb segment exhibited no identity with the sequence in the genome project involving strain S288C. Deletion analysis indicated that one open reading frame encoding a predicted protein of 229 amino acids is indispensable for L-azetidine-2-carboxylic acid resistance. The protein sequence was found to be a member of the N-acetyltransferase superfamily. Genomic Southern analysis and gene disruption showed that two copies of the novel gene with one amino acid change at position 85 required for L-azetidine-2-carboxylic acid resistance were present on chromosomes X and XIV of Sigma 1278b background strains. When this novel MPR1 or MPR2 gene (sigma 1278b gene for L-proline analogue resistance) was introduced into the other S. cerevisiae strains, all of the recombinants were resistant to L-azetidine-2-carboxylic acid, indicating that both MPR1 and MPR2 are expressed and have a global function in S. cerevisiae.

Amino Acid Sequence↗

Congenital defects of the vomer.

Six cases of congenital defect of the vomer, a rare nasal anomaly, are reported. All 6 patients visited Kobe University Hospital with other complaints, and the anomaly was incidentally detected. In all cases, the nasal septum showed a defect at the posteroinferior portion that appeared to coincide with the location of the vomer. None of the patients had a past history of nasal trauma, nasal surgery, drug abuse, or infectious disease. This anomaly may be attributable to an embryological disorder based on an immature ossification center of the vomer.

Adult↗

[Combined valvular and coronary artery surgery].

Between 1990 and 1999, 78 patients underwent combined valvular coronary artery operation. Aortic valve disease was present in 49 patients, mitral valve disease in 23 patients, aortic and mitral valve disease in 6 patients. The average age was 67 years. Twelve patients had had a previous myocardial infarction. The average number of grafts inserted was 1.82 per patients, and the average number of artery grafts inserted was 0.96 per patients. The most number of grafts were placed prior to valve replacement or plasty. And periods of myocardial ischemia were kept at a minimum by coronary perfusion through free grafts. Preoperative mortality was 1.3%. And event fee ratio after operation was 95% (mean follow up 42 month). Therefore the operative risk of combined surgery is, in general, low and the long term results are favorable.

Aged↗

The effect of graft perfusion with warm blood cardioplegia for cadaver heart transplantation.

This study was designed to verify the effect of reperfusion of donor hearts in a perfusion apparatus after 60 min of global ischemia prior to heart transplantation. Thirteen dogs were exsanguinated from the femoral artery and cardiac arrest was achieved. The hearts were left in situ at room temperature (25 degrees C) for 60 min. In group A (n = 7), the hearts were excised and reperfused 60 min after cardiac arrest in the perfusion apparatus with substrate-enriched warm blood cardioplegia (WBCP) containing a hydroxyl radical scavenger, EPC, followed by 45 min of blood perfusion. Next, the hearts were preserved in cold (4 degrees C) University of Wisconsin (UW) solution. In group B (n = 6), the hearts were perfused with cold (4 degrees C) St. Thomas' solution 60 min after cardiac arrest and preserved in cold UW solution. Thereafter, all hearts in both groups were transplanted orthotopically to recipient dogs. In group A, 6 of 7 dogs were weaned from cardiopulmonary bypass (CPB). In group B, only 2 of 6 dogs were weaned from CPB. Moreover, 3 of the 6 hearts in group B did not start beating after transplantation (stone heart). This study suggested reperfusion of the donor heart in the perfusion apparatus with WBCP to be a beneficial preconditioning method when utilizing 60-min arrested hearts for transplantation.

Animals↗

Sleep patterns during 20-m nitrox saturation dives.

The sleep patterns were examined through three simulated 20-m nitrox saturation dives. The standard polysomnography of 12 divers was recorded respectively for a total of 204 nights, as were patterns of change or consistency in sleep variables. For the 11 divers in their 20s and 30s there was nothing unusual about their sleep variables. However, a reduction of total sleep time in accordance with the lengthening of sleep latency was observed. This was recognized from the latter part of the bottom period to the postdive period. This tendency was notable for the diver in his 50s. These findings suggest that the decompression environment and the psychological stress of the long-term closed environment of a hyperbaric chamber have effects on divers' sleep.

Adult↗

Esophageal contractility synchronous with expiration.

On the basis of our previous finding that the cervical esophagus was closed during tracheoesophageal phonation, we postulated that the muscle of the cervical esophagus actually contracted during expiration and speculated on its possible regulation by the recurrent laryngeal nerve. Electromyography of the esophageal musculature and fluoroscopy of the esophagus were performed in laryngectomees to demonstrate whether the esophagus contracted during expiration or not. Electromyography, performed in 2 subjects, revealed a burst of discharges synchronous with expiration. Fluoroscopy during tracheoesophageal phonation was performed in 13 subjects to investigate the influence of resection of the esophageal branch of the recurrent nerve on esophageal motor activity. Among 13 subjects, 4 subjects who underwent paratracheal dissection (PTD) at the time of laryngectomy showed a lower superior limit of esophageal closure than did the 9 subjects without PTD, indicating that the cervical esophagus in PTD loses its contractility with the sacrifice of the esophageal branch of the recurrent nerve. We concluded that the cervical esophagus is closed by muscle contraction synchronous with expiration, preventing air entry into the stomach during deep expiration or phonation, and that the esophageal branch of the recurrent nerve is involved.

Electromyography↗

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↗

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↗

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↗

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↗

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↗

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↗