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Biomedical subjects

K Ichihara

Publications and source records attributed to K Ichihara.

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

[Microcirculation in the myocardium].

The coronary artery supplies the arterial blood that contains oxygen and nutrients for the myocardial tissue to produce high-energy phosphates aerobically. The left anterior descending and circumflex coronary arteries run on the epicardial surface of the left ventricle, turn toward the endocardium at a right angle, and nourish the tissues of the subendocardinal layers with the arterial blood. Cessation of coronary blood flow makes the myocardium ischemic. The endocardium is particularly susceptible to ischemia because the arteries that run to the endocardium are pressed due to extravascular compression during every systole. Coronary vasodilators are still used as anti-anginal drugs. However, a potent coronary vasodilator may cause coronary-steal and thereby worsen the ischemia-induced myocardial injury. We will demonstrate changes in the microcirculation of the ischemic myocardium caused by coronary vasodilators and demonstrate that a coronary vasodilator is not always effective on the ischemic myocardium.

Coronary Vessels↗
PubMed1999

[Are all HMG-CoA reductase inhibitors protective against ischemic heart disease?].

Effects of pravastatin, simvastatin, atorvastatin, fluvastatin and cerivastatin on myocardial contractile dysfunction during reperfusion after brief ischemia were examined in dogs. Pretreatment of the dog with lipophilic HMG-CoA reductase inhibitors for 3 weeks, simvastatin (2 mg/kg/day), atorvastatin (2 mg/kg/day), fluvastatin (4 mg/kg/day), and cerivastatin (40 micrograms/kg/day) worsened recovery of myocardial contraction during reperfusion after brief ischemia in association with reduced myocardial ATP level. A hydrophilic HMG-CoA reductase inhibitor, pravastatin (2 and 4 mg/kg/day), did not affect the recovery of myocardial contractile function and ATP level during reperfusion following ischemia. The lipophilic inhibitors may enter the myocardial cell, inhibit ubiquinone biosynthesis, and depress ATP generation in mitochondria, leading to worsening of the myocardial stunning after reperfusion subsequent to ischemia.

Adenosine Triphosphate↗
PubMed1999

Evaluation of cases with silicosis using the parameters related to Fas-mediated apoptosis.

To establish a new clinical index for immunological abnormalities occurring in silicosis, several clinical parameters related to Fas-mediated apoptosis; i.e., membrane Fas expression on peripheral blood lymphocytes (mFas), serum soluble Fas levels (sFas), serum soluble Fas ligand levels (sFasL), and soluble/membrane Fas mRNA expression ratios (s/mFas ExR) in peripheral blood mononuclear cells (PBMC) were investigated. Fifty-eight silicosis patients with no clinical symptoms of autoimmune diseases were the subjects of this study. Factor analysis was performed using 12 clinical parameters including four parameters related to Fas-mediated apoptosis. Two common factors were identified. Factor 1 which consisted of the following parameters; duration of exposure, symptomatic dyspnea, PO2, PCO2, and A-aDO2, should be designated as the respiratory factor for cases with silicosis. The parameters of factor 2 were serum IgG, sFas with high factor loading, titer of ANA, sFasL, and s/mFas ExR. These parameters of factor 2 are indicative of the immunological disorders occurring in silicosis cases. Some cases exhibited abnormalities in parameters of factor 2 but not factor 1. The factor analysis clearly demonstrated that the parameters related to Fas-mediated apoptosis should be the most beneficial for predicting the pre-clinical status of complicated autoimmune diseases in silicosis.

Aged↗
PubMed1999

[Acquisition of evidence and facts for a consulting service in the department of clinical laboratory to support effective usage of laboratory tests].

We are developing an integrated laboratory information database to share the evidences and facts with clinicians for effective application of diagnostic laboratory tests for the care of individual patients. It includes high quality evidence acquired from the clinical trials and systematic reviews as well as basic information about the analytical method, related disorders and so on of each laboratory test. We should also have the skills to appropriately obtain information from articles about relevant subjects and obtain the original facts from the laboratory database combined with the database from the department of medical records to review diagnostic data of individual cases. These strategies to acquire and accumulate those kinds of knowledge and information are essential for the management of a consulting service room as part of the clinical laboratory department. We must contribute to the improvement of clinical diagnoses and treatments, and serve as professional consultants with the expertise.

Clinical Laboratory Information Systems↗
PubMed1999

[Dynamic generation of diagnostic knowledge from a database of well defined case clinical records].

To promote an evidence-based practice of laboratory medicine, we created a database of 1584 typical case records consisting of 30 common diseases. Cases without therapy or major complication were carefully selected. Characteristic clinical symptoms and signs indicating the severity were recorded together with general laboratory test results. A user-friendly computer system for interpretive laboratory diagnosis was also created. It features (1) automatic graphics for visualizing distributions of laboratory values and/or prevalence of clinical symptoms and signs, (2) simultaneous display of distributions of common test values for any combination of diseases, (3) quick subclassification of cases within a disease group by any clinical characteristic, (4) diagnostic guidance by dynamic calculation of a novel similarity index that represents matching of a given set of signs/values with those of typical cases in the database.

Clinical Laboratory Techniques↗
PubMed1999

[Cost-effectiveness of exercise 201Tl myocardial SPECT in patients with chest pain assessed by decision-tree analysis].

To evaluate the potential cost-effectiveness of exercise 201Tl myocardial SPECT in outpatients with angina-like chest pain, we developed a decision-tree model which comprises three 1000-patient groups, i.e., a coronary arteriography (CAG) group, a follow-up group, and a SPECT group, and total cost and cardiac events, including cardiac deaths, were calculated. Variables used for the decision-tree analysis were obtained from references and the data available at our hospital. The sensitivity and specificity of 201Tl SPECT for diagnosing angina pectoris, and its prevalence were assumed to be 95%, 85%, and 33%, respectively. The mean costs were 84.9 x 10(4) yen/patient in the CAG group, 30.2 x 10(4) yen/patient in the follow-up group, and 71.0 x 10(4) yen/patient in the SPECT group. The numbers of cardiac events and cardiac deaths were 56 and 15, respectively in the CAG group, 264 and 81 in the follow-up group, and 65 and 17 in the SPECT group. SPECT increases cardiac events and cardiac deaths by 0.9% and 0.2%, but it reduces the number of CAG studies by 50.3%, and saves 13.8 x 10(4) yen/patient, as compared to the CAG group. In conclusion, the exercise 201Tl myocardial SPECT strategy for patients with chest pain has the potential to reduce health care costs in Japan.

Chest Pain↗
PubMed1998

Fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, scavenges free radicals and inhibits lipid peroxidation in rat liver microsomes.

We investigated the effect of fluvastatin sodium (fluvastatin) and pravastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, on the formation of thiobarbituric acid reactive substances both in vivo and in vitro in rat liver microsomes and on active oxygen species. Oral administration of fluvastatin at low doses (3.13 and 6.25 mg/kg) inhibited the formation of thiobarbituric acid reactive substances in rat liver microsomes, but high doses (12.5 and 25 mg/kg) did not change the formation of thiobarbituric acid reactive substances. Fluvastatin at any dose used had no effect on the content of cytochrome P-450 and the activity of NADPH-cytochrome P-450 reductase. In in vitro experiments, concentrations of fluvastatin ranging from 1 x 10(-6) - 1 x 10(-4) M markedly inhibited NADPH-dependent lipid peroxidation in liver microsomes, but pravastatin weakly inhibited lipid peroxidation. The order of magnitude of inhibition of each drug on in vitro lipid peroxidation was butylated hydroxytoluene > probucol > or = fluvastatin > pravastatin. Moreover, fluvastatin chemically scavenged active oxygen species such as hydroxyl radicals and superoxide anion generated by the Fenton reaction and by the xanthine-xanthine oxidase system, respectively, but pravastatin showed no scavenging of superoxide anion. These results indicate that the suppression of in vivo and in vitro lipid peroxidation in liver microsomes may be, at least in part, due to the scavenging by fluvastatin of free radicals.

Animals↗
PubMed1998

Phytanic acid alpha-hydroxylation by bacterial cytochrome P450.

Fatty acid alpha-hydroxylase, a cytochrome P450 enzyme, from Sphingomonas paucimobilis, utilizes various straight-chain fatty acids as substrates. We investigated whether a recombinant fatty acid alpha-hydroxylase is able to metabolize phytanic acid, a methyl-branched fatty acid. When phytanic acid was incubated with the recombinant enzyme in the presence of H2O2, a reaction product was detected by gas chromatography, whereas a reaction product was not detected in the absence of H2O2. When a heat-inactivated enzyme was used, a reaction product was not detected with any concentration of H2O2. Analysis of the methylated product by gas chromatography-mass spectrometry revealed a fragmentation pattern of 2-hydroxyphytanic acid methyl ester. By single-ion monitoring, the mass ion and the characteristic fragmentation ions of 2-hydroxyphytanic acid methyl ester were detected at the retention time corresponding to the time of the product observed on the gas chromatogram. The Km value for phytanic acid was approximately 50 microM, which was similar to that for myristic acid, although the calculated Vmax for phytanic acid was about 15-fold lower than that for myristic acid. These results indicate that a bacterial cytochrome P450 is able to oxidize phytanic acid to form 2-hydroxyphytanic acid.

Amino Acid Sequence↗
PubMed1998

Further characterization of hydrogen peroxide-dependent fatty acid alpha-hydroxylase from Sphingomonas paucimobilis.

Although fatty acid alpha-hydroxylase (FAAH) activity has been detected in various species, FAAH has not been sufficiently characterized. In this report, we describe the properties of FAAH highly purified from Sphingomonas paucimobilis. The FAAH was purified by about 5,200-fold. Blotting analysis with a specific antibody against the FAAH showed that its apparent molecular mass was approximately 43 kDa. FAAH showed alpha-hydroxylation activity in the presence of H2O2, but little if any activity with cumene hydroperoxide, t-butyl hydroperoxide, or t-butyl peroxybenzonate. The Km value for H2O2 was 72 microM. Highly purified FAAH oxidized various non-esterified saturated and unsaturated fatty acids including myristic acid, but not myristoyl-CoA. Potassium cyanide and sodium azide inhibited the FAAH activity in a concentration-dependent manner. Other respiratory chain inhibitors such as rotenone and antimycin A did not inhibit the activity. Among cytochrome P450 inhibitors, SKF-525A markedly inhibited the activity at the concentration of 2 mM, but CO did not. Imidazole, an inhibitor of plant alpha-oxidation, showed no inhibitory effect at 1 mM.

Catalysis↗
PubMed1998

Renal effects of the calcium channel blocker aranidipine and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats.

The purpose of this study was to investigate the renal effects of aranidipine, a novel calcium channel blocker of the dihydropyridine type, and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats (SHRs). When infused into the renal artery in anesthetized dogs, aranidipine (0.03 microg/kg/min) induced sustained increases in urine volume and urinary excretion of sodium and of potassium. This effect was greater than that elicited by nifedipine (0.1 microg/kg/min). The aranidipine metabolite, M-1 (0.1 microg/kg/min), also caused diuresis and natriuresis almost equal to those of nifedipine. The stop-flow experiment using the anesthetized dog showed that intrarenal infusion of aranidipine (0.03 microg/kg/min), as well as nifedipine (0.1 microg/kg/min), produced natriuresis at the distal tubular site rather than at the proximal site. Aranidipine (0.3, 1, and 3 mg/kg), when administered orally, dose-dependently increased urine volume and urinary excretion of electrolytes in conscious saline-loaded SHRs. M-1 (10 mg/kg, p.o.) also showed diuretic and natriuretic effects comparable to those of nifedipine (10 mg/kg) in SHRs. In addition, after repeated oral administration of aranidipine for 7 days, short-term tolerance was not found for its diuretic and natriuretic effects in SHRs. These results suggest that, apart from antihypertensive efficiency, aranidipine may offer a therapeutic advantage by producing diuresis and natriuresis in hypertensive patients. The metabolite of aranidipine may contribute, in part, to the diuretic, natriuretic, and antihypertensive effects of aranidipine.

Administration, Oral↗
PubMed1998

Effects of OG-VI, a nucleoside/nucleotide mixture, on stunned myocardium in dogs: is the adenosine A1 receptor involved?

BACKGROUND: OG-VI is a solution composed of 30 mmol/l inosine, 30 mmol/l sodium 5'-guanylate, 30 mmol/l cytidine, 22.5 mmol/l uridine and 7.5 mmol/l thymidine; it limits myocardial stunning in dogs. We examined whether adenosine A1 receptors were involved in the mechanism of action of OG-VI. METHODS: Dogs anesthetized with pentobarbital were subjected to 20 min of left anterior descending coronary artery ligation followed by 30 min of reperfusion. Saline, OG-VI in several doses, adenosine or inosine was infused at 0.1 ml/kg/min, starting 30 min before the ischemia. In some experiments, 1 or 3 mg/kg 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist, was injected intravenously 15 min before the start of the OG-VI infusion. The percentage myocardial segment shortening (%SS) was measured by sonomicrometry. The tissue concentration of ATP was measured in the 30-min-reperfused hearts. RESULTS: In the saline group, %SS that had been decreased by ischemia returned toward pre-ischemic values after reperfusion, although the metabolic recovery was incomplete, with a low concentration of ATP. The %SS was almost completely restored by 12 and 1.2 mumol/kg/min OG-VI, but 0.4 mumol/kg/min was less effective. Administration of adenosine or inosine did not modify the changes in %SS during ischemia/reperfusion. Pretreatment with DPCPX worsened the recovery of %SS during reperfusion after ischemia in both the saline and the OG-VI groups. Infusion of DPCPX (3 mg/kg) with saline caused the animals to die shortly after the onset of ischemia. However, the enhancement of %SS recovery during OG-VI reperfusion was observed in the presence of DPCPX. CONCLUSION: OG-VI improves the recovery of %SS during reperfusion after brief ischemia in a dose-dependent manner. This effect is not brought about by stimulation of adenosine A1 receptors.

Adenosine Triphosphate↗
PubMed1998

Sevoflurane preserves endocardial blood flow during coronary ligation in dogs: comparison with adenosine.

BACKGROUND: Sevoflurane has been reported to attenuate ischaemia-induced changes of myocardial metabolism, but the mechanism is still unclear. We examined the effect of sevoflurane on regional myocardial blood flow (RMBF) in the ischaemic area and compared the flow with that in the presence of adenosine. METHOD: Twenty-seven mongrel dogs were anaesthetized with fentanyl infused at the rate of 1 microgram.kg-1.min-1 throughout the experiment. Then they were divided into 4 groups; 0, 1, 2 MAC sevoflurane groups and adenosine group. Adenosine was infused into the left ventricle at a rate of 14.5 mg.kg-1.h-1. The left anterior descending coronary artery (LAD) was ligated for 3 min. RMBF in the endo- and epicardial layers were measured using coloured microspheres. RESULTS: Sevoflurane decreased both systolic and diastolic blood pressures and LV dp/dt max. Adenosine increased heart rate and coronary flow. The endocardial blood flow in 2 MAC sevoflurane was almost the same as that in the 0 MAC group. Adenosine significantly increased the myocardial blood flow. During 3-min ischaemia, endocardial blood flow in the ischaemic area under 2 MAC sevoflurane was essentially the same as those in 0 MAC and adenosine groups, though myocardial work in 2 MAC sevoflurane was lower compared with that of the other groups. CONCLUSION: Preservation of endocardial blood flow related to the myocardial work during ischaemia occurred during 2 MAC sevoflurane. The decrease in LV dp/dt max induced by 2 MAC sevoflurane is one of the factors responsible for the preservation of the endocardial blood flow during ischaemia.

Adenosine↗
PubMed1998

Effects of azelnidipine, a dihydropyridine calcium antagonist, on myocardial stunning in dogs.

Effects of azelnidipine, a dihydropyridine derivative, on stunned myocardium were examined in anesthetized open-chest dogs. The left anterior descending (LAD) coronary artery was ligated for 20 min and then released for 60 min. Dimethyl sulfoxide (DMSO), the solvent of azelnidipine, or azelnidipine (0.03, 0.1 or 0.3 mg/kg) was injected i.v. 20 min before ligation. Segment shortening was determined by sonomicrometry. The levels of high-energy phosphate were measured in 60-min reperfused hearts. Azelnidipine at 0.1 and 0.3 mg/kg significantly decreased diastolic blood pressure and increased % segment shortening. The increase in % segment shortening due to azelnidipine appeared to be abolished by propranolol and atropine pretreatment. Ischemia significantly decreased % segment shortening in all groups. The % segment shortening that had been decreased by ischemia recovered during reperfusion, but did not reach its preischemic level in each group. In the 0.1 and 0.3 mg/kg of azelnidipine-treated dogs, a significant enhancement of % segment shortening recovery during reperfusion was observed, as compared with that in the DMSO-treated dogs. Azelnidipine did not affect the high-energy phosphate levels in 60-min reperfused hearts. In conclusion, azelnidipine improved the contractile dysfunction in stunned myocardium, without any preservation of high-energy phosphate.

Animals↗
PubMed1998

Pharmacological effects of BAM-1120, a novel ergoline derivative, on central dopaminergic functions in rats.

BAM-1120, an ergoline derivative, has been found to display a relatively high affinity for dopamine D2-like receptor subtypes in a preliminary binding study. This study investigated whether BAM-1120 acts as a dopamine receptor agonist on prolactin-secreting and motor functions. BAM-1120 suppressed hyperprolactinemia induced by pretreatment with reserpine or estradiol in female rats. Furthermore, BAM-1120 was able to shrink a prolactin-secreting pituitary tumor (prolactinoma) in the estradiol-treated female rats. BAM-1120 induced rotations contralateral to the lesion side in rats with unilateral 6-hydroxydopamine-induced lesions of nigrostriatal dopamine pathway at a dose that was at least 30-fold higher than that required for the inhibition of prolactin secretion. These findings suggest that BAM-1120 is characterized as a putative dopamine D2-like receptor agonist that possesses a preference of inhibiting prolactin secretion over activating motor behaviors.

Animals↗
PubMed1998

Studies of repeated administration of FK-506 on myocardial metabolism in rats.

The effect of a 14-day administration of FK-506 at 1 or 3 mg/kg on plasma lipids and myocardial energy and glucose metabolism in rats was investigated. FK-506 increased the level of blood glucose in rats when given daily at an oral dosage of 3 mg/kg for 14 days. The plasma level of total cholesterol was significantly increased by FK-506 at either 1 or 3 mg/kg, whereas that of triglyceride was not changed. There was no significant difference in energy charge potential and the lactate/pyruvate ratio of the myocardial tissue between FK-506- and solvent-treated groups. Because FK-506 administration for 14 consecutive days did not disturb myocardial energy and glucose metabolism, its cardiotoxic side effects were not recognized in the present experimental toxicological evaluation of rats.

Animals↗
PubMed1998

[Decision tree sensitivity analysis for cost-effectiveness of chest FDG-PET in patients with a pulmonary tumor (non-small cell carcinoma)].

Decision tree analysis was used to assess cost-effectiveness of chest FDG-PET in patients with a pulmonary tumor (non-small cell carcinoma, < or = Stage IIIB), based on the data of the current decision tree. Decision tree models were constructed with two competing strategies (CT alone and CT plus chest FDG-PET) in 1,000 patient population with 71.4% prevalence. Baselines of FDG-PET sensitivity and specificity on detection of lung cancer and lymph node metastasis, and mortality and life expectancy were available from references. Chest CT plus chest FDG-PET strategy increased a total cost by 10.5% when a chest FDG-PET study costs 0.1 million yen, since it increased the number of mediastinoscopy and curative thoracotomy despite reducing the number of bronchofiberscopy to half. However, the strategy resulted in a remarkable increase by 115 patients with curable thoracotomy and decrease by 51 patients with non-curable thoracotomy. In addition, an average life expectancy increased by 0.607 year/patient, which means increase in medical cost is approximately 218,080 yen/year/patient when a chest FDG-PET study costs 0.1 million yen. In conclusion, chest CT plus chest FDG-PET strategy might not be cost-effective in Japan, but we are convinced that the strategy is useful in cost-benefit analysis.

Adult↗
PubMed1998

[Consultation service for efficacious usage of laboratory tests based on logical reasoning and evidence].

To effectively respond to the desire for consultation in clinical practice, we must prepare logical reasoning and evidence which rationally supports laboratory test selection, the interpretation of test results and recommendation of certain tests to physicians. Standard of medical decision making can be used for logic issues such as posttest probability, test characteristics and receiver operating characteristics (ROC) curves and establishing appropriate cut-off points. Although we usually obtain evidence by consulting authorities or the literature, good evidence can also be obtained from meta-analysis. In addition, we can demonstrate the relationship of laboratory tests among several frequently occurring diseases and epidemiological tendencies such as frequency of causative organisms at several infection sites and bacterial sensitivities to antimicrobial agents, because we have access to a large-scale laboratory database. To construct a well-organized knowledge base with explicit evidence, cooperation among many facilities is necessary to develop system, which allows the free exchange of data.

Artificial Intelligence↗