[The concept of normal values (reference values) and interpretation of laboratory results].
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Clinical Laboratory Techniques↗
Biomedical subjects
K Ichihara
Publications and source records attributed to K Ichihara.
[Peptidergic nerve distribution in the gallbladder in cholelithiasis].
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Adult↗
Analysis of Factors Associated with Quality of Life in Breast Cancer Patients after Surgery.
The objective of this study was to investigate the factors associated with the quality of life (QOL) in breast cancer patients after surgery. The QOL in 83 primary breast cancer patients after surgery was prospectively assessed using a newly developed Japanese QOL questionnaire: The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD). The demographic and medical factors relating to the QOL score in the subjects were investigated by multiple regression analyses. Factors related to the four categories of the QOL-ACE (activity, physical condition, psychological condition, and social relationship) were also analyzed. The results revealed that only hospitalization had a strong negative relation to the overall QOL score. With regard to the four categories of the QOL-ACE, hospitalization had strong negative relations to the three categories (activity, physical condition and social relationship) and had weak negative relation to the psychological condition. Other demographic and medical factors such as types of surgery or adjuvant therapy had no significant association with the QOL score, except for the performance status which had positive, but not significant, association with the activity. In conclusion, this study yielded useful information concerning the management of the breast cancer patients after surgery. We had better be more concerned with the hospitalized period than other demographic or medical factors such as types of therapy to improve the QOL.
Journal Article↗
Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in rat liver during ischemia.
Effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and simvastatin, on mitochondrial respiration in ischemic rat liver were examined. Either vehicle, pravastatin (2 or 4 mg/kg per day), or simvastatin (1 or 2 mg/kg per day) was orally administered for 3 weeks. Liver ischemia was induced by cessation of the systemic circulation for 60 min. Liver mitochondria were isolated and the respiration was determined by polarography using glutamate and succinate as substrates. In the vehicle-treated group, ischemia drcreased ZO3, respiratory control index (RCI: QO3/QO4), and ADP/O ratio. Pretreatments with pravastatin and simvastatin enhanced the decreases in QO3 measured with either glutamate or succinate, and in ADP/O ratio measured with succinate. Because of decreasing QO4, HMG-CoA reductase inhibitors did not modify the changes in RCI due to ischemia. There were no significant differences in respiratory indices between pravastatin- and simvastatin-treated groups. In conclusion, HMG-CoA reductase inhibitors may enhance respiratory impairment of liver mitochondria under pathophysiological conditions, such as ischemia.
Adenosine Diphosphate↗
Effects of tilisolol on ischemic myocardial metabolism in dogs.
The effects of tilisolol on ischemic myocardial energy and carbohydrate metabolism were examined, and compared with those of propranolol. Ischemia was induced by ligating the left anterior descending coronary artery for 3 or 30 min in anesthetized open-chest dogs, 5 min after saline, tilisolol (0.2 mg.kg-1, i.v.), or propranolol (1 mg.kg-1, i.v.) injection. During ischemia, the myocardial energy stores were depleted, and the levels of glycolytic intermediates were altered, associated with ST segment elevation and TQ segment depression of the epicardial electrocardiogram. Tilisolol prevented the myocardial energy depletion and alterations of carbohydrate metabolism caused by 3 min of ischemia, to the same extent as did propranolol. Even 30 min after ischemia, the prevention of these ischemic changes was sustained by tilisolol, but not by propranolol. Tilisolol briefly reduced the ST segment elevation and TQ segment depression induced by ischemia. These results suggest that the protective effects of tilisolol on the ischemic myocardium are more potent and long-lasting than those of propranolol.
Adrenergic beta-Antagonists↗
Separation and partial characterization of soluble fatty acid alpha-hydroxylase from Sphingomonas paucimobilus.
The crude extracts from Sphingomonas paucimobilus containing 2-hydroxy fatty acid-rich sphingolipids were found to oxidize [1-14C]-myristate to 2-hydroxymyristate in the presence of NADH. The myristate-oxidation activity was partially purified about 290-fold from the cell-free extracts by ammonium sulfate fractionation and hydroxylapatite chromatography. When laurate, myristate, and palmitate were used as the substrates, the reaction products were identified as the corresponding 2-hydroxy fatty acids by gas-chromatography (GC), HPLC, and GC-mass spectrometry. The enzyme preparation required NADH and molecular oxygen for its alpha-hydroxylation activity, suggesting that the bacterial alpha-hydroxylation is typical of monooxygenase reactions. Of fatty acids tested, myristate was the most efficient substrate.
Bacteria↗
[Case of sarcoidosis localized in the quadriceps femoris].
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Adult↗
Effects of nefiracetam on drug-induced impairment of latent learning in mice in a water finding task.
We investigated the effects of nefiracetam (DM-9384), a pyrrolidone derivative, on chlordiazepoxide-, apomorphine-, and methamphetamine-induced impairment of latent learning in a water finding test in mice. Pretreatment with nefiracetam reversed the inhibitory effects of chlordiazepoxide and apomorphine, but not those of methamphetamine, on latent learning. The ameliorative effects of nefiracetam on apomorphine-induced, but not chlordiazepoxide-induced impairment of latent learning were antagonized by scopolamine. These results provide further evidence that nefiracetam has anti-amnesic effects. Further, it is suggested that the cholinergic neuronal system may be involved in the ameliorative effects exerted by nefiracetam on apomorphine-induced impairment of latent learning.
Animals↗
Cloning and sequence analysis of a cDNA encoding rice glutaredoxin.
A full-length cDNA clone (RASC8) encoding glutaredoxin (thioltransferase) was isolated from a cDNA library of an aleurone layer prepared from a developing seed of rice (Oryza sativa L.). RASC8, 568bp in length, contained an ATG codon and two possible polyadenylation signals, and encoded 112 amino acid residues. Cys-Pro-Phe-Cys, which is the active site and a highly conserved sequence among thioltransferases, was found in the deduced amino acid sequence. RASC8 was introduced into an expression vector pMALc2 and the translated product possessed thioltransferase activity.
Amino Acid Sequence↗
Effects of diazoxide on norepinephrine-induced vasocontraction and ischemic myocardium in rats.
Effects of diazoxide on norepinephrine-induced vasocontraction in vitro and global ischemia-induced lactate accumulation in the myocardial tissue in vivo were studied in rats. Diazoxide produced relaxation of the isolated rat aorta contracted by norepinephrine in a dose dependent manner. The relaxation of the aorta was associated with reduction of intracellular Ca2+ concentration. This reduction may be due either to activation of KATP channels or Na(+)-K+ ATPase, or to both. Global ischemia induced by aorta constriction for 30 min in vivo increased the myocardial tissue level of lactate. Pretreatment with diazoxide (10 mg.kg-1, i.v.) significantly attenuated the accumulation of lactate due to global ischemia. The present study suggests that diazoxide reduces ischemic influence on the myocardium partly through its vasodilatory action.
Analysis of Variance↗
Synthesis and structure-activity relationships of new (5R,8R,10R)-ergoline derivatives with antihypertensive or dopaminergic activity.
A series of new (5R,8R,10R)-ergoline derivatives was synthesized, and their antihypertensive and dopaminergic activities were tested in conscious spontaneously hypertensive rats and in rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra. (5R,8R,10R)-6-Alkyl-8-ergolinemethanols, prepared from the corresponding ergolinecarboxylates, were converted to the tosylates, which were treated with various five-membered heterocycles containing nitrogen atoms to afford the new ergolines. (5R,8R,10R)-8-(1,2,4-Triazol-1-ylmethyl)-6-methylergoline (4s, maleate: BAM-1110) exhibited potent dopaminergic activity, about 18-fold greater than that of bromocriptine mesylate. (5R,8R,10R)-8-(1,2,4-Triazol-1-ylmethyl)-6-propylergoline (8b, fumarate: BAM-1602) showed extremely potent dopaminergic activity, being about 220 and 1.15 times more active than bromocriptine mesylate and pergolide mesylate, respectively. Several compounds exhibited potent antihypertensive activity. Structure-activity relationships for antihypertensive and dopaminergic activities are discussed.
Animals↗
Synthesis and structure-activity relationships of new (5R,8S,10R)-ergoline derivatives with antihypertensive or dopaminergic activity.
A series of new (5R,8S,10R)-ergoline derivatives was synthesized, and their antihypertensive and dopaminergic activities were evaluated in conscious spontaneously hypertensive rats and in rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra, respectively. (5R,8S,10R)-6-Methyl-8- ergolinemethanols, prepared from the corresponding ergolinecarboxylates, were converted to the tosylates, which were treated with various five-membered heterocycles containing nitrogen atoms to afford the new ergolines. (5R,8S,10R)-8-(1-Imidazolylmethyl)-6-methylergoline (5a, BAM-2101) and (5R,8S,10R)-2-bromo-6-methyl-8-(1,2,4-triazol-1-ylmethyl) ergoline (7c, BAM-2202) exhibited potent antihypertensive activities. The maximum falls of systolic blood pressure after oral administration of 5a and 7c at 3 mg/kg were 95 and 132 mmHg, respectively, while those of cianergoline, bromocriptine mesylate, hydralazine, and nifedipine at the same dose were 40, 37, 47, and 49 mmHg, respectively. The durations of significant antihypertensive effects of these compounds except nifedipine were more than 7 h. None of the ergolines exhibited potent dopaminergic activity. Structure-activity relationships are discussed.
Animals↗
Enhancement of ischemic myocardial metabolic derangement by glibenclamide.
We examined whether opening of the ATP-sensitive potassium (KATP) channels in the ischemic myocardium plays an important cardioprotective role during ischemia. Dogs were anesthetized with sodium pentobarbital (30 mg/kg, i.v.). Sixty minutes after treatment of the dog with glibenclamide (0.3 or 3 mg/kg, i.v.), the LAD was ligated. At 3 or 15 min after LAD ligation, left ventricular tissue was taken from the ischemic region to measure tissue metabolite levels. After ischemia, the tissue levels of ATP and creatine phosphate decreased to 49-74% and 26-34%, respectively, and lactate level increased to 380-660%. Ischemia (either 3 or 15 min) increased the levels of G6P and F6P and decreased the FDP level, indicating the inhibition of glycolysis. Glibenclamide at either dose decreased the level of blood glucose by 20-30% and increased the blood insulin level twice. The decrease in ATP and increase in lactate due to ischemia were significantly enhanced by glibenclamide at a dose of 3 mg/kg. The increase in G6P due to 15 min of ischemia were also enhanced significantly by 0.3 and 3 mg/kg of glibenclamide. Glibenclamide worsened the metabolic alterations produced by ischemia. These results suggest that KATP channels that can be inhibited by glibenclamide may perform some functions in the ischemic myocardium.
Adenosine Monophosphate↗
Species differences in the inhibiting effect of fluvastatin, a new inhibitor of HMG-CoA reductase, on cholesterol biosynthesis.
Cholesterol synthesis both ex vivo and in vivo in liver and ileum of hamsters was significantly inhibited by fluvastatin. This ex vivo inhibition was considerably lower in fluvastatin-treated hamsters than in fluvastatin-treated rats. In hamsters and rats, fluvastatin was more potent than pravastatin on inhibitory activities of sterol synthesis in liver, but not in the hamster ex vivo. This may indicate that, in part, the hydrophobicity of the fluvastatin molecule confers the selectivity and metabolism in the liver of hamsters and rats to originate from the species differences.
Animals↗
[Experimental techniques for developing new drugs acting on dementia (7)--A water-finding task for use with mice: utility for evaluating latent learning].
This article describes a water-finding (WF) task for use with mice in which the animals are not required to perform a special behavior and are not reinforced positively by water or feed during the training stage. The test apparatus consists of a rectangular open field with an alcove in the middle of one of the long walls of the enclosure. A metal drinking tube is inserted into the center of the alcove ceiling. Nonwater-deprived mice are placed individually into the test apparatus and are allowed to explore the environment freely during the training trial. In the test session, each mouse is placed back into this environment and the time between onset of exploration and initiation of drinking from the water tube is scored as a drinking latency. Learning is inferred if the animal finds the water tube more rapidly than an animal that had not been exposed previously to this environment. At that time, the WF task provides a measure of memory related mainly to the spatial construction of the test apparatus and to the specific object (water tube) in it. The water-finding performance during the test trial is thought to be based on latent learning, because the animals are deprived of water only before the test trial in order to promote recall of the location of the water tube to which they had been exposed in the training trial. Thus, the WF task may be advantageous in evaluating memory without manipulating reinforcers, although it can be improved upon.
Animals↗
[Evaluation of physicians' decision making processes in primary care medicine].
To investigate how primary care physicians select appropriate diagnostic tests in their clinical practice, we analyzed the physician's decision making processes by means of written case simulations. We allocated the physicians who participated in this study to three groups; nine residents and ten attending physicians from the Department of Primary Care Medicine, and nine specialists from the Department of Medicine in our hospital. After they read a history and findings in each presented case, the physicians were requested (1) to make diagnostic hypotheses and predict probability of each hypothesis, (2) to select diagnostic tests and their purpose, and (3) to estimate contribution of the tests to the diagnosis. The results revealed that the attending physicians tended to order the diagnostic tests more strictly based on their hypotheses than the residents and specialists did. The attending physicians selected diagnostic tests from specific varieties rather than from "Essential Laboratory Tests" when they were confident in their hypotheses. On the other hand, they selected the tests mainly from "Essential laboratory Tests" when they were uncertain of diagnosis or needed to exclude serious diseases. They regarded the contribution of tests to the diagnosis as high when specific diagnostic tests were available for the presumptive diagnosis, or severe conditions were expected. These findings suggest that, in the setting of primary care practice, the application of laboratory tests depends on the severity of presenting conditions and pre-test certainty of the diagnostic hypothesis. Therefore, it may not be always appropriate to apply "Essential Laboratory Tests" uniformly to every patient irrespective of his/her condition.
Adult↗
MPC-1304, another type of dihydropyridine, possessing highly potent vasodilating action.
We investigated the vasodilating action of MPC-1304, one of the most potent dihydropyridines causing hypotension, in anesthetized dogs and compared this with its binding properties. After intraarterial injection, MPC-1304 was 3 times less potent than other dihydropyridines (nitrendipine, nifedipine, nicardipine and nisoldipine) in increasing femoral blood flow. After infusion of these drugs, however, MPC-1304 was the most potent in increasing femoral blood flow. The onset and recovery of the effect of MPC-1304 on femoral blood flow were slower than for nifedipine. Higher doses of Bay K 8644 were needed to antagonize the stimulating activity of MPC-1304 than for nifedipine. In a competition assay of [3H]nitrendipine binding, MPC-1304 and its metabolites bound to the dihydropyridine receptor with lower affinity than the other dihydropyridines. The binding affinity of [3H]MPC-1304 was lower than that of [3H]nitrendipine, consistent with the potency of this drug to increase femoral blood flow by bolus injection. The association and dissociation of [3H]MPC-1304 was slower than those of [3H]nitrendipine, which is consistent with the slow onset and long-lasting vasodilating effects of MPC-1304 on femoral blood flow. Moreover, diltiazem reduced a part of [3H]MPC-1304 binding in a competitive manner. In ex vivo binding assays with serum and aorta obtained after oral administration of the drug in spontaneously hypertensive rats, MPC-1304 inhibited [3H]nitrendipine binding to membrane preparations less potently than nifedipine. From these results, we conclude that MPC-1304 is a different type of dihydropyridine possessing the most potent vasodilating action of the representative dihydropyridines tested. Its activity cannot be explained solely by a slow interaction with voltage-dependent Ca2+ channels.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Effects of MPC-1304, a novel Ca2+ entry blocker, on alpha-adrenoceptor-mediated pressor responses in pithed rats.
MPC-1304 is a novel Ca2+ entry blocker of the 1,4-dihydropyridine type. In the present study, the effect of oral administration of MPC-1304 on alpha-adrenoceptor-mediated pressor responses was examined in pithed rats and compared with that of nifedipine. Drugs were administered orally to conscious animals before pithing. MPC-1304 (0.3-3 mg/kg) and nifedipine (1-10 mg/kg) inhibited pressor responses to norepinephrine, phenylephrine (alpha 1-adrenoceptor agonist), UK-14304 (alpha 2-adrenoceptor agonist), and sympathetic nerve (spinal cord segments) stimulation. MPC-1304 was roughly 3 times more potent than nifedipine in inhibiting these responses. The inhibitory effect of MPC-1304 (3 mg/kg) on the pressor response to UK-14304 lasted longer than that of nifedipine (3 mg/kg). At the same time, plasma concentrations of MPC-1304 were lower than those of nifedipine. These results suggest that MPC-1304 has a great ability to inhibit pressor responses to norepinephrine and peripheral sympathetic stimulation after its oral administration, and that this effect of MPC-1304 is closely correlated with its potent antihypertensive activity.
Administration, Oral↗