PubMed Health⌕ Search

Biomedical subjects

M Iwase

Publications and source records attributed to M Iwase.

At least 73 records · Page 4Linked to original sources

In vivo and in vitro positive interference by cefpirome in measurement of serum creatinine by the Jaffe method.

We report the case of an 81-year-old female patient with diverticulitis of the colon, whose symptoms were relieved by intravenous administration of cefpirome. However, her serum creatinine levels were falsely increased by the Jaffe method when serum samples were drawn after intravenous administration of cefpirome. The serum creatinine level in the same sample was within the normal range by the enzymatic method in the automated analyzer. In vitro experiment demonstrated dose-dependent positive interference of the creatinine level with cefpirome. These results indicate that we should be aware of the positive interfering effect of cefpirome when we measure serum creatinine by the Jaffe method, and that the enzymatic method should be widely used to measure serum creatinine levels to eliminate false reactions due to certain chemicals.

Aged↗

The effects of organic solvents on trimethadione n-demethylation in rats.

Many organic solvents are frequently used as support solvents to dissolve chemicals in the study concerning drug metabolism mediated by cytochrome P450. However, some organic solvents used as the support solvents affect the chemical's metabolism. It has been reported that some organic solvents are metabolized by CYP2E1 or inhibit its enzymatic reaction. In this study we investigated the effects of organic solvents, such as acetonitrile (AN), dimethylsulfoxide (DMSO), ethanol (EtOH), methanol (MeOH), polyethylene glycol (PEG) and propylene glycol (PG) on TMO (trimethadione) metabolism, which is mainly mediated by CYP2E1 in the rat. In the in vivo study, male SD rats were pretreated with an organic solvent intraperitoneally at a dosage of 0.5, 1 or 2 mmol/kg 1 hour before TMO administration orally at the dose of 4 mg/kg. After 2 hours, serum concentrations of TMO and DMO were determined by gas chromatography/flame detection (CG/FTD) and the serum DMO/TMO ratio was employed for assessment of the metabolic capacity of TMO. In the in vitro study, hepatic microsomal fraction was used as an enzyme source of TMO N-demethylase and enzyme activities were determined by the production of DMO. Pretreatment with DMSO and PG decreased the DMO/TMO ratio in a dose-related manner in vivo study. Furthermore, in vitro study TMO N-demethylase activity was inhibited by DMSO, EtOH and PG with different potency in a concentration related manner. However, no remarkable effects were observed by AN or PEG both in vivo and in vitro study. These results indicated that there are variations in the inhibitory effects of these organic solvents on CYP2E1-mediated metabolism and AN and PEG will be useful solvents to dissolve chemicals in the metabolic study mainly mediated by CYP2E1.

Animals↗

[Clinical evaluation of acute and chronic pulmonary thromboembolism using intravascular ultrasound and angioscopy].

Pulmonary artery thrombi and parietal lesions were observed in 13 patients (mean age 58 +/- 18 years) with acute pulmonary thromboembolism (n = 4) and chronic pulmonary thromboembolism (n = 9) using intravascular ultrasound and angioscopy at the time of right heart catheterization. Patients with acute pulmonary thromboembolism without underlying disease mainly had non-echogenic intraluminal mass, and good pulsatile vessel without intimal thickening. Angioscopy directly showed red thrombi with white fibrin coating, and no parietal lesions. Patients with chronic pulmonary thromboembolism could be classified into 3 groups: 1) Poor extensibility of the vessel wall and intimal thickening with non-echogenic thrombi on intravascular ultrasound, and relatively fresh parietal thrombi consisting of a mixture of red blood cell and fibrin, and spider web-like fibrin net on angioscopy (6 patients). 2) Crescent parietal thrombi and wall irregularity on intravascular ultrasound, and probably organized thrombi with a mixture of red and white surface on angioscopy (one patient). 3) Marked and echogenic intimal thickening and poor extensibility on intravascular ultrasound, and intimal surface irregularities and yellowish changes on angioscopy (one patient). All patients suffering acute deterioration in the chronic phase belonged to groups 1) or 2). Intravascular ultrasound and angioscopy are useful for characterizing the thrombi and related pulmonary artery lesions in patients with pulmonary thromboembolism. The pulmonary artery intima and thrombus differ between acute and chronic pulmonary thromboembolism.

Acute Disease↗

Central histaminergic neurons regulate rabbit tracheal tension through the cervical sympathetic nerve.

We previously showed that stimulation of the posterior hypothalamus decreases tracheal tension and involves central histaminergic neurons. In the present study, we reveal that central histaminergic neurons project to the rostral ventrolateral medulla and affect cervical sympathetic nervous activity in rabbits. Administration of histamine into the fourth ventricle increased cervical sympathetic nervous activity and decreased tracheal tension. These effects were inhibited by administration of a histamine H receptor antagonist, pyrilamine, into the fourth ventricle. Unilateral injection of DL-homocysteic acid into the tuberomammillary nucleus increased cervical sympathetic nervous activity, an effect was antagonized by bilateral injection of pyrilamine into the rostral ventrolateral medulla. The pulse correlogram between the stimulation pulse applied to the tuberomammillary nucleus and the cervical sympathetic nerve activity showed a mode at 150 to 200 ms, which was reduced by pyrilamine administration into the fourth ventricle. Fibers anterogradely labeled by Phaseolus vulgaris leucoagglutinin (PHA-L) injected into the tuberomammillary nucleus were distributed in the A1, A2, C1, and C2 areas which are determined by tyrosine hydroxylase-immunohistochemistry. PHA-L positive neurons were in close contact with tyrosine hydroxylase-immunoreactive neurons in these four areas. Cell bodies in the tuberomammillary nucleus retrogradely labeled with fluorogold from the rostral ventrolateral medulla were immunoreactive with histamine. These results suggest that an excitatory efferent pathway projects from the tuberomammillary nucleus to the cervical sympathetic nerve and that the histaminergic neurons of this pathway influence tracheal tension through the rostral ventrolateral medulla.

Animals↗

Overexpression of myocardial Gsalpha prevents full expression of catecholamine desensitization despite increased beta-adrenergic receptor kinase.

Inotropic and chronotropic responses to catecholamines in young adult transgenic mice overexpressing myocardial Gsalpha are enhanced. One might predict that over the life of the animal, this chronically enhanced beta-adrenergic receptor stimulation would result in homologous catecholamine desensitization. To test this hypothesis, old transgenic Gsalpha mice and age-matched controls were studied physiologically in terms of responsiveness of left ventricular function (ejection fraction) to isoproterenol in vivo and in vitro in terms of beta-adrenergic receptor signaling. Old transgenic mice still responded to isoproterenol with augmented (P < 0.05) left ventricular ejection fraction (+44+/-3%) compared with age-matched controls (+24+/-1%). Although total beta-adrenergic receptor density was reduced in the old transgenic mice, and G protein receptor kinase 2 (beta-adrenergic receptor kinase) levels were increased, the fraction of receptors binding agonist with high affinity as well as isoproterenol- and G protein-stimulated adenylyl cyclase activities were enhanced. Thus, classical catecholamine desensitization is not effective in attenuation of persistently enhanced responses to sympathetic stimulation in mice overexpressing myocardial Gsalpha. To support this conclusion further, experiments were performed with chronic isoproterenol, which elicited effective desensitization in wild-type controls, but failed to elicit desensitization in overexpressed Gsalpha mice. The results of this study suggest that the lack of protective desensitization mechanisms may be responsible in part for the dilated cardiomyopathy which develops with chronic sympathetic stress over the life of these animals.

Adenylyl Cyclases↗

Vasopressin neuron activation and Fos expression by stimulation of the caudal ventrolateral medulla.

The present study demonstrates that projections ascending from the caudal ventrolateral medulla have direct effects on the expression of the immediate early gene c-fos and of the arginine-vasopressin gene in neurosecretory cells of the hypothalamic supraoptic nucleus. Intense Fos-like immunoreactivity (Fos-LI) was observed in many magnocellular neurons of the supraoptic nucleus after electrical stimulation of the caudal ventrolateral medulla. In sham-operated rats, Fos-LI was absent or present in very few magnocellular neurons in the supraoptic nucleus. Fos-LI was visible in neurons expressing arginine-vasopressin, and was seen rarely in oxytocin neurons by double-immunostaining method. This study showed that 76% of all Fos-positive cells were arginine-vasopressin immunoreactive, whereas only 4% of them showed oxytocin immunoreactivity in the supraoptic nucleus. With in situ hybridization, a high level of arginine-vasopressin mRNA was noted in the supraoptic nucleus 3 h after stimulation of the caudal ventrolateral medulla; the expression was highest 6 h after the stimulation compared with the same region in sham-operated animals. These findings suggest that noradrenaline, released from the axon terminals originating from the caudal ventrolateral medulla, may participate in the regulation of gene transcription of arginine-vasopressin in response to physiological stimuli.

Afferent Pathways↗

Laparoscopic repair of a paraduodenal hernia.

Paraduodenal hernias have traditionally been treated by conventional laparotomy. We report the first case of a left paraduodenal hernia treated laparoscopically. A 44-year-old man was admitted with abdominal pain and nausea. Computed tomography and an upper gastrointestinal series with small-bowel followthrough showed accumulation of the small bowel on the left side of the abdomen. A laparoscopic repair was performed. The small bowel was observed beneath a thin hernia capsule. Approximately 1.5 m of jejunum was easily reduced into the abdominal cavity. The hernia orifice (5-cm diameter) was closed intracorporeally with five interrupted sutures. Good exposure of the operative field is critical to this procedure; poor exposure may limit the applicability of the laparoscopic approach. This minimally invasive operation is currently indicated in nonobstructive paraduodenal hernias, especially on the left.

Adult↗

Advanced glycosylation end products induced tissue factor expression in human monocyte-like U937 cells and increased tissue factor expression in monocytes from diabetic patients.

Tissue factor (TF) plays a central role in the initial activation of the extrinsic coagulation pathway and is thought to be involved in the development of atherosclerosis and thrombosis. The effect of advanced glycosylation end products (AGEs) on TF expression and its mechanism were assessed by flow cytometric analysis. Human macrophage-like U937 cells, which were shown to contain mRNA encoding the receptors of advanced glycosylation end products (RAGE), expressed TF in a dose-dependent manner on incubation with AGE-albumin. AGE-albumin-induced TF expression was completely inhibited by the anti-oxidant agents, catalase and probucol. TF expression in peripheral monocytes from normal volunteers was also increased by AGE-albumin. Finally, TF expression in monocytes from individuals with diabetes mellitus, in whom the concentration of circulating AGEs is reported to be increased, was higher than that in monocytes from normal controls. These results suggest that AGE-induced TF expression in macrophages/monocytes is mediated by oxidant stress. AGEs may promote thrombosis and the development of atherosclerosis by inducing TF expression in monocytes in patients with diabetes mellitus.

Albumins↗

Autoregulation of histamine release in medulla oblongata via H3-receptors in rabbits.

The release of histamine (HA) from the rostral ventrolateral medulla (RVL), the raphe nuclei (nR), and the solitary nucleus (nTS) was investigated in anesthetized rabbits using microdialysis and high-performance liquid chromatography. HA release upon electrical stimulation of the posterior hypothalamus (PH), where histaminergic cell bodies are located, was increased to 168% of the baseline level in the RVL (n = 6), 139% of the baseline level in the nR (n = 5), and 166% of the baseline level in the nTS (n = 4). Upon perfusion of thioperamide, an H3-receptor antagonist, via a microdialysis probe, HA release from the RVL, nR and nTS increased. The increase in HA release from the RVL, nR and nTS following thioperamide perfusion was suppressed by co-perfusion of thioperamide and an H3-receptor agonist, imetit. We found that HA is released from the RVL, nR and nTS, that the HA release from all three areas is increased upon stimulation of the PH, and that the HA release is locally influenced in opposite directions by thioperamide and imetit. These results suggest that HA release in the medulla oblongata is controlled by the PH and that H3-receptors participate in the autoregulation of HA release by providing negative feedback locally. Autoregulation of HA release via H3-receptors may be important for maintaining tonic output to the sympathetic nervous system.

Animals↗

Stroke topography in diabetic and nondiabetic patients by magnetic resonance imaging.

Stroke is more frequent in diabetic than in nondiabetic patients. We studied lesion topography in 61 stroke patients with diabetes mellitus and 77 without diabetes using magnetic resonance imaging. Location, number and size of infarcts were investigated. Prevalence of hypertension did not differ between diabetic and nondiabetic patients. In elderly subgroups (> or = 65 years), infratentorial infarcts > or = 5 mm in diameter were more frequent in diabetic than in nondiabetic patients (32 vs. 12%, P < 0.05), while supratentorial infarcts were not different (56 vs. 68%, ns). Asymptomatic hemorrhage combined with silent infarction was significantly less frequent in diabetic than in nondiabetic patients (5 vs. 22%, P < 0.05). In nondiabetic patients with significant stenosis in the carotid system, supratentorial infarction measuring > or = 15 mm was more frequent than in those without stenotic lesions, but the number of infarcts per patient irrespective of size was smaller when stenosis was present. On the other hand, the number of infarcts in diabetic patients was similar between those with and without carotid system stenosis. The present study demonstrated that infratentorial infarcts were more common in elderly diabetic patients, suggesting the vulnerability of vertebrobasilar circulation in diabetes.

Aged↗

Effect of gemfibrozil on serum levels of prostacyclin and precursor fatty acids in hyperlipidemic patients with Type 2 diabetes.

Lipid-lowering fibrate drugs are known to affect the synthesis of fatty acids, which may alter the prostacyclin synthesis in diabetic patients. Therefore, the serum levels of precursor fatty acids and 6-keto-prostaglandin F1alpha (6-keto PGF1alpha) were determined in ten hyperlipidemic patients with Type 2 diabetes before and after administration of gemfibrozil (900 mg/day) for 3 months, in comparison with the results in seven non-diabetic hyperlipidemic patients. Gemfibrozil significantly reduced the serum concentration of dihomo-7-linolenic acid, total cholesterol and triglycerides, but did not affect the serum levels of arachidonic acid and 6-keto PGF1alpha in diabetic and non-diabetic patients. Thus, gemfibrozil did not affect the synthesis of prostacyclin in spite of the reduction of precursor fatty acids in diabetic and non-diabetic patients.

6-Ketoprostaglandin F1 alpha↗

Changes in bite force and occlusal contacts in patients treated for mandibular prognathism by orthognathic surgery.

PURPOSE: The purpose of this study was to evaluate changes in bite force and occlusal contacts before and after orthognathic surgery in patients with mandibular prognathism and to compare the findings with those in controls with normal occlusion. PATIENTS AND METHODS: Bite force and occlusal contacts were analyzed in 23 (7 male and 16 female) patients with mandibular prognathism before and after sagittal split ramus osteotomy, and in 20 (10 male and 10 female) controls with normal occlusion. The bite force and occlusal contacts were simultaneously measured by a computerized occlusal analysis system, the T-Scan system, immediately before surgery, and at 6 weeks, 3 months, 6 months, and 1 year postoperatively. RESULTS: Both the bite force and occlusal contacts in the patients were significantly less than those in the controls before surgery. Although both the bite force and occlusal contacts in the patients were improved by the orthognathic surgery, neither approached the level in the controls within 1 year. Bite force was correlated with the number of occlusal contacts in both patient and control groups. CONCLUSION: The postoperative masticatory function does not reach control levels even 1 year after the orthognathic surgery for mandibular prognathism. Therefore, further adjustment of the occlusion should be considered before the end of treatment.

Adult↗

Trimethadione metabolism by human liver cytochrome P450: evidence for the involvement of CYP2E1.

1. Caucasian liver samples were used in this study. N-demethylation of trimethadione (TMO) to dimethadione (DMO) was monitored in the presence of chemical inhibitors of CYPs, such as fluconazole, quinidine, dimethyl-nitrosamine, acetaminophen, phenacetin, chlorzoxazone and mephenytoin. Trimethadione N-demethylation was selectively inhibited by dimethylnitrosamine and chlorzoxazone (> 50%) and weakly inhibited by tolbutamide (12%) and fluconazole (22%), whereas other inhibitors showed no effect. This result suggested that TMO metabolism to DMO is mainly mediated by CYP2E1 and marginally by CYP2C and CYP3A4. 2. Fifteen human livers were screened and interindividual variability of TMO N-demethylation activity was 3-fold. Chlorzoxazone 6-hydroxylation activity was also measured and both activities were significantly correlated (r=0.735, p < 0.01). 3. DMO production by human cDNA expressed CYP enzymes was observed mainly for CYP2E1 (10.8 nmol/tube), marginally for CYP2C8 (0.22 nmol/tube) and not detectable for other CYP enzymes. 4. These results indicate that TMO metabolism is primarily catalysed by CYP2E1 and that trimethadione would be a suitable selective probe drug for the estimation of human CYP2E1 activity in vivo.

Anticonvulsants↗

A novel cis-acting element in promoters of plant B-type cyclin genes activates M phase-specific transcription.

Plant B-type cyclin genes are expressed late in the G2 and M phases of the cell cycle. Previously, we showed that the promoter of a Catharanthus roseus B-type cyclin, CYM, could direct M phase-specific transcription of a beta-glucuronidase reporter gene in synchronously dividing BY2 tobacco cells. In this study, we determined the regulatory elements contained within the CYM promoter by using a luciferase reporter gene. Mutational analysis showed that a 9-bp element is essential for M phase-specific promoter activity in synchronized BY2 cells. The CYM promoter contains three other sequences similar to this element. A gain-of-function assay demonstrated that when fused to a heterologous promoter, these elements are sufficient for M phase-specific expression; therefore, we named these elements M-specific activators (MSAs). We found MSA-like sequences in B-type cyclin promoters from tobacco, soybean, and Arabidopsis as well as in the promoters of two M phase-specific genes, NACK1 and NACK2, which encode tobacco kinesin-like proteins. Thus, MSA may be a common cis-acting promoter element that controls M phase-specific expression of cell cycle-related genes in plants.

Base Sequence↗

Selective large coronary endothelial dysfunction in conscious dogs with chronic coronary pressure overload.

Coronary vascular responses to acetylcholine (ACh, 3 micrograms/kg i.v.), nitroglycerin (NTG, 25 micrograms/kg i.v.), and a 20-s coronary artery occlusion (reactive hyperemia, RH) were investigated in seven conscious dogs with severe left ventricular (LV) hypertrophy and chronic coronary pressure overload (CCPO) due to supravalvular aortic banding and in seven control dogs. All dogs were instrumented for measurement of ultrasonic coronary diameter (CD) and Doppler coronary blood flow (CBF). LV-to-body weight ratio was increased by 82% in CCPO dogs. In control dogs, ACh increased CD (+ 5.9 +/- 1.7%). This response was reduced (P < 0.05) in CCPO dogs (+ 1.9 +/- 0.9%). Similarly, flow-mediated increases in CD after RH were blunted (P < 0.01) in CCPO (+ 2.1 +/- 0.8) vs. control dogs (+ 6.8 +/- 1.8%). In contrast, ACh and RH increased CBF similarly in both groups. Increases in both CD and CBF to NTG were not different between control dogs and CCPO. Peak systolic CBF velocity was greater, P < 0.01, in CCPO (94 +/- 17 cm/s) compared with control (35 +/- 7 cm/s) dogs, most likely secondary to the increased systolic coronary perfusion pressure (215 vs. 130 mmHg). Histological analyses of large coronary arteries in CCPO revealed medial thickening, intimal thickening, and disruption of the internal elastic lamina and endothelium. In contrast, small intramyocardial arterioles failed to show the intimal and endothelial lesions. Thus, in CCPO selective to the coronary arteries, i.e., a model independent from systemic hypertension and enhanced levels of plasma renin activity, endothelial control was impaired for both flow-mediated and receptor-mediated large coronary artery function, which could be accounted for by the major morphological changes in the large coronary arteries sparing the resistance vessels. The mechanism may involve chronically elevated systolic coronary perfusion pressure, CBF velocity, and potential disruption of laminar flow patterns.

Acetylcholine↗

Obesity induced by neonatal monosodium glutamate treatment in spontaneously hypertensive rats: an animal model of multiple risk factors.

The present study was designed to develop an animal model of multiple risk factors, including obesity, hypertension, non-insulin-dependent diabetes mellitus, and hyperlipidemia. Hypothalamic obesity was induced by neonatal monosodium glutamate (MSG) treatment in spontaneously hypertensive rats (SHR). Female newborn SHR were treated intraperitoneally with 2 or 4 mg/kg body weight of MSG for 5 days. Obesity developed in SHR treated with 4 mg/kg of MSG but not in SHR treated with 2 mg/kg of MSG. Obese SHR had impaired glucose tolerance, hyperinsulinemia, and hypertriglyceridemia. However, the severity of hypertension was attenuated in obese SHR as compared with control SHR. The degree of obesity was closely related to the metabolic abnormalities, but inversely correlated with the blood pressure level. Macrovascular changes were investigated in obese SHR at 14 months of age. Intimal thickening was accelerated in the carotid artery of obese SHR as compared with that of nonobese SHR. Aortic contents of DNA and total cholesterol were significantly increased in obese SHR. SHR associated with MSG-induced obesity showed major manifestations of metabolic syndrome X. This animal model may be useful to study the clustering of risk factors for the development of macrovascular diseases.

Animals↗

[Effect of attenuation by the cranium on quantitative SPECT measurements of cerebral blood flow and a correction method].

Attenuation correction for cerebral blood flow SPECT image reconstruction is usually performed by considering the head as a whole to be equivalent to water, and the effects of differences in attenuation between subjects produced by the cranium have not been taken into account. We determined the differences in attenuation between subjects and assessed a method of correcting quantitative cerebral blood flow values. Attenuations by head on the right and left sides were measured before intravenous injection of 123I-IMP, and water-converted diameters of both sides (Ta) were calculated from the measurements obtained. After acquiring SPECT images, attenuation correction was conducted according to the method of Sorenson, and images were reconstructed. The diameters of the right and left sides in the same position as the Ta (Tt) were calculated from the contours determined by threshold values. Using Ts given by 2Ts = Ta - Tt, the correction factor gamma = exp (mu(1)Ts) was calculated and multiplied as the correction factor when rCBF was determined. The results revealed significant differences between Tt and Ta. Although no gender differences were observed in Tt, they were seen in both Ta and Ts. Thus, interindividual differences in attenuation by the cranium were found to have an influence that cannot be ignored. Inter-subject correlation is needed to obtain accurate quantitative values.

Aged↗