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Biomedical subjects

M Iwase

Publications and source records attributed to M Iwase.

At least 55 records · Page 3Linked to original sources

Clinical usefulness of intravenous albunex for the Doppler assessment of aortic stenosis.

Optimal Doppler recordings of stenotic aortic flow are not always easy to obtain. Therefore, the present study investigated how useful intravenous Albunex injections were for improving the Doppler assessment of pressure gradients for aortic stenosis in 20 consecutive patients who underwent Doppler and left-heart catheterization studies within a 1-week period. Continuous-wave Doppler echocardiography was performed using both a 2.5 MHz duplex and a 1.9MHz independent transducer before and after Albunex injections. The maximum and mean pressure gradients were calculated from the highest Doppler velocity tracings using the simplified Bernoulli equation. Pullback catheterization pressure tracings from the left ventricle to the ascending aorta were superimposed for determination of the maximum instantaneous and mean pressure gradients. The Doppler-derived peak and mean pressure gradients showed significant underestimation compared with the catheterization gradients (23+/-17 mmHg and 11+/-7 mmHg, respectively). However, this underestimation disappeared with Albunex injection (-2+/-7 mmHg and -1+/-4mmHg, respectively). Although the Doppler-derived instantaneous and mean pressure gradients correlated well with the catheterization gradients (r=0.909 and r=0.879, respectively), they became much closer with Albunex (r=0.987 and r=0.963, respectively). The improvements in the Doppler-derived peak pressure gradients were significant from an apical window (n=12, 84-120mmHg, p<0.001). but less so from non-apical windows (n=8, 84-91 mmHg, p=0.0146). Accordingly, Albunex is most useful for Doppler recordings of stenotic aortic flow available from the apical window, but not less so from other acoustic windows.

Adult↗

Effects of monosodium glutamate-induced obesity in spontaneously hypertensive rats vs. Wistar Kyoto rats: serum leptin and blood flow to brown adipose tissue.

We compared the effects of hypothalamic obesity induced by neonatal monosodium glutamate (MSG) treatment between spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Newborn WKY and SHR were injected intraperitoneally with 4 mg/kg body weight of MSG daily for 5 days. At 6 months of age, the obesity of SHR was more advanced than that of WKY, but at 14 months of age the severity of obesity was similar between the two strains. Hypertriglyceridemia was enhanced in MSG-treated SHR as compared with MSG-treated WKY. Systolic blood pressure measured by the tail-cuff method was consistently lower in MSG-treated SHR than in control SHR, whereas blood pressure was not affected by neonatal MSG treatment in WKY. Food restriction reduced body weight more in control SHR than in control WKY, with the former also showing enhanced ketogenesis. Neonatal MSG treatment abolished the accelerated reduction of body weight in SHR. Serum leptin concentration was markedly increased in MSG-treated obese rats, though no differences were seen between WKY and SHR in the control or MSG-treated groups. Serum leptin was closely correlated with both Lee obese index and mesenteric fat weight over the strain. Blood flow in interscapular brown adipose tissue (BAT) measured by Laser Doppler flowmetry was significantly increased in response to beta3-adrenoceptor agonist BRL26830A in both the control and MSG-treated rats. However, the response of blood flow was not affected by MSG treatment or strain difference. The present study demonstrated some strain differences in response to neonatal MSG treatment between WKY and SHR. These differences could not be explained by the difference in serum leptin level or beta3-adrenergic reactivity in BAT.

Adipose Tissue, Brown↗

Sandwich enzyme-linked immunosorbent assay of canine leptin.

Leptin is the ob gene product secreted from adipocytes in mammals, and thereby its plasma level reflects body fat content. To establish an assay method for leptin in the dog, rabbit anti-canine leptin antibody was obtained using canine recombinant leptin as an antigen. This antibody reacted to canine leptin much stronger than mouse, rat and human leptins. Sandwich enzyme-linked immunosorbent assay (ELISA) using this antibody was developed. The serum leptin levels of 13 healthy dogs were in a range from 1.4 to 5.6 ng/ml with the mean +/- SEM of 3.0 +/- 0.3 ng/ml.

Amino Acid Sequence↗

Comparison of eye-movement patterns in schizophrenic and normal adults during examination of facial affect displays.

Patients with schizophrenia are known to have deficits in facial affect recognition. Subjects were 25 schizophrenic patients and 25 normal subjects who were shown pairs of slides of laughing faces and asked to compare the intensity of laughter in the two slides. Eye movements were recorded using an infrared scleral reflection technique. Normal subjects efficiently compared the same facial features in the two slides, examining the eyes and mouth, important areas for recognizing laughter, for a longer time than other regions of the face. Schizophrenic patients spent less time ex amining the eyes and mouth and often examined other regions of the face or areas other than the face. Similar results were obtained for the number of fixation points. That schizophrenic patients may have employed an inefficient strategy with few effective eye movements in facial comparison and recognition may help to explain the deficits in facial recognition observed in schizophrenic patients.

Adult↗

Ketoacidosis accompanied by epileptic seizures in a patient with diabetes mellitus and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).

We herein report a rare case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and diabetes mellitus with ketoacidosis. An 18-year-old female patient was diagnosed to have diabetes mellitus and insulin therapy was thereafter initiated. At 26 years of age, she was hospitalized for diabetic ketoacidosis, soon followed by a loss of consciousness, left-sided dysmetria, and ataxic speech. MELAS was diagnosed because of the presence of ragged red fibers in a muscle biopsy. At 33 years of age, she was admitted to our hospital because of ketoacidosis and partial status epilepticus. A blood gas examination revealed as follows; arterial pH, 6.88; bicarbonate, 2.1 mmol/l; base excess - 29.8 mmol/l. The serum level of glucose had also increased to 30 mmol/l. The serum levels of lactate and B-hydroxybutyrate were elevated to 11.4 mmol/l and 1,990 micromol/l, respectively. Ketoacidosis improved by fluid replacement and continuous intravenous insulin infusion. A brain MRI demonstrated hyperintensity areas on FLAIR images in the bilateral temporal lobes and the cerebellum. A proton MRS demonstrated the abnormal lactate accumulation in the bilateral temporal and occipital lobes. Since epileptic seizures are rare in patients with diabetic ketoacidosis, such seizures may indicate the existence of MELAS syndrome.

Adult↗

Beta-adrenergic receptor-G protein-adenylyl cyclase signal transduction in the failing heart.

The beta-adrenergic receptor signal transduction pathway is critical for rapid adjustments to increased cardiovascular demand (e.g., during exercise). In the face of chronic stimulation of this pathway, as occurs in the pathogenesis of heart failure, beta-adrenergic receptor stimulation may become maladaptive. Under these conditions, elevation of circulating catecholamines and depletion of cardiac tissue stores of norepinephrine occur in the failing heart, resulting in desensitization. Whether or not stimulation or inhibition of the beta-adrenergic receptor signaling pathway is beneficial in heart failure is controversial. One approach to address this question is to specifically overexpress a component of the beta-adrenergic receptor signaling pathway in a transgenic mouse heart. We have characterized young and old adult mice with overexpressed cardiac G(s alpha) which couples the beta-adrenergic receptor to adenylyl cyclase. In younger animals, beta-adrenergic receptor stimulation results in an augmented heart rate and cardiac contractility. Over the life of the animal, however, a picture of cardiomyopathy develops. The result is a dilated heart with a large amount of fibrosis and myocyte hypertrophy, degeneration atrophy, and apoptosis. Conversely, chronic beta-adrenergic receptor blockade prevents the development of cardiomyopathy. These experiments support the point of view that chronic beta-adrenergic stimulation during the development of heart failure is deleterious and that protecting the heart with chronic beta-adrenergic receptor blockade is salutary, conceptually consistent with results of recent clinical trials examining the effects of beta-adrenergic receptor blockers in patients with heart failure.

Adenylyl Cyclases↗

Smt3, a SUMO-1 homolog, is conjugated to Cdc3, a component of septin rings at the mother-bud neck in budding yeast.

SMT3 of Saccharomyces cerevisiae is an essential gene encoding a ubiquitin-like protein similar to mammalian SUMO-1. When a tagged Smt3 or human SUMO-1 was expressed from GAL1 promoter, either gene rescued the lethality of the smt3 disruptant. By indirect-immunofluorescent microscopy, the HA-tagged Smt3 was detected mostly in nuclei and also at the mother-bud neck just like septin fibers. Indeed immunoprecipitation experiments revealed that Cdc3, one of septin components, was modified with Smt3. Furthermore, the protein level of the Cdc3-Smt3 conjugate was reduced and the septin rings disappeared in a ubc9-1 mutant at a restrictive temperature, where the Smt3 conjugation system should be defective. Thus, we conclude that Smt3 was conjugated to Cdc3 in septin rings localized at the mother-bud neck. Around the time of cytokinesis the Cdc3-Smt3 conjugate disappeared. We discuss the biological significance of this Smt3 conjugation to a septin component.

Cell Cycle Proteins↗

Reduced subendocardial ryanodine receptors and consequent effects on cardiac function in conscious dogs with left ventricular hypertrophy.

The goal of this study was to examine the transmural distribution of ryanodine receptors in left ventricular (LV) hypertrophy (LVH) and its in vivo consequences. Dogs were chronically instrumented with an LV pressure gauge, ultrasonic crystals for measurement of LV internal diameter and wall thickness, and a left circumflex coronary blood flow velocity transducer. Severe LVH was induced by chronic banding of the aorta (12+/-1 months), which resulted in a 78% increase in LV/body weight. When ryanodine was infused directly into the circumflex coronary artery, it did not affect LV global function or systemic hemodynamics; however, it reduced LV wall thickening and delayed relaxation in the posterior wall in control dogs but was relatively ineffective in dogs with LVH. In LV sarcolemmal preparations, [3H]ryanodine ligand binding revealed a subendocardial/subepicardial gradient in normal dogs. In LVH there was a 45% decrease in ryanodine receptor binding and a loss in the natural subendocardial/subepicardial gradient, which roughly correlated inversely with the extent of LVH and directly with regional wall motion. Both mRNA and Western analyses revealed similar findings, with a reduction of the transmural mRNA levels and a loss in the natural gradient between subendocardial and subepicardial layers in LVH. Thus, ryanodine receptor message and binding in LVH is reduced preferentially in the subendocardium with consequent attenuation of the action of ryanodine in vivo. The selectively altered ryanodine regulation subendocardially in LVH could reconcile some of the controversy in this field and may play a role in mediating decompensation from stable LVH.

Animals↗

Impaired force-frequency relations in patients with hypertensive left ventricular hypertrophy. A possible physiological marker of the transition from physiological to pathological hypertrophy.

BACKGROUND: The extent to which force-frequency and relaxation-frequency relations (FFR and RFR, respectively) and exercise-induced adrenergic stimulation affect myocardial inotropic and lusitropic reserves has not been established in patients with left ventricular (LV) hypertrophy (LVH). METHODS AND RESULTS: We calculated the maximum first derivative of LV pressure (LV dP/dtmax) and the LV pressure half-time (T1/2) during pacing, exercise, and isoproterenol infusion in 17 patients with hypertensive LVH and 9 control subjects to investigate the influence of increases in heart rate (HR) and adrenergic stimulation on inotropic and lusitropic reserves. Group A consisted of 10 LVH patients who showed a progressive increase in the HR-LV dP/dtmax relation. Group B consisted of 7 LVH patients in whom the HR-dP/dtmax relation at physiological pacing rates was biphasic. The LV mass index was larger and the LV ejection fraction was smaller in group B than in group A (244+/-72 g/m2 versus 172+/-22 g/m2 and 55+/-18% versus 72+/-6%, respectively; both P<0.05). The increase in LV dP/dtmax was greater during exercise than pacing alone for similar increases in HR in all groups (P<0.05) (group A, 111+/-22% versus 25+/-14%; group B, 105+/-35% versus 14+/-10%; control, 111+/-24% versus 25+/-12%). T1/2 was shorter (P<0.05) during exercise than with pacing alone in all groups (group A, 41+/-6% versus 11+/-3%; group B, 38+/-9% versus 14+/-4%; control, 44+/-6% versus 12+/-5%). Isoproterenol infusion caused similar increases in LV dP/dtmax and similar decreases in T1/2 in all groups. CONCLUSIONS: The FFR was biphasic in patients with severe LVH irrespective of LV function but was preserved in patients with less severe LVH and control subjects. Importantly, the RFR and adrenergic control of both inotropic and lusitropic reserves were well preserved in all LVH patients. A biphasic FFR at physiological pacing rates may be one of the earliest markers of the transition from physiological adaptation to the pathological process in LVH patients.

Adrenergic beta-Agonists↗

Suppression of sodium-dependent glucose uptake by captopril improves high-glucose-induced morphological and functional changes of cultured bovine retinal pericytes.

The effects of captopril on glucose uptake, as well as morphological and functional changes of retinal pericytes, in a high-glucose medium were examined. Retinal pericytes were incubated in medium with 5 and 30 mM glucose and 30 mM glucose with 10(-6) to 10(-3) M captopril. Captopril decreased the cellular uptakes of d-glucose and alpha-methyl glucoside in the presence, but not in the absence, of sodium. The cellular size and contents of glucose, sorbitol, and fructose were increased in 30 mM glucose concomitant with the decreased thymidine, cellular DNA content, and ratios in glucose to sorbitol and to fructose, compared with those in 5 mM glucose. These changes observed in 30 mM glucose were reversed by 10(-4) M captopril. These data suggest that the suppression of d-glucose uptake through a sodium-coupled glucose transporter by captopril may attenuate the swelling and loss of pericytes observed in the early stage of diabetic retinopathy.

Angiotensin-Converting Enzyme Inhibitors↗

A profile analysis of personality disorders: beyond multiple diagnoses.

The authors applied cluster analysis and multidimensional scaling to the analyses of 59 patients with personality pathology. Cluster analysis yielded eight typologies of patients: detached, anankastic, phobic, dramatic, erratic, emotional, milder emotional, and masochistic negativistic. Multidimensional scaling identified the dimensions of classifying patients: anxious rumination versus behavioural acting out, overall severity of personality pathology, and assertiveness versus withdrawal. Considering the distinction between personality disorder (dysfunctional personality) and abnormal personality (extreme personality), the following changes in current classification system are proposed: use of a hierarchy and exclusion criteria in a categorical-type model or use of a personality profile in a dimensional-trait model, in either case, with a dimensional rating for severity of psychopathology to define personality 'disorder'.

Adult↗

Lysophosphatidylcholine molecular species in low density lipoprotein and high density lipoprotein in alloxan-induced diabetic rats: effect of probucol.

To elucidate the contribution of diabetic state toward the accumulation of lysophosphatidylcholine (LPC) in low density lipoprotein (LDL), the LPC molecular species in LDL and high density lipoprotein (HDL) obtained from alloxan-induced diabetic rats were determined by high performance liquid chromatography. The palmitoyl LPC (PLPC) per protein was increased in the LDL of diabetic rats (p < 0.05), whereas the stearoyl LPC (SLPC) decreased in both the LDL and HDL of diabetic rats (p < 0.001) in comparison to nondiabetic rats. After the dietary administration of probucol for 4 weeks, the concentrations of SLPC and PLPC in the LDL of diabetic rats and of SLPC in the LDL of nondiabetic rats all significantly decreased by probucol (all; p < 0.01), with a concomitant decrease of the plasma concentrations of total and HDL cholesterol, and phospholipid, compared with those without probucol. The level of TBARS per protein in LDL increased in diabetic rats, and decreased by probucol (p < 0.01). In conclusion, the oxidative stress is thought to be an important factor to accumulate LPC in LDL, although the paradoxical decrease of SLPC in diabetic LDL suggests a non-oxidative metabolism with a preference for the LPC molecular species. The reducing effect of probucol on LPC may not be solely attributed to its antioxidative effect.

Animals↗

Lysophosphatidylcholine molecular species in low density lipoprotein of type 2 diabetes.

To reveal the importance of lysoposphatidylcholine (LPC) in patients with Type 2 diabetes (DM), LPC in low density lipoprotein (LDL) was determined by high performance liquid chromatography in 38 patients with Type 2 DM and 31 age and sex-matched non-diabetic controls. Stearoyl LPC (SLPC) and palmitoyl LPC (PLPC) were detected in LDL. The contents of both LPCs per gram protein in LDL were increased in diabetic patients compared with the non-diabetics (1.99+/-0.94mg SLPC and 3.02+/-1.81 mg PLPC vs 1.47+/-0.57 mg SLPC and 2.30+/-0.83 mg PLPC, mean +/- SD, p < 0.01 and p < 0.05, respectively). PLPC showed a weak correlation with the levels of fasting plasma glucose (FPG) and HbA1c (r=0.27 and r=0.33, p < 0.05 and p < 0.01, respectively). The diabetic patients with macroangiopathy showed higher levels of PLPC per gram protein compared to those without macroangiopathy (4.60+/-2.61 mg vs 2.53+/1.15 mg, respectively, p < 0.05). The LPC molecular species may participate in the atherogenicity of LDL in patients with Type 2 diabetes.

Adult↗

Pyogenic infection of the pubic symphysis in a diabetic patient.

A 51-year-old woman with diabetes mellitus had swelling in the inguinal area leading to discharge. Insulin, irrigation of the wound and intravenous antibiotics had no effect. Fistulography and a fistula-CT showed a fistula connecting to the pubis symphysis. After curettage of the pubic symphysis, the wound was closed.

Abscess↗

Elevated production of salivary nitric oxide in oral mucosal diseases.

Nitric oxide (NO) is known to play an important role in biological systems. In this study, we measured levels of NO in the saliva of 39 patients with oral mucosal diseases: 21 had oral lichen planus (OLP) and 18 had recurrent aphthous ulceration (RAU). NO was assayed using the Griess reagent, which measures nitrite (NO2), the byproduct of NO. NO2 was detected in all tested samples, and levels in the saliva of patients were significantly increased relative to those of healthy subjects. We also examined the effect of NO on fibroblasts, keratinocytes and NA cells (an epithelial cancer cell line) in vitro. S-nitroso-N-acetyl-DL-penicillamine (SNAP) and 3-morpholinosydnonimine (SIN-1) were used as NO donating reagents. The results revealed that cell viability was significantly reduced by NO derived from SNAP and SIN-1 in a dose-dependent manner. Although the role of salivary NO in normal physiology is as yet unknown, these findings suggest that excessive salivary NO plays a potential role in modifying oral mucosal diseases as a physiopathological regulator.

Adult↗

Decreased antipyrine clearance following endotoxin administration: in vivo evidence of the role of nitric oxide.

Klebsiella pneumoniae endotoxin has been found to decrease hepatic P450-mediated drug-metabolizing enzyme activity in a time-dependent manner. In this study, we investigated the role of nitric oxide (NO) in the decrease in hepatic drug-metabolizing enzyme activity caused by endotoxin in vivo. We measured in vivo pharmacokinetic parameters of antipyrine in rats treated with endotoxin and/or a selective inhibitor of inducible NO synthase (iNOS), S-methylisothiourea. Intraperitoneal injection of endotoxin (1 mg/kg of body weight) dramatically decreased the systemic clearance of antipyrine, reflecting reduced hepatic drug-metabolizing enzyme activity, and significantly increased the level of nitrite and nitrate (NOx) in the plasma. S-Methylisothiourea (10 mg/kg) reversed this decreasing antipyrine clearance and reduced the level of NOx in plasma. Repeated injections of an NO donor, (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK-409; 10 mg/kg), at a dose which maintained plasma NOx at the same levels as those caused by endotoxin injection, also decreased the systemic clearance of antipyrine. These findings suggest that the overproduction of NO observed in this animal model is at least partially responsible for the significant reduction in the hepatic drug-metabolizing enzyme activity that may happen in a gram-negative bacterial infection.

Animals↗

Stimulation of intestinal glucoreceptors in rats increases pancreatic islet blood flow through vagal mechanisms.

The aim of the study was to evaluate whether intestinal glucoreceptors participate in the regulation of pancreatic islet blood flow. For this purpose, anesthetized rats were infused (0.1 ml/min for 3 min) with saline, glucose, or 3-O-methylglucose directly into the duodenum. The glucose (1 mg/kg body wt) infusion rate was chosen to prevent any effects on systemic or intraportal blood glucose concentrations. Intraduodenal infusion of D-glucose increased both serum insulin concentration and islet blood flow, whereas the osmotic control substance 3-O-methylglucose had no such effects. A bilateral abdominal vagotomy performed before the infusions totally abolished both the insulin and blood flow response to glucose infusion. The absence of an increased islet blood flow in response to glucose infusion in the denervated, transplanted pancreas was a further indication of the crucial importance of the regulation of islet blood flow by the vagus nerves. It is concluded that intestinal glucoreceptors participate in the mediation of glucose-induced islet blood flow increase.

3-O-Methylglucose↗

Diminished facial expression despite the existence of pleasant emotional experience in schizophrenia.

In order to investigate the relationship between pleasant emotional experience and facial expression (i.e., laughter), mood before and after watching comic film clips, self-rated pleasant emotional experience for each film clip and electromyographic activities of facial muscles involved in laughter while watching film clips were measured for 25 patients with schizophrenia and 20 normal controls. Patients with schizophrenia who showed a significant correlation between self-rated emotional experience and major zygomatic activity were equivalent to normal controls in self-rated emotional experience and in mood after film clips; they had a significant increase in mood scores related with pleasure. Although these patients were thought to have sufficient pleasant emotional experience, they showed significantly low major zygomatic activity as compared to normal controls. It is suggested that these patients have a disturbance in the process of emotional expression rather than emotional experience.

Adult↗