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Biomedical subjects

H Itoh

Publications and source records attributed to H Itoh.

At least 577 records · Page 32Linked to original sources

Decreased serum apolipoprotein A-I concentrations in cows infected with Salmonella typhimurium.

Serum apolipoprotein A-I concentrations in cows infected with Salmonella Typhimurium were evaluated to assess its relevance in salmonellosis. Apolipoprotein A-I has been shown in rats to be secreted by the intestine as well as the liver. Clinical symptoms such as diarrhea revealed an outbreak of salmonellosis in 22 cows on a farm, and sera were obtained at 6 (acute phase), 16, 28 (convalescent period) and 42 d (postconvalescent period) after the outbreak. Apolipoprotein A-I concentrations (mean +/- SD, mg/mL), determined by ELISA, were 0.598 +/- 0.497 (day 6), 0.111 +/- 0.060 (day 16), 0.432 +/- 0.311 (day 28) and 0.727 +/- 0.516 (day 42). Compared with the concentration at day 42, those at 16 and 28 d were significantly (P < 0.01, P < 0.05) lower, but that at day 6 was not. The serum concentration of apolipoprotein B-100 (of liver origin in cattle) was unaltered during the course of salmonellosis. The concentration of apolipoprotein A-I was positively correlated with those of serum total cholesterol (r = 0.589, P < 0.01) and phospholipids (r = 0.590, P < 0.01). These results suggest that apolipoprotein A-I in cattle is in part of intestinal origin, and also that its decreased serum concentration in salmonellosis can be attributed to the reduced intestinal synthesis or secretion of this apolipoprotein. Moreover, as a potential carrier for dietary lipids such as cholesterol, determination of serum apolipoprotein A-I concentration is suggested to be useful when assessing the nutritional status of the affected cows.

Animals↗

Standardization of low attenuation area versus total lung area in chest X-ray CT as an indicator of chronic pulmonary emphysema.

We examined the methods for measuring the LAA% (100 x low attenuation area/total lung area) on thoracic X-ray CT scans in order to develop a useful indicator of chronic pulmonary emphysema (CPE). First, we modified the method for calculating the LAA% to be applicable by the programming tool installed in a commercially available CT machine in order to minimize manual procedures. This new method proved to be applicable in all CT machines produced after 1987. Second, we examined the difference in the Hounsfield Unit (HU) between different CT machines using two kinds of phantoms. One phantom was composed of Styrofoam, which has a density similar to the low attenuation areas. The other phantom was composed of Styrofoam and water, which has a density similar to the lung. We proved that the difference of LAA% with the correct value was 5% at maximum among four different CT machines. Thus, the phantom developed in the present study may play an important role in the standardization of HU. Finally, the possibility of decreasing the X-ray levels was examined. Twenty-five percent of the standard electrical current provided the same LAA% in cases where the subject was an established CPE patient, whereas the LAA% was overestimated in subjects with a normal LAA% value. However, a correction using a linear regression equation may be possible in the latter cases. It may be concluded that LAA% analysis can easily be performed in many city hospital, without much investment of manual procedures or any corrections to the HU levels between different CT machines. This method may be useful as a routine follow up for CPE patients because of the smaller irradiated dose given when using a CT machine.

Algorithms↗

The inhibition of canine vein graft intimal thickening using a newly developed antiplatelet agent.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of a newly developed antiplatelet agent, 4-cyano-5, 5-bis[methoxyphenyl]-4-pentenoic acid (E5510) on intimal hyperplasia of experimental autologous vein grafts in a distal poor runoff canine model. METHOD: The femoral vein was implanted into the femoral artery preparing a distal poor runoff model. These animals were divided into three groups consisting of the E5510 group, the Aspirin group, and the Control group. The vein grafts were harvested at either 1 or 4 weeks after implantation. RESULTS: At 4 weeks, the degree of intimal hyperplasia of the graft of E5510 group was significantly less than that of the Aspirin group and the Control group (p < 0.05). No significant difference was observed between the Aspirin group and the Control group. At 1 week, the degree of intimal cell proliferation was determined by bromodeoxyuridine (BrdU) incorporation and was expressed as the BrdU labeling index. The BrdU labeling index of the E5510 group was also significantly lower than that of the Control group (p < 0.05). CONCLUSIONS: These data demonstrate the efficacy of E5510 in reducing intimal hyperplasia of vein grafts under distal poor runoff conditions by reducing the degree of smooth muscle cell proliferation.

Animals↗

[Natriuretic peptide system].

Natriuretic peptide system consists of three endogenous ligands, ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide) and CNP (C-type natriuretic peptide), and three receptor subtypes, natriuretic peptide receptor (NPR)-A or guanylate cyclase (GC)-A and NPR-B or GC-B and C receptor (NPR-C). ANP and BNP are mainly secreted from the atrium and ventricle of the heart respectively to act as cardiac hormones whereas CNP is secreted from the endothelium to act as an endothelium-derived relaxing peptide. ANP and BNP regulate body fluid and blood pressure to reduce cardiac pre- and after-load. Recent molecular biology and developmental biotechnology demonstrated the physiological role of ANP and BNP for the determination of basal blood pressure. CNP can modulate the phenotype of vascular smooth muscle cells to regulate vascular remodeling. Therefore, natriuretic peptide system is implicated in the pathophysiology of hypertension, congestive heart failure atherosclerosis and renal diseases. Clinical application of natriuretic peptide system is actively going on progress. Determination of plasma ANP and BNP levels are useful for the evaluation of congestive heart failure, cardiac hypertrophy and acute myocardial infarction. Infusion of ANP improves acute heart failure. Application of NEP (neutral endopeptidase) inhibitor for the treatment of congestive heart failure and hypertension is under clinical trial.

Animals↗

Inhibition of cholesterol biosynthesis by squalene epoxidase inhibitor avoids apoptotic cell death in L6 myoblasts.

The relationship between the inhibition of cholesterol biosynthesis and occurrence of myopathy was studied in L6 myoblasts using two lines of cholesterol biosynthesis inhibitors, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (simvastatin) and squalene epoxidase inhibitors (TU-2078 and NB-598). All inhibitors completely inhibited the cholesterol synthesis in L6 myoblasts at doses of 1 and 3 microM. Simvastatin (3 microM) inhibited the fusion reaction of L6 myoblasts followed by the severe cellular damage. The myoblasts also had failed actin fiber formation and creatinine phosphokinase (CPK) production. Additionally, this agent also caused apoptotic cell death in differentiated L6 muscle fiber, indicating that skeletal myopathy by HMG-CoA reductase inhibitors seems to occur not only in differentiating immature myoblasts but also in matured skeletal myotubes. In contrast, TU-2078 and NB-598 had no effect on the fusion reaction of differentiating myoblasts or on the cellular viability of muscle fiber at 3 microM, enough to completely inhibit cholesterol biosynthesis. It is conceivable that the mevalonate depletion and subsequent failure of ras farnesylation induced by simvastatin might cause the defects in differentiation and maintenance of the muscle fiber. Squalene epoxidase inhibitors did not show this adverse effect presumably because of the enzyme inhibition downstream of farnesyl synthesis. The present findings suggest the safe use of squalene epoxidase inhibitors in lipid-lowering therapy.

Actins↗

[Mechanism of increase in exercise tolerance in patients with acute myocardial infarction].

The contribution of cardiac output reserve and the skeletal muscle to exercise capacity was investigated in 24 patients with acute myocardial infarction. Symptom-limited exercise tests with a cycle ergometer were performed at 1 week, 3 weeks, and 3 months after the onset of the first infarction. Ventilatory gas was analyzed throughout the testing, and peak oxygen uptake (peak VO2) and anaerobic threshold (AT) were determined. During the test, the cardiac index (CI) was measured by the dye dilution method and the change in CI during exercise (delta CI) was calculated as an index of cardiac output reserve. The cross-sectional area of the thigh muscles (CSA) at the level of 10 cm above the patella was measured using computed tomography. Peak VO2 and AT increased significantly from 1 week to 3 months after the onset of infarction. delta CI increased significantly from 1 week to 3 weeks, and CSA increased significantly from 3 weeks to 3 months. Peak VO2 correlated significantly with both delta CI and CSA at each measurement point, as was AT with delta CI and CSA. Change in peak VO2 correlated with change of delta CI from 1 week to 3 weeks, and also with both delta CI and CSA from 3 weeks to 3 months. These results suggest that both cardiac output reserve and peripheral factors contribute to the exercise capacity up to 3 months after the onset of myocardial infarction. In particular, peripheral factors such as muscle volume are important to improve exercise capacity from 3 weeks to 3 months.

Aged↗

[Myotonic dystrophy with marked megacolon: report of a case].

A 45-year-old woman was incidentally suspected to have megacolon. Chest X-rays showed elevated left diaphragm due to colonic gas, and the heart was deviated to the midline. Barium enema revealed marked dilation of the sigmoid colon, confirming the diagnosis of megacolon. Maximal diameter of the sigmoid colon was 23 cm, but she had no gastrointestinal symptoms. During the work up for megacolon, the presence of myotonic dystrophy was suspected. She had hatchet face, but was not bald. Muscles of the neck and extremities were slightly atrophic. There was percussion myotonia of the tongue and both hands, and grip myotonia of the hands. Laboratory examinations showed impaired glucose tolerance and low level of serum IgG. EMG showed myotonic discharges and myopathic units in the limbs. Brain CT imaging revealed a thick skull. Cases of myotonic dystrophy associated with marked megacolon are rare in Japan. Megacolon presents a high risk for ileus, volvulus, and rupture, and myotonic dystrophy is associated with a high operative and anesthesic risk. Megacolon, therefore, is an important complication to look for in the management of myotonic dystrophy.

Female↗

Expression of natriuretic peptide system during embryonic stem cell vasculogenesis.

The natriuretic peptide family consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). We have elucidated that CNP is synthesized by endothelial cells. We have also shown that CNP secretion is potently suppressed by vascular endothelial growth factor (VEGF). In the present study, we examined the developmental gene expression of the natriuretic peptide system with the expression of VEGF and endothelial cell-specific receptor tyrosine kinases (RTKs), which expression is necessary for vasculogenesis, using embryoid bodies (EB) as an in vitro model for vascular development. When mouse embryonic stem (ES) cells were cultured in suspension culture, ES cells spontaneously differentiated into EB on day 4 and then into cystic EB (day 10). The VEGF gene transcript was detected early, on day 4. The expression of Flk-1, and flt-1 (the two VEGF receptors) and also of tie-2, which is crucial for blood island formation, was detected as early as day 4, and also on days 8 and 21. In contrast, the expression of flt-4, the receptor for VEGF-C, and tie-1, was first detected on day 21. Along with the developmental expression of these markers of differentiation for endothelial cells, the gene expression of CNP and its specific receptor, ANP-B receptor, was detected on days 4, 8, and 21. In contrast, the gene expression of BNP, which acts as a cardiac hormone, and the gene expression of the ANP-A receptor, which is specific to ANP and BNP, was first detected on days 8 and 21, respectively. These results indicate the distinct role of CNP in the natriuretic peptide family and the close linkage of CNP expression and endothelial cell differentiation, suggesting a possible role of CNP in vasculogenesis.

Animals↗

Role of cardiac nonmyocytes in cyclic mechanical stretch-induced myocyte hypertrophy.

In cardiac hypertrophy or ventricular remodeling, not only the enlargement of myocytes but also interstitial or perivascular fibrosis are observed simultaneously, which suggests an interaction between cardiac myocytes and fibroblasts. In this study, we examined the mechanism of cyclic mechanical stretch-induced myocyte hypertrophy, highlighting the interaction between myocytes and cardiac nonmyocytes, mostly fibroblasts. Ventricular myocytes (MC) and cardiac nonmyocytes (NMC) were separately extracted from neonatal rat ventricles by the discontinuous Percoll gradient method and primary cultures of cardiac cells were prepared. Cyclic mechanical stretch was applied to the cultures with a Flexercell Stress Unit. In addition to cell size, we examined atrial natriuretic peptide/brain natriuretic peptide (ANP/BNP) production as the most sensitive biological markers for MC hypertrophy. Cyclic stretch did not induce hypertrophic responses in MC when they were cultured without NMC. In contrast, when MC were co-cultured with NMC, cyclic stretch induced further increase in ANP/BNP production (2.2-fold and 2.1-fold increases versus non-stretch group, after 48-h incubation). This increase in ANP/BNP production in the co-culture was significantly suppressed by CV-11974, an angiotensin II type 1 receptor antagonist. Moreover, ANP/BNP production in the co-culture was significantly suppressed by BQ-123, an endothelin A receptor antagonist, whether cyclic stretch was applied or not. This study raised the possibility that NMC mediate the hypertrophic effect of mechanical stress on MC by increasing endothelin production. It was also suggested that, in this process, angiotensin II is involved in the crosstalk between MC and NMC.

Angiotensin Receptor Antagonists↗

Effect of training program based on anaerobic threshold in the early phase after acute myocardial infarction.

We devised a new physical training program on the basis of anaerobic threshold for rehabilitation in the early phase of acute myocardial infarction. Forty-four patients were divided into two groups, control and training. We measured the left ventricular ejection fraction using nuclear stethoscopy during the treadmill test and calculating radioactive cardiac output. In the training group, anaerobic threshold and exercise time to the anaerobic threshold point were significantly increased, and stroke volume at rest measured by the dye dilution method increased significantly. Radioactive cardiac output during exercise also increased after the exercise therapy. These results indicate that the rehabilitation program consisting of physical training based on the anaerobic threshold is effective.

Adult↗

Airway lesions and superoxide dismutase (SOD) distribution in bronchopulmonary dysplasia (BPD).

We examined 71 cases of bronchopulmonary dysplasia (BPD) at autopsy and divided them into five groups on the basis of the patients' survival time, studying on the histological changes in the airways for the purpose of clarifying the pathogenesis of BPD from hyaline membrane disease (HMD). Furthermore, bronchiolar occlusion was classified into four types: secretion, obliterative bronchiolitis, intraluminal plug, and hyperplasia of bronchiolar components. The same occlusive findings as in bronchioli and hyaline membrane were observed from respiratory bronchioles to alveolar ducts. However, there was no obvious correlation between airway lesions and accompanying alveolar lesions excepts three cases of obliterative bronchiolitis. Furthermore, immunohistochemical studies with anti-human SOD antibodies were performed. Mn-SOD was positive for alveolar macrophages in longer surviving infants without significant correlation with histological variation, whereas slightly positive or negative in infants who died within 1 week; CuZn-SOD was rarely positive in any cases. These results is highly correlated to the pathogenesis of BPD and to its pathological advancement with its clinical course.

Autopsy↗

C-type natriuretic peptide in human coronary atherosclerotic lesions.

BACKGROUND: C-type natriuretic peptide (CNP) belongs to the natriuretic peptide family and is considered to have regulatory effects on vascular tone and smooth muscle growth. Since these features play a role in atherogenesis, the presence of CNP at such sites was studied. METHODS AND RESULTS: Thirty-three coronary artery segments were harvested at autopsy: 10 normal, with diffuse intimal thickening, and 23 atherosclerotic lesions. Samples were snap-frozen and processed for immunohistochemical staining. For the identification of CNP, a mouse monoclonal antibody (KY-CNP-1) was used. 1A4, EBM-11 (CD68), and von Willebrand factor antibodies were used to stain smooth muscle cells, macrophages, and endothelial cells, respectively. CNP is present in several cell types. Normal arterial segments show CNP-positive endothelial cells. Hypercellular atherosclerotic lesions show distinct CNP positivity of smooth muscle cells and macrophages but a decrease in positivity of endothelial cells. Advanced atherosclerotic lesions contain CNP-positive macrophages, but the smooth muscle cells within the fibrous cap and the surface endothelial cells are almost all CNP-negative. CONCLUSIONS: These observations suggest that CNP has functional significance in atherogenesis.

Adolescent↗

Paraoxonase gene polymorphism in Japanese subjects with coronary heart disease.

We investigated the association of paraoxonase (PON) gene polymorphism with both the occurrence of coronary heart disease (CHD) and the severity of coronary artery stenosis in Japanese subjects. PON is a protein associated with plasma HDL. It has been hypothesized an A/B (Gln 192-->Arg) polymorphism of PON may be involved in the pathogenesis of CHD, especially among subjects with non-insulin-dependent diabetes mellitus (NIDDM). The polymorphism was determined in 134 patients with myocardial infarction (MI) or angina pectoris, and in 252 healthy subjects as controls. The frequencies of the AA, AB, and BB genotypes in the patients were 15, 50 and 35%, respectively, and these frequencies did not differ from those in control subjects (14, 49, and 37%). The relative risk of CHD was not found to be associated with these genotypes. These data also were similar among selected subgroups (patients with MIs, those with a low-risk lipoprotein profile for CHD, and those with NIDDM). Neither the number of affected vessels nor Gensini's scores differed among the genotype groups. Our case-control study in Japanese subjects did not show that the PON A/B polymorphism is associated with a risk of CHD.

Aged↗

Platelet accumulation induced by bacterial endotoxin in rats.

We studied the effects of i.v. administration of endotoxin (Escherichia coli, Serotype 0127:B8) on the kinetics of 111In-labelled platelets within the pulmonary, abdominal and splenic vascular beds of the rat, and on the radioactivity present in dissected samples of splenic and hepatic tissues. Bolus i.v. injection of endotoxin to anaesthetised rats caused a dose-dependent, transient accumulation of 111In-labelled platelets in the pulmonary vasculature. Increased radioactivity, suggestive of platelet sequestration, was detected in tissue samples from both the spleen and the liver at 4.5 h compared to the radioactivity detected in those organs in vehicle treated rats. The modulation of endotoxin-induced platelet accumulation within the lungs, spleen and liver by pharmacological agents was investigated. The pulmonary, hepatic and splenic platelet accumulation induced by endotoxin was unaffected by pre-treatment of the animals with indomethacin, Hirulog or L-NAME. Pre-treatment with dexamethasone significantly reduced the platelet accumulation within the liver and spleen, but not the lungs.

Animals↗

cDNA cloning of rat pS2 peptide and expression of trefoil peptides in acetic acid-induced colitis.

By using a combination of the methods of reverse transcription-PCR and rapid amplification of cDNA ends, a cDNA for rat pS2 peptide (rpS2) was successfully cloned and sequenced from rat stomach. By RNA blot analysis, the gene was shown to be expressed abundantly in the stomach and only faintly in the duodenum, but not in other tissues including the distal small and large intestines. rpS2 expression was also examined in the rectum during the course of acetic acid-induced colitis; rpS2 mRNA was detected during the acute phase of colitis but not in normal controls or during the recovery phase. On the other hand, expression of rat intestinal trefoil factor (rITF) was down-regulated during the acute phase of colitis and then up-regulated during the recovery phase, whereas rat spasmolytic peptide was not detectable throughout the course of the induced colitis. These results indicate that the patterns and timing of the expression of these trefoil peptides are different from each other. rpS2 may play an important role in the proliferation of intestinal epithelial cells during the acute phase of mucosal ulceration, whereas rITF may be involved in differentiation of the cells, particularly to form goblet cells, during the recovery phase.

Acetic Acid↗

Functional anatomy of GO/NO-GO discrimination and response selection--a PET study in man.

The purpose of this study was to identify the functional fields activated in relation to the NO-GO decision. Nine healthy subjects participated in the study which consisted of two test positron emission tomography (PET) scans (GO/NO-GO task and response selection task) and one control scan. In the response selection task, subjects were asked to flex their thumb of the right hand when a light emitting diode (LED) placed 60 cm from their eyes turned on red and to flex their index finger of the right hand when LED turned on green. In the GO/NO-GO task, subjects were asked to flex their thumb when the LED turned on red, however, they were asked not to move their fingers when LED turned on green. In the control state, they were asked simply to look at the LED without any movement of finger during the course of the scan. The mean regional cerebral blood flow (rCBF) change images for each task minus control and task minus task were calculated and fields of significant rCBF changes were identified. Several fields in the prefrontal cortex of the right hemisphere were specifically activated in relation to the GO/NO-GO task. The results indicate that the prefrontal cortex of the right hemisphere may be a key structure to make a decision not to move.

Adult↗

C-type natriuretic peptide as an autocrine/paracrine regulator of osteoblast. Evidence for possible presence of bone natriuretic peptide system.

C-type natriuretic peptide (CNP) is a local regulator in the brain and vascular wall. We present data to demonstrate the production and action of CNP in the osteoblast. CNP increased cGMP production, far more potently than atrial natriuretic peptide (ANP) in an osteoblastic cell line, MC3T3-E1. Since ANP and CNP are the ligands for two particulate guanylate cyclases, guanylate cyclase-A (GC-A) and guanylate cyclase-B (GC-B), respectively, these results reveal the expression of GC-B in MC3T3-E1. In addition, CNP mRNA and CNP-like immunoreactivity were detected in cell extracts from MC3T3-E1 and its culture medium, respectively. Both CNP and 8-bromo cGMP dose-dependently decreased [3H]thymidine uptake, without affecting alkaline phosphatase activity. These results indicate that CNP is a novel autocrine/paracrine regulator of osteoblast and suggest the presence of "bone natriuretic peptide system."

3T3 Cells↗