Angiolipoma of internal auditory canal presenting repeated sudden hearing loss.
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Adult↗
Biomedical subjects
Y Oka
Publications and source records attributed to Y Oka.
Renal disposition of recombinant human interleukin-11 in the isolated perfused rat kidney.
PURPOSE: To clarify the mechanism of the renal clearance of recombinant human interleukin- 11 (rhIL- 1), we investigated the renal disposition characteristics of rhIL-11 in the perfused rat kidney. METHODS: The disposition characteristics of (111)In-labeled rhIL-11 were analyzed using a single-pass indicator dilution technique and statistical moment analysis in the perfused rat kidney under filtering and nonfiltering conditions. RESULTS: Steady-state distribution volume (Vd) calculated from the venous outflow patterns of rhIL-11 at the doses of 0.3 to 10 microg/kidney was between 0.35 and 0.40 ml/g kidney. However, Vd at the highest dose decreased to a value almost identical to that of bovine serum albumin, suggesting that there is a reversible and saturable interaction between the capillary wall and rhIL-11 molecule. In filtering kidney, a remarkable accumulation of rhIL-11 was observed while its urinary excretion was highly restricted at all doses. In nonfiltering kidney, rhIL-11 showed a decreased but still significant renal uptake. Taken together, the marked renal uptake of rhIL-11 may be explained by both efficient tubular reabsorption and significant uptake from the capillary side. These processes were not saturable within the tested dose range. These characteristics of rhIL-11 are likely based on non-specific electrostatic interaction with the tissues due to its cationic charge in the cytokine. CONCLUSIONS: The renal disposition processes of rhIL-11 were clarified at organ level in a quantitative manner. These findings agree well with previous observations in an in vivo disposition study in mice.
Animals↗
Novel glycoproteins inhibiting the binding of colorectal cancer cells to E-selectin.
Novel glycoproteins carrying sialyl-LeA (SLeA) antigens (SL-GP) were isolated from ascites fluid from a patient with colorectal cancer by immunoaffinity chromatography. Their characteristics, including binding capacity to E-selectin, were investigated. SL-GP showed a typical mucin type amino acid composition in which Ser, Thr and Pro together accounted for greater than 50% of the total amino acid residues. A large amount of carbohydrate (about 80%) was present in SL-GP. The number of O-glycans carrying SLeA antigens comprised about 9% of the total number of O-glycosidic chains. SL-GP could bind to IL-1 beta treated HUVEC, and the binding was inhibited by anti-E-selectin and anti-SLeA monoclonal antibodies. The binding of colorectal cancer cells, LS 180, to HUVEC was assayed in the presence of SL-GP, oligosaccharides prepared from SL-GP and human milk SLeA hexasaccharide. SL-GP inhibited the binding most effectively, whereas equivalent amounts of the SL-GP oligosaccharides and milk SLeA hexasaccharide inhibited it only slightly. These results constitute direct evidence that a unique arrangement of SLeA antigens on the polypeptide chain, probably a cluster, is essential for the binding to E-selectin.
Antibodies↗
Apoptosis in cultured human colon cancer cells induced by combined treatments with 5-fluorouracil, tumor necrosis factor-alpha and interferon-alpha.
Biochemical analysis using nick end-labeling was performed to investigate the effect of various combinations of 5-fluorouracil, natural human tumor necrosis factor-alpha and natural human interferon-alpha on the induction of apoptosis in RPMI 4788 human colon cancer cells. After treatment with 5-fluorouracil (1 mM) for 48 h, the number of nick end-positive cells was significantly increased in comparison to the situation without treatment. When tumor cells were treated with 1 mM 5-fluorouracil, 2.86 Japan Reference Units (JRU)/ml natural human tumor necrosis factor-alpha and 1 x 10(3) IU/ml natural human interferon-alpha in combination for 48 h, the number of nick end-positive cells was significantly higher than that after treatment with 5-fluorouracil alone. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay revealed a significant decrease of relative viability, as compared to treatment with 5-fluorouracil (1 mM), 5-fluorouracil + natural human tumor necrosis factor-alpha, or 5-fluorouracil + natural human interferon-alpha for 48 h. Pretreatment with 5-fluorouracil (1 mM) for 24 h prior to treatment with natural human tumor necrosis factor-alpha (2.86 JRU/ml) and natural human interferon-alpha (10(3) IU/ml) for 24 h resulted in a significant increase of nick end-positive cells compared to pretreatment with natural human tumor necrosis factor-alpha and natural human interferon-alpha prior to treatment with 5-fluorouracil for 24 h (p < 0.05). These results suggest that 5-fluorouracil alone can induce apoptosis in RPMI 4788 tumor cells and that this effect can be enhanced by combination with natural human tumor necrosis factor-alpha and natural human interferon-alpha.
Antimetabolites, Antineoplastic↗
An immunoreactive protein to wheat-germ agglutinin antibody is induced in oat roots following invasion of the cereal cyst nematode Heterodera avenae, and by jasmonate.
A protein that cross-reacts to a wheat-germ agglutinin antibody was induced in oat roots following the invasion of second-stage juveniles (J2) of the cereal cyst nematode Heterodera avenae. This protein, designated ASP45, was acid soluble, and its molecular mass was about 45 kDa on a sodium dodecyl sulfate-polyacrylamide gel. ASP45 was induced in both compatible and incompatible interactions between the nematode and the plant, and also in roots by exposure to jasmonic acid (JA) or methyl jasmonate. However, ASP45 was not induced by elicitors of pathogenesis-related proteins, abscisic acid, or wounding. Lipoxygenase activity, which is involved in JA synthesis, was higher in nematode-infected and JA-treated roots than in their noninfected, untreated counterparts. Inhibition of lipoxygenase activity in roots abolished ASP45 induction in the nematode-infected roots. Amino acid sequences similar to that of ASP45 were found in chitinases of poplar tree and Arabidopsis, even though ASP45 showed no chitinase activity. Although the biological role of ASP45 in infected roots is not clear, JA is suggested to be involved in signal transduction after pathogen invasion of the plant.
Acetates↗
Co-localisation of insulin-like growth factor II and the proliferation marker MIB1 in hepatocellular carcinoma cells.
AIM: To assess the effect of insulin-like growth factor II (IGF-II) on proliferation of hepatocellular carcinoma (HCC) cells. METHODS: Expression of IGF-II mRNA and protein was detected in 10 archival HCC specimens using in situ hybridisation and immunohistochemistry, respectively. Expression of the Ki-67 antigen, a proliferation marker, was determined immunohistochemically on the same sections. RESULTS: Increased expression of IGF-II mRNA and protein was detected in five of the 10 HCCs in cells located at the periphery of tumour nests. The pattern of localisation of IGF-II was almost identical with that of Ki-67 antigen. CONCLUSIONS: Most of the Ki-67 antigen positive cells co-expressed IGF-II, suggesting that IGF-II may act as an autocrine or paracrine growth factor, and may play an important role in the development of HCC.
Carcinoma, Hepatocellular↗
Roles of PI 3-kinase and Ras on insulin-stimulated glucose transport in 3T3-L1 adipocytes.
The dominant negative p85alpha regulatory subunit (delta p85alpha) of phosphatidylinositol (PI) 3-kinase or dominant negative Ras (N17Ras) was overexpressed in 3T3-L1 adipocytes using an adenovirus-mediated gene transduction system. Functional expression of delta p85alpha and N17Ras was confirmed by marked inhibition of insulin-stimulated PI 3-kinase activity and mitogen-activated protein kinase activity, respectively. N17Ras expression did not affect glucose transport activity, whereas delta p85alpha expression inhibited insulin-stimulated glucose transport with impairment of GLUT-4 translocation, although inhibition of glucose transport activity was less remarkable than that of PI 3-kinase activity in delta p85alpha-expressing cells. Thus the Ras signaling pathway does not play a major part in either translocation or intrinsic activity of glucose transporters, but PI 3-kinase activation, via phosphotyrosyl proteins and heterodimeric PI 3-kinase, plays a pivotal role in insulin-stimulated glucose transport. However, a discrepancy was observed between PI 3-kinase activity and glucose transport activity, suggesting a possibility that a different pathway(s) is involved in insulin-stimulated intrinsic activity of glucose transporters.
3T3 Cells↗
Lesions of gonadotropin-releasing hormone-immunoreactive terminal nerve cells: effects on the reproductive behavior of male dwarf gouramis.
Functions of the terminal nerve (TN) are largely unknown. To examine whether gonadotropin-releasing hormone (GnRH)-immunoreactive TN cells (TN-GnRH cells) are involved in the control of reproductive behavior, effects of lesions of TN-GnRH cells were studied in male dwarf gouramis, Colisa lalia. After bilateral electrolytic lesion, a characteristic impairment was observed in one of the repertoires of male reproductive behavior, nest-building. The occurrence of mating trials in which males showed no nest-building was increased. However, the incidence of nest-building behavior during postoperative trials was not affected by the lesion. No impairment was observed in other reproductive repertoires. These results suggest that (1) TN-GnRH cells are involved in the control of the threshold for nest-building behavior initiation and (2) TN-GnRH cells are not a prerequisite for other aspects of reproductive behavior in the male gouramis.
Animals↗
The effects of post-treatment with lisofylline, a phosphatidic acid generation inhibitor, on sepsis-induced acute lung injury in pigs.
The effects of lisofylline [(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine] (LSF), an inhibitor of de novo phosphatidic acid (PA) generation, on sepsis-induced acute lung injury was studied using Hanford minipigs weighing 18 to 25 kg. Sepsis was induced by an intravenous infusion of Pseudomonas aeruginosa (1 x 10(6)/colony-forming units/kg/min over 2 h). Saline was used as the control vehicle. Six groups were studied: saline control group (SALINE: n = 5); sepsis control group (SEPSIS: n = 5); LSF control group (LSF: n = 5), which received a 25-mg/kgbolus of LSF 30 min before time zero followed by continuous infusion of 10 mg/kg/h throughout the study; LSF-treated septic groups, which were treated with LSF 30 min prior to sepsis (Pre: n = 5), 1 h postonset (Post-1 h: n = 8) or h postonset (Post-2 h: n = 8) of the bacterial infusion. Hemodynamics PaO2, neutrophil counts, and plasma porcine tumor necrosis factor-alpha concentrations were monitored for 6 h. After the minipigs were killed, lung tissue was sampled to measured wet-to-dry weight ratio (W/D), tissue albumin index (TAI), thiobarbituric acid-reactive material content (TBARM), and myeloperoxidase (MPO) activity. Compared with the SALINE group, the SEPSIS group showed significant systemic hypotension, pulmonary hypertension, arterial hypoxemia, neutropenia, and increase in TNF-alpha, MPO activity, W/D, TBARM, and TAI. LSF treatment attenuated sepsis-induced pulmonary hypertension, neutropenia, and hypoxemia, and increased MPO activity and lung injury measurements in the Pre and Post-1 h groups, but its efficacy was blunted in the Post-2 h group. Plasma TNF-alpha was decreased only in the Pre group. Thus, inhibition of intracellular PA generation through de novo pathways attenuates sepsis-induced acute lung injury.
Adjuvants, Immunologic↗
Direct stimulation of basal insulin secretion by physiological concentrations of leptin in pancreatic beta cells.
We examined a possible mechanism underlying the link between obesity and hyperinsulinemia, focusing on leptin, a peptide released from adipocytes which affects the satiety center in the brain. The leptin receptor isoforms, Ob-Ra and Ob-Rb, are present in the pancreatic beta cell line MIN6 and in rat pancreatic islets, based on RT-PCR. A 2 hr, but not a 30 min, incubation with 1 nM recombinant mouse leptin, the concentration observed in obese subjects, stimulated basal (at 5 mM glucose) insulin secretion by approximately 40% in both MIN6 and rat islets. Stimulatory effects were not observed without glucose or when the incubation medium containing 1 nM leptin had been preincubated with the immobilized leptin antibody. In contrast to the stimulatory effects on basal insulin secretion at 1 nM, the maximally stimulated insulin secretion at 25 mM glucose was not significantly changed by 1 nM leptin in isolated rat islets. In addition, 10 and 100 nM leptin exerted small but significant inhibitory effects on 16.7 mM glucose-stimulated insulin secretion. Thus, leptin acts directly on pancreatic beta cells, and stimulation of basal insulin secretion by physiological concentrations of leptin may account in part for the fasting hyperinsulinemia observed in obese subjects.
Animals↗
Targeting of GLUT1-GLUT5 chimeric proteins in the polarized cell line Caco-2.
Caco-2, a human differentiated intestinal epithelial cell line, is a promising model for investigating the mechanism of polarized targeting of apical and basolateral membrane proteins. We stably transfected rat GLUT5 cDNA and rabbit GLUT1 cDNA into Caco-2 cells with an expression vector. Immunohistochemical study revealed that the GLUT5 protein expressed was localized at apical membranes and that the GLUT1 expressed was present primarily in the basolateral membranes of cells grown on permeable support. Next, to investigate the domain responsible for determining apical vs. basolateral sorting in glucose transporters, we prepared several GLUT1-GLUT5 chimeric cDNAs and transfected them into Caco-2 cells. A GLUT1 [N terminus approximately sixth transmembrane domain (TM6)]-GLUT5 [intracellular loop (IL) approximately C terminus] chimera was observed exclusively at the apical membrane, while GLUT1 (N terminus approximately IL)-GLUT5 (TM7 approximately C terminus) and GLUT1 (N terminus approximately TM12)-GLUT5 (C-terminal domain) chimeras were observed mainly at the basolateral membrane, a localization similar to that of GLUT1. Moreover, using a recombinant adenovirus expression system, we expressed a GLUT5 (N terminus approximately TM6)-GLUT1(IL)-GLUT5(TM7 approximately C-terminus) chimera, which was observed at the basolateral membrane. Based on these results, the C-terminal domain does not determine isoform-specific targeting of GLUT1 and GLUT5. Rather, it is the intracellular loop in glucose transporters that appears to play a pivotal role in apical-basolateral sorting signals in Caco-2 cells.
Animals↗
Effects of ischemic preconditioning on ventricular arrhythmias during ischemia and reperfusion using a retrograde blood flow model in dogs.
We examined the effects of ischemic preconditioning on ventricular arrhythmias during ischemia and reperfusion from the electrophysiologic point of view by using the retrograde blood flow (RBF) model, which causes severe ischemia. A total of 51 anesthetized dogs were divided into 3 groups. Group 1 (10-min simple occlusion) consisted of 15 dogs; group 2 (10-min RBF) consisted of 20 dogs; and group 3 (10-min RBF with preconditioning) consisted of 16 dogs. Preconditioning consisted of 5 cycles of 2 min of ischemia (RBF) and 5 min of reperfusion. In the subepicardium, myocardial blood flow (MBF) in group 2 was significantly lower than in group 1 or group 3 [group 2 (4.7 +/- 2.3 ml/min per 100 g) vs group 1 (35.0 +/- 5.8) or group 3 (22.0 +/- 4.6); p < 0.01 and p < 0.05 respectively]. However, there were no differences in MBF in the subendocardium between the 3 groups. The incidence of conduction block in the subepicardium was significantly higher in group 2 than in group 1 or group 3 [group 2 (85%) vs group 1 (33%), p < 0.01; vs group 3 (38%), p < 0.01]. There were no differences in the incidence of conduction block in the subendocardium between the 3 groups. During 10-min ischemia, the incidences of ventricular fibrillation (VF) were 7% in group 1, 35% in group 2, and 6% in group 3 (group 2 vs group 1, p < 0.05; and group 2 vs group 3, p < 0.05). During 10-min reperfusion, the incidences of VF were 29% in group 1, 77% in group 2, and 33% in group 3 (group 2 vs group 1, p < 0.05; and group 2 vs group 3, p < 0.05). Ventricular arrhythmias were reduced during both 10-min ischemia and 10-min reperfusion as a result of the improvement in the conduction components by ischemic preconditioning which increased MBF in the subepicardium.
Animals↗
Pharmacological profiles of a novel non-peptide angiotensin II type I receptor antagonist HR720 in vitro and in vivo.
The pharmacological properties of 2-butyl-4-(methylthio)-1-[[2'-[[[(propylamino)carbonyl] amino]sulfonyl](1,1'-biphenyl)-4-yl]methyl]-1H-imidazole-5-carboxylate (HR720), a novel non-peptide angiotensin (Ang) II type I (AT1) receptor antagonist, were characterized in both in vitro and in vivo systems. In vitro autoradiography using 125I-[Sar1,Ile8]Ang II as a ligand revealed that HR720 competitively inhibited the specific binding of the ligand to the adrenal cortex. The IC50 value for the adrenal cortex was 1.5 x 10(-8) M, and the IC50 for medulla was 1.4 x 10(-6) M. Similar results were obtained in the adrenal cortex with CV-11974, a known potent AT1-receptor antagonist. Since AT1 receptors are known to predominate in the adrenal cortex and AT2-receptors in the adrenal medulla, it is considered that HR720 is highly selective for AT1 receptors. HR720 inhibited the Ang II-induced contraction of isolated rabbit aortic strips and human gastroepiploic arteries in a noncompetitive manner, pD'2=9.40 and 9.62 for rabbit aorta and human artery, respectively. With CV-11974, pD'2 values of 9.84 in isolated rabbit aorta and 10.00 in human artery were obtained. HR720 did not affect the norepinephrine-, serotonin- or KCl-induced contraction even at a concentration of 1 x 10(-5) M. In anesthetized hamsters, HR720 induced a dose-dependent inhibition of the pressure response to Ang II. The potency of HR720 to antagonize the Ang II-induced pressure response was similar to that of CV-11974. These results demonstrate that HR720 is a potent and selective AT1-receptor antagonist.
Adrenal Glands↗
Glucose intolerance in spontaneously hypertensive and Wistar-Kyoto rats: enhanced gene expression and synthesis of skeletal muscle glucose transporter 4.
To clarify the relationship between blood pressure and insulin resistance, we studied the role of glucose transporter 4 (GLUT4) in skeletal muscle and the effect of angiotensin-converting enzyme inhibitor on insulin resistance. Blood pressure and plasma glucose and plasma insulin responses to glucose loading (2 g/kg, i.p.) were measured in spontaneously hypertensive rats (SHRs), Wistar-Kyoto rats (WKYs), and Wistar rats at 8, 12, and 20 wk of age. GLUT4 gene expression and plasma membrane protein content were also determined in the gastrocnemius muscle. SHRs and WKYs at the age of 8 wk had significantly higher plasma glucose levels than did age-matched control Wistar rats. Insulin response also tended to be higher. Glucose intolerance was also present in 12-wk-old SHRs, but normalized at the age of 20 wk. In contrast, WKYs were glucose intolerant at 12 and 20 wk. Gene expression and plasma membrane content of GLUT4 were augmented in both 8-wk-old SHRs and WKYs, indicating a compensatory increase in these variables. Effects of captopril (20-30 mg/kg/d from 8 to 20 wk) on GLUT4 were also investigated in these three strains. Captopril improved steady state plasma glucose levels in association with 1.2- to 2.5-fold higher GLUT4 gene expression and a 1.4-fold increase in skeletal muscle GLUT4 protein in SHRs and WKYs. Our results suggest that (1) not only SHRs but also WKYs may have glucose intolerance and hence insulin resistance; (2) gene expression and protein synthesis of skeletal muscle GLUT4 are probably increased compensatorily, indicating that abnormalities in GLUT4 do not have a pivotal role in the development of insulin resistance in SHRs and WKYs; and (3) captopril stimulates skeletal muscle gene expression and synthesis of GLUT4, providing further evidence of its beneficial effect on glucose metabolism.
Angiotensin-Converting Enzyme Inhibitors↗
Symposium on gene abnormalities in medical diseases. 2. Genetic defects and diabetes mellitus-defects of glucokinase gene and mitochondrial gene in diabetic patients.
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Adolescent↗
[Glucose tolerance test].
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Diabetes Mellitus↗
Evaluation of acute ischemic mitral regurgitation following cardiopulmonary bypass assessed by biplane transesophageal echocardiography.
The aim of this study was to evaluate pathogenesis and outcome of acute ischemic mitral regurgitation (MR) in patients undergoing coronary artery bypass grafting (CABG) using biplane transesophageal echocardiography (TEE). Biplane TEE was continuously monitored in a total of 96 patients who were scheduled for elective CABG surgery. Of 96 patients, 10 with no MR at stages 1 (after anesthetic induction but before skin incision) and 2 (after cardiopulmonary bypass [CPB] and decannulation) were excluded. In the remaining 86 patients with MR between stages 1 and 2, 45 (group A) had an increase in MR, and 41 (group B) had a decrease in MR. An increase in MR at stage 2 in group A was associated with a significant increase in annular diameter (p < 0.05), and pulmonary capillary wedge pressure (p < 0.01) compared with stage 1. A significant decrease in the left ventricular end-diastolic area (p < 0.01), end-systolic area (p < 0.05) and the mean wall motion abnormality score (WMA score) (p < 0.001) was observed at stage 2 compared with stage 1 in group B. In 16 of 17 patients (94%) with an increased WMA score in group A, a regional wall motion abnormality (RWMA) was detected in the right coronary artery (RCA) and/or left circumflex coronary artery (LCX) areas. In 7 patients in group A, MR increased continuously until stage 3 (after sternal closure) despite treatment. In 2 of these 7 patients, pulmonary venous systolic flow (PVSF) decreased during stage 2 and persisted to stage 3. The post operative course of these 2 patients was complicated with atrial fibrillation (AF). The increase in annular diameter and worsening in RWMA in RCA and/or LCX areas are associated with acute ischemic MR following CPB. The majority of acute ischemic MR cases were resolved by pharmacological intervention. Post operative AF was noted in 2 patients with acute ischemic MR associated with persistently decreased PVSF following CPB despite treatment.
Acute Disease↗
[Insulin secretion--assay method and its significance].
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C-Peptide↗