Computed tomographic findings in two cases of cellulitis of the infratemporal fossa with abscess formation.
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Biomedical subjects
Publications and source records attributed to Y Masuda.
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Oxethazaine (OXZ), a potent topical anesthetic, was found to induce red blood cell (RBC) lysis in vitro, depending upon concentrations of OXZ, RBC and Ca2+. In a 2% RBC suspension, 100 microM OXZ caused almost complete hemolysis in the presence of 1.3 mM Ca2+ with only a minimal effect in its absence, while higher concentrations of OXZ (400 microM<) produced hemolysis without Ca2+. The hemolysis induced by OXZ plus Ca2+ was preceded by a rapid increase in 45Ca2+ uptake by RBCs, with both the hemolysis and Ca2+ uptake being inhibited by 1 mM CoCl2, NiCl2, and quinine. Together with the Ca2+ influx, rapid influx of Na+ and efflux of K+ occurred, and an increasing external K+/Na+ concentration ratio inhibited both hemolysis and Ca2+ influx. Morphologically, OXZ plus Ca2+ caused rapid transformation to spheroechinocytes, the formation of blebs and the pinching-off of blebs, whereas OXZ alone produced membrane invagination. SDS-PAGE analysis of the ghosts prepared from the RBCs treated with OXZ plus Ca2+ revealed derangement of cytoskeletal components. OXZ is a rare drug that exhibits a Ca2+ ionophore-like action, increasing the Ca2+ permeability of plasma membranes.
On the basis of structural information for the cyclic hexapeptide endothelin (ET) receptor antagonist, TAK-044, a series of thieno[2,3-d]pyrimidine-2,4-dione derivatives bearing a carboxyl group and aromatic rings that were important for receptor binding were designed, synthesized, and evaluated for ET receptor binding affinities and inhibitory activities against ET-induced vasoconstriction. Optimization of each substituent in the thieno[2,3-d]pyrimidine ring led to the discovery of a novel and potent nonpeptide ET receptor antagonist, 6-(4-methoxymethoxyphenyl)-5-methylsulfonylaminomethyl-1-(2- methylthiobenzyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]p yrimidine-3- acetic acid (32 g), which binded to human ETA and ETB receptor subtypes with affinities (IC50) of 7.6 and 100 nM, respectively. Compound 32 g effectively antagonized ET-induced vasoconstriction and the inhibitory effect mediated by the ETB receptor was more potent than that of bosentan, while the inhibitory effect mediated by the ETA receptor was slightly less potent than that of bosentan.
Previous reports have indicated that echocardiography with automatic boundary detection (ABD) is useful for the noninvasive estimation of left ventricular volume. However, few data exist regarding the measurement of left atrial (LA) volume, which also provides pivotal information in the clinical setting. Therefore, the feasibility of LA volume measurement by ABD in comparison with the manual tracing using modified Simpson's method (SM) was evaluated. Fifty-nine patients with coronary artery-disease with sinus rhythm were examined. Using ABD, a region of interest was set around the LA border and mitral annulus from an apical four-chamber view. The maximal and minimal LA volume (Vmax and Vmin) were measured from the volume waveform. Using the SM, the maximal and minimal LA volume were measured by the manual tracing on frozen frames at the apical four-chamber view. The ABD displayed a curve of LA volume change that consisted of passive emptying, diastasis, and active emptying phases during the left ventricular diastolic period. Under these conditions, the Vmax and Vmin were 43.7 +/- 11.2 ml and 21.1 +/- 7.6 ml, respectively, yielding the volume change of 22.6 +/- 6.0 ml. By the SM, Vmax and Vmin were 43.1 +/- 9.9 ml (r = 0.94, p < 0.0001, y(ABD) = 0.91x (SM) + 3.6) and 22.0 +/- 9.0 ml (r = 0.91, p < 0.0001, y = 0.94x + 0.7), respectively, and the volume change was 22.8 +/- 6.1 ml (r = 0.82, p < 0.0001, y = 0.84x + 3.8). These results indicate that the ABD from the apical four-chamber approach could provide an accurate estimation of LA volume change, suggesting the potential value of this method in assessing LA function, although some technical difficulties need to be further overcome.
Intrahepatic flow in rats was examined by systemic acridine orange (AO) labeling and succeeding microscopic observations of post-fixed livers. In controls, all periportal areas were stained evenly throughout the liver mass, and the staining often branched between the liver lobules in a acinous fashion. Intraportal endothelin-1 infusion caused a marked heterogenous staining; strong staining around large portal vein branches in the central portion of the liver, but much less in the periphery. Cirrhotic livers exhibited overall weaker staining intensity with no accentuation in periportal areas and restricted radial staining within pseudo-lobules. AO infusion may help detect hepatic flow disturbance in vivo.
The mechanism of the prophylactic effect against hyperlipidemia by monatepil maleate was investigated in animal models. Monatepil maleate is an antihypertensive agent with Ca2+-channel antagonistic, alpha1-adrenergic receptor-blocking, and lipid peroxidation inhibitory activity. In high cholesterol diet-fed rabbits, monatepil maleate (30 mg/kg, p.o., once daily for 9 weeks) showed a prophylactic effect against increases in total cholesterol and beta-lipoprotein. Monatepil maleate significantly accelerated the clearance of radioactivity from the blood after intravenous injection of low-density lipoprotein (LDL) labeled with [1alpha,2alpha (n)-3H]cholesterol, increasing biliary excretion of [3H]-bile acids without modifying bile acid composition. Furthermore, monatepil maleate tended to inhibit the absorption of orally administered [1alpha,2alpha (n)-3H]cholesterol from the gastrointestinal tract in these rabbits. In Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of hepatic LDL receptor deficiency, monatepil maleate (30 mg/kg, p.o., once daily for 6 months) did not suppress the increase in plasma lipids. These results suggest that the plasma lipid lowering effect of monatepil maleate requires the presence of hepatic LDL receptors. It is also suggested that monatepil maleate improves plasma lipid metabolism through two mechanisms: enhancement of clearance of plasma LDL, which may be mediated by up-regulation of hepatic LDL receptors, and acceleration of conversion of free cholesterol to bile acids in the liver.
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UNLABELLED: The Simple and Patlak models for estimating myocardial blood flow with 13N-ammonia have become attractive for clinical applications with PET because of their simplicity and ease of implementation. However, these models are sensitive to factors such as the data acquisition times and data integration times, which can cause errors in the estimation of myocardial blood flow, as demonstrated in this study. Limiting the application of these models to specific conditions can minimize the errors. METHODS: Dynamic PET images of the uptake of 13N-ammonia in the heart were obtained in seven humans under rest and dipyridamole stress. Myocardial blood flow was estimated using the Simple and Patlak models for different data acquisition times and data integration times. Blood flow values were compared to flow values computed with the two-compartment model as a reference. RESULTS: Blood flow values calculated with the Simple and Patlak models during the first 2 min of data acquisition were closely correlated to the two-compartment model values. Longer acquisition times resulted in significant underestimation of blood flow for the Simple model. Long integration times of greater than 60 sec also resulted in significant underestimation of blood flow for both models. CONCLUSION: The Simple and Patlak models produce estimates of myocardial blood flow that are well correlated with the two-compartment model estimated blood flows for the integration time of 60 sec from 60 to 120 sec postinjection. Because of the errors associated with longer data acquisition times and longer integration times, use of these models should be limited to a well-documented data acquisition paradigm.
We performed a clinical evaluation on the antiemetic profile and the plasma concentration of Azasetron Hydrochloride (a new selective 5-HT3 receptor antagonist), in transcatheter arterial chemoembolization using CDDP for unresectable hepatocellular carcinoma. Antiemetic effects were examined in 32 patients in the serotone group (administration of serotone 10 mg + methylprednisolone 125 mg) and in 77 patients of the control group (administration of metoclopramide 20-30 mg + methylprednisolone 500 mg). The response rate and the CR ratio in serotone group was 97% and 66%, respectively. These results were statistically higher than in the control group. Although all patients had chronic liver diseases, no side effects and complications related to administration of serotone were observed. The average area under the concentration (AUC) curve of plasma serotone in five patients with liver cirrhosis was 531 ng.h/ml, which was greater than that of a healthy volunteer. In conclusion, serotone is a new, safe and useful antiemetic drug in TACE therapy for hepatocellular carcinoma.
A correction method was proposed for measurement of the regional cerebral blood flow using one-point arterial blood sampling and a microsphere model with N-isopropyl-p-(123I)iodoamphetamine (123I-IMP). Instead of using continuous arterial blood sampling octanol-extracted counts, one-point arterial sampling whole blood counts corrected by the whole brain count ratio using 1-minute planar SPECT images were employed. The experimental subjects were 189 patients with cerebrovascular disorders. 123I-IMP, 222 MBq, was administered by intravenous infusion. Continuous arterial blood sampling was carried out for 5 minutes, and arterial blood was also sampled once at 5 minutes after 123I-IMP administration. Then the whole blood count of the one-point arterial sampling was compared with the octanol-extracted count of the continuous arterial sampling. A positive correlation was found between the two values (r = 0.87, p < 0.001). The correction method was carried out by calculation as follows. The ratio of the continuous sampling octanol-extracted count (OC) to the one-point sampling whole blood count (TC5) was compared with the whole brain count ratio (5:29 ratio, Cn) using 1-minute planar SPECT images, centering on 5 and 29 minutes after 123I-IMP administration. Correlation was found between the two values (r = 0.72, p < 0.001). The following relationship was shown from the correlation equation. OC/TC5 = 0.390969 x Cn-0.08924. Based on this correlation equation, we calculated the theoretical continuous arterial sampling octanol-extracted count (COC). COC = TC5 x (0.390969 x Cn-0.08924). There was good correlation between the value calculated with this equation and the actually measured value (r = 0.94, p < 0.001). The coefficient improved to r = 0.94 from the r = 0.87 obtained before using the 5:29 ratio for correction. For 23 of these 189 cases, another one-point arterial sampling was carried out at 6, 7, 8, 9 and 10 minutes after the administration of 123I-IMP. The correlation coefficient was also improved for these other point samplings when this correction method using the 5:29 ratio was applied. It was concluded that it is possible to obtain highly accurate input functions, i.e., calculated continuous arterial sampling octanol-extracted counts, using one-point arterial sampling whole blood counts by performing correction using the 5:29 ratio.
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UNLABELLED: A high-resolution PET system for small animals was tested for its applicability to the investigation of regional myocardial blood flow (MBF) in rabbits. METHODS: Nineteen measurements were performed in 10 closed-chest anesthetized rabbits at baseline and during infusions of adenosine (0.2 mg/kg/min) and propranolol (0.20-1.20 mg slow infusion) to obtain a wide range of MBF. Myocardial blood flow was assessed both by dynamic 13N-ammonia PET and by colored microspheres. Blood was withdrawn directly from the femoral artery, and arterial 13N activity was measured by coincidence type gamma detection system for the input function. Nitrogen-13 myocardial uptake was calculated by dividing the myocardial 13N activity by the integral value of the input function. RESULTS: Three or four contiguous cross-sectional myocardial images were obtained after 13N-ammonia injection. The left ventricular wall and cardiac cavity were clearly visualized. Moreover, initial passage of the tracer through the heart was obtained with serial 10-sec PET images. Nitrogen-13 myocardial uptake correlated well with flow measured with microspheres (r = 0.88). CONCLUSION: Our cardiac PET system can be used for in vivo imaging and quantitation of MBF in small animals and may play an important role in the future study of animal models of cardiovascular diseases.
Leukemia inhibitory factor (LIF) affects the growth of carcinoma cells, and we thus analyzed its underlying mechanisms. Carcinoma cells constitutively express LIF mRNA, and 23 lines (92.0%) and all (100%) of 25 lines express LIF receptor mRNAs of LIFRbeta and gp130, respectively. Exogenous addition of LIF promoted significant cell proliferation in 4 lines (MCF-7, ZR-75-1, Hs-700T and Panc-1) and suppressed cell growth in 3 lines (AZ-521, GBK-1 and HT-29). LIF significantly induced an immediate early response of genes c-fos and junB 3 hr after stimulation, but not of c-jun during the process of proliferation of MCF-7 and Hs-700T cells, with maximum levels at 30-60 min. The cell-cycle-related gene cyclin E was also induced in MCF-7 and Hs-700T cells, whereas cyclinA, cdk2, c-myc, c-myb and p53 mRNAs were not induced. On the other hand, LIF inhibited growth and increased the rate of cell death of AZ-521 and GBK-1 cells. LIF increased the number of TUNEL-positive cells in AZ-521 cells and DNA fragmentation in AZ-521 and GBK-1 cells. LIF induced apoptosis related genes c-myc and ICE during suppression of cell growth, but p53, p21, c-fos, cyclin A and cyclin E were not induced. Our results suggest that LIF is linked to cell proliferation and apoptosis in some human carcinoma cell lines. It is considered that this is related to differences in signal transduction and induction of oncogenes.
In a previous study, we demonstrated that bufalin, which is an active principle of Chinese medicine, chan'su, caused apoptosis in human leukemia U937 cells by anomalous activation of mitogen-activated protein kinase (MAPK) via the signaling pathway of Ras, Raf-1, and MAPK kinase-1. Here, we report the effect of overexpression of bcl-2 in U937 cells on the signaling pathway of apoptosis that is induced by bufalin. The results indicated that the apoptosis induced by bufalin in U937 cells was significantly inhibited by overexpression of the Bcl-2 protein. No significant difference was detected in the activation of MAPK kinase-1 that is induced by bufalin in wild-type or Bcl-2-overexpressed U937 cells; however, the activation of MAPK by bufalin was significantly attenuated in the cells overexpressing Bcl-2. Bufalin treatment activated activator protein-1 transcriptional activity; however, this activation was decreased to 40% in bcl-2-overexpressed U937 cells. These results indicate that Bcl-2 acts downstream of MAPK kinase-1 but upstream of MAPK and suggest that, in the signaling pathway of the apoptotic process induced by bufalin, the transcriptional activity of activator protein-1 may be down-regulated through the inhibition of MAPK activity by Bcl-2.
It has been reported that platelet-derived growth factor B-chains homodimer (PDGF-BB) improves learning function of mice, and that sugar chain structure Lewis-X of N-glycosylated glycoprotein promotes PDGF-BB secretion from platelets. Based on these findings, we assumed that learning dysfunction in some patients with mental retardation might be due to abnormality in PDGF-BB metabolism and/or Lewis-X structure. No difference in the reactivity of PDGF-BB and Lewis-X was found between the serum of patients with mental retardation and that of normals. But sialic acid reactivity of the Lewis-X fraction in some patients was remarkably higher than that in other patients and in normals. These findings suggest that sialic acids in the Lewis-X fraction may have a relation to one of the causes of learning dysfunction in these patients.
We previously reported that, in isolated perfused rat livers in a constant flow system, oxethazaine (OXZ) rapidly increased portal pressure (PP) accompanied by inhibition of oxygen uptake and the subsequent metabolic effects. In this study, hemodynamic changes were studied by using an indicator dilution technique and by microscopic observation of post-fixed liver samples stained with acridine orange or trapped fluorescence microspheres (FMSs). During the increase in PP induced by OXZ, the mean transit times of both red blood cells and azoalbumin were shortened markedly, and the vascular and extravascular albumin spaces decreased to 55 and 18% of the controls, respectively. With acridine orange, in the control livers, all the dye infused was taken up and the periportal zones were uniformly stained over all the liver sections, whereas in the OXZ-treated livers, about 30% of the dye drained out, and extensive staining was observed in the central portion of the liver mass, but the peripheral portions of the liver were much less stained. The staining was often localized around large portal vein branches and spread toward the hepatic veins. These changes were recoverable in the absence of OXZ. Distributions of 1-microm and 15-microm FMSs were likewise altered by OXZ. Thus, uneven perfusion may be the primary cause of decreased tissue spaces and also of the metabolic effects produced by OXZ. Endothelin 1 also produced OXZ-like changes, while U-46619 had lesser effects. The methodology used in this study may help delineate the hepatic perfusion disturbance caused by various vasoconstrictors.
In a previous study, we showed that geranylgeraniol (GGO) is a potent inducer of apoptosis in human leukemia cells. The present study describes the effects of GGO on the activity of cysteine-dependent aspartate-directed proteases (caspases) in human leukemia U937 cells. The caspase-3 (CPP32) activity was increased in a time-dependent manner by treatment with 50 microM GGO, whereas no activation of caspase-1 (interleukin-1beta converting enzyme (ICE)) was observed in any time period under the same experimental conditions. Other isoprenyl compounds such as geraniol, geranylgerany-lacetone, and vitamin K2 had no measurable effects on the activities of either caspase-3 or caspase-1. A inhibitor that preferentially inhibits the caspase-3 related caspases, Z-DEVD-FMK, strongly blocked the GGO-induced DNA fragmentation. These results suggest the involvement of caspase-3 in GGO-induced apoptosis in U937 human leukemia cells.