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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 487 records · Page 27Linked to original sources

Oxidative stress response in iron-induced renal carcinogenesis: acute nephrotoxicity mediates the enhanced expression of glutathione S-transferase Yp isozyme.

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces acute renal proximal tubular necrosis, a consequence of free radical-mediated oxidative tissue damage, that eventually leads to a high incidence of renal adenocarcinoma in rodents. In the present study, we investigated the free radical-induced oxidative stress response in this carcinogenesis model, focusing on the expression of glutathione S-transferases (GSTs) which catalyze the conjugation of reactive chemicals with glutathione and play an important role in protecting cells. A single intraperitoneal Fe-NTA treatment (15 mg Fe/kg body weight) induced a rapid oxidative stress, which was monitored by the accumulation of lipid peroxidation products and the loss of sulfhydryl contents in the kidneys, resulting in a 30% reduction of GST activity 1 h after an Fe-NTA treatment. The enzyme activity returned to the control level after 16 h. The immunoblot analysis of GST isozymes demonstrated that the level of alpha-class GSTs (GST-Ya and GST-Yc) and pi-class GST (GST-Yp), major GST isozymes constitutively produced in the kidney, decreased immediately within 1 h of the Fe-NTA treatment. The onset of the recovery of GST-Yp protein levels was detected 3 h after the Fe-NTA treatment. The enhanced production of GST-Yp in gene expression was evident in the drastic elevation of mRNA levels and these increases coincided with a substantial rise in the GST activity and protein levels. The alpha-class GSTs were not inducible by treatment with Fe-NTA. The immunohistochemical analysis demonstrated that the expression of GST-Yp was strongly induced in the regenerating proximal tubular cells. A steady accumulation of GST-Yp protein was observed in the subacute toxicity experiments with multiple injections of Fe-NTA. These results suggest that the enhanced expression of GST-Yp is important in mediating cell repairs or increasing the resistance to subsequent injury.

Adenocarcinoma↗

Changes in regional cerebral blood flow during self-paced arm and finger movements. A PET study.

The purpose of this study was to identify the functional fields activated in relation to the self-paced proximal and distal arm movements. The regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and 15O-labelled H2O (H2(15)O) in eight healthy subjects. All subjects performed the following three tasks: (1) repetitive opposition of thumb and index finger of the right hand, (2) repetitive co-contraction of biceps and tricepts brachii muscles of the right arm, and (3) rest. The mean rCBF change images for each task minus control was calculated and fields of significant rCBF changes were identified. Each movement activated different fields in the primary motor area (MI), the dorsal aspect of the premotor area (PMA) and the superior part of the prefrontal area (PFA) of the contralateral hemisphere. In these areas, arm fields were located relatively dorsally to the finger fields. In addition, specific fields in the ventral part of the PMA, the supplementary motor area (SMA), the superior parietal lobule (SPL) of the contralateral hemisphere, and the ipsilateral PFA were consistently activated during both movements. Due to a limited a field of view of the PET scanner in the axial direction, the PET scan could not cover the cerebellum. The results indicate that there may be somatotopical organization not only in the MI but also in the dorsal part of the PMA and the PFA, and that the specific fields in the ventral part of the PMA, the SMA, the SPL, and the PFA may be involved in self-paced movement.

Adult↗

Hemodynamic forces modulate the effects of cytokines on fibrinolytic activity of endothelial cells.

We investigated the effects of hemodynamic force on fibrinolytic activity of cultured human umbilical vein endothelial cells stimulated by cytokines, using a modified cone-plate viscometer in which well-controlled and -defined shear forces were generated. Treatment of the cells with interleukin (IL)-beta or tumor necrosis factor alpha (TNFalpha) under static conditions had no effect on tissue plasminogen activator (t-PA) secretion, while release of plasminogen activator inhibitor 1 (PAI-1) increased. When cells were exposed to increasing shear stress up to 24 dynes/cm2, levels of t-PA and t-PA/PAI-1 complex significantly increased relative to shear stress, while total PAI-1 and active PAI-1 secretion decreased gradually. In the presence of IL-1beta or TNFalpha, the increase in production of t-PA and the t-PA/PAI-1 complex was further augmented. Dot blot hybridization analysis of cultured cells in similar experimental conditions using t-PA and PAI-1 cDNA probes revealed no t-PA mRNA in 3 microg total RNA from static endothelial cells under resting or cytokine-stimulated conditions, but abundant t-PA mRNA was detected in cells subjected to a shear force of 18 dynes/cm2, and the increase was further augmented by addition of cytokines. In contrast, PAI-1 mRNA was detected in resting and cytokine-stimulated, nonsheared endothelial cells, but levels decreased after exposure to shear stress, even in the presence of cytokines. These results indicate a role for hemodynamic forces in regulating fibrinolytic activity with or without cytokine stimulation.

Cells, Cultured↗

Factors that affect the size of platelet aggregates in epinephrine-induced activation: a study using the particle counting method based upon light scattering.

Platelet aggregate size was determined with a newly-developed platelet aggregometer, PA-100 (KOWA), which can quantitatively evaluate the size and number of platelet aggregates by means of the particle counting method based upon light scattering. Epinephrine-induced platelet aggregation consists of two phases, the former characterized by the formation of small-sized aggregates (less than 100 cells), which is followed by the phase of large aggregate formation with concomitant decrease in the number of small aggregates. These findings suggest that small aggregates fuse to form large aggregates. Effects of various inhibitors and antibodies directed against platelet membrane glycoproteins were evaluated on the size of platelet aggregates induced by epinephrine. Cyclooxygenase inhibitors, thromboxane A2 receptor antagonists, and a Na+/H+ exchanger inhibitor (ethylisopropylamiloride) inhibited the formation of large aggregates (more than 100 cells) but not that of small aggregates. Cytochalasin B, which interferes with microfilaments, suppressed large aggregate formation, whereas taxol, which reacts with microtubules, had no effects. Anti-GPIIb/IIIa monoclonal antibody (MoAb) inhibited both the formation of small and large platelet aggregates, while antibodies directed against GPIb, thrombospondin, P-selectin, or PECAM-1 had no effects on platelet aggregate formation. These findings, taken together, suggest that intracellular alkalinization, thromboxane A2 formation and microfilament rearrangement are prerequisites for large platelet aggregate formation. GPIIb/IIIa is involved in the formation of small as well as large aggregates, but a membrane glycoprotein(s) responsible for the transition of small aggregates into large aggregates awaits to be determined.

Arachidonic Acid↗

Changes in rCBF during grasping in humans examined by PET.

To identify the functional fields involved in grasping for objects, we measured regional cerebral blood flow (rCBF) by positron emission tomography (PET) in eight normal volunteers. In the reaching and grasping tasks, the subjects were asked to touch or grasp one of five cylinders with their finger(s). Compared with reaching, grasping specifically increased the rCBF in the fields located in the bilateral premotor area (PMA), the posterior parietal area (PPA) and the prefrontal area (PFA). These results indicate that PMA, PPA and PFA might be key structures for the performance of grasping movements.

Adult↗

Specific inhibition of Na+,K(+)-ATPase activity by atractylon, a major component of byaku-jutsu, by interaction with enzyme in the E2 state.

Atractylon, a major component of the crude drug "Byaku-jutsu" (rhizomes of Atractylodes japonica), strongly inhibited Na+,K(+)-ATPase activity with an I50 value of 8.9 x 10(-6) M. It also inhibited Mg(2+)-ATPase, H+,K(+)-ATPase, H(+)-ATPase and Ca(2+)-ATPase activities, but less potently. No effects on alkaline and acid phosphatase activities were observed. The inhibition of Na+,K(+)-ATPase activity by atractylon was noncompetitive with respect to ATP and was greater with increasing K+ concentration, whereas it was not affected by Na+ concentration. The activity of K(+)-dependent p-nitrophenyl phosphatase, a partial reaction of Na+,K(+)-ATPase, was inhibited noncompetitively with respect to substrate (I50 value of 1.8 x 10(-5) M), and the inhibition rate was independent of the K+ concentration. Furthermore, atractylon increased the Ki value for Na+ from 130 to 190 mM, but did not alter the Ki value for ATP. Inhibition of the phosphoenzyme formation by atractylon was greater at 0.1 M than at 1 M NaCl. K(+)-dependent dephosphorylation (E2-P to K.E2) was inhibited by atractylon, whereas ADP-sensitive (Na.E1-P to Na.E1) and non-specific dephosphorylation steps were not affected. These results suggest that atractylon, a specific inhibitor of Na+,K(+)-ATPase, interacts with enzyme in the E2 state and inhibits the reaction step from E2-P to K.E2.

4-Nitrophenylphosphatase↗

Hepatocyte growth factor induces transglutaminase activity that negatively regulates the growth signal in primary cultured hepatocytes.

Transglutaminase (TGase) activity increased 2.5-fold at 6 h after treatment of rat hepatocytes with 117 nM hepatocyte growth factor (HGF). In the same manner, putrescine incorporation into proteins of cells occurred in HGF-treated cells but did not in those pretreated with monodansylcadaverine (MDC), a TGase inhibitor, even in the presence of HGF. These results suggest that HGF-induced TGase was active and catalyzed some cross-linkage reaction. Cycloheximide completely blocked the increase in TGase activity induced by HGF, suggesting that HGF stimulated de novo synthesis of TGase within 6 h. Both [35S]methionine incorporation and Northern blotting analyses supported this possibility. Pretreatment of cells with MDC additionally increased HGF-induced DNA synthesis and the ratio of cells in S-phase. Similarly, TGase antisense oligonucleotide inhibited de novo synthesis of TGase, resulting in increase in the ratio of S-phase cells in the presence of HGF. Analyses of cross-linking of HGF to the receptor indicated that the antisense oligonucleotide inhibited the downregulation of HGF receptor subsequent to HGF-addition. These results provide the first evidence for inducibility of de novo synthesis of TGase by HGF and suggest that TGase negatively regulates the growth signal of HGF through the downregulation of receptor.

Animals↗

Quantitative measurement of various 5-HT receptor antagonists on platelet activation induced by serotonin.

The effects of S2-serotonergic receptor antagonists, ketanserin, MCI-9042, and one of its major metabolite, M-1, were evaluated on human platelet activation induced by serotonin. A newly developed method for detecting particles in suspensions was used to assess serotonin-induced platelet aggregation. Serotonin added to platelets in plasma induced transient formation of small aggregates but not that of large ones. All the three antagonists in a dose-dependent manner suppressed serotonin-induced platelet aggregation. The ID50 values for ketanserin, MCI-9042, and M-1 are 10 nM, 0.6 microM, and 40 nM, respectively. The effects of these antagonists were also evaluated on [Ca+2]i elevation and shape change, the measurement of which does not require the presence of plasma proteins. These antagonists effectively inhibited [Ca+2]i elevation and shape change induced by serotonin. The ID50 value for MCI-9042 was approximately 1/10 for platelet aggregation. These findings suggest that MCI-9042 tightly binds to plasma proteins with resultant reduction in overall potency. The ID50 values obtained in this study are essentially equivalent to those reported for S2-serotonergic receptor binding in rabbit platelets, suggesting that these agents are also potent antagonists serotonin-induced activation of human platelets.

Blood Platelets↗

Transglutaminase induced by epidermal growth factor negatively regulates the growth signal in primary cultured hepatocytes.

Transglutaminase (TGase) activity increased 2.5-fold at 6 h after treatment of rat hepatocytes with 17 nM epidermal growth factor (EGF). In the same manner, putrescine incorporation into the proteins of cells occurred in EGF-treated cells, but not in those pretreated with monodansylcadaverine (MDC), a TGase inhibitor, even in the presence of EGF. These results suggest that EGF-induced TGase was active and catalysed some cross-linkage reaction. Cycloheximide completely blocked the increase in TGase activity induced by EGF, suggesting that EGF stimulated de novo synthesis of TGase within 6 h. Furthermore, Northern blotting analysis indicated that EGF increased the expression of TGase mRNA. Pretreatment of cells with MDC additionally increased EGF-induced DNA-synthesis and the ratio of cells in S-phase. TGase antisense oligonucleotide inhibited de novo synthesis of TGase, resulting in increases in the ratios of S- and G2/M-phase cells in the presence of EGF. This effect was the result of inhibition of EGF-induced down-regulation of high-affinity receptor expression. These results suggest that the EGF-induced increase in TGase activity is a negative regulator of a growth signal in rat hepatocytes.

Animals↗

Deficiency of plasma platelet-activating factor acetylhydrolase: roles of blood cells.

Platelet-activating factor (PAF), a potent mediator of inflammation and circulatory shock, is inactivated by the enzyme PAF acetylhydrolase. Plasma PAF acetylhydrolase deficiency occurs even in healthy subjects. We hypothesized that erythrocyte PAF acetylhydrolase could play a supplementary role in this plasma acetylhydrolase deficiency. We examined 1,030 subjects who participated in mass checkups, and assayed plasma and erythrocyte PAF acetylhydrolase. We also investigated the degradation of exogenous PAF by erythrocytes or other blood cells obtained from subjects who exhibited the plasma enzyme deficiency. The incidence of the plasma enzyme deficiency in this general Japanese population was 4.7% (48/1,030). None of the subjects with the deficiency had a history of allergy, circulatory shock, or chronic inflammatory diseases. The mean values for erythrocyte cytosolic PAF acetylhydrolase activity in the normal and deficient subjects were 0.51 +/- 0.15 (SD) and 0.71 +/- 0.28 nkat (nmol/s)/g protein, respectively, and the difference was significant (P < 0.001, Mann-Whitney U-test). The half-life of 10 nmol/l [3H]PAF in plasma from normal subjects was about 5 min, and the half-life in whole blood or erythrocyte suspension in autologous plasma was almost the same as that in plasma. In plasma from deficient subjects, unchanged PAF virtually remained and the degradation in whole blood or erythrocyte suspension was a little faster than in plasma. We conclude that erythrocytes contribute only little to PAF metabolism in normal blood but they account for almost all of the slow PAF degradation in blood from subjects deficient in plasma PAF acetylhydrolase.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

In vivo rapid magnetic field measurement and shimming using single scan differential phase mapping.

In vivo shimming is a powerful tool for alleviating subject-dependent magnetic field distortions in MRI, although the usually lengthy procedure has limited its use. A magnetic field measurement method called single scan differential phase mapping that can reduce the measurement time of conventional methods by more than half when used with multiple gradient-recalled echo imaging was developed. An automatic high-order shimming using the present method was implemented in a commercial MRI system. In vivo field inhomogeneity features and the shimming performances were investigated. The method was found to be useful for improving the quality of echo-planar images.

Abdomen↗

Carboxyl-terminal processing protease for the D1 precursor protein: cloning and sequencing of the spinach cDNA.

A previous study has demonstrated that the carboxyl-terminal (C-terminal) processing protease in spinach for the D1 precursor protein (pDl) of the photosystem II reaction center is a monomeric protein of about 45 kDa. Based on the amino acid sequence data of the purified protease, a cDNA clone encoding the enzyme has been identified and sequenced, from a spinach green leaf cDNA library. In order to determine the 5' end of the transcript, the rapid amplification of cDNA end (5'-RACE) technique was applied. By these analyses, the full-length transcript was established to consist of 1906 nucleotides and a poly(A) tail, containing an open reading frame (ORF) corresponding to a protein with 539 amino acid residues. By comparing the amino acid sequence of the purified protease with that deduced from nucleotide sequence of the cDNA clones, the enzyme was shown to be furnished with an extra amino-terminal extension characteristic of both a transit peptide and a signal sequence. This suggests that the protease is synthesized in the cytosol and translocated into the lumenal space of thylakoids. The mature part of the enzyme consists of 389 amino acid residues and exhibits a significant sequence homology with two groups of proteins as demonstrated by a computer homology search, i.e. (1) the deduced sequence of a protein proposed to be the C-terminal processing protease for pD1 in Synechocystis sp. PCC 6803, based on genetic experiments and (2) proteases for C-terminal cleavage identified in Escherichia coli and Bartonella bacilliformis.

Algal Proteins↗

Electron-microscopic study of dopaminergic structures in the medial subdivision of the monkey nucleus accumbens.

The medial subdivision of the monkey nucleus accumbens (NAC) is rich in dopamine (DA) and peptides. In the present investigation the mode of DA transmission in the medial subdivision was studied morphologically by light- and electron-microscopic immunocytochemistry using a monoclonal antibody raised against dopamine. The medial subdivision showed extremely dense accumulation of thick DA-immunoreactive varicose fibers. Electron-microscopic observation of single sections revealed that DA afferents had a relatively high incidence (33.2%) of asymmetric junctions in this area. Approximately 50% of the targets were dendritic shafts, 44.2% dendritic spines, and 5.1% somata. Some DA axons showed terminal profiles en passant within the synaptic complex, some of which showed synaptic triads. The unique ultrastructural features of DA terminals in the medial NAC indicate the existence of specific styles of DA transmission in the limbic structure.

Animals↗

Accumulation of Tc-99m MIBI in breast lymphoma: comparison with Ga-67 citrate.

We report 2 cases of malignant lymphoma of the breast which were clearly shown on total body imaging as well as on SPECT with Ga-67 and Tc-99m MIBI. Tumor accumulation of Ga-67 was seen in all cases including a recurrent tumor. Ga-67 scintigraphy is useful for follow up in detecting relapse, as well as in predicting responses to therapy. Tc-99m MIBI was found to accumulate in the malignant lymphoma of the breast, and especially SPECT images of breast lesions provided better contrast than planar images, and Tc-99m MIBI SPECT could diagnose localization of the tumor because there was no uptake by the breast. But the Tc-99m MIBI accumulation of the tumor was lower than Ga-67.

Breast Neoplasms↗

Effects of pravastatin sodium and simvastatin on plasma fibrinogen level and blood rheology in type II hyperlipoproteinemia.

Elevated plasma fibrinogen level is known to progress atherosclerosis and to be one of the risk factors for the occurrence of cardiovascular diseases. The objective of this study is to evaluate the changes in plasma fibrinogen level and blood rheology in patients with type II hyperlipoproteinemia before and after random administrations of HMG-CoA (3-hydroxy-e-methylglutaryl-cocarboxylase-A) reductase inhibitors, pravastatin sodium and simvastatin, and compare with results in normal subjects. Of a total of 28 patients with type II primary hyperlipoproteinemia with > 230 mg/dl fasting total plasma cholesterol, 16 patients (mean, 59.7 years old) were administered 10-15 mg/day of pravastatin sodium for an average of 10.2 weeks, and 12 patients (mean, 62.0 years old) were administered 5-10 mg/day of simvastatin for an average of 13.9 weeks. Patients were evaluated before and after drug administration and results were compared with those of 16 normal subjects of similar age (mean, 56.9 years old). Blood viscosities were measured using a cone-plate viscometer (Biorheolizer, BRL-1000, Japan). The following were measured before and after drug administration: whole blood viscosity at shear rates of 75-375 s-1, corrected blood viscosity at low (112.5 s-1) and high (225.0 s-1) shear rates for the standard hematocrit of 45%, plasma viscosity, hematocrit, total protein, serum albumin, and plasma fibrinogen. Total cholesterol level was significantly decreased (from 270 to 225, mg/dl, mean values; P < 0.0007) an average of 10.2 weeks after start of pravastatin sodium administration. In addition to the reductions of whole blood viscosity, at every shear rate examined, corrected blood viscosity, and plasma viscosity, plasma fibrinogen levels were significantly decreased (from 354 to 309 mg/dl, mean values; P < 0.0007) after start of pravastatin sodium administration. Fibrinogen level and blood rheology were not significantly changed after start of simvastatin administration despite similar significant reductions in total cholesterol level (from 260 to 207 mg/dl, mean values; P < 0.0001) to those in the case of pravastatin sodium. From the results, we conclude that administration of pravastatin sodium, but not simvastatin, reduced the plasma fibrinogen level and blood viscosities to normal levels in type II hyperlipoproteinemic patients while both drugs reduced total cholesterol level. The hydrophilicity and a small binding capacity with plasma protein of pravastatin sodium may be responsible in part for the beneficial hemorheologic effects observed in the patients with type II hyperlipoproteinemia. Further investigations should be conducted to confirm the findings observed.

Acyl Coenzyme A↗

Congenital bilateral zygomatico-mandibular fusion with mandibular hypoplasia.

We report a very rare case of congenital bilateral zygomatico-mandibular fusion with mandibular hypoplasia. Soon after birth, the patient underwent tracheotomy because of upper airway obstruction. At the age of one and a half years, reconstruction of the temporomandibular joint and lengthening of the ramus with a costochondral graft were performed. Only a few cases of congenital bony syngnathia revealed in this case have been described in the literature.

Humans↗

Deficiencies of automatic endoscopic reprocessors: a method to achieve high-grade disinfection of endoscopes.

BACKGROUND: We show that disinfection using the automatic endoscopic reprocessor is not complete and propose a method for high-grade disinfection of endoscopes. METHODS: We used an automatic endoscopic reprocessor, Pyser System 83, and 2% glutaraldehyde. After each endoscopic procedure, the endoscopes were divided into three groups. Endoscopes in group A were washed only by the reprocessor. Group B endoscopes were washed by the reprocessor after the connectors were soaked in glutaraldehyde for 5 minutes. The channels, valves, connecting sections of group C endoscopes, and the connectors of the machine were sprayed with glutaraldehyde before machine-washing. Swabs were taken from all 13 parts of each endoscope and machine for microbiologic culture. RESULTS: Six endoscopes were positive, cumulatively, for bacterial contamination in group A. Among group B endoscopes, one remained contaminated. No endoscope was positive in group C. The difference between group A and C was statistically significant (p < .05). CONCLUSIONS: Machine washing by automatic endoscopic reprocessors may not achieve complete disinfection. Additional procedures are necessary. High-grade disinfection of the connectors is critical. Disinfection of the interface between the connectors is important.

Disinfection↗