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R Sato

Publications and source records attributed to R Sato.

At least 109 records · Page 6Linked to original sources
PubMed1999

Androgen-producing ovarian tumors: a clinicopathological study of 3 cases.

The clinical course and pathological findings of 3 rare cases of androgen-producing ovarian tumors are presented. The ages of the 3 patients (Cases 1, 2, and 3, respectively) were 43, 34, and 57 years, respectively. Their preoperative serum testosterone levels were 506, 491, and 231 ng/dl, respectively. The pathological diagnoses of Cases 1, 2, and 3 were a Sertoli-stromal cell tumor of intermediate differentiation, a stromal tumor containing Leydig cells, and a stromal tumor with minor sex cord elements, respectively. Patient 1 experienced a recurrence, of a lesion at the vaginal stump 1 year and 2 months after the initial surgery. The clinical courses of Cases 2 and 3 have been non-contributory.

Adult↗
PubMed1999

Efficacy of RD3-0028 aerosol treatment against respiratory syncytial virus infection in immunosuppressed mice.

RD3-0028, a benzodithiin compound, has antiviral activity against respiratory syncytial virus (RSV) in cell culture. We used a mouse model of RSV infection to determine the in vivo effect of RD3-0028. Cyclophosphamide (CYP)-treated, immunosuppressed mice were inoculated intranasally. The lungs of the mice were removed on day 4. The virus titers of the lungs of RD3-0028-treated mice were compared to the virus titers of the lungs of virus-inoculated, untreated control mice. In an effort to increase the therapeutic effectiveness of this compound, RD3-0028 was administered by aerosol to RSV-infected mice by using a head-exposure system. Aerosols generated from reservoirs containing RD3-0028 (7 mg/ml) administered for 2 h twice daily for 3 days significantly reduced the pulmonary titer of RSV-infected mice. It is clear that the minimal effective dose of RD3-0028 for RSV-infected mice is significantly less than that of ribavirin, the only compound currently available for use against RSV disease. Furthermore, the RD3-0028 aerosol administration appeared to protect the lungs of infected, CYP-treated mice against tissue damage, as evidenced by the preservation of the lung architecture and a reduction in pulmonary inflammatory infiltrates. RD3-0028 aerosol was not toxic for mice at the therapeutic dose. The present study demonstrates the effectiveness of aerosol administration of RD3-0028 for RSV-infected mice.

Aerosols↗
PubMed1999

A novel splicing isoform of mouse sterol regulatory element-binding protein-1 (SREBP-1).

We cloned a cDNA encoding the NH2-terminal portion of mouse SREBP-1. The deduced amino acid sequence was 76% and 90% identical to human and hamster SREBP-1, respectively. We found out a novel splicing isoform of mouse SREBP-1 that lacks 42 amino acid residues composing a PEST sequence observed in unstable proteins. It has been reported that SREBP-1 is rapidly turned over in the nucleus. Although this isoform was not a dominant isoform, it might be possible that the produced protein functions differently from other isoforms including a complete PEST sequence.

Alternative Splicing↗
PubMed1999

Evidence for norepinephrine-activated Ca2+ permeable channels in guinea-pig hepatocytes using a patch clamp technique.

To determine whether the hepatocyte plasma membrane possesses a Ca2+ channel. we applied a patch clamp technique to isolated guinea-pig hepatocytes. In a cell-attached configuration, using an internal pipette solution of 110 mM BaCl2 or CaCl2, we observed sporadic inward single channel currents (Po = 0.004 +/- 0.002, n = 6) at various membrane potentials. The unit amplitude was 0.60 +/- 0.15 pA (n = 6) at resting membrane potential. The single channel conductance was 20.4 +/- 4.6 pS (n = 6) and this channel showed no rectification and no voltage dependence. Bay K 8644, a dihydropyridine Ca2+ channel activator, did not affect this channel activity. Although norepinephrine in the pipette solution did not activate this channel, its external application increased channel activity. These observations suggest that guinea-pig hepatocytes possess Ca2+ permeable channels that differ from the voltage-operated Ca2+ channels found in excitable cells and that such channels are responsible for the agonist-stimulated Ca2+ entry in hepatocytes.

Animals↗
PubMed1999

Experimental hypocalcemia induced by hemodialysis in goats.

To evaluate whether hemodialysis with a dialysate containing no calcium (Ca-free HD) can induce hypocalcemia and restore the clinical signs and blood biochemical changes in naturally occurred hypocalcemic disorder in ruminants, the clinical signs and the changes in plasma electrolytes and minerals concentrations were observed in goats during 6-hr hemodialysis. The four goats received hemodialysis with the dialysate containing calcium (Ca HD), and 10 days later they had Ca-free HD. The plasma ionized Ca (Ca++) and total Ca (TCa) concentrations were not affected by Ca HD, whereas the levels significantly decreased during whole period of Ca-free HD. The Ca++ and TCa concentrations were 0.69+/-0.06 mmol/l and 5.9+/-0.3 mg/dl at 6 hr of Ca-free HD, respectively. The clinical signs observed during Ca-free HD seemed to resemble to those in naturally occurred hypocalcemic cases that were reported previously. Therefore, Ca-free HD was suggested to be one of the possible methods to induce experimental hypocalcemia in ruminants.

Animals↗
PubMed1999

N-acetyl-beta-D-glucosaminidase activity in urine of cows with renal parenchymal lesions.

OBJECTIVE: To measure N-acetyl-beta-D-glucosaminidase (NAG) activity in urine of cows with renal diseases and to correlate values for NAG activity with renal lesions. ANIMALS: 8 lactating Holstein cows and a Japanese Shorthorn cow, all of which had renal disease. PROCEDURE: Urine samples were collected, and urinary NAG activity and creatinine concentration were measured. The NAG activity was expressed as units per gram of creatinine (NAG index). Cows were euthanatized, necropsy was performed, and correlations between results for urinary NAG index and histopathologic findings for the kidneys were evaluated. RESULTS: The NAG activity and NAG index in urine samples obtained from cows with interstitial nephritis were high, ranging from 4.2 to 13.6 U/L and 3.5 to 23.0 U/g, respectively. A cow with renal amyloidosis also had high values for urinary NAG activity and NAG index. Histologic examination of the kidneys revealed various kinds of parenchymal lesions. However, urinary NAG index in cows with enzootic bovine leukosis was low. CONCLUSIONS AND CLINICAL RELEVANCE: Cows with renal diseases had high urinary NAG indexes that correlated well with their renal lesions, except for cows with enzootic bovine leukosis. Therefore, measurement of NAG index in urine samples has the potential to provide new perspectives on clinical diagnosis of renal disease in cattle.

Acetylglucosaminidase↗
PubMed1999

Lipid peroxides and antioxidants in serum of neonatal calves.

OBJECTIVE: To examine the association between oxidative stress and antioxidants in neonatal calves after birth. SAMPLE POPULATION: Sera from 6 healthy Holstein-Friesian cows and 7 of their newborn calves were obtained at various intervals after birth. PROCEDURE: Lipid peroxides in serum of cows and their newborn calves were estimated by measuring concentrations of thiobarbituric acid-reactive substances (TBARS). The antioxidative activities of neonatal sera were evaluated by measuring their superoxide-scavenging activities, ferroxidase activities, and the concentration of bilirubin-associated albumin. RESULTS: Concentration of TBARS in neonatal sera within 1 day after birth was significantly higher than concentrations > or = 2 days after birth and concentrations in serum of the dams. In contrast, antioxidative activities of neonatal sera, evaluated on the basis of superoxide-scavenging activities, ferroxidase activities, and concentration of bilirubin-associated albumin 3 hours after birth, were significantly lower than antioxidative activities in sera of the dams. CONCLUSIONS: Susceptibility of calves to oxidative stress during the neonatal period may be explained by the immature defense system against superoxide radicals.

Animals↗
PubMed1999

Temporal differences in actions of calcium channel blockers on K+ accumulation, cardiac function, and high-energy phosphate levels in ischemic guinea pig hearts.

We investigated temporal differences in the protective action of three types of Ca2+ channel blockers in myocardial ischemia, focusing particularly on the blocking ability under depolarizing conditions. The effects of diltiazem, verapamil, and nifedipine on extracellular potassium concentration ([K+]e), acidosis, and level of metabolic markers were examined during 30-min global ischemia and postischemic left ventricular (LV) function in isolated guinea pig hearts. Diltiazem and verapamil, but not nifedipine, inhibited the late phase (15-30 min) of [K+]e elevation, whereas all three blockers delayed the onset of the early phase (0-8 min) of [K+]e elevation. Diltiazem and verapamil inhibited ischemic contracture and improved postischemic LV function to a greater extent. These differences appeared to be linked to preservation of ATP and creatine phosphate and delay of cessation of anaerobic glycolytic activity. Maneuvers to preserve energy sources during ischemia (decrease in external Ca2+ concentration or pacing at a lower frequency) attenuated the late phase of [K+]e elevation. Inhibition of LV pressure was potentiated 12- and 8.2-fold by diltiazem and verapamil, respectively, at 8.9 mM K+ as compared with 2.9 mM K+, whereas that by nifedipine was unchanged. These results indicate that the differential cardioprotection of Ca2+ channel blockers in the late period of ischemia correlates with preservation of high-energy phosphates as a result of different Ca2+ channel blocking abilities under high [K+]e conditions.

Acidosis↗
PubMed1999

[Sterol regulatory element binding protein that controls cholesterol metabolism].

Sterol regulatory element-binding proteins, designated as SREBP-1 and -2, are synthesized as membrane-bound proteins. They are localized on the endoplasmic reticulum membrane and the nuclear envelope, and activated by a two-step proteolytic processing. The NH2-terminal processed forms are released in the cytosol only when the intracellular cholesterol level is low, and translocated to the nucleus, resulting in the stimulation of transcription of the target genes. The transcriptional regulation requires either Sp1 or NF-Y, which binds its specific DNA-binding site close to the SREBP-binding site. On the contrary, the transcription of the MTP (Microsomal Triglyceride transfer Protein) gene is down-regulated by SREBPs without any participation of either Sp1 or NF-Y.

CCAAT-Enhancer-Binding Proteins↗
PubMed1998

Differences in the electrophysiological response to I- and the inhibitory anions SCN- and ClO-4, studied in FRTL-5 cells.

The electrophysiological properties of the Na+/I- symporter (NIS) were examined in a cloned rat thyroid cell line (FRTL-5) using the whole-cell patch-clamp technique. When the holding potential was between -40 mV and -80 mV, 1 mM NaI and NaSCN induced an immediate inward current which was greater with SCN- than with I-. The reversal potential for I- and SCN- induced membrane currents was +50 mV. This is close to the value of +55 mV calculated by the Nernst equation for Na+. These results are consistent with I- and SCN- translocation via the NIS that is energized by the electrochemical gradient of Na+ and coupled to the transport of two or more Na+. There was no change in the membrane current recording with ClO-4 indicating that ClO-4 was either not transported into the cell, or the translocation was electroneutral. ClO-4 addition, however, did reverse the inward currents induced by I- or SCN-. These effects of I-, SCN- and ClO-4 on membrane currents reflect endogenous NIS activity since the responses duplicated those seen in CHO cells transfected with NIS. There were additional currents elicited by SCN- in FRTL-5 cells under certain conditions. For example at holding potentials of 0 and +30 mV, 1 mM SCN- produced an increasingly greater outward current. This outward current was transient. In addition, when SCN- was washed off the cells a transient inward current was detected. Unlike SCN-, 1-10 mM I- had no observable effect on the membrane current at holding potentials of 0 and +30 mV. The results indicate FRTL-5 cells may have a specific SCN- translocation system in addition to the SCN- translocation by the I- porter. Differences demonstrated in current response may explain some of the complicated influx and efflux properties of I-, SCN- and ClO-4 in thyroid cells.

Animals↗
PubMed1998

Roles of A- and D-type K channels in EPSP integration at a model dendrite.

We examined the roles of A- and D-type K channels in the integration of EPSPs, particularly EPSP reduction, in a model dendrite using a computer simulation program (NEURON), instead of conventional electrophysiological methods which present technical difficulties. We obtained two important results: (1) KD channels play a crucial role in every synaptic input event, and (2) KA channels affect reduction of the second EPSP only when the second synaptic input is applied with a short interval (<100 ms). These results suggest that KD channels, which have not yet been analyzed experimentally, play a major role in synaptic integration in dendrites by altering their cable properties.

Animals↗
PubMed1998

Selection of DNA binding sites for human transcriptional regulator GATA-6.

The DNA-binding sites for transcriptional regulator GATA-6 were selected and amplified by means of a PCR-mediated random-site selection method involving filter binding and gel-mobility shift analysis using the zinc finger region of human GATA-6 fused with GST. Sequencing and comparison of the selected clones suggested that (A/T/C)GAT(A/T)(A) is the consensus binding sequence, which is similar to the GATA motif (A/T)GATA(A/G) and the gastric motif (G/C)PuPu(G/C)NGAT(A/T)PuPy. GATA-6 also binds to a similar sequence containing the GATC but not the GATG sequence. These results indicated that GATA-6 shows broader sequence specificity as to DNA binding. However, adenine is favored on both sides of the core for strong binding [AGAT(A/T)A], and the order of binding is GATA > GATT > GATC. Full-length human GATA-6 expressed in COS-1 cells showed essentially the same binding specificity, suggesting that the zinc finger region of GATA-6 mainly contributes to the selection of the binding sequence. Furthermore, the non-RI method presented in this paper is convenient for determination of the binding sites of other DNA-binding proteins.

Binding Sites↗
PubMed1998

Antiplatelet effect of Z-335, a new orally active and long-lasting thromboxane receptor antagonist.

We investigated the pharmacological characteristics of Z-335 ((+/-)-sodium[2-[4-(chlorophenylsulfonylaminomethyl)indan-5-yl]ace tate monohydrate), a new indan derivative. Z-335 inhibited the specific binding of [3H]SQ-29548 to human platelets and guinea pig platelet membranes. The IC50 values of Z-335 for human platelets and guinea pig platelet membranes were 29.9 +/- 3.1 nM with a slope of 1.09 +/- 0.05 and 32.5 +/- 1.7 nM with a slope of 1.07 +/- 0.02, respectively. Z-335 inhibited thromboxane A2 receptor-mediated human and guinea pig platelet aggregation in vitro and oral administration of this drug to guinea pigs inhibited U-46619- and collagen-induced platelet aggregation for 24 h. Z-335 dose-dependently prevented the occurrence of U-46619-induced pulmonary thromboembolism in mice and the protective effect of this drug (0.3 and 3 mg/kg, p.o.) lasted for 24 h. These results strongly suggest that Z-335 is a potent, orally active and long-lasting thromboxane A2 receptor antagonist, which may be useful as an antiplatelet drug.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Characterization of the stretch-activated chloride channel in isolated human atrial myocytes.

Macroscopic and unitary currents through stretch-activated Cl- channels were examined in isolated human atrial myocytes using whole-cell, excised outside-out and inside-out configurations of the patch-clamp technique. When K+ and Ca2+ conductances were blocked and the intracellular Ca2+ concentration ([Ca2+]i) was reduced, application of positive pressure via the pipette activated membrane currents under whole-cell voltage-clamp conditions. The reversal potential of the current shifted by 60 mV per 10-fold change in the external Cl- concentration, indicating that the current was Cl- selective. The current was inhibited by bath application of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and 9-anthracenecarboxylic acid (9-AC). beta-Adrenergic stimulation failed to activate a Cl- current. In single channel recordings from outside-out patches, positive pressure in the pipette activated the unitary current with half-maximal activation of 14.7 mm Hg at +40 mV. The current-voltage relationship of single channel activity obtained in inside-out patches was linear in symmetrical Cl- solution with the averaged slope conductance of 8.6 +/- 0.7 pS (mean +/- SD, n = 10). The reversal potential shift of the channel by changing Cl- concentration was consistent with a Cl- selective channel. The open time distribution was best described by a single exponential function with mean open lifetime of 80.4 +/- 9.6 msec (n = 9), while at least two exponentials were required to fit the closed time distributions with a time constant for the fast component of 11.5 +/- 2.2 msec (n = 9) and that for the slow component of 170.2 +/- 21.8 msec (n = 9). Major changes in the single channel activity in response to pressure were caused by changes in the interburst interval. Single channel activity was inhibited by DIDS and 9-AC in a manner similar to whole-cell configuration. These results suggest that membrane stretch induced by applying pressure via the pipette activated a Cl- current in human atrial myocytes. The current was sensitive to Cl- channel blockers and exhibited membrane voltage-independent bursting opening without sensitive to beta-adrenergic stimulation.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Effect of liposome-encapsulated hemoglobin, neo red cells, on hemorrhagic shock.

We examined the effects of liposome-encapsulated hemoglobin, neo red cells (NRCs), on hemorrhagic shock in a canine model. The dogs were divided into the three groups according to treatment. In group 1, composed of six dogs, NRCs were substituted for blood without shock being induced; in group 2, composed of six dogs, NRCs were administered immediately after mild shock had been induced by exsanguination through the vein; and in group 3, composed of seven dogs, NRCs were administered after they had been left untreated for 30 min inducing severe shock. In group 2, administration of NRCs at a dose equivalent to the volume of exsanguinated blood improved the symptoms of shock; however, in group 3, a dose of NRCs 1.6-times the volume of exsanguinated blood was required. Peripheral vascular resistance (PVR) decreased after NRC administration in groups 1 and 2, but increased in group 3. On the other hand, the cardiac index (CI) increased in groups 1 and 2, and decreased in group 3. Concerning oxygen kinetics, there were no increases in the oxygen requirements or arteriovenous differences of the oxygen content per hemoglobin (AV/Hb) for NRCs in groups 1 and 2. Conversely, in group 3, the oxygen requirements increased and the NRCs compensated for the decrease in CI with an increase in AV/Hb by enhancing the oxygen transport efficiency to cope with the increased oxygen requirements.

Animals↗
PubMed1998

Effect of sulfhydryl oxidoreduction on permeability of cardiac tetrodotoxin-insensitive sodium channel.

Effects of sulfhydryl oxidizing and reducing agents on permeability of the tetrodotoxin (TTX)-insensitive Na-channel were investigated in guinea-pig ventricular myocytes using the whole-cell patch-clamp technique. Mercury chloride (HgCl2) at 1-100 microM irreversibly blocked Na+ currents with no significant changes in the gating kinetics. In contrast, the hydrophilic sulfhydryl oxidizing agent, thimerosal at 50-100 microM little affected Na+ permeation through the Na-channel. The Hg2+-induced block of Na+ current could be readily reversed by 1,4-dithiothreitol (DTT), an agent that reduces disulfide bonds. These results indicate that the formation of sulfur-Hg-sulfur bridge is essential for Hg2+ block. Pretreatment with DTT prevented the Hg2+ block of Na+ current, whereas Zn2+ and Cd2+ retained their abilities to block Na+ current after DTT treatment. An application of Zn2+ or Cd2+ resulted in the restoration of Hg2+ sensitivity of the DTT-treated channel. A conformational model for the Na-channel with multiple free sulfhydryl groups and native disulfide bonds could account for our experimental data regarding the effects of sulfhydryl modifying agents on the channel permeability. We conclude that the cardiac TTX-insensitive Na-channel contains functionally important free sulfhydryl groups and disulfide bonds which are accessible from the extracellular side by an aqueous pathway. These sulfhydryls would be capable of modulating the Na-channel permeability by affecting the conformation of channel pore region.

Algorithms↗
PubMed1998

Kinetics of buccal absorption of propafenone single oral loading dose in healthy humans.

Buccal absorption has an advantage when compared with other administration routes because of its rapid onset of action. We examined the pharmacokinetics of buccal-absorbed propafenone in healthy humans. 1. After a single oral administration of 150 mg of propafenone, the average peak concentration of propafenone was 27.9+/-2.5 ng/ml, and that of 5-hydroxypropafenone was 61.7+/-6.6 ng/ml (n=5). The times to reach peak serum concentrations of propafenone and 5-hydroxypropafenone were 1.8+/-0.1 hr and 1.5+/-0.2 hr, respectively. 2. After a buccal absorption of 150 mg of propafenone, the time to reach peak serum concentration of propafenone was 16.9+/-2.3 min (n=8). The average peak concentration of propafenone was 30.4+/-1.4 ng/ml (n=8), and the concentrations of 5-hydroxypropafenone were below the detection limit in all subjects. The rapid upstroke of serum concentrations of propafenone by buccal administration may cause rapid onset of pharmacological conversion.

Absorption↗