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T Nakatsu

Publications and source records attributed to T Nakatsu.

At least 19 recordsLinked to original sources
PubMed2000

Uncoupling effect of anacardic acids from cashew nut shell oil on oxidative phosphorylation of rat liver mitochondria.

Anacardic acids are one of natural products found in not only the cashew nut shell oil but also the nut and fruit juice. The present study was conducted to investigate the uncoupling effect of anacardic acids on oxidative phosphorylation of rat liver mitochondria using succinate (plus rotenone) as a substrate. Four anacardic acids with C15:0, C15:1, C15:2 or C15:3 as an alkyl side chain exhibited uncoupling effects similar to the classical uncoupler, 2,4-dinitrophenol on ADP/O ratio, state 4 and respiratory control ratio (RCR). Anacardic acid with C15:1 side chain was most effective for uncoupling of these compounds. Salicylic acid, which has no alkyl side chain, exhibited a very weak uncoupling effect on oxidative phosphorylation. When the carboxyl group in anacardic acids was lost converting them to the corresponding cardanols, uncoupling activity dramatically decreased regardless of the number of double bonds in the long alkyl chain. These results suggest that the C15 alkyl side chain as well as the carboxyl group may play an important role in assisting the uncoupling activity of anacardic acids in liver mitochondria of animals. This study provides the first evidence of an uncoupling effect of anacardic acids on liver mitochondria

2,4-Dinitrophenol↗
PubMed1999

Structure of tropinone reductase-II complexed with NADP+ and pseudotropine at 1.9 A resolution: implication for stereospecific substrate binding and catalysis.

Tropinone reductase-II (TR-II) catalyzes the NADPH-dependent reduction of the carbonyl group of tropinone to a beta-hydroxyl group. The crystal structure of TR-II complexed with NADP+ and pseudotropine (psi-tropine) has been determined at 1.9 A resolution. A seven-residue peptide near the active site, disordered in the unliganded structure, is fixed in the ternary complex by participation of the cofactor and substrate binding. The psi-tropine molecule is bound in an orientation which satisfies the product configuration and the stereochemical arrangement toward the cofactor. The substrate binding site displays a complementarity to the bound substrate (psi-tropine) in its correct orientation. In addition, electrostatic interactions between the substrate and Glu156 seem to specify the binding position and orientation of the substrate. A comparison between the active sites in TR-II and TR-I shows that they provide different van der Waals surfaces and electrostatic features. These differences likely contribute to the correct binding mode of the substrates, which are in opposite orientations in TR-II and TR-I, and to different reaction stereospecificities. The active site structure in the TR-II ternary complex also suggests that the arrangement of the substrate, cofactor, and catalytic residues is stereoelectronically favorable for the reaction.

Alcohol Oxidoreductases↗
PubMed1999

Crystal structure of tobacco PR-5d protein at 1.8 A resolution reveals a conserved acidic cleft structure in antifungal thaumatin-like proteins.

The crystal structure of tobacco PR-5d, an antifungal thaumatin-like protein isolated from cultured tobacco cells, was determined at the resolution of 1.8 A. The structure consists of 208 amino acid residues and 89 water molecules with a crystallographic R-factor of 0.169. The model has good stereochemistry, with respective root-mean-square deviations from the ideal values for bond and angle distances of 0.007 A and 1.542 degrees. Of the homologous PR-5 proteins, only those with antifungal activity had a common motif, a negatively charged surface cleft. This cleft is at the boundary between domains I and II, with a bottom part consisting of a three-stranded antiparallel beta-sheet in domain I. The acidic residues located in the hollow of the cleft form the beta-sheet region. Sequence and secondary structure analyses showed that the amino acid residues comprising the acidic cleft of PR-5d are conserved among other antifungal PR-5 proteins. This is the first report on the high-resolution crystal structure of an antifungal PR-5 protein. This structure provides insight into the function of pathogenesis-related proteins.

Amino Acid Sequence↗
PubMed1999

Comparison of 26,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 and 1 alpha,25-dihydroxyvitamin D3 on the resorption of bone explants ex vivo.

26,27-Hexafluoro-1 alpha,25-dihydroxyvitamin D3 [F6-1,25-(OH)2D3] is more potent than 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] in stimulating bone resorption in vitro and in vivo. The reason why F6-1,25(OH)2D3 is more active remains unclear. To clarify the relationship between the bone-resorbing activity of each vitamin D3 analogue and the metabolism of each analogue, in the present study, we used an ex vivo method that was established by Reynolds et al (Calcif Tissue Res, 1974, 15, 333-339). The effect of F6-1,25(OH)2D3 or 1,25(OH)2D3 on 45Ca release from parietal bones, prepared at 3, 14 and 24 h after injection of 1.9, 3.8, 7.6 or 15.2 pmol vitamin D analog/g body weight, was examined. F6-1,25(OH)2D3 was more potent than 1,25(OH)2D3 during each in vivo time period. 1,25(OH)2D3 at 3 h after the injection was more active compared to the control (no injection of 1,25(OH)2D3) but not at 14 and 24 h. The radioactivity of the bones after the injection of [3H]-F6-1,25(OH)2D3 was retained even at 24 h. In the case of [3H]-1,25(OH)2D3, the radioactivity of bones decreased with an increase in the in vivo period. In a HPLC analysis of the lipid extract of bone homogenate, [3H]-F6-1,25(OH)2D3 alone was detected at 3 h after the injection and both [3H]-F6-1,25(OH)2D3 and [3H]-26,27-hexafluoro-1 alpha, 23S,25-trihydroxyvitamin D3 [F6-1,23,25(OH)3D3] were detected at 14 and 24 h after the injection. [3H]-1,25(OH)2D3 was highly detected at 3 h after the injection, but it decreased with an increase in the in vivo period. In the ex vivo test, the activity of F6-1,23,25(OH)3D3 was less than that of F6-1,25(OH)2D3 but similar to that of 1,25(OH)2D3. The present study indicates that F6-1,25(OH)2D3 is more active and more long-lasting than 1,25(OH)2D3 in the ex vivo method. A higher potency of F6-1,25(OH)2D3 is explained, at least partly, by the results that the amounts of both F6-1,25(OH)2D3 and its active metabolite, F6-1,23,25(OH)3D3, in the bones are higher than that of 1,25(OH)2D3, and that F6-1,25(OH)2D3 and its metabolite are retained in bones longer than 1,25(OH)2D3.

Animals↗
PubMed1998

Crystal structures of two tropinone reductases: different reaction stereospecificities in the same protein fold.

A pair of tropinone reductases (TRs) share 64% of the same amino acid residues and belong to the short-chain dehydrogenase/reductase family. In the synthesis of tropane alkaloids in several medicinal plants, the TRs reduce a carbonyl group of an alkaloid intermediate, tropinone, to hydroxy groups with different diastereomeric configurations. To clarify the structural basis for their different reaction stereospecificities, we determined the crystal structures of the two enzymes at 2.4- and 2.3-A resolutions. The overall folding of the two enzymes was almost identical. The conservation was not confined within the core domains that are conserved within the protein family but extended outside the core domain where each family member has its characteristic structure. The binding sites for the cofactor and the positions of the active site residues were well conserved between the two TRs. The substrate binding site was composed mostly of hydrophobic amino acids in both TRs, but the presence of different charged residues conferred different electrostatic environments on the two enzymes. A modeling study indicated that these charged residues play a major role in controlling the binding orientation of tropinone within the substrate binding site, thereby determining the stereospecificity of the reaction product. The results obtained herein raise the possibility that in certain cases different stereospecificities can be acquired in enzymes by changing a few amino acid residues within substrate binding sites.

Alcohol Oxidoreductases↗
PubMed1998

Crystal structure of asparagine synthetase reveals a close evolutionary relationship to class II aminoacyl-tRNA synthetase.

The crystal structure of E. coli asparagine synthetase has been determined by X-ray diffraction analysis at 2.5 A resolution. The overall structure of the enzyme is remarkably similar to that of the catalytic domain of yeast aspartyl-tRNA synthetase despite low sequence similarity. These enzymes have a common reaction mechanism that implies the formation of an aminoacyl-adenylate intermediate. The active site architecture and most of the catalytic residues are also conserved in both enzymes. These proteins have probably evolved from a common ancestor even though their sequence similarities are small. The functional and structural similarities of both enzymes suggest that new enzymatic activities would generally follow the recruitment of a protein catalyzing a similar chemical reaction.

Amino Acid Sequence↗
PubMed1998

Endoscopic papillary dilation by balloon and isosorbide dinitrate drip infusion for removing bile duct stone.

BACKGROUND: Endoscopic papillary dilation (EPD) by balloon in the management of bile duct stones has recently been claimed to be effective for removing bile duct stones. METHODS: Without endoscopic sphincterotomy, we attempted to remove large or multiple bile duct stones through EPD combined with drip infusion of isosorbide dinitrate in 35 patients. Isosorbide dinitrate, at a rate of 5 mg/h, was administered intravenously, and a balloon dilator with a 10-mm diameter was inflated within 3 min across the papilla. Stones were then smashed using a mechanical lithotriptor, and the fragments were extracted with a basket or the balloon. RESULTS: Extraction of stones was successful in 33 (94%) of 35 patients by the combined therapy. Two of them (6%) developed mild pancreatitis. CONCLUSION: EPD combined with medical sphincter dilation was effective for large and multiple bile duct stones.

Adult↗
PubMed1998

Pseudosarcomatous myofibroblastic tumor of the urinary bladder with massive intraperitoneal hemorrhage in a child.

A 3-year-old boy presented with persistent abdominal pain, hematuria and facial pallor with progressive anemia. A computed tomography scan showed a massive intraperitoneal hemorrhage and tumor mass in the bladder. Histological examinations of the resected tumor revealed findings of pseudosarcomatous myofibroblastic tumor (PMT). The clinico-pathological features of this case warn us that PMT can cause acute abdomen syndrome with massive intraperitoneal hemorrhage.

Abdomen, Acute↗
PubMed1998

Double-sector Lorenz plot scattering in an R-R interval analysis of patients with chronic atrial fibrillation: incidence and characteristics of vertices of the double-sector scattering.

Animal experiments have demonstrated that the minimum R-R interval during atrial fibrillation is proportional to the functional refractory period of the atrioventricular node. On Lorenz plots, atrial fibrillation is characterized by sector-shaped scattering; the vertex of the sector (ie, the minimum R-R interval) represents the functional refractory period. According to the atrioventricular nodal dual-pathway theory, it was hypothesized that the dual atrioventricular nodal pathways associated with chronic atrial fibrillation represent two vertices with two sectors. Detection of two-sector Lorenz plot scattering was attempted in 48 patients with chronic atrial fibrillation who underwent 24-hour ambulatory electrocardiography. Lorenz plot scattering was constructed by means of a computer. Two sectors, suggesting dual pathways, were detected in 19 (40%) of the 48 patients. The two vertices, located at 388 +/- 61 ms (mean +/- SD) and 580 +/- 60 ms were considered to represent the functional refractory periods of the fast and slow pathways, respectively. The vertex indicating the fast pathway showed greater circadian variation than that indicating the slow pathway. In one patient with dual-sector Lorenz plot scattering, whose atrial fibrillation spontaneously converted to sinus rhythm, an electrophysiologic study demonstrated dual atrioventricular nodal pathways. Thus, the Lorenz plot analysis identified two sectors, indicating the dual pathways, in approximately 40% of the patients with chronic atrial fibrillation, and the characteristics of the functional refractory periods of both pathways were estimated from the characteristics of the vertices. Although this study did not provide direct evidence of the dual atrioventricular nodal pathways, the analysis of Lorenz plot scattering may be clinically useful for studying the effects of drugs and/or ablation on the ventricular response in patients with atrial fibrillation based on the dual atrioventricular nodal pathway theory.

Aged↗
PubMed1997

Purification and characterization of tobacco pathogenesis-related protein PR-5d, an antifungal thaumatin-like protein.

Cultured tobacco cells accumulate several pathogenesis-related proteins. A neutral PR-5 protein, PR-5d, was purified to homogeneity from such cells. PR-5d has highly hydrophobic characteristics, but hydropathy analysis of its primary structure did not show a hydrophobic domain. In a series of bioassays, purified PR-5d showed inhibitory activity against several phytopathogenic and non-phytopathogenic fungi as do other members of the PR-5 protein family. To study the antifungal mechanism based on three dimensional structure of PR-5d, purified PR-5d was crystallized. The preliminary X-ray analysis of the crystal revealed that the crystals belong to space group C2, with cell dimensions a = 80.2 A, b = 63.8 A, c = 45.7 A, and beta = 107.2 degrees, and diffract at least 1.8 A resolution.

Amino Acid Sequence↗
PubMed1997

A large right coronary artery-left ventricle fistula with mild volume overload on the left ventricle owing to its capacitive action--pulsed Doppler and cineangiographic analyses in a patient.

A 54-year-old woman was admitted to our hospital because of a heart murmur without subjective symptoms. Angiography disclosed an enlarged right coronary artery and flow drainage into the left ventricle, ie, a large right coronary artery-left ventricle fistula. Analysis of pulsed Doppler studies and cineangiograms indicated considerable capacitance of this fistula owing to Windkessel action, which attenuated volume overload on the left ventricle. The features in this case suggest that evaluation of fistula hemodynamics is important in determining the overload on the ventricle through the fistula.

Blood Flow Velocity↗
PubMed1997

Decremental oscillation curve fitting of heart rate response following face immersion into cold water.

Using 18 healthy volunteers, we attempted to fit the heart rate response to a decremental oscillation curve by the least-squares method following facial immersion into cold water. The decremental oscillation equation was as follows: HR = alpha.e(-betat) sin omegat + gamma, where HR is the instantaneous heart rate at t s, alpha the maximum amplitude of the decremental oscillation, beta the decremental rate, omega the angular velocity and gamma the basal heart rate. Each subject immersed his/her face fully in a basin filled with ice-cold water (4 degrees C) for 30 s. The heart rate response to facial immersion was significantly fitted to the decremental oscillation curve with a correlation coefficient > 0.75 in all the trials. Double trials with a 15-min intertrial interval did not show any significant change in the coefficients. Atropine sulfate decreased the value of coefficient omega and increased that of gamma but did not change alpha or beta, indicating that omega is determined mainly by parasympathetic tone. There were no differences for any coefficient between men and women. The coefficients beta and gamma increased in association with age. Given the significant fitting to the decremental oscillation curve of the heart rate response, we propose that the corresponding electrical circuit consists of a resistance and an inductor connected in series, with a condenser in a parallel circuit with a direct current impulse. This method of fitting with the corresponding electric circuit may be useful for analysis of the heart rate response to physiological stimulus.

Age Factors↗
PubMed1997

Endoscopic lithotomy of common bile duct stones with sublingual nitroglycerin and guidewire.

OBJECTIVE: In 21 patients, our objective was the endoscopic removal of common bile duct stones by sphincter dilation with the application of sublingual nitroglycerin. METHODS: Nitroglycerin 0.3-0.6 mg was needed for proper dilation of the orifice and for successful cannulation of the Dormia basket into the bile duct. Cannulation of the Dormia basket was simplified by placing the guidewire in the common bile duct beforehand. Because of possible stone impaction, a mechanical lithotriptor was applied smoothly in two patients. RESULTS: Complete stone removal was successful in 18 of the 21 (86%) patients. One patient who developed a mild form of acute pancreatitis recovered in a few days by conservative management with drip infusion of protease inhibitor. Blood pressure dropped transiently in a patient receiving nitroglycerin, but the general condition of the patient was stable. CONCLUSIONS: This procedure was found to be safe, easy, and effective in extracting common bile duct stones.

Acute Disease↗
PubMed1996

Increased expression of cytokines in liver and serum in patients with extrahepatic diseases.

To determine whether the liver plays an immunological role in certain extrahepatic disorders, we investigated the expression of interleukin (IL)-1 beta, IL-6, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha in 11 patients who had recovered from cholecystolithiasis, 12 patients with gastric cancer, 20 patients with chronic hepatitis, and 6 healthy controls. Cytokine mRNAs in the liver were detected by semiquantitative reverse transcribed-polymerase chain reaction. Serum cytokines and soluble IL-2 receptor (sIL-2R) were investigated by enzyme-linked immunosorbent assays. Increases in TNF-alpha, IL-6, IL-1 beta, and IFN-gamma mRNAs were found in the livers of patients with extrahepatic diseases. TNF-alpha and IL-6 peptides were increased in the sera of patients with gastric cancer. TNF-alpha in the sera and TNF-alpha mRNA in the liver were correlated in gastric cancer patients. Surprisingly, sIL-2R in the serum of gastric cancer patients was significantly higher than the level in healthy controls. Our findings suggest that the liver produces cytokines in reaction to extrahepatic lesions. Further, the increase in sIL-2R in gastric cancer patients indicates that malignancy may affect the immune network in vivo.

Biopsy, Needle↗
PubMed1996

Scanning of polypoid gallbladder lesions by ultrasonic microprobes using transpapillary catheterization.

BACKGROUND AND STUDY AIMS: Polypoid lesions of the gallbladder can be diagnosed by transabdominal ultrasonography and endoscopic ultrasonography. However, the image resolution is limited, and the histopathology of these lesions is difficult to determine. We report here on our preliminary results in four patients using a high-frequency (20 MHz) ultrasonic microprobe introduced into the gallbladder via the transpapillary approach. PATIENTS AND METHODS: Insertion of the microprobe into the gallbladder through the papilla of Vater was attempted in four patients with gallbladder diseases without preceding endoscopic sphincterotomy. RESULTS: The lesions in the gallbladder were clearly visualized in three of the four patients. We tried to correlate the characteristic ultrasound findings with the histopathology of the lesions, which were found to be early cancer, adenoma, and adenomyomatosis on histopathology of the specimens after cholecystectomy. No complications occurred. CONCLUSIONS: High-resolution endoscopic transpapillary ultrasonography of the gallbladder is feasible and safe, and may contribute to the diagnosis of gallbladder diseases, particularly of small polypoid lesions.

Adenoma↗
PubMed1995

Papillary dilation vs sphincterotomy in endoscopic removal of bile duct stones. A randomized trial with manometric function.

To circumvent the long-term effects of papillary ablation for extracting common bile duct stones (< 12 mm in diameter) in endoscopic sphincterotomy (EST), endoscopic papillary dilation (EPD) was attempted in 20 patients. To evaluate papillary function before and after the procedures, manometry of the sphincter of Oddi was carried out in 13 with EPD and 10 of 20 patients with EST. Extraction of all stones was successful (100%) in both groups at an equal rate. Repeated numbers of procedures were common in both groups. However, the mean duration of the procedure was high in EPD compared to EST (63 min vs 42 min, P < NS). Adjunctive therapies like mechanical lithotripsy (ML), nasobiliary drainage, and choledochoscopy were included in EPD, while EST required a basket catheter and ML. There was no significant difference on manometry before and after the procedures (P = NS), although papillary function was found to have decreased after the EPD. In contrast, all patients in the EST group lost papillary function after the procedure. Thirty-day morbidity and mortality rate were absent in both groups. Immediate and 2.5-year follow up complications were uncommon in both groups. As a simple method, EPD may be an effective and safe alternative to EST in the management of patients with bile duct stones who require maintenance of papillary function.

Aged↗
PubMed1995

[A study on the effect of cepharanthin, a biscoclaurine alkaloid, on enhancement of mitogen-induced histidine decarboxylase activity in mice spleens and the effect of histamine on the production of cytokines].

The effect of cepharanthin on the enhancement of mitogen-induced histidine decarboxylase (HDC) activity in mice spleens and the effect of histamine on the production of cytokines were investigated. Cepharanthin enhanced LPS-induced HDC activity in normal mice spleens and also enhanced it in genetically T cell-deficient nude mice spleens and T and B cell-deficient scid mice spleens. Therefore, cepharanthin can exert its effect on macrophages without T cells or B cells. Cepharanthin enhanced LPS-induced cytokine production by macrophages. Histamine induced cytokine production and enhanced LPS-induced cytokines production by macrophages. However, diphenhydramine and cimetidine, histamine receptor antagonists, did not block this process. Alpha-fluoromethylhistidine, a suicide inhibitor of HDC, suppressed LPS-induced cytokine production. These results suggest that cytokine production by macrophages is regulated by both histamine added exogenously and histamine induced by macrophages themselves and that histamine participates in enhancement of cytokine production by cepharanthin.

Alkaloids↗