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Biomedical subjects

T Yamato

Publications and source records attributed to T Yamato.

At least 37 records · Page 2Linked to original sources
PubMed1999

Frequent expression of mucin core protein MUC1 in non-neoplastic gallbladder mucosa from patients with pancreaticobiliary maljunction.

BACKGROUND: Gallbladder carcinoma is known to develop frequently in patients with pancreaticobiliary maljunction, though the causal relationship remains speculative. METHODS: Histopathologic changes, expression of mucin core protein MUC1 and MUC2, and cell proliferative activities in the gallbladder mucosa from 27 patients with panceaticobiliary maljunction and 21 control gallbladders were examined. Three cases of pancreaticobiliary maljunction were associated with gallbladder carcinoma. RESULTS: The lining epithelia of the non-neoplastic gallbladder mucosa of pancreaticobiliary maljunction showed frequently papillary hyperplasia and higher proliferative activities, when compared to the control. In 3 cases with carcinoma, MUC1 was expressed on the luminal border and in the cytoplasm of carcinoma cells, particularly in de-differentiated and invasive areas. MUC1 was variably expressed on the luminal surface of the lining epithelia of non-neoplastic gallbladder mucosa in babies, children, youths and adults with pancreaticobiliary maljunction. However, such expression was focally seen in 2 of the 21 control cases (p<0.01). MUC2 was scattered in the hyperplastic and carcinomatous epithelial cells appearing as goblet cells in pancreaticobiliary maljunction and control groups. CONCLUSIONS: This study suggests that persistent MUC1 expression and increased cell proliferative activities of non-neoplastic gallbladder epithelium of the patients with pancreaticobiliary maljunction after birth reflect an altered phenotype of epithelial cells and these abnormalities may be related to carcinogenesis in such patients.

Adult↗
PubMed1999

Isolation and characterization of the novel gene, TU3A, in a commonly deleted region on 3p14.3-->p14.2 in renal cell carcinoma.

We previously identified a 700-kb region of common allelic loss on 3p14.3-->p14.2 in renal cell carcinoma (RCC). We further analyzed this region and constructed a sequence ready bacterial artificial chromosome (BAC) contig. This region was totally covered by six overlapping BAC clones and was roughly estimated to be 700 kb. Furthermore, we isolated a gene in this region that we termed TU3A. This gene encodes a protein consisting of 144 amino acids. Homology search did not show any significant similarities with known genes or proteins. Northern analysis with normal tissue identified a 3.0-kb transcript that was expressed ubiquitously. Although our mutation search using 37 primary RCCs as well as five RCC cell lines failed to detect any somatic alterations in the TU3A gene, two of five RCC cell lines had totally lost its expression. Considering the fact that we found no genetic alterations in TU3A, it is possible that some epigenetic alteration may have suppressed its expression.

Amino Acid Sequence↗
PubMed1998

Molecular dynamics study of femtosecond events in photoactive yellow protein after photoexcitation of the chromophore.

Molecular dynamics simulations were carried out to study what happens in a photoreceptor protein, photoactive yellow protein (PYP), immediately after the vertical transition of the chromophore from the ground to the excited state. A photon absorption simulation was performed to investigate the movement of amino acid residues upon photoexcitation. To calculate the excited state of the chromophore, SCF-CI calculation was carried out with INDO/S Hamiltonian. We observed that some amino acid residues have strong interactions with the chromophore. Most of these amino acid residues are conserved in PYPs from three different species of bacteria. This observation indicates the biological importance of these residues.

Amino Acid Sequence↗
PubMed1998

Intrahepatic cholangiocarcinoma arising in congenital hepatic fibrosis: report of an autopsy case.

We report an autopsy case of a 60-year-old woman who had congenital hepatic fibrosis with intrahepatic cholangiocarcinoma. A white nodular lesion with a surrounding vague gray area was detected in the right lobe of the liver. Microscopically, most of the nodular lesion was a poorly-differentiated adenocarcinoma. In the surrounding gray area, small bile ducts and bile ductules showed prominent epithelial overgrowth, some of which was composed of dysplasia and well-differentiated adenocarcinoma. The background liver showed the characteristic features of congenital hepatic fibrosis. Immunohistochemically, biliary oncofetal markers (mucin core protein 1 and carcinoembryonic antigen) were more frequently and extensively expressed in poorly-differentiated than well-differentiated adenocarcinoma. This is the 4th reported case of intrahepatic cholangiocarcinoma arising in congenital hepatic fibrosis and suggests that malignant transformation via dysplasia occurs in the abnormal intrahepatic biliary tree of older congenital hepatic fibrosis patients.

Autopsy↗
PubMed1998

Novel method to detect a motif of local structures in different protein conformations.

In order to detect a motif of local structures in different protein conformations, the Delaunay tessellation is applied to protein structures represented by C(alpha) atoms only. By the Delaunay tessellation the interior space of the protein is uniquely divided up into Delaunay tetrahedra whose vertices are the C(alpha) atom positions. Some edges of the tetrahedra are virtual bonds connecting adjacent residues' C(alpha) atoms along the polypeptide chain and others indicate interactions between residues nearest neighbouring in space. The rules are proposed to assign a code, i.e., a string of digits, to each tetrahedron to characterize the local structure constructed by the vertex residues of one relevant tetrahedron and four surrounding it. Many sets comprised of the local structures with the same code are obtained from 293 proteins, each of which has relatively low sequence similarity with the others. The local structures in each set are similar enough to each other to represent a motif. Some of them are parts of secondary or supersecondary structures, and others are irregular, but definite structures. The method proposed here can find motifs of local structures in the Protein Data Bank much more easily and rapidly than other conventional methods, because they are represented by codes. The motifs detected in this method can provide more detailed information about specific interactions between residues in the local structures, because the edges of the Delaunay tetrahedra are regarded to express interactions between residues nearest neighbouring in space.

Models, Molecular↗
PubMed1998

Inhibitory effects of lipid oxidation on the activity of plasma lecithin-cholesterol acyltransferase.

We investigated the effects of free radical generation on the esterification of cholesterol by lecithin-cholesterol acyltransferase (LCAT). A water-soluble free radical initiator, 2,2'-azobis-amidinopropane dihydrochloride (AAPH), inhibited the activity of plasma LCAT as a function of the incubation time after its addition. When a small amount of oxidized HDL was added to plasma, LCAT activity was dose-dependently inhibited. To identify the effects of HDL oxidation on LCAT activity, a purified enzyme and cofactor in a vesicle solution (an artificial substrate) were used. i) LCAT activity was inhibited by the oxidation of substrate vesicles, this inhibition being related to the degree of oxidation. ii) This inhibition was observed even if apolipoprotein A-I was not oxidized. iii) Oxidized phosphatidylcholine, but not oxidized cholesterol, in the vesicles affected LCAT activity. iv) The addition of 0-40% of oxidized vesicles to normal substrate vesicles resulted in the activity of LCAT being inhibited in a dose-dependent manner. These results suggest that the esterification of cholesterol by LCAT may be affected by the oxidation of substrate phosphatidylcholine via free radical generation in the plasma.

Cholesterol↗
PubMed1997

Mechanical property of a TIM-barrel protein.

The mechanical response of a TIM-barrel protein to an applied pressure has been studied. We generated structures under an applied pressure by assuming the volume change to be a linear function of normal mode variables. By Delaunay tessellation, the space occupied by protein atoms is divided uniquely into tetrahedra, whose four vertices correspond to atomic positions. Based on the atoms that define them, the resulting Delaunay tetrahedra are classified as belonging to various secondary structures in the protein. The compressibility of various regions identified with respect to secondary structural elements in this protein is obtained from volume changes of respective regions in two structures with and without an applied pressure. We found that the beta barrel region located at the core of the protein is quite soft. The interior of the beta barrel, occupied by side chains of beta strands, is the softest. The helix, strand, and loop segments themselves are extremely rigid, while the regions existing between these secondary structural elements are soft. These results suggest that the regions between secondary structural elements play an important role in protein dynamics. Another aspect of tetrahedra, referred to as bond distance, is introduced to account for rigidities of the tetrahedra. Bond distance is a measure of separation of the atoms of a tetrahedron in terms of number of bonds along the polypeptide chain or side chains. Tetrahedra with longer bond distances are found to be softer on average. From this behavior, we derive a simple empirical equation, which well describes the compressibilities of various regions.

Compressive Strength↗
PubMed1996

Strain tensor field in proteins.

The tensor fields of pressure strain imposed on protein molecules have been visualized by computer graphics and computational geometry. The pressure-induced deformations of lysozyme and myoglobin were analyzed by the present method, which regards each molecule as a patchwork of microscopic continuous bodies of Delaunay tetrahedra. The strain tensor describes the deformation of each tetrahedron. The illustrated deformations turned out to be complex and inhomogeneous ones in which local expansions and contractions concomitantly occurred. Not only the pressure deformation but also any other type of moderate deformation can be analyzed by this method.

Computer Graphics↗
PubMed1996

Inhibition of contractile tension by capsaicin in isolated rat papillary muscle.

1. We examined effects of capsaicin (10(-9) - 10(-5) M), a pungent agent extracted from red pepper, on the contractile tension of rat ventricular papillary muscles stimulated at various cycle lengths (0.2, 0.5, 1, 2 and 5 sec). 2. Capsaicin produced a marked concentration-dependent decrease in the amplitude, the rate of rise (dp/dt) and the rate of relaxation (dr/dt) of the tension. 3. However, the half relaxation time and the time to peak tension of the tension were slightly affected by the agent. 4. The negative inotropic effect of capsaicin was stimulus cycle length (CL) dependent. In particular, IC50 (50% inhibitive concentration) of the agent in the amplitude of the tension was stimulus CL dependent. That is, the values of IC50 were around 10(-7) M at longer CLs (1, 2 and 5 sec), and the value of IC50 at CL 0.2 sec was 4 x 10(-6) M. 5. These capsaicin-induced negative inotropic effects were reversible. Other studies from our laboratory show that the negative inotropic effects may be largely due to a decrease in Ca2+ current.

Animals↗
PubMed1996

Capsaicin does not inhibit the intracellular calcium handling process in rat ventricular papillary muscle.

1. We studied the effects of capsaicin, a pungent agent extracted from red pepper, on rested-state contraction (RSC) of isolated rat ventricular papillary muscles. 2. The RSC was induced by stimulation, after a rest interval of 5 sec to 10 min, after the twitch tension of the muscle preparation stimulated at the regular stimulus frequency of cycle lengths of 5, 1 or 0.2 sec attained the steady state. 3. Drug effects were evaluated on the RSC in the presence of capsaicin 10(-5) M, caffeine 10(-2) M or ryanodine 10(-7) M, respectively. 4. All drugs inhibited the RSC but to different degrees. Ryanodine was the most effective in inhibiting RSC, followed by caffeine and capsaicin, in that order. However, the inhibitory mode varied, depending on the drugs. 5. These findings suggest that capsaicin may not inhibit the function of intracellular Ca2+ store in rat cardiac muscle.

Alkaloids↗
PubMed1995

Effects of randomization of partially hydrogenated corn oil on fatty acid and cholesterol absorption, and tissue lipid levels in rats.

Randomization of partially hydrogenated corn oil containing approximately 45% of trans octadecenoic acid only slightly, but not significantly, increased the lymphatic fatty acid absorption in rats. No effect of randomization was observed on cholesterol absorption. When rats were fed these fats at the 8.8% level (with 1.2% safflower oil) for three weeks, the concentrations of serum cholesterol, and serum and liver phospholipid were significantly higher in randomized fat than in control fat, which was composed of 9% high-oleic safflower oil and 1% palm oil. Liver cholesterol tended to be higher in randomized fat. In contrast, nonrandomized fat was not hyperlipidemic compared to control fat. Although the fatty acid composition of liver phospholipids suggested a possible interference of trans fatty acid with the metabolism of linoleic acid to arachidonic acid, there was no effect of randomization. In the two hydrogenated fat groups, trans octadecenoic acid was incorporated and distributed similarly in adipose tissue triacylglycerol. These observations indicated that randomization of partially hydrogenated fat is not beneficial to various lipid parameters in rats.

Absorption↗
PubMed1995

[Two cases of chondrosacoma of rib].

Chondrosarcoma of rib origin is rare in Japan. We treated two cases of chondrosarcoma of rib origin. Case 1: A 68-year-old man with anterior chest wall mass and chest pain was underwent aspiration biopsy in Inami General Hospital. The histological examination showed Class V. Operation was done in our department and the histological diagnosis was chondrosarcoma. The tumor was 30 x 20 x 20 mm in size arising from the left fourth rib. The defect of bony chest wall was repaired with a double layer of Marlex mesh. His postoperative course was uneventful. Case 2: 66-year-old man noticed a tumor in left anterior part of the chest 7 months ago. He was underwent incisional biopsy and the histological diagnosis was chondrosarcoma. Radical resection was performed. The tumor was 70 x 50 x 50 mm in size arising from the left rib. His postoperative course was uneventful.

Aged↗
PubMed1993

Conformational deformation in deoxymyoglobin by hydrostatic pressure.

Pressure effect on the equilibrium conformation in sperm whale deoxymyoglobin and its volume fluctuation are studied by the normal mode analysis and strain tensor analysis. The pressure-induced deformation of interhelix regions are found to be remarkably more compressed than the other parts of the molecule. The intrahelix compressibility is shown to be relatively small. We also calculate the compressibility of the three hydrophobic clusters, located at the bottom, distal, and proximal side of the heme. Its value is found to decrease in the indicated order. The average compressibility of these hydrophobic clusters is less than the average interhelix compressibility, even though there are large cavities in these clusters. In order to study overall deformation, we define a linear compressibility and calculate it for all pairs of C alpha atoms. The pressure-induced deformation is observed to be heterogeneous also in this analysis. The calculated root-mean-square displacement of the constituent atoms in the equilibrium conformation at 1,000 atm from those at 0 atm is 0.12 A, which is much smaller in magnitude than the average value of the atomic fluctuations at room temperature. In the water solvent, the volume excluded by the protein molecule in the equilibrium conformation is reduced by 0.9%, when the pressure is raised from 0 to 1,000 atm. The calculated magnitude of the root-mean-square volume fluctuation is 0.3% of the excluded volume at room temperature. The square of the volume fluctuation is given as a sum of contributions from individual normal modes. Contributions from low frequency normal modes are found to dominate over those from higher frequency normal modes. The estimated value of the isothermal compressibility of deoxymyoglobin is 9.37 x 10(-12) cm2/dyn.

Animals↗
PubMed1990

[Pharmacokinetic study of aztreonam transfer from mother to fetus].

Aztreonam (AZT) was administered to 73 cases and its usefulness and safety were evaluated upon review of the transfer of the drug into maternal blood, umbilical cord blood and amniotic fluid. The result obtained are summarized as follows. 1. AZT was intravenously administered by single injection to obtain actual data. Based on the data, theoretical changes of drug concentrations in serum in mother were reviewed according to the lapse of time. Drug concentration in maternal blood showed its peak immediately after administration and gradually decreased thereafter. Umbilical cord blood concentration showed a lower peak, which was reached with a slight delay to the Tmax for maternal blood concentration, then decreased. The decrease, however, was more moderate than the decrease in maternal blood concentration and, according to the theoretical values, umbilical cord blood concentration was higher than maternal blood concentration at 2.23 or 2.24 hours after administration. AZT concentrations in amniotic fluid slowly increased after administration and were higher than umbilical cord blood concentrations at 1.68, 1.73 hours after administration, higher than maternal blood concentrations at 1.82, 1.85 hours after administration, and they reached their peak somewhat later. Subsequently, high concentrations of AZT in amniotic fluid were maintained for a long time. The result suggests that AZT is useful for prophylaxis and treatment of amniotic fluid infections. 2. Theoretical values were analyzed by applying two-compartment model and three-compartment model to the actually-measured values, and each parameter was compared. T 1/2 of AZT concentrations in maternal blood and in umbilical cord were 1.29 hours, 1.29 hours, 2.14 hours, 2.00 hours; Cmax 187.09 micrograms/ml, 184.15 micrograms/ml, 30.63 micrograms/ml, 30.66 micrograms/ml and AUC 153.25 micrograms.hr/ml, 153.40 micrograms.hr/ml, 123.19 micrograms.hr/ml, 123.09 micrograms.hr/ml respectively showing approximate values. Cmax values of AZT in amniotic fluid were 47.08 micrograms/ml, 47.74 micrograms/ml; AUC 948.03 micrograms.hr/ml, 1,028.70 micrograms.hr/ml also showing approximate values. However, volume of distribution of umbilical cord blood and amniotic fluid showed a difference according to compartment model. 3. It was considered from the above results that application of only two-compartment open model would make analysis possible when only T 1/2, Cmax and AUC values must be measured for mother-to-fetal transfer of a drug. 4. No subjective and objective side effects nor abnormal laboratory values were observed in any of these cases (both mothers and fetuses).

Amniotic Fluid↗
PubMed1987

[Pharmacokinetic, bacteriological and clinical studies on cefuzonam in the field of obstetrics and gynecology].

The distribution of cefuzonam (CZON, L-105) into the uterus and uterine adnexa was investigated and the usefulness and the safety of CZON in obstetric and gynecological infections were studied. The results are summarized as follows: 1. Following one shot intravenous injection of CZON 1 g, a good distribution of the drug into tissues of uterus and uterine adnexa was observed, with Cmax values of 15.7-33.9 micrograms/g, Tmax of 7.3-34.0 minutes and AUC values of 18.7-35.3 micrograms X hr/g. 2. In all of the 30 cases of obstetric and gynecological infections treated, CZON was evaluated effective. 3. Bacteriologically, 93.9% of total bacteria that had been isolated were eliminated by the administration of the drug. 4. Against all the strains of bacteria isolated before the treatment and replaced bacteria, MIC50, MIC80 and MIC90 of CZON were 0.20 micrograms/ml, 12.5 micrograms/ml and 25 micrograms/ml, respectively, showing low values. 5. Subjective and objective findings and clinical laboratory test values during and after the trial showed no side effects associated with CZON.

Adult↗