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Biomedical subjects

T Ishida

Publications and source records attributed to T Ishida.

At least 883 records · Page 49Linked to original sources

Prominent stacking interaction with aromatic amino acid by N-quarternization of nucleic acid base: X-ray crystallographic characteristics and biological implications.

In order to investigate the mode of interaction between the N-quarternized cytosine base and the aromatic amino acid, the crystal structure of the 3-methyl-cytidine-5'-monophosphate:tryptamine complex was analyzed by X-ray diffraction. The complex crystals were stabilized by extensive hydrogen bond formations in which eight independent water molecules per complex pair participated. A prominent stacking interaction, characterized by a parallel alignment of both rings with a separation distance of ca. 3.4 A, was observed between the cytosine base and the indole ring. Combining the present results with X-ray crystallographic data on the adenine--and guanine--aromatic amino acid interactions, we summarize the structural characteristics observed in the stacking interaction of the N-quarternized nucleic acid base with the aromatic amino acid and discuss their biological implications, especially in connection with the significance of N-protonation of nucleic acid base for selective recognition by protein.

Adenine↗

Alveolar soft-part sarcoma of the tongue. Report of a case.

A case of alveolar soft-part sarcoma (ASPS) of the tongue in a 19-year-old boy is presented. He underwent a hemiglossectomy and received chemotherapy and has been free of disease for 3 years. The origin of intracytoplasmic periodic acid-Shiff(PAS)-positive crystals found in the tumor and the histogenesis of ASPS are briefly discussed.

Adult↗

Orally potent human renin inhibitors derived from angiotensinogen transition state: design, synthesis, and mode of interaction.

A three-dimensional structure of the complex of human renin and the scissile site P4 Pro to P1' Val of angiotensinogen was deduced in order to design potent human renin inhibitors rationally. On the basis of this structure, an orally potent human renin inhibitor (1a) was designed from the angiotensinogen transition state and synthesized. The inhibitor 1a contains a (2R)-3-(morpholinocarbonyl)-2-(1-naphthylmethyl)propionyl residue (P4-P3) with a retro-inverso amide bond, L-histidine, and a novel amino acid, (2R,3S)-3-amino-4-cyclohexyl-2-hydroxybutyric acid, named cyclohexylnorstatine (2a). The optically pure cyclohexylnorstatine was efficiently prepared from Boc-L-cyclohexylalaninol (3), and the stereochemistry of 1a was established by X-ray crystal analysis. The analyses of interaction between 1a and human renin using modeling techniques indicated that (1) the cyclohexyl group of P1 and the naphthyl group of P3 were accommodated in large hydrophobic subsites S1 and S3, respectively; (2) the imidazole of P2 His was hydrogen bonded to the side chain OH of Ser-233 to contribute to the selectivity of renin inhibition; (3) cyclohexylnorstatine isopropyl ester residue was accommodated in S1-S1'. The importance of the stereochemistry in the potent and specific inhibitor was clearly shown. Oral administration to monkeys of this inhibitor resulted in a drop of 10-20 mmHg in mean blood pressure and a reduction of plasma renin activity for a 5-h period.

Administration, Oral↗

Detection of the growth fraction in colorectal tumours by a monoclonal antibody against DNA polymerase alpha.

The cell kinetics of 54 colorectal tumours were examined by immunohistochemical methods, using the monoclonal antibody DNA polymerase alpha which reacts with an antigen found only in proliferating cells. The rate of DNA polymerase alpha positive cells in colorectal cancer was 44.8%, a figure that was significantly higher than the 21.9% found in colorectal adenomas. The rate of DNA polymerase alpha positive cells tended to rise as the degree of differentiation decreased according to the standard histological grading criteria for colorectal cancer. Positive cells were detected in much greater numbers in tumours with liver metastasis (55.4%) than in those without metastasis (41.7%). The rate of DNA polymerase alpha positive cells for aneuploid lesions was higher than that for lesions with a diploid pattern. The determination of growth fractions with a monoclonal antibody (DNA polymerase alpha) may be a biological marker of great prognostic significance.

Adenocarcinoma↗

Hemolysis after intravenous immune globulin therapy: relation to IgG subclasses of red cell antibody.

A patient with chronic idiopathic thrombocytopenic purpura (ITP), a 28-year-old group A, Rh-positive woman, also had hemolytic anemia. At that time, her red cells typed as group A, but the serum typed as group O. This typing followed intravenous high-dose immune globulin therapy, (400 mg/kg for 5 successive days) and was attributable to A antibody of the IgG type, composed of IgG1, IgG2, IgG3, and IgG4, in the immune globulin preparation, which had been given for treatment of ITP. All lots of commercial human plasma preparation products (heat-treated human plasma protein, albumin, factor VIII or IX products, and immune globulin) examined were found to contain A and/or B antibodies of the IgM or IgG type, with titers of 1 to 1024. Twelve of the 20 lots of immune globulin contained RBC antibodies of the IgG type. Subclass IgG1 was found in all 12 of these lots, and all four subclasses, including IgG3, were detected in 8 lots. All 8 showed antibody titers higher than 64.

ABO Blood-Group System↗

Large cell carcinoma of the lung. Prognostic implications of histopathologic and immunohistochemical subtyping.

Fifty-four patients with large cell carcinoma of the lung were treated surgically, and the prognostic factors were examined histologically and immunohistochemically. Based on evidence of intercellular cohesion, as seen in the histologic results, the patients were placed into two subtypes, compact growth type and louse structure type. The survival rates were 46% and 28% at five years, respectively (P less than 0.05). Immunohistochemically, keratin, epithelial membrane antigen (EMA), secretory component, lactoferrin, and carcinoembryonic antigen (CEA), as histologic markers of epithelial differentiation, were detectable in large cell carcinoma of both types and more frequently in the compact growth type than in the loose structure type. The difference was significant in case of detection of keratin, EMA, and CEA (P less than 0.05). These observations suggest that a large cell carcinoma may differentiate into an adenocarcinoma or squamous cell carcinoma. The presence of intercellular cohesion and use of these markers reflect prognosis of the disease.

Adult↗

Effects of repeated temporary clipping of the middle cerebral artery on pial arterial diameter, regional cerebral blood flow, and brain structure in cats.

Temporary clipping of the major arterial trunk is an important maneuver to control excessive unexpected bleeding in neurosurgical operations; however, repeated temporary clipping can give rise to severe neurological deficits after surgery. The present study was performed to confirm and explain these clinical findings. Initially, a single 20-minute or 1-hour occlusion of the middle cerebral artery was performed in each of 5 cats. Pial arterial diameter was determined by video imaging, regional cerebral blood flow was measured by autoradiography, and cerebral edema and infarction were observed. In the 20-minute occlusion group, no abnormal changes were found 5 hours after recirculation. In the 1-hour occlusion group, pial arteries were dilated by 45%, and regional cerebral blood flow increased to more than twice the resting cortical values. The extent of cerebral edema was 41.2 +/- 7.5% (SE) and infarction was 34.5 +/- 9.5% (SE) of the hemisphere. In the second experiment, three 20-minute occlusions of the middle cerebral artery in a 1-hour interval were performed in 20 cats. In 10 of them, thiopental (40 mg/kg) was used to protect the brain. In the group without barbiturate treatment, pial arteries were dilated by 40% at the end of experiment, regional cerebral blood flow decreased to about 70% compared with single 20-minute occlusion, cerebral edema was 19.5 +/- 8.1% (SE), and infarction was 8.1 +/- 3.7% (SE) of the hemisphere. In the treated group, these were only trivial changes. The effect of repeated clipping may cumulatively cause brain damage, and barbiturates should be used whenever repeated clipping is necessary.

Animals↗

Tumor growth rate and prognosis of breast cancer mainly detected by mass screening.

To investigate the relationship between the tumor growth rate of the primary breast cancer and its prognosis, records for 122 breast cancer patients in 9 hospitals in Japan were retrospectively reviewed. These records contained at least two measurements of the same tumor mass in the breast. So the growth rate was estimated from these measurements taken at different points in time. The doubling time of the breast tumors showed an approximately log-normal distribution. The geometric mean of doubling times for all cases was 174 days. The solid-tubular histologic type of carcinoma had the shortest geometric mean of doubling time (126 days), the scirrhous carcinoma had the second shortest one (205 days), and the papillotubular carcinoma had the longest one (252 days). The patients with shorter doubling time of tumor tended to have a poorer prognosis. The Cox multiple regression analysis showed that the tumor growth rate was related significantly with survival, after adjusting for other covariates such as clinical stage, lymph node metastasis, age of patient, histological type, and year of treatment.

Adult↗

Cardiovascular anomalies of cephalothoracopagus synotus. A case report and review of the literature of 23 Japanese autopsied cases.

A case of cephalothoracopagus female twins is reported, and the anatomical and pathologic features are described in detail. The central nervous systems were completely double. However, there were three eyeballs, two on the well-formed face and one in the cranial base, forming a saddle-shaped ridge of orbital plates. The latter was supplied by optic nerves of both individuals. On the other hand, there was a single esophagus, stomach and duodenum, but the intestine was shared equally at the jejunum by the two individuals. The larynges, tracheae, lungs, hearts, livers, pancreases, spleens and urogenital organs were also duplicated. Previously unreported abnormalities of the hearts are described, and a comparison with similar autopsy cases reported previously in Japan is given.

Blood Vessels↗

Flow-cytometric analysis of colorectal cancer with hepatic metastases and its relationship to metastatic characteristics and prognosis.

Studying the DNA ploidy patterns of 52 primary tumors, diploid tumors accounted for 48.1% and aneuploid tumors for 51.9%. Out of 31 patients with liver metastases, 35.5% had diploid tumors and 64.5%, aneuploid tumors. Heterogeneity (difference in DNA ploidy pattern between the primary lesion and liver metastases) was found in 20% of the patients examined. In 28 of the patients, the liver metastases were unresectable, and their prognoses were such that the 1- and 2-year survival rates from the diploid tumors were 42.9 and 14.3%, respectively, while 1-year survivors from aneuploid tumors died within 2 years. In resected cases of hepatic metastases, the DNA ploidy pattern of the metastatic lesions did not correlate with the metastasis period, extent of spread or number of lesions. The recurrence rate of aneuploid tumors in the residual livers was 50%, which was slightly higher than the rate of 36.4% for diploid tumors. The prognoses in patients with diploid tumors were significantly better than those in patients with aneuploid tumors: 5-year survival was 71.1% in diploid tumor patients, compared with 21% in aneuploid tumor patients.

Colorectal Neoplasms↗

The diagnosis of mild emphysema. Correlation of computed tomography and pathology scores.

Early and accurate diagnosis of emphysema is said to be invaluable for identification of clinically silent and mild emphysema. Recently, computed tomography (CT) has been much advocated for its efficacy in detailed diagnosis of emphysema, and the results have been compared with the pathology grade of emphysema in resected lung specimens. To assess the ability of high resolution CT scan in detecting and grading mild emphysema, we correlated the high resolution CT scan with the pathology grade of emphysema and the destructive index (DI) of lung specimens from 42 patients undergoing thoracotomy for a solitary pulmonary nodule. The high resolution CT scan and the cut surface of the lung, corresponding exactly to the same plane of the CT scan image, were assessed using the picture-grading system of Thurlbeck and coworkers on a scale of zero to 100. The CT scores for all patients ranged from 12 to 57, with a mean +/- SD of 22.1 +/- 9.6 using 1-mm collimation (n = 35), and from 7 to 46 with a mean +/- SD of 16.5 +/- 8.3 using 5-mm collimation (n = 33). The pathology scores ranged from 10 to 57, with a mean +/- SD of 23.2 +/- 9.8 (n = 42). The DI ranged from 15.4 to 67.1, with a mean +/- SD of 31.4 +/- 10.8 (n = 42). The CT scores using 1-mm and 5-mm collimation correlated significantly with the pathology scores (r = 0.68 and 0.76, respectively, p less than 0.001), and with the DI (r = 0.62 and 0.74, respectively, p less than 0.001). The pathology scores correlated significantly with the DI (r = 0.72, p less than 0.001). We therefore concluded that high resolution CT can help to identify the presence and grading of mild emphysema.

Adult↗

Molecular conformations of aminophenylimidazoles exhibiting antiulcer activities.

To experimentally clarify a possible stereostructure-activity relationship proposed for H2-receptor antagonists, three 5-aminophenylimidazoles (1, 2 and 3), in which respective amino groups are located on the ortho, meta and para positions of the benzene ring, were synthesized and examined for their conformational characteristics using X-ray diffraction and proton nuclear magnetic resonance (1H-NMR) methods, and for antiulcer activities on rats and H2-receptor antagonist activities in guinea pig. The ortho isomer 1, which preferentially formed an intramolecular N-H (amino)...N (imidazole) hydrogen bond, showed the highest antiulcer activity with half the efficacy of cimetidine. On the other hand, none of 1, 2 and 3 showed significant H2-receptor antagonist activity. Based on these results, the conformational characteristic for the exhibition of antiulcer activity has been discussed.

Aniline Compounds↗

Conformational characteristics of opioid kappa-receptor agonist: crystal structure of (5S,7S,8S)-(-)-N-methyl-N-[7-(1-pyrrolidinyl)-1- oxaspiro[4.5]dec-8-yl]benzeneacetamide (U69,593), and conformational comparison with some kappa-agonists.

(5S,7S,8S)-(-)-N-Methyl-N-[7-(1-pyrrolidinyl)-1- oxaspiro[4.5]dec-8-yl]benzeneacetamide (U69,593) is a potent agonist to opioid kappa-receptor. The crystal structure of U69,593 has been analyzed by the X-ray diffraction method. The molecule, as a whole, took an open conformation, and four cyclic rings composing the main skeleton were far apart from each other. The N and O atoms substituted for the cyclohexane ring were all in the equatorial position. The best planes of two 5-membered rings were almost perpendicular to that of the cyclohexane ring, and the N-methylamide linkage was also orthogonal to this ring plane. The conformation of the U69,593 molecule was compared with other kappa-agonists.

Benzeneacetamides↗

Molecular dynamics simulation of papain-E-64 (N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl]agmatine) complex.

To investigate the possible binding mode of E-64 (N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl]agmatine), a potent cysteine protease inhibitor, to papain active site, molecular dynamics simulations were applied to two complex forms: R- and S- configurational forms of E-64 C2 atom for the covalent bond formation with the papain Cys-25 SH group. The tertiary structures of the papain-E-64 complexes were built by visual interactive modelling and the energy minimization technique, and were subjected to the dynamics simulations of 10 ps. Although no significant difference was observed between the potential energies of energy-minimized R- and S-complex forms, the molecular dynamics simulations suggested that the hydrogen bonding mode of the former form is more advantageous than that of the latter one. Comparing with the hydrogen bonds observed in the papain-E-64 complex crystal, it could be concluded that the present molecular dynamics simulation reflects well the three-dimensional structure concerning the interaction of E-64 with the papain active site. The conformational characteristics of E-64 and its possible interaction mode with papain were also discussed.

Computer Simulation↗