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Biomedical subjects

T Itoh

Publications and source records attributed to T Itoh.

At least 487 records · Page 27Linked to original sources
PubMed1997

Stereoselective pharmacokinetics of ibuprofen in rats: effect of enantiomer-enantiomer interaction in plasma protein binding.

Stereoselective pharmacokinetics of ibuprofen (IB) enantiomers were studied in rats. Unidirectional conversion from R-ibuprofen (R-IB) to S-ibuprofen (S-IB) was observed following intravenous administration. S-IB concentrations in plasma following racemate administration were simulated according to a conventional compartmental model using the parameters obtained after the administration of individual enantiomers, and resulted in overestimation of S-IB concentrations. Binding of IB enantiomers measured in rat plasma was stereoselective, the binding of R-IB being more favorable than that of S-IB. Moreover, there are interactions between IB enantiomers in binding, which may cause the increase of distribution volumes of IB enantiomers in the presence of their antipodes. Hence simulated S-IB concentrations according to a conventional compartment model were significantly greater than those observed. Indeed, when the enantiomer-enantiomer interactions were taken into account, simulation of S-IB concentrations in plasma following racemate administration was in good agreement with observed values. Therefore, interactions between stereoisomers as well as dispositional stereoselectivity have to be considered when pharmacokinetics of stereoisomers after administration of the racemate are compared to those after administration of individual isomers.

Animals↗
PubMed1997

Stereoselectivity and enantiomer-enantiomer interactions in the binding of ibuprofen to human serum albumin.

Binding of ibuprofen (IB) enantiomers to human serum albumin (HSA) was studied using a chiral fluorescent derivatizing reagent, which enabled the measurement of IB enantiomers at a concentration as low 5 x 10(-8) M. Scatchard analyses revealed that there were two classes of binding sites for both enantiomers. For the high affinity site, the number of the binding sites was one for both enantiomers, and the binding constant of R-IB was 2.3-fold greater than that of S-IB. The difference in the affinity at the high affinity site may result in the stereoselective binding of IB enantiomers at therapeutic concentrations. It was confirmed that the high affinity site of IB enantiomers is Site II (diazepam binding site) by using site marker ligands. Also, significant enantiomer-enantiomer interactions were observed in the binding. The binding data were quantitatively analyzed and a binding model with an assumption of competitive interactions only at the high affinity site simulated the binding characteristics of IB enantiomers fairly well.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

DNA fragmentation is not the primary event in glucocorticoid-induced thymocyte death in vivo.

Thymocyte death has been recognized as one of the best models for studying apoptosis. Our recent study, however, indicated that most thymocytes die without DNA fragmentation and become terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling-positive (TUNEL+) only after being phagocytosed by macrophages. In this study, we used histological techniques using the TUNEL method, histochemistry, immunohistochemistry, and transmission electron microscopy as well as flow cytometry to examine in vivo the effect of glucocorticoid (GC), a well-known agent for inducing thymocyte apoptosis in vitro, on thymocyte death to determine whether or not DNA fragmentation was the first event of GC-induced thymocyte death. At 2 h and 4 h after GC injection, a large number of cortical thymocytes were TUNEL+. Most TUNEL+ cells were aggregated to form clusters. Double staining of the section showed that the TUNEL+ thymocytes were phagocytosed by acid phosphatase+ and Mac-2+ macrophages. An ultrastructural study indicated that a far greater number of small pyknotic thymocytes were present in the cortex of the GC-treated thymus than were observed in the control thymus, that all those pyknotic thymocytes were TUNEL-, and moreover, that at the electron microscopic level, TUNEL+ cells were all phagocytosed by macrophages. Flow cytometric analysis did not detect a single TUNEL+ thymocyte even 4 h after the GC treatment, suggesting that virtually no free dead thymocytes were present after DNA fragmentation. These results indicate that, consistent with our previous findings with normal thymocyte death and B cell death in the germinal centers, DNA fragmentation is not involved in the cell death process of the GC-induced rapid thymocyte death in vivo.

Animals↗
PubMed1997

Ultrastructural analysis of mouse thymocyte subpopulations.

To understand the lineage relationship and to define morphological characteristics of each thymocyte subset, we have performed ultrastructural analysis of highly purified thymocyte subpopulations. By flow cytometry, five subpopulations were sorted based on the expression of CD4 and CD8 and on cell size (forward scatter): large and small CD4+8+, CD4-8-, CD4+8-, and CD4-8+ thymocytes. Small CD4+8+ thymocytes were the smallest among lymphoid cells, and had a round and smooth cell outline with condensed nuclei, the cytoplasm was scanty and the cell organelles were not developed, suggesting the majority of this subset might be inactive by morphological criteria. CD4+8- thymocytes appeared to be similar to peripheral CD4+ T cells. The CD4-8- thymocyte subset contained morphologically immature cells in terms of cell size, presence of cell surface villi, and euchromatic appearance of the nucleus. CD4-8+ thymocytes heterogeneous in cell size, nuclear chromatin contents and amount of cytoplasm, could be divided into two distinct types. Type 1 CD4-8+ thymocytes were intermediate in size, and therefore similar to peripheral mature CD8+ T cells. Type 2 CD4-8+ thymocytes were large and irregular in shape (large CD4-8+) with irregular-shaped and euchromatic nuclei. Large CD4-8+ cells were, thus, considered to be at the transitional stage from CD4-8- to CD4+8+. At least two groups of large CD4+8+ cells were ultrastructurally classified by the nuclear chromatin content. Large CD4+8+ cells with heterochromatic nuclei were round with a smooth cell membrane, whereas large CD4+8+ cells with euchromatic nuclei were spherical with projections. Cytological features of heterochromatic large CD4+8+ cells are similar to those of small CD4+8+ thymocytes except for cell size. Euchromatic large CD4+8+ cells could be regarded as active blasts potentially leading to mature cells. Taken together, this is the first report that describes the ultrastructural characteristics of each thymocyte subset highly purified by flow cytometry.

Animals↗
PubMed1997

Loss of heterozygosity of the retinoblastoma gene in liver cirrhosis accompanying hepatocellular carcinoma.

Carcinogenesis is a multistep process. Most hepatocellular carcinoma (HCC) is preceded by liver cirrhosis, but the genetic changes involved in cirrhosis are not known well. The present study was conducted to evaluate aberration of the retinoblastoma (RB) gene in HCC and adjacent non-tumorous liver using 22 patients with chronic liver damage accompanying HCC. The specimens obtained by microdissection from paraffin-embedded tissues were analyzed using an assay based on the polymerase chain reaction for highly polymorphic nucleotide sequences of microsatellites in the RB gene. Out of 22 cases, 15 showed constitutional heterozygosity for the microsatellite markers. In 11 (73.3%) of these 15 informative cases, the primary HCC foci showed loss of heterozygosity (LOH). In 8 of these 11 doubly informative (informative and LOH-positive in primary HCC) cases, LOH was found in 20 (64.5%) of 31 microdissected non-tumorous foci. All of the non-tumorous foci showing RB loss were cirrhotic lesions but there were no foci of chronic hepatitis. The remaining 4 cases without LOH in HCC foci showed no LOH in non-tumorous lesions. In our study, LOH of the RB gene was frequently observed in liver cirrhosis surrounding tumor.

Aged↗
PubMed1997

Genome plasticity as a paradigm of eubacteria evolution.

To test the hypotheses that eubacterial genomes leave evolutionarily stable structures and that the variety of genome size is brought about through genome doubling during evolution, the genome structures of Haemophilus influenzae, Mycoplasma genitalium, Escherichia coli, and Bacillus subtilis were compared using the DNA sequences of the entire genome or substantial portions of genome. In these comparisons, the locations of orthologous genes were examined among different genomes. Using orthologous genes for the comparisons guaranteed that differences revealed in physical location would reflect changes in genome structure after speciation. We found that dynamic rearrangements have so frequently occurred in eubacterial genomes as to break operon structures during evolution, even after the relatively recent divergence between E. coli and H. influenzae. Interestingly, in such eubacterial genomes of high plasticity, we could find several highly conservative regions with the longest conserved region comprising the S10, spc, and alpha operons. This suggests that such exceptional conservative regions have undergone strong structural constraints during evolution.

Bacteria↗
PubMed1997

An approach to prebiotic synthesis of alpha-oligoribonucleotides and description of their properties: selective advantage of beta-RNA over alpha-RNA.

Oligomerization of alpha-adenosine 5'-phosphorimidazolide (alpha-ImpA) has been done in an aqueous solution using a uranyl-ion catalyst or a poly(U) template as a model process of prebiotic synthesis of RNA with alpha-glycosidic linkage. alpha-Oligoriboadenylates up to hexamer were formed from alpha-ImpA by the uranyl-ion catalyst. 3'-5' Linkage was mainly formed in the oligomerization. The poly(U) template mediated the oligomerization of alpha-ImpA, but to a very low extent. The yield and chain length of the resulting alpha-oligomers were far lower than those of the corresponding beta-oligomer formation under the same conditions. Physico-chemical properties of alpha-oligoriboadenylates are presented along with those of the corresponding beta-oligoriboadenylates. The results indicate that beta-RNA is more advantageous than alpha-RNA from the points of their synthesis and properties.

Circular Dichroism↗
PubMed1997

Septum-like structures in lipoma and liposarcoma: MR imaging and pathologic correlation.

OBJECTIVE: To investigate the septum-like structures in predominantly lipomatous tumors, by correlating fat-suppressed MR images with histopathologic findings. DESIGN AND PATIENTS: The MR findings of three cases of well-differentiated liposarcoma (atypical lipoma), one case of lipoma-like component of dedifferentiated liposarcoma, and nine cases of lipoma were analyzed. T1-, T2-, and fat-suppressed T1-weighted images after Gd-DTPA administration were obtained. Surgical specimens from five patients (four with liposarcoma and one with lipoma) were also scanned with a MR unit, and compared with the pathologic findings. RESULTS AND CONCLUSIONS: Enhancement features of lipoma and liposarcoma were well visualized on fat-suppressed T1-weighted images after Gd-DTPA administration. The septum-like structures of liposarcoma are thick and enhanced considerably, while septa of lipoma are thin and enhanced only slightly. Pathologically, the septum-like structures of liposarcoma contained muscle fibers and the septa of lipoma represented fibrous capsule. Identification of well-enhanced septa in a predominantly lipomatous tumor helps to differentiate malignant tumors from lipomas. As the septum-like structures of liposarcoma contain a skeletal muscle component the tumor might need more extensive surgical procedures including resection of adjacent muscles.

Aged↗
PubMed1997

Incidence of cardiac sarcoidosis in Japanese patients with high-degree atrioventricular block.

In Japan the majority of sarcoidosis-related deaths are due to cardiac sarcoidosis. One of the most common electrocardiographic abnormalities in patients with this disease is atrioventricular block. This study surveyed the incidence of cardiac sarcoidosis in Japanese patients (40 men and 49 women; mean age, 69.1 years) with high-degree atrioventricular block who were admitted to the hospital to receive a permanent pacemaker. We excluded cases in which sarcoidosis had been diagnosed from the involvement of other organs. Patients with the characteristic signs of sarcoidosis underwent echocardiography, radionuclide imaging, and biopsy. Ten cases (11.2%) of cardiac sarcoidosis were diagnosed, most frequently in women aged 40 to 69 years (8 of 25, 32%). Thus the possibility of cardiac sarcoidosis should be carefully considered in middle-aged or elderly Japanese women who show high-degree atrioventricular block.

Aged↗
PubMed1997

Changes in the noradrenaline and acetylcholine content of three major salivary glands and in the salivation and protein component patterns of whole saliva in chronically isoprenaline-administered mice.

One group of mice was injected subcutaneously with 20 mg/kg body wt isoprenaline each day for 10 days; another group (control) was injected with saline. Half the animals of each group were kept untreated for a further 10 days for restoration. Chronic administration of isoprenaline caused enlargement of parotid (4-fold) and submandibular glands (1.7-fold) but had no effect on sublingual glands. Concomitantly, noradrenaline and acetylcholine contents were, in parallel, increased in parotid, decreased in sublingual, and unchanged in submandibular glands. Under these conditions, pilocarpine- or isoprenaline-induced salivation was not affected but phenylephrine-induced salivation was augmented; the protein component patterns of saliva characteristic of the three sialogogues were also changed. In addition, secretory proteins whose synthesis was induced by isoprenaline were found to be secreted by stimulation with different types of sialogogues. Most changes were reversible. These results indicate that continued beta-adrenoceptor stimulation not only causes broadly altered forms of saliva, probably by involving, in part, alpha-adrenoceptor hypersensitivity, but also changes the activities of both sympathetic and parasympathetic nerves to salivary glands in parallel, though the extent differs among the three glands.

Acetylcholine↗
PubMed1997

Quantitative analysis of cyclooxygenase-2 gene expression on acute gastric injury induced by ischemia-reperfusion in rats.

The rat model of acute gastric damage induced by ischemia-reperfusion (I-R) has been used to evaluate the protective effect of various drugs on gastric injury. However, the quantitative expression state of cyclooxygenase-2 (COX-2), a protein which induces cytoprotective prostaglandins during inflammation, is still unknown in acute gastric injury induced by I-R. Therefore, we have quantitatively investigated the level of expression of COX-2 mRNA in injured gastric tissue of this model using the reverse transcription-competitive polymerase chain reaction method. The mRNA for COX-2 was expressed at low or undetectable levels in the normal gastric tissues in control rats, which were fasted for 18 hrs without I-R. The mRNA levels of COX-2 in injured gastric tissues were higher than those of control tissues between 6 hrs and 48 hrs after I-R. The maximum expression of COX-2 mRNA was recorded at 24 hrs (approximately a 200-fold increase). The expression state of COX-2, which has been ascertained in this study, should be useful in evaluating the effect of various drugs on the expression of COX-2 in acute gastric damage.

Actins↗
PubMed1997

Inhibition by cigarette smoke of lipid peroxidation-induced neurotransmitter release.

Effects of water-soluble substance in cigarette smoke on neurotransmitter release were investigated using nerve terminals (synaptosomes) prepared from rat cerebral cortex. 2,2'-Azobis (2-amidinopropane) dihydrochloride (ABAP), a peroxyl radical-generator, enhanced the depolarization-evoked release of glutamate and aspartate from synaptosomes with concomitant increase in thiobarbituric acid-reactive substances (TBA-RS) levels in membrane lipids of synaptosomes. The trapped smoke-substance attenuated the lipid peroxidation-enhanced release of excitatory amino acids during the depolarization with reduction in TBA-RS, although it failed to affect the basal release of neurotransmitters. These data suggest that cigarette smoke may possess antioxidant properties to reduce oxidation-induced enhancement of transmitter release from nerve terminals.

Amidines↗
PubMed1997

Late development of bile duct cancer after sphincteroplasty: a ten- to twenty-two-year follow-up study.

BACKGROUND: Transduodenal sphincteroplasty is designed to destroy the sphincteric muscle fibers, producing a terminal choledochoduodenostomy. In the absence of Oddi's sphincter, intestinal contents with both activated pancreatic juice and bacterial flora are refluxed into the bile duct and remain there for a prolonged time. The long-term effect of producing the reflux has not been evaluated to date. METHODS: One hundred nineteen consecutive patients undergoing transduodenal sphincteroplasty between February 1973 and July 1984 were included in this study. Postoperative clinical courses of 108 patients could be evaluated by means of a retrospective review of the hospital records. Median follow-up was 18 years. RESULTS: Eight cases (7.4%) of primary bile duct cancer were found among the 108 cases at intervals of 1 to 20 years after sphincteroplasty. Two patients had concurrent hepatolithiasis. The patency of sphincteroplasty was confirmed in all cases, and the bile was infected in seven cases. Pathologic specimens obtained demonstrated cholangiocarcinomas and various degrees of atypical hyperplastic lesions under the background of chronic cholangitis. CONCLUSIONS: Chronic cholangitis can be an important causative factor in late development of bile duct cancer after sphincteroplasty. Any patients treated with choledochoduodenostomy should be closely monitored for late cholangiocarcinoma.

Adult↗
PubMed1997

An experimental study of the removal of cemented dowel-retained cast cores by ultrasonic vibration.

A technique for the removal of cemented post-cores by means of ultrasonic vibration was studied clinically and histologically. The removal time was measured for 80 extracted human teeth, including 40 single-rooted teeth and 40 multiple rooted ones and then statistically analyzed. The periapical tissue reaction to the ultrasonic vibration was also examined histologically in dogs. The best result was achieved when lateral vibration was simultaneously given by 2 removal tips using 2 ultrasonic generators. There was little harmful influence on the periodontal tissue, excluding a transient reversible reaction.

Animals↗
PubMed1997

Conformation of nucleoplasmin and its interaction with DNA-protamine complex as a simple model of fish sperm nuclei.

Nucleoplasmin was isolated from Xenopus laevis eggs and purified by an improved method using an open column. Its conformation was investigated spectrophotometrically by UV, CD and fluorescence. It was shown that alpha-helix content of nucleoplasmin was 30-40%, and one of the two tryptophan residues in nucleoplasmin located in the hydrophobic surroundings and the other in the relatively hydrophilic surroundings. The isolated nucleoplasmin was found to decondense sperm nuclei of salmon also, suggesting a possibility of the existence of nucleoplasmin-like protein in fish as well. Collapse of the protamine (salmine)-DNA complex as a simple model for fish sperm nuclei by nucleoplasmin was directly observed by measuring OD320 of aqueous protamine-DNA mixtures. This is a molecular level observation for the removal of protamine from DNA-protamine complex.

Amino Acid Sequence↗
PubMed1997

Production, purification and characterization of reutericin 6, a bacteriocin with lytic activity produced by Lactobacillus reuteri LA6.

A bacteriocin (Reutericin 6) produced by Lactobacillus reuteri LA6, was purified by hydrophobic chromatography from the modified MRS broth (D'-MRS) with 6180-fold increase in specific activity with 14% recovery. The molecular weight of reutericin 6 was determined to be 2.7 kDa by SDS-PAGE and ESI-MS. By amino acid analysis, reutericin 6 comprised of 67% hydrophobic and polar neutral amino acids. Lanthionine was not detected. The lytic activity against Lactobacillus delbrueckii subsp. bulgaricus JCM 1002T and N1A1 B6 was detected by the decrease of both turbidity and the number of viable cells, and by leaking of beta-galactosidase.

Amino Acids↗
PubMed1997

Prognostic value of nucleolar organizer regions in supraglottic carcinoma.

The relationship of nucleolar organizer regions (NORs) to proliferative activity and tumor progression was studied in 16 supraglottic carcinomas. The number of NORs stained by a silver colloid staining method (AgNOR staining method) was determined. The mean AgNOR number tended to be higher (but not significantly so) in poorly differentiated tumors. Moreover as T and N categories and stage of the tumor rose, the AgNOR number also rose, but not significantly. More interestingly, the mean AgNOR number was significantly higher in the presence than in the absence of lymph node metastasis. These studies indicate that the AgNOR number might be of clinical value as a predictor of lymph node metastasis of supraglottic carcinomas.

Aged↗