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Biomedical subjects

H Hirano

Publications and source records attributed to H Hirano.

At least 253 records · Page 14Linked to original sources

Minimum number of water molecules required for inclusion of d-limonene in the cyclodextrin cavity.

The ratios of inclusion of d-limonene in alpha-, beta-, and gamma-cyclodextrin (CD) cavities were measured under low moisture conditions by a micro-aqueous method, and the minimum numbers of water molecules required for inclusion of d-limonene in alpha-, beta-, and gamma-CD cavities were determined by the auto-catalytic inclusion model. The minimum number of water molecules required for alpha-, beta-, and gamma-CD inclusion calculated from the proposed model were comparable with that in the CD cavity in the crystal state. The effect of ethanol upon the inclusion process was investigated, particularly with a low water content. This is the first study involving measurement of the minimum number of water molecules required for the inclusion of organic molecules (d-limonene) in the CD cavity.

Carbohydrate Conformation↗

Tyrosine-specific protein kinase participates in the pathogenesis of acute immune complex alveolitis in rats.

Rabbit IgG antibodies against ovalbumin (OA) was injected intravenously into Wistar rats. When the animals were challenged with OA aerosolized by ultrasonic nebulization, acute lung injury occurred as reflected by increased recovery of bronchoalveolar cells, especially polymorphonuclear leukocytes (PMN) in bronchoalveolar lavage fluid (BALF). Lung morphology demonstrated cellular infiltration in the alveolar septa and intra-alveolar hemorrhage. When the rats were administered ST-638, a novel tyrosine kinase inhibitor, intraperitoneally prior to nebulization, the number of PMN in BALF decreased in a dose-dependent manner and superoxide anion (O2-)-producing activity in peripheral leukocytes was significantly suppressed. Furthermore, the reagent inhibited migration of human peripheral blood neutrophils induced by the chemotactic peptide f-met-leu-phe in vitro. These studies strongly indicate that tyrosine kinase plays an important role in immune complex-triggered neutrophil-related lung disorders, and the novel tyrosine kinase inhibitor ST-638 attenuates lung injury by preventing superoxide production and neutrophil migration.

Animals↗

Non-congeneric structure-pharmacokinetic property correlation studies using fuzzy adaptive least-squares: oral bioavailability.

Quantitative relationship between chemical structure and oral bioavailability of 188 non-congeneric organic medicinals were studied to construct an expert system for predicting pharmacokinetic properties of organic chemicals. The compounds studied were classified into three groups: non-aromatics, aromatics, and heteroaromatics. Their oral bioavailability data observed in human adults were allotted into three ratings, and the relationships with chemical structure were analyzed using fuzzy adaptive least-squares. Quantitative relationship models formulated for the three structure groups gave significant information about factors influencing bioavailability, and were statistically reliable in both recognition and leave-one-out prediction despite the diversity and complexity of the structures of the compounds investigated.

Administration, Oral↗

Non-congeneric structure-pharmacokinetic property correlation studies using fuzzy adaptive least-squares: volume of distribution.

The correlation of chemical structures with the volume of distribution of 373 miscellaneous medicinals was studied to construct an expert system for predicting the pharmacokinetic properties of organic chemicals. The compounds studied were classified into three groups; non-aromatics, aromatics, and heteroaromatics. Their total body volumes of distribution observed in human adults were allotted into three ratings, and the relationships with chemical structure were analyzed using the fuzzy adaptive least-squares method recently developed in our laboratory. Quantitative relationship models formulated for the three structure groups gave significant information about factors influencing the volume of distribution, and were statistically reliable both in recognition and leave-one-out prediction despite the diversity and complexity of the structures of the compounds investigated.

Biological Availability↗

Pharmacological profile of gastric mucosal protection by marmin and nobiletin from a traditional herbal medicine, Aurantii fructus immaturus.

We studied the effects of marmin and nobiletin on the experimental acute gastric lesions, gastric transmucosal potential difference (PD) and gastric motor activity in rats and the contractions of isolated guinea pig ileum. Oral administration of marmin and nobiletin inhibited both the appearance of ethanol-induced gastric hemorrhagic lesions dose-dependently in a dose range of 10-50 mg/kg, with ED50 values for marmin and nobiletin being 17.2 and 8.0 mg/kg, respectively. However, marmin and nobiletin had minimal effects on aspirin-induced gastric lesions at a dose of 50 mg/kg, respectively. Marmin and nobiletin had no significant influence on the basal PD. Intragastrical administration of marmin and nobiletin at a dose of 25 mg/kg significantly prevented the PD reduction induced by ethanol. Both marmin and nobiletin given intragastrically at 25 mg/kg significantly inhibited gastric motor activity measured as intraluminal pressure recordings. Marmin and nobiletin exhibited concentration-dependent relaxations of contractions induced by acetylcholine, transmural electrical stimulation and histamine in isolated guinea pig ileum, respectively. These findings suggest that the anti-ulcer effects of marmin and nobiletin are ascribed primarily to the maintenance of the mucosal barrier integrity and inhibition of gastric motor activity and secondarily due to the prevention of the effects of endogenous acetylcholine and histamine.

Acetylcholine↗

Okadaic acid induces marked shape change of human platelets.

Okadaic acid (OA) induced marked shape changes of human platelets but neither granule secretion nor increase in [Ca2+]i occurred. Morphological changes induced by OA were unique and different from those observed with thrombin mainly in two respects. One is that the pseudopods formed by OA treatment were longer and straighter than those by thrombin. The other is that no granule centralization was observed with OA-treatment, although central condensation of cytofilaments was observed as was with thrombin. The immunocytochemical analysis employing anti-myosin antibody revealed that myosin was distributed in the elongated pseudopods. Since OA induced phosphorylation of the 20-kDa myosin light chain (MLC20) corresponding to the change in shape of platelets but did not induce phosphorylation of the 47-kDa protein (pleckstrin) (Higashihara M. et al. FEBS Lett. 307:206-210, 1992), these results suggest that phosphorylation of MLC20 plays an important role in OA-induced unique morphological changes of platelets.

Blood Platelets↗

The healing process of chronic colitis in rats, induced by 2,4,6-trinitrobenzene sulfonic acid, with special reference to the role of fibronectin.

BACKGROUND: The healing process of rat chronic colitis was investigated to evaluate the role of fibronectin produced by fibroblasts in the healing tissue. METHODS: Chronic colitis was produced by intrarectal instillation of 2,4,6-trinitrobenzene sulfonic acid. The healing process was observed by light and electron microscopy and immunocytochemistry. Time course of fibronectin mRNA expression was measured by Northern blot hybridization. RESULTS: By light and electron microscopy, an abundance of young fibroblasts had gathered at the healing tissue and were involved in incorporation into the endothelium of the preexisting vessels, as vasoformative cells, and in transformation to new muscle cells in muscular regeneration. Such processes became pronounced from day 3 and persisted for 6 weeks. Immunocytochemical data showed that fibronectin, produced in the rough endoplasmic reticulum of the fibroblasts and released to the extracellular surface, played inductive roles in the movement and aggregation of such cells and in their contacts with neighboring endothelial cells of the preexisting capillaries. Northern hybridization showed that mRNA coding for fibronectin rapidly reached maximum on day 3 and gradually decreased almost to the control level at 6 weeks. CONCLUSIONS: These observations elucidate the role of young fibroblasts, as multipotent cells, and of fibronectin in acceleration of the healing process in this model of chronic colitis.

Animals↗

Hydrocephalus due to villous hypertrophy of the choroid plexus in the lateral ventricles. Case report.

A case is reported of hydrocephalus due to overproduction of cerebrospinal fluid (CSF) caused by villous hypertrophy of the choroid plexus in the lateral ventricles. A 7-year-old girl with mental retardation developed gait disturbance; hydrocephalus and a Dandy-Walker cyst were detected on computerized tomography. She was initially treated with a ventriculoperitoneal shunt; however, shunting failed to control the hydrocephalus. The excessive outflow of CSF suggested choroid plexus abnormality, and magnetic resonance (MR) imaging revealed enlargement of the choroid plexus in both lateral ventricles. The patient was therefore diagnosed as having hydrocephalus induced by overproduction of CSF, which was controlled by resection of the choroid plexus. Histological examination showed the structure typical of normal choroid plexus. This is a rare case of villous hypertrophy of the choroid plexus in which MR imaging assisted in the diagnosis.

Brain Diseases↗

[Outcome evaluation in putaminal hemorrhage by multiple regression analysis].

The aim of this study was to determine the factors that influence the prognosis of hypertensive putaminal hemorrhage. We investigated the outcome of the activity of daily living (ADL 1: full recovery at social life, 2: self cared, 3: required partial care at home, 4: remained bedridden, 5: vegetative state, 6: dead) one year after the onset of putaminal hemorrhage in comparison with initial data obtained on the day when it occurred. The following parameters were assessed: sex, age, side of hematoma, classification of computed tomography (CT) findings, neurological grade, degree of muscle power, hematoma volume, treatment, past history of cerebrovascular disease, and laboratory data. In 67 patients with putaminal hemorrhage, the relationships among these parameters were examined using Spearman's rank correlation analysis. Additionally, in 55 patients (24 male and 31 female) with complete data from the day of onset, multiple regression analysis was performed. The data of muscle power were handled by the quantification method. The result of Spearman's rank correlation coefficient indicated that the outcome had a positive correlation with age (correlation coefficient = 0.375), CT classification (0.595), neurological grade (0.714), hematoma volume (0.689), a past history of cerebrovascular disease (0.475), the white blood cell count (0.541), and the lactate dehydrogenase level (0.347). The outcome had a negative correlation with muscle power (-0.579) and the cholinesterase (-0.340).(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

CD44 expression on activated B cells. Differential capacity for CD44-dependent binding to hyaluronic acid.

CD44 expression and the functional capacity for CD44-dependent binding of hyaluronic acid (HA) were analyzed on unstimulated B cells and on B cells stimulated with a variety of polyclonal B cell activators. Whereas essentially all LPS-activated and anti-IgD-dextran-activated B cells and a subpopulation of IL-5-activated B cells expressed increased levels of cell surface CD44 relative to unstimulated B cells, only IL-5-activated CD44hi B cells constitutively bound to FITC-conjugated hyaluronic acid (FITC-HA). Preincubation of LPS or anti-IgD-dextran-activated B cells with the CD44-specific mAb IRAWB14.4 (IRA) induced a high degree of FITC-HA binding in these populations; preincubation of unstimulated B cells with this CD44-specific mAb induced minimal FITC-HA binding. In contrast, preincubation with mAb IRA failed to induce FITC-HA binding by the IL-5-activated CD44lo B cell subset. Neither the amount of constitutive FITC-HA binding nor the level of IRA-inducible FITC-HA binding correlated simply with the overall level of CD44 expressed by the different B cell populations. Biochemical analysis of immunoprecipitated CD44 molecules revealed that relative to CD44 isolated from all other populations examined, CD44 isolated from IL-5-activated B cells was of a lower molecular weight. Treatment with N-Glycanase eliminated this observed difference in molecular weight, indicating that it reflected differences in N-glycosylation of CD44 on activated B cells. Polymerase chain reaction analysis of amplified cDNA showed that each B cell population expressed a common dominant CD44 mRNA. These findings suggest that post-translational modification of CD44 and/or differential association of CD44 with other cellular components plays a critical role in activation-specific ligand binding by CD44.

Animals↗

Subcellular localization of blood group Leb carbohydrate antigen (MSN-1-reactive antigen) in endometrial cancer cells.

MSN-1 is a monoclonal antibody, which was raised by immunizing mice with a human endometrial cancer cell line, SNG-II. The MSN-1 specifically recognizes a blood group carbohydrate antigen, Leb. We investigated the subcellular and suborganellar localization of the MSN-1-reactive carbohydrate antigens in the endometrial adenocarcinomas and the normal endometria using immunofluorescence microscopy, confocal laser scanning microscopy, and immunoelectron microscopy. In normal endometrium, the apical plasma membranes of endometrial glandular cells were weekly positive. In contrast, in endometrial adenocarcinoma specimens, the apical plasma membranes, the lateral plasma membranes, intracytoplasmic vesicular structures, and the Golgi apparatus were strongly positive. We also found that there are differences in the manner of the distribution of the MSN-1 antigen within the Golgi apparatus between the normal and tumor samples; namely, in the endometrial adenocarcinoma cells the antigens are found abundantly throughout the Golgi apparatus or tend to be located not only at the trans side but also close to the cis side, while the localization of this antigen in normal counterpart is restricted to the trans-Golgi cisternae. These findings imply that aberrant glycosylation occurs in endometrial adenocarcinomas, presumably as a result of abnormal expression of some glycosyltransferases involving the expression of the Leb carbohydrate antigen in the Golgi apparatus.

Adenocarcinoma↗

Induction of mitochondrial chaperonin, hsp60, by cadmium in human hepatoma cells.

Mitochondrial dysfunction is readily induced by a low level of cadmium both in vivo and in vitro. The gene expression of mitochondrial hsp60 was induced in a dose- and time-dependent manner and also in parallel with the accumulation of cadmium in mitochondria. The levels of hsp60 mRNA increased with time until 18 h, while the induction of heat shock 70 (hsp70) gene peaked at 6 h and then declined. On the other hand, the levels of metallothionein mRNA reached to a plateau at 6 h and were maintained at this level continuously. These results suggest that the regulatory mechanism and/or the signals for hsp60 induction by cadmium are independent from those of hsp70 and metallothionein.

Biological Transport↗

Molecular cloning of rat liver glucocorticoid-receptor translocation promoter.

We previously found a new endogenous factor in rat liver cytosol, named ATP-stimulated glucocorticoid-receptor translocation promoter (ASTP), that increased the binding of activated glucocorticoid-receptor to nuclei in the presence of ATP. We have cloned and sequenced a cDNA (2989 bp) encoding the ASTP protein. An open reading frame of 524 amino acids encodes a protein with a molecular weight of 57 kDa. Amino-acid sequences of six peptides obtained by Edman degradation of various cleavage products of the purified ASTP were identified in the cDNA-derived sequence. Northern analysis of mRNA from rat liver revealed a major band of about 3.8 kb. Database searches show no homology to other known proteins from mammalian origin, however, the amino-acid sequence in the middle portion of ASTP protein shows 48% homology to glycerol kinase from Escherichia coli. The region of homology to other species may help to define sites of protein-protein interaction, as well as sites of possible interaction of ASTP with ATP.

Amino Acid Sequence↗

cDNA cloning and expression of cysteine synthase B localized in chloroplasts of Spinacia oleracea.

The cDNA clones for cysteine synthase B, which is localized in chloroplasts of Spinacia oleracea L., were isolated by screening a library with synthetic oligonucleotides encoding a partial peptide sequence of the purified protein. Nucleotide sequence analysis revealed an open reading frame encoding a polypeptide of 383 amino acids containing a putative transit peptide of 52 amino acids. A bacterial expression vector of the cDNA clone could genetically complement an Escherichia coli auxotroph lacking cysteine synthase and could produce the functionally active and immuno-reactive cysteine synthase in E. coli. RNA blot hybridization suggested that the transcripts were primarily accumulated in leaves of spinach.

Amino Acid Sequence↗

The role of N-glycosylation in the targeting and stability of GLUT1 glucose transporter.

The cDNAs encoding the GLUT1 glucose transporter protein were altered by site-directed mutagenesis at consensus sites for the addition of N-linked glycosylation. These cDNAs were transfected into CHO cells with an expression vector and the subcellular distribution and stability of the expressed glycosylation-defective GLUT1 protein were analyzed. Immunohistochemical analysis with a specific antibody demonstrated that a significant portion of glycosylation-defective GLUT1 protein remained in the intracellular compartment. By contrast, most of the wild-type GLUT1 protein expressed with the same procedures resided in the plasma membranes. Metabolic labeling studies revealed that the half-life of the glycosylation-defective GLUT1 protein was significantly shorter than that of wild-type GLUT1 protein. These results indicate that N-glycosylation of the glucose transporter affects its intracellular targeting and protein stability.

Animals↗