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Biomedical subjects

H Katayama

Publications and source records attributed to H Katayama.

At least 109 records · Page 6Linked to original sources

Human AIM-1: cDNA cloning and reduced expression during endomitosis in megakaryocyte-lineage cells.

The rat AIM-1 gene encoding an Aurora- and Ipl1-like midbody-associated protein serine/threonine kinase has a mitotic regulator function playing a key role in the onset of cytokinesis during mitosis. This report presents a cDNA sequence and megakaryocytic differentiation-dependent expression profile of the human AIM-1 gene. The nucleotide sequences of the human AIM-1 were identified from cDNAs of three cell lines, including cervical carcinoma HeLa cells, colorectal tumor SW480 cells, and normal human diploid skin fibroblast NHDF cells, and no mutation was found. The expression levels of AIM-1 transcript were markedly reduced during differentiation into megakaryocytic cell lineage in human leukemia cells induced by 12-o-tetradecanoyl-phorbol-13-acetate (TPA), suggesting that the downregulation of AIM-1 contributes to the differentiation by repeated duplication of DNA without cytokinesis (endomitosis).

Amino Acid Sequence↗

Multinuclearity and increased ploidy caused by overexpression of the aurora- and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells.

Aurora- and Ipl1-like midbody-associated protein (AIM-1) is a serine/ threonine kinase that is structurally related to Drosophila aurora and Saccharomyces cerevisiae Ipl1, both of which are required for chromosome segregation. A kinase-negative form of AIM-1 inhibits the formation of cleavage furrow without affecting nuclear division, indicating that the gene controls entry into cytokinesis during M phase in mammalian cells. A human gene that encodes the protein AIM-1 was overexpressed in colorectal and other tumor cell lines. The regulation of AIM-1 expression was cell cycle dependent in normal and tumor cells, and the maximum accumulation was observed at G2-M. Exogenous overexpression of wild-type AIM-1 produced multinuclearity in human cells, suggesting that the excess amount of AIM-1 had a dominant-negative effect on the overexpressing cells. In long-term culture of AIM-1-overexpressing cells, multiple nuclei in a cell were occasionally fused, and then an increased ploidy and aneuploidy were induced. Thus, the overexpression of AIM-1 in colorectal tumor cell lines is thought to have a causal relationship with multinuclearity and increased ploidy. Cytokinesis error caused by AIM-1 overexpression is a major factor in the predisposition of tumor cells to the perturbation of chromosomal integrity that is commonly observed in human neoplasia. Thus, defects of pathways essential for mitotic regulation are important during human cancer development.

Amino Acid Sequence↗

Regulation of cyclic GMP and cyclic AMP production by S-nitroso-cysteine in rat thymocytes.

Nitrogen monoxides regulate cellular functions via cyclic GMP accumulation induced by nitric oxide (NO). However, the effects of NO on the cyclic AMP system have not been studied in detail. In this study, we investigated the effects of various NO donors on cyclic GMP and cyclic AMP accumulation in rat thymocytes. Addition of S-nitroso-cysteine stimulated cyclic GMP accumulation at concentrations up to 10 microM, but was inhibitory at higher concentrations. Other NO donors such as sodium nitroprusside stimulated cyclic GMP accumulation markedly without causing inhibition. S-Nitroso-cysteine, but not other NO donors, inhibited forskolin-stimulated cyclic AMP accumulation in intact thymocytes and thymocyte membrane preparations. The inhibitory effect of S-nitroso-cysteine on cyclic AMP accumulation in membranes was partially reversed by dithiothreitol treatment. These findings suggest that the cyclic AMP system in thymocytes is specifically modified by S-nitroso-cysteine, and not by the NO/cyclic GMP system.

Adenylyl Cyclase Inhibitors↗

In-Situ Direct Analysis of the Growing Species by 119Sn NMR Spectroscopy: Living Cationic Polymerization of Isobutyl Vinyl Ether with HCl/SnCl4/nBu4NCl1

119Sn NMR spectroscopy was employed for analysis of the interaction and reaction of SnCl4 with the HCl-IBVE adduct [1; CH3CHCl(OiBu)] in the presence of nBu4NCl in CH2Cl2 solution at -78 degreesC, which are model reactions for the living cationic polymerization of isobutyl vinyl ether (IBVE). The addition of 1 to an SnCl4 solution led to upfield shifts of the tin nucleus as the 1/SnCl4 mole ratio (<1) increases, which indicates the formation of SnCl5-, via the interaction between SnCl4 and the chlorine atom in 1. On further addition of 1, the pentacoordinated anion is converted into the hexacoordinated SnCl62-. These tin species are in fast equilibrium among each other, and the 119Sn NMR analyses support the formation of a carbocation [2; CH3CH+(OiBu)] from 1 and the dynamic equilibrium between 1 and 2. More effective chloride-anion donors such as nBu4NCl and Ph3CCl can quantitatively convert SnCl4 into SnCl5-, and then into SnCl62-. Thus under the conditions where living cationic IBVE polymerization proceeds (1 < nBu4NCl/SnCl4 < 2), SnCl4 is fully converted into a weaker Lewis acid, SnCl5-, with the aid of added nBu4NCl. The suppression of the carbocationic species in the living system has thus been found due to the interaction between the added salt and SnCl4.

Journal Article↗

Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor.

CrkII adaptor protein becomes tyrosine-phosphorylated upon various types of stimulation. We examined whether tyrosine 221, which has been shown to be phosphorylated by c-Abl, was phosphorylated also by other tyrosine kinases, such as epidermal growth factor (EGF) receptor. For this purpose, we developed an antibody that specifically recognizes Tyr221-phosphorylated CrkII, and we demonstrated that CrkII was phosphorylated on Tyr221 upon EGF stimulation. When NRK cells were stimulated with EGF, the tyrosine-phosphorylated CrkII was detected at the periphery of the cells, where ruffling is prominent, suggesting that signaling to CrkII may be involved in EGF-dependent cytoskeletal reorganization. The EGF-dependent phosphorylation of CrkII was also detected in a c-Abl-deficient cell line. Moreover, recombinant CrkII protein was phosphorylated in vitro by EGF receptor. These results strongly suggest that EGF receptor directly phosphorylates CrkII. Mutational analysis revealed that the src homology 2 domain was essential for the phosphorylation of CrkII by EGF receptor but not by c-Abl, arguing that these kinases phosphorylate CrkII by different phosphorylation mechanisms. Finally, we found that the CrkII protein phosphorylated upon EGF stimulation did not bind to the phosphotyrosine-containing peptide and that CrkII initiated dissociation from EGF receptor within 3 min even with the sustained tyrosine phosphorylation of EGF receptor. This result implicated phosphorylation of Tyr221 in the negative regulation of the src homology 2-mediated binding of CrkII to EGF receptor.

Animals↗

Stable capillary coating with successive multiple ionic polymer layers.

A stable modification of the inner wall of a fused silica capillary was established by a simple coating procedure, successive multiple ionic-polymer layer (SMIL) coating. An anionic polymer was tightly fixed to the capillary wall by the SMIL coating, in which a cationic polymer was sandwiched between the anionic polymer and the uncoated fused silica capillary by noncovalent bonding. The SMIL-coated capillary showed a long lifetime. The endurance of the SMIL-coated capillary was more than 100 runs, and it was also tolerant to organic solvents, 1 M NaOH, and a surfactant. The coating efficiency did not depend on capillary sources, and the relative standard deviation of capillary-to-capillary reproducibility was less than 1%. In this study, dextran sulfate (DS) was used as the anionic polymer, and Polybrene was used as the cationic polymer for SMIL modification. The DS-modified capillary (SMIL-DS capillary) exhibited a pH-independent electroosmotic flow (EOF) from anode to cathode in the pH range of 2-11. The SMIL-DS capillary showed good performance for acidic protein analyses under physiological conditions (pH 7.4). Also, the presence of EOF under acidic conditions permitted new applications. Simultaneous separations of cationic, anionic, and neutral amino acids were achieved by capillary zone electrophoresis, and separations of cresol isomers were achieved by micellar electrokinetic chromatography under the acidic conditions. The SMIL-DS capillary was also useful for fast and precise determination of the pKa of acidic functional groups.

Amino Acids↗

Usefulness of thallium-201 SPECT imaging for the evaluation of local recurrence of colorectal cancer.

PURPOSE: To clarify the accumulation of thallium-201 in recurrent tumors in patients who had undergone resection of colorectal cancer and to evaluate the usefulness of thallium-201 single photon emission computed tomography (SPECT) images for distinguishing recurrent tumors from postoperative changes. MATERIALS AND METHODS: Thallium-201 SPECT images and CT images of 22 consecutive patients suspected to have local recurrence of colorectal cancer based on clinical symptoms and signs were reviewed. CT was performed on all patients. RESULTS: In nine of the 11 patients who had local recurrence, SPECT images showed positive thallium uptake, but in 10 of the 11 patients confirmed to have no recurrence, SPECT images showed negative thallium uptake. Sensitivity was 81.8% (9/11) specificity was 90.9% (10/11), and accuracy was 86.4% (19/22). There were five patients in whom CT results were inconclusive. All of them had rectal cancer and had undergone Miles' operation, and all were correctly diagnosed by thallium-201 SPECT. CONCLUSION: Thallium-201 exhibited intense uptake in recurrent colorectal cancer. Thallium-201 SPECT is considered to be a useful diagnostic tool for the detection of recurrence of colorectal cancer, particularly in patients with inconclusive CT results.

Adult↗

Studies on relationships between chemical structure and beta-blocking potency of bopindolol and its two metabolites.

The structure-activity relationships of bopindolol and its two metabolites (18-502 and 20-785) and their beta-blocking potencies in the human beta2-adrenoceptor (AR) were assessed using molecular modeling on an INDIGO2 workstation (SGI Co., Ltd.) and DISCOVER/INSIGHT II (Biosym Co., Ltd.). Through modeling, possible binding sites for these agents were hypothesized to involve the 3rd, 4th, 5th and 6th helices of the beta2-AR, and these shared a common interaction site at Asp113 in helix 3. The different chemical structure of these three agents, however, showed binding to different binding sites (amino acids). This study therefore suggests that different beta-blocking potencies of these agents may be due to different chemical structure.

Adrenergic beta-Antagonists↗

Urinary metabolites of valproic acid in epileptic patients.

The urinary excretion of valproic acid (VPA) and its metabolites (3-keto VPA, 3-OH VPA, and VPA-glucuronide) in 6 epileptic patients was studied using gas chromatography-mass spectrometry. The amount of VPA and 3-OH VPA excreted in the urine was low (0.1-0.5% of the dose of VPA and 0.6-1.5% of the dose of 3-OH administered). The amount of 3-keto VPA and glucuronide (VPA-Glu) excreted was marked (5.8-26.2% and 13.1-88.7% of the dose of VPA administered, respectively). The urinary excretion of VPA and its metabolites by patients who have taken a normal amount of a VPA preparation was almost the same as that of healthy volunteers. Two epileptic patients who took a large amount of the VPA preparation showed a high excretion of VPA-Glu without an increase in their plasma VPA-Glu.

Adolescent↗

Rapid diagnosis at the outpatient clinic for breast tumors by fine needle aspiration cytology. The utility.

The aim of this study was to emphasize the utility and prove the accuracy of rapid diagnosis at the outpatient clinic for breast tumors by fine needle aspiration cytology [FNAC]. Rapid diagnosis for breast tumors by FNAC is performed on the same day just after mammography and echonography are carried out at our hospital and the result reported to the patients while they are waiting at the outpatient clinic. We evaluated FNAC by rapid diagnosis at the outpatient clinic for 1,786 breast tumors during the last ten years. The cases of no judgement (Class 0) were 11%, negative cases (Class I & II) 72%, suspicious cases (Class III) 7%, and positive cases (Class IV & V) 10%. We experienced only 4 false negative cases and 0 false positive cases among 1,198 cases during the last 5 years, whereas there were 8 false negative cases and 2 false positive cases among 588 cases during the first 5 years. Two false positive cases in the the first 5 years were judged as Class IV, but definitive surgery [mastectomy] was not performed because rapid diagnosis during the operation by frozen section confirmed no malignancy. As a result, all the cases in which mastectomies were performed up to now were confirmed malignant. We emphasize that rapid diagnosis at the outpatient clinic for breast tumors by FNAC is very useful for early detection and treatment and it is very important to consider the histological type of breast tumors by FNAC to prevent misjudgement.

Adult↗

Inhibitory effect of ambroxol on superoxide anion production and generation by murine lung alveolar macrophages.

We examined the effect of ambroxol on superoxide anion production before and generation after phorbol-myristate acetate (PMA) stimulation of lung alveolar macrophages. Lung free cells including lung alveolar macrophages were obtained from Fischer 344 rats and guinea pigs using bronchoalveolar lavage. The superoxide anion produced by lung alveolar macrophages with or without stimulation of PMA was measured by lucigenin-dependent chemiluminescence method using a photon counter. Ambroxol inhibited the superoxide anion production and generation by lung alveolar macrophages harvested from both F344 rats and guinea pigs in a dose-dependent fashion. Approximately 16 mumol/L of ambroxol inhibited 50% of superoxide production of lung alveolar macrophages in rats and guinea pigs, whereas a slightly greater dose of ambroxol, i.e., 18-26 mumol/L, was necessary to inhibit 50% of PMA-enhanced superoxide generation by lung alveolar macrophages. These results suggest that ambroxol acts as an antioxidant in murine lungs and may be a potential therapeutic option for reactive oxygen species-associated lung disorders including bronchial asthma.

Acridines↗

[Influence of kyphosis on the age-related decline in pulmonary function].

To examine the influence of kyphosis on pulmonary function in the elderly, 300 consecutive healthy subjects (aged 20-94 years old) were evaluated using pulmonary function tests (TLC, VC, FEV1, RV) and static maximal pressures (PImax and PEmax). Kyphosis of the thoracic bones was measured at Cobb's angle. VC, FEV1. PImax and PEmax showed a significant age-dependent decline. Cobb's angle had a positive relationship with age and was negatively correlated with TLC, VC, FEV1 and PImax. Further, RV/TLC strongly correlated with Cobb's angle and PImax. Stepwise regression analysis revealed that the kyphotic angle was an independent determinant for PImax and RV/TLC. These results indicate that kyphosis significantly affects lung volume and maximal inspiratory pressure in the elderly and those affected should have careful assessment of their pulmonary function and respiratory pressures.

Adult↗

[An animal model of aspiration and aspiration pneumonia using lacZ gene expression in lungs by adenoviral vectors].

To examine the relationship between disturbed upper airway reflexes and aspiration pneumonia, we administered a total volume of 20 microliters of Ad-CMV-lacZ (Ad vector) or 20 microliters of phosphate buffer solution (PBS) intranasal to C57 black mice. In nostrils, the lacZ gene expression was investigated in each mouse with or without anesthesia. Under anesthesia, the lacZ gene expression was detected by Xgal staining in the lungs of every mouse given the Ad vector. However, no gene expression was measured in the lungs of those given the Ad vector without anesthesia. In mice treated with PBS, there was no lacZ gene expression in the nostrils, trachea, or lungs, irrespective of anesthesia. These results suggest that unconsciousness or disturbed upper airway reflexes caused by anesthesia caused aspiration, resulting in an intranasal bolus that can reached the lower airways. This process can be analyzed in mice tracted with adenovirus vectors carrying the E. coli LacZ gene. Mice given Ad-CMV-lacZ transnasally can be used to study aspiration pneumonia in relation to unconsciousness.

Adenoviridae↗

[2D-FASE MRCP for pediatrics with congenital biliary dilatation: usefulness of non-breath-hold one-shot MRCP].

The usefulness of magnetic resonance cholangiopancreatography (MRCP) using the non-breath-hold one-shot technique was evaluated. Ten children suffering from congenital biliary dilatation (CBD) were included. Four of them were preoperative cases, and the remaining six postoperative. All MR images taken were compared with endoscopic retrograde cholangiopancreatography or intraoperative cholangiography. MR images using the non-breath-hold one-shot technique clearly showed the confluence of the common bile duct and the main pancreatic duct in seven of the cases. The confluence of the common bile duct and main pancreatic duct was obscure in the other three cases, mainly due to motion artifact. These results show that this non-breath-hold one-shot technique is useful for diagnosis and postoperative follow-up of congenital biliary dilatation in children.

Adolescent↗

[Determinant factors of pulmonary function and respiratory muscle strength on exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD)].

The effects of pulmonary function and respiratory muscle strength on exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD) have not been fully elucidated. We examined the relationships between pulmonary function, static respiratory pressure, and dyspneic sensation during exercise in 48 patients with COPD. Dyspneic sensation during exercise was quantitated by a Borg scale slope (BSS, BS/VO2) and the threshold load of dyspnea (TLD). BSS was negatively correlated with VC, FEV1, V 25, RV/TLC (%). DLCO and PImax, whereas TLD was positively correlated with VC, FEV1, V 25, FRC and RV/TLC. Linear regression analysis revealed that FEV 1 and FRC were independent predictors for TLD, and that RV/TLC (%) was an independent predictor for BSS. These results suggest that an increase of air trapping as indicated by RV/TLC may be a major factor contributing to both decreased TLD and increased BSS, resulting in an increased sensation of dyspnea during exercise in patients with COPD.

Dyspnea↗

[A modified method of cardiac functional analysis for ECG gated SPECT: study of functional G-maps].

To evaluate the cardiac function accurately using ECG gated SPECT images, we performed a modified method of cardiac functional analysis (Functional G-maps). One hour after the intravenous injection of 1,110 MBq of 99mTc-tetrofosmin, gated SPECT data was acquired dividing a cardiac cycle into 12 frames. Every short-axis images were usually reconstructed using first 11 of 12 frames. The reconstruction of these images was repeated performing slice thickness correction. Because the apex-to-base length is different at any frame during a cardiac cycle, 10 slices of short-axis images were obtained with the same thickness for each frame. Subsequently each short-axis image was divided by 40 radii, and the time activity curve was generated from the total counts included in each segment plus both neighboring segments. Afterwards the curve fitting was performed using the second reverse Fourier function. From fitted curves and their differentials, we estimated a variety of parameters including Max (End-systolic count), Min (End-diastolic count), %CI (Percent count increase), Uptake, PCR (Peak contraction rate), PDR (Peak distention rate) and CT (Contraction time). In 5 normal subjects, %Max was greater in the anterior and septal regions, whereas %Min was greater in the apex and lateral regions. %CI and %PCR were similarly greater in the septal, anterior and inferior regions. On the other hand, %PDR in the lateral or inferior region was lower than the values in the other regions. In conclusion, this modified method is expected to be useful for accurate assessment of regional cardiac function and myocardial perfusion.

Adult↗

[Effects of thyroid hormone replacement therapy on nocturnal apnea in elderly patients with hypothyroidism].

Because the incidence of sleep apnea is known to increase in both hypothyroidism and with age, elderly hypothyroid patients may experience more sleep apnea than younger hypothyroidism patients. However, the features of nocturnal disturbed breathing in elderly hypothyroid patients have not been fully elucidated. Concise polysomnographic studies including respiratory movement and oxyhemoglobin saturation (SaO2) were done on 18 elderly subjects with hypothyroidism (73.6 +/- 5.9 years old) before and after thyroid hormone replacement therapy. Fourteen of the patients exhibited a significant incidence of nocturnal apnea. Lower incidence of nocturnal apnea and higher nocturnal nadir SaO2 were observed in the patients 3 to 6 months after thyroxine therapy. Although the levels of thyroid hormones returned to normal in the patients, 9 patients had more than 5 bouts of nocturnal apnea per hour after the hormone replacement therapy. Further, no relationship was found between the level of thyroid hormones and the frequency of nocturnal apnea. These results suggest that levels of thyroid hormones are not indicators of the potential severity of nocturnal apnea in elderly hypothyroid patients, and that sleep studies may be necessary to assess the efficacy of thyroid hormone replacement therapy in the treatment of nocturnal apnea.

Aged↗