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Biomedical subjects

H Katayama

Publications and source records attributed to H Katayama.

At least 91 records · Page 5Linked to original sources
PubMed1999

Epidermal growth factor-dependent dissociation of CrkII proto-oncogene product from the epidermal growth factor receptor in human glioma cells.

Human glioma cells frequently overexpress epidermal growth factor receptor (EGFR). We found that the CrkII proto-oncogene product was associated with the EGFR in human glioma cells in the absence of epidermal growth factor (EGF). EGF stimulation of glioma cells induced the phosphorylation of tyrosine 221 of the CrkII protein, which correlates with its dissociation from the EGFR. By contrast, Shc and Grb2 were inducibly associated with the EGFR in response to EGF stimulation of glioma cells. In A431 cells, epidermoid carcinoma cells which overexpress EGFR, CrkII was tyrosine-phosphorylated and associated with the EGFR in an EGF-dependent manner. Therefore, the dissociation of CrkII from the EGFR upon stimulation with EGF appears to be specific to glioma cells. The Cbl oncogene product was also tyrosine-phosphorylated in U87MG glioma cells upon EGF stimulation. However, unlike in other cell lines, CrkII was not inducibly bound to Cbl in U87MG glioma cells. Thus, EGF-dependent binding of CrkII to phosphotyrosine-containing proteins appears to be suppressed in glioma cells. To evaluate the physiological role of dissociation of CrkII from EGFR, we expressed the CrkII-23 mutant in glioma cells. CrkII-23 mutant, which was isolated as a suppressor gene of the EGF-dependent transformation of NRK cells, binds constitutively to EGFR. We found that expression of CrkII-23 inhibited the anchorage-independent growth of the glioma cells in the presence of EGF. Taken together, these data implicate EGF-dependent dissociation of CrkII from EGFR in the oncogenicity of human glioma cells.

Cell Adhesion↗
PubMed1999

beta-Adrenergic receptor subtypes in melanophores of the marine gobies Tridentiger trigonocephalus and Chasmichthys gulosus.

The subtype of beta-adrenergic receptors in melanophores of the marine gobies Tridentiger trigonocephalus and Chasmichthys gulosus was studied. Pigment of denervated melanophores in isolated, split caudal fins was preliminarily aggregated by incubating the specimens in a physiological saline containing 10 microM phentolamine and 30-100 microM verapamil or 2-10 nM melatonin, and the responses of the melanophores to a beta-adrenergic agonist added to the incubating medium were recorded photoelectrically. The beta-adrenergic agonists noradrenaline, adrenaline, isoproterenol, salbutamol and, dobutamine were all effective in evoking a dispersion of melanophore pigment in the presence of phentolamine and verapamil or melatonin. The pigment-dispersing effect of noradrenaline (beta 1-selective agonist) was inhibited by metoprolol (beta 1-selective antagonist), propranolol,- and butoxamine. Whereas, the effect of salbutamol (beta 2-selective agonist) was hardly inhibited by metoprolol, though it was considerably inhibited by propranolol and ICI-118551. It was estimated that beta 1- and beta 2-adrenergic receptors coexist at ratios of 8.6:91.4, in the melanophore of Tridentiger trigonocephalus, and 25:75, in the melanophore of Chasmichthys gulosus, through the analyses of Hofstee plots of the effects of the beta-adrenergic drugs. It was suggested that the relation between the pigment-dispersing effect of a beta-adrenergic agonist on the melanophores and the concentration of the drug follows mass action kinetics, when the effect is mainly caused by the activation of beta 2-adrenergic receptors of the melanophores. However, when it is mainly caused by the activation of beta 1-adrenergic receptors of the melanophores, the relation does not follow mass action kinetics.

Adrenergic alpha-Agonists↗
PubMed1999

Increased levels of circulating ICAM-1, VCAM-1, and L-selectin in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) may be one of the most important risk factors of cardiovascular disorders, although the exact mechanism remains to be elucidated. In the present study, we hypothesized that OSAS-induced hypoxic stress might be involved in the etiology of cardiovascular disorders by activating adhesion molecules, including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and L-selectin. To examine this hypothesis, we measured circulating ICAM-1, VCAM-1, and L-selectin levels before and after sleep in OSAS patients and age-matched controls. The circulating ICAM-1, VCAM-1, and L-selectin levels increased in the OSAS patients before sleep compared with the normal subjects (ICAM-1: 392.9 +/- 48.5 vs. 201.2 +/- 55.0 ng/ml, P < 0.05; VCAM-1: 811.0 +/- 87.8 vs. 574.2 +/- 42.7 ng/ml, P < 0.05; L-selectin: 1,386.6 +/- 77.9 vs. 1,038.8 +/- 78.6 ng/ml, P < 0.01, respectively). After sleep, significantly greater levels of ICAM-1 and L-selectin, but not VCAM-1, were observed in the OSAS group. These observations suggest that OSAS-induced hypoxia activates adhesion molecules, resulting in the important risk factor of cardiovascular disorders. Treatment of OSAS can be, therefore, a potential approach to prevention of cardiovascular events.

Adult↗
PubMed1999

ICAM-1 mediates lung leukocyte recruitment but not pulmonary fibrosis in a murine model of bleomycin-induced lung injury.

Bleomycin-induced lung injury has been extensively used as a model of interstitial pneumonia and pulmonary fibrosis. Intercellular adhesion molecule (ICAM)-1 is a ligand for lymphocyte function-associated antigen (LFA)-1alpha and has been shown to be required for leukocyte migration into inflamed areas. The purpose of this report was to investigate the role of the ICAM-1/LFA-1alpha pathway in a murine model of bleomycin-induced lung injury. Animals received 75 mg x kg(-1) bleomycin (BLM) i.v. followed by treatment with phosphate-buffered saline (BLM group), anti-ICAM-1 and LFA-1alpha monoclonal antibodies (mAb) (BLM+mAb group). Inflammatory cell counts of bronchoalveolar lavage (BAL) fluid, hydroxyproline content and histological findings were compared between these groups. In the BLM group, significant increases in total cell count, macrophage count and neutrophil count of BAL fluid were observed on days 7 and 14. In the BLM+mAb group, bleomycin-induced accumulation of neutrophils was significantly reduced on days 7 and 14 (p<0.01). However, the administration of mAb to ICAM-1 and LFA-1alpha did not decrease the lung hydroxyproline content or the histopathological fibrosis grading score, indicating that the antagonism of ICAM-I and LFA-1alpha did not attenuate bleomycin-induced pulmonary fibrosis. This study suggests that the intercellular adhesion molecule-1/lymphocyte function-associated antigen-1alpha pathway mediates the accumulation of inflammatory cells in the injured lung caused by bleomycin; however, other mechanisms are important for the subsequent development of pulmonary fibrosis.

Animals↗
PubMed1999

Effect of acute renal failure on the disposition of cefoperazone.

The effect of acute renal failure on the disposition of cefoperazone was investigated. Rats, 3 days after uranyl nitrate treatment, were used to model acute renal failure. Although plasma-protein binding of cefoperazone decreased significantly in acute renal failure compared with control rats, the plasma clearance of total (bound plus unbound) drug after intravenous administration (50 mg kg(-1)) did not differ significantly between the two groups (5.61+/-2.37 mL min(-1) for control and 4.75+/-2.82 mL min(-1) for acute renal failure). Consequently the plasma clearance of the unbound drug in acute renal failure (6.14+/-1.16 mL min(-1)) was significantly lower than in control rats (15.6+/-3.7 mL min(-1), P < 0.025). Plasma clearance of the drug (both total and unbound) was also dependent on bile flow, and clearance of the unbound drug in acute renal failure rats was lower than in control rats with identical bile flow rates. To examine the mechanism of reduced unbound cefoperazone clearance, an in-vitro experiment using a simultaneous perfusion system of rat liver and kidney was performed. By changing perfusate plasma protein from bovine serum albumin to human serum albumin, the plasma clearance of the total cefoperazone changed to one-sixth in proportion to the unbound cefoperazone in the perfusate plasma. On the other hand, the plasma clearance of the total and unbound drug in acute renal failure rats decreased significantly compared with controls. These results demonstrate that the plasma clearance of unbound cefoperazone, which is mainly eliminated by the liver, decreased in acute renal failure in rats, probably due to changes in hepatic transport.

Acute Kidney Injury↗
PubMed1999

Sustained release liquid preparation using sodium alginate for eradication of Helicobacter pyroli.

We prepared a new liquid preparation for eradication of Helicobacter pylori (HP), and examined drug release in vitro and in vivo. The liquid preparation mainly consisted of a sodium alginate (AG) aqueous solution containing ampicillin (ABPC), an antibiotic drug, or methylene blue, a dye. Drug release was retarded by Ca pre-treatment (0.10 M, 20 s) of the AG preparation in in vitro drug release studies due to gel-formation at the liquid surface. In in vivo experiments, the AG preparations were administered orally to rats. The rats were divided into two groups, with or without pre-administration of ranitidine hydrochloride (RH, an H2-blocker). The total remaining % of ABPC in the stomach was high in the rats administered the AG preparation compared to the ABPC solution. The AG preparation might float in the stomach without adhering to the gastric wall in the rats without pre-administration of RH. The total remaining % of ABPC at 30 min was almost 100% in the RH pre-administration rats administered the AG preparation, and about 80% of the drug existed in fraction 2 (implying adhesion of the preparation on the gastric mucus). At 60 min, the total remaining % in the AG preparation plus Ca (mean 87%) increased about 2-fold compared to that in the AG preparation alone (mean 44%). In this case, a large portion of the remaining ABPC also existed in fraction 2. This preparation may be useful for eradication of HP.

Administration, Oral↗
PubMed1999

Valproic acid elimination rate and urinary excretion of its glucuronide conjugate in patients with epilepsy.

We previously encountered a patient with epilepsy who exhibited rapid elimination of sustained-release valproic acid (VPA) administered at the dose of 2.8 g/d as a sodium salt. The purpose of this study was to clarify the relationship between the VPA elimination rate and the proportion of the dose excreted in urine as its glucuronide conjugate (VPA-G) in epileptic patients. Twenty-four-hour urine was collected from four epileptic patients who had taken VPA orally (age: 16-39 y, weight: 50-63 kg, dose: 1.0-2.8 g/d). VPA and its metabolites were detected by gas chromatography-mass spectrometry. The amounts of VPA, VPA-G, 3-keto VPA, and 3-OH VPA excreted in the 24-h urine were 1.8-13.2, 178-2158, 125-320, and 8.6-18.7 mg (converted into VPA), respectively, and 0.2-0.5, 20.5-88.7, 5.8-18.7, and 0.6-1.0% of the dose administered, respectively. The dose of VPA correlated well with the proportion of the dose excreted in urine as VPA-G in each patient, and the patients administered a high dose excreted a large amount of VPA-G in the urine. Thus, differences in the VPA-G production rate may be one of the major variable factors affecting the elimination of administered VPA. We also present a dynamic model of VPA in the kidney which may explain the VPA elimination phenomena in humans on the basis of the data obtained here regarding the concentrations of VPA and its metabolites in plasma and their urinary excretion levels.

Adolescent↗
PubMed1999

Synthetic inhibitors of DNA topoisomerase I and II.

A new type of synthetic inhibitor of DNA topoisomerase I and II was examined and several of these derivatives exhibited strong dual activity against these enzymes. This series of compounds showed high cytotoxic activities against cancer cells, but only a limited number of compounds showed any noticeable activity in an in vivo test against murine P388. Non-specific toxicity was observed in the in vivo tests.

Animals↗
PubMed1999

Effects of angiotensin-converting enzyme (ACE) inhibitors on oxygen radical production and generation by murine lung alveolar macrophages.

We examined the effect of angiotensin-converting enzyme (ACE) inhibitors on oxygen radical production before and generation after phorbol-myristate acetate (PMA) stimulation of lung alveolar macrophages. Lung free cells, predominantly pulmonary alveolar macrophages, were obtained from Fischer 344 rats and guinea pigs using bronchoalveolar lavage. The oxygen radicals produced by pulmonary alveolar macrophages with or without stimulation of PMA were measured by lucigenin-dependent chemiluminescence method using a photon counter, Lumat 9501 (Berthold, Germany). Alacepril, an ACE inhibitor with SH-group, inhibited the oxygen radical production and generation by lung alveolar macrophages harvested from both rats and guinea pigs in a dose-dependent fashion. Approximately 0.3 mM of alacepril inhibited 50% of oxygen radical production of lung alveolar macrophages in both rats and guinea pigs, whereas a higher concentration (1-5 mM) of lisinopril, an ACE inhibitor without SH-group, was necessary to inhibit 50% of oxygen radical production of lung alveolar macrophages in the animals. These results suggest that an ACE inhibitor with SH-group acts as an antioxidant in murine lungs and the treatment with the ACE inhibitor may reduce oxidant stress in hypertensive patients with asthma.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Hyperimmunoglobin E syndrome: a sign of TH1/TH2 imbalance?

We report on a patient with hyperimmunoglobulin E syndrome, who developed pruritic vesiculopapules from the age of six months and also had recurrent episodes of skin abscesses and oral thrush. Serum IgE was extremely elevated at 59,514 IU/ml and specific IgE antibody to Staphylococcus aureus was positive. Histological examination from a vesiculopapule on the face revealed that eosinophil-rich infiltration involved hair follicles, similar to eosinophilic pustular folliculitis. We also examined cytokine profiles of circulating CD4+ T cells by intracellular cytokine staining and flow cytometry. The ratio of cells positive for interferon-gamma was significantly reduced compared with a control. Several reports have shown decreased interferon-gamma production by peripheral blood mononuclear cells of patients with hyperimmunoglobulin E syndrome. We think that this cytokine profile and the histological findings of our patient support the hypothesis that TH1/TH2 imbalance is involved in hyperimmunoglobulin E syndrome.

CD4-Positive T-Lymphocytes↗
PubMed1999

[Diagnosis of breast cancer extent and enhancement patterns using 3D-dynamic MR imaging: correlation with intraductal component].

The usefulness of 3D-dynamic MR imaging with fat suppression and magnetization transfer contrast for assessing breast cancer extent and tumor profile was evaluated in 74 breasts with 67 malignant and 7 benign lesions. We classified breast cancer by the intraductal component of the main tumor. Five histological types were assigned: type 1 (DS 0) invasive carcinoma without intraductal component, type 2 (DS 1): intraductal component is less than 50% of whole tumor, type 3 (DS 2): intraductal component is nearly equal to 50%, type 4 (DS 3): intraductal component is more than 50%, type 5 (DS 4): pure DSIC or DCIS associated with microinvasive foci. Histologic results and preoperative MR imaging were analyzed regarding tumor size and enhancement pattern for the various tumor types (DS 0, 1, 2, 3 and 4). The three tumors occult to MR imaging were two DCIS and one Paget's disease. The other 64 breast cancers were detected on MR imaging. Tumor size measured with MR imaging correlated closely with histologic measurement in DS 0, 1 and 2, whereas less accuracy was noted in DS 3 and 4. Rapid enhancement was frequently seen in DS 0, 1, 2 and 3. Peripheral enhancement was highly specific for breast cancer. However, peripheral enhancement was not found in all cases of DS 4. Linear and nodular enhancement was frequently seen in DS 3 and 4. MR imaging was useful in predicting the intraductal component.

Adult↗
PubMed1999

[Effect of mechanical damage on ex vivo DNA virus vector-mediated gene transduction in epithelial cells of murine trachea].

The mechanism of Adenovirus (Ad) and Adeno-associated virus (AAV) vector-mediated gene transduction in murine tracheae has not been fully understood. Excised tracheae from mice were exposed to either Ad vector (Ad-CMV-LacZ) or AAV vector (AAV-CMV-LacZ) for 1 hour. LacZ gene expression in tracheal epithelial cells was detected by X-gal staining. Only patch distributions of LacZ expressing cells were observed. The percentage of LacZ expressing cells to total cells was less than 1% with either vector. Ad-mediated LacZ transduction was increased by mechanical damage using forceps. AAV-mediated gene transduction in tracheal epithelial cells was also increased by mechanical damage. Furthermore, this increased expression of vector LacZ by damaged epithelial cells was not affected by pretreatment with anti-ICAM-1 mAb or platelet-activating factor receptor antagonist. Although the Ad and AAV vectors were inefficient in transferring genetic material to murine trachea ex vivo, our results suggest that mechanical damage can enhance their transduction efficiency.

Adenoviruses, Human↗
PubMed1999

[Perioperative change of ionized magnesium concentration--effect of blood transfusion].

In order to evaluate the effect of intra-operative blood transfusion on post-operative decrease of ionized Mg (Mg2+), we performed following studies. 1) We measured ionized Mg (Mg2+), total Mg, ionized Ca (Ca2+), total Ca and citrate before and after operation in 70 patients. 2) We evaluated the effect of citrate on Mg2+ and Ca2+ in vitro. 3) We also measured these values during blood transfusion in 8 patients. There was no significant difference between post-operative Mg2+ of 45 patients without blood transfusion (0.49 +/- 0.07 mmol.l-1, % decrease from pre-operative value was 13.4 +/- 9.2%; mean +/- SD), and that of 25 patients with blood transfusion (0.48 +/- 0.09 mmol.l-1, 17.9 +/- 10.2%). Mean value of post-operative citrate concentration of patients with blood transfusion was 0.15 +/- 0.11 mmol.l-1, and this value decreased Mg2+ about 2% in in vitro study. During blood transfusion, Mg2+ (0.41 +/- 0.05 mmol.l-1) and ionized % (54.5 +/- 8.3%) decreased significantly just like Ca2+ with elevated citrate concentration (0.95 +/- 0.59 mmol.l-1). In conclusion, intra-operative blood transfusion had minor effect on the post-operative decrease of Mg2+, and the major cause was thought to be the dilution of extracellular fluid by Mg-free fluid administered during operation.

Adult↗
PubMed1999

Measuring respiration of cultured cell with oxygen electrode as a metabolic indicator for drug screening.

New trend in methods for assessing pharmacological action to bacteria and cell is to measure their metabolic activities induced, while the conventional methods used population growth. We focused on respiration volume as an indicator of cell metabolism, and developed inexpensive disposable oxygen electrode sensor and multi-channel dissolved oxygen meters (DOX-10 and DOX-96KB). Using these instruments, cytotoxicity was measured for 48 hrs and the method showed superior features to conventional methods in its handiness of one step assay, and excellent adaptability to automated systems. Total usability of this oxygen electrode method is being evaluated in bacterial drug susceptibility test, anticancer drug susceptibility test, and alternatives to animal experiment.

Antineoplastic Agents↗
PubMed1998

Stable cationic capillary coating with successive multiple ionic polymer layers for capillary electrophoresis.

A coated capillary modified with a cationic polymer was developed by using a novel coating procedure, successive multiple ionic-polymer (SMIL) coating. The SMIL coating was achieved by first attaching the cationic polymer to the capillary inner wall, and then the anionic polymer to the cationic polymer layer, and finally the cationic polymer to the anionic polymer layer. The stability of Polybrene (PB)-modified capillary made by SMIL coating was remarkably improved in comparison with a conventional PB-modified capillary. It endured during 600 replicate analyses and also showed strong stability against 1 M NaOH and 0.1 M HCl. The relative standard deviation of the run-to-run, day-to-day, and capillary-to-capillary coating was all below 1%, and good reproducibilities were obtained. The PB-modified capillary made by SMIL coating was applied to the basic protein analyses. It gave good performances for the protein analyses even when the pH of the electrolyte was near the isoelectric point (pI) of the protein. In addition, 0.1 M NaOH rinse prior to the sample injection allowed the reproducible analysis of a highly adsorptive sample such as plasma because the adsorbed sample could be flushed out of the capillary. Besides protein analyses, an efficient analysis of the cationic drugs by capillary electrophoresis/mass spectrometry (CE/MS) was also possible.

Cations↗