Search PubMed⌕ Search

Biomedical subjects

E Tanaka

Publications and source records attributed to E Tanaka.

At least 325 records · Page 18Linked to original sources

Regulation of heat production of brown adipocytes via typical and atypical beta-adrenoceptors in the rat.

Previous studies in our laboratory demonstrated that microcalorimetry is an appropriate method for estimating the physiological function of isolated rat brown adipocytes. In the present study, to elucidate the mode of action of typical and atypical beta-adrenoceptors on heat production of this cell, the effect of novel adrenergic beta 3-agonists was compared with that of other typical adrenergic reagents by direct microcalorimetry. Isoproterenol and beta 3-agonists, BRL37344, ICI215001, and CGP12177, increased heat production in a dose-dependent manner, however, phenylephrine had no effect. Propranolol and pindolol did not increase the heat production but attenuated the effect of isoproterenol and BRL37344 in a dose-dependent manner. Molar IC50 values of propranolol and pindolol for BRL37344 were about 10(-5) and 3 x 10(-6) M, respectively, whereas those of the two antagonists for isoproterenol were about 3 x 10(-7)M. The pA2 values by Schild analysis of propranolol vs. isoproterenol and BRL37344 were 7.91 and 6.13, respectively. These results suggest that heat production may be regulated via both beta 3- and typical beta-adrenoceptors in brown adipocytes.

Adipose Tissue, Brown↗

Changes in the metabolism of three model substrates catalysed by different P450 isozymes when administered as a cocktail to the carbon tetrachloride-intoxicated rat.

1. Caffeine (CA) metabolism in animal and man is mainly catalysed by P4501A2. Lidocaine (LID) and phenytoin (PHT) are metabolized by P4503A2 and 2B1/2 in animals and 3A4 and 2C9 in man, respectively. 2. We investigated the possibility of predicting liver damage from changes in blood concentrations after simultaneous i.v. administration (cocktail study) of the three probe drugs CA (10 mg/kg), LID (4 mg/kg) and PHT (4 mg/kg), and their main metabolites, paraxanthine (PX), monoethylglycinexylide (MEGX) and 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) respectively. 3. The metabolism of CA, LID and PHT and production of their metabolites (PX, MEGX and p-HPPH) in the carbon tetracholride (CCl4 0.25 and 0.5 ml/kg)-treated rat were reduced in comparison with the control group. 4. The ratios (PX/CA and p-HPPH/PHT) of CA and PHT to the serum levels of the their metabolites 2 h after i.v. administration of three drugs to the CCl4-treated rat were significantly reduced. 5. The correlation coefficients among CLs of CA, LID and PHT, and the PX/CA and p-HPPH/PHT ratios in rat pretreated with different doses of CCL4 are very high. 6. These results suggest that different estimates of hepatic oxidizing capacity, catalysed mainly by P4501A2, 2C and 3A, may be related to the extent of liver disease in the CCl4-intoxicated rat. Therefore a 'cocktail' is not in fact needed to assess hepatic damage in the CCl4-intoxicated rat.

Animals↗

Influence of partial hepatectomy in dogs on trimethadione metabolism and microsomal monooxygenases.

1. The recovery of trimethadione (TMO) metabolism and its association with liver weight and the activity of TMO N-demethylase have been reported in rat following partial (68%) hepatectomy. In the present study, we examined the effect of liver regeneration on hepatic P450 isozymes and TMO metabolism in dog. 2. The ratio of dimethadione (DMO), being the only TMO metabolite, to TMO at 2 h after i.v. injection of TMO (4 mg/kg) fell to 80% of that in the preoperative animals by 24 h after hepatectomy. The DMO/TMO ratio gradually recovered from days 7 to 14, and by day 21 after hepatectomy it had increased to about 25%. At 28 days post-hepatectomy the ratio had returned to preoperative levels. 3. The activity of benzphetamine N-demethylase, TMO N-demethylase, p-nitro-anisole O-demethylase and aniline hydroxylase increased 3 days post-hepatectomy, exhibiting levels 4.77, 3.45, 1.51 and 1.91 times greater respectively than that of the preoperative liver in the same animal. Two weeks post-hepatectomy these activities had returned to normal. The activity of the 16 beta- and 2 beta-hydroxylation of testosterone was unchanged. However, the activity of 6 beta-hydroxylase decreased 7 days post-hepatectomy, while 16 alpha-hydroxylation had increased at 3 and 7 days post-hepatectomy compared with controls. 4. The changes in liver weight were nearly restored to preoperative levels 7 days post-hepatectomy. 5. Although the P450 content was unchanged from days 1 to 7 post-hepatectomy, it had decreased by 30% at day 14 and by 20% at day 28. The P4502B11 content 3, 7 and 14 days post-hepatectomy had increased 8, 10 and 2 times respectively, while the P4503A12 content at 7 and 14 days decreased by 30 approximately 50% compared with that of the pre-operative liver. 6. The data presented above do not reveal any relationship between P4502B11 induction and liver regeneration. The reason for such a change is unknown, therefore further investigation needs to be carried out.

Animals↗

Stress distributions in the TMJ during clenching in patients with vertical discrepancies of the craniofacial complex.

This study was designed to investigate stresses in the TMJ during clenching in patients with skeletal discrepancies in the vertical direction. A three-dimensional model of the mandible including the TMJ was used for finite element analysis for the stresses. The model, referred to as a standard model, consists of 2,088 nodes and 1,105 solid elements, comprising the cortical and cancellous bones, articular disc and cartilage layer, and periodontal ligament. The standard model was modified by varying the gonial and mandibular plane angles to simulate vertical discrepancies between the maxilla and mandible observed in open and deep bites. Stresses were analyzed on the surfaces of the condyle, the glenoid fossa, and the articular disc, and the values were compared to those found with the standard model. Stresses increased substantially for the condyle, the glenoid fossa, and the articular disc with greater gonial and mandibular plane angles, and those changes were more obvious in association with the divergent mandibular plane. Thus, the nature of stress distributions in the TMJ was substantially affected by vertical discrepancies of the craniofacial skeleton. It is also suggested that these changes in stresses produce a lack of biomechanical equilibrium in the TMJ, which may have some association with temporomandibular disorders.

Cartilage, Articular↗

Effects of thapsigargin on aequorin-injected and skinned preparations of ferret ventricular muscles.

OBJECTIVE: We investigated the effects of thapsigargin (TG) (0.1-1 microM) on the relation between intracellular Ca2+ concentration and tension in ferret papillary muscles using aequorin-injected and skinned preparations. METHODS: Aequorin was injected into the superficial cells of ferret papillary muscles; the Ca2+ signals of aequorin and tension in twitch and those with the application of 15 mM caffeine were simultaneously measured. The alteration of Ca2+ sensitivity of the contractile elements was examined by measuring the pCa-tension relation in Triton-X-treated skinned preparations. RESULTS: TG decreased the peak of the Ca2+ signal accompanied by a prolonged decay time. However, the tension was scarcely altered even at 1 microM TG. TG inhibited the caffeine-induced Ca2+ signal. Prolongation of decay of the Ca2+ signal by TG in twitch was further enhanced by isoprenaline (10 nM). The pCa-tension relation of the skinned preparation was slightly but significantly shifted to the right by TG. CONCLUSIONS: The apparent dissociation of the effects of TG on the Ca2+ signal and tension in intact preparations is not a result of alteration of the Ca2+ sensitivity of the myofilaments. The effects of TG in multicellular preparations are probably limited to the outer layer of the preparation. The slower time course of the Ca2+ signal induced by TG is due to the inhibition of Ca2+ uptake by sarcoplasmic reticulum, which is more significantly observed when the intracellular Ca2+ transient is increased by isoprenaline.

Aequorin↗

[Planning for brachytherapy using a 3D-simulation model].

A 3D-simulation model made with a milling system was applied to HDR-brachytherapy. The 3D-simulation model is used to simulate the 3D-structure of the lesion and the surrounding organs before the actual catheterization for brachytherapy. The first case was recurrent prostatic cancer in a 61-year-old man. The other case was lymph node recurrence of a 71-year-old woman's upper gum cancer. In both cases, the 3D-simulation model was very useful to simulate the 3D-conformation, to plan the treatment process and to avoid the risk accompanying treatment.

Aged↗

Overall time in telecobalt therapy for T1 glottic carcinoma treated with 2 Gy per day.

BACKGROUND/AIM: We already reported the tumor response during radiotherapy as a prognostic factor for T1 glottic carcinoma. In these reports, we did not evaluate the overall treatment time. There were many reports of correlation between local control and overall treatment time of radiation for head and neck cancer. Our aim was to evaluate the overall treatment time as a prognostic factor of the local control for T1 glottic carcinoma or not. PATIENTS AND METHODS: From 1967 through 1985, 295 patients of T1 glottic carcinoma were treated with telecobalt therapy at the Department of Radiology, Osaka University Medical School. Of 295 patients, 219 patients treated with 2 Gy per day were evaluated. The median of total doses was 60 Gy (42 to 72 Gy). Overall treatment times of patients with tumor clearance at 40 Gy were significantly shorter than those with tumor persistence at 40 Gy. RESULTS: According to the univariate analysis, there were no statistically significant factors for local control except tumor response during treatment. Of 124 patients treated with a total dose of 60 Gy and the overall treatment time of 40 to 46 days, local control rates of patients treated with the overall treatment time of 40 to 42 days and 43 to 46 days were 88% and 78%, respectively (p = 0.3072). For 91 patients with tumor clearance at 40 Gy, local control rates of patients treated with the overall treatment time of 40 to 42 days and 43 to 46 days were 96% and 82%, respectively (p = 0.1645). Corresponding figures for 31 patients with tumor persistence at 40 Gy were 63% and 65%, respectively (p = 0.4227). CONCLUSION: We compare the treatment results of patients treated with the same total dose and the same tumor response during radiotherapy. We concluded that the overall treatment time was not a prognostic factor for T1 glottic tumor treated with overall time of 40 to 46 days.

Carcinoma↗

Biosynthesis of S-(2-chloro-1,1,2-trifluoroethyl)glutathione in rat and human hepatocytes and in Hep G2 cells.

Chlorotrifluoroethene is nephrotoxic in rats, and glutathione S-transferase-catalyzed S-(2-chloro-1,1,2-trifluorethyl)glutathione (CTFG) formation is the initial step in its bioactivation. CTFG biosynthesis and the activities of cytosolic and microsomal glutathione S-transferases were measured in rat and human hepatocytes and in human hepatoma-derived Hep G2 cells. Hepatocytes of > or = 88% viability were obtained from rat or human liver slices by collagenase or collagenase+dispase digestion, respectively. Hep G2 cells were grown in modified Earle's medium supplemented with 10% (v/v) fetal calf serum. Cells and subcellular fractions were exposed to chlorotrifluoroethene, and CTFG formation was quantified by HPLC. Both human liver and Hep G2 cell subcellular fractions catalyzed CTFG formation, and human and rat microsomal fractions exhibited higher specific activities than cytosolic fractions with chlorotrifluoroethene as the substrate. Time-dependent formation of CTFG was observed in all cell preparations. The presence of microsomal glutathione S-transferase was demonstrated by Western blotting with antimicrosomal glutathione S-transferase antibodies in rat and human liver tissue and in Hep G2 cells. Cytosolic and microsomal glutathione S-transferase activities were lower in Hep G2 cells than in rat and human liver tissues. These results demonstrate that human hepatocytes and Hep G2 cells are competent to synthesize CTFG and that Hep G2 cells may provide a useful model for studying human liver-catalyzed glutathione S-conjugate formation.

Animals↗

[Clinical and etiological studies of IgG antibodies to Helicobacter pylori detected by enzyme-linked immunosorbent assay].

Recently, Helicobacter pylori (H. pylori) has been reported that it is involved in the pathogenesis of duodenal ulcer and might be a risk factor for gastric cancer. To diagnose H. pylori infection, detection of serum antibody is much less stressful and more cost effective than gastric biopsy. Using a serological method, We have reported that the prevalence of serum anti-H. pylori IgG was elevated with age among healthy subjects and over 80% among elder people. Thus, it would be essential to investigate the specificity of the ELISA system (PirikaplateG Helicobacter) for the detection of serum anti-H. pylori IgG. Sera from healthy controls (n = 653) and patients (n = 116) with gastritis, gastric ulcer, and/or duodenal ulcer were studied for anti-H. pylori IgG. Cross reactivity of the anti-H. pylori IgG with closely related bacteria was less than 10% (with C. jejuni: 7.4%, C. laridis: 0.2%, E. coli: -2.4%) in the ELISA system. Anti-H. pylori IgG from both normal controls and the patients were equally neutralized with the extract of H. pylori. Of note was that the prevalence of anti-H. pylori IgG among patients was significantly higher than that among normal controls. Referring to the diagnoses by gastric biopsy, the sensitivity and specificity of this ELISA were 88.2% and 74.2%, respectively. We also demonstrated the clinical usefulness of this ELISA by receiver operating characteristic curve (ROC). Interestingly, several healthy subjects positive for serum anti-H. pylori IgG were voluntarily subjected to gastric biopsy, and proved positive for H. pylori infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[A case of Mycobacterium avium disease presenting as a solitary pulmonary nodule and resected under a suspicion of lung cancer].

A 43 year old female smoker was admitted to our hospital for evaluation of solitary pulmonary nodule (SPN). She had no symptoms, and no past history or family history that might suggest compromised defense against pulmonary infections. Physical examination and laboratory findings including humoral and cell-mediated immunity revealed no abnormality. The chest radiography taken 2 years ago looked normal, but those on admission showed SPN in a left lower field. Computed tomography (CT) revealed solitary elipsoid nodule in S5. Because two trials of transbronchial biopsy, brushing and washing could not give any diagnostic findings, thoracotomy was performed under tentative diagnosis of lung cancer. The lesion was located in the outer portion of S5 and was found to consist of 2 elastic hard nodule surrounded by a atelectasis with inflammation. The nodule had supprative substance with several acid fast bacilli, and its intraoperative pathology revealed epitheloid cell granulomas. The lesion was resected completely. In a mean while, seventy smooth colonies grew on an Ogawa egg medium, which was identified as M. avium by the probe analysis using SNAP TEST. The final diagnosis of pulmonary M. avium disease was made, and the patient was administered RFP, EB, OFLX, and CAM in a outpatient clinic. Some discussions were also made about CT findings of pulmonary M. avium complex disease developed in patients without any predisposing conditions.

Adult↗

[Healing process of high porous EPTFE graft wrapped in the omental pedicle flap--experimental study of portal vein replacement].

This study investigates the healing process of high porous EPTFE graft wrapped in the omental pedicle flap. One way to provide good pseudointima is to use grafts with more porosity which allows increased cell infiltration into the inner capsule, and it is facilitated more by using grafts wrapped in the omental pedicle flap. We implanted two kinds of grafts at the portal veins of mongrel dogs. They are 60 microns fibril length EPTFE grafts, one with its outer surface covered by fluoridized rubber. (F-EPTFE graft), and the other without the covering (EPTFE graft). Grafts were extirpated and examined the implanted grafts at 1, 2, and 4 weeks after the implantation. We were seen on both grafts the developments of organization at the inner capsules, mainly from the anastomotic lines toward the midportion of the grafts. In addition, some developments of organization from outer side to inner side of the capsules were also seen. Light microscopy demonstrated endothelial lining at parts of insides of both grafts after 4 weeks with Factor-VIII staining. EPTFE grafts showed more developments of organization than F-EPTFE grafts and the degree of organization correlated with the degree of cell infiltration into the graft wall. The thickest pseudointima was found with the F-EPTFE grafts examined two weeks after the implantation. These results suggest that the cell infiltration into the graft wall facilitates the organization of inner capsules. We also investigated the expression of TGF-beta, which was potent cytokine that promote fibrosis by enhancing the synthesis of extracellular matrix components. The immunohistochemical staining of TGF-beta positively stained vessels, vascular endothelial cells, macrophages, and spindle cells. Northern blot analysis suggested that TGF-beta was induced in the course of graft healing, and it promoted the production of extracellular matrix components.

Animals↗