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Biomedical subjects

E Tanaka

Publications and source records attributed to E Tanaka.

At least 361 records · Page 20Linked to original sources

Dermatophytosis in a Steller sea lion (Eumetopias jubatus).

Serious dermatophytosis caused by Trichophyton mentagrophytes was found in a Steller sea lion (Eumetopias jubatus) at Yomiuri Land Marine Aquarium in Tokyo. The external clinical signs were extensive depilation and hyperkeratosis, as well as redness and depigmentation of the skin. Histopathological findings of the skin revealed PAS positive fungal hyphae with septa in the corneum layer of the epidermis. Further microscopic examination suggested that this lesion of the skin was typical chronic dermatophytosis. Based on morphological and growth characteristics, the isolate was identified as Trichophyton mentagrophytes. It was thought that the infection was due to some factors including species and individual specific and environmental factors and so on.

Animals↗

Serum collagen type IV for the assessment of fibrosis and resistance to interferon therapy in chronic hepatitis C.

Sixty-nine patients with chronic hepatitis C (CH-C) were treated with interferon therapy, and serum collagen type IV (s-collagen IV) levels were measured by enzyme immunoassay to analyze the responsiveness to interferon therapy. Classified by the improved pattern of serum alanine aminotransferase levels after interferon administration, 23 patients were judged as sustained responders, 23 as transient responders, and 23 as non-responders. Fibrotic grades of the liver sample correlated statistically with the levels of s-collagen IV (P < 0.01). Pre-therapy s-collagen IV levels of sustained responders were significantly lower than those of the other responders, and only sustained responders showed a significant decrease of s-collagen IV levels after interferon therapy, in accordance with histologic improvement. Multivariate analysis showed that s-collagen IV and hepatitis C virus genotype were the most important factors affecting the response to interferon therapy of all variates. Thus, s-collagen IV is one of the most useful aids for the evaluation of liver fibrotic grade in CH-C and a potent predicting indicator for the responsiveness to interferon therapy.

Adult↗

Effect of E-5110, a novel non-steroidal anti-inflammatory drug, on trimethadione metabolism as an indicator of hepatic drug-oxidizing capacity in beagle dog.

1. We examined the effects of N-methoxy-3-(3,5-di-tert-butyl-4- hydroxybenzylidene pyrrolidin-2-one (E-5110), a novel non-steroidal anti-inflammatory drug, on the pharmacokinetics of trimethadione (TMO) and characterized the P450 isozymes involved in the metabolism of TMO in beagle dog. 2. In the E-5110-treated dog (50 mg/kg/day for 7 days: oral) the plasma half-life (t1/2) and the area under the curve (AUC) of TMO (4 mg/kg, i.v.) in vivo were decreased, and total body clearance (CL) was increased; the apparent volume of distribution (Vd) was relatively unchanged. 3. Contents of P450 and b5, and the activity of p-nitroanisole O-demethylase and benzphetamine N-demethylase in vitro were significantly increased compared with controls by repeated E-5110 treatment in dog. 4. Contents of CYP2B and 3A were increased by E-5110 pretreatment in dog. 5. TMO N-demethylation was inhibited by the anti-CYP2B and 3A IgG fractions in liver microsomes obtained from the E-5110-treated dog. 6. Results of both the in vivo and in vitro studies of the effects of E-5110 treatment in dog on TMO indicate that these effects may be attributed to the induction of CYP2B and 3A.

Animals↗

Dual effects of a novel thienodiazepine platelet-activating factor antagonist, on drug-oxidizing enzymes in beagle dog.

1. We have examined the effects of (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8, 11-dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3, 2-f][1, 2, 4]triazolo[4, 3-a][1, 4]diazepine (E-6123), a novel thienodiazepine platelet-activating factor antagonist, on drug-oxidizing capacity in beagle dog, using antipyrine (AP) and trimethadione (TMO) as two model substrates. 2. The plasma half-life (t1/2) and area under the curve (AUC) of AP (0.5 mg/kg, i.v. injection) increased in a dose-dependent manner after a single oral dose of E-6123 (0.2, 1 or 10 mg/kg), whereas the total body clearance (Cl) of AP was decreased, and the apparent volume of distribution (Vd) was unchanged. 3. The pharmacokinetic parameters (t1/2, Cl and AUC) of the metabolism of TMO (4 mg/kg, i.v.) after repeated oral administration of E-6123 (10 mg/kg for 7 days) were not significantly changed in comparison with findings in control dog. The ratio of dimethadione (DMO), being the only TMO metabolite, to TMO in plasma after i.v. administration of TMO in E-6123-treated dog was increased only 5 and 15 min after the final dose, but was not changed at other sampling times (0.5, 1, 2 4, 6, 8 and 12 h). 4. The content of b5, the activity of p-nitroanisole O-demethylase and benzphetamine N-demethylase were significantly increased, compared with controls, by repeated E-6123 treatment. However, aniline hydroxylase activity was not significantly changed. 5. Content of P450 2B was significantly increased in E-6123 treated dog, while that of 3A was not.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prevalence of hepatitis C virus with different genotypes determined by a group-specific antibody assay in Japanese patients with chronic liver diseases due to hepatitis C virus infection.

Hepatitis C virus (HCV) genotypes (groups I and II) were determined by a newly developed C14 assay in which antibodies against group-specific recombinant proteins of the NS4 region were measured by ELISA (enzyme-linked immunosorbent assay). The genotypes determined by the C14 assay were compared to those determined by a polymerase chain reaction (PCR) in 50 patients. The HCV genotypes determined by both methods were consistent in 78% of the patients. The results of the assays were not contradictory in any patient. The sensitivity of the C14 assay was as high as over 90%. Frequency of HCV genotypes was studied in 300 patients with chronic liver diseases type C by using the C14 assay. The prevalence of groups I and that of II in patients with chronic hepatitis were 73% and 21%, the correspondence figures in those with liver cirrhosis 80% and 13%, and in those with hepatocellular carcinoma 81% and 13%, respectively. The clinical characteristics were similar between the patients with group I and II HCV infections in each disease category. In conclusion, the C14 assay is useful for epidemiological studies of HCV genotypes, and group I is a major HCV genotype of chronic liver diseases type C in Japan.

Adult↗

[Evolution of hepatitis C virus (HCV) viremia and adaptation of HCV in persistent infection in patients with acute hepatitis].

HCV viremia had ceased in majority of patients with acute resolving hepatitis C, and it continued for at least 1 year in all patients with chronicity. The HCV RNA titer in serum decreased markedly after the onset of acute hepatitis and then re-elevated in patients with chronicity. During this period, amino acid substitution rate in the E2/NS1 region (especially in HVR) was significantly higher in patients with acute hepatitis than in patients with chronic hepatitis. When patients with acute hepatitis C became persistent HCV carriers, the substitution rate decreased to the level seen in patients with chronic hepatitis. These observations suggest that rapid substitution of the amino acid sequence in the HVR of the E2/NS1 region may be one of the mechanisms of persistent HCV infection.

Acute Disease↗

Effects of a newly synthesized dihydropyridine, NZ-105, on intracellular Ca transients and tension in ferret ventricular muscles.

We investigated the effects of a newly synthesized dihydropyridine (DHP) derivative (NZ-105) on intracellular Ca transients and contraction in ferret ventricular muscles, using the aequorin method. Low concentrations of NZ-105 (10(-9)-10(-7) M) showed no significant effects on the light signal of aequorin and tension in twitch. High concentrations of NZ-105 (10(-6)-10(-5) M) inhibited the peaks of the light signal and tension without altering their time courses. The relation between the peaks of the light signal and tension in twitch, measured in solutions with varying Ca2+ concentrations, was shifted to the left by NZ-105. The relation between [Ca2+]i and tension measured in tetanic contraction was also shifted to the left by NZ-105. These results suggest that the inhibitory effect of NZ-105 on contraction in mammalian cardiac muscle is curtailed by an increase in Ca sensitivity of the contractile elements.

Animals↗

Effect of the adrenergic beta 3-agonist, BRL37344, on heat production by brown adipocytes in obese and in older rats.

Heat production by isolated brown adipocytes, from hypothalamic obese rats and from older rats, was investigated by microcalorimetry. The obese and older rats were 12 and 40 weeks-old, respectively. The basal heat production by the brown adipocytes was significantly less in the obese and older rats than in control rats 12 weeks of age. Isoproterenol and a novel adrenergic beta 3-agonist, BRL37344, increased heat production in a concentration-dependent manner in all rats. The effects of isoproterenol were significantly less in the obese group than in the controls, while BRL37344 stimulated heat production in all rats almost identically. These results suggest that (1) the heat producing capacity of brown adipocytes is reduced by hypothalamic obesity and aging, and (2) BRL37344 might be useful as an anti-obesity drug.

Adipose Tissue, Brown↗

Chloride-dependent potentials and their effects on firing pattern in guinea-pig cingulate cortical neurons.

Intracellular recordings were made from pyramidal neurons in the anterior cingulate cortex layer V of the guinea-pig slice preparation. An oscillation in membrane potential occurred when the membrane was depolarized to a subthreshold level (e.g. -60 mV), and the oscillation triggered repetitive firing. The frequency of the spontaneous firing varied with the membrane potential: frequencies were 2.9 +/- 1.4, 6 +/- 1, 13 +/- 3, and 17 +/- 3 Hz at the membrane potentials of -60, -58, -55, and -40 mV, respectively. Bicuculline (500 nM to 10 microM) increased the firing rate when the membrane potential was kept around threshold level by DC current injection. 2-Hydroxysaclofen and low Cl- (43 mM) also increased the firing rate, but 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonate (SITS, 250 microM) did not change the firing rate. Strychnine (1 to 3 microM) had no effect on the spontaneous firing. These results suggest that the firing frequency of cingulate pyramidal neurons is modulated by GABA tonically released by interneurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Opioid actions on rat anterior cingulate cortex neurons in vitro.

Intracellular recordings were made from layer V pyramidal neurons in slices of rat anterior cingulate cortex, using electrodes that contained potassium methylsulfate and biocytin. [Met5]enkephalin (300 nM to 30 microM) reversibly reduced the amplitude of EPSPs evoked by stimulation of the subcortical white matter; the half-maximal concentration was about 800 nM. These EPSPs were blocked by (+/-)-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione. [Met5]enkephalin also reduced the amplitude of bicuculline-sensitive IPSPs evoked by stimulation within layer V; the half-maximal concentration was about 60 nM. Both these actions of [Met5]enkephalin were mimicked by the delta-selective agonist DPDPE (Tyr-D-Pen-Gly-Phe-D-Pen) but not by the mu-selective agonist DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol); they were blocked by the delta-selective antagonist naltrindole (apparent dissociation constant of about 0.3 nM) but not by the mu-selective antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2). [Met5]enkephalin did not change the amplitudes of depolarizations evoked by direct application of glutamate or hyperpolarizations evoked by direct application of muscimol (at -55 mV). Fifty percent (22 of 45) of pyramidal cells were hyperpolarized by [Met5]enkephalin; this resulted from an increase in potassium conductance, and it was mimicked by DPDPE and blocked by naltrindole. Five of seven nonpyramidal cells were hyperpolarized by [Met5]enkephalin; this was mimicked by DAMGO and blocked by CTOP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Antiplatelet therapy in patients with cerebral thrombosis at the chronic phase--assessment of its effect on coagulation and fibrinolytic parameters].

We studied the effect of antiplatelet therapy not only on the secondary prevention of stroke but also on the suppression of vascular damages in patients with cerebral thrombosis at the chronic phase. We measured von Willebrand factor (vWF) as a marker for the endothelial system, and coagulation and fibrinolytic parameters in addition to platelet functions. The platelet aggregation and markers for platelet activation were monitored for the adequate inhibition of platelets. Twenty-one patients were treated with 200 mg ticlopidine. 9 patients with 100 mg ticlopidine and 60-150 mg acetylsalicylic acid, and 18 patients with 200 mg cilostazol daily. The mean duration of follow up was 8.4 +/- 3.0 months. A patient was attacked by a recurrent stroke, but no fatal vascular events occurred during the period. A significant decrease was observed in the collagen- and ADP-induced platelet aggregation and markers for platelet activation such as platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) by the antiplatelet therapy. In addition, the activities of coagulation factor VIII (FVIII) and vWF, markers for vascular damages, showed a significant decrease. The results suggest that the antiplatelet therapy could ameliorate the vascular damage through the inhibition of platelet function. Moreover, thrombin-antithrombin III complex (TAT) and alpha 2-plasmin inhibitor-plasmin complex (PIC), markers for the activation of coagulation and fibrinolytic systems, decreased significantly, suggesting that the treatment inhibits the activation of coagulation and fibrinolytic systems induced by the platelet activation. The activities of FVIII and vWF decreased significantly when the level of beta TG or that of PF4 lowered sufficiently by the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[A case of Mycobacterium avium complex pulmonary disease in the early phase].

A 51-year-old female was admitted to our hospital due to hemoptysis. Chest radiography revealed infiltrations in the middle lobe. Computed tomography (CT) of the thorax showed clusters of small nodules associated with a small cavity in the middle lobe, ligula and lower lobe of the right lung. Bronchiectasis was not detected. Transbronchial lung biopsy specimen (B4a) showed epithelioid cell granulomas with giant cells, and Mycobacterium avium was isolated in 4-week cultures of bronchial washings. This could be a case of early phase of pulmonary Mycobacterium avium complex infection in a patient without a so-called underlying condition. CT findings were characteristic and useful for the early diagnosis of MAC infection.

Biopsy↗

Cocaine enhancement of the action of 5-hydroxytryptamine in rat cingulate cortex in vitro.

Intracellular recordings were made in vitro from pyramidal neurons in layer V of the anterior cingulate cortex of the rat. 5-Hydroxytryptamine (5-HT) reduced the amplitude of the excitatory postsynaptic potential; receptor-selective agonists and antagonists indicated that this resulted from activation of the 5-HT1B receptor. The action of 5-HT was enhanced by cocaine (300 nM-3 microM); 1 microM cocaine increased sensitivity to 5-HT about 10-fold. The results suggest that cocaine is similarly effective to potentiate the action of 5-HT in the prefrontal cortex as in other brain regions. This may contribute to its overall in vivo effects.

Animals↗

Detection of hepatitis C virus markers and hepatitis C virus genomic-RNA after needlestick accidents.

BACKGROUND: Needlestick accidents are a problem among health care workers. Using sensitive new assays, we evaluated the prevalence and features of hepatitis C virus (HCV) infection following a needlestick accident. METHOD: The clinical outcome and evolution of serum HCV markers were assessed in 90 hospital employees (recipients) who sustained needlestick injuries (selected from 146 episodes) involving 92 patients with clinical non-A, non-B hepatitis (donors). RESULTS: Of the 92 patient donors, 62 (67%) and 88 (96%) were anti-C100-3 and second-generation anti-HCV positive, respectively, at the time of the needlestick accident. During the follow-up period (> or = 6 months), acute non-A, non-B hepatitis developed in three of 90 recipients about 1 month after the accident. The three respective donors were positive for serum HCV-RNA at the time of the accident. Two of the three recipients became HCV-RNA positive just after the onset of hepatitis, and subsequently, HCV antibodies developed. None of the remaining 87 recipients had any clinical or laboratory evidence of hepatitis during follow-up, or experienced seroconversion for anti-C100-3 or second-generation anti-HCV. We measured additional HCV markers in 20 of the 89 donors; 16 had evidence of HCV infection (HCV-RNA). However, none of the respective recipients of any of these 20 became positive for HCV markers during follow-up. CONCLUSION: Although transmission of HCV infection by needlestick injury may be infrequent, such transmission does occur. Appropriate precautions should be taken to protect health care workers.

Accidents, Occupational↗

Abrogation of tumor-inhibitory MRC-OX8+ (CD8+) effector T-cell generation in rats by selective depletion of neutrophils in vivo using a monoclonal antibody.

These studies were designed to examine the role of neutrophils in transplantation immunity to syngeneic rat tumors. We have earlier reported that specific transplantation immunity to syngeneic transplanted tumors is abrogated by selective depletion of peripheral-blood neutrophils by administration of a monoclonal antibody (MAb) (RP-3) at the time of immunization with X-irradiated tumor cells. In order to elucidate the mechanisms of this phenomenon, we have now examined whether induction of the sensitized spleen cells that inhibit the growth of tumor cells is inhibited by RP-3 treatment at the time of in vivo priming with tumor-associated antigen (TAA). Neutrophils were required to induce the sensitized T cells responsible for tumor inhibition with Winn's assay. In addition, CD8+ T cells are proved to be effector cells in an assay system of tumor-growth inhibition using a diffusion chamber. Our results indicate that neutrophils are required for priming rats with TAA to induce CD8+ effector T cells in tumor inhibition.

Animals↗

Tumor necrosis factor stimulates the synthesis and secretion of biologically active nerve growth factor in non-neuronal cells.

Tumor necrosis factor-alpha (TNF) markedly stimulates the synthesis and secretion of immunoreactive nerve growth factor (NGF) in quiescent mouse fibroblasts, which is a result of increase in the NGF mRNA level. NGF produced by TNF-treated fibroblasts has a molecular mass of 13 kDa on SDS-polyacrylamide gel electrophoresis, which is consistent in size with the subunit of mouse beta-NGF, and induces neurite outgrowth in paravertebral sympathetic neurons. Several peptide growth factors such as basic fibroblast growth factor (bFGF) and epidermal growth factor also stimulate NGF production in the cells, but not platelet-derived growth factor. The dose responses of TNF and bFGF to stimulate NGF production in the cells are, respectively, similar to those to induce cell proliferation. However, no correlation is observed between the ability of these growth factors to stimulate NGF production and that to induce cell proliferation. Thus, the stimulation of NGF production in the cells seems to be a specific activity of TNF and some other growth factors. TNF stimulates the synthesis and secretion of NGF also in other cells such as human glioblastoma cells. These findings suggest that TNF plays a role in regulating neuronal cell function through an indirect mechanism by which it stimulates NGF production in glial cells and fibroblasts.

3T3 Cells↗