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Biomedical subjects

T Goto

Publications and source records attributed to T Goto.

At least 163 records · Page 9Linked to original sources
PubMed2000

The analgesic effect profile of FR122047, a selective cyclooxygenase-1 inhibitor, in chemical nociceptive models.

The pharmacological profile of the analgesic agent, 1-[(4, 5-bis(4-methoxyphenyl)-2-thiazoyl)carbonyl]-4-methylpiperazine hydrochloride (FR122047), was investigated. In recombinant human cyclooxygenase enzyme assays, the inhibition of prostaglandin E(2) formation by FR122047 was 2300 times more selective for cyclooxygenase-1 than cyclooxygenase-2. Oral administration of FR122047 (3.2-100 mg/kg) dose dependently reduced the phase 2 response (10-60 min) of the formalin test in rats. This effect was 3 times less potent than that of indomethacin. FR122047 (1-32 mg/kg; p. o.) showed a dose-dependent analgesic effect against the acetic acid-induced writhing response in mice. Furthermore, FR122047 (0. 01-10 mg/kg, p.o.) inhibited the increase in 6-keto prostaglandin F(1alpha) level in acetic acid-injected mouse peritoneal cavity. However, a selective cyclooxygenase-2 inhibitor, NS-398, had no effect in these cyclooxygenase-1 sensitive pain models. These results suggest that FR122047, a selective cyclooxygenase-1 inhibitor, shows an analgesic effect in chemical nociceptive models and may be a useful analgesic agent.

Acetic Acid↗
PubMed2000

Role of troponin I isoform switching in determining the pH sensitivity of Ca(2+) regulation in developing rabbit cardiac muscle.

Skinned muscle fibers prepared from fetal rabbit heart (28 days of gestation) showed a marked resistance to acidic pH in the Ca(2+) regulation of force generation, compared to the fibers prepared from adult heart. SDS-PAGE and immunoblot analysis showed that the slow skeletal troponin I was predominantly expressed in the fetal cardiac muscle, while the cardiac isoform was predominantly expressed in the adult cardiac muscle. Direct exchange of purified slow skeletal and cardiac troponin I isoforms into these skinned muscle fibers revealed that cardiac troponin I made the Ca(2+) regulation of contraction sensitive to acidic pH just as in the adult fibers, whereas slow skeletal troponin I made the Ca(2+) regulation of contraction resistant to acidic pH just as in the fetal fibers. These results demonstrate that the troponin I isoform switching accounts fully for the change in the pH dependence of Ca(2+) regulation of contraction in developmental cardiac muscle.

Aging↗
PubMed2000

Highly efficient electro-gene therapy of solid tumor by using an expression plasmid for the herpes simplex virus thymidine kinase gene.

We report successful electro-gene therapy (EGT) by using plasmid DNA for tumor-bearing mice. Subcutaneously inoculated CT26 tumor was subjected to EGT, which consists of intratumoral injection of a naked plasmid encoding a marker gene or a therapeutic gene, followed by in vivo electroporation (EP). When this treatment modality is carried out with the plasmid DNA for the green fluorescent protein gene, followed by in vivo EP with the optimized pulse parameters, numerous intensely bright green fluorescent signals appeared within the tumor. EGT, by using the "A" fragment of the diphtheria toxin gene significantly inhibited the growth of tumors, by about 30%, on the flank of mice. With the herpes simplex virus thymidine kinase gene, followed by systemic injection of ganciclovir, EGT was far more effective in retarding tumor growth, varying between 50% and 90%, compared with the other controls. Based on these results, it appears that EGT can be used successfully for treating murine solid tumors.

Animals↗
PubMed2000

Zinc deficiency and taste dysfunction; contribution of carbonic anhydrase, a zinc-metalloenzyme, to normal taste sensation.

The present study was designed to clarify the effect of zinc deficiency on sodium chloride preference, the lingual trigeminal and taste nerves transduction, and carbonic anhydrase (CA) activity of the tongue surface and salivary gland. Male SD rats, 4 weeks old, were divided into four groups, and fed zinc-deficient (Zn-Def), low-zinc (Low-Zn), and zinc-sufficient diets with free access (Zn-Suf) and pair-feeding (Pair-fed). After taking part in the preference tests for 42 days, the rats were provided for the chorda tympani and lingual trigeminal nerves recordings, then finally sacrificed and the tongue and submandibular gland excised to measure CA activity. Sodium chloride preference increased only after 4 days of the feeding of zinc-deficient and low-zinc diets, which means that the taste abnormality appears abruptly in zinc deficieny and even though in marginal zinc deficiency. Reduced CA activities of the taste-related tissues in zinc-deficient group paralleled well with the decreased taste and lingual trigeminal nerves sensitivities.

Animals↗
PubMed2000

Partial functional recovery of paraplegic rat by adenovirus-mediated gene delivery of constitutively active MEK1.

Spinal cord injury in adult mammals results in little axonal regeneration, although the mechanism of regeneration failure still remains elusive. Recent research has revealed that activation of the extracellular-signal-regulated kinases (ERKs) plays an important role in the neurite outgrowth. In the present study, we constructed a replication-defective adenovirus vector carrying mutated form of MEK1 (CA-MEK virus), which constitutively activate ERK pathway, and investigated its effect on thoracic spinal cord injury model in young adult rats as well as neurite outgrowth in vitro. In rat pheocromocytoma cell line PC12 cells, CA-MEK virus infection induced sustained activation of ERKs and stimulated neurite outgrowth in the absence of neurotrophic factors. In rat spinal cord transection model, injection of CA-MEK virus into the completely transected spinal cord efficiently activated ERKs in the supraspinal neurons and induced axonal regeneration across the transection site, which was confirmed by anterograde labeling with wheat-germ-agglutinin conjugated peroxidase (WGA-HRP). Spinal cord evoked potentials (SCEP) showed that these regenerated axons were electroconductive. Most importantly, CA-MEK virus-treated rats showed significant recovery of hind limb function 2 weeks after operation compared to the control rats treated with no virus or LacZ virus. These results suggest that adenovirus-mediated CA-MEK gene transduction offers a novel strategy for the gene therapy of spinal cord injury.

Adenoviridae↗
PubMed2000

Craniocervical and aortic atherosclerosis as neurologic risk factors in coronary surgery.

BACKGROUND: Advanced age is associated with increased systemic atherosclerosis and is a consistent neurologic risk factor after coronary artery bypass grafting (CABG). METHODS: We studied prospectively whether varying degrees of a total atherosclerotic score derived from the brain, carotid arteries, and ascending aorta predicted postoperative neuropsychologic (NP) dysfunction and stroke in 177 elderly patients (> or = 60 years) undergoing CABG. RESULTS: Group L (low total atherosclerotic score) had rates of NP dysfunction of 25% and 4%, group I (intermediate) had rates of 33% and 22%, and group H (high) had rates of 79% and 43% on postoperative days 1 and 7, respectively (p < 0.001). The incidence of stroke was higher in group H (14.3%) than in groups I and L (7.8% and 0.9%; p = 0.013). Stepwise logistic regression analysis demonstrated the significant predictors of NP dysfunction on postoperative day 7 to be total atherosclerotic score, peripheral vascular disease, and diabetes mellitus, and those of stroke to be total atherosclerotic score, peripheral vascular disease, and hyperlipidemia. CONCLUSIONS: Perioperative evaluation of craniocervical and aortic atherosclerosis is useful to identify a high-risk patient at postoperative NP dysfunction and stroke after CABG.

Aged↗
PubMed2000

The spinal antinociceptive effect of FR140423 is mediated through kyotorphin receptors.

We investigated the antinociceptive effect of a novel anti-inflammatory and analgesic drug, 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyraz ole (FR140423), in the tail-pinch test in mice, and evaluated the mechanism of action of FR140423 using L-leucyl-L-arginine (Leu-Arg), a kyotorphin (endogenous Met-enkephalin releaser) receptor antagonist, L-NG-nitroarginine methylester (L-NAME), an inhibitor of nitric oxide (NO) synthase, and methylene blue (MB), an inhibitor of activation of guanylate cyclase. Oral administration of FR140423, at doses of 5-80 mg/kg, produced a dose-dependent antinociceptive effect with an ED50 value of 18 mg/kg. This antinociception was reversed by intrathecal (i.t.) (10 microg/mouse), but not by intracerebroventricular (i.c.v.) (100 microg/mouse), injection of Leu-Arg. Moreover, the antinociceptive effect of i.t. injection of FR140423 with an ED50 value of 3.7 microg/mouse was completely antagonized by co-administered Leu-Arg 10 microg/mouse. However, L-NAME (2000 mg/kg s.c.) and MB (200 mg/kg s.c.) did not antagonize the antinociception of FR140423. These findings suggest that FR140423 plays a role in nociceptive modulation in the spinal cord, being antinociceptive via the kyotorphin-Met-enkephalin pathway but not via the peripheral NO-cyclic GMP pathway.

Analgesics, Opioid↗
PubMed2000

Disinfection potential of electrolyzed solutions containing sodium chloride at low concentrations.

Electrolyzed products of sodium chloride solution were examined for their disinfection potential against hepatitis B virus (HBV) and human immunodeficiency virus (HIV) in vitro. Electrolysis of 0.05% NaCl in tap water was carried out for 45 min at room temperature using a 3 A electric current in separate wells installed with positive and negative electrodes. The electrolyzed products were obtained from the positive well. The oxidation reduction potential (ORP), pH and free chlorine content of the product were 1053 mV, pH 2.34 and 4.20 ppm, respectively. The products modified the antigenicity of the surface protein of HBV as well as the infectivity of HIV in time- and concentration-dependent manner. Although the inactivating potential was decreased by the addition of contaminating protein, recycling of the product or continuous addition of fresh product may restore the complete disinfection against bloodborne pathogens.

Acids↗
PubMed2000

Contrast-enhanced immunoelectron microscopy for Helicobacter pylori.

Since a method of contrast enhancement for immunoelectron microscopy has not been available in bacteriology, the morphological localization of proteins of Helicobacter pylori is not well known. In this report, we established a method of contrast enhancement in immunoelectron microscopy in this organism. Immunostained ultrathin sections are stained with a mixture of alcian blue and osmium tetroxide prior to staining with uranyl acetate. This method of staining provided good contrast enhancement of the bacterial cell wall and membrane without any loss of immunolabeled gold particles on the ultrathin section.

Acrylic Resins↗
PubMed2000

Fusion of uninfected T-cells occurs with immature HIV-1 protease-mutant, but not morphologically similar protease inhibitor derived particles.

Protease inhibitors are widely used in the treatment of human immunodeficiency virus type 1 (HIV-1)-infected individuals and show a drastic effect on the reduction of virus load. We previously reported that doughnut-shaped, protease-defective gp120-containing HIV-1 particles from an L-2 cell clone, carrying a provirus with mutations at the pol (protease), env (gp41) and nef genes, rapidly and more effectively induces virus particle-mediated syncytia formation of uninfected T-cells, than a parental wild-type laboratory strain of HIV-1 (LAI). In this study, we examined the possibility of whether enhanced syncytia formation is mediated by morphologically similar doughnut-shaped particles obtained after treatment of LAI-infected cells with the protease inhibitors L-689, 502, DMP-323, RO-31-8959, and KNI-272. Utilizing such protease inhibitor-induced particles and a clone of MOLT-4 cells, we could not detect any enhancement of syncytia formation, over that seen with wild-type LAI particles. This result should alleviate concerns of patients on highly active antiretroviral therapy (HAART), that protease inhibitors might accelerate progression of the disease through enhanced production of defective, 'immature'-appearing particles.

Anti-HIV Agents↗
PubMed2000

FK506 inhibition of histamine release and cytokine production by mast cells and basophils.

Histamine release and cytokine production by mast cells and basophils are thought to be closely involved in the pathogenesis of allergic diseases. Some reports show that FK506 (tacrolimus hydrate) inhibited histamine release and cytokine production by mast cells and basophils. However, as the effects of FK506 has not been compared with those of clinically used drugs in those reports, the clinical relevancy of FK506 inhibition remained unclear. In this paper, we compared the actions of FK506 with those of steroids or disodium cromoglycate (DSCG) which has been clinically used. FK506 inhibited histamine release by Brown-Norway rat peritoneal mast cells more potently than steroids and especially DSCG. FK506 also inhibited histamine release by a mast rat basophilic leukemia (RBL)-1 cell line and human peripheral blood basophils, whereas steroids failed to inhibit histamine release by human basophils. FK506 as well as steroids inhibited TNF-alpha and IL-4 production by RBL-1 cells. FK506 was therefore more effective than steroids and DSCG in inhibiting histamine release, and it also had the ability of inhibiting cytokine production by mast cells as steroids do. We concluded that FK506 might regulate allergic diseases via these actions, judging from the viewpoint of clinical relevancy.

Animals↗
PubMed2000

Simultaneous analysis of naproxen, nabumetone and its major metabolite 6-methoxy-2-naphthylacetic acid in pharmaceuticals and human urine by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method for simultaneous determination of naproxen (NAP), nabumetone (NAB) and its major metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA), was developed for the application to pharmaceuticals and human urine. Isocratic reversed-phase HPLC was employed for quantitative analysis using triethylamine and 1-heptanesulfonic acid sodium salt (HSA) as ion-pair reagents. Urine samples were purified by solid-phase extraction using Bond-Elut Certify II cartridges containing reversed-phase and anion exchange functionalities. The HPLC assay was carried out using a Wakosil ODS 5C18 column (5 microm, 150 x 4.6 mm, i.d.). The mobile phase consisted of 0.5 g of HSA dissolved in 1,000 ml of a mixture of acetonitrile, water and triethylamine (500:500:1, v/v) adjusted with phosphoric acid to pH 3. The calibration curves of NAP and NAB showed good linearity in the concentration range 32-160 microg/ml with UV detection (270 nm) for pharmaceuticals. In the low concentration ranges (8-96 ng of NAP per ml, 24-288 ng of NAB per ml and 5.6-67.2 ng of 6-MNA per ml), the calibration curves were also obtained with fluorimetric detection (excitation 280 nm, emission 350 nm) for biological fluids. The correlation coefficients were better than 0.999 in all cases. The lower limits of detection (defined as a signal-to-noise ratio of about 3) were approximately 0.3 ng for NAP, 1.5 ng for NAB and 0.2 ng for 6-MNA. The procedure described here is rapid, simple, selective, and is suitable for routine analysis of pharmaceuticals and pharmacokinetic studies in human urine samples.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Ultrasonographic demonstration of manipulation-related aortic injuries after cardiac surgery.

OBJECTIVES: This study was performed to evaluate the frequency and risk factors associated with new aortal lesions induced by surgical manipulation and their correlation with postoperative stroke. BACKGROUND: Little is known about the causative mechanism of intraoperative atheroembolism after cardiac surgery. METHODS: Epiaortic echocardiography was performed before cannulation and after decannulation in 472 patients undergoing cardiac surgery with extracorporeal circulation. RESULTS: A new lesion in the ascending aortal intima was identified in 16 patients (3.4%) after decannulation. New lesions were severe, with mobile lesions or disruption of the intima in 10 patients. Six of the severe lesions were related to aortic damping and the other four to aortic cannulation. Three patients in this group had postoperative stroke. Univariate analysis identified only the maximal thickness of the atheroma near the aorta manipulation site as a predictor of new lesions. The incidence of new lesions was 11.8% if the atheroma was approximately 3 to 4 mm thick and as high as 33.3% if the atheroma was >4 mm, but only 0.8% when it was <3 mm. Total 10 patients (2.1%) sustained neurological complications. Arteriosclerosis obliterans, atherosclerosis of the aorta and new mobile lesions were identified as predictors of strokes. CONCLUSIONS: This study demonstrated an association between new lesions created by surgical maneuvers and postoperative stroke. Embolic strokes were more likely to occur if new lesions were complicated with intimal disruption, especially of the mobile type. Modifications in surgical procedures will be needed if thick plaque (especially >4 mm) is noted near the manipulation site.

Adult↗