Biomedical subjects

K Yabe

Publications and source records attributed to K Yabe.

At least 37 records · Page 2Linked to original sources

PubMed1999

Involvement of adenosine receptor, potassium channel and protein kinase C in hypoxic preconditioning of isolated cardiomyocytes of adult rat.

A possible mechanism for hypoxic preconditioning of adult rat cardiomyocytes was pharmacologically investigated. Isolated cardiomyocytes in all experimental groups were incubated for 120 min under hypoxic conditions followed by 15-min reoxygenation (sustained H/R). Sustained H/R decreased rod-shaped cells. Exposure of the cardiomyocytes to 20-min of hypoxia/30-min reoxygenation (hypoxic preconditioning) attenuated the sustained H/R-induced decrease in rod-shaped cells. The effects of hypoxic preconditioning were abolished by treatment with the protein kinase C (PKC) inhibitor polymyxin B, but abolished by neither the adenosine A1/A2-antagonist sulfophenyl theophylline (SPT) nor the ATP-sensitive potassium channel (K(ATP) channel) blocker glibenclamide. In another series of experiments, cardiomyocytes were incubated without hypoxic preconditioning in the presence of either the PKC activator PMA, adenosine or K(ATP)-channel opener nicorandil and then subjected to sustained H/R. Treatment of the cells with PMA, adenosine or nicorandil mimicked the effects of hypoxic preconditioning. The effects of treatment with adenosine and nicorandil were abolished by polymyxin B treatment. Combined treatment with both SPT and glibenclamide abolished the effects of hypoxic preconditioning, whereas it failed to abolish PMA-induced cytoprotection. These results suggest that the activation of PKC in hypoxic preconditioned cardiomyocytes coupled independently with stimulation of adenosine receptor or opening of K(ATP) channel, either of which is fully enough to exert the cytoprotective effects.

Animals↗

PubMed1999

[Is portal infusion chemotherapy uneffective for hepatic recurrence after resection for colorectal cancer?].

Sixty-six patients with colorectal cancer were studied regarding effects of prevention of hepatic recurrence in completely performed portal infusion chemotherapy. The regimen was continuous administration of 500-875 mg/body of 5-FU for 7 days and intraportal administration of 10 mg of MMC before and after 5-FU administration. Hepatic recurrence rate was 7.6% and the five year survival rate was 83.3% in portal infusion group, and 16% and 71.3% in the control group; the difference was not significant. However, the hepatic recurrence rate in patients administered more than 4 g of 5-FU was 2.5%; there was a significant difference between the portal group and control group. The five-year survival rate for patients administered more than 4 g of 5-FU was 92.3%, which was significantly higher than at less than 4 g. Excellent effects for prevention of hepatic recurrence and prognosis were obtained in patients administered more than 4 g of 5-FU. Thus, the compliance of 5-FU in portal infusion chemotherapy is important. Also, administration of MMC is suspected to enhance the effect of portal infusion chemotherapy.

Adult↗

PubMed1998

Transcript of a homolog of aflR, a regulatory gene for aflatoxin synthesis in Aspergillus parasiticus, was not detected in Aspergillus oryzae strains.

Some strains of Aspergillus oryzae were shown to have homologs of aflR, a regulatory gene for aflatoxin synthesis in Aspergillus parasiticus. Transcription of an aflR homolog was examined in six strains of A. oryzae having the homologs, using polymerase chain reaction (PCR) coupled with reverse transcription. No PCR product was obtained when the RNA prepared from the A. oryzae strains cultivated under aflatoxin-producing condition was used as template for amplification of the aflR cDNA. By contrast, a PCR product of the expected size was obtained with RNA from A. parasiticus NIAH-26 processed by the same procedure. From genomic DNA of these strains, PCR products of the same size as above were obtained. Possible degradation of the aflR mRNA in the RNA preparation of the A. oryzae strains was negligible, because the calmodulin transcript was detected by PCR from the same RNA samples. Thus, the aflR homologs in the non-aflatoxigenic A. oryzae strains examined are not expressed even under aflatoxin-producing condition.

Aflatoxins↗

PubMed1998

Quantitative mapping analyzer for determining the distribution of neurochemicals in the human brain.

We developed a human brain mapping analyzer to determine the quantitative distribution of specific molecules, such as neurotransmitters or neuromodulators, based on a fluorescence microphotometry system that we had previously developed. The immunohistochemical fluorescence emitted from each microarea of a brain slice is collected into a photomultiplier tube through the pinhole and objective lens of a microscope. The brain slice is moved in the x- or y-direction by a motorized scanning stage under the objective lens, and the fluorescence intensities are measured quantitatively. The scanning speed is approximately 100 microareas/s, the maximum stage motion is 150 x 150 mm, and an unlimited amount of data can be gathered continuously by transfer to external memory devices. In this paper, this analyzer is characterized in detail, and the methods used for the preparation and analysis of human brain slices are described. As an example, the cholinergic distribution in hemispheric coronal slices of the adult human brain is analyzed. Each slice, immunohistochemically stained for choline acetyltransferase, was divided into approximately 3 million microareas (one area is 50 microm in diameter), and the distribution of the cholinergic neurons is shown.

Aged↗

PubMed1998

Beta-casomorphin-5 stimulates neurite outgrowth in a mouse neuroblastoma cell line (Neuro-2a).

We studied the effect of beta-casomorphin-5 (mu-acting opioid peptides derived from milk protein beta-casein) on neurite outgrowth of mouse neuroblastoma cell line, Neuro-2a. Beta-casomorphin-5 stimulated neurite outgrowth of Neuro-2a cells in a naloxone-reversible manner. The stimulating effect of beta-casomorphin-5 was observed even at picomolar concentrations. The selective mu-agonist, (D-Ala2, N-Me-Phe4, Gly5-ol)-enkephalin (DAMGO) exhibited the similar stimulating effect only at micromolar concentrations. On the other hand, (D-Pen(2,5))-enkephalin (DPDPE) (a delta-agonist), U-50,488 (a kappa-agonist), and endogenous opioid peptides, such as enkephalins and dynorphin A (1-13), showed no such stimulating effect. These results suggest that the neurite outgrowth-stimulating action of beta-casomorphin-5 may be mediated via a receptor which has mu-like characteristics and high sensitivity to beta-casomorphin-5, and that beta-casomorphins may play a role as a neurite elongation factor during the suckling period.

Animals↗

PubMed1998

Effects of high-intensity resistance training on bone mineral density in young male powerlifters.

The effects of high-intensity resistance training on bone mineral density (BMD) and its relationship to strength were investigated. Lumbar spine (L2-L4), proximal femur, and whole body BMD were measured in 10 male powerlifters and 11 controls using dual-energy X-ray absorptiometry (DXA). There were significant differences in lumbar spine and whole body BMD between powerlifters and controls, but not in proximal femur BMD. A significant correlation was found between lumbar spine BMD and powerlifting performance. These results suggest that high-intensity resistance training is effective in increasing the lumbar spine and whole body BMD.

Absorptiometry, Photon↗

PubMed1998

Aspergillus oryzae with and without a homolog of aflatoxin biosynthetic gene ver-1.

Part of the nucleotide sequence of the ver-1 homolog in each of two strains of Aspergillus oryzae, Aspergillus sojae, and Aspergillus flavus were compared with two homologs in Aspergillus parasiticus. The homologs in A. oryzae and A. sojae (non-aflatoxin-producers) exhibited an extremely high degree (93.8-99.8% for A. oryzae, and 96.0-99.5% for A. sojae) of sequence identify with that of A. flavus and A. parasiticus. No two strains within the same species, except A. sojae, were identical. No sequence fingerprint was found to distinguish between A. oryzae and A. flavus, or between A. sojae and A. parasiticus. The predicted partial amino acid sequences (181 amino acids) of the ver-1 homologs had at most two amino acid changes relative to A. parasiticus SYS-4 ver-1. Transcripts of ver-1 homologs in the strains of A. oryzae and A. sojae examined were not detected by the polymerase chain reaction coupled with reverse transcription. By Southern analysis, a total of 46 strains of A. oryzae were examined for the presence of the ver-1 homolog. The homolog was detected in 38 strains, but not in 8 strains. Morphologically, strains with and without the ver-1 homolog were indistinguishable. Thus, A. oryzae contains strains with and without a homolog of the aflatoxin biosynthetic gene ver-1.

Aflatoxins↗

PubMed1998

Pharmacokinetic disposition and arthropathic potential of oral ofloxacin in dogs.

We examined the relation between the pharmacokinetic disposition and arthropathic potential of ofloxacin, a new quinolone antibacterial agent, using both male immature (3-month-old) and mature (18-month-old) beagles. Ofloxacin was orally administered to these dogs at 20 mg/kg once daily for 8 consecutive days, and the animals were killed 2 h after the last treatment. Serum ofloxacin concentrations were repeatedly measured on days 1 and 7 by use of high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were calculated. In addition, on day 8, the drug concentrations in the joint synovial fluid and humeral and femoral condyles were measured. Clinico-pathological tests of blood and serum or histopathological examination of bone specimens were also performed. Arthropathy was macroscopically observed in the cartilage surface of all immature dogs, but not in mature dogs. There were, however, no noticeable differences in pharmacokinetic parameters between the two age groups of dogs or between single and 7-day treatments. In contrast to the occurrence of arthropathic lesions, the synovial fluid and condylar drug concentrations in immature dogs was equal to or lower than those in mature dogs, suggesting that the pharmacokinetic disposition of ofloxacin may not be essential for cartilage lesions.

Administration, Oral↗

PubMed1998

Pharmacologic preconditioning induced by beta-adrenergic stimulation is mediated by activation of protein kinase C.

Ischemic preconditioning (I-PC) occurs via activation of protein kinase C (PKC). This study was undertaken to determine whether pharmacologic preconditioning by beta-adrenergic stimulation (beta-PC) is mediated by PKC activation. Isolated rat hearts were subjected to 40-min ischemia and 30-min reperfusion. Beta-PC was induced by 0.25 microM isoproterenol pretreatment for 2 min followed by 10-min normoxic perfusion. Beta-PC enhanced the recovery of rate-pressure product of the ischemic/reperfused heart (79.1 +/- 8.4% vs. 12.4 +/- 1.6% of initial for Non-PC group, n = 6) and attenuated the release of creatine kinase during 30-min reperfusion (30.2 +/- 2.2 vs. 59.8 +/- 6.1 nmol/min/g wet wt for Non-PC group, n = 6), similar to an I-PC stimulus of 5-min ischemia and 5-min reperfusion. Treatment with 50 microM polymyxin B, a PKC inhibitor, abolished the cardioprotection of both beta-PC and I-PC. Furthermore, similar changes in subcellular distribution of PKC were induced by both beta-PC and I-PC. The changes in subcellular distribution of PKC-delta suggested its translocation from cytosol to membrane fraction, a marker of PKC activation. These results suggest that the cardioprotection induced by beta-PC, like I-PC, is mediated by PKC activation.

Adrenergic beta-Agonists↗

PubMed1998

Application of hepatic tolerance tests to the functional reserve assessment in rat models of fatty liver.

The present study was designed to define whether maximal removal rate of indocyanine green (ICG Rmax), plasma cyclic 3',5'-adenosine monophosphate (cAMP) response to exogenous glucagon (peak to basal ratio of cAMP level: P/B cAMP) and plasma half-life of galactose (t1/2 galactose) can measure the hepatic functional reserve of fatty liver prepared in rats fed choline-deficient (9 weeks), 2% cholesterol (2 weeks) or 0.25% DL-ethionine (2 weeks) diet. Although changes in cholesterol and phospholipid values in serum during feeding periods differed among the models, histopathologic examinations in the liver of almost all animals revealed intermediate to severe fatty liver with or without fibrosis at each termination. ICG Rmax and P/B cAMP were significantly decreased in rats fed choline-deficient or DL-ethionine diet, implying reductions in hepatic functional mass and disturbances in hepatic cAMP production. Meanwhile, t1/2 galactose showed no change in any of the models, suggesting that glucose metabolisms in the models used may be preserved. These findings demonstrate that ICG Rmax and P/B cAMP can apply to measurement of hepatic surviving reserve of fatty liver with fibrosis.

Animals↗

PubMed1998

[Adjuvant chemotherapy with UFT or UFT with OK-432 to patients with gastric and colorectal cancer. Kanto Adjuvant Study Group].

In Japan, long-term oral therapy with tegafur in combination with immunopotentiators is commonly used as adjuvant therapy after curative resection of gastric or colorectal can for gastric and colorectal cancer. When the outcome was analyzed in terms of the relative performance (R.P.) and the individual dose intensity (I.D.I.) of OK-432, gastric cancer patients with a R.P. of 0.5 or higher tended to have a better survival curve. There were no marked differences in lymphocytes subsets, except that the Leu 7 level at 3 months after gastric cancer resection was significantly higher (p < 0.05) in group B than in group A. Thus, no inhibition of the anticancer effect of UFT was noted during long term combination therapy with UFT and an immunopotentiator as postoperative adjuvant therapy for patients who underwent curative resection of gastric or colorectal cancer. The results suggest that UFT combined with long-term OK-432 maintenance therapy may contribute to improve survival rates in gastric cancer patients.

Adjuvants, Immunologic↗

PubMed1998

Effects of long-term treatment with eicosapentaenoic acid on the heart subjected to ischemia/reperfusion and hypoxia/reoxygenation in rats.

The effects of eicosapentaenoic acid (EPA) and long-term treatment with EPA-ethylester (EPA-E) were examined in perfused rat hearts subjected to ischemia/reperfusion and adult rat cardiomyocytes subjected to hypoxia/reoxygenation. EPA (0.1 microM) improved postischemic contractile dysfunction of the ischemic/reperfused heart. EPA (10 microM) attenuated hypoxia/reoxygenation-induced morphological deterioration of cardiomyocytes. The results suggest the presence of direct cardioprotective effects of EPA. Rats were orally treated for 4 weeks with 1 g/kg/day of EPA-E to elucidate ex vivo effects of EPA, and the fatty acid composition of cardiac phospholipids was determined. The percent ratio of EPA in total fatty acids of cardiac phospholipids increased whereas that of arachidonic acid decreased. The percent ratio of n-3/n-6 fatty acid did not increase. Treatment with EPA-E did not improve the post-ischemic contractile function, but attenuated the ischemia/reperfusion-induced release of prostaglandins during reperfusion. Treatment with EPA-E preserved a better morphological appearance of the cardiomyocytes subjected to hypoxia/reoxygenation. The results suggest that the mechanisms responsible for cytoprotective effects of hypoxic/reoxygenated cardiomyocytes or inhibition of metabolic alterations of the ischemic/reperfused heart by long-term EPA-E treatment did not contribute substantially to recovery of post-ischemic contractile dysfunction. The direct in vitro effects of EPA may play a role in the protection of the heart from ischemia/reperfusion or hypoxia/reoxygenation injury.

Animals↗

PubMed1997

Does glycogen depletion play an important role in ischemic preconditioning?

The present study was undertaken to determine whether or not tissue glycogen depletion prior to ischemia, and subsequent attenuation of tissue lactate accumulation during ischemia, correlates with postischemic functional recovery of the preconditioned heart. Isolated rat hearts were subjected to 40-min ischemia and 30-min reperfusion. Preconditioning with 5-min ischemia and 5-min reperfusion reduced the preischemic glycogen and postischemic lactate levels of the heart to 60.5 +/- 5.6% and 66.9 +/- 7.7% respectively, of values in non-preconditioned hearts (n = 6), and improved the recovery of the rate-pressure product (RPP) of the ischemic/reperfused heart (87.0 +/- 5.8% versus 25.2 +/- 4.5% of the initial value for the non-preconditioned group, n = 8). Treatment with polymyxin B (50 microM) abolished the preconditioning-induced postischemic recovery of the RPP. Treatment of the non-preconditioned heart with phorbol 12-myristate 13-acetate (15 pmol/5 min) resulted in an improvement in the postischemic recovery of RPP. Neither of these treatments affected the preischemic glycogen and postischemic lactate levels. The results suggest that preischemic glycogen depletion and subsequent attenuation of ischemic lactate accumulation do not play a major role in the preconditioning-induced protection against postischemic contractile dysfunction in perfused rat hearts.

Animals↗

PubMed1997

Activation of cardiac muscarinic receptor and ischemic preconditioning effects in in situ rat heart.

Activation of cardiac muscarinic receptors by vagal stimulation decreases cardiac work, which may have a protective effect against ischemic injury. To determine whether cardiac muscarinic receptors contribute to the mechanisms of preconditioning effects, we examined the effect of carbachol on ischemia/reperfusion damage and the effect of vagotomy on cardioprotection induced by ischemic preconditioning. Rats were subjected to 30 min of left coronary artery occlusion followed by 30-min reperfusion in situ. Pre-conditioning was induced by three cycles of 2-min coronary artery occlusion and, subsequently by 5 min of reperfusion. The incidence of ischemic arrhythmias, such as ventricular tachycardia (VT) and ventricular fibrillation (VF), and the development of myocardial infarction were markedly reduced by the preconditioning. Carbachol infusion (4 micrograms/kg per min) delayed the occurrence of VT and VF during ischemia and reduced the infarct size. Compared with non-ischemic left ventricle, the cyclic guanosine monophosphate (GMP) content in the ischemic region of the left ventricle was decreased by ischemia/reperfusion, whereas the cyclic adenosine monophosphate (AMP) content of this region was increased. These changes were reversed by preconditioning. Similar changes in cyclic GMP and AMP content in the ischemic region were seen in rats undergoing carbachol treatment. These results suggest the possible contribution of muscarinic receptor stimulation to preconditioning. Vagotomy prior to preconditioning diminished the antiarrhythmic effects, whereas it did not block the anti-infarct effect afforded by pre-conditioning. Vagotomy abolished the preconditioning effect on the tissue cyclic GMP, but it did not attenuate the decrease in tissue cyclic AMP. The results suggest that muscarinic stimulation exerts preconditioning-mimetic protective effects in ischemic/reperfused hearts, but that a contribution of reflective vagal activity to the mechanism for preconditioning is unlikely.

Animals↗

PubMed1997

Preconditioning preserves mitochondrial function and glycolytic flux during an early period of reperfusion in perfused rat hearts.

OBJECTIVE: The purpose of the present study was to examine the effects of preconditioning on glycolysis and oxidative phosphorylation during reperfusion in perfused rat hearts. METHODS: Preconditioning was induced by 5 min of ischemia and 5 min of reperfusion before 40 min of sustained ischemia and subsequent 30 min of reperfusion. Tissue energy metabolite levels, mitochondrial oxygen consumption capacity and adenine nucleotide translocator content of the perfused hearts were assessed at 40 min of ischemia, 5 and 30 min of reperfusion. RESULTS: Preconditioning improved the postischemic recovery of rate x pressure product (92.5 +/- 8.7 vs. 24.9 +/- 1.2% for non-preconditioned group) and high-energy phosphate content (ATP and CrP; 39.5 +/- 2.0 and 96.2 +/- 4.9% of initial vs. 24.1 +/- 0.9 and 56.1 +/- 4.3% of initial for the non-preconditioned group). The mitochondrial oxygen consumption capacity and the adenine nucleotide translocator content of the non-preconditioned heart were decreased by sustained ischemia and remained decreased throughout reperfusion. Preconditioning prevented these decreases. The tissue lactate level of the non-preconditioned heart was high throughout reperfusion (16.5-fold vs. basal), whereas in the preconditioned heart it returned to the basal level within a few minutes of reperfusion. Furthermore, the ratios of [fructose 1,6-bisphosphate]/([glucose 6-phosphate] + [fructose 6-phosphate]) at 5-min reperfusion were higher (2.2-fold) than those of the non-preconditioned heart. CONCLUSIONS: The results suggest that preconditioning preserves the capacity for normal mitochondrial function and the facilitation of glycolysis during reperfusion, which may play an important role in the improvement of postischemic contractile function and high-energy phosphate content.

Adenosine Triphosphate↗

PubMed1997

Beta-adrenoceptor stimulation-mediated preconditioning-like cardioprotection in perfused rat hearts.

To determine whether adrenergic stimulation induces preconditioning-like cardioprotection, rat hearts were perfused for 2 min with either norepinephrine, phenylephrine, or isoproterenol followed by 10-min drug-free perfusion. Then the hearts were subjected to 40-min ischemia and 30-min reperfusion. Little recovery of left ventricular developed pressure (LVDP) and loss of the myocardial creatine kinase (CK) during reperfusion were observed in the drug-untreated heart. Preperfusion with norepinephrine (0.25 microM) or isoproterenol (0.25 microM), but not phenylephrine (10 microM), resulted in a better recovery of LVDP in the postischemic reperfused heart and a reduction in CK release during reperfusion. A similar improvement of postischemic cardiac contractile dysfunction and CK loss was seen in the heart subjected to 5-min ischemia followed by 5-min reperfusion (ischemic preconditioning) before the prolonged period of ischemia/reperfusion. Pretreatment with timolol, a beta-adrenoceptor blocker, abolished the protective effect of norepinephrine, whereas pretreatment with bunazosin, an alpha 1-adrenoceptor blocker, did not affect the protective effect of isoproterenol. The results suggest that a brief period of stimulation of cardiac beta-adrenoceptor exerts the preconditioning-mimetic protective effect against postischemic contractile dysfunction in perfused rat hearts.

Adrenergic alpha-Agonists↗

PubMed1997

Diagnosis of quinolone-induced arthropathy in juvenile dogs by use of magnetic resonance (MR) imaging.

The present study was carried out to confirm whether arthropathy in juvenile dogs induced by ofloxacin, a new quinolone antibacterial agent, may be diagnosed by magnetic resonance (MR) imaging. Three-month-old male beagle dogs were orally administered ofloxacin at 20 mg/kg once daily for 7 consecutive days. On day 8, MR images were obtained with a 4.7-tesla (T) super-conductive high magnetic field strength unit. An irregular cartilage surface and dissecans changes in the distal femoral condyle were observed. These MR findings were essentially consistent with pathologic observation showing multifocal blisters on the articular cartilage with an increased amount of turbid synovial fluid in the joint. The results demonstrate that occurrence of ofloxacin arthropathy in juvenile dogs can be clearly diagnosed by use of MR imaging.

Administration, Oral↗

PubMed1995

Hypoxic preconditioning in isolated rat hearts: non-involvement of activation of adenosine A1 receptor, Gi protein, and ATP-sensitive K+ channel.

Activation of the adenosine A1(A1) receptor, Gi protein, and ATP-sensitive K+ (KATP)-channel system has been shown to play an important role in the cardioprotective effects of ischemic preconditioning in dogs. The present study was undertaken to elucidate the possible involvement of this system in hypoxic preconditioning, which ameliorates injury induced by prolonged ischemia and subsequent reperfusion in perfused rat hearts. Ten minutes of hypoxic preconditioning resulted in an appreciable improvement of post-ischemic cardiac contractile recovery. This was associated with a significant reduction in the release of creatine kinase (CK) from reperfused hearts. Hypoxic preconditioning shortened the time to ischemic contracture onset and prevented a further rise in left ventricular end-diastolic pressure (LVEDP) during reperfusion. Neither the selective A1 receptor antagonist, 8-cyclopentyltheophylline (CPT) nor the KATP channel blocker, glibenclamide, altered the beneficial effects of hypoxic preconditioning. In vivo pretreatment with an inhibitor of Gi protein, pertussis toxin (PTX), also did not diminish the preconditioning effect. The results suggest that, although hypoxic preperfusion ameliorates post-ischemic contractile dysfunction, neither the activation of the A1 receptor, nor the opening of the KATP-channel, nor transduction through Gi protein are involved in the post-ischemic functional recovery of hypoxic preconditioning in the perfused rat heart.

Adenosine Triphosphate↗