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Biomedical subjects

K Nakamoto

Publications and source records attributed to K Nakamoto.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of tylosin tartrate on humoral immune responses in chickens.

While many antimicrobial agents have been reported to cause immunosuppression in animals, macrolide antibiotics enhance the immune function. Tylosin tartrate is a macrolide antibiotic approved for the control of mycoplasmosis in poultry. The purpose of this investigation was to determine the effect of tylosin on the humoral immune functions in chickens. Three days after oral tylosin tartrate administration, 4- or 8-week-old chickens were immunized intravenously with carbolic acid-killed Brucella abortus bacterin or sheep red blood cells. Seven days (plasma antibodies titre) or 4 days (antibody forming cells) post-immunization, there was a significant increase in antibody production as well as in the numbers of antibody-producing cells in tylosin tartrate-administered chickens compared with the untreated controls. However, 3 days after tylosin tartrate administration, there was no difference in the distribution of T-lymphocyte subpopulations (CD4 or CD8 positive cells) or B lymphocytes (surface immunoglobulin positive cells) in either the peripheral blood or spleens or untreated control chickens.

Animals↗
PubMed1998

Direct measurement of nitric oxide release in gastric mucosa during ischemia-reperfusion in rats.

Nitric oxide (NO) generation in the rat gastric mucosa during ischemia-reperfusion was measured using an NO-sensitive electrode. Under pentobarbital sodium anesthesia, an electrode was inserted into the submucosa from the serous membrane side in the fundus. After steady-state baseline recording, the celiac artery was clamped for 30 min, and then ischemia-reperfusion was achieved by removing the clamp. The clamping of the celiac artery caused a decrease in blood flow and an increase in NO level in the gastric tissue. Just after the removal of the clamp, the NO level rapidly fell and returned to the baseline level. Administration of NG-nitro-L-arginine methyl ester (an NO synthase inhibitor, 30 mg/kg i.p.) before ischemia significantly attenuated both the increase in NO level during ischemia and the formation of acute gastric mucosal lesions observed after 60 min reperfusion. Administration of superoxide dismutase (a superoxide radical scavenger, 10,000 U/kg i.v.) at the end of ischemia inhibited both the rapid decrease in NO level during the reperfusion and the gastric mucosal erosions. Because NO and superoxide radical produce a highly reactive peroxynitrite, it can be argued that NO has an important pathological role in acute gastric mucosal injury induced by ischemia-reperfusion. Our conclusion was strongly supported by immunohistochemical staining of nitrotyrosine residues, an indication of peroxynitrite formation.

Animals↗
PubMed1998

Preoperative diagnosis with video-assisted thoracoscopy with miniaturized endoscopes in general thoracic surgery: a preliminary study.

Video-assisted thoracoscopy using a miniaturized endoscope (mini-VAT) was applied for preoperative diagnosis in general thoracic surgery. Thirty-one patients, including 27 with indeterminate pulmonary nodule and 4 with suspected pleural involvement of lung cancer or metastatic pleural tumor, underwent mini-VAT. As a pilot study, 14 of the former 27 patients underwent mini-VAT while receiving general anesthesia. As a prospective study, all the remaining 17 patients underwent mini-VAT while receiving local anesthesia. Solid scopes of three different sizes, 0.9, 1.9, or 4.0 mm diameter, were used. An artificial pneumothorax for scope introduction was produced by needle thoracentesis under atmospheric pressure. Automatic cutting needle biopsy was used for tissue sampling. In the pilot study group, mini-VAT with a 4.0-mm scope provided excellent visibility and diagnostic sensitivity of 100%. This study group showed the diagnostic sensitivity of needle biopsy for pulmonary nodule to be 100%. Hemorrhages and air leaks at biopsy sites were sealed with blood coagulation in a short time. In the prospective study group, mini-VAT with a 4.0-mm scope with the patients receiving local anesthesia provided a diagnostic sensitivity of 91% for pulmonary nodule and a diagnostic accuracy of 100% for suspected pleural involvement. Causes of failure of mini-VAT with the use of local anesthesia were cough reflex during needle biopsy and incomplete lung collapse for deeply located target in two cases. The adverse effects of the mini-VAT were paradoxical respiration in two cases in which local anesthesia was used. The patients who received only local anesthesia required no chest tube drainage. Mini-VAT is a simple, minimally invasive procedure suitable as a preoperative examination technique for histologic diagnosis, evaluation of disease progression, and selection of strategy in thoracic surgery.

Adult↗
PubMed1998

Distribution and excretion of boron after intravenous administration of disodium mercaptoundecahydro-closo-dodecaborate to rats.

Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is an important compound for boron neutron capture therapy. The pharmacokinetics of boron by BSH were studied in normal rats after rapid intravenous injection at three doses (30, 100, 300 mg/kg) or continuous infusion (100 mg/kg/30 min). The boron concentration in biological samples was measured by inductively coupled plasma atomic emission spectroscopy. The blood half-lives of boron in the elimination phase (t1/2 beta) after rapid injection of BSH at doses of 30, 100 and 300 mg/kg were 1.7, 17 and 19 hr, respectively. AUC (32, 219 and 4030 micrograms.hr/ml) increased with the dose, but there was no proportionality among the values. Total clearance decreased drastically from 233 ml/hr/kg (100 mg/kg) to 38 ml/hr/kg (300 mg/kg). As boron was excreted mainly into urine, these results suggest that renal function failure might occur with dosing of 300 mg/kg. In the case of continuous infusion of 100 mg/kg of BSH for 30 min, the pharmacokinetic parameters were similar to those of rapid injection of 100 mg/kg. The highest boron concentration was observed in the kidney and the lowest in the brain. After multiple dosing of BSH at 100 mg/kg/day x 14 days, the boron concentrations in blood, liver, lung and kidney at 24 hr after the last dosing were higher than those after single dosing and were similar to those of simulated values calculated from the single dosing parameters. These results clearly indicated that boron does not accumulate unexpectedly in any tissue with multiple dosing of 100 mg/kg of BSH for two weeks.

Animals↗
PubMed1997

Lipopolysaccharide-induced increase in plasma nitrotyrosine concentrations in rats.

Since the production of peroxynitrite may contribute to the pathophysiology of endotoxemia or sepsis, the quantities of the produced peroxynitrite were evaluated in rats after lipopolysaccharide (LPS) treatment by measuring plasma nitrotyrosine concentrations with a new method. The intraperitoneal administration of LPS caused a persistent increase in plasma nitrotyrosine concentrations, which reached a maximum with 6-fold level of the base line (105 pmol ml-1) at 24 h and gradually declined to 3-fold level of the base line at 7 days. However, plasma concentrations of nitrite and nitrate peaked at 18 h, returning to base line within 48 h. The effect of LPS on the increase in plasma concentration of nitrotyrosine was dose-dependent and consistent with that of nitrite and nitrate concentrations. On the other hand, intravenous injection of nitrotyrosine revealed a rapid clearance with a plasma half-life of 1.67 h. These results indicate that the elevation of plasma nitrotyrosine concentrations may persist for more than a week after LPS treatment, and that the determination of plasma nitrotyrosine concentrations may be useful to detect the previous peroxynitrite-dependent oxidative damages.

4-Chloro-7-nitrobenzofurazan↗
PubMed1997

Loss of heterozygosity of the retinoblastoma gene in liver cirrhosis accompanying hepatocellular carcinoma.

Carcinogenesis is a multistep process. Most hepatocellular carcinoma (HCC) is preceded by liver cirrhosis, but the genetic changes involved in cirrhosis are not known well. The present study was conducted to evaluate aberration of the retinoblastoma (RB) gene in HCC and adjacent non-tumorous liver using 22 patients with chronic liver damage accompanying HCC. The specimens obtained by microdissection from paraffin-embedded tissues were analyzed using an assay based on the polymerase chain reaction for highly polymorphic nucleotide sequences of microsatellites in the RB gene. Out of 22 cases, 15 showed constitutional heterozygosity for the microsatellite markers. In 11 (73.3%) of these 15 informative cases, the primary HCC foci showed loss of heterozygosity (LOH). In 8 of these 11 doubly informative (informative and LOH-positive in primary HCC) cases, LOH was found in 20 (64.5%) of 31 microdissected non-tumorous foci. All of the non-tumorous foci showing RB loss were cirrhotic lesions but there were no foci of chronic hepatitis. The remaining 4 cases without LOH in HCC foci showed no LOH in non-tumorous lesions. In our study, LOH of the RB gene was frequently observed in liver cirrhosis surrounding tumor.

Aged↗
PubMed1997

Quantitative analysis of cyclooxygenase-2 gene expression on acute gastric injury induced by ischemia-reperfusion in rats.

The rat model of acute gastric damage induced by ischemia-reperfusion (I-R) has been used to evaluate the protective effect of various drugs on gastric injury. However, the quantitative expression state of cyclooxygenase-2 (COX-2), a protein which induces cytoprotective prostaglandins during inflammation, is still unknown in acute gastric injury induced by I-R. Therefore, we have quantitatively investigated the level of expression of COX-2 mRNA in injured gastric tissue of this model using the reverse transcription-competitive polymerase chain reaction method. The mRNA for COX-2 was expressed at low or undetectable levels in the normal gastric tissues in control rats, which were fasted for 18 hrs without I-R. The mRNA levels of COX-2 in injured gastric tissues were higher than those of control tissues between 6 hrs and 48 hrs after I-R. The maximum expression of COX-2 mRNA was recorded at 24 hrs (approximately a 200-fold increase). The expression state of COX-2, which has been ascertained in this study, should be useful in evaluating the effect of various drugs on the expression of COX-2 in acute gastric damage.

Actins↗
PubMed1997

Inhibition by cigarette smoke of lipid peroxidation-induced neurotransmitter release.

Effects of water-soluble substance in cigarette smoke on neurotransmitter release were investigated using nerve terminals (synaptosomes) prepared from rat cerebral cortex. 2,2'-Azobis (2-amidinopropane) dihydrochloride (ABAP), a peroxyl radical-generator, enhanced the depolarization-evoked release of glutamate and aspartate from synaptosomes with concomitant increase in thiobarbituric acid-reactive substances (TBA-RS) levels in membrane lipids of synaptosomes. The trapped smoke-substance attenuated the lipid peroxidation-enhanced release of excitatory amino acids during the depolarization with reduction in TBA-RS, although it failed to affect the basal release of neurotransmitters. These data suggest that cigarette smoke may possess antioxidant properties to reduce oxidation-induced enhancement of transmitter release from nerve terminals.

Amidines↗
PubMed1997

Substances in the aqueous fraction of cigarette smoke inhibit lipid peroxidation in synaptosomes of rat cerebral cortex.

The effects of water-soluble substances in cigarette smoke on lipid peroxidation were investigated using nerve terminals prepared from the rat cerebral cortex. The prepared smoke-substances significantly reduced the spontaneous increase in thiobarbituric acid-reactive substances in synaptosomes in a dilution factor-dependent manner. Furthermore, the aqueous extract also inhibited the elevation of lipid peroxidation induced by 2,2'-azobis (2-amidinopropane) dihydrochloride, a peroxyl radical generator. Smoke-substances scavenged superoxide radicals generated from stimulated human leukocytes and from the xanthine/xanthine oxidase system. These effects were not mimicked by nicotine. The antioxidant effects of smoke-substances were preserved for several days at 5 degrees or -80 degrees C. The results suggest that the smoke-substances may possess long half-lives and scavenge the radicals which cause lipid-peroxidation in synaptosome membranes.

Animals↗
PubMed1997

Effect of plaunotol on gastric injury induced by ischaemia-reperfusion in rats.

Plaunatol, an anti-ulcer drug, increases prostaglandin content in gastric tissue but its effect on radical-mediated gastric damage or activity against reactive oxygen species is unknown. We examined the effects of oral administration of plaunotol (Kelnac) on the acute gastric mucosal lesion and its progression to ulcer lesion induced by ischaemia-reperfusion in rats. Plaunotol (30 and 100 mg kg-1, 15 min before ischaemia) significantly reduced the total erosion area observed immediately after ischaemia-reperfusion. When plaunotol (30 and 100 mg kg-1, once a day) was administrated orally 60 min after reperfusion, it prevented the progression from erosion to ulcer. At 72 h after ischaemia-reperfusion, the total area of ulcers lesions was significantly reduced compared with that without plaunotol administration. Furthermore, treatment with plaunotol (100 mg kg-1) significantly increased prostaglandin E2 content in gastric tissues of both acute gastric mucosal lesion and gastric ulcer lesion. In in-vitro experiments, plaunotol (1-3 mg mL-1) reduced the superoxide radicals generated by leucocytes, but not by xanthine oxidase. These results indicate that plaunotol has protective effects on both the onset of acute gastric mucosal injury and its progression to ulcer lesion induced by ischaemia-reperfusion. Both effects of plaunotol on increase in prostaglandin content in gastric tissues and inhibition of superoxide radical from leucocytes may play important roles on the protection against gastric mucosal injury.

Animals↗
PubMed1997

Effects of sucralfate on acute gastric mucosal injury and gastric ulcer induced by ischemia-reperfusion in rats.

We have revealed that acute gastric mucosal injury induced by a single ischemia-reperfusion (I-R) treatment develops into an ulcerative lesion within a few days. In the present studies, we examined the effects of oral administration of sucralfate on gastric damage induced by I-R. Sucralfate (1-100 mg/kg, 15 min before I-R) significantly reduced the total erosion area observed immediately after I-R. A high dose of sucralfate (30-100 mg/kg) inhibited the increase in the thiobarbituric acid-reactive substances, an index of lipid peroxidation, induced by I-R, although a low dose of it failed. When sucralfate (30 mg/kg, once a day) was orally administered after I-R, it prevented mucosal damage from developing into gastric ulcers: the total area of the ulcers was significantly reduced compared to that without sucralfate administration 72 h after I-R. High concentrations of sucralfate (3-10 mg/ml) reduced the superoxide radicals generated by leukocytes or xanthine-xanthine oxidase, and protected erythrocyte membrane ghosts against lipid peroxidation induced by hydrogen peroxide and Fe2+ in vitro. These results indicate that sucralfate may prohibit both the generation of acute gastric mucosal injury and its progression to ulcer induced by I-R, probably due to a cytoprotective action on the mucosal surface. However, the protective mechanism may involve an inhibitory action on superoxide and hydroxyl radicals at high doses.

Animals↗
PubMed1997

Protective effect of acetaminophen against acute gastric mucosal lesions induced by ischemia-reperfusion in the rat.

We examined the effect of acetaminophen, an analgesic and antipyretic drug, on acute gastric mucosal injury induced by ischemia-reperfusion in rats. Ischemia-reperfusion was induced by clamping the celiac artery for 30 min with a small clip. Sixty minutes after reperfusion, the total area of erosions was measured. Acetaminophen (300 and 500 mg/kg) administered intraperitoneally 90 min before the ischemia significantly reduced the total area of erosions. The drug also inhibited the increase in lipid peroxide levels induced by ischemia-reperfusion in the gastric tissue and the increase in lipid peroxidation caused by the hydroxyl radical, OH., in vitro. Gastric prostaglandin E2 (PGE2) contents tended to increase after ischemia-reperfusion in both control and acetaminophen-treated groups. A significant difference in gastric PGE2 contents between control and acetaminophen-treated groups was not observed. The results indicate that acetaminophen may protect the gastric mucosa against ischemia-reperfusion injury, probably by blocking hydroxyl-radical-induced membrane damage.

Acetaminophen↗
PubMed1997

Effects of cimetidine on acute gastric mucosal injury induced by ischemia-reperfusion in rats.

We investigated the effects of cimetidine on acute gastric mucosal injury induced by ischemia-reperfusion in rats. Under pentobarbital anesthesia, the celiac artery was clamped for 30 min and reperfused for 60 min. Cimetidine, famotidine and omeprazole caused a dose-dependent suppression in the total area of erosions that were induced by ischemia-reperfusion. Whereas, none of them inhibited the increase in thiobarbituric acid-reactive substances in the stomach, as an index of lipid peroxidation. The inhibitory effect of intraperitoneally administered cimetidine on mucosal damage was abolished by continuous luminal perfusion with HCl solution (pH 1.5, 1 ml/min) during ischemia-reperfusion, while luminal perfusion with the solution containing HCl and cimetidine (3 mmol/l) significantly reduced the total area of erosions compared to luminal perfusion with HCl solution alone. Cimetidine (3 mmol/l) inhibited hydroxyl radical-induced lipid peroxidation of human erythrocyte membranes by 60% in vitro. These results indicate that cimetidine possesses a protective effect against acute gastric mucosal injury induced by ischemia-reperfusion not only due to the suppression in gastric acid secretion, but also due to the antioxidant action when it is present at a high concentration in the intragastric environment.

Animals↗
PubMed1996

Sensitive determination of nitrotyrosine in human plasma by isocratic high-performance liquid chromatography.

A highly sensitive and simple isocratic high-performance liquid chromatographic method was developed for determination of 3-nitrotyrosine in human plasma with precolumn derivatization with 4-fluoro-7-nitrobenzo-2-oxa-1,3-diazole. The precision of the method was satisfactory (coefficient of variation 4.8%), and the detection limit was established at 0.1 pmol of 3-nitrotyrosine allowing the determination at the level of 6 pmol/ml in human plasma. The recoveries of 3-nitrotyrosine and alpha-methyltyrosine, an internal standard, were 89.3 +/- 7.1 and 85.7 +/- 7.6%, respectively. The 3-nitrotyrosine level was 31 +/- 6 pmol/ml (mean +/- S.D., n = 9) in plasma from healthy volunteers. Since 3-nitrotyrosine is a stable product of peroxynitrite, an oxidant formed by a reaction of nitric oxide and superoxide radicals, the measurement of its plasma concentration may be useful as a marker of nitric oxide-dependent oxidative damage.

4-Chloro-7-nitrobenzofurazan↗
PubMed1996

Effect of cystathionine as a scavenger of superoxide generated from human leukocytes or derived from xanthine oxidase in vitro.

We studied the direct effects of cystathionine on human leukocyte-generated or xanthine-xanthine oxidase-derived superoxide radicals in vitro. Washed leukocyte suspensions (10(6) cells/ml) prepared from healthy male volunteers were stimulated with phorbol myristate acetate (1 mu M) or opsonized zymosan (1 mg/ml) to generate superoxide radicals, which were measured with a 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo[1,2-alpha] pyrazin-3-one hydrochloride (MCLA)-chemiluminescence method. Cystathionine (30 mu M to 10 mM) significantly reduced superoxide radical-dependent chemiluminescence in the leukocyte system in a concentration-dependent manner. In addition, in the two different methods of determination of superoxide radicals (MCLA chemiluminescence and nitroblue tetrazolium reduction), cystathionine significantly scavenged the superoxide radicals derived from the xanthine-xanthine oxidase system. However, cystathionine did not inhibit the activity of xanthine oxidase during superoxide generation. On the other hand, cystathionine did not show a scavenging effect against hydroxyl radicals derived from Fe2+ -H2O2 on the erythrocyte membrane. These results indicate that cystathionine itself may possess a scavenging function against superoxide radicals rather than against hydroxyl radicals in vitro.

Cystathionine↗
PubMed1996

Release of taurine and its effects on release of neurotransmitter amino acids in rat cerebral cortex.

Taurine has been postulated to function as a neurotransmitter or neuromodulator. The possibility of depolarization-evoked release of taurine from nerve terminals, and the effects of taurine on release of endogenous glutamate (Glu), aspartate (Asp), and gamma-aminobutyrate (GABA) were examined using a superfusion of crude synaptosomes prepared from rat cerebral cortex. Taurine contents in cerebral cortex and its synaptosomes were 31.7 and 25.2 nmol/mg protein, respectively. Although the basal rate of taurine release was 35.3 pmol/min/mg protein of synaptosomes (second highest releasing rate), the 2-min stimulation with KCl (30 mM) evoked only a 1.3-fold increase in release of taurine (47.3 pmol/min/mg). The increase was largely Ca(2+)-dependent. The addition of taurine to the perfusion medium significantly reduced the depolarization-evoked increases in Glu, Asp, and GABA release. The taurine-induced reduction in GABA release was attenuated by phaclofen, a GABAB antagonist, but not by bicuculline, a GABAA antagonist. However, these antagonists did not block the effects on Glu and Asp release. These data suggest that taurine may be only partly released from nerve terminals by depolarization in the cerebral cortex, but that taurine may act upon nerve terminals to regulate the release of excitatory and inhibitory amino acid transmitters.

Animals↗
PubMed1996

Frequent loss in chromosome 8p loci in liver cirrhosis accompanying hepatocellular carcinoma.

Most hepatocellular carcinoma (HCC) is preceded by liver cirrhosis, but the genetic changes involved in cirrhosis are not well understood. We therefore studied loss of heterozygosity (LOH) in cirrhotic and neoplastic foci in livers of 14 patients with HCC. The samples, microdissected from paraffin-embedded tissues, were analyzed using a polymerase-chain-reaction-based assay for dinucleotide repeat polymorphisms on 8p. Of the 14 cases, 13 showed constitutional heterozygosity for the microsatellite markers. In 7 (54%) of these 13 informative cases, LOH was detected in the primary HCC and, in these 7 doubly informative (informative and LOH-positive in primary HCC) cases, LOH was found in 16 (70%) of 23 liver cirrhotic foci. The pattern of 8p allelic loss was identical in each doubly informative tumor; however, some of the liver cirrhotic foci harbored an 8p loss identical to that seen in the primary HCC, some harbored a different 8p loss, and some did not harbor any 8p loss. The remaining 6 cases without LOH on 8p in HCC showed no 8p loss in any cirrhotic foci. Presumably HCC could develop from cirrhotic cells harboring 8p loss.

Adult↗