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Biomedical subjects

M Kitano

Publications and source records attributed to M Kitano.

At least 109 records · Page 6Linked to original sources
PubMed1996

Dose-related increases in quantitative values for altered hepatocytic foci and cytochrome P-450 levels in the livers of rats exposed to phenobarbital in a medium-term bioassay.

The dose-response relationship between liver tumor promoting activity and cytochrome P-450 (CYP) induction by phenobarbital sodium (PB) was investigated using the liver medium-term bioassay system of Ito. Two weeks after a single dose of N-nitrosodiethylamine (DEN) (200 mg/kg body weight, i.p.), rats were given PB at dietary levels of 500, 250, 125, 60, 30, 15 and 8 parts per million (ppm) for 6 weeks. All rats were subjected to partial hepatectomy at week 3, and were killed at week 8. Quantitative values for glutathione S-transferase placental form positive hepatocytic (GST-P+) foci were increased in the high dose groups dose-dependently. In contrast, the values in the low dose groups were rather lower than that of the control. CYP2B1, 2C6 and 3A2 were predominantly immunostainable in hepatocytes around the central vein. While Western blotting revealed CYP2B1 and 2C6 proteins to be increased with strict dose-dependence, CYP3A2 was only elevated at high doses. Thus, a good correlation between increase of GST-P+ foci and CYP3A2 induction was observed, as well as with CYP2B1 and 2C6 in high dose groups.

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

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↗
PubMed1996

A new gastric ulcer model induced by ischemia-reperfusion in the rat: role of leukocytes on ulceration in rat stomach.

A new model of gastric ulcer involving damage to the muscularis mucosae was developed by clamping the celiac artery in rat to induce ischemia-reperfusion (I-R) injury. Although erosions with falling off of the gastric mucosa were observed immediately, 24 and 36 hours after the I-R, gastric ulcers involving the injury of muscularis mucosae were observed in the area of gastric glands at 48 and 72 hours after initiation of injury. Administration of omeprazol, a proton pump inhibitor, or pentoxifylline, an anti-leukocyte drug, just after the initiation of injury significantly decreased the total area of ulcers at 72 hours. A combination of omeprazol and pentoxifylline was more effective than either drug alone. An anti-leukocyte adhesion molecule (anti-CD18 antibody) also showed significant inhibitory effect on the development of ulcers at 72 hours and the infiltration of leukocytes into both submucosa and mucosa. These results indicate that in our model, gastric acid together with leukocytes contribute to the development of ulcers following erosions. This model may be used to investigate the mechanisms of the development of gastric ulcer and evaluate antiulcer drugs in a preclinical setting.

Animals↗
PubMed1996

Analysis of right ventricular function during bypass of the left side of the heart by afterload alterations in both normal and failing hearts.

This study investigated the mechanism of right ventricular failure during bypass of the left side of the heart by precisely assessing right ventricular function with use of a conductance catheter. Bypass of the left side of the heart was established with a centrifugal pump in 10 mongrel dogs weighing 11 to 19 kg. Right ventricular function during left heart bypass was evaluated by two parameters that were both derived from measurement of relative change in right ventricular volume by the conductance catheter technique. One parameter was the right ventricular end-systolic pressure-volume relationship as a load-independent index, and the other was the peak right ventricular pressure-right ventricular stroke volume relationship as a "force-velocity relationship." These parameters were measured in both normal and failing hearts while afterload was increased by bilateral intrapulmonary balloon inflation. Moreover, changes in these relationships were observed by varying assist ratios of left heart bypass from 0% to 100%. Failing heart models were induced by normothermic aortic clamping for 20 minutes. The right ventricular end-systolic pressure-volume relationship in normal hearts did not change, irrespective of the assist ratio of left heart bypass, whereas that in failing hearts decreased from 4.25 +/- 1.41 mm Hg/ml without bypass of the left side of the heart to 3.53 +/- 1.30 mm Hg/ml after 100% assist of left heart bypass (p < 0.05). In the peak right ventricular pressure-right ventricular stroke volume relationship, right ventricular stroke volume was almost constant in normal hearts when afterload was increased regardless of the assist ratio of left heart bypass. Moreover, right ventricular stroke volume was maintained at a higher level during bypass of the left side of the heart compared with that without left heart bypass. However, that slope of the relationship in failing hearts was inversely linear and became significantly steeper after 100% assist of bypass of the left side of the heart compared with that without left heart bypass (-0.131 +/- 0.042 versus -0.051 +/- 0.038, p < 0.005). Therefore ++these two slopes of the relationship intersected at a point that was considered the critical point of afterload during bypass of the left side of the heart. In other words, right ventricular stroke volume was decreased by 100% left heart bypass above the critical point of afterload. In conclusion, this study demonstrates not only that bypass of the left side of the heart results in an increase in right ventricular stroke volume in both normal and failing hearts at the physiologic range of afterload, but also that right ventricular function against higher afterload is impaired by 100% assist of bypass of the left side of the heart in failing hearts.

Animals↗
PubMed1996

Kimura's disease: a clinicopathologic study of 54 Chinese patients.

Kimura's disease, a chronic inflammatory condition of unknown cause, is endemic in Orientals. The present study documented 54 cases of Kimura's disease in patients from mainland China. The main clinical features of this series included young and middle-aged male predominance (male:female = 3.5:1), predilection for the head and neck regions, and a long duration. The disease presented as either single (31 cases), or multiple lesions (23 cases), and mainly involved subcutaneous tissues (29 cases), major salivary glands (21 cases), and lymph nodes (17 cases) in isolation or in combination. Histopathologically, the lesion was characterized by hyperplasia of lymphoid tissue with well-developed lymphoid follicles, marked infiltration of eosinophils, proliferation of thin-walled capillary venules, and varying degrees of fibrosis. Distinctive features of salivary glands and nodal involvement were also described. Differences between Kimura's disease and angiolymphoid hyperplasia with eosinophilia, mostly reported in the West, were discussed to draw attention to their distinction.

Adolescent↗
PubMed1996

Genetic controls of susceptibility and resistance to 4-nitroquinoline 1-oxide-induced tongue carcinomas in rats.

We analyzed the incidence of infiltrative mass-type tongue carcinomas (IMTC) induced in 550 rats by continuous oral administration of 0.001% 4-nitroquinoline 1-oxide solution for 180 days. The study included various crosses of susceptible Dark-Agouti rats (DA) and resistant Wistar/Furth rats (WF). DA showed a 93.6% incidence of IMTC measuring more than 5 mm in their largest diameter, while WF showed only a 4% incidence. Reciprocal F1 and F2 hybrids mated by DA and WF showed 47.5% and 45.8% incidences, respectively. Meanwhile, reciprocal backcrossed hybrids to DA and WF showed 73.7%, and 24.6% incidences, respectively. Segregation of the incidences suggests that there are two autosomal dominant genes, one linked to the susceptibility of DA and the other to the resistance of WF.

4-Nitroquinoline-1-oxide↗
PubMed1996

Increased urinary endothelin excretion in patients with liver cirrhosis.

The urinary endothelin level in patients with chronic liver disease was determined in order to explore its possible involvement in renal function. The plasma endothelin level was significantly higher in patients with liver cirrhosis (LC) than in those with chronic hepatitis (CH) or in control patients (C). Similarly, urinary endothelin excretion in LC was significantly increased, compared with CH and C. Urinary endothelin demonstrated a significant positive correlation with creatinine clearance. The ratio of endothelin clearance/creatinine clearance did not differ statistically among the three groups. Urinary sodium excretion in LC was positively correlated with plasma endothelin, but not with urinary endothelin. Urinary endothelin excretion demonstrated a significant negative correlation with urinary kallikrein in LC. The present data suggest that increased urinary endothelin excretion in cirrhotic patients primarily depends upon elevated plasma levels of endothelin, but not renal production. Also, a possible link between endothelin and the kallikrein-kinin system in liver cirrhosis is indicated.

Aged↗
PubMed1996

Pravastatin transport across the hepatocyte canalicular membrane requires both ATP and a transmembrane pH gradient.

Hepatic excretion of non-bile acid organic anions is reported to be ATP-dependent and a defect of this transport has been reported in congenitally jaundiced rats, animal models of human Dubin-Johnson syndrome. To investigate the effect of the transmembrane pH gradient on hepatocyte canalicular membrane transport of ATP-dependent organic anions, uptake of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase-inhibiting organic anion, by hepatocyte canalicular membrane vesicles was observed in the presence or absence of transmembrane pH gradients. Uptake was assessed by a rapid filtration technique. ATP-dependent pravastatin uptake was stimulated in the presence of a transmembrane pH gradient (in > out) in Sprague-Dawley (SD) rats. Uptake was dependent on both pravastatin and ATP concentrations and showed saturation kinetics. After intravenous injection of [14C]-pravastatin (0.3 mumol), 81% of the dose was excreted in the bile within 35 min in SD rats, whereas only 20% was excreted in the bile in Eisai hyperbilirubinuria rats. ATP and the pH gradient also co-stimulated the uptake of pravastatin in Eisai hyperbilirubinuria rats, although the K(m) was much higher and Vmax was much lower than corresponding values in SD rats. This coincided well with the marked reduction in vivo biliary excretion of pravastatin in jaundiced rats.

Adenosine Triphosphate↗
PubMed1996

Structure-antibacterial activity and cytotoxicity relationships of thiazolo and thiazetoquinolone derivatives.

In the course of our search for derivatives with potent antibacterial activity and low cytotoxicity, we have studied the relationships among the structure, antibacterial activity and cytotoxicity of thiazoloquinolone and thiazetoquinolone derivatives (the term quinolone as used in this paper includes the quinolone, 1,8-naphthyridine and pyridopyrimidine nuclei). The antibacterial activities and cytotoxicity of these derivatives were compared with those of norfloxacin, ofloxacin, enoxacin and ciprofloxacin. The antibacterial activities of the thiazoloquinolone derivatives were more potent than those of the dihyrothiazoloquinolone derivatives, and comparable to that of ciprofloxacin. All of the thiazoloquinolone derivatives were highly cytotoxic against mammalian cells, but some of the dihyrothiazoloquinolone derivatives were less cytotoxic, being comparable in cytotoxicity to the reference drugs. The thiazetoquinolone derivatives were less cytotoxic than the thiazoloquinolone derivatives, and one of them, 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazeto[3,2-a] quinoline-3-carboxylic acid, showed the most potent antibacterial activity of all compounds tested in this study, as well as a very low cytotoxicity. The antibacterial activity and cytotoxicity of this compound were similar to that of ciprofloxacin.

4-Quinolones↗
PubMed1996

Preparation and drug release characteristics of the conjugates of mitomycin C with glycol-chitosan and N-succinyl-chitosan.

Mitomycin C (MMC) was covalently attached to glycol-chitosan (Gly-chitosan) and N-succinyl-chitosan (N-Suc-chitosan) through a spacer of the glutaryl group, and each conjugate was obtained as a water-soluble product. Stability of 1a-(4-carboxybutyryl)-MMC (Glu-MMC) in vitro was investigated by incubation in 1/15 M phosphate buffers of pH 5, 6, 7.4, 8 and 9 at 37 degrees C. The release rate of MMC from Glu-MMC was very slow at neutral pH, gradual at basic pH and relatively fast at acidic pH, but the quick decomposition of MMC proceeded simultaneously at acidic pH. Release of MMC from the conjugates in vitro was investigated by incubation in 1/15 M phosphate buffers of pH 5, 7.4 and 9 at 37 degrees C. The release rate of MMC from the conjugates was slight at acidic pH, accelerated at basic pH, and was gradual at pH 7.4. In a plasma-buffer (pH 7.4) mixture (1:1, v/v), the release rate of MMC from the conjugates was rather similar to that in only the buffer (pH 7.4).

Antibiotics, Antineoplastic↗
PubMed1996

Water uptake and growth of cucumber plants (Cucumis sativus L.) under control of dissolved O2 concentration in hydroponics.

Dissolved O2 concentration ([O2]) in nutrient solution was controlled at 0.01, 0.10 and 0.20 mM with accuracy of +/- 0.005 mM in a newly developed hydroponic system, and the effects of [O2] on water uptake and growth of cucumber plants (Cucumis sativus L.) were analyzed. For evaluating water uptake rate under the control of [O2], water flux at the stem base was measured on-line with +/-5% in accuracy, 1 mg s-1 in resolution and 1 min in time constant by heat flux control (HFC) method. Water uptake rate was drastically increased by lighting to the plant at each [O2], and water uptake per day was depressed in proportion to decrease in [O2]. In the plants grown for 10 days, leaf area, fresh weight and dry weight of leaves decreased at lower [O2], while stem length and number of leaves were scarcely affected. These facts suggest that membrane permeability of root cells reduces at lower [O2] through respiration-dependent processes, and growth is inhibited through leaf turgor loss caused by the depressed water uptake of roots in O2-deficient nutrient solution in hydroponics.

Biomass↗
PubMed1995

Protective effect of cystathionine on acute gastric mucosal injury induced by ischemia-reperfusion in rats.

We studied the protective effect of cystathionine on acute gastric mucosal injury induced by ischemia-reperfusion in rats. Under pentobarbital anesthesia, the celiac artery was clamped for 30 min and reperfused. Sixty minutes after the reperfusion, the total area of erosions and thiobarbituric acid-reactive substances in the stomach, as an index of lipid peroxidation, were measured and compared between control and cystathionine-treated groups. Intraperitoneal administration of cystathionine (1-20 mg/kg) 10 min before the ischemia significantly reduced both the total area of erosions and the level of thiobarbituric acid-reactive substances. When cystathionine (10 mg/kg) was administered orally, the significant reductions in the total area of erosions and level of thiobarbituric acid-reactive substances were also observed. There was a good correlation between the total area of erosions and the level of thiobarbituric acid-reactive substances. Cystathionine did not affect blood flow during ischemia-reperfusion. These results indicate that the protective effect of cystathionine on acute gastric mucosal injury induced by ischemia-reperfusion may be due to the scavenging action against superoxide radicals in vivo.

Animals↗
PubMed1995

Biodegradation ranks of priority organic compounds under anaerobic conditions.

The biodegradations of 52 priority organic compounds were evaluated under anaerobic conditions by two tests developed in a preceding paper (Urano et al., 1995). Namely, the biodegradabilities of the compounds were classified into 13 ranks by the method proposed by Urano et al. (1995). Most of the aliphatic alcohols and carboxylic acids were not inhibitory and were biodegraded, but the compounds having ether bonds or branched hydrocarbon groups were biodegraded slowly. Aliphatic aldehyde and amines were not so much inhibitory but were hardly biodegraded. The benzene substitutes having groups of -CH2OH, -CHO, -CH2CH(NH2)COOH, -COOH and -OH were easily biodegraded, but the compounds having groups of -NO2, -NH2 and -SO3H were hardly biodegraded. Most of the nitro compounds were inhibitory in the higher concentration test though they were reduced into amino compounds. Since the biodegradation characteristics of many organic compounds could be classified and discussed appropriately, the suitability of the proposed method is substantiated.

Anaerobiosis↗
PubMed1995

Testing and classification methods for the biodegradabilities of organic compounds under anaerobic conditions.

Biodegradability is one of the most important characteristics of an organic compound for predicting its fate and life in the environment and its application in biological wastewater treatment. But there is no general testing method for biodegradability under anaerobic conditions. The biodegradabilities of thirteen principal organic compounds was investigated in a batch test using vials under various conditions, such as the concentration of an organic compound, the cultivation method and the concentration of anaerobic bacteria for seeding. Two test methods in the standard concentration and the low concentration were developed. A new method to classify the biodegradabilities of organic compounds into thirteen ranks was proposed by considering inhibition, complete biodegradation and first step biodegradation.

Bacteria, Anaerobic↗
PubMed1995

Characterization of nodules induced by bioactive glass on cultured periodontal-ligament fibroblasts.

We previously reported that materials leached from bioactive glass (BG) and vitamin D3 induced the formation of nodules on cultured periodontal-ligament fibroblasts (PLF). In this study, we have investigated the relationship between the conditions of the materials and nodule formation, analyzed morphologically, and also studied whether the production of nodules was specific to cultured PLF. PLF and skin fibroblasts were cultured in the presence or absence of BG. The amounts of calcium, phosphate, sodium and silicon in the culture medium and the number of nodules were measured at the 55th day. The nodules were observed microscopically and analyzed using an X-ray microanalyzer. In PLF, nodules were formed regardless of the presence or absence of BG; however, they were more numerous in the presence of BG. In skin fibroblasts, nodules were not observed. The amounts of calcium and silicon were higher in the presence of BG, while the amount of phosphate was lower. The nodules appeared crystalline with a spongy structure and contained calcium and phosphorus. Our results show that the nodules were associated with PLF and precipitated by the materials (higher concentrations of calcium and silicon), and they were spongy crystal composed of calcium and phosphorus.

Biocompatible Materials↗
PubMed1995

Spatially distributed responses induced by contrast reversal in cat visual cortex.

Field potentials were recorded from cat striate cortex, either between an epidural screw electrode and a cannula-electrode inserted deep in the gray matter (transcortical recording) or with a pair of metal microelectrodes. Electrodes were placed bilaterally near the cortical projection of the area centralis. The horizontal separation of the recording tips was approximately 2 mm and approximately 300 microns, respectively. The area of the visual field providing input to the recording site (receptive field) was determined by measuring the field potentials generated by contrast reversal of high-contrast, achromatic bar gratings. Five-degree-diameter grating patches were presented individually over a large area of the visual field. The gratings were contrast-reversed at 4, 6 or 10 Hz, while also being swept in spatial frequency between 0.56 and 5.24 c/deg. The receptive fields were approximately 20 deg across or more, substantially larger than expected on the basis of cortical retinotopy. Responses were also elicited by stimulation of the hemi-field contralateral to that contributing to the classical receptive field, implicating the presence of a callosal projection. The large, spatially distributed receptive fields consisted of patches of high and low sensitivity. Continuous cortical infusion of either 100 microM tetrodotoxin or 10 mM muscimol at the recording site totally suppressed the transcortically recorded field potentials, proving that the local field potentials were generated postsynaptically. The present findings suggest that a cluster of cortical cells near the projection site of the area centralis receives input from remote cortical regions to an extent that is comparable with that of anatomically demonstrated long-range lateral connections.

Animals↗