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Biomedical subjects

M Ohnishi

Publications and source records attributed to M Ohnishi.

At least 19 recordsLinked to original sources
PubMed1995

Chemoprevention of azoxymethane-induced colon carcinogenesis by dietary feeding of S-methyl methane thiosulfonate in male F344 rats.

Modifying effects of dietary exposure of S-methyl methane thiosulfonate (MMTS) isolated from cauliflower Brassica oleracea L. var. botrytis on rat colon carcinogenesis induced by azoxymethane (AOM) and on the expression of cell proliferation biomarkers were investigated in two experiments. In experiment 1, male F344 rats were given three s.c. injections of AOM (15 mg/kg body weight) and fed 100 ppm MMTS for 5 weeks, starting 1 week before the first dose of AOM. The frequency of colonic aberrant crypt foci was determined at 5 weeks after the start. Feeding of 100 ppm MMTS for 5 weeks significantly decreased the number of aberrant crypt foci/colon. Colonic mucosal ornithine decarboxylase activity and the number of silver-stained nucleolar organizer regions per nucleus in colonic epithelium were significantly decreased by MMTS treatment compared with those of AOM alone. In experiment 2, effects of dietary feeding of MMTS at two doses (20 and 100 ppm) during the postinitiation phase on intestinal tumorigenesis initiated with AOM were investigated by using a long-term experiments in male F344 rats. Incidence of intestinal neoplasms of rats fed MMTS-containing diets after AOM exposure were reduced in a dose-dependent manner. Feeding of MMTS during the postinitiation phase decreased the number of aberrant crypt foci/colon, colonic ornithine decarboxylase activity, 5-bromodeoxyuridine-labeling index in colonic epithelium, and polyamine level in blood compared with those of AOM alone. These results suggest that MMTS might be a possible chemopreventive agent for intestinal neoplasia.

Animals↗
PubMed1995

Chemoprevention of rat oral carcinogenesis by naturally occurring xanthophylls, astaxanthin and canthaxanthin.

The chemopreventive effects of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX) on oral carcinogenesis induced by 4-nitroquinoline 1-oxide (4-NQO) was investigated in male F344 rats. Rats were given 20 ppm of 4-NQO in their drinking water for 8 weeks to induce oral neoplasms or preneoplasms. Animals were fed diets containing 100 ppm AX or CX during the initiation or postinitiation phase of 4-NQO-induced oral carcinogenesis. The others contained the groups of rats treated with AX or CX alone and untreated. At the end of the study (week 32), the incidences of preneoplastic lesions and neoplasms in the oral cavity of rats treated with 4-NQO and AX or CX were significantly smaller than those of rats given 4-NQO alone (P < 0.001). In particular, no oral neoplasms developed in rats fed AX and CX during the 4-NQO exposure and in those given CX after the 4-NQO administration. Similarly, the incidences of oral preneoplastic lesions (hyperplasia and dysplasia) in rats treated with 4-NQO and AX or CX were significantly smaller than that of the 4-NQO-alone group (P < 0.05). In addition to such tumor inhibitory potential, dietary exposure of AX or CX decreased cell proliferation activity in the nonlesional squamous epithelium exposed to 4-NQO as revealed by measuring the silver-stained nucleolar organizer regions protein number/nucleus and 5'-bromodeoxyuridine-labeling index. Also, dietary AX and CX could reduce polyamine levels of oral mucosal tissues exposed to 4-NQO. These results indicate that AX and CX are possible chemopreventers for oral carcinogenesis, and such effects may be partly due to suppression of cell proliferation.

Animals↗
PubMed1995

Molecular cloning and expression of mouse mg(2+)-dependent protein phosphatase beta-4 (type 2C beta-4).

A full-length complementary DNA (cDNA) clone (pTK-3) encoding an isoform of Mg(2+)-dependent protein phosphatase beta (MPP beta-4) was isolated for the first time from a mouse melanocyte cDNA library. It was strongly suggested that the mRNA corresponding to the pTK-3 insert was a splicing variant of a single pre-mRNA that also encodes MPP beta-1 and -2 (T. Terasawa, T. Kobayashi, T. Murakami, M. Ohnishi, S. Kato, O. Tanaka, H. Kondo, H. Yamamoto, T. Takeuchi, and S. Tamura, 1993, Arch. Biochem. Biophys. 307, 342-349). The amino acid sequence of MPP beta-4 differed from those of MPP beta-1 and -2 only at the carboxyl terminal region. Analysis by reverse transcriptase polymerase chain reaction (RT-PCR) revealed that MPP beta-4 mRNA was expressed only in testis and intestine and not in other mouse tissues tested. Specific expression of the mRNA signals of two other isoforms of MPP beta, MPP beta-3 and -5 (a novel isoform), in testis and intestine was also demonstrated by the RT-PCR. The carboxyl terminal region of MPP beta-5 was found to have a chimera structure composed of part of MPP beta-1 and part of MPP beta-3. The recombinant MPP beta-3 and -4 and the putative MPP beta-5 expressed in Escherichia coli cells exhibited Mg(2+)-dependent and okadaic acid-insensitive protein phosphatase activities. It was demonstrated that the mRNA expression levels of MPP beta-3, -4, and -5 alter according to the maturation of mouse testis. These results suggest that the complex structure of MPP beta isoforms and their tissue- and developmental stage-specific expression reflect the variety of their physiological functions.

Alternative Splicing↗
PubMed1995

Differences in body temperature changes during dressing change in surviving and non-surviving burned patients.

Change in body temperature (delta BT) while dressings were being changed was measured in 52 extensively burned adults. The patients were divided into four groups based on outcome and the prognostic burn index (PBI; age + burn index): group I (15 survivors, PBI less than or equal to 80), group II (15 survivors, PBI between 80 and 120), group III (14 non-survivors, PBI between 80 and 120), and group IV (eight non-survivors, PBI greater than 120). The body temperature before the change of dressings was the same in the four groups. The mean(s.d.) delta BT in all patients was -0.5(0.8) degrees C. The magnitude of delta BT was not related to the time required for changing dressings (r = 0.04) or to the non-epithelialized area present at each change of dressings (r = -0.05). All groups showed a similar increase in delta BT during the early period after the burn, but in group I it began to decrease progressively after the 16th day after the burn (P < 0.05). A reduction in delta BT was noted in group II from day 25, whereas it was unchanged in groups III and IV (P < 0.05). It also significantly increased 2 days before the diagnosis of sepsis (P < 0.05). These results emphasize that delta BT may provide useful information about prognosis and the development of sepsis.

Adult↗
PubMed1995

Estimation of the total saliva volume produced per day in five-year-old children.

Fifteen boys and 15 girls were asked to record for 2 days the time spent awake, eating meals or snacks, and sleeping. The salivary flow rates elicited by chewing foods were also determined. The mean flow rate (+/- SD) of unstimulated saliva was 0.26 +/- 0.16 ml/min and that of saliva while chewing six different foods was 3.6 +/- 0.8 ml/min. The mean times spent eating, and awake but not eating, were 80.8 +/- 27.3 and 820 +/- 59 min, respectively, and the volumes of saliva produced during those periods would average about 288 and 208 ml, respectively. If the flow rate is virtually zero during sleep, the estimated total salivary volume produced per day is calculated to be about 500 ml.

Child, Preschool↗
PubMed1995

Low oxygen extraction despite high oxygen delivery causes low oxygen consumption in patients with burns recovering slowly from operative hypothermia.

BACKGROUND: Patients with burns who eventually succumbed to their injuries tended to recover more slowly from operative hypothermia than those who survived. Slower recovery was associated with a lower postoperative oxygen consumption (VO2). We have now investigated whether this was due to impairment of oxygen delivery or extraction. METHODS: This study was performed in 13 adult patients with severely burns. One hundred four measurements of VO2 by indirect calorimetry were made during recovery from 23 episodes of operative hypothermia in 11 patients. Sixty-six measurements of oxygen transport variables by balloon-tipped pulmonary artery catheter were made after 17 episodes of operative hypothermia in six patients. Body temperature was monitored in the urinary bladder. RESULTS: The rate of temperature rise (T) showed a strong positive correlation with VO2 measured both by indirect calorimetry (r = 0.91, p < 0.001) and by balloon-tipped pulmonary artery catheter (r = 0.83, p < 0.001). Oxygen delivery (DO2) was above normal in nearly all patients. Oxygen extraction was low in patients recovering slowly (T < 1.0 degree C/hr) and high in those recovering quickly (T > or = 1.0 degree C/hr). During fast recovery VO2 (373 +/- 77 ml.min-1.m-2; mean +/- SD) was approximately three times normal and was independent of DO2. In contrast, a strong linear relationship existed between VO2 and DO2 during slow recovery (r = 0.76, p < 0.001). CONCLUSIONS: Patients with burns with slow recovery from operative hypothermia exhibited impaired oxygen extraction and dependence of VO2 on DO2 over a wide range. This picture resembles that in patients with critical illness.

Adult↗
PubMed1995

Chemoprevention of urinary bladder carcinogenesis by the natural phenolic compound protocatechuic acid in rats.

The modifying effect of dietary administration of protocatechuic acid (PCA) during the initiation and postinitiation phases on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder carcinogenesis was investigated in male F344 rats. Animals were divided into nine groups and groups 1-7 were given 0.05% BBN in drinking water for 6 weeks to induce bladder neoplasms. Rats in groups 2, 3 and 4 were fed diets containing 500, 1000 and 2000 p.p.m. PCA respectively for 8 weeks, starting 1 week before BBN exposure. Groups 5, 6 and 7 were fed the PCA-containing diets at three dose levels for 33 weeks. Group 8 was fed the diet containing 2000 p.p.m. PCA alone throughout the study. Group 9 was given tap water without BBN and the basal diet without PCA and served as an untreated control. At 41 weeks after the start, all animals were killed. The incidence of bladder tumors and preneoplastic lesions, and cell proliferation activity estimated by the numbers of silver-stained nucleolar organizer regions proteins (AgNORs) and proliferating cell nuclear antigen (PCNA)-immunoreactive cells were compared among the groups. PCA administration at 1000 and 2000 p.p.m. during the initiation and postinitiation phases significantly decreased the carcinoma incidence in a dose-dependent manner. Also, PCA at all doses given during either initiation or postinitiation phases reduced the development of the preneoplastic lesions. PCA feeding significantly reduced the numbers of AgNORs and PCNA-positive cells in the non-lesional transitional epithelium, preneoplasms, and neoplasms in the urinary bladder of rats treated with BBN. These results indicate that dietary administration of PCA is quite effective in preventing BBN-induced bladder carcinogenesis.

Animals↗
PubMed1995

Inhibition of oral carcinogenesis by the arotinoid mofarotene (Ro 40-8757) in male F344 rats.

The chemopreventive effect of dietary administration of a new arotinoid, mofarotene (Ro 40-8757), which contains a morpholine structure in the polar end group, during the initiation phase of 4-nitroquinoline 1-oxide (4-NQO)-induced oral carcinogenesis was investigated in male F344 rats. Also, modulatory effects of this compound on polyamine levels (biomarkers of proliferation), the 5-bromodeoxyuridine-labeling index and the number of silver stained nucleolar organizer region proteins (AgNORs)/nucleus were assessed in the target epithelium. Rats were fed Ro 40-8757 at concentrations of 250 and 500 p.p.m. for 10 weeks. One week after the commencement of the diets, 4-NQO (20 p.p.m.) was administered in the drinking water for 8 weeks. Feeding of Ro 40-8757 at both doses caused a 78% reduction in the incidence of tongue neoplasms (squamous cell papilloma and carcinoma) by 32 weeks when compared with rats treated with 4-NQO alone (P < 0.05). Similarly, in rats treated with 4-NQO together with Ro 40-8757 the incidence of preneoplastic lesions (hyperplasia and dysplasia) was significantly less than the 4-NQO alone group (P < 0.05). Expression of three biomarkers was also decreased significantly by dietary treatment with Ro 40-8757. Thus a new arotinoid, Ro 40-8757, inhibited the oral carcinogenesis induced by 4-NQO when it was administered concurrently with the carcinogen. These results might suggest the possible application of Ro 40-8757 for cancer chemoprevention in the oral cavity, in addition to the breast.

Animals↗
PubMed1995

Inhibition of 4-nitroquinoline-1-oxide-induced rat oral carcinogenesis by dietary exposure of a new retinoidal butenolide, KYN-54, during the initiation and post-initiation phases.

The modifying effect of dietary exposure of a newly synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone (KYN-54) during the initiation and post-initiation phases of oral carcinogenesis initiated with 4-nitroquinoline-1-oxide (4-NQO) was investigated in male F344 rats. At 6 weeks of age, rats were divided into experimental and control groups. At 7 weeks of age, all animals except those treated with KYN-54 alone and those in a control group were given 4-NQO (20 p.p.m.) in the drinking water for 8 weeks to induce oral neoplasms. Seven days after stopping 4-NQO exposure, groups of animals fed the diets containing 100 and 200 p.p.m. KYN-54 for 10 weeks starting 1 week before 4-NQO exposure were switched to the basal diet and kept on this diet until the end of the experiment. Starting 1 week after the cessation of 4-NQO administration, the groups given 4-NQO and the basal diet were switched to the diets containing 100 or 200 p.p.m. KYN-54 and maintained on these diets for 22 weeks. The other group consisted of rats given 200 p.p.m. KYN-54 alone or untreated rats. All animals were necropsied at the termination of the study (week 32). The incidences of tongue neoplasms and preneoplastic lesions, polyamine levels in the tongue tissue, and cell proliferation activity estimated by bromodeoxyuridine (BrdU)-labeling index and by morphometric analysis of silver-stained nucleolar organizer regions protein (AgNORs) were compared among the groups. Feeding of KYN-54 during either initiation or post-initiation phase caused a significant reduction in the frequency of tongue carcinoma (48-71% reduction, P < 0.05) and such chemopreventive efficacy was dose-related. The incidences of preneoplastic lesion in rats fed the diets mixed with KYN-54 at both doses were also decreased (P < 0.05). Dietary administration of KYN-54 also significantly decreased the labeling index of BrdUrd and the number of AgNORs per cell nucleus of the tongue squamous epithelium (P < 0.05). In addition, polyamine levels in the oral mucosa were lowered in rats given 4-NQO and test compound when compared to those given 4-NQO alone, but no significant difference was obtained. These results indicate that the novel synthesized retinoidal butenolide KYN-54 inhibits oral carcinogenesis initiated with 4-NQO and such inhibition may be related to suppression of cell proliferation.

4-Butyrolactone↗
PubMed1995

Analysis of functional domains of Rts1 RepA by means of a series of hybrid proteins with P1 RepA.

The RepA protein of the plasmid Rts1, consisting of 288 amino acids, is a trans-acting protein essential for initiation of plasmid replication. To study the functional domains of RepA, hybrid proteins of Rts1 RepA with the RepA initiator protein of plasmid P1 were constructed such that the N-terminal portion was from Rts1 RepA and the C-terminal portion was from P1 RepA. Six hybrid proteins were examined for function. The N-terminal region of Rts1 RepA between amino acid residues 113 and 129 was found to be important for Rts1 ori binding in vitro. For activation of the origin in vivo, an Rts1 RepA subregion between residues 177 and 206 as well as the DNA binding domain was required. None of the hybrid initiator proteins activated the P1 origin. Both in vivo and in vitro studies showed, in addition, that a C-terminal portion of Rts1 RepA was required along with the DNA binding and ori activating domains to achieve autorepression, suggesting that the C-terminal region of Rts1 RepA is involved in dimer formation. A hybrid protein consisting of the N-terminal 145 amino acids of Rts1 and the C-terminal 142 amino acids from P1 showed strong interference with both Rts1 and P1 replication, whereas other hybrid proteins showed no or little effect on P1 replication.

Bacterial Proteins↗
PubMed1995

Effects of separate and combined ETA and ETB blockade on ET-1-induced constriction in perfused rat lungs.

To evaluate the role of endothelin (ET) receptors in ET-1-induced pulmonary vasoreactivity, we studied the effects of ET-receptor agonists and antagonists in isolated perfused rat lungs. ET-1 (1-10 nM) caused concentration-dependent pulmonary vasoconstriction and gross pulmonary edema at a concentration of 10 nM. The combination of the selective ETA antagonist BQ-123 and the selective ETB antagonist BQ-788 inhibited ET-1-induced pulmonary vasoconstriction more effectively than BQ-123 alone, whereas BQ-788 alone enhanced the constriction. ET-1-induced hydrostatic pulmonary edema was prevented by the combination of BQ-123 and BQ-788 but not by either BQ-123 or BQ-788 alone. After the addition of 125 ng of exogenous ET-1, the perfusate levels of ET-1 were significantly higher in BQ-788-treated lungs than in either the vehicle control or BQ-123-treated lungs. The selective ETB agonist IRL-1620 also caused pulmonary vasoconstriction and edema, both of which were completely inhibited by BQ-788. ET-1-induced transient vasodilation was abolished by BQ-788 but was unaffected by BQ-123. These results suggest that in the isolated perfused rat lung, ET-1-induced vasoconstriction is mediated by both ETA and ETB receptors, whereas ET-1-induced transient vasodilation is mediated exclusively by the ETB receptor. Blockade of ETB receptors may result in enhanced ET-1 activity (via the ETA receptor) through inhibition of the ETB-mediated clearance of ET-1. Thus combined ETA and ETB blockade is required for the complete inhibition of ET-1-induced vasoconstriction in the rat pulmonary circulation.

Animals↗
PubMed1995

Involvement of annexin-I in glucose-induced insulin secretion in rat pancreatic islets.

Annexin-I was demonstrated to specifically present in islets and not in exocrine tissues of the rat pancreas and to have a diffuse and homogeneous distribution in all islet cells in our previous study. In the present report, to clarify the functions of annexin-I in rat pancreatic islets, especially in beta-cells, we investigated the role of annexin-I in insulin secretion. Immunoelectron microscopic analysis of pancreatic beta-cells demonstrated that immunogold particles reactive to annexin-I were almost exclusively observed on most of the insulin-containing granules (approximately 90%) and less frequently located in cytosol and other organelles, such as the endoplasmic reticulum and mitochondria. The number of annexin-I gold particles located on insulin granules after oral glucose administration was significantly increased compared with that observed in fasted rats. Moreover, when the isolated islets were stimulated by a high concentration of glucose (20 mM), the phosphorylation of annexin-I was markedly enhanced, and it was synchronized to insulin secretion. This phosphorylation mainly occurred on serine residues. H-7 (100 microM), a potent inhibitor of protein kinase-C, inhibited the phosphorylation to about 90%. These findings suggest that annexin-I might be involved in the regulatory mechanism of glucose-induced insulin secretion in rat pancreatic islets via phosphorylation-dephosphorylation processes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Potentiation of excito-toxicity by glutamate uptake inhibitor rather than glutamine synthetase inhibitor.

The neuroprotective functions of glia cells in the presence of excessive amounts of extracellular glutamate (Glu) were examined using glia-rich and glia-poor cultured cerebellar granule cells that contained the same number of neurons. In order to focus on the metabolic enzyme glutamine synthetase (GS) and the uptake system in glia cells, selective inhibitors such as L-methionine sulfoximine (MSO) and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) were used as pharmacological tools. The increased amount of lactate dehydrogenase (LDH) leakage induced by 50 microM Glu and SITS was equivalent to that of 1 mM Glu. However, the simultaneous treatment with 50 microM Glu and 5 microM MSO did not increase the LDH leakage. The larger quantities of extracellular Glu were sustained in both glia-rich and glia-poor cultures. After the administration of Glu and MSO, however, the larger quantities of Glu were not sustained. Taking these results into consideration, the Glu uptake system in glia cells seems to be more important than the Glu metabolic enzyme system in the regulation of neuronal protection from Glu toxicity.

Animals↗
PubMed1995

Taste responses to the optical isomers of potassium warfarin and dipotassium glutamyl glutamate and the synergistic response to a mixture of both substances in mice.

The taste responses to the optical isomers of potassium warfarin, dipotassium glutamyl glutamate, and a mixture of both the substances in laboratory mice were studied using licking activity as an indicator of taste effectiveness. The offensive effectiveness of the optical isomers of potassium warfarin was the same. Every optical isomer of dipotassium glutamyl glutamate was avoided, the taste avoidance of dipotassium D-glutamyl D-glutamate being the strongest. The taste avoidance of potassium warfarin was greatly increased by the addition of every isomers of dipotassium glutamyl glutamate, and its cause was related to synergistic effects.

Animals↗
PubMed1995

Structure-activity relationship between the hydrophobicity of alkali metal salts of warfarin [3-(alpha-acetonyl-benzyl)-4-hydroxycoumarin] and the effectiveness of the taste response to these salts in mice.

The taste responses to five alkali metal salts of warfarin, aqueous rodenticides, in laboratory mice were observed at a short measurement time of 20 min by the two-bottle preference test using a licking time monitoring system newly developed. It was made clear that the order of taste avoidance to the warfarin salts was as follows: cesium salt > rubidium salt > lithium salt > sodium salt > potassium salt. The relationship between the hydrophobicity of the warfarin salts and the effectiveness of the taste avoidance was analyzed. The effectiveness of the taste avoidance largely depended on the hydrophobicity.

Alkalies↗
PubMed1995

[Cytokines of nasal inverted papilloma: quantification and distribution].

We previously found that an increased number of mucosal mast cells accumulated in the tumor site of nasal inverted papilloma as well as in the epithelial layer of the allergic nasal mucosa. However, the mechanism of accumulation of mucosal mast cells has not yet been clarified. The purpose of this study was to evaluate the cytokines produced by inverted papilloma cells, which would be important for the accumulation of mucosal mast cells. We found that the supernatant of the monolayer of cultured inverted papilloma cells contained GM-CSF, IL-6 and IL-8. IL-2, IL-3, IL-4 and IL-5 were not detected. Contrary to the quantities of cytokines detected in the supernatant of cultured allergic nasal epithelial cells, the quantities of IL-6 and IL-8 were greater in the supernatant of cultured inverted papilloma, whereas that of GM-CSF was less. Immunohistochemical study revealed the distribution of cytokines: GM-CSF was detected near the basement membrane of the tumor site, while IL-6 and IL-8 were detected in the superficial layer of nasal inverted papilloma. Interestingly, the tumor site near the basement membrane is also the site of accumulation of mucosal mast cells, suggesting that GM-CSF produced by nasal inverted papilloma cells may be one of the most important factors in the accumulation of mucosal mast cells.

Adult↗
PubMed1995

Inhibitory effects of newly synthesized Ser-contained GABA-peptides administered into either caudate putamen or amygdala on methamphetamine-induced hyperactivity.

The locomotor activities induced by methamphetamine (MAP: 1 mg/kg) following the microinjection of either GABA or three synthesized GABA-peptides (PLG, PSLG, PDSLG) into the rat caudate putamen or the amygdala were measured by using behavioral analysis. The ip administration of MAP induced hyperactivities in a time-dependent manner, and the maximum activity was measured 30 min after MAP administration. This hyperactivity was observed for more than 2 hrs. By the microinjection of GABA-peptides (0.054-540 nmol) into each brain region, the MAP-induced hyperactivity was significantly reduced in a dose-dependent manner, although the single administration of examined dosages of these peptides did not influence the locomotor activity. In the case of microinjection of GABA into either one of the brain regions, only the larger dosage (27,000 nmol) significantly reduced the MAP-induced hyperactivity, whereas this inhibition was less than that seen at the dose of 540 nmol of GABA-peptides. Furthermore, the microinjection of newly synthesized GABA-peptides, PSLG and PDSLG, into the caudate putamen was more effective than those obtained by injection into the amygdala. However, either microinjection of PLG or GABA into both regions showed similar inhibition. These results suggest that the pharmacological properties of newly synthesized GABA-peptides are different compared to those of PLG and GABA, and that these differences might be due to the primary inhibitory effects of the serine-contained GABA-peptides on dopaminergic neuronal activity, but not on GABA neurons.

Amygdala↗