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Biomedical subjects

A Hara

Publications and source records attributed to A Hara.

At least 271 records · Page 15Linked 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

Correspondence of RLGS-M spot behavior with tissue expression on mouse homologue of DP1/TB2 gene.

RLGS-M is a novel method which enables visual and quantitative detection of many methylatable loci as two-dimensional gel spots. We isolated and characterized a mouse genomic clone corresponding to the RLGS-M gel spot #109v, which showed different intensities between two tissues: the spot was much more faint in liver than in brain. Southern and Northern blot analysis disclosed this spot behavior to be related to the methylation state of NotI site and also to be correlated with the differential expression in both tissues; the transcripts for #109v were observed in the brain but hardly any in the liver. Furthermore, in the base sequence analysis, this #109v gene was found to be the mouse homologue of human DP1/TB2 gene and had a CpG island adjacent to the NotI site. These results indicate that the mouse DP1/TB2 gene is expressed corresponding to its RLGS-M spot behavior which is related to its methylation condition.

Animals↗
PubMed1995

Reduction of drug ketones by dihydrodiol dehydrogenases, carbonyl reductase and aldehyde reductase of human liver.

In this study, we compared the enzymatic reduction of 10 drugs with a ketone group by homogeneous carbonyl reductase, aldehyde reductase and three dihydrodiol dehydrogenases of human liver cytosol. At least one and in some cases all of the three dihydrodiol dehydrogenases reduced each of the ten drugs. Among these naloxone, naltrexone, befunolol, ethacrynic acid and ketoprofen were substrates specific for the dehydrogenases. The other drugs--haloperidol, metyrapone, loxoprofen, daunorubicin and acetohexamide--were highly reduced by carbonyl reductase and/or aldehyde reductase. The dihydrodiol dehydrogenases also showed lower Km values for haloperidol and loxoprofen than did carbonyl reductase. The results indicate that the three dihydrodiol dehydrogenases, as well as the two reductases, are implicated in the reduction of ketone-containing drugs in human liver cytosol.

Alcohol Oxidoreductases↗
PubMed1995

Suppression of azoxymethane-induced colonic aberrant crypt foci by dietary exposure to a novel synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)ethenyl)-2(5H)-furanone, in rats.

The modifying effect of dietary exposure to a novel synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)ethenyl)-2(5H)-furanone (KYN-5) on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in male F344 rats. Animals were given weekly s.c. injections of AOM (15 mg/kg body wt.) for 3 weeks to induce ACF. These rats were fed diet containing 100 or 200 ppm KYN-54 for 5 weeks, starting 1 week before the first dosing of AOM. All rats were killed 2 weeks after the last AOM injection, to measure the number of ACF, ornithine decarboxylase (ODC) activity, mucosal polyamine level, and silver-stained nucleolar organizer regions protein (AgNORs) count per nucleus in the colon. In rats given AOM and KYN-54, the frequency of ACF/colon was significantly decreased compared with that in rats given AOM alone. ODC activity and polyamine levels, and the mean AgNORs number in the colon of rats given AOM and KYN-54 at both doses were also significantly lower than that of rats treated with AOM alone. These results provide further evidence that KYN-54 could be a chemopreventive agent against rat colon carcinogenesis.

4-Butyrolactone↗
PubMed1995

Evidence for indirect utilization of glycine for production of N-bases of glycerophospholipids and sphingolipids in mouse neuroblastoma cells by using 15N-labeled glycine.

After mouse neuroblastoma cells were cultured with [15N]glycine in Dulbecco's modified Eagle's medium for total four days, they gave significant amounts of 15N-atom% excess in phosphatidylserine, phosphatidylethanolamine, ethanolamine plasmalogen, phosphatidylcholine, sphingomyelin and ceramide. These results were compared with those of [15N]choline, [15N]ethanolamine and [15N]DL-serine used in place of [15N]glycine for the experiments. It was suggested that [15N]glycine is taken into the cells and metabolically converted to [15N]L-serine, which is well known to be used for the production of polar head groups of glycerophospholipids and sphingosine.

Animals↗
PubMed1995

Molecular cloning and characterization of mouse estradiol 17 beta-dehydrogenase (A-specific), a member of the aldoketoreductase family.

Several mammalian livers contain monomeric 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) with A-stereospecificity in hydrogen transfer, which differs from the B-specific dimeric enzyme of human placenta in its ability to catalyze the oxidoreduction of xenobiotic trans-dihydrodiols of aromatic hydrocarbons and carbonyl compounds. Here, we report the isolation and characterization of a mouse cDNA clone encoding monomeric 17 beta-HSD of the liver. This clone had an entire coding region for a protein of 323 amino acid residues with a molecular weight of 37,055. The deduced sequence of the protein aligned with a high degree of identity with rat and rabbit 20 alpha-HSDs, rat and human 3 alpha-HSD/dihydrodiol dehydrogenases, and bovine prostaglandin F synthase, which are members of the aldoketoreductase family, but was distinct from human 17 beta-HSD and carbonyl reductase, members of the short chain dehydrogenases. The expression of the cDNA in Escherichia coli resulted in synthesis of a protein that was active toward androgens, estrogens, and xenobiotic substrates. The recombinant and mouse liver 17 beta-HSDs also exhibited low 20 alpha-HSD activity toward progestins, which is similar to bifunctional activity of human placental 17 beta-HSD. Therefore, the mouse enzyme was given the designation of estradiol 17 beta-dehydrogenase (A-specific). Northern analysis of mouse tissues revealed the existence of a single 1.7-kilobase 17 beta-HSD mRNA species in the liver, kidney, testis, and stomach. The liver mRNA content was considerably more abundant than those found in the other tissues, as 17 beta-HSD protein was mainly detected in the liver by Western analysis.

Amino Acid Sequence↗
PubMed1995

Modifying effects of naturally occurring products on the development of colonic aberrant crypt foci induced by azoxymethane in F344 rats.

Modifying effects of dietary exposure of seven naturally occurring products on the development of colonic aberrant crypt foci (ACF) induced by azoxymethane (AOM) were investigated in male F344 rats. The effects of these compounds on proliferation biomarkers such as the number of silver-stained nucleolar organizer region protein, ornithine decarboxylase activity, and polyamine concentration in the colon were also estimated. The naturally occurring products tested included four terpenoids (rebaudioside A, oleanolic acid, costunolide, and soyasaponin A2), one flavonoid (liquiritin), and two isocoumarins (phyllodulcin and hydrangenol). Animals were given 3 weekly s.c. injections of AOM (15 mg/kg body weight) to induce ACF. These rats were fed the diet containing 200 ppm of each test chemical for 5 weeks, starting 1 week before the first dosing of AOM. All rats were sacrificed 2 weeks after the last AOM injection to estimate their modulatory effects on the occurrence of ACF and the cell proliferation biomarkers in the colon. In groups of rats given AOM and hydrangenol, oleanolic acid, or costunolide, the frequencies of ACF/colon were significantly lower than that of AOM alone (P < 0.05, P < 0.005, and P < 0.05, respectively). In groups of rats given AOM and costunolide and those treated with AOM and soyasaponin A2, both ornithine decarboxylase activity and polyamine concentration of the colonic mucosal tissue were significantly decreased compared with those in rats given AOM alone (P < 0.05 and P < 0.001 for costunolide and P < 0.001 and P < 0.05 for soyasaponin A2, respectively). In groups of rats given AOM and liquiritin, oleanolic acid, or costunolide, the numbers of silver-stained nucleolar organizer regions/nucleus were significantly lower than that of AOM alone (P < 0.05, P < 0.01, and P < 0.05, respectively). Costunolide decreased four AOM-induced biomarkers, such as the frequencies of ACF/colon, ornithine decarboxylase activity, polyamine concentration level, and silver-stained nucleolar organizer region number in the colon. These results indicate that, among the test chemicals, costunolide has blocking effects against rat colon carcinogenesis and is a possible chemopreventive agent against colon tumorigenesis. Also, the short-term model described here could be a very useful prescreening tool for chemopreventive agents against colon cancer.

Animals↗
PubMed1995

Cloning, expression and tissue distribution of mouse tetrameric carbonyl reductase. Identity with an adipocyte 27-kDa protein.

We previously cloned a cDNA for pig lung tetrameric carbonyl reductase which shows significant similarity to a putative 27-kDa protein predicted from the cDNA for murine adipocyte RNA which had been increased in its differentiation [Nakanishi, M., Deyashiki, Y., Nakayama, T., Sato, K. & Hara, A. (1993) Biochem. Biophys. Res. Commun. 194, 1311-1316]. In this investigation, we isolated and sequenced a full-length cDNA for the tetrameric enzyme from a mouse lung cDNA library. It consisted of 984 bp and coded for a protein of 244 amino acid residues, of which 202 residues were identified by protein sequencing. The expression of the cDNA in Escherichia coli resulted in synthesis of a protein structurally and functionally similar to the enzyme purified from mouse lung. The nucleotide sequence of the cDNA was virtually identical to that of the cDNA for the adipocyte 27-kDa protein. Although Northern-blot analysis of mouse tissues showed that enzyme mRNA to be 1.1 kb only in lung, low expression of the mRNA in all the extrapulmonary tissues, including adipose tissue, was demonstrated by a reverse-transcription PCR method. Western-blot analysis also indicated the presence of the enzyme in the adipose tissue. This is the first report on an identification of the putative gene product of adipocytes as tetrameric carbonyl reductase, the expression of which is tissue-specifically regulated.

Adipocytes↗
PubMed1995

Temporal profile of nuclear DNA fragmentation in situ in gerbil hippocampus following transient forebrain ischemia.

To determine the time course of nuclear DNA damage in the gerbil hippocampus following transient ischemia, brain sections 48, 72, 96 h and 7 days following 5 min ischemia were evaluated by a specific in situ labeling method of DNA breaks. After 72 h, only the neurons located in the medial part of the CA1 sector were labeled. And then, DNA damage extended to the lateral part of the sector with time.

Animals↗
PubMed1995

Laparoscopic splenectomy in children. Preliminary results and comparison with the open technique.

To determine the safety and efficacy of laparoscopic splenectomy (LS) in children, a retrospective review of our preliminary experience using LS was compared to results in patients who previously underwent open splenectomy (OS). From July 1993 to January 1995, we performed eight LS procedures in six children with hereditary spherocytosis (HS) and two with immune thrombocytopenic purpura (ITP). Laparoscopic cholecystectomy was simultaneously done in one case with HS. There were 4 males and 4 females who ranged in age from 5 to 15 years--an average age of 8.8 years. Two cases in the early series required a counterincision because of bleeding. Eleven patients who previously underwent OS in our department were used to compare demographics, operative courses, and surgical outcomes. The ages, genders, diseases, body weights, and spleen weights were comparable between LS group and OS groups. The operative time for the LS group was statistically longer than for the OS group (226 +/- 24 min vs 101 +/- 8 min, P < 0.001). The estimated blood loss in the LS group was similar to that of the OS group (100 +/- 39 ml vs 73 +/- 11 ml. P = 0.97). There were no peri- or postoperative complications in two groups. The postoperative hospital stay of LS group was statistically shorter than that of the OS (6.8 +/- 0.6 days vs 10.4 +/- .05 days, P < 0.0001). LS provided better cosmesis and minimized trauma in children over OS. LS appears to be a safe and effective procedure in children, and is useful in the management of pediatric patients with HS or ITP.

Adolescent↗
PubMed1995

Polymerase chain reaction fiber analysis and somatic mosaicism in autopsied tissue from a man with Duchenne muscular dystrophy.

Single muscle fibers, obtained at autopsy from a 22-year-old man with Duchenne muscular dystrophy were examined immunocytochemically and also using polymerase chain reaction (PCR). Dystrophin-positive cells were widespread in skeletal, cardiac, smooth muscle, and in brain cells. PCR and Southern blot analyses of DNA from peripheral blood lymphocytes revealed a deletion of exon 45 in the dystrophin gene. With PCR of single fibers, three bands corresponding to exons 44, 45, and 47 were present in the normal control muscle fibers and dystrophin-positive fibers from the patient, while only two bands, exons 44 and 47, were observed in dystrophin-negative fibers. Therefore, in this patient, the genotype of dystrophin-positive fibers differed from that of the dystrophin-negative fibers, possibly because of a somatic mosaicism for deletion in the dystrophin gene. A mutation of the dystrophin gene may have occurred in one cell at an early stage of ontogenesis.

Adult↗
PubMed1995

Effectiveness of intraoperative radiation therapy for recurrent supratentorial low grade glioma.

Twelve adult patients in the records of 38 patients with histologically verified supratentorial low grade glioma showed recurrence at the Gifu University Hospital between 1980 and 1992. A mean period to recurrence from the initial surgery and postoperative radiation was 38 months. Six of these patients underwent intraoperative radiation therapy. The other six patients received chemotherapy with conventional cytoreductive surgery in three cases and additional external irradiation in three cases. The 2-year survival rate of the former patients was 83.8% and significantly higher than that of the latter ones, 16.7% (p < 0.05). Most cases showing recurrence of supratentorial low grade glioma were occurred locally, and dissemination or remote metastasis of the lesion were rare. The results revealed that the local control is important for recurrent tumors of supratentorial low grade gliomas. The effectiveness of the intraoperative radiation therapy as the second operation for the recurrent supratentorial benign glioma is discussed.

Adolescent↗
PubMed1995

Effect of asphyxia on the composition of cationic elements in the perilymph.

To elucidate the role of free radicals in the cochlea, cationic elements in the perilymph of the scala tympani in normal and asphyxic guinea pigs were measured by an inductively coupled plasma atomic emission spectrometer. The concentrations of 7 cationic elements (i.e., calcium, copper, iron, magnesium, phosphorus, lead and zinc) were measured simultaneously in a sample of the perilymph taken before, during and after asphyxia. There was no significant change in these cationic elements during asphyxia for 3 min. In contrast to the stationary level during asphyxia, the iron concentration was significantly elevated at 5 min after re-ventilation following asphyxia and decreased rapidly toward the pre-asphyxic level thereafter, although no significant change was observed in other cationic elements. These results were comparable to the theory of non-protein-bound iron accumulation produced by an O2-dependent mechanism during re-perfusion.

Animals↗
PubMed1995

Nuclear transition of heat shock protein in guinea pig cochlea after hyperthermia.

The main reaction of heat shock protein (hsp) 70 family to heat shock is 2-fold, one is an increased synthesis in the cytoplasm and the other is a transition from the cytoplasm to the nucleus. Although the former has been already reported in the cochlea by several authors, there has been no description as to the latter. The present study was designed to determine whether this nuclear transition of hsp70 family is also present in the cochlea as in the other organs. Albino guinea pigs subjected to hyperthermia treatment (42 degrees C, 10 min) were killed at 0, 6, 18 or 24 h after the cessation of hyperthermia treatment. Immunohistochemical studies in the cochlea of the untreated animals revealed anti-hsp70 family immunoreactivity mainly in the cytoplasm of the various cells in the cochlea, including the interdental cells, the spiral ganglion cells or the outer hair cells. However, immunoreactivity remarkably increased in the nucleus immediately after the cessation of hyperthermia treatment and this increased immunoreactivity disappeared at 6 h or later. It is concluded that the nuclear transition of hsp70 family also takes place under hyperthermal stress in the cells of the cochlea as in other organs.

Animals↗
PubMed1995

The effect of the sympathetic nervous system upon susceptibility to acoustic trauma.

This study was designed to determine whether the sympathetic nervous system exerts a protective or enhancing effect in acoustic overstimulation. The compound action potential of the cochlea (CAP) was recorded in guinea pigs while the cervical sympathetic nervous system (SNS) was electrically stimulated or after it was surgically eliminated. The stimulation or the elimination of the cervical SNS has no effect on the threshold of CAP. The threshold shift in CAP after acoustic overstimulation (110, 115, or 130 dB SPL for 10 min) was measured in the cervical SNS stimulation group, in the cervical SNS elimination group, and in the control group. When the animal was under insufficient sedation, there was no difference among these three groups. However, the CAP threshold shift was significantly smaller in the cervical SNS stimulation group than in the other two groups when the animals were sufficiently sedated. The cervical SNS stimulation had some protective effect on the susceptibility to acoustic trauma when the systemic SNS activity was suppressed.

Acoustic Stimulation↗