Biomedical subjects

M Ochiai

Publications and source records attributed to M Ochiai.

At least 19 recordsLinked to original sources

PubMed1992

Detection of a Ha-ras point mutation by polymerase chain reaction-single strand conformation polymorphism analysis in 2-amino-3,4-dimethylimidazo[4,5-f]quinoline-induced mouse forestomach tumors.

Ha-ras activation in forestomach squamous cell carcinomas of CDF1 mice induced by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), one of the heterocyclic amines isolated from broiled sardine was analyzed. Mutations were detected in two of three primary original carcinomas and two of four cell lines derived from other independent carcinomas by the polymerase chain reaction followed by analysis of single strand conformation polymorphism and direct sequencing. All the mutations detected were G----T transversions at the second letter of codon 13 resulting in an amino acid change from Gly to Val. This finding together with the previous reports on squamous cell carcinomas of the rat Zymbal gland suggest that MeIQ induces a specific type of mutation at a specific site of the Ha-ras gene during squamous cell carcinogenesis, in a species-independent manner.

Animals↗

PubMed1992

Immunocytochemical localization of beta-1,3-glucan recognition protein in the silkworm, Bombyx mori.

A monospecific antibody against beta-1,3-glucan recognition protein (a 62 kDa protein) of the larval silkworm prophenoloxidase activating system was used to study the localization of the protein. Among tissues from 5th instar larvae, only hemocytes and plasma were shown to contain a 62 kDa polypeptide immunoreactive with the antibody. Ultra-thin sections of the hemocytes were stained by an indirect immunogold staining method. Labelling occurred in the granules and cytoplasm of granulocytes and in the spherules and cytoplasm of spherulocytes. It was most conspicuous in granules of granulocytes and uniformly labelled spherules of spherulocyte, whereas no labelling was evident in prohemocytes, plasmatocytes and oenocytoids. The results are discussed in relation to the mode of recognition of fungi as non-self in insect hemocoel.

Animals↗

PubMed1992

A novel protease obtained from FBS-containing culture supernatant, that processes single chain form hepatocyte growth factor to two chain form in serum-free culture.

The recombinant human hepatocyte growth factor (r-hHGF) produced by Chinese hamster ovary cells transfected with hHGF cDNA (CHO BD-24 cells) was the two chain form in fetal bovine serum (FBS) containing culture. However, in serum-free culture the non-processed r-hHGF, single chain form, was detected with two chain form r-hHGF. We purified the protease that proteolytically processed single chain r-hHGF to two chain form r-hHGF. A protease was purified to give a single peak from the culture supernatant by use of several column chromatographies. When this protease was added to serum-free culture of CHO BD-24 cells, the proteolytic processing of single chain r-hHGF to two chain form r-hHGF was completely achieved. This protease was found to be composed of two peptide chains with molecular mass of 38 kDa under non-reducing condition by SDS-PAGE. The results of N-terminal amino acid sequence analysis and inhibitor selectivity suggested that this protease was a novel serine protease originating from fetal bovine serum.

Amino Acid Sequence↗

PubMed1992

Some considerations on the biology of pancreatic serous cystadenoma.

Five cases of pancreatic serous cystadenoma were examined pathologically, and their nuclear DNA ploidy patterns were determined. Four were unifocal tumors, and one was a multifocal tumor. The four unifocal tumors were typical serous cystadenomas. However, the multifocal tumor exhibited an increased N/C ratio, irregular nuclear margins, various-sized nuclei, coarse nuclear chromatin, and neural invasion. All tumor cells were stained with antiCA19-9 but none with antiCEA. In the antiCA19-9 staining, the four unifocal tumors and the tumors of the pancreatic tail in the multifocal case were positive only on the apical membrane, whereas the tumor cells of the pancreatic head in the multifocal case were positive within the whole cytosol. The unifocal tumors were diploid with a DNA Index (DI) of 1.0 and proliferation indices (PI) from 4.9 to 20.9% with a mean of 14.4%. In the multifocal case, the tumor in the pancreatic head was aneuploid (DI = 1.9) and had a PI of 27.8%. The multifocal sites in the pancreatic body were aneuploid (DI = 1.9) with a PI of 22.4%. We suggest that the biological property of serous cystadenoma should be revisited.

Aged↗

PubMed1992

Dose-dependent formation of preneoplastic foci and DNA adducts in rat liver with 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

Dose responses to two heterocyclic amines, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), in induction of glutathione S-transferase placental form positive liver cell foci (GST-P+ foci) and DNA adduct formation in the liver were examined in male F344 rats. Beginning 2 weeks after a single diethylnitrosamine (DEN) injection (200 mg/kg, i.p.), rats received MeA alpha C or PhIP in the diet at various doses for 6 weeks. All rats were subjected to two-thirds partial hepatectomy (PH) 1 weeks after the test agents were added to the diet and were killed 8 weeks after DEN initiation. MeA alpha C (100, 200, 400 and 800 p.p.m.) significantly increased numbers and areas of GST-P+ foci over control levels in all dose groups with a clear dose-response. In contrast, PhIP (50, 100, 200 and 400 p.p.m.) only equivocally increased foci development in the highest dose group and rather was associated with decrease in the lower dose groups. DNA adduct formation assessed by 32P-postlabeling demonstrated a dose-dependent increase with both chemicals, the levels being much higher with MeA alpha C. Thus, two highly mutagenic heterocyclic amines that are produced in broiled foodstuffs exerted different influence on GST-P+ foci development and DNA adduct formation; these findings are consistent with liver carcinogenicity in rats and/or mice.

Animals↗

PubMed1992

Adduct formation at C-8 of guanine on in vitro reaction of the ultimate form of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine with 2'-deoxyguanosine and its phosphate esters.

We examined the reactivity of the N-hydroxyamino derivative of a carcinogenic heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), after its O-acetylation with four 2'-deoxyribonucleoside 3'-monophosphates. 32P-Postlabeling analysis demonstrated that the levels of adducts with 2'-deoxyguanosine 3'-monophosphate were much higher than those with the other three nucleotides. 1H-NMR, mass spectral and UV absorption spectral analyses of the major adducts formed by N-acetyoxy-PhIP with 2'-deoxyguanosine and with its phosphate esters indicated that PhIP bound at the C-8 position of guanine, as previously demonstrated with other heterocyclic amines.

Acetic Anhydrides↗

PubMed1992

[Study of nuclear DNA content with flow cytometer in pancreatic diseases].

Benign and malignant diseases of the pancreas were compared with nuclear DNA content by flow cytometry, and the relationship between nuclear DNA content and histopathological findings was studied in ductal carcinoma of the pancreas. The nuclear DNA content in the malignant disease was higher than that in the benign disease. No significant correlation between nuclear DNA content and histopathological findings was observed in ductal carcinoma of the pancreas. A tendency for the nuclear DNA content to increase in proportion to the tumor size and the stage was, however, observed. Study of the nuclear DNA content is believed to be an effective adjuvant modality in differential diagnosis between benign and malignant disease of the pancreas.

DNA↗

PubMed1992

Responses of human gastroepiploic arteries to vasoactive substances: comparison with responses of internal mammary arteries and saphenous veins.

We examined the responses of human gastroepiploic arteries to histamine, serotonin, and norepinephrine, comparing those of internal mammary arteries and saphenous veins. Fresh specimens of the vessels were obtained intraoperatively from 21 patients. The vessels were suspended in organ chambers to record isometric tensions. With gastroepiploic arteries, histamine induced relaxations in the endothelial rings (85% +/- 7%) but failed to induce any contractions or relaxations in the rings without endothelium. The relaxations were prevented by methylene blue or hemoglobin and the H1-histaminergic receptor antagonist chlorpheniramine. With internal mammary artery rings with endothelium, histamine at a low concentration (10(-8) to 10(-5.5) mol/L) induced relaxations (53% +/- 12%) but evoked contractions at a higher concentration (10(-5) to 10(-4.5) mol/L). With saphenous veins, histamine caused only contractions. Serotonin induced markedly greater contractions in saphenous veins than in either artery. The endothelium inhibited the maximal contraction in response to serotonin in both arteries but not in veins. With the gastroepiploic artery, the responses to norepinephrine and serotonin were similar to those of the internal mammary artery. Histamine induces endothelium-dependent relaxations only, and histaminergic receptors that induce contractions may be absent on vascular smooth muscle cells. These vasoactive properties may contribute to the high patency as a coronary graft.

Acetylcholine↗

PubMed1992

[A case of pulmonary metastasis of ovarian leiomyosarcoma responsive to CTP therapy].

One case of pulmonary metastasis of leiomyosarcoma responsive to CTP therapy was reported. The patient was a 44-year-old woman who had undergone total simple hysterectomy for uterine myoma 6 years before. Five years after the operation she underwent ovariectomy for ovarian tumor. Based on the histopathological findings, she was diagnosed to have leiomyosarcoma. One year later the patient was referred to use because of pulmonary metastasis. After admission to our hospital CTP therapy was started. Disappearance of the metastatic lesion was demonstrated by the chest X-ray findings at the end of five courses of treatment.

Adult↗

PubMed1991

Marked increases of two kinds of two-exon-skipped albumin mRNAs with aging and their further increase by treatment with 3'-methyl-4-dimethylaminoazobenzene in Nagase analbuminemic rats.

Nagase analbuminemic rats (NARs) have a 7-base-pair deletion at the 5' splice site of the HI intron of the albumin gene. The level of immunohistochemically albumin-positive hepatocytes is about 1 per 10(5) cells in neonatal NARs, increases with age, and further increases with chronic oral treatment with 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). The mechanisms involved in the increase in albumin-positive hepatocytes during aging of NARs and their treatment with 3'-MeDAB were analyzed. NARs were found to have four species of albumin mRNA: intact mRNA and those lacking the regions corresponding to exon H, exon G-H, and exon H-I. In 4-week-old NARs, the level of intact albumin mRNA was about 1/4000 of that in normal rats and mRNA lacking the exon H sequence was the major species. In aged and 3'-MeDAB-treated aged NARs, all four species of mRNA increased and the relative proportion of mRNAs lacking two exon sequences to mRNAs lacking one exon sequence was greatly increased, suggesting that aging is associated with changes of the splicing pattern and that 3'-MeDAB treatment enhanced these changes. In aged NARs and 3'-MeDAB-treated aged NARs, there was an increase in the amount of aberrant 60-kDa albumin. The 60-kDa protein could be a translation product of mRNAs lacking two exons, the amount of which increases in aged NARs and 3'-MeDAB-treated NARs.

Aging↗

PubMed1991

Dynamic sweating response of man to infrared irradiation in various spectral regions.

In an attempt to detect differences in the thermal effect of infrared irradiation of different wave-lengths, transient sweating response to infrared irradiation in various spectral regions was examined. In Series 1, the ventral or dorsal surface of the nude subject was irradiated repetitively for a period of 4 min (2 min on, 2 min off) by each of three kinds of infrared heaters with main emissivity in 'near-infrared' (NIR; 0.7-2.8 microns), 'intermediate-infrared' (MIR; 1.5-5.8 microns), and 'far-infrared' (FIR; 2.8-25 microns) regions. The sweating response on a non-irradiated area tended to be the greatest with MIR, while the magnitude of the sweating response on the irradiated area showed no consistent differences among various wavelengths. The results infer that MIR stimulated cutaneous thomoreceptors most effectively, while its direct effect on local sweat gland activity was minimal. In Series 2, the effects of 9-12 min irradiations in more restricted ranges of wavelength were compared by the combination of the three kinds of heaters with filters (translucent to wavelength ranges of 1.3-2.7, 2.7-3.5, 3.6-8.0 microns, respectively). The sweating response on a remote area was predominantly greater with the range of 2.7-3.5 microns than with the other wavelength ranges, while the local effect on sweating was minimal with this range. The results of Series 2 reinforce those of Series 1, indicating that the degree of stimulation of cutaneous thermoreceptors and of direct thermal effect on sweat gland activity differ with spectral regions incident on the skin, thus affecting local and remote effects on the sweating response.

Adolescent↗

PubMed1991

Multifocal pancreatic serous cystadenoma with atypical cells and focal perineural invasion.

A case of multifocal pancreatic serous cystadenoma with atypical cells is reported. The patient was a 72-yr-old female who complained of jaundice. The distal common bile duct was obstructed, and the proximal bile duct was remarkably dilated on cholangiography. The main portal vein was obstructed and collateral vessels had developed on portal angiography. Total pancreatectomy was performed. The resected specimen contained one tumor in the head of the pancreas, five in the body, and one in the tail. The tumors of the head and body were morphologically the same. Microscopically, both contained spongelike multilocular cysts on their cut surfaces. These cysts were covered with low cuboid epithelium containing clear cytoplasm and abundant glycogen. Neural invasion was also found. The tumor cells exhibited an increased N/C ratio, variable nuclear size, irregular nuclear margins, and coarse nuclear chromatin. These tumors had aneuploid nuclear DNA with a DNA index of 1.9 and a proliferation index of 0.28. We feel that it is necessary to reconsider the biological concept of serous cystadenoma.

Aged↗

PubMed1991

The formation of heart DNA adducts in F344 rat following dietary administration of heterocyclic amines.

Most heterocyclic amines formed during the cooking of meat and fish have been shown to form adducts in the livers of rats. Recently, however, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), administered in the diet to Fischer 344 (F344) rats for 4 weeks, was shown to produce the highest levels of adducts in the heart. In the present study 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 2-amino-6-methyldipyrido[1,2-a:1',2'-d]imidazole (Glu-P-1) were given to F344 rats at carcinogenic dose levels (IQ 0.03%, MeIQx 0.04%, Trp-P-1 0.015%, Glu-P-1 0.05%) in the diet for 4 weeks. DNA adducts in the liver and heart were analyzed by 32P-postlabeling. DNA adducts were demonstrated to appear in the hearts of all animals exposed to heterocyclic amines at the following levels: IQ, 1.8 adducts/10(7) nucleotides, MeIQx, 3.8/10(7) ntd, Trp-P-1, 20/10(7) ntd and Glu-P-1, 7.2/10(7) ntd. Values for the heart were 10-20% of the respective liver adduct levels. Heart adducts increased linearly throughout the observed period when MeIQx was administered for up to 40 weeks. When MeIQx feeding was discontinued after 20 weeks and the animals subsequently given the basal diet, the adduct level at 20 weeks did not change during the following 20 weeks. A possible role for heart DNA alterations caused by food-borne heterocyclic amines in the development of age-related myopathies and cardiovascular disease is not inconceivable.

Administration, Oral↗

PubMed1991

Induction of intestinal adenocarcinomas by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Nagase analbuminemic rats.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant mutagenic heterocyclic amine in cooked foods, was examined for carcinogenic potential using Nagase analbuminemic rats (NARs), which are sensitive to various carcinogens. The concentration of PhIP in the diet was 0.04% at the beginning of the experiment, this being subsequently gradually reduced to 0.01% to avoid severe body weight loss. Ten of 13 treated NARs developed a total of 36 intestinal tumors within the 311-day experimental period. Among these, 22 were adenocarcinomas and 2 were adenomas of the small intestine, 4 were adenocarcinomas of the cecum and 8 were adenocarcinomas of the large intestine. The results suggest that PhIP could represent a significant risk to human populations exposed to foods containing heterocyclic amines.

Adenocarcinoma↗

PubMed1991

Bile acids and biliary carcinoma in pancreaticobiliary maljunction.

Pancreaticobiliary maljunction is frequently associated with biliary carcinoma, whether or not there is choledochal dilatation. In this anomalous condition, pancreatic juice regurgitates and the mixture of bile and pancreatic juice stagnates in the biliary tree. In cystic choledochal dilatation, cancers arise, mainly in the dilated bile ducts, while in patients not having cystic dilatation, tumors arise in the gallbladder. Gallbladder bile and/or bile duct bile from fifteen cases of pancreaticobiliary maljunction, including five cancer patients, was analysed biochemically and compared with control bile from 6 patients with a normal pancreaticobiliary junction. Bile levels of pancreatic enzymes were extremely high in the anomalous junction group. In the bile duct bile from patients with cystic choledochal dilatation with pancreaticobiliary maljunction, the concentrations of deoxycholic acid (DCA), lithocholic acid (LCA) and unconjugated bile acid fractions were increased regardless of the presence of cancer. Increases of these bile acid fractions, which are known to have a cancer-promoting effect, were also seen in gallbladder bile from the cancer patients without cystic dilatation.

Adolescent↗

PubMed1991

[Factors relating to postoperative infections in cancer patients].

Some factors relating to the increasing prevalence of postoperative infections after gastroenterological surgery were investigated from the standpoint of both patients profile and isolated bacteria. Data were collected from 542 cancer patients comprising 39 with esophagus cancer, 229 with gastric cancer, 149 with hepato-biliary tract and pancreatic cancer and 125 with colon cancer. Respiratory infections after operations were most frequently caused by aging, disturbance of glucose tolerance and respiratory dysfunction, whereas with intraabdominal abscess the major factors were disturbance of glucose tolerance, hepatic dysfunction and respiratory dysfunction in this order. Two factors in the management of patients during operation were singled out as mainly contributing to infection: these were prolonged operative time as in the case of esophagus cancer or hepato-biliary tract and pancreatic cancer, and massive intraoperative bleeding as in hepato-biliary tract, pancreatic and gastric cancer. As isolated bacteria, the most frequent clinical isolates were MRSA, Enterococcus, P. aeruginosa and Enterobacter, and it is noteworthy that all of these were strongly resistant to all antimicrobial agents. The greater emphasis on prevention control of postoperative infections, therefore, should be focussed on aging, preoperative risk factors, surgical stress and the kinds of antimicrobial agents administered.

Bacterial Infections↗

PubMed1990

Stretch may enhance the release of endothelium-derived relaxing factor in rabbit aorta.

The effect of vascular stretch on the release of EDRF was studied by measuring tissue cGMP levels of rabbit. Aortic rings of rabbit were quick-frozen in liquid nitrogen during varying resting tensions, and cGMP contents were determined by radio-immunoassay. The tissue cGMP levels significantly elevated with the increase in resting tension in endothelium-intact rings, but not in endothelium-denuded rings. Deprivation of extracellular calcium abolished the stretch-induced elevation of tissue cGMP levels in endothelium-intact segments. These stretch-induced endothelium dependent tissue cGMP elevations were unaffected by Ca2+ channel blockers, nicardipine and diltiazem. Data suggest that vascular stretch may release EDRF via mechanism dependent on extracellular calcium, but probably not through voltage-dependent calcium channel.

Animals↗

PubMed1990

DNA adducts formed by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in rat liver: dose-response on chronic administration.

The effect of administration of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) at various doses on DNA adduct formation in male rats was examined by 32P-postlabeling analysis. Administration of MeIQx in the diet at 0.4 ppm, 4 ppm, 40 ppm and 400 ppm for one week resulted in the formations of 0.04, 0.28, 3.34 and 39.0 adducts per 10(7) nucleotides in rat liver cells. Continuous administration of 400 ppm of MeIQx in the diet for 61 weeks to rats induced hepatocellular carcinomas in all rats. The carcinogenicity of MeIQx at doses of 40 ppm or less is not known yet, but the above results show a linear relationship between the level of MeIQx administered and the adduct level. In rats treated with low doses of 0.4, 4 and 40 ppm of MeIQx, adduct levels increased linearly with time of treatment, the levels in week 12 being two to three times those in week 1. In contrast, on treatment with 400 ppm of MeIQx, the adduct level in the liver increased until week 4, when it was 110 adducts per 10(7) nucleotides, and then remained constant for the next 8 weeks. Induction of the multidrug-resistance gene was suggested to be involved in development of this plateau level.

Animals↗