Search PubMed⌕ Search

Biomedical subjects

M Hirose

Publications and source records attributed to M Hirose.

At least 505 records · Page 28Linked to original sources
PubMed1990

Stomach carcinogenicity of caffeic acid, sesamol and catechol in rats and mice.

The carcinogenic potential of caffeic acid, sesamol and catechol was examined in male and female F344 rats and B6C3F1 mice, groups of 30 animals being treated with diets containing 2% caffeic acid, 2% sesamol or 0.8% catechol for 104 weeks (rats) or 96 weeks (mice). Histological examination revealed that caffeic acid induced forestomach squamous cell carcinoma in 57% (P less than 0.001 vs. controls) and 50% (P less than 0.001) of male and female rats, respectively, whereas sesamol was associated with squamous cell carcinoma at incidences of 31% (P less than 0.001) in male rats, and 38% (P less than 0.001) and 17% (P less than 0.05) in male and female mice, respectively. Catechol induced glandular stomach adenocarcinomas in 54% (P less than 0.001) and 43% (P less than 0.001) of male and female rats, respectively. The results thus clearly demonstrated that all three antioxidants are carcinogenic in rodent stomach epithelia.

Animals↗
PubMed1990

Structure-activity relations in promotion of rat urinary bladder carcinogenesis by phenolic antioxidants.

The urinary bladder tumor-promoting potentials of the phenolic antioxidants, 2-tert-butyl-4-methylphenol (TBMP), propylparaben, catechol, resorcinol and hydroquinone, which are structurally related to butylated hydroxyanisole (BHA), were investigated in 170 male F344 rats. The animals were initially given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as an initiator in their drinking water for 4 weeks. Three days later, groups of 20 rats received diet containing 1.0% TBMP, 3% propylparaben, 0.8% catechol, 0.8% resorcinol, 0.8% hydroquinone or basal diet alone until the end of week 36. Significant increases in the incidences and average numbers of the putative preneoplastic lesions, papillary or nodular (PN) hyperplasia, and papillomas of the urinary bladder were only observed in the group given TBMP after BBN. Development of these lesions was not enhanced by diet containing the other test compounds and no induction was associated with any of the test chemicals alone. The results thus clearly showed that TBMP, which most closely resembles BHA, promoted urinary bladder carcinogenesis. The similar effects of TBMP and BHA on urinary bladder carcinogenesis suggest a direct link between chemical structure and biological potency.

Animals↗
PubMed1990

Effects of sodium nitrite and catechol or 3-methoxycatechol in combination on rat stomach epithelium.

The effects of sodium nitrite (NaNO2) and catechol or 3-methoxycatechol in combination were examined in male F344 rats. Animals were treated with 0.3% NaNO2 in the drinking water and 0.8% catechol or 2% 3-methoxycatechol in powdered diet for 24 weeks. While catechol or 3-methoxycatechol alone induced low incidences of mild or moderate hyperplasia, simultaneous administration of NaNO2 markedly enhanced the degree of hyperplasia and papilloma formation. In contrast, induction of submucosal hyperplasia and adenomas in the glandular epithelium was reduced. Thus, the results indicate that NaNO2 can modulate the metabolism of antioxidants, so that, possibly via production of new active moieties, targeting of forestomach epithelium is enhanced.

Adenoma↗
PubMed1990

Inhibitory effects of antioxidants on N-bis(2-hydroxypropyl)nitrosamine-induced lung carcinogenesis in rats.

Potential second-stage modifying effects of 8 antioxidants on lung tumorigenesis initiated by N-bis(2-hydroxypropyl)nitrosamine (DHPN) were examined in male F344 rats. After an initial 2-week treatment with DHPN (0.1% in drinking water), rats were administered one of the antioxidants supplemented in the diet for 30 weeks. Although the incidences of lung adenomas were not affected, those of carcinomas were lowered by 2% butylated hydroxyanisole (BHA, 2 rats/20 rats), 1% butylated hydroxytoluene (BHT, 1/20), 0.8% ethoxyquin (EQ, 3/20) and 1% a-tocopherol (a-TP, 2/20) treatments as compared to the control level (9/20), while 5% sodium L-ascorbate (SA), 0.8% catechol (CC), 0.8% resorcinol (RN), and 0.8% hydroquinone (HQ) did not exert any significant effect on incidence. Quantitative analysis of adenomas and carcinomas (numbers and areas of lesions per unit area of lung section) revealed obvious inhibitory effects of SA, CC, and RN as well as BHA, BHT, EQ, and a-TP. Among the antioxidants, BHT exerted the strongest inhibitory activity. In contrast, DHPN-induced thyroid tumorigenesis was significantly enhanced by BHT (14/20) and EQ (20/20) treatments (control = 5/20). Thus the antioxidants showed opposite effects on lung and thyroid carcinogenesis in the rat.

Adenoma↗
PubMed1990

Integrity of the cytoskeletal system is important for phagocytosis by Kupffer cells.

The mechanism of phagocytosis by Kupffer cells is believed to involve the Ca2(+)-calmodulin system. However, the role of myosin in this system is still unknown. In this study, we found that myosin light chain kinase inhibitor (ML-9) inhibited phagocytosis by cultured Kupffer cells using polystyrene beads, a time-lapse VTR system and fluorescent staining techniques. The inhibitory effects of ML-9 suggest that myosin may be involved in this complex cellular function and that the integrity of the cytoskeletal system is essential for normal phagocytosis.

Animals↗
PubMed1990

Isolation of multiple cytomegalovirus strains from a patient with adult T cell leukemia.

A 66-year-old male with adult T cell leukemia had an ulcer on the left medial thigh. The biopsy of the skin lesion revealed enlarged endothelial cells with acidophilic intranuclear inclusion bodies, suggesting cytomegalovirus (CMV) infection. At autopsy, CMV was isolated from a nodular skin lesion of the scrotum. The urine constantly tested positive for CMV. Restriction endonuclease cleavage analysis of DNA of the isolates from the skin and urine indicated that this patient was infected with two different strains of CMV.

Aged↗
PubMed1990

[A case of renal pelvic tumor due to phenacetin abuse].

An 80-year-old female had been taking phenacetin-containing analgesics due to severe pain in her legs and headache caused by SMON since 1957. The total accumulated dose of phenacetin that she had taken was about 2.3 kg. She visited the department of urology in our hospital complaining of gross hematuria in May, 1987. DIP showed that bilateral kidney were atrophic and her left pyelogram was non-visualized. A solid mass was located in her renal pelvis on the CT scan. Under the diagnosis of a left renal pelvic tumor, nephrectomy was performed on her left kidney in January, 1988. Histological diagnosis was interpreted as a transitional cell carcinoma, at a grade 1 greater than 2 and interstitial nephritis was detected. She died 8 months after the operation because of lung and bone metastasis. In autopsy, interstitial nephritis of the right kidney was also recognized. Our case is the fourth report of renal pelvic tumor due to phenacetin abuse in Japan.

Aged↗
PubMed1989

Modification by catechol and resorcinol of upper digestive tract carcinogenesis in rats treated with methyl-N-amylnitrosamine.

Modifying effects of the environmental contaminant catechol, and its isomers resorcinol and hydroquinone, on methyl-N-amylnitrosamine (MNAN)-induced carcinogenesis were studied in male F344 rats. Groups of 15 rats were given three i.p. injections of 25 mg/kg of body weight of MNAN within the initial 2-wk period, and commencing 1 wk thereafter they were administered 0.8% catechol, 0.8% resorcinol, or 0.8% hydroquinone in powdered basal diet or were given basal diet alone for 49 wk. Additional groups of 10 to 15 rats were similarly treated without prior carcinogen exposure. Histological examination after sacrifice at wk 52 revealed that the incidences of tongue papillomas and esophageal squamous cell carcinomas in the groups given MNAN followed by catechol (57.1% and 64.3%) or resorcinol (50% and 58.8%) were significantly higher than those in the carcinogen only controls (9.1, and 0%, respectively). Hydroquinone also enhanced the development of esophageal squamous cell carcinomas but was less active than catechol or resorcinol. The incidence of alveolar hyperplasia in the lungs of the group given MNAN followed by catechol (0%) was, in contrast, significantly reduced as compared to the control value (54.5%). Hydroquinone and resorcinol showed a similar but non-significant tendency. These results indicated that the environmental contaminant, catechol and its isomers, may play a role in the development of human upper gastrointestinal cancer, in addition to exerting modifying effects in other organs.

Animals↗
PubMed1989

Renaturation of ovotransferrin under two-step conditions allowing primary folding of the fully reduced form and the subsequent regeneration of the intramolecular disulfides.

A two-step procedure was found to be useful for the efficient refolding of a complex protein, ovotransferrin. In the first step, the reduced and denatured form of the protein was incubated at a low temperature in a nondenaturing buffer containing reduced glutathione; in the second step, the reduced form was reoxidized at a higher temperature in the presence of oxidized glutathione. Under these conditions, the fully reduced forms of ovotransferrin and its half-molecules were almost quantitatively reoxidized to regain iron-binding abilities and conformations, very similar to the native form. The circular dichroism spectra revealed that at low temperatures the fully reduced forms have partially folded conformations, which are fluctuating like "molten globule" states. The reoxidization kinetics compared between whole ovotransferrin and the two half-molecules supported independent refolding of the N- and C-terminal domains.

Circular Dichroism↗
PubMed1989

Lack of modifying effects of linolic acid hydroperoxides and their secondary oxidative products on combined 7,12-dimethylbenz[a]anthracene and 1,2-dimethylhydrazine-initiated mammary gland, ear duct and colon carcinogenesis in female Sprague-Dawley rats.

Effects of hydroperoxides, autoxidation products of linolic acid (HPO) and secondary oxidative products of HPO (SOP) (5% each in diet) were examined in female Sprague-Dawley rats. HPO and SOP administration was carried out during or subsequent to two injections of dimethylhydrazine (DMH) (40 mg/kg body wt s.c.), and a single i.g. dose of 7,12-dimethylbenz[a]anthracene (DMBA) (50 mg/kg body wt). No significant differences in the incidences of tumors in the mammary gland, colon, ear duct and hematopoietic system associated with HPO or SOP treatment were evident, during or after carcinogen exposure. The present results therefore indicate that the environmental contaminants, HPO and SOP, lack any potential for modification of mammary gland or colon carcinogenesis under the conditions of the investigation.

1,2-Dimethylhydrazine↗
PubMed1989

Promotion by dihydroxybenzene derivatives of N-methyl-N'-nitro-N-nitrosoguanidine-induced F344 rat forestomach and glandular stomach carcinogenesis.

Modifying effects of resorcinol, hydroquinone, p-tert-butylcatechol (PTBC), p-methylcatechol (PMC), and o-methylcatechol on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced forestomach and glandular stomach carcinogenesis were investigated in F344 rats. Groups of 15 to 16 male 6-wk-old animals were given a single intragastric administration of 150 mg/kg of body weight of MNNG and starting 1 wk later were administered powdered diet containing 0.8% resorcinol, 0.8% hydroquinone, 1.5% PTBC, 1.5% o-methylcatechol, 1.5% PMC, or basal diet alone for 51 wk. Additional groups of 10 to 15 rats each were treated with the phenolic compounds or received basal diet without prior carcinogen exposure. Histological examination after sacrifice at Wk 52 revealed that squamous cell carcinoma development in the forestomachs of rats treated with MNNG followed by PTBC (75%, P less than 0.001) or MNNG followed by PMC (100%, P less than 0.001) was significantly greater than in animals receiving MNNG alone (20%). Treatment with PMC alone also resulted in a 40% yield of papilloma. In the glandular stomach, incidences of adenomatous hyperplasias in rats treated with MNNG followed by PTBC (31.3%, P less than 0.05) or PMC (100%, P less than 0.001) and the incidence of adenocarcinomas in rats treated with MNNG followed by PMC (100%, P less than 0.001) were significantly higher than in controls. In addition, PMC alone induced a 100% yield of adenomatous hyperplasias and 6.7% of adenocarcinomas. Thus, the results demonstrated that PTBC and PMC treatment significantly enhances forestomach and glandular stomach carcinogenesis and that PMC itself may possess weak carcinogenic potential in these organs. The ortho-position appears to be important for this dihydroxybenzene activity.

Adenocarcinoma↗
PubMed1989

The primary structure and structural characteristics of Achromobacter lyticus protease I, a lysine-specific serine protease.

The complete amino acid sequence of Achromobacter lyticus protease I (EC 3.4.21.50), which specifically hydrolyzes lysyl peptide bonds, has been established. This has been achieved by sequence analysis of the reduced and S-carboxymethylated protease and of peptides obtained by enzymatic digestion with Achromobacter protease I itself and Staphylococcus aureus V8 protease and by chemical cleavage with cyanogen bromide. The protease consists of 268 residues with three disulfide bonds, which have been assigned to Cys6-Cys216, Cys12-Cys80, and Cys36-Cys58. Comparison of the amino acid sequence of Achromobacter protease and other serine proteases of bacterial and mammalian origins has revealed that Achromobacter protease I is a mammalian-type serine protease of which the catalytic triad comprises His57, Asp113, and Ser194. It has also been shown that the protease has 9- and 26-residue extensions of the peptide chain at the N and C termini, respectively, and overall sequence homology is as low as 20% with bovine trypsin. The presence of a disulfide bridge between the N-terminal extension Cys6 and Cys216 close to the putative active site in the C-terminal region is thought to be responsible for the generation of maximal proteolytic function in the pH range 8.5-10.7 and enhanced stability to denaturation.

Alcaligenes↗
PubMed1989

Immunocytochemical localization of myosin in normal and phalloidin-treated rat hepatocytes.

To clarify the intracellular distribution of myosin in normal rat hepatocytes and its alterations in phal-loidin-treated rat hepatocytes as a morphologic basis for the dysfunction of microfilaments, we performed indirect immunofluorescence using monospecific antibody raised against rat hepatocyte myosin. Cryostat rat liver sections analyzed by the use of this antibody showed a characteristic polygonal staining pattern, indicating that myosin is localized close to the plasma membrane including the region of bile canaliculi. The observed myosin staining pattern of normal liver coincides with the pattern of actin distribution as demonstrated by double-staining on the same liver section with antimyosin antibody and rhodamine-phalloidin. Upon administration of phalloidin to rats, the following changes in the myosin staining pattern were observed. (a) Peripheral fluorescence along the plasma membrane, especially around the bile canaliculi and sinusoids, was greatly enhanced. (b) Numbers of small fluorescent dots appeared in the cytoplasm of hepatocytes. These changes in the localization of myosin are shown to overlap with those of actin filament distribution. Accompanying these changes of localization, cellular myosin content appears to be increased, as the myosin marker-enzyme NH4+(-)ethylenediaminetetraacetic acid-adenosine triphosphatase activity in hepatocyte extracts was elevated threefold after 7 days of phalloidin treatment. This increase of myosin may be due to the previously observed stabilizing effect on microfilaments of phalloidin against cellular proteases. Thus, phalloidin, which primarily alters actin filament distribution, induces the changes in myosin localization and the increase in cellular myosin content without causing dissociation of myosin from actin in the hepatocyte.

Animals↗
PubMed1989

DNA-adduct formation in the forestomach of rats treated with 3-tert-butyl-4-hydroxyanisole and its metabolites as assessed by an enzymatic 32P-postlabeling method.

Formation of DNA-adducts by 3-BHA or its metabolites, i.e., tert-butyl-1,4-benzoquinone (TBQ) and 5-methoxy-3-tert-butyl-1,2-benzoquinone (3-TBOQ), as well as DNA-adduct formation by 4-nitroquinoline-N-oxide (4NQO), in rat forestomach were examined by an enzymatic 32P-postlabeling assay. Four DNA-adducts were clearly detected in the forestomach after treatment of rats with 4NQO. The sensitivity was 1.9 certain adducts per 10(8) normal nucleotides. On the contrary, no DNA adducts were detected in the forestomach of rats given either a single or repeated oral administration (5 days) of 3-BHA, TBQ or 3-TBOQ. The analyses were carried out under conditions which could detect the DNA-adducts produced by reaction of TBQ with calf thymus DNA in vitro. The results suggest that formation of aromatic adducts in vivo by 3-BHA, TBQ or 3-TBOQ in the rat forestomach-DNA is not evident or at least below the detection limits of the current bioassay.

4-Nitroquinoline-1-oxide↗
PubMed1989

Antioxidants--carcinogenic and chemopreventive properties.

Synthetic and naturally occurring antioxidants have a wide variety of biological actions in rodents in addition to their primary antioxidant activity. Some of the included biological effects are of direct interest in relation to studies of carcinogenicity and/or modulation of carcinogenesis. Since the synthetic antioxidant BHA was first found to exert carcinogenic potential in rat and hamster forestomach epithelium, many other synthetic and naturally occurring antioxidants have been examined for their ability to induce proliferative activity in the alimentary canal. These studies have revealed that caffeic acid and sesamol are also tumorigenic for rat forestomach epithelium, whereas catechol and p-methylcatechol induce neoplasia in rat glandular stomach epithelium. Although the proliferative response is very rapid, with inflammation and ulceration, it takes a very long time before carcinomas develop. The proliferative lesions in the forestomach induced by BHA or caffeic acid are largely reversible, in contrast to those induced by genotoxic carcinogens, which generally persist and develop into cancer. Therefore, chronic irritation is considered to be responsible for the induction of stomach cancer by antioxidants. Butylated hydroxyanisole can undergo oxidative metabolism in vitro, and some of the metabolites formed have the potential for binding to proteins. Neither BHA nor its metabolites binds to DNA in vivo, but protein binding in the forestomach was greater than 10 times higher than that in the glandular stomach. It is thus conceivable that BHA is oxidatively metabolized in the forestomach epithelium (possibly entering into redox cycling), and reactive metabolites including semiquinone radicals or active oxygen species are responsible for the carcinogenesis by a mechanism involving binding to macromolecules. Many antioxidants have been shown to modify carcinogenesis, and as a rule, they inhibit the initiation stage by reducing the interaction between carcinogen and DNA. However, both promotion and inhibition have been reported for second-stage carcinogenesis, depending on the organ site, species of animal, or initiating carcinogen. They can also block reaction of amine and nitrite to form nitrosamines or reduce TPA promotion of skin carcinogenesis. Generally high doses of antioxidants are required for carcinoma induction or modification of chemical carcinogenesis. The significance of the reported tumorigenicity and strong promoting activity of antioxidants for forestomach epithelium of animals to the development of human cancer appears limited mainly because humans do not have a forestomach. The carcinogenic and strong promoting activities of catechol and its structurally related compounds on rat glandular stomach epithelium are of greater concern because this tissue is directly analogous to human gastric epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗