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Biomedical subjects

M Hirose

Publications and source records attributed to M Hirose.

At least 487 records · Page 27Linked to original sources

Myosin in hepatocytes is essential for bile canalicular contraction.

Active dynamic contraction of bile canaliculi has been observed in cultured doublet hepatocytes using time-lapse cinephotomicrography. This contractile movement plays an important role in normal bile formation. The mechanism of bile canalicular contraction has been proved to involve the Ca(2+)-calmodulin system and pericanalicular actin filaments. However, the role of myosin in this system is still unknown. In this study, using the newly synthesized myosin light-chain kinase inhibitor ML-9, we found that the treatment of cultured doublet hepatocytes with ML-9 inhibited canalicular contraction. This inhibitory effect suggests that myosin is involved in this complex cellular function and that the integrity of the actin-myosin system, as well as the Ca(2+)-calmodulin system is essential for normal bile canalicular contraction.

Actins↗

If the fetus can vocalize, how can we detect it?

In this paper, a method to detect the vocal activities of the fetus is reported. An estimation of the intensity and frequency of the voice was made on the assumption that the fetus can vocalize. Based upon these results, experiments to detect the voice were made. From the analysis of the results, it was made clear that the voice seemed to be buried in the noise and difficult to detect.

Female↗

Evaluation of hydrophobic interaction between acidic drugs and bovine serum albumin by reversed-phase high-performance liquid chromatography.

The contribution of hydrophobic interaction to the protein binding of acidic drugs has been evaluated in terms of a new hydrophobic index (r-value), defined as the slope of the log-log plots of capacity factor vs. reciprocal of methanol concentration in an aqueous binary mobile phase, measured by the reversed-phase high-performance liquid chromatography. The logarithms of the binding constants (log K1) of the selected acidic drugs and the related aromatic carboxylic acids indicated linear relationship with their r-values, suggesting that the effect of hydrophobicity on protein binding can be explained similarly to that on the retention onto the reversed-phase stationary ligand.

Carboxylic Acids↗

[Effect of a proton pump inhibitor AG-1749 (lansoprazole) on intragastric pH: 24-hour intragastric pH monitoring].

Proton pump inhibitors, as agents for use against peptic ulcers, potently suppress gastric acid secretion, as is the case with H2 receptor antagonists. To evaluate this antisecretory action as objectively as possible, intragastric pH was continuously monitored during 24 hours. Eight subjects were enrolled and divided into 2 treatment groups: a group receiving a daily dose of 30 mg of AG-1749 (lansoprazole) and the other group receiving 60 mg. Intragastric pH recording was made in each subject before and after the consecutive administration of the drug, and the corresponding pH holding time was calculated to evaluate the effect obtained in each group. The result indicated that the proportion of time in 24 hours after medication during which the pH was maintained above each level was significantly larger than that after placebo administration, and the duration of action was superior to that of H2-receptor antagonists. From the above, it was concluded that the consecutive administration of ag-1749, at doses of 60 mg as well as 30 mg, exhibits excellent antisecretory action in terms of intragastric pH control.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[Detection of human papillomavirus types 16, 18 and 33 in exfoliated cervical cells by polymerase chain reaction].

Human papillomavirus (HPV) types 16, 18 and 33 were identified by means of the polymerase chain reaction using exfoliated cells from the uterine cervix in 361 patients. Of 261 patients without cervical lesions, 10(3.8%) patients had HPV DNA whereas 7(70.0%) of 10 patients with invasive cervical carcinomas had HPV DNA. The younger patients' group (29 year-old or less) without cervical lesions had a 6.5% HPV positive rate which was distinctly higher than the older patients' groups. No menopausal patient without cervical lesions had HPV DNA. In the cervical dysplasia group, the HPV DNA positive rate tended to be higher in the older patients. Type 16 was detected more often than types 18 or 33. However, the detectable incidence of type 16 in the follow up group was lower than in the cervical carcinoma groups. The younger patients without cervical lesions had a higher incidence of type 16 than the older patients. The younger patients with cervical neoplastic lesions had a lower incidence of type 16 than the older patients. These results suggest that type 16 has a higher frequency of cervical HPV infections than types 18 and 33. In addition, human papillomavirus is not the only causative factor in cervical carcinomas.

Adult↗

Effects of naturally occurring antioxidants on combined 1,2-dimethylhydrazine- and 1-methyl-1-nitrosourea-initiated carcinogenesis in F344 male rats.

The effects of treatment with naturally occurring antioxidants, selenium, beta-carotene, ferulic acid, esculin and eugenol during the promotional phase of tumor development were investigated in male F344 rats pre-treated with 1,2-dimethylhydrazine (DMH) and 1-methyl-1-nitrosourea (MNU). Animals were given 3 subcutaneous injections of DMH at a dose of 40 mg/kg body wt. within 1 week and then were injected with MNU i.p. at a dose of 20 mg/kg body wt. 2 times per week, for 2 weeks. Thereafter, the rats were maintained on diet containing either 0.2% beta-carotene, 2 ppm selenium, 1% ferulic acid, 1% esculin or 0.8% eugenol. At week 52, surviving rats were killed and complete histological examinations were performed. Administration of eugenol enhanced the development of both hyperplasia and papillomas in the forestomach. Although treatment with beta-carotene tended to decrease the incidence and number of large intestinal carcinomas, beta-carotene, selenium, esculin and eugenol all decreased the incidence of kidney nephroblastomas, the differences were not statistically significant. The results thus showed that eugenol exerts promoting activity for forestomach carcinogenesis while the other antioxidants might have weak organ-specific inhibitory effects under these experimental conditions.

1,2-Dimethylhydrazine↗

Determination of sulfhydryl groups and disulfide bonds in a protein by polyacrylamide gel electrophoresis.

A general method by polyacrylamide gel electrophoresis for the determination of sulfhydryls and disulfides in a protein was developed. The method included a two-step alkylation procedure: the first step consisted of alkylation of the sulfhydryl groups with iodoacetic acid in the presence and absence of 8 M urea; the second step consisted of alkylation of the disulfide groups with iodoacetamide after reduction with a thiol. By high-pH urea gel electrophoresis, all the half-cystine residues in a protein could be categorized into three states: reactive sulfhydryls, nonreactive sulfhydryls, and disulfide bonded. The particular advantage of the method is that the states of half-cystines in different protein species can be analyzed independently both in isolated protein and in biological translation systems.

Alkylation↗

Phalloidin-induced accumulation of myosin in rat hepatocytes is caused by suppression of autolysosome formation.

Administration of phalloidin in vivo to rats causes marked changes in the distribution of actin and myosin in hepatocytes, which accompanies reduced bile flow. We have found that in hepatocytes treated with phalloidin for 3 and 7 days, cellular myosin content increased about 1.5-fold and 4.7-fold, respectively. In addition, total cell protein content and several marker enzyme activities were also elevated by 30-120% depending on the duration of phalloidin treatment. These observations allow us to speculate that phalloidin somehow elicits inhibition of cellular protein degradation, which results in the increase of these protein levels. To examine this possibility further, we analyzed leupeptin-induced density shift of phagolysosomes. In normal liver, the injection of leupeptin/E64c caused an increase in the density of both heterolysosomes and autolysosomes, due to retarded digestion of sequestered proteins as a result of the inhibition of lysosomal cathepsins. Accumulation, in these denser autolysosomes, of lactic dehydrogenase, pyruvate kinase, aldolase, and myosin was demonstrated by enzyme assays and immunoblot analysis. In the phalloidin-treated liver, the increase in the density of autolysosomes and the accumulation of above cytoplasmic enzymes were markedly inhibited. However, phalloidin did not affect the shift in the density of heterolysosomes. From these data, we concluded that autolysosome formation was specifically hindered in phalloidin-treated rat hepatocytes, which results in the reduction of autophagic protein degradation and eventual increase in intracellular protein levels.

Acid Phosphatase↗

Para-methoxyphenol strongly stimulates cell proliferation in the rat forestomach but is not a promoter of rat forestomach carcinogenesis.

The modifying effects of para-methoxyphenol (PMP) second stage treatment on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-initiated rat forestomach carcinogenesis were investigated. Groups of 15 6 week old male F344 rats were given a single intragastric administration of 150 mg/kg body wt MNNG and starting 1 week later were administered powdered diet containing 2.0, 1.0, 0.5, 0.25 or 0% PMP until they were killed at week 52. PMP caused epithelial damage and hyperplasia in a dose-dependent manner in the forestomach epithelium, but nevertheless was not associated with any increase in the incidence of either papillomas or squamous cell carcinomas. The results thus clearly indicated that stimulation of cell proliferation does not necessarily correlate with promotion in the second stage of two-stage forestomach carcinogenesis.

Animals↗

Regression of butylated hydroxyanisole (BHA)-induced hyperplasia but not dysplasia in the forestomach of hamsters.

The reversibility of butylated hydroxyanisole (BHA)-induced hamster forestomach hyperplasia was examined histopathologically. Groups of 10-15 male Syrian golden hamsters were treated with 2% BHA, for 12, 24 or 48 weeks and in each case then placed on basal diet until termination of the experiment at week 72, or treated with 2% BHA continuously for 72 weeks. Although sequential sampling revealed that BHA-induced hyperplasia reverted after cessation of antioxidant treatment, dysplastic lesions such as squamous cell dysplasia and basal cell dysplasia persisted and tended to increase with time on BHA. Basal cell dysplasia was observed in some hamsters later than squamous cell dysplasia, i.e. those treated with BHA for 24 weeks or more and killed up to 48 weeks later. Whereas the increase in labeling index evident in areas of hyperplasia during treatment returned to control level after cessation, this was not the case for the dysplastic lesions which continued to demonstrate elevated proliferation. The results thus suggest that basal cell dysplasia, including regions of squamous cell dysplasia, may be of particular importance as a precursor pre-neoplastic lesion.

Animals↗

Early proliferative responses of forestomach and glandular stomach of rats treated with five different phenolic antioxidants.

The effects of 8 weeks of oral administration of five different phenolic antioxidants, e.g. catechol (CC), resorcinol, hydroquinone (HQ), 2-tert-butyl-4-methylphenol (TBMP) and propylparabene (PP), on forestomach and glandular stomach epithelium of male F344 rats were evaluated using a combined immunohistochemical and histopathological approach. Treatment with CC and TBMP induced a significant elevation of DNA synthesis in the forestomach epithelium, associated with hyperplasia. CC administration also brought about an increase of DNA synthesis in the pyloric gland mucosa, cell proliferation in this case being reflected by an increment in the crypt height. In addition to causing an increase in the pepsinogen-isozyme-1-altered pyloric glands (PAPG), which are considered to be putative preneoplastic precursor lesions in the rat glandular stomach, CC treatment was associated with submucosal growth of pyloric mucosal cells tending to decreased pepsinogen isoenzyme 1 binding. However, DNA synthesis values in these latter areas were lower than in pyloric glands of the control group. In contrast, other phenolic compounds, resorcinol, HQ and PP, did not induce any changes in the stomach mucosa. The present results demonstrated strong proliferative responses in the stomach epithelium for CC and TBMP, indicative of promoting potential in both cases, and suggest that CC and TBMP may exert detrimental effects leading to promotion of stomach carcinogenesis or cancer development via an early proliferative response.

Animals↗

Effects of dietary perilla oil, soybean oil and safflower oil on 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethyl-hydrazine (DMH)-induced mammary gland and colon carcinogenesis in female SD rats.

The effects of diet supplemented with perilla oil, which contains a large amount of n-3 alpha-linolenic acid, and n-6 linoleic acid rich soybean and safflower oil supplemented diets on 7,12-dimethylbenz[a]anthracene (DMBA)- and 1,2-dimethylhydrazine (DMH)-induced mammary gland and colon carcinogenesis were investigated in female SD rats. Groups of 23 or 24, 5 week old animals were first given three s.c. injections of 40 mg/kg body wt DMH followed by a single intragastric administration of 50 mg/kg body wt DMBA within 2 weeks of the commencement. Starting 1 week after the DMBA treatment, they were administered pellet diet containing 10% perilla oil, soybean oil or safflower oil for the succeeding 33 weeks. Histological examination revealed that the resultant numbers of mammary tumors per rat were significantly lower in rats given perilla oil diet (4.4 +/- 2.5) than in the soybean oil diet group (6.5 +/- 3.9). Furthermore, colon tumor incidence was significantly lower in animals receiving the perilla oil supplement (18.2%) than in those given safflower oil diet (47.4%), and the numbers of colon tumors per rat tended to be lowest in rats administered perilla oil. Also the incidence of nephroblastomas in rats receiving perilla oil diet (0%) was significantly lower than that for the soybean oil diet group (23.8%). The results thus indicate that the alpha-linolenic acid (n-3)-rich perilla oil diet inhibits development of mammary gland, colon and kidney tumors as compared to linoleic acid (n-6)-rich safflower or soybean oil diet.

1,2-Dimethylhydrazine↗

Formation of a nitro derivative of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline by photo-irradiation.

A direct-acting mutagen to Salmonella typhimurium TA98 was found to be formed by exposing 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) in acetone to sunlight for 60 min. The direct-acting mutagen in the irradiated sample was purified by HPLC and identified as 3,4-dimethyl-2-nitroimidazo-[4,5-f]quinoline (NO2-MeIQ). The yield of NO2-MeIQ from MeIQ was estimated to be 0.3%.

Chromatography, High Pressure Liquid↗

Epithelial cell proliferation in rat forestomach and glandular stomach mucosa induced by catechol and analogous dihydroxybenzenes.

An investigation of antioxidant-induced lesions in stomach epithelia was performed using F344 rats of both sexes. Histopathological changes, levels of DNA synthesis and pepsinogen isozyme 1 altered pyloric gland (PAPG) induction were assessed following 4 weeks oral administration of catechol (CC) or analogs such as hydroxyhydroquinone (HHQ), protocatechuic acid (PCA), protocatechualdehyde (PCAH), dopamine and DL-dopa. While epithelial hyperplasia of the forestomach was only observed in the groups given CC, DNA synthesis in this epithelium was increased in groups of both sexes treated with CC, HHQ or dopamine. In the glandular stomach, CC induced submucosal growth of pyloric mucosal cells and an increase in crypt height associated with an elevation of DNA synthesis and numbers of PAPG. In contrast, dopamine brought about significant reduction in DNA synthesis in the pyloric mucosa of both sexes. The other CC analogs did not exert any obvious influence on glandular stomach mucosa. Since cell proliferation is well correlated to tumor promotion, the results suggested that HHQ and dopamine may have promoting potential for rat two-stage forestomach carcinogenesis in common with CC, while dopamine might be expected to inhibit glandular stomach carcinogenesis.

Animals↗

Crystallization of and preliminary crystallographic data for the N-terminal half-molecule of ovotransferrin.

The N-terminal half molecule of ovotransferrin has been crystallized from a polyethylene glycol 6000 solution by means of the vapor diffusion method. The crystals belong to the orthorhombic system, space group P2(1)2(1)2(1), with cell dimension of a = 47.0, b = 90.2, and c = 76.2 A. The crystals diffract X-rays to a resolution limit of at least 2.0 A and are resistant to X-ray radiation damage. They appear to be suitable for X-ray structure analysis.

Conalbumin↗