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Biomedical subjects

M Miyamoto

Publications and source records attributed to M Miyamoto.

At least 559 records · Page 31Linked to original sources

[Intraperitoneal transplantation derived from spontaneous colonic cancer of WF rat strain].

Intraperitoneal transplantation of spontaneous colon carcinoma of WF strain has been established. There are two lines of transplantable colon carcinoma derived from the male and female rat of the same litter (MM4-48H). These two lines are now (Sept. '83) at the 16th generation. They have been succeeded every 3 weeks intraperitoneally using 4-weeks old male and female siblings of WF strain. Histology of these transplantable colon carcinoma was well-differentiated tubular adenocarcinoma at the first few generations but changed gradually medullary tubular pattern at the 16th generation. We believe this is the first report of transplantable tumor lines from the spontaneous colon carcinoma itself and these lines can be used for screening test of carcinostatics.

Adenocarcinoma↗

Effects of long-term blockade of angiotensin converting enzyme with captopril on blood pressure and aortic prolyl hydroxylase activity in spontaneously hypertensive rats.

In order to determine if long-term treatment with captopril affects vascular collagen biosynthesis we administered the agent at a dose of 30 or 100 mg/kg/day p.o. for 6 weeks to spontaneously hypertensive rats. At the 6th week of captopril treatment the aorta was excised and the activity of prolyl hydroxylase, the rate-limiting enzyme of collagen biosynthesis, was measured. Vascular enzyme activity was decreased by 7.0% and 34.6% in the low- and high-dose groups, respectively. A single oral administration of captopril, on the other hand, did not decrease the enzyme activity in the aorta. Furthermore, captopril had no direct inhibitory effect on the enzyme activity in vitro. These findings suggest that the decrease in vascular prolyl hydroxylase activity resulted from a sustained decrease in blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗

Thyrotropin-releasing hormone (TRH) and its analog (DN-1417): interaction with pentobarbital in choline uptake and acetylcholine synthesis of rat brain slices.

TRH or its analog DN-1417 (gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-proliamide) given 15 min after intravenous (i.v.) administration of pentobarbital (30 mg/kg) markedly shortened the pentobarbital-induced sleeping time in rats. This effect was almost completely abolished by intracerebroventricular pretreatment with atropine methylbromide (20 micrograms/rat), thereby suggesting the involvement of cholinergic mechanism. The action mechanism was investigated using rat brain slices. TRH (10(-6)-10(-4)M) or DN-1417 (10(-7)-10(-5)M) caused significant increases in the uptake of [3H]-choline into striatal slices. TRH(10(-4)M) or DN-1417(10(-5)M) also stimulated the conversion of [3H]-choline to [3H]-acetylcholine in striatal slices. A 30% reduction of acetylcholine synthesis from [3H]-choline in hippocampal slices and a 40% reduction of [3H]-choline uptake in slices of cerebral cortex, hippocampus and hypothalamus were observed in rats pretreated with pentobarbital (60 mg/kg, i.v.). TRH or DN-1417 (20 mg/kg, i.v.) given 15 min after the administration of pentobarbital markedly reversed both of the pentobarbital effects. Direct application of pentobarbital (5 X 10(-4)M) to slices in vitro also caused a 20-40% reduction of [3H]-choline uptake of cerebral cortex, hippocampus and diencephalon. A concomitant application of TRH(10(-4)M) or DN-1417(10(-5)M) and pentobarbital abolished the pentobarbital effect. These results provide neurochemical evidence that the antagonistic effects of TRH and DN-1417 on pentobarbital-induced narcosis are closely related to alterations in the rat brain choline uptake and acetylcholine synthesis, which are considered to be measures of the activity of cholinergic neurons.

Acetylcholine↗

A TRH analog (DN-1417): effects on local cerebral glucose utilization in conscious and pentobarbitalized rats determined by the autoradiographic 2-deoxy-[14C]glucose method.

Effects of a TRH (thyrotropin-releasing hormone) analog, DN-1417 (gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate), with regard to the rate of local cerebral glucose utilization (LCGU) were assessed using the autoradiographic 2-deoxy-D-[14C]glucose method to clarify the possible sites of action in conscious and pentobarbitalized rats. DN-1417 (0.5-5 mg/kg, i.v.) significantly shortened the pentobarbital-induced sleeping time in a dose dependent manner, and this effect of DN-1417 was reduced by intracerebroventricular (i.c.v.) pretreatment with atropine methylbromide (20 micrograms). DN-1417 (5 mg/kg, i.v.) by itself slightly increased the LCGU in the thalamus dorsomedial nucleus and mammillary body and significantly increased it in the septal nucleus. Pentobarbital (30 mg/kg, i.v.) alone produced a marked and diffuse reduction in LCGU throughout the brain at a rate of about 46% of the control. DN-1417 (5 mg/kg, i.v.) markedly reversed the reduction of LCGU induced by pentobarbital. The antagonistic effect of DN-1417 in LCGU was about twice as potent as that of TRH. Locally, significant reversal effects by DN-1417 were observed in the hypothalamus, septal nucleus, hippocampus, mammillary body, thalamus dorsomedial nucleus, caudate-putamen, nucleus accumbens, pontine gray matter and so on. These actions of DN-1417 were almost completely abolished in all areas except for the visual cortex under the condition of pretreatment with atropine methylbromide (20 micrograms, i.c.v.). On the other hand, pimozide (1 mg/kg, i.p.) augmented the actions of DN-1417. Thus, DN-1417 seems to act on the level of consciousness via a reticulo-thalamo-cortical system, and reverses the LCGU reduction induced by pentobarbital via a cholinergic mechanism. The hypothalamus appears to be a crucial site in mediation of the antagonistic action of DN-1417 on pentobarbital.

Animals↗

[Effects of pentylenetetrazol on conflict behavior and interactions with anxiolytics in rats].

Effects of pentylenetetrazol (PTZ) on conflict behavior were studied using a punished water-lick (conflict) paradigm in rats. PTZ (5-20 mg/kg, ip) produced a dose-related enhancement of conflict behavior as demonstrated by a suppression of lick responding in low shock intensity (1.3-2.0 mA). Furthermore, PTZ (2-20 mg/kg, ip) clearly antagonized the release of punished responding induced by diazepam (5 mg/kg, ip), chlordiazepoxide (10 mg/kg i.p.) or meprobamate (75 mg/kg, ip) when a high intensity of shock (2.5 or 3 mA) was used. Bemegride also showed a similar suppressive effect on the anticonflict action of diazepam. However, bicuculline, picrotoxin or strychnine neither enhanced conflict behavior nor inhibited the anticonflict action of diazepam, even in high doses. In addition, PTZ (10 or 20 mg/kg, ip) did not show any significant effect on unpunished drinking or flinch-jump threshold, suggesting that the conflict enhancing action of PTZ may not be due to the secondary action including decrease in drive for drinking or increase in sensitivity to shock. These results suggest that PTZ may exert facilitation of conflict behavior or suppression of the anticonflict action of anxiolytics via an activation of the conflict generating mechanisms.

Animals↗

Increased sensitivity of cultured fibroblasts from colon cancer-prone rats to cytotoxicity of carcinogens and to viral transformation: a comparison with fibroblasts from patients with adenomatosis coli.

Lethal effects of mitomycin C (MMC), 4-nitroquinoline 1-oxide (4NQO) and ultraviolet light (UV) on fibroblast cell lines derived from a colon cancer-prone substrain of Wistar-Furth rats (WF/OSAKA rats) were measured in terms of the cellular colony-forming ability, and compared with the sensitivity to these agents of human fibroblasts from patients with adenomatosis coli and rectum (ACR). All 6 fibroblast strains from the cancer-prone WF/OSAKA rats were significantly more sensitive (though to various extents) to MMC as well as 4NQO than normal rat fibroblasts derived from the parental WF Hiroshima rats. These WF/OSAKA cell strains were slightly more sensitive to UV than normal rat cell strains. Similarly, 5 out of 6 fibroblast strains derived from ACR patients were hypersensitive to both MMC and 4NQO. Further, the WF/OSAKA cell strains were more susceptible to morphological transformation induced by Kirsten murine sarcoma virus than normal rat strains. The observed higher sensitivity to chemical agents and to viral transformation suggests a close similarity in cellular terms between the colon cancer-prone WF/OSAKA rats and human individuals affected with ACR.

4-Nitroquinoline-1-oxide↗

Genetic control of susceptibility of rats to gastric carcinoma.

Genetic control of the induction of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in susceptible ACI rats, resistant Buffalo rats, and their F1 and F2 offspring. Both sexes of all strains, initially 7 to 9 weeks old, were given MNNG at a concentration of 83 micrograms/ml in their drinking water for 32 weeks and were sacrificed at experimental Week 72. The incidence of gastric adenocarcinoma in ACI rats was 80% in males and 47% in females; in Buffalo rats, the incidence was 18% in males and 0% in females. F1 hybrids showed the same resistance to MNNG as did Buffalo rats; the incidence of gastric adenocarcinoma was 17% in males and 8% in females. These results suggest that resistance to induction of gastric adenocarcinoma by MNNG is a dominant characteristic. The incidence of gastric adenocarcinoma in the F2 generation was 36% in males and 14% in females, which is close to the 3:1 ratio expected from the segregation of a single resistant gene. In ACI and Buffalo strains and their hybrids, males were more susceptible than females to induction of gastric carcinoma by MNNG. Intestinal tumors were observed mainly in the duodenum and jejunum in both strains and their hybrids, and the incidences were as follows: ACI: males, 67% and females 42%; Buffalo: males, 12% and females, 18%; F1: males, 18% and females, 15%; and F2: males, 15% and females, 19%. Thus, there seems to be a common genetic basis for both gastric and intestinal carcinogenesis by MNNG.

Animals↗

Long-term effects of captopril on passive sodium permeability and contractility in vascular smooth muscles of spontaneously hypertensive rats.

Long-term effects of captopril on passive sodium permeability and cellular sodium concentration in the aorta of spontaneously hypertensive rats were examined in terms of contractile properties of the muscle. In cold lithium solution, cellular sodium in the aorta isolated from spontaneously hypertensive rats leaked more rapidly than did that isolated from Wistar Kyoto rats (WKY), suggesting an increased sodium permeability in the aorta of spontaneously hypertensive rats. Six weeks of treatment with captopril reduced the increased sodium permeability after hydralazine had failed. Inhibition of the sodium pump by incubating the aorta in potassium-free solution produced a slowly developing contraction which was associated with accumulation of cellular sodium. Both the magnitude of contraction and the accumulation of sodium during exposure to potassium-free solution for 1 hour were significantly less in the aorta isolated from spontaneously hypertensive rats treated with captopril compared with those from control spontaneously hypertensive rats. These data suggest that after prolonged administration, captopril alters the abnormal sodium permeability of vascular smooth muscle in spontaneously hypertensive rats and that the restoration of normal permeability reduces vascular tone.

Animals↗

Congenital mesoblastic nephroma.

For more than a decade congenital mesoblastic nephroma of infancy has been recognized as an entity different from Wilms tumor in its clinical and histopathologic features. However, this tumor is sometimes confused with Wilms tumor and consequently, inadvertent and vigorous therapy compatible with that for Wilms tumor is given. we reviewed the literature and analyzed 90 cases of congenital mesoblastic nephroma in the English and Japanese literature. The importance of early and accurate histopathologic diagnosis of the resected specimen to avoid inappropriate post-operative therapy is emphasized, and the peculiar features of congenital mesoblastic nephroma are characterized.

Birth Weight↗

TRH and its novel analog (DN-1417): antipentobarbital action and involvement of cholinergic mechanisms.

Possible neuroanatomical loci and the mode of action of thyrotropin-releasing hormone (TRH) or its analog, gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide citrate (DN-1417), in reducing the pentobarbital-induced sleeping time were investigated by using an intracerebral microinjection technique in rats. Intravenous, intraperitoneal or intracerebroventricular (ICV) injection of TRH or DN-1417 produced a dose-related reduction of the sleeping time induced by pentobarbital. TRH or DN-1417 given into the posterior hypothalamic regions including the dorsal premammillary nucleus, lateral hypothalamic area and posterior nucleus of hypothalamus had a significant pentobarbital sleep shortening action in low doses. Injection of these peptides into the dorsomedial nucleus of thalamus, mesencephalic reticular formation, medial septal nucleus or hippocampus was also effective, in comparatively low doses. However, higher doses were required to elicit the effect when the injections were made into the nucleus accumbens, lateral preoptic area or caudate nucleus. In this respect, the parietal cortex was insensitive to TRH or DN-1417. The pentobarbital sleep shortening action of TRH or DN-1417 injected peripherally or into the hypothalamic regions was markedly antagonized by ICV or intrahypothalamic pretreatment with atropine methyl bromide. On the contrary, ICV injection of atropine methyl bromide had a weak or no antagonizing action on the effect of TRH injected ICV or into the reticular formation, medial septal nucleus or hippocampus. These results suggest that possible neuroanatomical sites mediating the pentobarbital sleep shortening action of TRH or DN-1417 may be posterior hypothalamic regions, dorsomedial nucleus of thalamus, reticular formation, medial septal nucleus or hippocampus. A cholinergic mechanism may also be involved in the effect of TRH on the hypothalamus.

Animals↗

Natural killer cell activities of several inbred strains of the guinea pig and their susceptibilities to rabbit antiserum directed to guinea-pig brain tissue.

Natural killer (NK) cell activities of spleen and peripheral blood leukocytes from several inbred guinea-pig strains, established in this Institute, were assessed in an 18-hr 51Cr-release assay. As target cells in the NK assay, a human myeloid cell line, K562, appeared to be the most suitable among several cultured cell lines tested. Intensities of cytolysis were different from strain to strain, but generally high in JY-2, JY-4 and JY-10 and low in JY-1. Treatment of the effector cells with rabbit anti-guinea-pig brain tissue serum plus complement reduced the NK activity, whereas treatment with rabbit anti-guinea-pig thymocyte serum, or rabbit anti-asialo GM1 serum, plus complement showed no significant effect on the NK activity.

Animals↗

Alkaline phosphatase isoenzyme of colonic carcinoma in Wistar-Furth rats.

Wistar-Furth (WF) strain rats have been shown to have a high incidence of spontaneous colon cancer. We have compared the alkaline phosphatase (AP) isoenzymes in colonic carcinomas of these inbred WF strain rats with the isoenzymes in the non-carcinomatous colon of the same strain and the normal colon of Wistar strain rats, from which the WF strain was derived. On electrophoresis of AP specimens partially purified by acetone fractionation, the non-carcinomatous colon was found to have three main isoenzymes, while the normal colon had two. Colonic carcinomas gave one band which migrated slower than any bands from either normal or non-carcinomatous colon. The electrophoretic mobility of AP from colonic carcinomas was retarded by neuraminidase treatment. This did not influence the isoenzymes from non-carcinomatous and normal colon. The inhibition patterns of the enzyme from colonic carcinoma by amino acids, inorganic phosphate and urea were different from those of the isoenzymes in the other two tissues. AP of colonic carcinoma was also the most heat-labile. There were no significant differences in the enzymic properties of the isoenzymes from non-carcinomatous and normal colon. The enzymic properties except for electrophoretic mobility were found to be the same between APs of colonic carcinoma and the placenta.

Aging↗