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Biomedical subjects

J Yamada

Publications and source records attributed to J Yamada.

At least 217 records · Page 12Linked to original sources

Inhibition by topiramate of seizures in spontaneously epileptic rats and DBA/2 mice.

The effects of topiramate, a novel antiepileptic drug, on tonic and absence-like seizures in spontaneously epileptic rats (SER; zi/zi, tm/tm) and on sound-induced seizures in DBA/2 mice were investigated. Topiramate (20 and 40 mg/kg i.p.) inhibited both tonic and absence-like seizures in a dose-dependent manner, whereas phenytoin (20 mg/kg i.p.) and zonisamide (40 mg/kg i.p.) inhibited only the tonic seizures. The inhibitory effects of topiramate on absence-like seizures were antagonized by pretreatment with haloperidol (0.5 mg/kg i.p.), but those on the tonic seizures remained unaffected. Topiramate inhibited sound-induced seizures in DBA/2 mice (ED50 = 8.6 mg/kg p.o.). These findings suggest that topiramate may be effective for treatment of both convulsive and absence seizures of human epilepsy. The inhibitory effect of topiramate on absence-like seizures in SER may be mediated through the central dopaminergic system.

Acoustic Stimulation↗

Effects of testosterone, hypophysectomy and growth hormone treatment on clofibrate induction of peroxisomal beta-oxidation in female rat liver.

Induction of peroxisomal beta-oxidation by clofibrate under altered hormonal states was investigated in female rat liver. Treatment of rats with clofibric acid (CPIB) caused a significant increase in hepatic peroxisomal beta-oxidation, with female rats being less responsive than males (4.2- vs 12.2-fold increase). However, testosterone treatment following ovariectomy of female rats resulted in an enhanced response to CPIB, giving an induction (11.7-fold) comparable to that seen in male rats. Hypophysectomy of female rats also enhanced the induction (8.2-fold compared with 5.1-fold), suggesting a suppressive effect of a pituitary-dependent factor on CPIB induction of peroxisomal beta-oxidation. Continuous infusion of growth hormone to the hypophysectomized female rats suppressed the enhanced induction nearly to the initial level (6.1-fold). The stimulatory effects of testosterone and hypophysectomy on the enzyme induction were additive. These findings suggest the involvement of growth hormone, as well as male sex hormone, in regulating the responsiveness to CPIB induction of peroxisomal beta-oxidation in rat liver.

Animals↗

Purification and properties of long-chain acyl-CoA hydrolases from the liver cytosol of rats treated with peroxisome proliferator.

Two long-chain acyl-CoA hydrolases, referred to as ACH1 and ACH2, were purified from the liver cytosol of rats fed a diet containing di(2-ethylhexyl)phthalate, a peroxisome proliferator. The molecular mass of ACH1 was estimated to be 73 kDa by gel filtration, and that of the subunits, 36 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The corresponding values of ACH2 were 42 and 43 kDa, respectively. Both enzymes were active toward fatty acyl-CoAs with chain-lengths of C12-16, but ACH1 had relatively broad specificity as acyl-CoAs with C8-18 were good substrates. A marked difference in their catalytic properties was found in the maximal velocity; for palmitoyl-CoA, 553 and 4.23 mumol/min/mg with Km values of 5.9 and 5.4 microM for ACH1 and ACH2, respectively. ACH2 underwent severe substrate inhibition with high concentrations of long-chain acyl-CoAs, whereas ACH1 did not. Examination with various reagents including divalent cations, sulfhydryl-blocking reagent, nucleotides, and hypolipidemic drugs, characterized ACH1 and ACH2 with several properties distinct from those of mitochondrial and microsomal hydrolases. ACH1 and ACH2 were also discernible in that the former, but not the latter, was inhibited by ATP. In the liver cytosol of rats treated with di(2-ethylhexyl)phthalate, about 90% of palmitoyl-CoA hydrolase activity was titrated with anti-ACH1 and anti-ACH2 antibodies. Immunoblot analysis suggested the presence of the enzymes also in extrahepatic tissues, especially in the brain and testis (ACH1), and in the heart and kidney (ACH2).

Animals↗

Effects of tryptamine on plasma glucagon levels in mice.

Our previous study indicated that tryptamine induces a dose-related increase in plasma glucagon levels of mice and that this effect is mediated by the peripheral serotonin2 (5-HT2) receptor. The present paper further investigated the involvement of serotonergic and catecholaminergic systems in hyperglucagonemia elicited by tryptamine. An inhibitor of 5-HT synthesis, p-chlorophenylalanine, did not affect tryptamine-induced increases in plasma glucagon levels. Tryptamine-induced hyperglucagonemia was not inhibited by adrenalectomy or by an inhibition of catecholamine synthesis by alpha-methyl-p-tyrosine. These findings indicate that tryptamine-induced hyperglucagonemia is elicited by its direct activation of 5-HT2 receptors and is not mediated by levels of endogenous 5-HT and catecholamines. The results further suggest that the peripheral 5-HT2 receptor has a possible role in the release of glucagon.

Adrenalectomy↗

Inhibitory effects of tryptamine on tolbutamide-induced hypoglycemia in mice: mediation by 5-HT receptors.

Effects of tryptamine on tolbutamide-induced hypoglycemia were investigated in mice. Tryptamine significantly inhibited hypoglycemia elicited by tolbutamide. The inhibitory effects of tryptamine were strongly blocked by the 5-HT1 and 5-HT2 receptor antagonist methysergide and the 5-HT2 receptor antagonist ketanserin, while the 5-HT3 receptor antagonist ICS 205-930 was without effect. Tryptamine induced hyperglucagonemia in tolbutamide-treated mice, and this effect elicited by tryptamine was strongly inhibited by the 5-HT2 receptor antagonist ketanserin. These results suggest that the inhibitory effects of tryptamine on tolbutamide-induced hypoglycemia are mediated by 5-HT2 receptors and that tryptamine is involved in glucagon release.

Animals↗

Characteristics of the hepatocarcinogenesis caused by dehydroepiandrosterone, a peroxisome proliferator, in male F-344 rats.

The characteristics of the hepatocarcinogenesis induced by dehydroepiandrosterone (DHEA) were compared with that induced by other peroxisome proliferators such as [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) and di(2-ethylhexyl)phthalate (DEHP). Male F-344 rats were given a diet containing DHEA at 0.5 or 1%, Wy-14,643 at 0.1% and DEHP at 2% for up to 78 weeks. In rats fed 0.5 or 1% DHEA the incidence of neoplasias was 20% after 52 weeks. At 78 weeks all rats treated with 1% DHEA had numerous grossly visible nodules and the incidence of hepatic neoplasia was dose-dependent. The magnitude of hepatocellular tumorigenicity after DHEA treatment was less potent than that after Wy-14,643, but more than that after DEHP treatment. Peroxisomal beta-oxidation activity increased three- or six-fold after a 10 week course of 0.5 or 1% DHEA respectively and this was significantly lower than that induced in Wy-14,643- or DEHP-fed rats. From 52 to 78 weeks these activities increased 3-9 times over that in controls. In both the group of rats treated with Wy-14,643 and those treated with DEHP, peroxisomal beta-oxidation constantly increased 11- to 15-fold during the experiment. Catalase activity increased 1.3- to 1.5-fold for the first 10 weeks of DHEA treatment and then recovered to the control level. The activities of glutathione peroxidase and glutathione S-transferase decreased markedly after 30 weeks in DHEA-treated rats and the decreases were sustained for up to 78 weeks. The profile of changes in enzyme activities in the rats fed DHEA was not significantly different from that of those fed Wy-14,643 or DEHP. There were no increases in 8-hydroxydeoxyguanosine, oxidative DNA damage or lipid peroxide level in the liver in any of the treated rats at 10 or 30 weeks. Since these results showed that the characteristics of hepatocarcinogenesis caused by DHEA were basically similar to those caused by Wy-14,643 and DEHP, typical peroxisome proliferators, hepatocarcinogenesis induced by DHEA is probably due to the same mechanisms as that induced by general peroxisome proliferators.

8-Hydroxy-2'-Deoxyguanosine↗

The alymphoplasia (aly) mutation co-segregates with the intercellular adhesion molecule-2 (lcam-2) on mouse chromosome 11.

A new spontaneous autosomal recessive mutation alymphoplasia (aly), which causes a systemic defect of lymph nodes and Peyer's patches, was mapped on mouse chromosome 11 by linkage analysis using (ALY x MSM)F1 x ALY backcross progeny (155 mice). The gene order and map distances on the chromosome were as follows (cM +/- SD); D11Mit14 (AntP91a), Krt-1 -(0.7 +/- 0.6)--D11Mit59--(1.9 +/- 1.1)--D11Mit52, D11Nds7 (Gfap)--(0.7 +/- 0.6)--aly, D11Mit10, D11Mit13 (Ace), D11Mit58 (Myla), lcam-2--(8.4 +/- 2.2)--D11Mit12. No recombinant was found among aly, D11Mit10, D11Mit13, D11Mit58 and lcam-2, suggesting the possible involvement of lcam-2 in the aly mutation. However, the nucleotide sequence of the lcam-2 gene of aly/aly mouse was identical to that of the control mouse. No difference was detected between aly/aly and the control mouse for expression of the gene by both Northern blot and reverse transcriptase polymerase chain reaction analyses. Furthermore, immunohistochemical analysis using a mAb revealed that the ICAM-2 protein was normally distributed in various tissues. These findings indicate that aly/aly mice do not suffer from defects of lcam-2. The four polymorphic microsatellite markers tightly linked with the aly gene will serve as admirable guideposts for a chromosomal walk to the aly gene.

Animals↗

Morphological study of the surface structure of the omasal laminae in cattle, sheep and goats.

The mucosal relief of the omasum in cattle, sheep and goats was examined by the naked eye, stereoscopic microscope and scanning electron microscope. The mucosal relief of the omasum showed wide variations both between and within these species. Omasal papillae on the laminae varied highly in shape, i.e. conical, rounded, claw-like, wart-like, finger-like etc. They decreased gradually in size from the oral to the aboral region of the omasal lamina. Ridge-like structures and linear arrangements of the papillae were also seen on the omasal laminae of cattle and sheep. Many grooves and folds were found on the lateral surface of the omasal papillae in adult cattle and on the inter-papillar surface of the laminae of all three species. The mucosal relief of the omasum in cattle seemed to be more well-developed than those of sheep and goats. Dietary effects on the omasal mucosa were also discussed.

Animals↗

Is lamina muscularis mucosae present in the ruminal mucosa of cattle? Immunohistochemical and ultrastructural approaches.

The cells in the condensed fibrous layer in the lamina propria of the ruminal mucosa of the calves and cows were studied at the light microscopic level. Abundant actin-immunoreactive cells were detected both in the calves and cows, while desmin-immunoreactive cells were moderate in frequency in the cows and low or absent in the calves. Vimentin-immunoreactive cells were abundant in the cows but moderate to low in frequency in the calves. These cells were distributed to form a condensed layer being more abundant in the ruminal papillae than the interpapillar mucosae in the cows and equal in the papillae and interpapillar mucosae in the calves. At the ultrastructural level, smooth muscle cells and fibroblasts were abundant in the deep core of the ruminal papilla of the cows. The present results suggest that the condensed fibrous layer revealed in the ruminal mucosae contains smooth muscle cell population which could be regarded as the specialized lamina muscularis mucosae.

Animals↗

Immunohistochemical study of the distributions of the peptide- and catecholamine-containing nerves in the omasum of the sheep.

The distribution in the sheep omasum of peptide- and catecholamine-containing neurons was investigated by an immunohistochemical technique using antibodies against six neuropeptides and two catecholamine-synthesizing enzymes. In the myenteric plexus, both nerve cell bodies and nerve fibers were positively immunostained for substance P (SP), methionine enkephalin (ENK), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) and galanin (GAL). In contrast, immunoreactivity specific for calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) was detected only in nerve fibers. In the omasal wall, nerve fibers with SP- and ENK-like immunoreactivity were prominent in the outer muscle layer, while numerous nerve fibers with VIP-, NPY- and GAL-like immunoreactivity were observed in the inner muscle layer. In the lamina propria mucosae, and in particular in the omasal papillae, a dense network of peptide-containing nerves was found. The distribution of nerves with CGRP-like immunoreactivity was different from that of other immunoreactive nerves. The networks of nerves with TH-, DBH- and NPY-like immunoreactivity were concentrated around the vascular components. The results of this study indicate the complexity of the enteric nervous system in the sheep omasum, reflecting the multiple functions of the nerves in the regulation of motility and/or absorption and secretion.

Animals↗

Immunohistochemical study of the distribution of endocrine cells in the gastrointestinal tract of the lesser mouse deer (Tragulus javanicus).

The occurrence and distribution of endocrine cells in the gastrointestinal tract of the lesser mouse deer, Tragulus javanicus, were studied immunohistochemically. Fourteen types of endocrine cells immunoreactive for serotonin, somatostatin, enteroglucagon, pancreatic glucagon, bovine pancreatic polypeptide (BPP), gastrin, substance P, motilin, gastric inhibitory polypeptide (GIP), cholecystokinin (CCK), methionine-enkephalin-Arg6-Gly7-Leu8 (MENK-8), secretin, neurotensin, peptide tyrosine tyrosine (PYY) and chromogranin were revealed. Chromogranin-, serotonin-, somatostatin- and enteroglucagon-immunoreactive cells were detected in all regions examined, while pancreatic glucagon-immunoreactive cells, except in the proper gastric gland region, were not found in other regions of the gastrointestinal tract. Few BPP-immunoreactive cells in either the proper gastric gland or pyloric gland regions and abundant gastrin-immunoreactive cells in the pyloric gland region were observed. Restricted distributions of substance P-, GIP-, gastrin-, motilin-, CCK-, MENK-8-, secretin-, neurotensin- and BPP-immunoreactive cells in the small intestine, and BPP-, substance P-, PYY- and motilin-immunoreactive cells in the large intestine were noted. The important findings include the presence of BPP-immunoreactive cells in the abomasum, pancreatic glucagon-immunoreactive cells in the proper gastric gland region, and substance P- and motilin-immunoreactive cells in the large intestine. It is suggested that the distribution pattern of gut endocrine cells in the lesser mouse deer is more similar to that in the pig than in the domestic ruminants so far reported.

Abomasum↗

The nerve cell bodies found in the ovine omasal laminae.

A histological study was made on the omasum of sheep, cows, sika deer, and Japanese serows in order to confirm the existence of the submucosal nerve cell bodies in the omasal laminae. In the present study, seventeen submucosal nerve cell bodies were found in seven sections from four out of twenty-two sheep.

Animals↗

Genetic profiles of 12 inbred rat strains for 46 microsatellite loci selected as genetic monitoring markers.

Genetic profiles for 46 microsatellite loci of 12 inbred strains of rats, including 2 congenic strains and a coisogenic strain, have been demonstrated. Rates of loci with different alleles between 2 inbred strains, which are not closely related to each other in origin, were from 71.7% between ACI/N and IS/Kyo strains to 41.3% between F344/N and TM/Kyo. On the other hand, the rates were 0% in both of 2 sets of congenic strains; between F344/N and F344/N-rnu, or between BN/fMaiKyo and BN.IS. When WTC/Kyo and the coisogenic strain TRM/Kyo (WTC/Kyo-tm) were compared for 115 microsatellite loci, no loci with different alleles between the strains were found. The 46 loci should be useful as genetic monitoring markers, since all of the primer pairs generate distinct PCR-products at a fixed annealing temperature of 55 degrees C.

Alleles↗