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91.
Tsuchiya M Fujiwara Y Kanai Y Mizutani M Shimada K Suga O Ueda S Watson JW Nagahisa A 《Pharmacology》2002,66(3):144-152
The anti-emetic effects of a novel tachykinin NK(1) receptor antagonist, ezlopitant ((2S,3S-cis)-2-diphenylmethyl)- N-[(2-methoxy, 5-isopropylphenyl)methyl]-1-azabicyclo- [2.2.2]octan-3-amine), were investigated in ferrets. Ezlopitant inhibited [(3)H]substance P ([(3)H]SP) binding to the human, guinea pig, ferret and gerbil NK(1) receptors (K(i) = 0.2, 0.9. 0.6 and 0.5 nmol/l, respectively), but had no affinity to NK(2) and NK(3) receptors up to 1 micromol/l. Ezlopitant also inhibited SP-induced contraction of guinea pig trachea with a pA(2) value of 7.8, but had no effects on the baseline tension and maximum contractile response. In ferrets, ezlopitant, either orally (0.03-3 mg/kg) or subcutaneously (0.3-3 mg/kg), prevented acute retching and vomiting responses induced by intraperitoneal injection of cisplatin (10 mg/kg). In addition, repeated subcutaneous injection of ezlopitant significantly inhibited delayed retching and vomiting responses that occurred in ferrets treated with the lower dose of cisplatin (5 mg/kg, i.p.). Ezlopitant (0.1-1 mg/kg, s.c.) also produced a dose-dependent inhibition of hindpaw tapping induced by intracerebroventricular injection of [Sar(9),Met(O(2))(11)]SP in gerbils, which is known to be mediated by NK(1) receptors in the brain. These findings indicate that ezlopitant is a potent and selective NK(1) receptor antagonist, and that it inhibits both acute and delayed emetic reactions induced by cisplatin in ferrets via acting on NK(1) receptors in the central nervous system. 相似文献
92.
Ogawa Y Iwama M Ohgi K Tsuji T Irie M Itagaki T Kobayashi H Inokuchi N 《Biological & pharmaceutical bulletin》2002,25(6):722-727
The sialic acid binding lectin from bullfrog oocytes (cSBL) is known to have anti-tumor activity. In a previous report, to elucidate the relationship between the net charge and anti-tumor activity of cSBL, we examined the effect of chemical modifications of cSBL with a water-soluble carbodiimide in the presence of various nucleophiles. The results suggested that the anti-tumor activity and internalization into tumor cells increased with an increase in the net charge of cSBL. However, in the chemically modified cSBL, a modification site was observed on average in two of the carboxyl groups of cSBL. To confirm these previous results and to determine which modified carboxyl group contributes to the increase in anti-tumor activity, we prepared mutants with substitutions of Asn/Gln and Arg at three acidic amino acid residues of cSBL and studied their anti-tumor activity and internalization efficiency. The results showed the enhancing effect of charge on anti-tumor activity and internalization, and suggested that the replacement of D24 and E88 of cSBL with arginine is more effective than that of E97. The double mutant D24RE88R showed comparable anti-tumor activity to the ethylenediamine-modified cSBL reported previously. The mutant was well-characterized as a pure cSBL derivative suitable for studying the mechanism of the anti-tumor action of cSBL. 相似文献
93.
Transient cochlear ischemia causes delayed cell death in the organ of Corti: an experimental study in gerbils 总被引:4,自引:0,他引:4
Koga K Hakuba N Watanabe F Shudou M Nakagawa T Gyo K 《The Journal of comparative neurology》2003,456(2):105-111
To elucidate whether ischemia-reperfusion can cause delayed cell death in the cochlea, the effects of transient cochlear ischemia on hearing and on neuronal structures in the cochlea were studied in Mongolian gerbils. Ischemia was induced by bilaterally occluding the vertebral arteries for 5 minutes in gerbils, which lack posterior cerebral communicating arteries. In gerbils, the labyrinthine arteries are fed solely by the vertebral arteries. Occlusion of the vertebral arteries caused a remarkable increase in the threshold of compound action potentials (CAPs), which recovered over the following day. However, 7 days after the onset of reperfusion, the threshold began to increase again. Morphologic changes in the hair cell stereocilia were revealed by electron microscopy. The number of nuclear collapses was counted in cells stained for DNA and F-actin to evaluate the degree of cell death in the organ of Corti. Changes in spiral ganglion cell (SGC) neuron number were detected, whether or not progressive neuronal death occurred in the SGC. These studies showed that sporadic fusion of hair cells and the disappearance of hair cell stereocilia did not begin until 4 days after ischemia. On subsequent days, the loss of hair cells, especially inner hair cells (IHCs), and the degeneration of SGC neurons became apparent. Ten days after ischemia, the mean percentage cell loss of IHCs was 6.4% in the basal turn, 6.4% in the second turn, and 0.8% in the apical turn, respectively, and the number of SGC neurons had decreased to 89% of preischemic status. These results indicate that transient ischemia causes delayed hearing loss and cell death in the cochlea by day 7 after ischemia. 相似文献
94.
Myocardium tissue ablation with high-peak-power nanosecond 1,064- and 532-nm pulsed lasers: influence of laser-induced plasma 总被引:1,自引:0,他引:1
Ogura M Sato S Ishihara M Kawauchi S Arai T Matsui T Kurita A Kikuchi M Ashida H Obara M 《Lasers in surgery and medicine》2002,31(2):136-141
BACKGROUND AND OBJECTIVES: We investigated the mechanism and characteristics of porcine myocardium tissue ablation in vitro with nanosecond 1,064- and 532-nm pulsed lasers at laser intensities up to approximately 5.0 GW/cm(2). Particular attention was paid to study the influence of the laser-induced plasma on the ablation characteristics. The applicability of these two lasers to transmyocardial laser revascularization (TMLR) was discussed. STUDY DESIGN/MATERIALS AND METHODS: Porcine myocardium tissue samples were irradiated with 1,064- and 532-nm, Q-switched Nd:YAG laser pulses, and the ablation depths were measured. The temporal profiles of the laser-induced optical emissions were measured with a biplanar phototube. For the ablated tissue samples, histological analysis was performed with an optical microscope and a polarization microscope. RESULTS: The ablation efficiency at 1,064 nm was higher than that at 532 nm. The ablation threshold at 1,064 nm (approximately 0.8 GW/cm(2)) was lower than that at 532 nm (approximately 1.6 GW/cm(2)), in spite of the lower absorption coefficient being expected at 1,064 nm. For the 1,064-nm laser-ablated tissues, thermal damage was very limited, while damage presumably caused by the mechanical effect was observed in most of the cases. For the 1,064-nm laser ablation, the ablation threshold was equal to the threshold of the laser-induced optical emission (approximately 0.8 GW/cm(2)), while for the 532-nm laser ablation, the optical emission threshold ( approximately 2.4 GW/cm(2)) was higher than the ablation threshold. CONCLUSIONS: We considered that for the 1,064-nm laser ablation, the tissue removal was achieved through a photodisruption process at laser intensities of > approximately 0.8 GW/cm(2). At laser intensities of > 3.0 GW/cm(2), however, the ablation efficiency decreased; this can be attributed to the absorption of incoming laser pulses by the plasma. For the 532-nm laser ablation, the tissue removal was achieved through a photothermal process at laser intensities of > approximately 1.6 GW/cm(2). At laser intensities of > 2.4 GW/cm(2), a photodisruption process may also contribute to the tissue removal, in addition to a photothermal process. With regard to the ablation rates, the 1,064-nm laser was more suitable for TMLR than the 532-nm laser. We concluded that the 1,064-nm Q-switched Nd:YAG laser would be a potential candidate for a laser source for TMLR because of possible fiber-based beam delivery, its compact structure, cost effectiveness, and easy maintenance. Animal trials, however, have to be carried out to evaluate the influence of the tissue damage. 相似文献
95.
96.
A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures 总被引:8,自引:0,他引:8
Nakayama J Fu YH Clark AM Nakahara S Hamano K Iwasaki N Matsui A Arinami T Ptácek LJ 《Annals of neurology》2002,52(5):654-657
A naturally occurring mutation of the mass1 (monogenic audiogenic seizure-susceptible) gene recently has been reported in the Frings mouse strain, which is prone to audiogenic seizures. The human orthologous gene, MASS1, was mapped to chromosome 5q14, for which we previously have reported significant evidence of linkage to febrile seizures (FEB4). We screened for MASS1 mutations in individuals from 48 families with familial febrile seizures and found 25 DNA alterations. None of nine missense polymorphic alleles was significantly associated with febrile seizures; however, a nonsense mutation (S2652X) causing a deletion of the C-terminal 126 amino acid residues was identified in one family with febrile and afebrile seizures. Our results suggest that a loss-of-function mutation in MASS1 might be responsible for the seizure phenotypes, though it is not likely that MASS1 contributed to the cause of febrile seizures in most of our families. 相似文献
97.
Hayashi M Araki S Arai N Kumada S Itoh M Tamagawa K Oda M Morimatsu Y 《Brain & development》2002,24(8):196-775
Spinal muscular atrophy (SMA) is a hereditary motor neuron disease, and three clinical subtypes of autosomal recessive SMA, including Werdnig Hoffmann disease (type 1), have been shown to be induced by deletion within the same genes. In order to clarify the pathogenesis of motor neuron degeneration in SMA, we immunohistochemically examine the expressions of oxidative stress-related materials (oxidative products) and glutamate transporters, which can prevent glutamate neurotoxicity, in five autopsy cases of SMA type 1. Age-matched controls did not show any deposition of oxidative products in the brain. In contrast, the abnormal deposition of 4-hydroxy-2-nonenal-modified protein, a product of membrane lipid oxidation, was observed in the spinal motor neurons in three cases, although the motor neurons did not show an increase of nitrotyrosine, which was observed in adult-onset amyotrophic lateral sclerosis. In addition, the nuclei of neurons and glial cells in the precentral gyrus, thalamus or cerebellar cortex were immunoreactive for 8-hydroxy-2′-deoxyguanosine in two cases, which was one of the most commonly used markers for oxidative DNA damage. Regarding glial glutamate transporters, three of five cases of SMA type 1 showed a reduction in immunoreactivity for excitatory amino acid transporter-1 (GLAST) in the ventrolateral nucleus of the thalamus, in which there was neither neuronal loss nor gliosis in routine histochemistry. One case, having mechanical ventilation, demonstrated a reduced expression of another glial glutamate transporter (GLT-1) throughout the central nervous system. These data suggest that oxidative stress and disturbed glutamate transport can partly be involved in the motor neuron devastation and/or latent thalamic degeneration in SMA type 1. 相似文献
98.
Tuyet Mai TT Takasaki S Yasue M Kitabatake K Chuyen NV 《Journal of nutritional science and vitaminology》2002,48(4):298-304
The effects of brewer's yeast, casein, and soy protein intakes on the absorption and retention as well as the incorporation into hemoglobin and systemic iron stores of dietary iron were examined in an animal experiment with growing rats. Relative biological values (RBV) of iron in the rats fed casein (C), soy protein (SP), and yeast (Y) diets were 1.00, 0.31, and 1.77, respectively. The apparent absorption of iron in Y-diet-fed rats was significantly higher than that in C- or SP-diet-fed rats. The hemoglobin regeneration efficiency (HRE) of iron in Y group was significantly higher than those in C and SP groups. As a result of search for iron-absorptive enhancers (IAE) in yeast, RBV and HRE of the yeast-cell-wall-including diet turned out to be significantly higher than those of its lacking diet. These results suggest that IAE occurring in the yeast cell wall may be effective for iron absorption. 相似文献
99.
100.
Yuyama N Mizuno J Tsuzuki H Wada-Takahashi S Takahashi O Tamura K 《Brain research》2002,948(1-2):8-16
c-Fos protein is a nuclear protein coded by c-fos proto-oncogene subsequent to synaptic activation of the neurons. We used immunohistochemical methods to visualize the expression of c-Fos protein in myenteric neurons of the guinea pig distal colon and examined the effects of the extrinsic autonomic inputs on the enteric circuits. No c-Fos immunoreactivity was observed in the colonic segments fixed immediately after removal from the animal body. A number of c-Fos-immunoreactive nuclei of myenteric neurons, however, appeared in all preparations that were incubated in Krebs solution in vitro (n=10). Application of tetrodotoxin (0.2 microM) abolished the expression of c-Fos-immunoreactivity (n=6), but hexamethonium (100 microM) failed to decrease the number of c-Fos-positive neurons despite a complete suppression of spontaneous peristaltic movements (n=5). Neither the electrical stimulation (n=8) nor the severing of the pelvic nerves (n=5) changed the number of c-Fos-positive neurons. Application of clonidine, an alpha(2)-agonist, (0.1 microM) abolished the expression of c-Fos protein in all preparations (n=5), while denervation of the sympathetic fibers in the lumbar colonic and hypogastric nerves in vivo increased the number of c-Fos-positive neurons (n=5). The results indicate that the enteric circuit in the distal part of the gastrointestinal tract is under tonic inhibition by the sympathetic nervous system from the lumbar spinal cord. c-Fos immunoreactivity expressed in the colonic preparations in vivo might be the results of enhanced activation of non-nicotinic receptors after removal of the sympathetic inhibition. 相似文献