Effect of extract of Agkistrodon blomhoffii on acute gastric mucosal lesions induced by ischaemia-reperfusion in rats.
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Agkistrodon↗
Biomedical subjects
Y Kishimoto
Publications and source records attributed to Y Kishimoto.
Effects of sucralfate on acute gastric mucosal injury and gastric ulcer induced by ischemia-reperfusion in rats.
We have revealed that acute gastric mucosal injury induced by a single ischemia-reperfusion (I-R) treatment develops into an ulcerative lesion within a few days. In the present studies, we examined the effects of oral administration of sucralfate on gastric damage induced by I-R. Sucralfate (1-100 mg/kg, 15 min before I-R) significantly reduced the total erosion area observed immediately after I-R. A high dose of sucralfate (30-100 mg/kg) inhibited the increase in the thiobarbituric acid-reactive substances, an index of lipid peroxidation, induced by I-R, although a low dose of it failed. When sucralfate (30 mg/kg, once a day) was orally administered after I-R, it prevented mucosal damage from developing into gastric ulcers: the total area of the ulcers was significantly reduced compared to that without sucralfate administration 72 h after I-R. High concentrations of sucralfate (3-10 mg/ml) reduced the superoxide radicals generated by leukocytes or xanthine-xanthine oxidase, and protected erythrocyte membrane ghosts against lipid peroxidation induced by hydrogen peroxide and Fe2+ in vitro. These results indicate that sucralfate may prohibit both the generation of acute gastric mucosal injury and its progression to ulcer induced by I-R, probably due to a cytoprotective action on the mucosal surface. However, the protective mechanism may involve an inhibitory action on superoxide and hydroxyl radicals at high doses.
Animals↗
Effects of cimetidine on acute gastric mucosal injury induced by ischemia-reperfusion in rats.
We investigated the effects of cimetidine on acute gastric mucosal injury induced by ischemia-reperfusion in rats. Under pentobarbital anesthesia, the celiac artery was clamped for 30 min and reperfused for 60 min. Cimetidine, famotidine and omeprazole caused a dose-dependent suppression in the total area of erosions that were induced by ischemia-reperfusion. Whereas, none of them inhibited the increase in thiobarbituric acid-reactive substances in the stomach, as an index of lipid peroxidation. The inhibitory effect of intraperitoneally administered cimetidine on mucosal damage was abolished by continuous luminal perfusion with HCl solution (pH 1.5, 1 ml/min) during ischemia-reperfusion, while luminal perfusion with the solution containing HCl and cimetidine (3 mmol/l) significantly reduced the total area of erosions compared to luminal perfusion with HCl solution alone. Cimetidine (3 mmol/l) inhibited hydroxyl radical-induced lipid peroxidation of human erythrocyte membranes by 60% in vitro. These results indicate that cimetidine possesses a protective effect against acute gastric mucosal injury induced by ischemia-reperfusion not only due to the suppression in gastric acid secretion, but also due to the antioxidant action when it is present at a high concentration in the intragastric environment.
Animals↗
The molecular nature of zebrafish swirl: BMP2 function is essential during early dorsoventral patterning.
Early dorsoventral pattern formation in vertebrate embryos is regulated by opposing activities of ventralizing bone morphogenetic proteins (BMPs) and dorsal-specific BMP antagonists such as Chordin, Noggin and Follistatin. Specific defects in early dorsoventral patterning have been recently found in a number of zebrafish mutants, which exhibit either a ventralized or dorsalized phenotype. One of these, the ventralized mutant chordino (originally called dino) is caused by a mutation in the zebrafish chordin homologue and interacts genetically with the dorsalized mutant swirl. In swirl mutant embryos, dorsal structures such as notochord and somites are expanded while ventral structures such as blood and nephros are missing. Here we demonstrate that the swirl phenotype is caused by mutations in the zebrafish bmp2 gene (zbmp2). While injection of mRNAs encoded by the mutant alleles has no ventralizing effect, injection of wild-type zbmp2 mRNA leads to a complete rescue of the swirl mutant phenotype. Fertile adult mutant fish were obtained, showing that development after gastrulation is not dependent on zbmp2 function. In addition zBMP2 has no maternal role in mesoderm induction. Our analysis shows that swirl/BMP2, unlike mouse BMP2 but like mouse BMP4, is required for early dorsoventral patterning of the zebrafish embryo.
Alleles↗
Hydra regeneration from recombined ectodermal and endodermal tissue. II. Differential stability in the ectodermal and endodermal epithelial organization.
Hydra tissue consists of the ectodermal and the endodermal layers. When the two layers were separated by procaine treatment and then recombined, the ectodermal epithelial cells spread as a single cell layer over the endoderm as in epiboly in vertebrate embryogenesis, and the resultant spherical structure subsequently regenerated into a complete hydra. In this study, light and electron microscopy were used to examine the structural changes which took place in the cells and tissue during this epibolic ectodermal spreading process. Within a few hours after tissue recombination, the endoderm underwent dramatic changes; it lost its epithelial sheet organization, and turned into a mass of irregularly shaped cells without the apical-basal cell polarity initially present. In contrast, the ectoderm maintained its basic epithelial sheet organization as it spread over the endoderm. Later, the endodermal epithelial cells reorganized themselves into a single-layered epithelial sheet underneath the spreading ectodermal layer. The resultant spherical structure consisted of a single layer of ectodermal epithelial cells outside, a single layer of endodermal epithelial cells inside, and an empty cavity in the center as in normal hydra tissue. This structure regenerated into hydra in the following days. These and other observations demonstrate that the two-layered epithelial sheet organization is highly dynamic, and that its stability is maintained by strong interactions between the two layers in normal hydra. It is suggested that this dynamic nature of the hydra tissue, particularly the high plasticity of the endodermal epithelial sheet organization, may be an important element for the high regenerative capacity of this organism.
Animals↗
Aplastic anemia complicating Sjögren's syndrome.
A 47-year-old woman was referred to our hospital because of severe anemia and polyclonal gammopathy. She developed sicca syndrome after admission. Laboratory data revealed pancytopenia (white blood cells, 2,800/microliter; hemoglobin, 6.4 g/dl; platelets, 6.1 x 10(4)/microliter) and hyper gamma globulinemia (5.2 g/dl), and bone marrow was hypoplastic. Histology of the salivary gland showed infiltration of lymphocytes. We report a good response to immunosuppressive therapy in a rare case of aplastic anemia complicating Sjögren's syndrome.
Anemia, Aplastic↗
Polyangiitis overlap syndrome.
A 33-year-old man was admitted to our hospital because of intermittent claudication and finger tip ulceration with a skin rash on the upper and lower extremities. He later developed a massive melena. Angiography revealed arterial occlusion in the hand and foot, skin biopsy showed vasculitis with eosinophilic infiltration, and biopsy of the colon showed mucosal vasculitis with thrombosis. A diagnosis of polyangiitis overlap syndrome was made, and all these symptoms improved after corticosteroid therapy.
Adult↗
Induction of apoptosis in megakaryocytic leukemia cell lines by MX2, a morpholino anthracycline.
Leukemia with megakaryocytic involvement has a poor prognosis. MX2 is a new morpholino anthracycline that is effective against various leukemic cell lines. This study examined the antitumor activity of MX2 against human megakaryocytic cell lines, including CMK, CMK11-5, MEG-01, and UT-7, and investigated the role of apoptosis in the cytotoxicity of this drug. To quantify the extent of apoptosis induced by MX2, we used the in situ terminal deoxynucleotide transferase assay and the histone-associated DNA fragmentation assay. The cytotoxic effect of MX2 on CMK cells was reduced by various inhibitors of apoptosis. To our knowledge, this is the first report showing that apoptosis is involved in the killing of megakaryocytic cell lines by an antileukemic agent. We suggest that MX2 may be useful for the treatment of megakaryocytic leukemia.
Antibiotics, Antineoplastic↗
Sensitive determination of nitrotyrosine in human plasma by isocratic high-performance liquid chromatography.
A highly sensitive and simple isocratic high-performance liquid chromatographic method was developed for determination of 3-nitrotyrosine in human plasma with precolumn derivatization with 4-fluoro-7-nitrobenzo-2-oxa-1,3-diazole. The precision of the method was satisfactory (coefficient of variation 4.8%), and the detection limit was established at 0.1 pmol of 3-nitrotyrosine allowing the determination at the level of 6 pmol/ml in human plasma. The recoveries of 3-nitrotyrosine and alpha-methyltyrosine, an internal standard, were 89.3 +/- 7.1 and 85.7 +/- 7.6%, respectively. The 3-nitrotyrosine level was 31 +/- 6 pmol/ml (mean +/- S.D., n = 9) in plasma from healthy volunteers. Since 3-nitrotyrosine is a stable product of peroxynitrite, an oxidant formed by a reaction of nitric oxide and superoxide radicals, the measurement of its plasma concentration may be useful as a marker of nitric oxide-dependent oxidative damage.
4-Chloro-7-nitrobenzofurazan↗
Frequent loss in chromosome 8p loci in liver cirrhosis accompanying hepatocellular carcinoma.
Most hepatocellular carcinoma (HCC) is preceded by liver cirrhosis, but the genetic changes involved in cirrhosis are not well understood. We therefore studied loss of heterozygosity (LOH) in cirrhotic and neoplastic foci in livers of 14 patients with HCC. The samples, microdissected from paraffin-embedded tissues, were analyzed using a polymerase-chain-reaction-based assay for dinucleotide repeat polymorphisms on 8p. Of the 14 cases, 13 showed constitutional heterozygosity for the microsatellite markers. In 7 (54%) of these 13 informative cases, LOH was detected in the primary HCC and, in these 7 doubly informative (informative and LOH-positive in primary HCC) cases, LOH was found in 16 (70%) of 23 liver cirrhotic foci. The pattern of 8p allelic loss was identical in each doubly informative tumor; however, some of the liver cirrhotic foci harbored an 8p loss identical to that seen in the primary HCC, some harbored a different 8p loss, and some did not harbor any 8p loss. The remaining 6 cases without LOH on 8p in HCC showed no 8p loss in any cirrhotic foci. Presumably HCC could develop from cirrhotic cells harboring 8p loss.
Adult↗
Formalin- and carrageenan-induced inflammation attenuates place preferences produced by morphine, methamphetamine and cocaine.
Morphine-, methamphetamine- and cocaine-induced place preferences under inflammation produced by unilateral injections of 2.5% formalin (50 microliters) and 1% carrageenan (100 microliters) into the hind paw were examined in rats. Formalin and carrageenan reduced the paw pressure threshold, and this hyperalgesia lasted for 9 and 13 days, respectively. Morphine-, cocaine- and methamphetamine-induced place preferences were significantly attenuated in inflamed groups as compared with the respective noninflamed groups. However, indomethacin failed to produce a place preference in either group. Furthermore, the morphine-induced place preference in the inflamed group gradually recovered to the respective control level as the inflammation healed. These results suggest that the rewarding effects of morphine, cocaine and methamphetamine are attenuated in the presence of inflammatory nociception.
Animals↗
A new gastric ulcer model induced by ischemia-reperfusion in the rat: role of leukocytes on ulceration in rat stomach.
A new model of gastric ulcer involving damage to the muscularis mucosae was developed by clamping the celiac artery in rat to induce ischemia-reperfusion (I-R) injury. Although erosions with falling off of the gastric mucosa were observed immediately, 24 and 36 hours after the I-R, gastric ulcers involving the injury of muscularis mucosae were observed in the area of gastric glands at 48 and 72 hours after initiation of injury. Administration of omeprazol, a proton pump inhibitor, or pentoxifylline, an anti-leukocyte drug, just after the initiation of injury significantly decreased the total area of ulcers at 72 hours. A combination of omeprazol and pentoxifylline was more effective than either drug alone. An anti-leukocyte adhesion molecule (anti-CD18 antibody) also showed significant inhibitory effect on the development of ulcers at 72 hours and the infiltration of leukocytes into both submucosa and mucosa. These results indicate that in our model, gastric acid together with leukocytes contribute to the development of ulcers following erosions. This model may be used to investigate the mechanisms of the development of gastric ulcer and evaluate antiulcer drugs in a preclinical setting.
Animals↗
Mutations associated with carcinomas arising from pleomorphic adenomas of the salivary glands.
Pleomorphic adenoma (PA) is the most common benign tumor of salivary glands. Carcinomas in pleomorphic adenomas (CPAs) may arise by malignant transformation of the epithelial components of PAs. Occasionally, transitional zones containing cells with histological features intermediate between those of the benign PA and carcinomatous components of CPA are identified. After careful microdissection of archival microslides, the authors studied 12 cases of CPAs and their attendant adenomatous and transitional areas for mutations in the p53, RB, and K-ras genes, and at chromosomal loci 5q and 9p. The authors failed to find mutations in the K-ras gene or 9p locus. A relatively high rate of mutations (loss of heterozygosity [LOH] and microsatellite alterations) at the p53 gene were detected in CPAs (58%), and at somewhat lower frequencies at the RB gene (33%) and chromosomal location 5q (17%). Mutational frequency in the associated transitional and adenomatous areas were slightly lower than in the corresponding CPAs. No mutations were detected in adenomatous or transitional areas unless they also were present in the corresponding CPAs. Mutations of these three genes were absent in four cases of CPA, and in seven PAs without malignant change. These findings indicate that most CPAs arise from adenomas as the result of mutations in the three genes, especially p53. In addition, other, as yet unidentified genes may also be involved both in the development of PA and in its malignant progression to CPA. Mutational analysis of PAs may provide information of prognostic importance.
Adenocarcinoma↗
Effects of cigarette smoke on nitric oxide-induced increase in cyclic GMP in nerve terminals of rat cerebral cortex.
Since nitric oxide (NO) has been widely accepted as a novel neuromodulator, which activates soluble forms of guanylate cyclase to increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels, the effect of water-soluble substance in cigarette smoke on cyclic GMP levels were investigated using nerve terminals prepared from rat cerebral cortex. Although the smoke-substance itself failed to affect cyclic GMP levels in the synaptosomes, the smoke-substance significantly inhibited the increases in cyclic GMP levels induced by NO donors. The blocking effect of the smoke-substance was inhibited by concomitant incubation with superoxide dismutase, but not with mannitol. In addition, the effect of smoke-substance was mimicked by products of the xanthine/xanthine oxidase system, but not by nicotine. The effect of smoke-substance was preserved at least 7 days after they were stored at room temperature. Therefore, these results suggest that the smoke-substance may possess long half-lives to produce the radicals which inactivate NO, and to inhibit the increase in cyclic GMP levels in nerve terminals. The interference with NO may explain the part of mechanism in effects of cigarette smoke on neuronal functions.
Analysis of Variance↗
Hydra regeneration from recombined ectodermal and endodermal tissue. I. Epibolic ectodermal spreading is driven by cell intercalation.
Cell-cell interaction and cell rearrangement were examined in the process of epithelial sheet formation during regeneration from hydra cell aggregates. The ectodermal and endodermal epithelial cell layers of Hydra magnipapillata were separated by procaine treatment. Each of the separated layers was then dissociated into single cells and reaggregated to produce ectodermal or endodermal cell aggregates. When the two aggregate types were recombined, a firm adhesion was quickly established between them. This was followed by a vigorous spreading of the ectodermal epithelial cells as a thin layer over the endoderm in a manner similar to the 'epiboly' in some developing embryos. Cell movement in this spreading process was examined using fluorescent dyestaining. It revealed that cells initially located in the inside of the aggregate migrated to intercalate themselves among the cells originally present in the contact surface. This radial cell intercalation took place continuously in the contact surface of both the ectodermal and endodermal aggregates, and produced a rapid growth of the contact surface, eventually leading to complete envelopment of the entire endoderm by the ectoderm. The resulting structure was a small sphere having a two-layered epithelial organization as in normal hydra. This sphere regenerated into a complete hydra a few days later. A tryptic extract of hydra membrane fraction specifically inhibited the ectodermal spreading over the endoderm, but not the initial adhesion or the later regeneration processes. These observations suggest that radial cell intercalation at the contact surface plays a crucial role in producing ectodermal spreading and establishing epithelial sheet organization in the recombined aggregates. The intercalation is presumably activated by a signal exchange through the contact surface. The inhibitory effect of the membrane extract suggests that it contains a factor that is involved in some way in this signaling mechanism.
Animals↗
[Saposins and sphingolipid metabolisms].
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Amino Acid Sequence↗
Allele-specific loss in chromosome 9p loci in preneoplastic lesions accompanying non-small-cell lung cancers.
BACKGROUND: Carcinogenesis is a multistep process, which may begin as a consequence of chromosomal changes. Deletions in the short arm of chromosome 9 (9p) have been observed in lung carcinomas. In addition, morphologically recognizable preneoplastic lesions, frequently multiple in number, precede onset of invasive carcinomas. PURPOSE: We tested for deletions and loss of heterozygosity (LOH) at 9p loci in preneoplastic and neoplastic foci in lungs of patients with non-small-cell lung carcinomas (NSCLCs). METHODS: Seven archival, paraffin-embedded, surgically resected NSCLC specimens were selected. They were predominantly from patients with adenocarcinomas and contained multiple preneoplastic lesions, including hyperplasia, metaplasia, dysplasia, and carcinoma in situ (CIS). Fifty-three histologically identified preneoplastic and malignant lesions present in bronchi, bronchioles, and alveoli were precisely microdissected from stained tissue sections with a micromanipulator. Stromal lymphocytes were used to determine constitutional heterozygosity. The specimens were analyzed for LOH using polymerase chain reaction-based assays for polymorphism in dinucleotide repeats (microsatellite markers) in interferon alfa (IFNA) and D9S171 loci on 9p. RESULTS: All seven cases were constitutionally heterozygous for one or both microsatellite markers. Five of seven cases had LOH at one or both 9p loci in the invasive primary cancers (doubly informative cases). Four of these five cases also revealed LOH in preneoplastic foci. In the doubly informative cases, LOH was detected in five (38%) of 13 foci of hyperplasia, four (80%) of five foci of dysplasia, and three (100%) of three CIS lesions. LOH was detected in preneoplastic lesions from all regions of the respiratory tract, including bronchi, bronchioles, and alveoli, and involved five different cell types. The identical allele was lost from both the preneoplastic lesions and the corresponding tumors (12 of 12 lesions, 17 of 17 comparisons), a phenomenon we have referred to as "allele-specific mutation." Statistical analyses employing a cumulative binomial test demonstrated that the probabilities of such findings occurring by chance are 2.4 x 10(-4) and 7.6 x 10(-6), respectively. From comparisons with the previously published data on other chromosomal abnormalities in the same tissue specimens, it appears that LOH at 3p and 9p loci occurred early in the hyperplasia stage, but the ras gene point mutations were relatively late, at the CIS stage. CONCLUSIONS: LOH at 9p loci occurs at the earliest stage in the pathogenesis of lung cancer and involves all regions of the respiratory tract. LOH in NSCLC is not random but targets a specific allele in individuals. Studying preneoplastic lesions may help identify intermediate markers for risk assessment and chemoprevention.
Adenocarcinoma↗
Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma.
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Base Sequence↗