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Biomedical subjects

A Mori

Publications and source records attributed to A Mori.

At least 91 records · Page 5Linked to original sources
PubMed2000

Effect of norepinephrine receptors on trigeminal rhythm generation in newborn rats.

N-methyl-D,L-aspartate acid and bicuculline are required to enhance the trigeminal rhythmic activities in an in vitro isolated brainstem block preparation. In this study, we analyzed the effect of norepinephrine on the trigeminal neural circuit underlying rhythmic jaw movements. Rhythmic trigeminal activity is observed in brainstem preparations (inferior colliculus to obex) only following blockade of alpha(2)-adrenoceptors with idazoxan. This observation, combined with the inhibition of rhythm by alpha(2)-adrenoceptor agonists suggests endogenous alpha(2)-adrenoceptor mediated inhibition of trigeminal networks. A complex noradrenergic modulation of trigeminal systems is further supported by the prazosin-sensitive potentiation of rhythm by bath application of the alpha(1)-adrenoceptor agonist phenylephrine.

Adrenergic alpha-1 Receptor Agonists↗
PubMed2000

Role of E-cadherin in peritoneal dissemination of the pancreatic cancer cell line, panc-1, through regulation of cell to cell contact.

The present study was designed to clarify the molecules responsible for peritoneal dissemination of cancer cells. We established sublines with high (HP cells) and low (LP cells) passing activity through the membrane of a transwell chamber. The cell lines were established from the human pancreatic cancer cell line, Panc-1. LP cells demonstrated an octagonal shape and tight adhesion, whereas HP cells exhibited a spindle shape and grew with less cell-cell contact in vitro. It was found that HP cells demonstrated a high degree of peritoneal dissemination in nude mice following peritoneal injection of these cells compared to LP cells. We subsequently investigated the expression of certain adhesion molecules. Consequently, we found that LP cells exhibited a stronger expression of E-cadherin than HP cells. On the other hand, there was no difference in the expression of CD44H and beta1 integrin between these two sublines. Passing activity of LP cells through the membrane of the invasion chamber increased to nearly equal levels with HP cells following treatment with anti-human E-cadherin antibody. Moreover, transfection of mouse E-cadherin cDNA into HP cells reduced both passing activity through the membrane of the invasion chamber and peritoneal dissemination in nude mice to levels similar to that of LP cells. In conclusion, these results indicated that loss of E-cadherin facilitates both passing activity in an invasion chamber and peritoneal dissemination, playing a causative role in peritoneal dissemination of cancer cells.

Animals↗
PubMed2000

Spleen-derived dendritic cells engineered to enhance interleukin-12 production elicit therapeutic antitumor immune responses.

The major goal in cancer immunotherapy is the induction of tumor-specific T lymphocytes capable of killing tumor cells. As both dendritic cells (DCs) and interleukin-12 (IL-12) can play immunostimulatory roles in vivo, the use of a combination of these has become a promising approach. In the present study, we used a murine tumor model to examine whether spleen-derived DCs transduced with the IL-12 gene could elicit tumor-specific immune responses. BALB/c mice injected peritumorally with adenovirus-mediated IL-12 gene-transduced antigen-unpulsed DCs inhibited the growth of day 5-established subcutaneous CT26 tumors. Splenocytes from treated mice responded specifically to parental tumor cells and showed increased production of interferon gamma (IFN-gamma) and antitumor cytotoxic T-lymphocyte (CTL) activity. Increased numbers of both CD4(+) and CD8(+) T cells were detected in the treated tumors. The inhibition of tumor growth was significantly greater in mice injected with IL-12 gene-transduced DCs than in those injected with IL-12 gene-transduced fibroblasts or the IL-12 gene-encoding adenovirus itself. Taken together, these results indicate that DCs transduced with the IL-12 gene by a recombinant adenovirus are effective in inducing tumor-specific Th1 and CTL responses that inhibit the growth of established subcutaneous tumors.

Adenocarcinoma↗
PubMed2000

Palladium-catalyzed cross-coupling of silanols, silanediols, and silanetriols promoted by silver(I) oxide

Palladium-catalyzed cross-coupling of aryl- or alkenylsilanols, silanediols, and silanetriols with a variety of iodoarenes by the catalysis of palladium(0) and in the presence of silver(I) oxide furnished the coupling products in good to excellent yields. The reactions of silanediols or silanetriols under similar conditions proceeded much faster than those of silanols to afford the corresponding coupling products in excellent yields within shorter reaction periods (5-12 h). The measurement of the X-ray diffraction (XRD) pattern of the silver residue after the reaction revealed that silver(I) oxide was converted to silver(I) iodide.

Journal Article↗
PubMed2000

Antioxidant activity of nasunin, an anthocyanin in eggplant peels.

The free radical scavenging activities and inhibitory effect of lipid peroxidation of a delphinidin derivative in eggplant were investigated. Delphinidin-3-(p-coumaroylrutinoside)-5-glucoside (nasunin), an anthocyanin, was isolated as purple colored crystals from eggplant peels. Using electron spin resonance spectrometry and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), hydroxyl radicals (OH) or superoxide anion radicals (O(2)(-)) generated by the Fenton reaction or the hypoxanthine-xanthine oxidase system were measured as DMPO-OH or DMPO-OOH spin adducts. L-Ascorbic acid 2-[3, 4-dihydro-2,5,7,8-tetramethyl-2-(4,8, 12-trimethyltridecyl)-2H-1-benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1) and bovine erythrocyte superoxide dismutase (SOD) were used as standards for OH and O(2)(-) scavengers, respectively. Nasunin showed potent O(2)(-) scavenging (143+/-8 SOD-equivalent U/mg) and OH scavenging (0. 65+/-0.07 EPC-K1-equivalent micromol/mg) activities. Then, by changing the concentration of DMPO to vary the trapping rate of OH, the presence of a competitive reaction between nasunin and OH was studied. The 50% inhibition dose (ID(50)) obtained from the inhibition curve did not change, indicating OH scavenging of nasunin is not due to direct scavenging but inhibition of OH generating system by chelating ferrous ion. Nasunin protection against H(2)O(2)-induced lipid peroxidation in rat brain homogenate was measured at 586 nm using the indicator of malonaldehyde and 4-hydroxyalkenals. Nasunin (<50 microM) protected against lipid peroxidation of brain homogenates. The findings suggest that nasunin is a potent O(2)(-) scavenger and has protective activity against lipid peroxidation.

Anthocyanins↗
PubMed2000

Implication of vascular endothelial growth factor and p53 status for angiogenesis in noninvasive colorectal carcinoma.

BACKGROUND: It still is unclear when angiogenic potential, which is believed to be a prerequisite for tumor development, is acquired. The current study was designed 1) to clarify when the phenotypic change of angiogenicity occurs during the development of colon carcinoma and 2) to investigate the possible roles of vascular endothelial growth factor (VEGF) and p53 in angiogenesis. METHODS: Colon carcinomas were classified according to the following criteria: m carcinomas were tumors in which carcinoma cells were observed within the mucosa (excluding adenomas with severe atypia) according to the World Health Organization criteria. sm carcinomas were defined by invasion into the submucosa but not into the muscularis propria. Using 27 adenomas, 26 m carcinomas, and 20 sm carcinomas, VEGF expression was analyzed with reverse transcriptase-polymerase chain reaction and immunohistochemistry. Microvessel density, VEGF, and p53 status were evaluated by immunohistochemistry. RESULTS: Neither VEGF mRNA nor VEGF protein was detected in any of the mild-to-moderate dysplastic adenomas, whereas 16 of 26 m carcinomas (62%) and all sm carcinomas exhibited VEGF protein. The microvessel density in adenomas, m carcinomas, and sm carcinomas was 3 +/- 0.55, 6.1 +/- 1.12, and 12 +/- 1.35 (0.739 mm(2) per field), respectively. In m carcinomas, positive VEGF expression was coincident with the expression of p53, and stainability for both VEGF and p53 was similar with regard to spatial distribution in tumor tissues. In m and sm carcinomas, there was a statistically significant correlation between the intensity of VEGF expression and microvessel density. CONCLUSIONS: The results of the current study demonstrated that angiogenesis develops in association with tumor progression from adenoma to noninvasive colorectal carcinoma, at least in part due to VEGF, and suggested that VEGF in m carcinomas is induced by mutant p53, although alternative mechanisms of VEGF up-regulation may exist in sm carcinomas.

Adenoma↗
PubMed2000

Coupling Reactions of Alkynylsilanes Mediated by a Cu(I) Salt: Novel Syntheses of Conjugate Diynes and Disubstituted Ethynes.

Reaction of 1-trimethylsilylalkyne with copper(I) chloride in a polar solvent, DMF, at 60 degrees C under an aerobic conditions smoothly undergoes homo-coupling to give the corresponding symmetrical 1,3-butadiynes in 70-99% yields. In addition, (arylethynyl)trimethylsilanes are found to couple with aryl triflates and chlorides in the presence of Cu(I)/Pd(0) (10 mol %/5 or 10 mol %) cocatalyst system to give the corresponding diarylethynes in 49-99% yields. The cross-coupling reaction is applied to a one-pot synthesis of the corresponding unsymmetrical diarylethynes from (trimethylsilyl)ethyne via sequential Sonogashira-Hagihara and the present cross-coupling reactions using two different aryl triflates. The reactions of (arylethynyl)trimethylsilanes with aryl(chloro)ethynes in the presence of 10 mol % of CuCl also yield the corresponding unsymmetrical 1,3-butadiynes in 43-97% yields.

Journal Article↗
PubMed2000

The suppression of small GTPase rho signal transduction pathway inhibits angiogenesis in vitro and in vivo.

Angiogenesis consists of multistep pathways such as the degradation of the matrix, proliferation of the endothelial cells, motility of the endothelial cells, formation of the cord structure and network formation of microvessels. The small GTPase Rho participates in cell motility through actin fiber polymerization. The role of the small GTPase Rho signal transduction pathway in regulating angiogenesis, however, is still unknown. In this study, we investigated the role of the small GTPase Rho signal transduction pathway in angiogenesis in vitro and in vivo using the exoenzyme, Clostridium botulinum C3 transferase, which specifically suppresses Rho and a compound, Y-27632, which suppresses p160ROCK (Rho-associated coiled-coil containing protein kinase). In this paper, we showed that the small GTPase Rho-p160ROCK signal transduction pathway played an important role in angiogenesis both in vitro and in vivo. These results suggest that inhibition of the small GTPase Rho signal transduction pathway by the p160ROCK inhibitor could be a possible new strategy for angiogenic diseases.

Amides↗
PubMed2000

Protection by vascular endothelial growth factor against sinusoidal endothelial damage and apoptosis induced by cold preservation.

BACKGROUND: It is well known that sinusoidal endothelial cell (SEC) damage during cold preservation of liver tissue is closely involved in early graft failure. The objective of this study was to investigate the involvement of apoptosis in the SEC damage induced by cold preservation and to demonstrate the protective effect of vascular endothelial growth factor (VEGF) on SEC injury, including apoptotic changes. METHODS: Isolated SECs and liver tissue of Wistar rats were cold-preserved in University of Wisconsin (UW) solution, and the protective effect of VEGF was then investigated. Isolated SECs were cultured for 24 hr, and divided into the following 3 groups: Group A, in which the cells were cultured for an additional 27 hr, Group B, in which the cells were cold-preserved in UW solution for 3 hr, and then recultured for 24 hr, and Group C, in which 20 ng/ml of VEGF was added to both the culture medium and the UW solution of cells cultured according to the Group B protocol. Each group of SECs was morphologically examined using the phase contrast microscopic method and the transmission electron microscopic method (TEM), and quantitatively analyzed using the WST-1 assay. Rat livers were cold-preserved in UW solution and divided into the VEGF(+) group and the VEGF(-) group, depending on whether VEGF was added or not. Each group of livers were analyzed by scanning electron microscopic method (SEM) after 24 hr of preservation. The hyaluronic acid uptake rate (HUR) was also determined after 6 hr of preservation. After 24 hr of preservation and 6 hr of reperfusion, tissues were examined by TEM and by the terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling (TUNEL) assay. RESULTS: The phase contrast microscopic method and the WST-1 assay showed a protective effect of VEGF against the injury to isolated SECs during cold preservation and subsequent reculturing. Apoptosis was detected immediately by TEM after isolation of SECs, and the number of apoptotic cells increased with the incubation time. This increase was accelerated after cold preservation. The scanning electron microscopic method and the hyaluronic acid uptake rate showed a protective effect of VEGF against SEC damage in the cold-preserved livers. In the liver tissue, the TEM and the TUNEL assay detected apoptosis of SECs only after cold preservation and subsequent reperfusion. VEGF suppressed the apoptosis of SECs induced by cold preservation in both isolated cells and liver tissue. CONCLUSIONS: We demonstrated that SEC damage in the cold preservation of liver tissue was caused mainly by apoptosis, which required subsequent reperfusion. Moreover, isolated SECs showed spontaneous occurrence of apoptotic changes during culture, and these changes were accelerated by the preceding cold preservation. This is the first report to demonstrate the apoptotic changes of SECs seen here were inhibited by VEGF.

Animals↗
PubMed2000

Fatal cerebral hemorrhage associated with cyclosporin-A/FK506-related encephalopathy after allogeneic bone marrow transplantation.

We report a case of cerebral hemorrhage associated with cyclosporin A (CsA)/FK506-related encephalopathy that developed in a 16-year-old woman after allogeneic bone marrow transplantation. Hematopoietic engraftment occurred on day 15, and the patient developed systemic convulsions after CsA was replaced by FK506 for the treatment of acute graft-versus-host disease (GVHD). Based on magnetic resonance imaging, laboratory findings and cerebrospinal fluid studies, she was diagnosed as having CsA/FK506-related encephalopathy with cerebral hemorrhagic infarction. Although she recovered completely after discontinuation of FK506, she developed convulsions again 15 days after re-administration of FK506. A computed tomography scan showed cerebral hemorrhage. She died of respiratory failure. Vascular damage induced by immunosuppressive drugs and enhanced by acute GVHD seemed to be the cause of the cerebral hemorrhage. Since hypertension, which was present during both of the central nervous system events, seemed to have contributed to the development of the cerebral hemorrhage, it is proposed that CsA and FK506 should be reduced or discontinued when patients who have risk factors of hypertension become hypertensive even if they have no symptoms of neurotoxicity.

Adolescent↗
PubMed2000

Selective perfusion of segmental arteries in patients undergoing thoracoabdominal aortic surgery.

BACKGROUND: Reattachment of segmental arteries is one method used to prevent paraplegia associated with thoracoabdominal aortic repair. Nevertheless, even when important segmental arteries are reattached, ischemia causing spinal injury may occur during anastomosis. METHODS: In 27 patients undergoing thoracoabdominal aortic repair, we attempted to perfuse the segmental arteries to be reattached with catheters connected to the distal bypass circuit. To identify perioperative risk factors for spinal ischemia, we examined changes in spinal somatosensory evoked potentials. RESULTS: A median value of four segmental arteries were perfused in 20 (74%) of the 27 patients. Changes in somatosensory evoked potential indicative of spinal ischemia were observed in 13 patients (48%). The only risk factor associated with changes in evoked potentials revealed by a multivariate analysis was prolonged aortic cross-clamp time (> 120 minutes). Of the 2 patients who suffered paraplegia, one had the longest clamp time and the other showed spinal cord necrosis due to embolic shower. CONCLUSIONS: Despite selective perfusion of segmental arteries, spinal ischemia associated with aortic cross-clamping may occur when clamping is prolonged over 120 minutes. Most of the changes appear to be reversible, however.

Adult↗
PubMed2000

Exogenous aspartate neurotoxicity in the spinal cord under metabolic stress in vivo.

BACKGROUND: Considerable evidence exists that neurotoxicity of excitatory amino acids is related to the neuronal injury, including paraplegia. However, little is known about aspartate neurotoxicity in the spinal cord in vivo. We evaluated the detrimental effects of exogenous aspartate on spinal cord neurons under metabolic stress. METHODS: New Zealand white rabbits underwent an infrarenal aortic isolation. Group A animals (n = 7) received segmental aspartate 50 mmol/L) infusion for 10 minutes. Group B animals (n = 7) received saline as a negative control. Group C animals (n = 5) received segmental aspartate 100 mmol/L) infusion for 5 minutes. Group D animals (n = 7) were pretreated with segmental infusion of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine (MK-801) (6 mg/kg), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist for 1 minute, followed by segmental infusion of aspartate (50 mmol/L) for 9 minutes. Group E animals (n = 7) received vehicle only, followed by aspartate (50 mmol/L) infusion as a control of group D. Neurologic status was assessed at 12, 24, and 48 hours after operation using the Tarlov score. RESULTS: Group A animals exhibited paraplegia or paraparesis with marked neuronal necrosis. Group B and C animals recovered fully. Group D animals showed significantly better neurologic function (p = 0.0007) compared with group E animals that exhibited paraplegia or paraparesis. CONCLUSIONS: Exogenous aspartate can have detrimental effects on spinal cord neurons under metabolic stress. This model may be useful in assaying neuronal injury mediated by NMDA receptor in vivo.

Animals↗
PubMed2000

Gliclazide scavenges hydroxyl and superoxide radicals: an electron spin resonance study.

The role of reactive oxygen species in diabetes and its complications are well known. Two therapeutic agents commonly used in the treatment of diabetes are the sulfonylureas gliclazide and glibenclamide. These drugs effectively reduce blood sugar in non-insulin-dependent diabetes mellitus, by augmenting insulin release. Gliclazide is known to be a general free radical scavenger as shown by its inhibition of o-dianisidine photo-oxidation. In this study, the effects of gliclazide and glibenclamide on free radicals were examined in vitro, using electron spin resonance spectroscopy. Superoxide radical (O2*-) generated from the hypoxanthine-xanthine oxidase system or hydroxyl radical (OH*) generated via the Fenton reaction were analyzed as spin adducts of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Gliclazide scavenged O2*- and OH* in a dose-dependent manner whereas glibenclamide was without effect. These findings suggest that gliclazide is not only effective in reducing blood sugar, but may also be beneficial as a result of inhibition of lipid and protein denaturation, which is believed to lead to the development of diabetic complications.

Electron Spin Resonance Spectroscopy↗