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Biomedical subjects

M Fujishima

Publications and source records attributed to M Fujishima.

At least 55 records · Page 3Linked to original sources
PubMed2000

Hypothermia inhibits ischemia-induced efflux of amino acids and neuronal damage in the hippocampus of aged rats.

Brain hypothermia has been reported to protect against ischemic damages in adult animals. Our goal in this study was to examine whether brain hypothermia attenuates ischemic neuronal damages in the hippocampus of aged animals. We also determined effects of hypothermia on ischemia-induced releases of amino acids in the hippocampus. Temperature in the hippocampus of aged rats (19-23 months) was maintained at 36 degrees C (normothermia), 33 degrees C (mild hypothermia) or 30 degrees C (moderately hypothermia) using a thermoregulator during 20 min of transient forebrain ischemia. Cerebral ischemia increased extracellular concentrations of glutamate and aspartate by 6- and 5-fold, respectively, in the normothermic group. Mild and moderate hypothermia, however, markedly inhibited the rise of these amino acids to less than 2-fold. Elevation of extracellular taurine, a putative inhibitory amino acid, was 16-fold in the normothermic rats. Mild hypothermia attenuated ischemia-induced increase in taurine (10-fold), and moderate hypothermia inhibited the increase. Ischemic damages, evaluated by histopathological grading of hippocampal CA1 area 7 days after ischemia, was significantly ameliorated in the mild (1.3+/-0.5, mean+/-S.E.M.) and moderate hypothermic rats (0.8+/-0.3) compared with the normothermic ones (3.4+/-0.4). These results suggest that brain hypothermia protects against ischemic neuronal damages even in the aged animals, and the protection is associated with inhibition of excessive effluxes of both excitatory and inhibitory amino acids.

Aging↗
PubMed2000

Adenovirus-mediated gene transfer to cerebral circulation.

Gene therapy may, be a promising approach for treatment of cerebrovascular disease. An adenoviral vector encoding beta-galactosidase was administered intracisternally or intraventricularly into the brain of rats. Efficient expression of the reporter gene was observed at the cerebral blood vessels and perivascular tissues. When the adenoviral vector was delivered into CSF of dogs suffering from subarachnoid hemorrhage, prominent expressions of transgene were observed. Introduction of the vector to the ischemic brain of rats provided efficient transgene expression in the peri-ischemic area. Therefore, gene transfer to the cerebral blood vessel and brain may be a promising approach for gene therapy of stroke. Atherosclerotic lesion plays an important role in stroke. We evaluated efficacy of adenovirus-mediated gene transfer to the atherosclerotic vessels from monkeys and rabbits using an ex vivo gene transfer system. Efficiency of transgene expression in the atherosclerotic endothelium was better than that of normal vessels in both animals. Thus, the endothelium of atherosclerotic vessels may be a good target for gene therapy. Next, we transfected atherosclerotic carotid arteries from rabbits with an adenoviral vector encoding endothelial nitric oxide synthase (eNOS). After overexpression of eNOS in the atherosclerotic arteries, the response to acetylcholine was augmented, showing similar relaxation with normal vessels. These results suggest that gene transfer to atherosclerotic vessels improves endothelial function, which may be a new therapeutic approach for cerebrovascular disease.

Adenoviridae↗
PubMed2000

Impact of Helicobacter pylori infection on gastric cancer incidence in a general Japanese population: the Hisayama study.

BACKGROUND: Several nested case-control studies have reported the potentially causal relationship between Helicobacter pylori infection and the development of gastric cancer. However, there has been no prospective study evaluating this issue. The purpose of this study is to examine the impact of H pylori infection on gastric cancer occurrence in a general Japanese population (Hisayama, Japan) stratified according to sex, using a prospective study design. METHODS: A total of 2602 subjects aged 40 years or older (1070 men; mean age, 57 years; 1532 women; mean age, 59 years) without a history of gastrectomy or gastric cancer were classified according to the status of the serum IgG antibodies to H pylori and observed prospectively for 9 years from 1988. RESULTS: Infection of H pylori was more common in men (71.5%) than in women (62.5%; P<.001). The age-adjusted incidence of gastric cancer for men (5.3 per 1000 person-years) was 4-fold higher than that for women (1.3; P<.001). In men, the age-adjusted incidence of gastric cancer was significantly higher in the subjects with H pylori infection than in those without it (6.2 vs 2.5; relative risk, 2.59 [95% confidence interval, 1.03-6.50]), whereas no significant difference was observed in women (1.2 vs 1.1; relative risk, 0.99 [95% confidence interval, 0.36-2.68]). These results were similar even after controlling for other risk factors in multivariate analysis. It was estimated that 40.1% of gastric cancers for men in this cohort were attributable to H pylori infection. CONCLUSION: A significant relationship exists between infection with H pylori and subsequent occurrence of gastric cancer for men but not for women in this Japanese population.

Adult↗
PubMed2000

A PML/RARA chimeric gene on chromosome 2 in a patient with acute promyelocytic leukemia (M3) associated with a new variant translocation: t(2;15;17)(q21;q22;q21).

We describe a patient with acute promyelocytic leukemia (APL) carrying a new complex variant translocation of t(2;15;17)(q21;q22;q21). The karyotypic interpretation was confirmed by fluorescence in situ hybridization (FISH) with the use of painting probes of chromosomes 2, 15, and 17 and a PML/RARA dual color DNA probe. FISH showed a PML/RARA fusion gene on the der(2) instead of the der(15). These results suggest that the critical event in the development of APL is the formation of a PML/RARA chimeric gene, regardless of its locus in the genome.

Chromosomes, Human, Pair 15↗
PubMed2000

Metabotropic glutamate receptor subtypes involved in cardiovascular regulation in the rostral ventrolateral medulla of rats.

We have previously reported that metabotropic glutamate receptors (mGluR) participate in cardiovascular regulation in the rostral ventrolateral medulla (RVLM) of rats. In the present study, we have tried to elucidate which subtype of mGluR contributes to cardiovascular responses elicited by L-glutamate in the RVLM. Adult male Wistar rats (348 +/- 11 g, n = 21) were anesthetized and artificially ventilated. Microinjections of agonists and antagonists for each mGluR subtype were done into unilateral RVLM. Each of group I, II and III mGluR agonist (1 nmol/50 nl) produced significant increases in arterial pressure (18 +/- 2, 9 +/- 2 and 34 +/- 3 mmHg, respectively) and heart rate (18 +/- 4, 13 +/- 3 and 33 +/- 12 bpm, respectively). Microinjections of group I, II and III mGluR antagonists failed to inhibit the cardiovascular responses induced by subsequently injected agonists. However, group I antagonist [(RS)-1-aminoindan-1,5-dicarboxylic acid] elicited transient increases in arterial pressure and heart rate, followed by decreases in both variables (-19 +/- 4 mmHg and -22 +/- 4 bpm). These results suggest that all of three subtypes of mGluR participate in cardiovascular responses induced by L-glutamate, and group I mGluR may play an important role in the maintenance of arterial pressure.

Animals↗
PubMed2000

Dissociation between the Ca(2+) signal and tube formation induced by vascular endothelial growth factor in bovine aortic endothelial cells.

The correlation between the intracellular Ca(2+) signal and the tube formation in collagen gels induced by vascular endothelial cell growth factor (VEGF) was investigated using cultured bovine aortic endothelial cells. The VEGF-induced sustained elevation of cytosolic Ca(2+) concentration ([Ca(2+)](i)) was similarly inhibited by 10 microM 1-¿beta-[3-(4-methoxyphenyl)propyl]-4-methoxyphenethyl¿-1H-imidazole hydrochloride (SKF 96365) and 10 microM troglitazone. However, 10 microM diltiazem had no effect. The basal tube formation obtained with 1% serum was augmented twofold by 100 ng/ml VEGF. SKF 96365 (0. 1-10 microM) inhibited the VEGF-induced and basal tube formation, while 10 microM troglitazone or 10 microM diltiazem had no effect. The proliferation of endothelial cells was markedly inhibited by SKF 96365 but only slightly by troglitazone and diltiazem. The inhibition of tube formation by three Ca(2+) entry blockers thus correlated with the inhibition of cell proliferation. The [Ca(2+)](i) elevation is thus not a prerequisite for VEGF to induce tube formation.

Animals↗
PubMed2000

Peroxisome proliferator-activated receptor gamma1 (PPARgamma1) expresses in rat mesangial cells and PPARgamma agonists modulate its differentiation.

Thiazolidinediones, synthetic ligands of peroxisome proliferator-activated receptor gamma (PPARgamma), are reported to have direct beneficial effects on diabetic nephropathy without lowering blood glucose levels in human and rat. We hypothesized these effects of thiazolidinediones might be derived from PPARgamma activation of kidney cells, and we examined the expression of PPARgamma and the effect of PPARgamma agonists, troglitazone and 15-deoxy-delta-prostaglandin J2 (15d-PGJ2), on the proliferation and differentiation in rat mesangial cells. A single band of mRNA of PPARgamma with a predicted size was detected in reverse transcription-polymerase chain reaction products (RT-PCR) using established PCR probes of PPARgamma. PPARgamma protein in rat mesangial cells was identified as PPARgamma1 by a Western blot. In a gel mobility shift assay to determine a binding activity of PPARgamma, the nuclear protein from rat mesangial cells bound to a (32)P-labeled oligonucleotide probe, including PPAR response elements. A synthetic and a natural ligand of PPARgamma, troglitazone and 15d-PGJ2, decreased thymidine incorporation in a dose dependent manner. After 7 days incubation with troglitazone and 15d-PGJ2, alpha-smooth muscle actin expression, a marker of mesangial cell de-differentiation, was decreased significantly compared to that of control. These results indicate that PPARgamma1 is expressing in rat mesangial cells, and PPARgamma1 activation with its agonists modulates the proliferation and differentiation of cultured rat mesangial cells.

Animals↗
PubMed2000

A clinicopathologic study of primary small intestine lymphoma: prognostic significance of mucosa-associated lymphoid tissue-derived lymphoma.

BACKGROUND: It remains unclear whether the presence of mucosa-associated lymphoid tissue (MALT) lymphoma has prognostic implications for patients with primary small intestine lymphoma. METHODS: The clinicopathologic features of 80 patients with primary small intestine lymphoma were examined retrospectively in relation to the presence of MALT lymphoma. Survival was compared univariately and multivariately among the groups divided by clinicopathologic findings. RESULTS: Twenty-one cases (26%) were diagnosed as low grade B-cell lymphoma (15 marginal zone B-cell lymphoma of MALT type, 2 mantle cell lymphoma, and 4 follicle center lymphoma), 46 cases (58%) were diagnosed as high grade B-cell lymphoma (19 secondary large cell lymphoma with a low grade MALT component, 17 diffuse large cell lymphoma without MALT features, 7 Burkitt lymphoma, and 3 lymphoblastic lymphoma), and 13 cases (16%) were diagnosed as T-cell lymphoma. A significantly better survival was noted for patients without colorectal and/or gastric involvement, diffuse infiltration under macroscopy, high grade histology, and perforation. Those patients with MALT type tumors, less advanced stage of disease, B-cell phenotype, benign lymphoid follicular hyperplasia, and radical tumor resectability appeared to have a better survival rate. Based on Cox multivariate analysis, early stage disease and MALT-derived tumors were determined to be independent prognostic factors (P < 0.05). CONCLUSIONS: The presence of MALT-derived lymphoma appears to have a favorable prognosis among patients with primary small intestinal lymphoma.

Adolescent↗
PubMed2000

Troglitazone enhances glycolysis and improves intracellular glucose metabolism in rat mesangial cells.

To clarify the action of the new antidiabetic agent, troglitazone, on rat mesangial cells, we assessed its effect on the uptake and intracellular metabolism of glucose. Troglitazone increased the uptake of 2-deoxyglucose (2DOG) in a dose-dependent manner with an upregulation of glucose transporter 1 (GLUT1) mRNA, whereas it had no effect on the uptake of alpha-methyl glucoside (AMG). This troglitazone-induced glucose uptake was not suppressed by phlorizin. In 5 mmol/L glucose, 2 microg/mL (4.5 micromol/L) troglitazone increased glucose consumption 2.9-fold, similar to that in 20 mmol/L glucose. Troglitazone increased the production of pyruvate and lactate as a consequence of the increase in glycolysis, but did not increase the cellular ATP content. Troglitazone improved the high-glucose-induced accumulation of intracellular sorbitol and fructose and elevation of the cellular redox potential. These data suggest that troglitazone enhances glucose uptake through GLUT1 with an acceleration of glycolysis, and improves the abnormal intracellular glucose metabolism under high-glucose conditions in rat mesangial cells.

Adenosine Triphosphate↗
PubMed2000

Normal pressure hydrocephalus in diabetic patients with recurrent episodes of hypoglycemic coma.

The pathophysiology of brain damage induced by severe hypoglycemia is still unknown. We experienced a case with type 1 diabetes and recurrent severe hypoglycemic coma who showed a central brain atrophy and an abnormal cerebrospinal fluid flow, suggesting normal pressure hydrocephalus. Following this case, the CSF flow was studied using 111In-DTPA cisternography in six consecutive diabetic patients admitted for repeated episodes of hypoglycemic coma. All the patients showed the central brain atrophy on computed tomography and four of them (67%) had the ventricular reflux, with delayed clearance of 111In-DTPA. Two patients with abnormal CSF flow showed cognitive dysfunction by WAIS or WAIS-R. In contrast, none of five randomly selected diabetic patients, without hypoglycemic coma showed abnormal CSF flow. Our results suggest the presence of normal pressure hydrocephalus in diabetic patients with recurrent hypoglycemic coma. It may associate with the cognitive dysfunction.

Aged↗
PubMed2000

Effects of adrenomedullin and PAMP on membrane potential and neurotransmission.

The effects of adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) on membrane potential and sympathetic neurotransmission were studied in rat mesenteric arteries by using microelectrodes. AM (10(-7) M) but not PAMP (10(-6) M) produced membrane hyperpolarization, which was abolished by high K solution or by glibenclamide, an ATP-sensitive K(+) (KATP) channel blocker. Neither AM nor PAMP affected excitatory junction potentials, a measure of sympathetic, purinergic neurotransmission. These findings suggest that AM hyperpolarizes the membrane via activation of KATP channels, which may contribute to the vasodilatory action of AM, whereas the mechanisms of the vasodepressor action of PAMP remain unclear.

Adrenomedullin↗
PubMed2000

Calcium antagonist isradipine reduces metabolic alterations in acute cerebral ischemia in spontaneously hypertensive rats.

The present study was designed to examine the effect of a calcium antagonist isradipine (PN200-110: PN) on local cerebral blood flow and brain tissue metabolism after 1-hour supratentorial ischemia induced by bilateral carotid artery ligation (BCL) in spontaneously hypertensive rats (SHR). PN, dissolved in ethanol plus polyethylene glycol 400, diluted with saline to make the final concentration of 0.25mg/ml and 2.5mg/ml, was administered subcutaneously either 30 min prior to BCL or just after the induction of incomplete cerebral ischemia (n = 7 in each group). Vehicle injection was served as a control group (n = 7). Cerebral blood flow in the parietal cortex (CBF) and the cerebellar cortex (CeBF) was measured by hydrogen clearance technique, and the supra- and infratentorial metabolites of the brain frozen in situ were determined by the enzymatic method. Blood pressure was lowered, but CBF was increased by PN administration in pre-BCL treatment study. After 1 hour of BCL, CBF decreased to around 10% or less of the resting value, being insignificant among the groups. Brain adenosine triphosphate was better preserved in PN-administered groups. The increase in lactate level tended to reduce dose dependently by PN treatment. PN also reduced the metabolic alterations in brain tissue with significance, even when administered just after the induction of forebrain ischemia. It is considered that pre- as well as post-BCL administration of PN is beneficial to attenuate the metabolic alterations in incomplete forebrain ischemia in SHR.

Acute Disease↗
PubMed2000

Effect of selective brain hypothermia on regional cerebral blood flow and tissue metabolism using brain thermo-regulator in spontaneously hypertensive rats.

To investigate the effect of selective hypothermia of the brain (brain cooling) on regional cerebral blood flow and tissue metabolism, we have developed a brain thermo-regulator. Brain temperature was modulated by a water-cooled metallic plate placed on the surface of the rats' scalp to get the appropriate brain temperature precisely with ease. Regional cerebral blood flow and brain temperature were measured simultaneously using a Teflon-coated platinum electrode and thermocouple probe inserted stereotaxically into the parietal cortex and thalamus in spontaneously hypertensive rats. Experimental forebrain ischemia was induced by the occlusion of bilateral common carotid artery under normo- and hypothermic brain condition, and the supratentorial brain tissue metabolites were measured enzymatically after 60 min of forebrain ischemia. When cortical temperature was set to hypothermia, cortical blood flow was significantly lowered by 40% at 30 degree C and 20% at 33 degree C as compared with that at 36 degree C (p < 0.0001 and p < 0.05, respectively). Thalamic blood flow was also significantly reduced by 20% when cortical temperature was set to 30 degree C as compared with 36 degree C (p < 0.05). There were no significant differences in arterial blood pressure and gas parameters throughout these experiments. In the rats with selective brain hypothermia (30 degree C) immediately after the induction of cerebral ischemia, the level of brain ATP concentration after 60 min of ischemia was significantly higher than that in normothermia rats (36 degree C) (p < 0.05). Our findings indicate that: 1) the metallic plate brain thermo-regulator is useful in small animal experiments; 2) regional brain temperature regulates regional cerebral blood flow; and 3) selective brain hypothermia, even started after the forebrain ischemia, ameliorates the derangement of brain metabolism, suggesting its effectiveness as a cytoprotective strategy.

Animals↗
PubMed2000

Discordance of p53 mutations of synchronous colorectal carcinomas.

It is unclear whether synchronous multiple tumors arise from multicentric or monoclonal origins. To verify the multicentric origin of synchronous colorectal carcinomas at a genetic level, immunohistochemical and molecular techniques were used to determine the p53 alterations in individual lesions of synchronous colorectal carcinomas. This study was based on a total of 32 colorectal tumors from 16 patients. Twenty-one of the 32 (66%) advanced tumors examined had positive staining for p53. Single-strand conformation polymorphism and polymerase chain reaction direct sequencing were carried out for exons 5 to 8 of p53. All cases had p53 mutations in one or more tumors of synchronous lesions. In nine patients in this series, individual lesions were found to carry a different mutated codon of the p53 gene. In the other seven patients, a p53 mutation was found in one tumor but not in another. These results indicate discordance of the mutation pattern of p53 in individual lesions of multiple colorectal carcinomas and support the idea that most synchronous colorectal carcinomas are genetically distinguishable and are multicentric in origin. We also confirmed the high frequency of p53 mutations in left-sided (71%) and rectal (91%) carcinomas, rather than right-sided (43%; P = .04) carcinomas, suggesting that the molecular mechanism of synchronous colorectal carcinomas might differ between right- and left-sided tumors in the same patient.

Adenocarcinoma↗
PubMed2000

Endoscopic ultrasound features of protein-losing gastropathy with hypertrophic gastric folds.

BACKGROUND AND STUDY AIMS: We aim to clarify the endoscopic ultrasound (EUS) features of protein-losing gastropathy with hypertrophic gastric folds (PLGH), including Ménétrier's disease. PATIENTS AND METHODS: We analyzed the EUS and histologic findings in five patients who underwent both endoscopic ultrasonography and endoscopic resection. RESULTS: Histologically, we diagnosed one patient as having acute gastritis, three patients as having Ménétrier's disease, and the remaining patient as having hypertrophic lymphocytic gastritis (HLG). Helicobacter pylori was recognized in all but one patient. At EUS every patient was found to have giant gastric folds (13 to 20 mm in diameter), resulting from echogenic thickening of the mucosal layer with or without cystic components. Two patients who underwent eradication therapy of H. pylori showed both clinical and morphologic resolution. CONCLUSIONS: Echogenic thickening of the mucosal layer may be a characteristic EUS feature of protein-losing gastropathy with hypertrophic gastric folds, and H. pylori may be one of the causative agents.

Adolescent↗
PubMed2000

Cystic submucosal tumors in the gastrointestinal tract: endosonographic findings and endoscopic removal.

BACKGROUND AND STUDY AIMS: The aim of the present study was to describe the endosonographic findings in gastrointestinal cystic submucosal tumors. PATIENTS AND METHODS: The endosonographic and clinicopathological findings in 51 patients with a confirmed diagnosis of cystic submucosal tumors were reviewed. RESULTS: Endosonographically, cystic submucosal tumors were classified into simple cystic, multicystic, and solid cystic tumor types. The simple cystic tumor type was frequently identified in cysts, and rarely in Brunner's gland hamartomas or in heterotopic gastric mucosa. The multicystic tumor type was common in lymphangiomas, followed by gastric cystic malformations, hemangiomas, and Brunner's gland hamartomas. The solid cystic tumor type included duplication cysts, heterotopic gastric mucosa, heterotopic pancreas, myogenic tumors with advanced cystic degeneration, and gastric tuberculomas. Based on the endosonographic findings, 14 lesions were safely treated with endoscopic removal, using in particular the unroofing technique (cutting off the upper part of the tumors) in nine lesions. CONCLUSIONS: Endosonography is a useful diagnostic modality for investigating cystic submucosal tumors.

Cysts↗