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Biomedical subjects

M Fujita

Publications and source records attributed to M Fujita.

At least 109 records · Page 6Linked to original sources
PubMed2001

Regulation of aquaporin-4 expression in astrocytes.

Aquaporin-4 (AQP4), a mercury-insensitive water channel protein, is abundant in the central nervous system and is localized in astrocytes and ependymal cells. AQP4 is speculated to maintain the homeostasis of intracellular and extracellular water in the brain, but little is known about the mechanism of induction of its expression. To investigate the expressional regulation of AQP4, we analyzed changes in its expression during chemically induced differentiation of embryonal carcinoma cells (P19) to neuronal and astrocytic cells, and during the cell cycle of glioma cells. After exposure to retinoic acid for 4 days AQP4 mRNA expression started at the initiation of astrocytic differentiation of P19 cells at 6 days, and increased markedly by 21 days. AQP4 expression was parallel to that of GFAP, a marker intermediate filament of astrocytes. In glioma cell lines, AQP4 mRNA was not detected in the growing phase, but was induced when the cell cycle was arrested at G0/G1 by transient expression of p21. Although quiescent astrocytes in the G0/G1-phase cultured under the serum-free condition exhibited a high expression of AQP4, serum supplement moved them to the S-phase and markedly decreased the AQP expression. These results suggest that AQP4 expression may be induced not only at the initiation of astrocytic differentiation of neural stem cells, but also at the G0/G1-phase during the cell cycle of astrocytes.

Animals↗
PubMed2001

Reproducibility of in vivo brain measures of 5-HT2A receptors with PET and.

The test/retest reproducibility of brain measures of 5-HT2A receptors with positron emission tomography (PET) and [18F]deuteroaltanserin was examined in a group of eight healthy human subjects. PET measures of 5-HT2A receptors were obtained under an equilibrium paradigm, with a 40-min PET acquisition starting approximately at 300 min (308+/-11 min) after bolus plus constant infusion of the radiotracer. Three brain outcome measures were obtained at equilibrium, V(3) (ratio of specific brain uptake to free parent plasma concentration of radiotracer), V(3)' (ratio of specific brain uptake to total parent plasma concentration) and RT (ratio of specific to non-displaceable brain uptakes). V(3)' and RT had high test/retest reproducibility, as measured by mean intra-subject% change for cortical brain areas of 14.1 and 11.0%, respectively. They also had high reliability, as measured by mean intra-class correlation coefficients (ICC) for cortical brain areas of 0.86 and 0.88, respectively. V(3) had low test/retest reproducibility, due to high variability in the measures of free parent tracer in plasma. This study supports the feasibility of equilibrium imaging of 5-HT2A receptors with PET and [18F]deuteroaltanserin. The equilibrium imaging method with [18F]deuteroaltanserin allows a single acquisition and blood measurement to provide an image whose pixel values equal a receptor volume of distribution. Since the single image pixel values are proportional to receptor densities, the images can be used in pixel-by-pixel statistical methods, such as SPM, to assess the distribution and density of 5-HT2A receptors in neuropsychiatric disorders.

Adult↗
PubMed2001

Clonal analysis of hepatocellular carcinoma and dysplastic nodule by methylation pattern of X-chromosome-linked human androgen receptor gene.

To investigate the monoclonality of hepatocellular carcinoma (HCC) and dysplastic nodule (DN) and the origin of multiple lesions, patterns of inactivation of X-linked human androgen receptor gene were studied. Fourteen of 15 patients (93%) were heterozygous in the size of the target, and were informative for clonal analysis. Monoclonal composition was demonstrated in all 17 HCCs and two DNs, whereas all non-cancerous hepatic tissues were polyclonal. Of four patients with more than two lesions of HCC or DN, two patients had two lesions with different patterns of X-chromosome inactivation, indicating that the two lesions were multicentric in origin.

Adult↗
PubMed2001

Functional annotation of a full-length mouse cDNA collection.

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

Animals↗
PubMed2001

Peripheral neuroglial death induced by cisplatin administration in newborn rats.

To determine the target of cytotoxicity of cisplatin (CDDP), we injected newborn rats with 2 mg/kg CDDP and examined the trigeminal ganglion for possible cell death. A nick translation method for DNA fragmentation revealed CDDP-induced glial cell death. DNA fragmentation was detected in both Schwann cells and satellite cells. Satellite cell death was observed as early as 0.5 day after injection, most frequent at 1-3 days and subsided thereafter. The incidence of neuronal death was very low and comparable to that observed in vehicle control rats. CDDP has selective toxicity to peripheral glial cells, though the damage did not culminate in cell death in adults. The glial toxicity may contribute to clinical symptoms of CDDP neuropathy.

Animals↗
PubMed2001

Regulation of rat hippocampal neural cadherin in the kainic acid induced seizures.

Regulation of neural (N-) cadherin expression in the hippocampus was examined by in situ hybridization and immunohistochemistry methods in the rat model of kainic acid (KA) induced seizures. After 12 and 24 h of KA administration, mRNA expression level of N-cadherin decreased in the hippocampal CA1 and CA3 area in parallel with decrease of the number of neural cells. In contrast, after 48 h and 7 days, mRNA expression level recovered partially, although the number of neural cells remained small. In addition, immunohistochemical staining indicated that N-cadherin protein expression of survived neurons increased significantly after 48 h of KA administration. These results indicated that N-cadherin might be involved in neuronal reconstruction at the hippocampus.

Animals↗
PubMed2001

Removal of soluble selenium by a selenate-reducing bacterium Bacillus sp. SF-1.

In order to develop a biological process for removal of selenium from industrial wastewater, Bacillus sp. strain SF-1 was isolated from selenium-contaminated sediment. The bacterium reduces selenate to selenite and subsequently to nontoxic insoluble elemental selenium using lactate as an electron donor and selenate as an electron acceptor in an anaerobic condition. Elemental selenium transformed from soluble selenium was deposited both inside and outside of the cells. Since the selenate reduction rate of the strain SF-1 was higher than the selenite reduction rate, selenite was transiently accumulated. In an experiment of the repeated soluble selenium reduction by strain SF-1, 0.5 mM of selenate was sequentially treatable with a cycle of one day. Thus, our sequential system for removal of soluble selenium is very useful.

Bacillus↗
PubMed2001

Pericardial fluid from patients with ischemic heart disease induces myocardial cell apoptotis via an oxidant stress-sensitive p38 mitogen-activated protein kinase pathway.

Factors produced by the heart are accumulated at high concentrations in pericardial fluid. We recently reported that pericardial fluid from patients with ischemic heart disease induces apoptosis in an F2 cell line. To characterize factors in pericardial fluid from patients with ischemic heart disease, we investigated signaling pathways by which this pericardial fluid induces apoptosis in cardiac myocytes. Pericardial fluid from patients with ischemic heart disease markedly increased the percentage of TUNEL-positive myocytes compared with fetal bovine serum. Apoptosis was also confirmed by ladder formation and morphologic features. Apoptosis mediated by this pericardial fluid occurs as readily in cardiac myocytes prepared from neonatal mice nullizygous for p53 as in wild-type littermates. This indicates that p53 is not required for this process. We have found that pericardial fluid from ischemic heart disease elicits a robust increase in phosphorylation of p38 mitogen-activated protein kinase. Specific inhibition of the p38 mitogen-activated protein kinase pathway with SB 203580 almost completely blocked apoptosis mediated by pericardial fluid from ischemic heart disease. Activation of p38 mitogen-activated protein kinase is caused by cellular stress, including oxidants. We have also found that anti-oxidant catalase inhibited pericardial fluid-induced activation of p38 mitogen-activated protein kinase and apoptosis. These findings demonstrate that myocardial cell apoptosis induced by pericardial fluid from patients with ischemic heart disease is mediated by an oxidant stress-sensitive p38 mitogen-activated protein kinase pathway. A possible application of SB 203580 to preserve cardiac function in patients with ischemic heart disease should be discussed.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Design of PCR primers and a gene probe for extensive detection of poly(3-hydroxybutyrate) (PHB)-degrading bacteria possessing fibronectin type III linker type-PHB depolymerases.

For rapid and sensitive detection of poly(3-hydroxybutyrate) (PHB)-degrading bacteria, a PCR primer set (PHB primers) and a gene probe (PHB probe) were designed, based on the homologous regions of six fibronectin type III linker domain-encoding sequences laid on a variety of PHB depolymerase genes listed in the GenBank. PCR using PHB primers amplified DNA fragments with the expected sizes from all the tested bacterial strains used for primer design; and all of the amplified fragments gave positive signals by Southern hybridization with the PHB probe. No amplified fragments were observed from negative controls. To evaluate the availability of the PHB primers and PHB probe, they were applied to 57 wild-type, PHB-degrading bacteria newly isolated from a variety of environments. The PHB primers amplified DNA fragments with expected sizes from 50 of the 57 wild-type strains, while the PHB probe showed positive signals against the amplified fragments from 47 strains. These results suggest that the primer and probe system established in this study can detect a considerable proportion of the potential PHB-degrading bacteria and can be applied to evaluate PHB-degradation potential in a natural environment, in combination with direct DNA extraction methods.

Bacteria↗
PubMed2001

Myocardial metabolism of 123I-BMIPP during low-flow ischaemia in an experimental model: comparison with myocardial blood flow and 18F-FDG.

Risk stratification of coronary artery disease may provide a basis for selection of treatment to prevent myocardial events and to assist functional recovery. Iodine-123 (rho-iodophenyl)-3-R,S-methylpentadecanoic acid (123I-BMIPP) is a radioiodinated fatty acid analogue for single-photon emission tomographic (SPET) imaging, and several reports have demonstrated that the abnormal uptake of 123I-BMIPP is associated with wall motion abnormality and severe coronary artery stenosis. Clarification of the contribution of fatty acids to myocardial metabolism would be highly valuable in recognising this critical condition. In this study, we investigated the myocardial uptake of 123I-BMIPP under low-flow ischaemia, and compared it with the uptake of fluorine-18 fluorodeoxyglucose (18F-FDG). Using open chest dogs, the flow of the left anterior descending coronary artery was controlled using a pneumatic occluder in order to maintain a 30%-40% reduction of Doppler flow. 123I-BMIPP and 18F-FDG were injected into the left atrium after 90 min of ischaemia (protocols 1 and 3). Canine hearts were excised after 120 min of ischaemia for the measurement of radioactivity. In protocol 2, 123I-BMIPP alone was injected and hearts were excised 8 min after the injection. A time-course biopsy study was also performed at the same time (protocol 3). Wall thickening was evaluated using a wall tracker module. The uptake of 18F-FDG increased significantly in the ischaemic region (232%+/-135% vs non-ischaemic, P<0.05 in protocol 1) even on mild reduction of myocardial blood flow (MBF). The increased uptake of 18F-FDG did not correlate well with the severity of MBF. On the other hand, 123I-BMIPP uptake decreased gradually (78.9%+/-23.6%, P<0.05 in protocol 1, and 85.9%+/-24.3% in protocol 2) in the ischaemic region, specifically in the endocardium (64.0%+/-28.9%, P<0.05 in protocol 1, and 75.1%+/-28.8%, P<0.05 in protocol 2), and correlated strongly with MBF (r=0.93 in protocol 1 and r=0.97 in protocol 2) as a logarithmic function. This indicated that the abnormal uptake of 123I-BMIPP was associated not only with wall motion abnormality but also with the severity of MBF. In the biopsy study (protocol 3), the radioactivity of either 123I-BMIPP or 18F-FDG correlated well with the MBF at the time of tracer injection and was similar to post-mortem analysis. It is concluded that 18F-FDG is a valid tool for identifying ischaemic myocardium even in its earliest stages. On the other hand, 123I-BMIPP might be used to detect moderately to severely ischaemic myocardium such as hibernation, suggesting the potential value of 123I-BMIPP in the risk stratification of patients with severe coronary artery disease who require revascularisation without delay.

Animals↗
PubMed2001

Genetic analysis of a local recurrent tumor after colonic polypectomy.

After polypectomy, the cut end of the polyp is usually examined by light microscopy to assess the risk of recurrent cancer. Here, we report a recurrent tumor that appeared in the colon 6 years after polypectomy, although cancer cells were not observed in hematoxylin and eosin-stained sections of the cut end of the primary polyp. Retrospectively, the primary polyp and the recurrent tumor were analyzed for mutations of the p53 gene. We detected p53 mutations in the primary polyp, even in the cut end of the polyp. The same set of two p53 mutations was detected in the recurrent tumor. These observations indicate a common origin of the primary tumor and the recurrent tumor. We conclude that it is important to analyze p53 mutations in colonic polyps, especially when the cut end of the polyp is difficult to evaluate histologically, in order to predict recurrence.

Adenocarcinoma↗
PubMed2001

Jejunal carcinoid tumor mimicking leiomyosarcoma: preoperative diagnosis by endoscopic biopsy.

Primary carcinoid tumor of the jejunum is rare, and is an unusual cause of massive gastrointestinal bleeding. A case of primary jejunal carcinoid tumor in a 39-year-old woman who presented with massive hematochezia is described. Both upper and lower gastrointestinal endoscopies showed no abnormalities. An abdominal computed tomographic scan, small-bowel barium contrast studies, and small-bowel endoscopy showed a subserosal mass, of 5 x 4 cm, with a cavity suggesting central necrosis, and a deep mucosal ulceration, located in the proximal jejunum. Although these clinical presentations were strongly suggestive of a leiomyosarcoma, histologic examination of biopsy samples obtained by enteroscopy confirmed the diagnosis of jejunal carcinoid tumor. The patient underwent radical jejunal resection and recovered uneventfully. In spite of the large size of the tumor, there was one solitary lymph node metastasis, but no evidence of liver metastases. This kind of jejunal carcinoid tumor, presenting with massive gastrointestinal bleeding and a subserosal bulky growth mimicking a leiomyosarcoma, has not been reported previously. Moreover, this is a rare case of a jejunal carcinoid which was diagnosed preoperatively by small bowel-endoscopic biopsy.

Adult↗
PubMed2001

Relationship between serum lipoprotein(a) level and thrombin generation to the circadian variation in onset of acute myocardial infarction.

A high incidence of acute myocardial infarction (AMI) has been reported between 06:00 and 12:00 h. This may be related to an abnormality in hemostasis. An association has been founded between the serum lipid level and coronary atherosclerosis, as well as the serum lipid level and a hemostatic abnormality. We investigated the association between the time of AMI, the level of serum lipid, and of hemostatic factor. Of the 42 subjects evaluated retrospectively, 20 had experienced an AMI between 06:00 and 12:00 h (group A), while 22 had developed an AMI during some other period (group B). All patients received emergency coronary angiography, which identified a total occlusion of coronary artery in the proximal portion of the left antecedent branch. The serum level of several lipid factors and of hemostatic factors were compared between the two groups. Characteristics of patients were similar in both groups. The serum levels of lipoprotein(a) (Lp(a)) and of thrombin-antithrombin III complex (TAT) were higher in group A than in group B, respectively. The level of other factors were similar in both groups. Group A showed a significant correlation between the level of Lp(a) and TAT, with a tendency (not statistically significant), toward a positive correlation between Lp(a) and PAI-1, and a negative correlation between Lp(a) and t-PA. In a subgroup that experienced AMI in the early morning, a higher level of Lp(a) was associated with an elevation of TAT, a marker for thrombin generation, and with the level of fibrinolytic factor. This suggests that Lp(a) is closely related to the increase in the early morning incidence of AMI via a change in the prothrombotic state.

Antithrombin III↗
PubMed2001

Spontaneous middle cerebral artery occlusion leading to moyamoya phenomenon and aneurysm formation on collateral arteries.

BACKGROUND: Spontaneous middle cerebral artery occlusion associated with moyamoya phenomenon is distinct from moyamoya disease. The hemodynamic stress on the collateral channel occasionally leads to aneurysm formation, which may manifest as hemorrhage. The etiology of this disease has not been fully understood. CASE DESCRIPTION: A 63-year-old woman presented with left putaminal hemorrhage. The cerebral angiogram revealed a significant stenosis in the proximal segment of the left middle cerebral artery. Collateral arteries originating from the horizontal segment of the ipsilateral anterior cerebral artery and the ambient segment of the ipsilateral posterior cerebral artery supplied the middle cerebral artery distal to the stenosis. Both of the collateral channels had associated aneurysms that were surgically obliterated. The aneurysm on the collateral artery from the posterior cerebral artery was responsible for the putaminal hemorrhage. CONCLUSIONS: Spontaneous middle cerebral artery occlusion may lead to focal moyamoya phenomenon and aneurysmal intracerebral, intraventricular, or subarachnoid hemorrhage. The presence of a co-existing anomalous collateral artery in the present case suggests a congenital etiology of the focal middle cerebral artery occlusion.

Arterial Occlusive Diseases↗
PubMed2001

Pericardial fluid as a new material for clinical heart research.

This article will review the results of recent clinical studies relating to the pericardial fluid in patients with various heart diseases. In ischemic patients, several angiogenic growth factors are accumulated in a high concentration in pericardial fluid. These may contribute to the angiogenesis and arteriogenesis, which are self-protecting mechanisms of myocardial ischemia. In congestive heart failure, natriuretic peptides are released into the pericardial fluid in a higher concentration compared with plasma levels. This suggests that these peptides may act as autocrine and/or paracrine factors. Pericardial fluid from ischemic patients induces cell proliferation and apoptosis depending on the cell type. Intrapericardial drug administration may provide a reasonable therapeutic strategy for heart diseases. In conclusion, the analysis of pericardial fluid appears to be a logical approach for elucidation of the pathophysiology of the heart.

Angiogenesis Inducing Agents↗
PubMed2001

Evidence for involvement of dysfunctional teeth in the senile process in the hippocampus of SAMP8 mice.

In order to evaluate the involvement of dysfunctional teeth in age-related deficits in hippocampal function, we examined the effect of removal of molar teeth (molarless condition) on neuronal degeneration and glial fibrous acidic protein (GFAP) expression in the hippocampus and on learning ability in a water maze test in young, middle-aged, and aged accelerated senescence-prone mice (SAMP8). The molarless condition enhanced an age-dependent decrease in both learning ability and the number of neurons in the hippocampal CA1 subfield and the age-dependent increase in the number and hypertrophy of GFAP-labeled astrocytes in the same subfield. These observations suggest that the molarless condition may be involved in the senile process in the hippocampus in SAMP8 mice.

Aging, Premature↗