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Biomedical subjects

K Maeda

Publications and source records attributed to K Maeda.

At least 37 records · Page 2Linked to original sources
PubMed2002

Promotion of lupus in NZB x NZWF1 mice by plasmids encoding interferon (IFN)-gamma but not by those encoding interleukin (IL)-4.

The present study extended our previous observation that interferon (IFN)-gamma may be responsible for the active disease that develops in NZB x NZWF1 mice and serves as a model for human systemic lupus erythematosus. Treatments with cytokine-encoding plasmids were delivered intraperitoneally every 4 weeks, starting at 3 months of age (i.e. before the onset of lupus). In comparison with the control plasmid and the IL-4-encoding plasmid, the IFN-gamma-encoding plasmid promoted increased blood urea nitrogen values and reduced the survival rate, and these changes were accompanied by the development of anti-nuclear antibody. There were no differences, however, between treatment with control plasmids and treatment with IL-4-encoding plasmids in terms of the development of lupus. The findings clearly indicated that IFN-gamma but not IL-4 contributed to the development of lupus in the NZB x NZWF1 mice.

Animals↗
PubMed2002

Mediastinitis after percutaneous dilatational tracheostomy.

In our experience, PDT after total arch replacement, especially after dissection of neck vessels, should be approached with caution. A long skin incision that allows discharge to drain from the wound and a sufficiently long postoperative tracheostomy period to allow tissue healing in the neck are necessary for prevention of mediastinitis.

Aged↗
PubMed2002

Rapidly progressive dementia syndrome associated with a novel four extra repeat mutation in the prion protein gene.

OBJECTIVE: To gain a better understanding of how mutations of the prion protein (PrP) gene are responsible for progressive dementia syndrome and to clarify the correlation between genotype and phenotype, which should help to explain how the prion promotes neurological symptoms. BACKGROUND: Genetic prion diseases are associated with point or insertional mutations in the PrP gene. The insertional mutations described so far consist of one to nine extra octapeptide repeats, except three repeats. Insertions of one to four extra octapeptide repeats cause Creutzfeldt-Jakob disease (CJD) in patients without a family history of neurological disorders. CJD generally presents as progressive dementia. METHODS: Routine clinical assessment and sequence analysis of the PrP gene of DNA from a 56 year old Japanese man with progressive dementia syndrome. RESULTS: Sequence analysis disclosed a novel four octapeptide repeat insertion within the PrP gene. The patient was initially affected by progressive cerebellar and brainstem signs; a few months later myoclonus and rapidly progressive dementia appeared. These symptoms were similar to those of sporadic CJD. CONCLUSION: Taken together with previous investigations of CJD patients with insertional mutations, the current observation strengthens the notion that small octapeptide insertions from one to four extra repeats within the PrP gene cause CJD, which is characterised by late onset after the sixth decade, rapid progression, death within a few months, and lack of a family history of neurological disorders, the latter suggesting incomplete penetrance. Different patients with four extra octapeptide repeats have different patterns of extra insertions, suggesting that progression of the disease depends on the number of extra repeats.

Creutzfeldt-Jakob Syndrome↗
PubMed2002

Expression of glucocorticoid receptor and 11beta hydroxysteroid dehydrogenase in a case of pulmonary epithelioid haemangioendothelioma.

This report describes a case of pulmonary epithelioid haemangioendothelioma in which the tumour cells expressed the glucocorticoid receptor and 11beta-hydroxysteroid dehydrogenase. The patient, a 15 year old girl, who had no other complaints or past illnesses, was found to have an abnormal shadow on a chest roentgenogram obtained at a school medical examination. Multiple nodular shadows in the bilateral lungs were also confirmed by computerised axial tomography scan. A diagnosis of pulmonary epithelioid haemangioendothelioma was made on the basis of lung biopsy specimens. The tumour cells were immunohistochemically positive for factor VIII related antigen, CD31, and CD34, but not surfactant apoprotein A. In addition, almost all of the tumour cells showed simultaneous expression of the glucocorticoid receptor and 11beta hydroxysteroid dehydrogenase, suggesting that steroid treatment would be effective.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2002

FR183998, a Na+/H+ exchange inhibitor, suppresses both IL-8 content and myocardial infarct size in a cardiac ischaemia-reperfusion model in rats.

The aim of this study was to determine the effect of FR183998 (5-(2,5-dichlorothiophen-3-yl)-3-[(2-dimethylaminoethyl)carbamoyl]benzoylguanidine dihydrochloride), an Na+/H+ exchange inhibitor, on myocardial interleukin-8 (IL-8) content and myocardial infarct size in a rat ischaemia and reperfusion model. Rats underwent 30 min of ischaemia followed by 1 to 24 h of reperfusion. IL-8 content rapidly increased in reperfused rat hearts. The maximum increase in IL-8 was obtained after 3 h of reperfusion. Intravenous administration of FR183998 at 1 and 3.2 mg kg(-1), 5 min before ischaemia, significantly reduced the IL-8 level after 3 h of reperfusion (122 +/- 16 and 149 +/- 23 pg mg(-1) protein, respectively), compared with that of the saline-treated group (258 +/- 27 pg mg(-1) protein). Myeloperoxidase activity after 3 h of reperfusion was also reduced by FR183998 (from 0.83+0.19 unit g(-1) weight of tissue in the saline-treated group to 0.36 +/- 0.09 and 0.33 +/- 0.06 unit g(-1) weight of tissue in FR183998-treated groups at 1.0 and 3.2 mg kg(-1), respectively). Myocardial infarction induced by 30 min of ischaemia and 24 h of reperfusion was significantly suppressed by the same doses of FR183998 (14.0 +/- 1.5,13.5 +/- 1.9% at 1.0 and 3.2 mg kg(-1)), compared with 22.2+2.7% in the saline-treated group. These results suggestthat IL-8 may contribute to the generation of myocardial infarction in an ischaemia and reperfusion model in rats.

Animals↗
PubMed2001

Production of beta-defensin-2 by human colonic epithelial cells induced by Salmonella enteritidis flagella filament structural protein.

We recently showed that FliC of Salmonella enteritidis increased human beta-defensin-2 (hBD-2) expression, and now describe the signaling responsible pathway. FliC increased the intracellular Ca(2+) concentration ([Ca(2+)](in)) in Caco-2 cells. The [Ca(2+)](in) increase induced by FliC was prevented by U73122 and heparin, but not by chelating extracellular Ca(2+) or pertussis toxin. The FliC-induced increase in hBD-2 promoter activity via nuclear factor kappaB (NF-kappaB) was also inhibited by chelation of intracellular Ca(2+) or by U73122. We conclude that FliC increased [Ca(2+)](in) via inositol 1,4,5-trisphosphate, which was followed by up-regulating hBD-2 mRNA expression via an NF-kappaB-dependent pathway.

Caco-2 Cells↗
PubMed2001

Increase in hepatocyte growth factor receptor tyrosine kinase activity in renal carcinoma cells is associated with increased motility partly through phosphoinositide 3-kinase activation.

Dysregulated cell motility is one of the major characteristics of invasion and metastatic potentials of malignant tumor cells. Here, we examined the hepatocyte growth factor (HGF)-induced cell motility of two human renal carcinoma cell lines, ACHN and VMRC-RCW. Scattering and migration was induced in ACHN in an HGF-dependent manner, whereas they were maintained in VMRC-RCW even in the absence of HGF. In VMRC-RCW, HGF receptor (HGFR) tyrosine kinase was constitutively active, and sequence analysis showed N375S, A1209G and V1290L mutations. However, transfection experiments using porcine aortic endothelial (PAE) cells demonstrated that no single mutation or combination of two or three mutations caused HGF-independent constitutive activation. Conversely, the expressed amount of receptor protein had a pivotal role in the basal kinase activity. With respect to downstream signaling molecules of HGFR in ACHN or VMRC-RCW, the Ras-MAPK pathway was downregulated, whereas phosphoinositide 3-kinase (PI3-kinase) was not further activated by HGF-treatment in VMRC-RCW cells. The PI3-kinase inhibitors, wortmannin and LY294002 strongly inhibited spontaneous migration of VMRC-RCW. One transfected PAE cell line with massive overexpression of HGFR demonstrated scattered morphology and increased PI3-kinase activity in association with increased motility, which was partially inhibited by LY294002. Taken together, our results indicate that the overexpression of HGFR causes increase in cellular motility and PI3-kinase shows the important contribution on the increased motility of renal carcinoma cells.

Animals↗
PubMed2001

Relationship between transcardiac extraction of aldosterone and left ventricular remodeling in patients with first acute myocardial infarction: extracting aldosterone through the heart promotes ventricular remodeling after acute myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate whether plasma aldosterone (ALD) is extracted or produced through the heart in patients with acute myocardial infarction (AMI) and to determine the relationship between transcardiac extraction of plasma ALD and left ventricular (LV) remodeling. BACKGROUND: Although we demonstrated that circulating ALD was extracted through the failing heart and that transcardiac extraction of ALD correlated with LV end-diastolic volume index (LVEDVI) in patients with congestive heart failure, the existence and increase of ALD synthase in the hearts of infarct rats were reported, suggesting cardiac production of ALD in patients with AMI. METHODS: We measured plasma ALD in the aortic root (Ao) and coronary sinus (CS) in 57 consecutive patients who received successful revascularization and enalapril, with first AMI at acute phase and after one month. We also measured plasma procollagen type III aminoterminal peptide (PIIINP) in the CS. RESULTS: Plasma ALD was significantly lower in the CS than it was in the Ao at the acute phase (84.7 +/- 6.3 pg/ml vs. 105.5 +/- 8.0 pg/ml, p < 0.0001). Significant positive correlations exist between the transcardiac gradient of ALD at the acute phase and the LVEDVI at one month. Moreover, the transcardiac gradient of plasma ALD at the acute phase has a significant correlation with plasma PIIINP, a biochemical marker of fibrosis, after one month. Stepwise multivariate analysis showed that transcardiac extraction of plasma ALD at the acute phase had an independent and significant positive relationship with a large LVEDVI after one month. CONCLUSIONS: These results indicate that plasma ALD is extracted through the heart in patients with AMI at the acute phase and that the extracted ALD plays an important role in modulating post-infarct LV remodeling.

Acute Disease↗
PubMed2001

Relationship between plasma level of cardiotrophin-1 and left ventricular mass index in patients with dilated cardiomyopathy.

OBJECTIVES: The study evaluated the relationship between plasma cardiotrophin-1 (CT-1) concentration and left ventricular (LV) mass in dilated cardiomyopathy (DCM) patients with congestive heart failure (CHF). BACKGROUND: Cardiotrophin-1 is a newly identified member of the interleukin-6 (IL-6) family of cytokines and one of the endogenous ligands for gp130 signaling pathways in the heart, and it has potent hypertrophic and survival effects on cardiac myocytes. However, the clinical significance of CT-1 is poorly understood. METHODS: We measured the plasma CT-1 level in 51 consecutive patients with DCM. Patients were classified into two groups: small LV mass index group and large LV mass index group, based on the median level of LV mass index. RESULTS: The plasma CT-1 level was increased in DCM patients with the severity of CHF and was significantly higher in the large LV mass group than in the small LV mass group, despite the absence of a difference in LV ejection fraction between the two groups. In addition, there was a significant positive correlation between the plasma CT-1 level and the LV mass index (r = 0.627, p < 0.0001). According to stepwise multivariate analyses among hemodynamic and neurohumoral factors, a high plasma CT-1 level showed an independent and significant positive relationship with a large LV mass index in patients with DCM. CONCLUSIONS: These results indicate that the plasma CT-1 level is increased in patients with DCM and is significantly correlated with the LV mass index, suggesting that CT-1 plays an important role in structural LV remodeling in patients with DCM.

Adolescent↗
PubMed2001

The presence of chemokine receptor (CCR5, CXCR3, CCR3)-positive cells and chemokine (MCP1, MIP-1alpha, MIP-1beta, IP-10)-positive cells in human periapical granulomas.

The infiltration of leukocytes into inflammation sites such as observed in human periapical granulomas is considered to be mediated by chemotactic factors. In this study, we examined the presence of chemokine- and chemokine receptor-positive cells in samples obtained from human subjects by means of immunohistochemical methods. Macrophage chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and IFN-inducible protein 10 (IP-10)-producing cells were present in periapical granulomas. In addition, chemokine receptor CCR3-, CCR5-, and CXCR3-positive cells were also present. In contrast, no factor expression was observed in clinically healthy periodontal ligament, serving as a negative control. Our findings suggest that these chemokines are responsible for modulating the process of disease, such as human apical periodontitis.

Adolescent↗
PubMed2001

PU.1 is involved in the regulation of B lineage-associated and developmental stage-dependent expression of the germinal center-associated DNA primase GANP.

Germinal center-associated DNA primase (GANP) associated with MCM3 of the DNA replication complex is up-regulated selectively in germinal center B cells. We studied promoter activity of the 5' region involved in the developmental stage-dependent expression in B lineage cells by luciferase reporter assay. Selective regulation of ganp expression was observed in the -737-bp promoter region in B and plasma cell lines but was significantly low in pre-B and T cell lines. The deletion constructs displayed a gap decrease after shortening the region from -134 to -108 bp. Further narrowing suggested the involvement of the PU.1 consensus sequence at -126 bp by electrophoretic mobility shift assay. The protein component PU.1 complex is not inhibited with mutated probes at the consensus site but is inhibited with the known PU.1 probe of CD72 and with anti-PU.1 antibody. Moreover, introduction of PU.1 cDNA enhanced the reporter gene activity in a dose-dependent manner in B cells, whereas the reporter construct with the mutated PU.1 site did not respond. Anti-CD40 stimulation induced the reporter activity with a 100% increase, which is not observed with the PU.1-mutated reporter construct. These results demonstrate that the germinal center-associated DNA primase expression is partly regulated by the transcription factor PU.1 expressed in B lineage cells.

Acetyltransferases↗
PubMed2001

Differential osteopontin expression in lung cancer.

Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including cancer development, progression and metastasis. Its expression is induced by a variety of stimuli such as TNF-alpha and Ras proto-oncogene. However, differential OPN expression and its regulation in each histologic type of lung cancer are not well established. In this study, we assessed expression of OPN in lung cancer tissues with immunohistochemical analysis. OPN was predominantly expressed in tumor cells of non-small cell lung cancer (NSCLC) tissues: 11 of 16 cases (68.8%) of squamous cell carcinoma (SCC), five of 24 cases (20.8%) of adenocarcinoma (AD), but only two of 18 cases (11%) of small cell lung cancer (SCLC). Expectedly, OPN was principally expressed in NSCLC cell lines (H322 cells and HL460 cells) but not in SCLC cell line (H69 cells) by Western blotting and Northern blotting. Interestingly, Ras-p21 was specifically co-expressed with OPN staining in eight of eight cases with SCC (100%), whereas it was demonstrated in three of ten cases (30%) with AD and only one of 18 cases (5%) with SCLC. Collectively, these results suggest that OPN is mainly expressed in NSCLC, especially among SCC. OPN expression may be tightly regulated by Ras oncogene, and its concomitant induction with Ras activation may play a crucial role in the development of SCC.

Adenocarcinoma↗
PubMed2001

Altered sensitivity to a novel vasoconstrictor endothelin-1 (1-31) in myometrium and umbilical artery of women with severe preeclampsia.

We have suggested that a novel endothelin-1 with 31 amino acids [ET-1 (1-31)] plays an important role in fetal circulation, owing to a strong contractile activity on the umbilical artery. To clarify the pathophysiological significance of ET-1 (1-31) in the development of severe preeclampsia, its contractile activities on human umbilical arteries and uterine smooth muscle from patients with preeclampsia were studied. The contraction by ET-1 (1-31) was stronger in uterine smooth muscle of the patients with severe preeclampsia than that of normal subjects. On the contrary, the constriction of umbilical artery of the patients with eclampsia was significantly weaker than that of normal pregnant women. The stronger contraction of myometrium by ET-1 (1-31) in patients with severe preeclampsia observed for the first time in the present study suggests that ET-1 (1-31) might be involved in the development of preeclampsia.

Case-Control Studies↗
PubMed2001

Fate of the black string instability.

Gregory and Laflamme showed that certain nonextremal black strings (and p-branes) are unstable to linearized perturbations. It is widely believed that this instability will cause the black string horizon to classically pinch off and then quantum mechanically separate, resulting in higher dimensional black holes. We argue that this cannot happen. Under very mild assumptions, classical event horizons cannot pinch off. Instead, they settle down to new static black string solutions which are not translationally invariant along the string.

Journal Article↗
PubMed2001

Identification of N(omega)-carboxymethylarginine, a new advanced glycation endproduct in serum proteins of diabetic patients: possibility of a new marker of aging and diabetes.

A new advanced glycation end product (AGE), N(omega)-carboxymethyl-arginine (CMA), was found in acid-soluble skin collagen of a newborn bovine prepared by in vitro glycation with 1 M glucose incubation at 37 degrees C for about 30 days [ 1 ]. CMA production was increased with incubation time in parallel, and after 30 days incubation the yield was 100 times higher than that of pentosidine [ 1 ]. This result suggested the importance of CMA as a major AGE in collagen. We have detected and measured the CMA level in human serum proteins by electrospray ionization/liquid chromatography/mass spectrometry (ESI/LC/MS), using CMA standard concentration curve. In this report, we first show the existence of CMA in vivo, and its serum level is significantly elevated in diabetic serum proteins, compared to age-matched control serum proteins. These results provide strong evidence that CMA is a new diagnostic marker of glycation in diabetes.

Aging↗