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Biomedical subjects

S Maeda

Publications and source records attributed to S Maeda.

At least 19 recordsLinked to original sources
PubMed2006

ELMO1 increases expression of extracellular matrix proteins and inhibits cell adhesion to ECMs.

We have previously identified the engulfment and cell motility 1 (ELMO1) as a susceptibility gene for diabetic nephropathy. To elucidate the role of ELMO1 in the pathogenesis of chronic renal injury, we examined the expression of Elmo1 in the kidney of a rat model for chronic glomerulonephritis (uninephrectomy plus anti-Thy1.1 antibody [E30] injection). We found that the expression of the Elmo1 was significantly increased in the renal cortex and glomeruli of uninephrectomized rats injected with E30 compared to controls. By in situ hybridization, the expression of Elmo1 was shown to be elevated in the diseased kidney, especially in glomerular epithelial cells. In COS cells, the overexpression of ELMO1 resulted in a substantial increase in fibronectin expression, whereas the depletion of the ELMO1 by small interfering RNA (siRNA) targeting ELMO1 significantly suppressed the fibronectin expression in ELMO1 overexpressing and control cells. We also found that the expression of integrin-linked kinase (ILK) was significantly increased in ELMO1 overexpressing cells, and the ELMO1-induced increase in fibronectin was partially, but significantly, inhibited by siRNA targeting ILK. Furthermore, we identified that the cell adhesion to ECMs was considerably inhibited in cells overexpressing ELMO1. These results suggest that the ELMO1 contributes to the development and progression of chronic glomerular injury through the dysregulation of ECM metabolism and the reduction in cell adhesive properties to ECMs.

Animals↗
PubMed2006

Improvement of pulmonary function and dyspnea by tiotropium in COPD patients using a transdermal beta(2)-agonist.

BACKGROUND: A combination of bronchodilators may be effective in the treatment of chronic obstructive pulmonary disease (COPD). We examined the effect of adding a long-acting anti-cholinergic agent (tiotropium) to a transdermal-type beta(2)-agonist (tulobuterol) on dyspnea as well as pulmonary function. METHODS: In a multicentre, randomized, parallel design study, 60 COPD patients treated with the transdermal beta(2)-agonist tulobuterol were divided into a tiotropium added group (Tulo+Tio group, n=40) or transdermal beta(2)-agonist tulobuterol alone group (Tulo group, n=20), and then treated for 4 weeks after a 2 week run-in period. Pulmonary function and a dyspnea (Medical Research Council (MRC)) scale were assessed before and after the treatment. Daily peak expiratory flow (PEF) monitoring was also performed. RESULTS: After 4 weeks, the Tulo+Tio group showed a significant increase in pulmonary function compared with the Tulo group; DeltaFVC (0.31+/-0.06 L vs. 0.06+/-0.05 L, p< 0.01), DeltaFEV(1) (0.15+/-0.03 L vs. -0.02+/-0.02 L, p<0.0001), and DeltaPEF (41.0+/-5.1 L/min vs. 0.5+/-3.5 L/min, p<0.0001). The MRC dyspnea scale was also significantly improved in Tulo+Tio, but not in Tulo group. CONCLUSION: These results suggest that tiotropium caused a significant improvement in both pulmonary function and dyspnea in COPD patients already treated with the transdermal beta(2)-agonist tulobuterol.

Administration, Cutaneous↗
PubMed2006

Effects of leg resistance training on arterial function in older men.

BACKGROUND: Little information is available on the effect of strength training on vascular function, particularly in older people. OBJECTIVE: To determine the effect of resistance training on arterial stiffness and endothelial function in older adults. METHOD: Eleven healthy men (mean (SEM) age 64 (1) years) performed 12 weeks of resistance training involving knee flexion and extension (three sets a day, two days a week). RESULTS: Resistance training increased maximal muscle power by 16% (p<0.0001). Arterial stiffness as assessed by aortic pulse wave velocity did not change with resistance training. Plasma concentration of nitric oxide (NO), measured as its stable end product (nitrite/nitrate), had increased (p<0.05) after resistance training (61.2 (10.4) v 39.6 (3.2) micromol/l). There was no change in plasma concentration of endothelin-1. CONCLUSION: The results suggest that short term resistance training may increase NO production without stiffening central arteries in healthy older men.

Aged↗
PubMed2006

Gastric cancer among peptic ulcer patients: retrospective, long-term follow-up.

BACKGROUND: Patients with duodenal ulcer are not at high risk although Helicobacter pylori infection is no doubt associated with gastric cancer development. However, little is known about the risk after long-term follow-up. AIMS: We investigated the incidence for gastric cancer development in peptic ulcer patients in a long term. PATIENTS AND METHODS: Between 1965 and 2004, endoscopic follow-up of more than 1 year was conducted on 1504 peptic ulcer patients in our hospital. They consisted of 978 gastric ulcer patients, 444 duodenal ulcer patients and 82 gastric and duodenal ulcer patients. Gastric and duodenal ulcer patients were excluded from the analysis because of their limited number. RESULTS: Gastric cancers developed in 32 (3.3%) of gastric ulcer patients and 3 (0.68%) of duodenal ulcer patients. Kaplan-Meier analysis showed that the incidence of gastric cancer in duodenal ulcer patients was significantly lower than that in gastric ulcer patients (log-rank test, p=0.0059). Cox's proportional hazard model denoted the relative risk for duodenal ulcer against gastric ulcer adjusted by sex and age as 0.23 (95% CI: 0.072-0.77, p=0.016). CONCLUSION: The risk for patients with duodenal ulcer to develop gastric cancer over the long term is significantly less than in those with gastric ulcer.

Duodenal Ulcer↗
PubMed2006

A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas.

Tumor markers can facilitate understanding molecular cell biology of neoplasia and provide potential targets for the diagnosis and insight for intervention. We here identify a novel murine gene, hepcarcin (hcn), encoding a 7-kb mRNA-like transcript. The gene appears to be the murine ortholog of the human alpha gene, that is, MALAT-1. The gene and homologs lack credible open reading frames, consistent with a highly conserved large noncoding RNA (ncRNA). In all nodules of procarcinogen-induced murine hepatocellular carcinomas (HCCs) and human HCCs, expression was markedly elevated compared to the uninvolved liver. Quantitative analyses indicated a 6-7-fold increased RNA level in HCCs versus uninvolved liver, advancing this as a molecule of interest. This ncRNA was overexpressed in all five non-hepatic human carcinomas analysed, consistent with a potential marker for neoplastic cells and potential participant in the molecular cell biology of neoplasia.

Amino Acid Sequence↗
PubMed2006

Video-assisted subtotal or near-total thyroidectomy for Graves' disease.

BACKGROUND: Surgery remains the treatment of choice for patients with Graves' disease. The purpose of the present study was to assess the usefulness and efficacy of video-assisted subtotal or near-total thyroidectomy in patients with Graves' disease. METHODS: Between March 2000 and December 2004, 63 patients with Graves' disease underwent video-assisted subtotal, near-total or total thyroidectomy. Fifty-three patients (84 per cent) were considered for surgery after failure of antithyroid drug and radioiodine therapy, whereas the other ten patients were initially selected for surgical treatment based on their own preference. Treatment outcome was evaluated, including surgical complications, thyroid function, quality of life and patient satisfaction with the surgical result. RESULTS: All patients were operated on using a video-assisted technique, with some modifications depending on time and experience. There were no conversions to open surgery. Three patients (5 per cent) had temporary recurrent laryngeal nerve palsy that recovered spontaneously. Most patients were satisfied with the surgical results, particularly regarding the placement of the surgical scars. CONCLUSION: Video-assisted subtotal or near-total thyroidectomy is a safe and effective procedure for treatment of Graves' disease.

Adolescent↗
PubMed2006

CagA protein secreted by the intact type IV secretion system leads to gastric epithelial inflammation in the Mongolian gerbil model.

Helicobacter pylori causes various gastro-duodenal diseases, including gastric cancer. The CagA protein, an H. pylori virulence factor, induces morphological changes in host cells and may be associated with the development of peptic ulcer and gastric carcinoma. The present study has analysed the role of CagA protein in the pathogenesis of H. pylori infection in the Mongolian gerbil model. Mongolian gerbils were challenged with wild-type H. pylori strain TN2, which has a functional cag pathogenicity island or isogenic mutants with disrupted cagA (DeltacagA) or cagE (DeltacagE) genes. They were sacrificed at 7, 13, and 25 weeks after inoculation. Pathological changes of the gastric mucosa were determined and apoptosis was assessed by the TUNEL assay. Immunohistochemistry for PCNA, phospho-IkappaBalpha, and phospho-Erk was also performed. All of the bacterial strains colonized the gerbil stomach at similar densities; however, the DeltacagA mutant induced milder gastritis than did the wild type. The extent of apoptosis and lymphoid follicle formation in the epithelium appeared to depend on intact cagA. The DeltacagA mutant induced less phosphorylation of IkappaBalpha and Erk, and less expression of interferon-gamma and interleukin-1beta mRNA in the epithelium than did the wild type. It is concluded that CagA protein may be essential for the induction of severe gastritis in the Mongolian gerbil model.

Animals↗
PubMed2006

Contribution of systemic arterial compliance and systemic vascular resistance to effective arterial elastance changes during exercise in humans.

BACKGROUND: Effective arterial elastance (Ea), an index of arterial load, increases with elevations in left ventricular elastance to maximize the efficiency of left ventricular stroke work during exercise. Systemic arterial compliance (C) and vascular resistance (R) are the primary components contributing to Ea, and R plays a greater role in determining Ea at rest. We hypothesized that the contribution of C to Ea increases during exercise to maintain an optimal balance between arterial load and ventricular elastance, and that the increase in Ea is due primarily to a reduction in C. AIM: The aim of this study was to investigate the contributions of C and R to Ea during exercise. METHODS: Ea (0.9 x systolic blood pressure/stroke volume), C (stroke volume/pulse pressure), R (mean blood pressure/cardiac output), and cardiac cycle length (T) were measured at rest and during exercise of 40%, 60% and 80% maximal oxygen uptake (O(2max)) using Doppler echocardiography in 45 healthy men. RESULTS: Ea did not differ between rest and 40%O(2max), but it was greater at 60% and 80%O(2max). C markedly decreased during exercise in an exercise intensity-dependent manner. The changes in R/T during exercise were small, whereas it decreased at 40%O(2max) and gradually increased at 60% and 80%O(2max). CONCLUSIONS: The present results suggest that the contribution of systemic arterial compliance to effective arterial elastance increases during exercise. Therefore, we propose that the increase in arterial load during exercise is mainly driven by a reduction in systemic arterial compliance.

Adult↗
PubMed2006

[Surgical approach for lung cancer with multiple pulmonary nodules].

A computed tomography (CT) and high-resolution CT (HRCT) have provided us an increasing opportunity to find multiple small pulmonary nodules, which sometimes appear ground glass opacity (GGO). Recently, fluorodeoxyglucose-positron emission tomography (FDG-PET) had a great contribution to our assessment for these small pulmonary nodules. However, since it is yet difficult to establish a diagnosis for these nodules during preoperative workup, a surgical lung biopsy is often required for an accurate diagnosis. We have experienced 9 patients who had undergone lung resection for primary lung cancer accompanied by multiple pulmonary lesions. Since the multiple lesions were consisted of malignant and benign lesions, it is still uncertain whether excessive lung resection should be performed in such patients. In this brief article, we summarized the characteristics of the pulmonary lesions in those patients and discussed difficulty of preoperative diagnosis, viability of pulmonary resection and problems underlining a surgical treatment.

Aged↗
PubMed2005

In vitro activity of fluoroquinolones against Mycoplasma genitalium and their bacteriological efficacy for treatment of M. genitalium-positive nongonococcal urethritis in men.

We investigated the minimum inhibitory concentrations of some fluoroquinolones for Mycoplasma genitalium and their bacteriological efficacy in the treatment of M. genitalium-positive nongonococcal urethritis. In vitro, levofloxacin was less active than gatifloxacin, tosufloxacin, and sparfloxacin. In vivo, the bacteriological efficacy of gatifloxacin was superior to that of levofloxacin or tosufloxacin.

Fluoroquinolones↗
PubMed2005

Single nucleotide polymorphisms in the gene encoding Krüppel-like factor 7 are associated with type 2 diabetes.

AIMS/HYPOTHESIS: Although genetic susceptibility plays an important role in the pathogenesis of type 2 diabetes, most of the genes that influence susceptibility to type 2 diabetes have yet to be identified. Krüppel-like transcription factors are known to play important roles in development and cell differentiation, and have recently been implicated in the pathogenesis of type 2 diabetes. The present study aimed to examine the associations of single nucleotide polymorphisms (SNPs) in genes encoding members of the Krüppel-like-factor (KLF) family with type 2 diabetes in a large cohort of Japanese subjects. METHODS: We genotyped 33 SNP loci found in 12 KLF genes in subjects with type 2 diabetes and in subjects from the general population using the PCR-Invader assay. We also examined the effects of the overexpression of KLF7 on adipogenesis in 3T3-L1 cells. RESULTS: We identified a significant association between an SNP in KLF7 and type 2 diabetes (A vs C: p=0.004 after Bonferroni's correction, odds ratio=1.59, 95% CI 1.27-2.00). The expression of Klf7 decreased in response to the differentiation of 3T3-L1 adipocytes, and the overexpression of KLF7 resulted in significant inhibition of adipogenesis in 3T3-L1 cells. CONCLUSIONS/INTERPRETATION: These results indicate that the gene encoding KLF7 is a novel candidate for conferring genetic susceptibility to type 2 diabetes.

3T3 Cells↗
PubMed2005

Polymorphism of the solute carrier family 12 (sodium/chloride transporters) member 3, SLC12A3, gene at exon 23 (+78G/A: Arg913Gln) is associated with elevation of urinary albumin excretion in Japanese patients with type 2 diabetes: a 10-year longitudinal study.

AIMS/HYPOTHESIS: We have shown previously that the SLC12A3 +78G/A polymorphism in exon 23 (Arg913Gln) was a new candidate for conferring susceptibility to diabetic nephropathy. The aim of this study was to confirm the effect of this polymorphism on the elevation of urinary albumin excretion in type 2 diabetic patients. METHODS: We retrospectively studied 264 Japanese patients with type 2 diabetes over a ten-year period. The subjects were classified into two groups: (1) persistent normoalbuminuria or microalbuminuria, or improvement from microalbuminuria to normoalbuminuria (group N); and (2) progression from normoalbuminuria to microalbuminuria or overt proteinuria, or progression from microalbuminuria to overt proteinuria (group P). They were assessed for association with the +78G/A polymorphism. RESULTS: The frequency of the +78A allele was significantly higher in group N than in group P (10% vs 1%, p=0.021). By logistic regression analysis and discriminant analysis, the substituted allele was shown to be an independent factor correlating negatively to the elevation of albumin excretion (p=0.043 and 0.022, respectively). CONCLUSIONS/INTERPRETATION: The SLC12A3 +78A(+) genotype may have a protective effect against the development and/or progression of diabetic nephropathy in Japanese type 2 diabetic patients.

Albuminuria↗
PubMed2005

Alpha-synuclein-positive structures induced in leupeptin-infused rats.

Abnormal accumulation of alpha-synuclein is regarded as a key pathological step in a wide range of neurodegenerative processes, not only in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) but also in multiple-system atrophy (MSA). Nevertheless, the mechanism of alpha-synuclein accumulation remains unclear. Leupeptin, a protease inhibitor, has been known to cause various neuropathological changes in vivo resembling those of aging or neurodegenerative processes in the human brain, including the accumulation of neuronal processes and neuronal cytoskeletal abnormalities leading to neurofibrillary tangle (NFT)-like formations. In the present study, we administered leupeptin into the rat ventricle and found that alpha-synuclein-positive structures appeared widely in the neuronal tissue, mainly in neuronal processes of the fimbria and alveus. Immunoelectron microscopic study revealed that alpha-synuclein immunoreactivity was located in the swollen axons of the fimbria and alveus, especially in the dilated presynaptic terminals. In addition colocalization of alpha-synuclein with ubiquitin was rarely observed in confocal laser-scan image. This is the first report of experimentally induced in vivo accumulation of alpha-synuclein in non-transgenic rodent brain injected with a well-characterized protease inhibitor by an infusion pump. The present finding suggests that the local accumulation of alpha-synuclein might be induced by the impaired metabolism of alpha-synuclein, which are likely related to lysosomal or ubiquitin-independent proteasomal systems.

Animals↗
PubMed2005

Acute exercise causes an enhancement of tissue renin-angiotensin system in the kidney in rats.

AIMS: Initially, the renin-angiotensin system (RAS) produced through the classical endocrine pathway was well known for its regulation of blood pressure. However, it was revealed that a local autocrine and/or paracrine RAS may exist in a number of tissues (such as kidney). Exercise causes a redistribution of tissue blood flow, by which the blood flow is greatly increased in active muscles, whereas it is decreased in the splanchnic circulation (such as in the kidney). We hypothesized that exercise causes an enhancement of tissue RAS in the kidney. METHODS: We studied whether exercise affects expression of angiotensinogen and angiotensin-converting enzyme (ACE) and tissue angiotensin II level in the kidney. The rats performed treadmill running for 30-min. Immediately after this exercise, kidney was quickly removed. Control rats remained at rest during this 30-min period. RESULTS: The expression of angiotensinogen mRNA in the kidney was markedly higher in the exercise rats than in the control rats. ACE mRNA in the kidney was significantly higher in the exercise rats than in the control rats. Western blot analysis confirmed significant upregulation of ACE protein in the kidney after exercise. Tissue angiotensin II level was also increased by exercise. CONCLUSION: The present study suggests that the exercise-induced enhancement of tissue RAS in the kidney causes vasoconstriction and hence decreases blood flow in the kidney, which are helpful in increasing blood flow in active muscles, thereby contributing to the redistribution of blood flow during exercise.

Angiotensin II↗
PubMed2005

Gene expression profiling of exercise-induced cardiac hypertrophy in rats.

AIMS: Exercise training causes physiological cardiac hypertrophy, which acts to enhance cardiac function during exercise. However, the underlying molecular mechanisms are unclear. We investigated gene expression profile of exercise training-induced cardiac hypertrophy using left ventricle (LV) excised from exercise-trained and sedentary control rats (12-week old). METHOD: Rats in the training group exercised on a treadmill for 8-week. RESULTS: Left ventricular mass index and wall thickness in the exercise-trained group were significantly greater than that in the control group, indicating that the trained rats developed cardiac hypertrophy. Of the 3800 genes analysed in the microarray analyses, a total of 75 relevant genes (upregulation of 33 genes and downregulation of 42 genes) displayed alterations with exercise training. Among these genes, we focused on glycogen synthase kinase (GSK)-3beta, calcineurin-inhibitor (Cain), and endothelin (ET)-1 for their implicated roles in pathological cardiac hypertrophy, and confirmed the results of microarray analysis at mRNA and protein/peptide levels using quantitative PCR, Western blot, and EIA analyses. The gene expression of GSK-3beta decreased significantly and those of Cain and ET-1 increased significantly with exercise training. Furthermore, LV mass index was significantly correlated with GSK-3beta protein activity (r = -0.70, P < 0.01) and tissue ET-1 concentration (r = 0.52, P < 0.05). There were no changes in gene expressions in brain natriuretic peptide (BNP), angiotensin-correcting enzyme (ACE), interleukin-6, and vascular cell adhesion molecule (VCAM)-1. CONCLUSION: These findings suggest that physiological and pathological LV hypertrophy may share some of the same molecular mechanisms in inducing LV hypertrophy (e.g. GSK-3beta, Cain, and ET-1) and that other genes (e.g. BNP, ACE) may differentiate physiological from pathological LV hypertrophy.

Adaptation, Physiological↗
PubMed2005

Assessment of patients with intellectual disability using the International Classification of Functioning, Disability and Health to evaluate dental treatment tolerability.

BACKGROUND: Patients with serious intellectual disability (ID) are occasionally unable to tolerate dental treatment when intravenous sedation or general anaesthesia (IVS/GA) is involved. In order to make a decision regarding the application of IVS/GA, the International Classification of Functioning, Disability and Health (ICF) is useful. Therefore, in this study, a set of codes involved in dental problems were chosen from the ICF, and patients with ID who could tolerate dental treatments were compared with those who could not. METHODS: From preliminary interviews of six patients with ID, 16 codes were chosen, and an objective five-rank scale was then constructed for use with all chosen codes. Forty-nine ID patients who visited the Okayama University Hospital for dental treatment between January and April 2003 were evaluated. Facility workers were interviewed according to the code set chosen. The participants were then divided into two subgroups depending on their tolerability of dental treatment. The results of these groups for all 16 codes were then compared. RESULTS: Of the 49 patients interviewed, 23 were able to tolerate the dental treatment. In the 'Activities & Participation' section of the ICF, the tolerable group showed lower disability levels with regard to d110 Watching, d540 Dressing and d550 Eating. In other sections, there were no significant differences between the groups. The code set chosen in this study and the five-rank scales in each code were useful as they enabled easy interviewing. CONCLUSIONS: The ICF was raised as a possibility for considering the application of IVS/GA for dental treatment on patients with ID. For clinical use of the ICF, it is recommended that significant codes should be selected and that the five-rank scale is used so that more objective results are obtained from interviews.

Adult↗
PubMed2005

[Analysis of acute exacerbation from focal usual interstitial pneumonia following to lung cancer resection].

To evaluate the susceptibility of patient with focal interstitial pneumonia (IP) to postoperative acute exacerbation, and to determine whether measuring serum level of several markers is useful for early detection of postoperative IP or not, we analyzed a total of 753 patients with primary lung cancer underwent thoracotomy. Twelve (1.6%) had postoperative IP. Eight of the 12 died due to IP and 9 of the 12 had focal IP findings on chest computed tomography (CT). Chest CT of 477 patients were reviewed retrospectively, and 51 (10.7%) had IP findings (diffuse 2.1%, focal 8.6%). Postoperative IP occurred in 17.6% of patients with IP findings, but only in 0.7% without such findings (p<0.01). Values of serum KL-6 decreased after lung resection. There were no changes in the value of serum TNF-alpha, IL-1beta, thrombomodulin and sICAM-1 after surgery. We conclude that focal IP is a risk factor of postoperative IP, and that it is not useful to measure serum markers for early detection of postoperative IP.

Aged↗