Biomedical subjects

K Sugimura

Publications and source records attributed to K Sugimura.

At least 19 recordsLinked to original sources

PubMed2006

Expression and function of human steroid receptor RNA activator in prostate cancer cells: role of endogenous hSRA protein in androgen receptor-mediated transcription.

Steroid receptor RNA activator (SRA) was first isolated as a steroid receptor co-activator that functioned as an RNA transcript. Later, we demonstrated that SRA needs to be translated in order to co-activate androgen receptor (AR). Here, we showed that three isoforms of human SRA enhanced AR activities. Small interfering RNA against SRA suppressed AR activities in PC-3 cells transfected with pSG5AR and in LNCaP cells that have an endogenous mutated-AR. Western blot showed that SRA protein was expressed at a higher level in PC-3 than in LNCaP cells, suggesting that SRA may be related to hormone-independent growth of prostate cancer.

Base Sequence↗

PubMed2006

Treatment with edaravone improves the survival rate in renal warm ischemia-reperfusion injury using rat model.

Renal ischemia-reperfusion (I/R) injury during renal transplantation is a significant cause of renal dysfunction. The pathological role of free radicals in this process is a major concern. We investigated the effect of a free radical scavenger, edaravone (MCI-186), in renal I/R injury. Male Lewis rats (270 to 320 g) were used for the model. The right kidney was harvested and left renal artery and vein were clamped as laparotomy. The kidney was reperfused after 90 minutes of ischemia. Edaravone (10 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent the neutrophil activation. In the nontreatment I/R group, no rat survived beyond 4 days. However, in the edaravone I/R treatment group, one among five rats survived more than 7 days. These results suggested that treatment with edaravone ameliorated renal I/R injury, and that the agent has the potential to ameliorate preservation injury in renal transplantation.

Animals↗

PubMed2006

A case of primary extragonadal seminoma arising in the perineum.

We report the first case of primary extragonadal seminoma arising in the perineum. A 34-year-old-man presented with a 2-cm painless mass in the perineum. He underwent surgical resection, and histology showed poorly differentiated adenocarcinoma. Three months later, local recurrence occurred. Whole evaluation including ultrasound and MRI of the testes were normal, so he underwent surgical wide excision, and pathology showed the tumor was pure seminoma. He received two courses of bleomycin, etoposide and cisplatin (BEP) therapy, and there has been no evidence of recurrence for 1 month.

Adult↗

PubMed2005

MR tractography for the evaluation of functional recovery from lenticulostriate infarcts.

OBJECTIVE: To evaluate the anatomic and clinical relationship between the lenticulostriate artery (LSA) territory and the corticospinal tract (CST) in patients with acute infarcts in this territory using MR tractography. METHODS: Thirteen consecutive patients who presented with acute infarcts in the LSA territory and who also had undergone an MRI study within 3 days after symptom onset were studied. Visualization of the CST was achieved by postprocessing the acquired diffusion tensor imaging data. To classify lesion location, the LSA territory was divided into four subsegments, the boundaries of which were drawn by axial and coronal planes crossing through the foramen of Monro. Infarct volume and extent of CST involvement were measured and compared with neurologic findings. RESULTS: All of the infarcts were located in the posterior segment. All of the depicted CSTs crossed the LSA territory only at the posterosuperior quadrant. The extent of CST involvement within the infarcts was correlated with the severity of the patient's motor deficit (p < 0.01) and with the clinical outcome (p < 0.05). CONCLUSIONS: The corticospinal tracts (CSTs) crossed the lenticulostriate artery territory exclusively at the posterosuperior quadrant, and the degree of CST involvement within the infarcts was directly related to stroke severity and functional recovery.

Adult↗

PubMed2004

Molecular characterization of a 10-kDa buckwheat molecule reactive to allergic patients' IgE.

BACKGROUND: Using the sera from buckwheat (BW)-allergic patients, several putative causative molecules were reported. However, few molecules were determined on the molecular structure. We demonstrated in 2000 that the major allergen with 24 kDa (BW24KD) is a legumin-like storage protein. OBJECTIVE: The aim of this study was to isolate and characterize further a major allergen with 10 kDa by molecular cloning. METHODS AND RESULTS: Buckwheat allergens were identified by immunoblotting analysis using sera from 14 allergic and two nonallergic individuals. We identified a protein with 10 kDa (BW10KD) that reacted with immunoglobulin E (IgE) more strongly than with IgG and IgA in 57% of the allergic patients but not with IgE in nonallergic individuals. Analyses were performed by N-terminal amino acid sequencing and molecular cloning. Physiological significance was assessed by an immunoblotting experiment showing that the reactivity of an allergic patient's serum IgE to BW10KD was competitively inhibited by natural BW extracts. CONCLUSION: Molecular cloning experiments indicated that BW10KD as a BW allergen was a member of the 2S-albumin multigene family.

Adolescent↗

PubMed2003

Association between K469E allele of intercellular adhesion molecule 1 gene and inflammatory bowel disease in a Japanese population.

BACKGROUND AND AIMS: The genetic contribution to inflammatory bowel disease (IBD) is under investigation. Recent evidence indicates a significant linkage between a locus on chromosome 19p13 and IBD. We investigated the association between an intercellular adhesion molecule 1 gene (ICAM-1) polymorphism located on chromosome 19p13 and IBD in a Japanese population. METHODS: We compared 207 Japanese patients who had IBD (79 with Crohn's disease (CD); 128 with ulcerative colitis (UC)) with 103 unrelated Japanese controls. We determined R241G and K469E polymorphisms of the ICAM-1 gene using polymerase chain reaction (PCR) techniques. RESULTS: Both frequency and carriage rate of the K469 allele were significantly higher in IBD patients than in controls (allelic frequency, p(c)=0.0026; carriage rate, p(c)=0.0034; odds ratio 2.59; 95% confidence interval 1.42-4.68). Furthermore, the frequency of the K469 allele was significantly increased in both CD and UC. Subgroup analysis demonstrated that both K469 allelic frequency and K469 carriage rate were significantly higher in patients with the small bowel and colon type of CD and entire colitis compared with healthy controls. CONCLUSIONS: We identified an overall association between IBD and ICAM-1 K469 in a Japanese population. Further studies of this chromosome region are required to elucidate the gene responsible for IBD.

Adolescent↗

PubMed2002

Correlation between serum phospholipase A(2) IIA levels and histological activity in patients with ulcerative colitis.

BACKGROUND AND AIMS: Phospholipase A(2) (PLA(2)) participates in the regulation of phospholipid metabolism and biosynthesis of eicosanoids, serum levels of PLA(2) are suggested to reflect the disease activity in patients with ulcerative colitis (UC). We examined the relationship between histological disease activity and serum levels of PLA(2) IIA and also clarified mucosal production sites of PLA(2) IIA by immunohistochemistry. PATIENTS AND METHODS: Serum samples from 44 patients with UC, 125 with Crohn's diseases (CD), and 68 controls were studied. Biopsy specimens of colonic mucosa obtained from 23 patients with UC were used for assessment of histological activity. The histological score was determined active (1) or inactive (0), and the sum of each histological score from ten segments of the large intestine was assessed as disease activity. The levels of PLA(2) IIA in sera were measured by a radioimmunoassay kit using a specific monoclonal antibody; immunohistochemical study was performed using the same monoclonal antibody. RESULTS: The serum PLA(2) IIA levels in patients with UC and CD were significantly higher than those of controls. Serum PLA(2) IIA levels in UC were closely correlated with histological disease activity. Immunohistochemical study showed the production of PLA(2) IIA by the polymorphonuclear cells, macrophages, and colonic epithelial cells. CONCLUSION: Serum PLA(2) IIA is a good candidate for assessing disease activity in UC as one of clinical laboratory tests.

Biomarkers↗

PubMed2002

Interleukin-6, tumour necrosis factor alpha and interleukin-1beta in patients with renal cell carcinoma.

As regulators of malignant cell behaviour and communication with stroma, cytokines have proved useful in understanding cancer biology and developing novel therapies. In renal cell carcinoma, patients with inflammatory reactions are known to have poor prognosis. In order to elucidate the relation between renal cell carcinoma and the host, serum levels of inflammatory cytokines, interleukin-6, tumour necrosis factor alpha, interleukin-1beta, were measured. One hundred and twenty-two patients with renal cell carcinoma and 21 healthy control subjects were studied, and serum cytokine levels were measured using a highly sensitive ELISA kit. As a result, in the control group, interleukin-6, tumour necrosis factor alpha and interleukin-1beta levels were 1.79+/-2.03, 2.74+/-0.94 and 0.16+/-0.17 pg ml(-1), respectively. In the renal cell carcinoma patients, they were 8.91+/-13.12, 8.44+/-4.15 and 0.53+/-0.57 pg ml(-1), respectively, and significantly higher. In the comparison of stage, interleukin-6 level was significantly higher in the stage IV group compared to the other stage groups including the control group, while tumour necrosis factor alpha level was significantly higher in each stage group compared to the control group. As for grade, interleukin-6 level was significantly higher in the grade 3 group compared to the control, grade 1 and grade 2 groups, while tumour necrosis factor alpha level was significantly higher in each grade group compared to the control group. All cytokines had a positive correlation with tumour size. In regard to the correlation with CRP, all cytokines had a positive correlation with CRP, while interleukin-6 had a particularly strong correlation. In conclusion, interleukin-6 may be one of the factors for the poor prognosis of patients with renal cell carcinoma. In addition, tumour necrosis factor alpha may be useful in the early diagnosis of renal cell carcinoma and post-operative follow-up.

Biomarkers, Tumor↗

PubMed2002

Case of radiation-induced esophageal ulcer worsened after endoscopic biopsy.

Esophageal ulcer is one of the most important late complications of the esophagus treated with radiation therapy, especially with intraluminal brachytherapy. We encountered a patient with esophageal cancer treated with external radiation therapy and intraluminal brachytherapy, who developed radiation ulcer and who had severe dysphagia soon after endoscopic biopsy of the ulcer edge. A 55-year-old man was diagnosed as esophageal cancer without symptoms. He received 60 Gy/30 Fr of external radiation therapy and 12 Gy/3 Fr of intraluminal brachytherapy at a point of 5 mm in depth from the mucosa surface. He developed an asymptomatic esophageal ulcer 13 months after treatment, and endoscopic biopsy was obtained from the edge of the ulcer. Thereafter, swallowing difficulties appeared, and endoscopy revealed severe esophageal stenosis and a deep ulcer. A possibility that the biopsy contributed to worsening the ulcer can be considered. Except for cases where relapse is apparent, endoscopic biopsy is considered to be avoided.

Biopsy, Needle↗

PubMed2002

Human single-chain Fv (scFv) antibody specific to human IL-6 with the inhibitory activity on IL-6-signaling.

Human anti-IL-6 antibody may be useful for the immunotherapy of various inflammatory diseases, such as rheumatoid arthritis. Since IL-6 is a growth factor for B cell hybridoma, it is not easy to isolate murine B cell hybridomas producing the anti-IL-6 antibody with the IL-6-signaling inhibitory activity. In this study, the antibody library (Vgamma-Vkappa, Vgamma-Vlambda, Vmu-Vkappa or micro-Vlambda ligated into the pCANTAB 5E phagemid vector) was prepared from peripheral blood mononuclear cells of 20 healthy subjects. The phage display library was panned with an IL-6-coated plastic plate, and the binding specificity was confirmed by ELISA and BIAcore. From the antibody library (Vgamma-Vlambda), five IL-6-specific phage clones were isolated. The effects of the soluble scFvs purified from these phage clones were tested on the growth of the IL-6-dependent human cell line, KT-3. Two of these clones significantly inhibited the growth of KT-3, and three showed no inhibition.

Amino Acid Sequence↗

PubMed2001

Additional gene therapy with Ad5CMV-p53 enhanced the efficacy of radiotherapy in human prostate cancer cells.

PURPOSE: The aim of this study was to investigate the efficacy of combination therapy of ionizing radiation (IR) and adenoviral p53 gene therapy and to evaluate its molecular mechanisms. METHODS AND MATERIALS: Two human prostate cancer cell lines, DU145 and PC-3 cells, containing different types of p53 gene mutations, were investigated. The recombinant adenovirus vector containing the wild-type p53 gene (Ad5CMV-p53) was used for this study. Cells were irradiated (in 0, 2, 4, and 6 Gy, 300 cGy/min) and after 12 h of irradiation, the cells were infected with various doses of Ad5CMV-p53 (0-40 multiplicity of infection [MOI]). Cytotoxicity was determined by clonogenic assay. The molecular mechanisms were evaluated by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), apoptotic cell detection, and cell cycle analysis. RESULTS: The cell growth inhibition in DU145 (p53-mutated) cells by IR was strongly enhanced by additional Ad5CMV-p53 infection in a viral dose-dependent manner. In DU145 cells, IR alone induced minimal p53 mRNA expression. However, IR combined with Ad5CMV-p53 infection stimulated significant increase in p53 mRNA expression supplemented with Bax and p21 mRNA expressions. In PC-3 (p53-null), IR induced Bax and p21 mRNA expression, while the combination effects were observed in p53, Bax, and p21 mRNA expression. Apoptotic cell deaths were rarely observed after IR alone (DU145: 3%, PC-3: 5%). However, after combination therapy, the proportion of apoptotic cells greatly increased (sevenfold in DU145 cells, and twice in PC-3 cells). G1 cell cycle arrest was observed after Ad5CMV-p53 infection and the combination in both cell lines. CONCLUSION: In this study, we demonstrated that the combination of IR and Ad5CMV-p53 gene therapy resulted in remarkable synergistic effects in human prostate cancer cells. This combination therapy could be one of the optimal treatment strategies for radioresistant prostate cancer.

Adenoviridae↗

PubMed2001

Drug-resistant human bladder-cancer cells are more sensitive to adenovirus-mediated wild-type p53 gene therapy compared to drug-sensitive cells.

We investigated the therapeutic potential and molecular mechanism of adenovirus-mediated wt p53 gene therapy for drug-resistant human bladder cancers. KK47, a human bladder-cancer cell line, along with the drug-resistant sublines KK47/DDP10, KK47/DDP20 (cisplatin-resistant) and KK47/ADM (doxorubicin-resistant) were used for the experiments. All 4 KK47 cell lines had genetically normal p53 genes. Using an in vitro cytotoxicity assay, the drug-resistant cell lines were more sensitive to Ad-CMV-p53 cell killing than the KK47 parental cell line. Ad-CMV-p53 induced higher levels of p53 protein and mRNA in the drug-resistant cell lines than in the parental cell line and, consequently, higher levels of p21 and Bax mRNA, which resulted in higher percentages of G(1) cell-cycle arrest and apoptosis. The higher efficiencies of adenoviral gene transfer in the drug-resistant cell lines were confirmed by X-gal staining after infection with Ad-CMV-beta-gal. In conclusion, adenovirus-mediated wt p53 gene therapy was more effective in the drug-resistant bladder-cancer cell lines than in the drug-sensitive bladder-cancer cell line.

Adenoviridae↗

PubMed2001

Clinical significance of serum pulmonary surfactant proteins a and d for the early detection of radiation pneumonitis.

PURPOSE: Radiation pneumonitis (RP) is one of the most serious complications for patients who receive thoracic irradiation. To avoid this, early diagnosis of radiation pneumonitis is extremely important. The purpose of the present study is to investigate whether serum pulmonary surfactant proteins A and D (SP-A and SP-D, respectively) could be useful markers for RP. METHODS AND MATERIALS: Eighty-six patients (lung cancer: 42 [primary: 39, metastatic: 3], breast cancer: 23, esophageal cancer: 21) who underwent radiation therapy were prospectively studied. Radiation doses ranged from 30-76 Gy (median, 58 Gy). Serum SP-A and SP-D levels were evaluated sequentially by a sandwich enzyme-linked immunosorbent assay (ELISA) method before, during, and throughout the follow-up period until the development of symptomatic RP or until one year after completion of radiotherapy. Specificity of the ELISA results was confirmed by Western blot analysis. Patients symptomatic for RP were graded according to the Common Toxicity Criteria. RESULTS: RP occurred in 19 patients. Serum SP-D levels of patients with RP were sequentially higher than those in patients without RP. In the monitoring, serum SP-D levels at 50-60 Gy showed greater sensitivity and positive predictive values for RP detection (74% and 68%, respectively) than SP-A (26% and 21%, respectively). Western blot analysis showed that the development of RP was due to overproduction, but not proteolysis of surfactant proteins. CONCLUSION: We confirm that serum SP-A and SP-D monitoring is a practical and useful diagnostic method for the early detection of RP.

Aged↗

PubMed2001

Severely reduced production of klotho in human chronic renal failure kidney.

We recently identified a novel gene, termed klotho (kl) that is involved in the development of a syndrome in mice resembling human aging. A defect of the kl gene expression in mice leads to multiple disorders including arteriosclerosis, osteoporosis, ectopic calcification, and skin atrophy together with short life-span and infertility. Patients with chronic renal failure (CRF), develop multiple complications that are reminiscent of phenotypes observed in kl mutant mice. Furthermore, the kl gene is mainly expressed in kidney and brain. These evidences above suggest the possible involvement of Klotho function in the complications arising in CRF patients. To investigate the above possibility, we examined the kidneys of 10 clinically or histologically diagnosed CRF cases. The level of kl gene expression was measured by utilizing RNase protection assay. The expression of Klotho protein was assayed by utilizing Western blot analysis and by immunohistochemistry. The levels of kl mRNA expression were greatly reduced in all CRF kidneys. Moreover, the production of Klotho protein was also severely reduced in all CRF kidneys. These results suggest that the decrease in kl gene expression in CRF patients may underlie the deteriorating process of multiple complications in the CRF patients.

Adult↗

PubMed2001

Multiphase ECG-triggered 3D contrast-enhanced MR angiography: utility for evaluation of hilar and mediastinal invasion of bronchogenic carcinoma.

The purpose of this study was to evaluate the usefulness of cardiac synchronized magnetic resonance angiography [electrocardiographically (ECG)-triggered MRA] for improving image quality and detection of hilar and mediastinal invasion of bronchogenic carcinoma. Fifty patients, suspected of having hilar or mediastinal invasion of bronchogenic carcinoma, underwent contrast-enhanced computed tomography and MR imaging including conventional and ECG-triggered MRA. Twenty patients subsequently also underwent surgical resection. Vascular enhancement-to-background ratio (VBR), vascular enhancement-to-tumor ratio (VTR), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and image quality scores of thoracic vessels obtained with both MRA techniques were determined and compared. In addition, the diagnostic accuracy of tumor invasion of pulmonary vessels was compared. VBRs and VTRs of both MRA techniques were not significantly different. ECG-triggered MRA significantly improved SNRs and CNRs (P < 0.05). Two readers judged that overall image quality of ECG-triggered MRA was better than that of conventional MRA (kappa > or = 0.41). In conclusion, ECG-triggered MRA improves the image quality and the detection of hilar and mediastinal invasion of bronchogenic carcinoma.

Adult↗

PubMed2001

Anatomy and physiology of the female pelvis: MR imaging revisited.

This article reviews the normal anatomy of the female pelvis and focuses on uterine physiology, presenting the kinematics of the uterus that can be identified on ultra-fast MR imaging. It also discusses the many facets of the junctional zone on MR imaging. Ultra-fast MR imaging seems to be a powerful tool for evaluating normal anatomy, physiology, and pathology of the uterus. J. Magn. Reson. Imaging 2001;13:842-849.

Female↗

PubMed2001

Neurilemoma of the renal capsule: MR imaging and pathologic correlation.

We report a case of neurilemoma arising from the renal capsule. Renal neurilemoma is an especially rare tumor, with only 15 cases previously reported. We attempted to correlate MR findings with microscopic components of the tumor. On T2-weighted images the solid part of the tumor was heterogeneous hyperintense. The MR signal intensity on T2-weighted images help estimate microscopic components of the renal neurilemoma.

Aged↗

PubMed2001

Covered Gianturco stent for tracheal stricture: application of polychlorovinylidene and polyurethane as covering materials.

The aim of this study was to assess the efficacy and safety of thin membranes of polychlorovinylidene (PCV) or polyurethane (PU) as covering materials for Gianturco stents in the treatment of severe tracheal stricture caused by intraluminal tumor. Manufactured Gianturco stents covered with PCV or PU membrane were used to treat six malignant and one benign tracheal stricture. The initial results, complications, clinical follow-up, bronchoscopic findings, and three autopsy microscopic examinations were reviewed. Informed consent was obtained after the nature of the treatment had been fully explained before every procedure. The stents successfully dilated the tracheal strictures, providing immediate relief of respiratory symptoms in all patients with no major complications. During the follow-up period, the covering materials prevented tumor ingrowth until death or intraluminal granuloma formation. Autopsies proved that no histological change occurs in the tracheal mucosa in response to the presence of PCV or PU; however, ulcer formation occurred in one patient and penetration of the stent struts into the tracheal wall in two. Bloody sputum with ulcer formation, minimal granuloma formation at the distal end of the stent, and abnormal bacterial load in the sputum were long-term complications. The Gianturco stent covered with PCV or PU membrane is a useful option as a palliative treatment for malignant and an emergent salvage for benign tracheal stricture, because both materials are thinner and less voluminous than the others. However, the indications for its use are limited to patients with poor prognoses, because hemoptysis, granuloma formation, and bacterial propagation remain problematic.

Aged↗