Biomedical subjects

Naoki Yoshimura

Publications and source records attributed to Naoki Yoshimura.

23 records · Page 2Linked to original sources

PubMed2002

Targeting afferent hyperexcitability for therapy of the painful bladder syndrome.

The involvement of C-fiber afferent pathways in urinary frequency and pain associated with painful bladder syndrome raises the possibility of multiple targets for the treatment of this disease. Using an in vivo measurement of bladder activity as well as whole-cell patch clamp recording techniques to examine the properties of bladder afferent neurons in animal models of chronic cystitis, we have documented that tetrodotoxin-resistant sodium channels encoded by the Na(v) 1.8 (PN3/SNS) gene and nitric oxide acting via a cyclic guanosine monophosphate (cGMP)-dependent mechanism are important in modulating bladder pain responses. Thus, suppression of C-fiber afferent nerve activity by blocking specific sodium channels, elevating nitric oxide levels, or activating cGMP-dependent pathways might represent novel strategies for the treatment of symptoms in patients with painful bladder syndrome. Another treatment strategy is suppression of release or activity of proinflammatory agents that can cause normally unexcitable C-fiber afferents to become hyperactive or hyperexcitable. This approach to management of bladder pain was tested in patients with painful bladder syndrome by examining the effectiveness of the antiallergic agent suplatast tosilate (IPD-1151T), which suppresses urinary frequency in a rat model of cystitis. IPD-1151T is an immunoregulator that suppresses cytokine production in T-helper 2 cells and inhibits immunoglobulin E antibody formation and antigen-induced histamine release from mast cells. Preliminary data from an open-label clinical trial showed that 16 of 23 (70%) patients responded to treatment with IPD-1151T (300 mg/day orally for 12 months). The finding that expression of platelet-derived endothelial cell growth factor, which can activate mast cells, was lower in the bladder of responders than nonresponders indicates that bladder levels of platelet-derived endothelial cell growth factor may be a useful marker for this disease.

Afferent Pathways↗

PubMed2002

Anomalous origin of the left coronary artery from the pulmonary artery A case using the autologous pulmonary arterial wall graft.

A 10-year-old girl with anomalous origin of the left coronary artery from the pulmonary artery underwent a two coronary system reconstruction with a new technique. Her left coronary artery was stenotic next to its origin and had a severe adhesion with the aorta. We made a bypass grafting between the aorta and the left coronary artery with a roll shaped transected main pulmonary arterial wall graft. The postoperative angiogram showed a good patency of a reconstructed left coronary artery. This technique is considered useful surgical option for bypass grafting to the left coronary artery when the left coronary artery has an obstructive lesion or a difficulty to dissect and mobilize.

Blood Vessel Prosthesis Implantation↗

PubMed2002

Simultaneous repair of pectus excavatum and congenital heart disease over the past 30 years.

OBJECTIVE: Pectus excavatum may be present in patient requiring operations for cardiac defects. The study was undertaken in order to assess our simultaneous repairs of pectus excavatum and congenital heart disease over past 30 years. METHODS: Between 1970 and 2000, 12 patients underwent simultaneous repair of pectus excavatum and congenital heart disease. Six of 12 patients had ventricular septal defects as cardiac malformations (subgroup A). Operative technique, after the intracardiac procedure using cardiopulmonary bypass, consists of total subperichondrial resection of deformed costal cartilages, transection of deformed portion of the sternum in 2-3 points, and fixation of the sternum in elevated position using two Kirschner wires and a bridge external traction. Postoperative catheterization was performed in five of 12 patients (subgroup B). We evaluated the operative data, the improvement of pectus deformity and right ventricular performance retrospectively. The operative data in subgroup A were compared with those in recent random patients with ventricular septal defects only or with pectus excavatum only (control groups). RESULTS: There was no operative death and non-serious complications were seen in nine patients (atelectasis in six, superficial wound infection in two, chylothorax in one). Pectus deformities improved with the drop of vertebral index postoperatively. The mean total operative time and postoperative drainage in subgroup A were 128.4% and 123.7%, respectively of those in the ventricular septal defect control group. The mean perioperative bleeding in subgroup A was more than the sum of those in control groups. Right ventricular end-diastolic (RVEDVI), end-systolic (RVESVI), stroke (RVSVI) volume indices and ejection fraction (RVEF) in subgroup B tended to increase after surgery. In particular, there were significant increases of RVEDVI (35%, P<0.05) and RVSVI (77%, P<0.01). CONCLUSION: Simultaneous cardiac and pectus repairs were performed successfully without serious complications. Moreover, simultaneous repair resulted in an improvement of right ventricular performance with significant increases of RVEDVI and RVSVI.

Abnormalities, Multiple↗

PubMed2002

Suppression of Helicobacter pylori-induced interleukin-8 production in gastric cancer cell lines by an anti-ulcer drug, geranylgeranylacetone.

BACKGROUND: Geranylgeranylacetone (GGA) is an antigastritis and anti-ulcer agent, with as yet an unknown mechanism of action. In this study, we investigated the effect of GGA on Helicobacter pylori-induced interleukin (IL)-8 production and IL-8 mRNA expression in KATOIII cells, an established gastric cell line. METHODS: Interleukin-8 production in H. pylori-infected KATOIII cells was measured by using enzyme-linked immunoassay. The cytotoxicity of H. pylori on KATOIII cells was measured by a 51Cr release assay. The effect of GGA on H. pylori-induced IL-8 mRNA expression was measured by using northern blotting. RESULTS: Interleukin-8 production increased with time and H. pylori dose; the most significant increase was seen within 6-24 h of coculture with H. pylori. A dose of 0.1 mmol GGA suppressed IL-8 production (P = 0.0077) and inhibited H. pylori-induced IL-8 mRNA expression (P = 0.0019). Furthermore, H. pylori-induced gastric mucosal cell injury associated with IL-8 and neutrophil activation was enhanced by NH3, and this enhancement was suppressed by GGA (P = 0.0043). CONCLUSIONS: Helicobacter pylori-infected gastric mucosal cells produce IL-8, which can promote neutrophil activation, thus contributing to mucosal tissue injury associated with H. pylori infection. Agents like GGA, which can suppress IL-8 production may have a protective role in the treatment of mucosal tissue damage seen in H. pylori infection.

Analysis of Variance↗

PubMed2002

Over expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in patients with interstitial cystitis and bladder carcinoma.

PURPOSE: We examined whether the expression of angiogenic factors, such as platelet-derived endothelial cell growth factor/thymidine phosphorylase (PDEGF/TP) and transforming growth factor-beta, in bladder tissue correlates with the severity of symptoms, such as urinary urgency and bladder pain, in patients with bladder carcinoma and interstitial cystitis. MATERIALS AND METHODS: Bladder biopsy was performed in 32 patients with bladder carcinoma, including 19 with interstitial cystitis and 3 controls. Immunohistological staining for PDEGF/TP, transforming growth factor-beta and CD44 was performed in bladder specimens. PDEGF/TP in bladder tissues was also measured by enzyme-linked immunosorbent assay to examine the correlation of the expression of this factor with painful symptoms in patients with bladder carcinoma or interstitial cystitis. RESULTS: Immunohistochemical staining showed that PDEGF/TP stained in the submucosal layer beneath the basement membrane in bladder tissues of patients with interstitial cystitis and peritumoral areas of those with bladder carcinoma. In addition, PDEGF/TP, transforming growth factor-beta and CD44 stained in the same submucosal region and staining was observed at deeper submucosal levels in interstitial cystitis cases with severe rather than mild bladder pain. Quantitative analyses revealed that mean PDEGF/TP expression plus or minus standard deviation in tumor tissues of 10 patients with bladder carcinoma and pain was significantly higher than in tumor tissues of 22 with asymptomatic bladder carcinoma (129.3 +/- 70.7 versus 37.6 +/- 29.2 units per mg. protein). The mean expression of PDEGF/TP in peritumoral mucosa of patients with bladder carcinoma and pain was also significantly higher than in those with asymptomatic bladder carcinoma (75.5 +/- 42.1 versus 12.6 +/- 5.4 units per mg. protein). For interstitial cystitis mean expression in 6 patients with severe bladder pain was significantly higher than in 13 with moderate pain (79.2 +/- 59.2 versus 16.6 +/- 17.5 units per mg. protein). Mean expression in bladder tissues of controls was less than 2.3 units per mg. protein. CONCLUSIONS: These results suggest that angiogenic factors, such as PDEGF/TP and transforming growth factor-beta, may be involved in the inflammatory process to induce painful symptoms in patients with interstitial cystitis or bladder carcinoma. Proteoglycans such as CD44 may contribute to the presentation of these soluble angiogenic factors at the inflammation site.

Aged↗