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Biomedical subjects

K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 55 records · Page 3Linked to original sources
PubMed2004

Mechanisms underlying the gastroprotective action of glucocorticoids released in response to ulcerogenic stress factors.

Our previous results demonstrate the gastroprotective but not ulcerogenic action of glucocorticoids released in response to ulcerogenic stress factors. The present study was undertaken to investigate the possible mechanisms underlying the gastroprotective action of glucocorticoids in rat stomachs. The effects of deficiency of glucocorticoid production, with or without corticosterone supplementation, on blood flow velocity in gastric microvessels, microvascular permeability, mucus production, motility as well as gastric lesions were studied 3 to 4 h after the onset of ulcerogenic stimuli: water-restraint stress or indomethacin administration. The contribution of glucocorticoids in the healing process of gastric injury was also evaluated. The deficiency in glucocorticoid production significantly potentiated the functional disorders induced by ulcerogenic stimuli, such as a decrease in blood flow velocity and mucus production and an increase in gastric motility and in microvascular permeability, which resulted in aggravation of the formation of gastric lesions as well as impairment of their healing. The changes observed were prevented by supplementation of corticosterone at a dose mimicking a stress-induced corticosterone rise. We conclude that a gastroprotective action of glucocorticoids may be provided by multiple actions, including maintenance of the gastric mucosal blood flow and mucus production, attenuation of the enhanced gastric motility and microvascular permeability as well as beneficial influences on healing processes.

Animals↗
PubMed2004

Synovectomy reduces stromal-cell-derived factor-1 (SDF-1) which is involved in the destruction of cartilage in osteoarthritis and rheumatoid arthritis.

We have compared the concentrations of stromal-cell-derived factor-1 (SDF-1), matrix metalloproteinase-1 (MMP-1), MMP-9 and MMP-13 in serum before and after synovectomy or total knee replacement (TKR). We confirmed the presence of SDF-1 and its receptor CXCR4 in the synovium and articular cartilage by immunohistochemistry. We established chondrocytes by using mutant CXCR4 to block the release of MMPs. The level of SDF-1 was decreased 5.1- and 6.7-fold in the serum of patients with OA and RA respectively, after synovectomy compared with that before surgery. MMP-9 and MMP-13 were decreased in patients with OA and RA after synovectomy. We detected SDF-1 in the synovium and the bone marrow but not in cartilage. CXCR4 was detected in articular cartilage. SDF-1 increased the release of MMP-9 and MMP-13 from chondrocytes in a dose-dependent manner. The mutant CXCR4 blocked the release of MMP-9 and MMP-13 from chondrocytes by retrovirus vector. Synovectomy is effective in patients with OA or RA because SDF-1, which can regulate the release of MMP-9 and MMP-13 from articular chondrocytes for breakdown of cartilage, is removed by the operation.

Aged↗
PubMed2004

Roles of endogenous prostaglandins and cyclooxygenase izoenzymes in mucosal defense of inflamed rat stomach.

Endogenous prostaglandins (PGs) are involved in adaptive gastric protection against acute injury, and cyclooxygenase (COX)-1 is responsible for the production of PGs in this phenomenon. In the present study, we examined the effect of various COX inhibitors on gastric ulcerogenic and acid secretory responses following daily exposure of the stomach to iodoacetamide (IA) and investigated the role for COX isozyme in gastric protection under subchronic mucosal irritation. Gastric mucosal irritation was induced by addition of 0.1% IA to drinking water, and the gastric mucosa was examined on the 6th day. Indomethacin (5 mg/kg) or SC-560 (selective COX-1 inhibitor, 5 mg/kg) or rofecoxib (selective COX-2 inhibitor, 5 mg/kg) was given p.o. twice 24 hr and 3 hr before the termination of IA treatment. Giving IA in drinking water for 5 days produced minimal damage in the stomach. The damage was significantly worsened by indomethacin, resulting in hemorrhagic lesions. Both SC-560 and rofecoxib also aggravated such lesions, although the effect of rofecoxib was more pronounced. Treatment with IA decreased acid secretion in pylorus-ligated stomachs, and this change was significantly reverted by indomethacin as well as SC-560 and rofecoxib. Mucosal PGE2 content was increased following IA treatment, with apparent expression of COX-2 mRNA in the stomach, and the increased PGE2 production was significantly suppressed by SC-560 and rofecoxib as well as indomethacin. These results suggest that endogenous PGs derived from both COX-1 and COX-2 are involved in the mucosal defense of the inflamed stomach, partly by decreasing acid secretion and contribute to maintaining the mucosal integrity under such conditions.

Administration, Oral↗
PubMed2004

Dual role of endogenous nitric oxide in development of dextran sodium sulfate-induced colitis in rats.

The role of nitric oxide (NO) in the etiology of ulcerative colitis is controversial with reports of the improvement and aggravation of colonic lesions by inducible NO synthase (iNOS) inhibitors. In the present study, we compared the effect of the selective iNOS inhibitor aminoguanidine and the nonselective NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on a dextran sulfate sodium (DSS)-induced model of colitis in rats. Experimental colitis was induced by a 3% DSS-solution added to drinking water for 7 days. Aminoguanidine (5 approximately 20 mg/kg) and L-NAME (10 mg/kg) were administered p.o. twice daily for the first 3 days, the last 3 days or all 6 days of DSS treatment. Body weight and severity of colitis (diarrhea, bloody feces) were observed over a period of 7 days. DSS treatment resulted in severe colonic lesions, accompanied by diarrhea, bloody feces, decrease of body weight and colon shortening. All of the parameters investigated improved significantly with aminoguanidine treatment at 20 mg/kg for 6 days or the last 3 days of DSS-treatment, but L-NAME did not significantly affect the colitis during these periods. When L-NAME or aminoguanidine was given in the first 3 days of DSS treatment, the colonic lesions were slightly aggravated by L-NAME but not affected by aminoguanidine. The expression of iNOS mRNA was observed from the 3(rd) day of DSS treatment. These results suggested that endogenous NO exerts a biphasic influence on DSS-induced colitis, depending on the NOS isoenzyme; a beneficial effect of NO derived from constitutive NOS and a detrimental effect of NO produced by iNOS in the development of colitis.

Animals↗
PubMed2003

Long-term outcome of benign paroxysmal positional vertigo.

To clarify long-term outcome of benign paroxysmal positional vertigo (BPPV), 50 patients were followed up for a mean of 52 months. Overall recurrence rate by Kaplan-Meier estimation was 37% at 60 months. The patients with horizontal canal BPPV (n = 19) had a significantly higher recurrence rate (50%) at 60 months than those with posterior canal BPPV (n = 28; 26%). There was no significant association between recurrence rates and sex or age.

Adult↗
PubMed2003

Comparative evaluation of measles virus-specific RT-PCR methods through an international collaborative study.

Comparison of RT-PCR assays established in house at various places revealed that laboratories could differ in sensitivity by as much as 1,000-fold in terms of the ability to detect measles virus sequences in clinical samples. The study indicates that PCR findings, positive or negative, are questionable if they are not supported by the associated data demonstrating the overall sensitivity of the assay applied. Measles virus-specific RT-PCR-based assays need to be validated using standard virus preparation or nucleic acid-based target templates. A correlation between real-time quantitative PCR and the conventional PCR for measles virus is highly desirable.

DNA Primers↗
PubMed2003

Changes of perivascular macrophages in the process of brain edema induced by cold injury.

Perivascular macrophages are considered as cerebral scavenger cells under physical and pathological conditions. In this study, we tried to examine changes of perivascular macrophages, especially changes of the characteristic lysosomal inclusion bodies that are rich in hydrolytic enzymes, in the process of brain edema induced by cold injury. Wistar male rats aged 4 months were treated with dry ice for 20 minutes through a drilled hole at the parietal bone. At different time points after the cold injury, cerebral cortex was excised and the immunoreaction for cathepsin D, one kind of lysosomal protease, was examined by post-embedding immuno-electron microscopy. The reactions of cathepsin D were located in the inclusion bodies of perivascular macrophages. At 5 and 10 hours after cold injury, the reactions increased dramatically. Then the reactions inclined to decrease, and reached the minimum at 1 week after cold injury. The reactions seemed to recover at 2 weeks after cold injury. The changes of cathepsin D reactions suggest that the function of perivascular macrophages as scavenger cells were activated in the early phase of the process of brain edema, their later declines might be caused by severe pathological conditions.

Animals↗
PubMed2003

Suicide gene therapy using AAV-HSVtk/ganciclovir in combination with irradiation results in regression of human head and neck cancer xenografts in nude mice.

The application of adeno-associated virus (AAV) vectors to cancers is limited by their low transduction efficiency. Previously, we reported that gamma-ray enhanced the second-strand synthesis, leading to the improvement of the transgene expression, and cytocidal effect of the herpes simplex virus type-1 thymidine kinase (HSVtk) and ganciclovir (GCV) system. In this study, we extended this in vitro findings to in vivo. First, the laryngeal cancer cell line (HEp-2) and HeLa were treated with AAVtk/GCV, the number of surviving cells was reduced as the concentration of GCV increased. Furthermore, the 4 Gy irradiation enhanced the killing effects of AAVtk/GCV by four-fold on HeLa cells and 15-fold on HEp-2 cells. Following the in vitro experiments, we evaluated the transgene expression and the antitumor activity of the AAV vectors in combination with gamma-ray in nude mice inoculated with HEp-2 subcutaneously. The LacZ expression was observed in the xenografted tumors and significantly increased by gamma-ray. The AAVtk/GCV system suppressed the tumors growth, and gamma-ray augmented the antitumor activity by five-fold. These findings suggest that the combination of AAVtk/GCV system with radiotherapy is significantly effective in the treatment of cancers and may lead to reduction of the potential toxicity of both AAVtk/GCV and gamma-ray.

Animals↗
PubMed2003

Enhancement of thymidine kinase-mediated killing of malignant glioma by BimS, a BH3-only cell death activator.

Herpes simplex virus thymidine kinase (HSV-tk)/gancyclovir (GCV) therapy has the ability to inhibit tumor formation in animal models but the results of clinical trials have been disappointing. To improve the performance of tk/GCV therapy, we tried combination therapy designed to enhance its cytotoxic effects by introducing genes that induce apoptosis of the tumor cells through different pathways. We concentrated our efforts on the use of Bim, a BH3-only member of death activators in the Bcl-2 superfamily, because Bim is not involved in the pathways through which HSV-tk/GCV therapy induces apoptosis in malignant glioma cells. Among three alternative splicing variants, BimEL, BimL, and BimS, BimS lacks the binding domain for the dynein light chain LC8, which negatively regulates the proapoptotic function of BimEL and BimL. All four malignant glioma cell lines, U251, A172, T-430, and U373 underwent cell death after transfer of BimS using an adenovirus vector (AVC2). Intriguingly, combination of AVC2-BimS with AVC2-tk markedly increased the sensitivity of U251 cells to GCV both in vitro and in vivo. In contrast, AVC2-BimL did not induce significant cell death. These results indicated that BimS had the ability to improve the efficiency of HSV-tk/GCV therapy in the treatment of malignant glioma and suggested that the targeting of different proapoptotic pathways may be a useful strategy for the development of an effective gene therapy approach to treatment.

Adenoviridae↗
PubMed2003

NSAIDs: the emperor's new dogma?

The spectacular marketing success of the selective cyclooxygenase 2 (COX-2) inhibitors is largely based on efficacy comparable with conventional non-steroidal anti-inflammatory drugs (NSAIDs) with vastly improved gastrointestinal safety. The additional key to the marketing success is the purity and simplicity of the message-that is, COX-1 inhibition causes the gastrointestinal side effects of NSAIDs (COX-1 dogma) while COX-2 blocking confers the therapeutic benefits (COX-2 dogma). Adherence to the COX dogmas with development of COX-2 selective agents has undoubtedly benefited many patients, but ironically their scientific basis is now seriously challenged by experimentation.

Animals↗
PubMed2003

Assessment of myocardial viability using coronary zero flow pressure after successful angioplasty in patients with acute anterior myocardial infarction.

OBJECTIVES: To investigate the relation between coronary flow reserve (CFR), coronary zero flow pressure (Pzf), and residual myocardial viability in patients with acute myocardial infarction. DESIGNS: Prospective study. SETTING: Primary care hospital. PATIENTS: 27 consecutive patients with acute anterior myocardial infarction. MAIN OUTCOME MEASURES: F-fluorodeoxyglucose (FDG) positron emission tomography (PET) was used in 27 patients who underwent successful intervention within 12 hours of onset of a first acute anterior myocardial infarction. Within three days before discharge they had < 25% stenosis in the culprit lesion as determined by angiography 24 (3) days after acute myocardial infarction. Pzf and the slope index of the flow-pressure relation (SIFP) were calculated from the simultaneously recorded aortic pressure and coronary flow velocity signals at peak hyperaemia.%FDG was quantified by comparing FDG uptake in the infarct myocardium with FDG uptake in the normal myocardium. RESULTS: There was a correlation between %FDG and CFR, where y = -1.477x + 62.517, r = -0.072 (NS). There was also a correlation between %FDG and SIFP, where y = -0.975x + 60.542, r = -0.045 (NS), and a significant correlation between %FDG and Pzf, where y = -0.98x + 85.108, r = -0.696 (p < 0.001). CONCLUSIONS: CFR does not correlate with FDG-PET at the time of postreperfusion evaluation of residual myocardial viability. The parameter that correlates best with residual myocardial viability is Pzf and this may be a useful index for predicting patient prognosis.

Aged↗
PubMed2003

Assessment of myocardial perfusion abnormalities by intravenous myocardial contrast echocardiography with harmonic power Doppler imaging: comparison with positron emission tomography.

BACKGROUND: Intravenous myocardial contrast echocardiography with harmonic power Doppler imaging (HPDI) enables assessment of myocardial perfusion. Its accuracy in comparison with positron emission tomography (PET), which is one of the most reliable clinical gold standards for myocardial perfusion, remains to be determined. OBJECTIVE: To assess the ability of HPDI to identify myocardial perfusion abnormalities, using PET as a gold standard. METHODS: 23 patients with myocardial infarction underwent HPDI. Images were obtained from the apical two and four chamber views at pulsing intervals of one to eight cardiac cycles with continuous infusion of Levovist (Schering, Germany). PET was done within two weeks of HPDI. The left ventricle was divided into 12 segments and myocardial opacification by HPDI and uptake of NH(3) by PET in each segment was graded as normal, mildly reduced, or severely reduced. RESULTS: Of the 276 segments examined, adequate image quality was obtained in 226 (82%) by HPDI; 50 segments were excluded because of inadequate image quality. There were more exclusions in the basal segments than in the mid or apical segments (p < 0.0001). Of the 226 segments analysed, overall concordance between HPDI and PET was 82% (chi = 0.70). In the apex, more segments were overestimated by HPDI than were underestimated (chi(2) = 6.25, p = 0.012). CONCLUSIONS: HPDI and PET gave similar results in the assessment of myocardial perfusion abnormalities. However, poor image quality in the basal segments and overestimation of perfusion in the apical segments are current limitations of HPDI.

Adult↗
PubMed2003

Real time quantification of low temperature radiofrequency ablation lesion size using phased array intracardiac echocardiography in the canine model: comparison of two dimensional images with pathological lesion characteristics.

OBJECTIVE: To evaluate the feasibility of quantifying low temperature radiofrequency catheter ablation (RFCA) lesions using a phased array intracardiac echocardiography (ICE) catheter--with better tissue penetration and in a deflectable device-in the canine model. INTERVENTION: Low temperature radiofrequency (RF) energy (50-60 degrees C at up to 40 W) was delivered to the left ventricle in 11 beagles for 60 seconds, using an 8 French catheter with a deflectable tip and a 4 mm distal electrode. MAIN OUTCOME MEASURES: Comparison of the width and depth of RFCA lesions measured by ICE with pathological findings. RESULTS: 33 RF energies were delivered in 11 dogs. 31 lesions (94%) were confirmed at necropsy. 27 of 31 ablation lesions (87%) were detected by ICE. The mean (SD) width and depth of the ICE detected lesions were 10.4 (2.6) mm and 5.7 (1.9) mm, respectively. Pathological findings showed that RFCA lesions consisted of inner and outer layers. Macroscopically, the mean (SD) width and depth of the inner layers were 7.6 (2.3) mm and 3.6 (1.2) mm and those for the whole layers were 10.0 (2.8) mm and 5.3 (1.5) mm, respectively. Microscopically, the inner and outer layers corresponded to necrotic and oedematous areas, respectively. The ICE detected lesion size had better correlation with the pathological measurements of the whole layers in width (r = 0.911) and in depth (r = 0.756). CONCLUSION: The real time evaluation of RFCA lesion size using the phased array ICE is feasible, even with a low temperature RF application. However, ICE slightly overestimates RFCA lesion size compared with pathological necrotic lesion size.

Animals↗
PubMed2003

[Conservative therapy for recurrent bronchial stump fistula occurred after surgery for lung cancer with cerebrovascular disease].

BACKGROUND: Although pyrothorax caused by bronchial stump fistula is 1 of the most severe respiratory complications frequently encountered after surgery for lung cancers, it is very difficult to prevent the development of pyrothorax. However, conservative treatment for bronchial stump fistula occurred after surgery for lung cancer was successfully performed in 1 of our elderly lung cancer patients with a history of cerebrovascular events. CASE: Patient was a 74-year-old man who developed cerebral infarction in October 2000, and was continuously undergoing rehabilitation for left hemiplegia. Chest computed tomography (CT) demonstrated a tumorous lesion in the right S6. Clinical diagnosis of stage IA squamous cell carcinoma was made. His performance status (PS) was degree IV, and he required complete assistance. In addition, since several abnormal florae were detected by preoperative examinations of sputum, the development of postoperative respiratory complications was suspected. In April 2001, thoracoscopy-assisted right inferior lobectomy and nodal dissection 1 (ND 1) were performed. Although the patient developed bronchial stump fistula on the 6th hospital day, it was successfully treated by conservative procedures after second surgery. CONCLUSION: Conservative therapy under nutritional management mainly consisting of central venous nutrition may be useful for some surgically treated lung cancer patients with bronchial stump fistula when they have mild inflammation and the reduction of pyrothorax cavity can be expected by re-expansion of the residual lobes of the lung.

Aged↗
PubMed2003

Laparoscopic gonadectomy in a case of a dicentric fluorescent Y-chromosome mosaicism with Turner-like phenotype and virilized external genitalia.

In few cases of Turner syndrome the karyotype reveals the presence of an additional Y-bearing cell line, which is referred to as a borderline case of mixed gonadal dysgenesis. We report a 20-year-old woman with primary amenorrhea, virilization and a few Turner stigmata, who revealed rare mosaicism of 45,X/46,X dic (Y; 5)(q12; q11), +5/46,X, der (Y), which was detected by conventional G-banding and multicolor spectral karyotyping. She underwent laparoscopic gonadectomy in which mixed gonadal dysgenesis was found and both gonads were removed. No evidence of gonadoblastoma was noted on the gonads. Virilization improved postoperatively. We recommend gonadectomy via laparoscope in women presenting with Turner-like phenotype, virilization and the presence of a Y chromosome. This report describes the role of cytogenetic and molecular genetic investigations in the definition of mosaicism in Turner syndrome.

Adult↗
PubMed2003

Clinical results of aortic arch replacement using a four branched prosthetic graft.

AIM: The aim of this study was to evaluate the operative techniques of total arch replacement, the clinical results and the survival curves of patients following this procedure. METHODS: Since December 2001, 92 patients have undergone surgical treatment for aortic dissection and aneurysm. The total aortic arch replacement was performed in 24 of these patients. There were 16 men and 8 women, and the age range was 42 to 81 years with a mean age of 59.4 years. As the operative technique for total arch replacement, we used the 4-branched prosthetic graft, selective cerebral perfusion (SCP), continuous cold blood cardioplegia (CCBC), and open distal anastomosis under circulatory arrest. The combined operations were coronary bypass grafting in 4 patients, aortic valve suspension in 1 patient and a Bentairs procedure in 1 patient. Eleven (73.3%) patients with acute dissection required emergency operation. RESULTS: The hospital mortality rate was 25% (6 of the 24 patients). The causes of death were multiple organ failure (MOF) due to renal and mesenteric ischemia in 3 patients, cerebral infarction in 2 patients, myonephropathic metabolic syndrome (MNMS) in 1 patient, respectively. The data concerning extracorporeal circulation was 204+/-53 min in total pump time, 136+/-43 min in aortic cross clamp time, 83+/-14 min in SCP time and 48+/-10 min in circulatory arrest time, respectively. The long-term result in actuarial survival rate was 76% for 5 years. CONCLUSION: We consider the technique of total arch replacement using 4-branched prosthetic graft, SCP, CCBC, and open distal anastomosis is a useful operative method in patients with aortic aneurysm.

Adult↗
PubMed2003

Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage.

Nonsteroidal antiinflammatory drugs (NSAIDs) such as indomethacin decrease mucosal PGE(2) production by inhibiting cyclooxygenase (COX) activity and produce damage in the small intestine. The development of intestinal lesions as induced by indomethacin was accompanied by increases in intestinal motility, enterobacterial invasion, and myeloperoxidase (MPO) as well as inducible nitric oxide synthase (iNOS) activity, together with the up-regulation of COX-2 and iNOS mRNA expression. Neither the selective COX-1 inhibitor, SC-560, nor the selective COX-2 inhibitor, rofecoxib, alone caused intestinal damage, but their combined administration produced lesions. SC-560, but not rofecoxib, caused intestinal hypermotility, bacterial invasion and the expression of COX-2 as well as iNOS mRNAs, yet the iNOS and MPO activity was increased only when rofecoxib was administered together with SC-560. Although SC-560 inhibited the PG production, the level of PGE(2) was recovered, in a rofecoxib-dependent manner. The intestinal hypermotility response to indomethacin was prevented by both 16,16-dimethyl PGE(2) and atropine but not ampicillin, yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 as well as the iNOS activity in the intestinal mucosa following indomethacin treatment, resulting in preventing the intestinal lesions. These results suggest that inhibition of COX-1, despite causing intestinal hypermotility, bacterial invasion and iNOS expression, up-regulates the expression of COX-2, and the PGE(2) derived from COX-2 counteracts deleterious events caused by COX-1 inhibition and maintains the mucosal integrity. These sequences of events explain why intestinal damage occurs when both COX-1 and COX-2 are inhibited.

Animals↗