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Biomedical subjects

T Ikeda

Publications and source records attributed to T Ikeda.

At least 55 records · Page 3Linked to original sources

Expression of E-cadherin, alpha-catenin, and beta-catenin in the process of lymph node metastasis in oral squamous cell carcinoma.

Regional lymph node metastasis is a very important prognostic indicator. In the metastatic process, reduction in cell to cell adhesion including E-cadherin-catenin cell adhesion complex is an essential step. We investigated immunohistochemical expression of E-cadherin, alpha-catenin and beta-catenin in 159 tissue samples from patients with oral squamous cell carcinoma and examined the correlation between their expressions and the presence of regional lymph node metastasis. Significantly greater reduction in expression levels of E-cadherin, alpha-catenin and beta-catenin was found in the metastatic group (n=64) compared to the nonmetastatic group (n=95) (P=0.007, 0.001, 0.001, respectively). However, there was no significant correlation between their expressions and the features of the regional metastasis, the number of metastatic lymph nodes or the presence of extracapsular metastasis. These data suggest that evaluation of the immunohistochemical expression of E-cadherin, alpha-catenin and beta-catenin is extremely valuable for the diagnosis of metastatic occurrence.

Adult↗

T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation.

In a trial of prophylactic implantation of a defibrillator, a mortality benefit was seen among patients with previous myocardial infarction and a left-ventricular ejection fraction of 0.30 or less. We identified 129 similar patients from two previously published clinical trials in which microvolt T-wave alternans testing was prospectively assessed. At 24 months of follow-up, no sudden cardiac death or cardiac arrest was seen among patients who tested T-wave alternans negative, compared with an event rate of 15.6% among the remaining patients. Testing of T-wave alternans seems to identify patients who are at low risk of ventricular tachyarrhythmic event and who may not benefit from defibrillator therapy.

Death, Sudden, Cardiac↗

Degradation of arginine and other amino acids by butyrate-producing asaccharolytic anaerobic Gram-positive rods in periodontal pockets.

The use of 20 amino acids by butyrate-producing asaccharolytic anaerobic Gram-positive rods (AAGPRs) in periodontal pockets, i.e. Eubacterium minutum, Filifactor alocis, E. infirmum, E. sulci and E. saphenum, was studied. E. minutum used only arginine and lysine, and produced substantial amounts of butyrate and ammonia as the main metabolic products from arginine, and acetate, butyrate and ammonia from lysine. Fi. alocis used arginine alone and produced butyrate and ammonia. E. infirmum, E. sulci and E. saphenum used lysine alone and produced acetate, butyrate and ammonia. The growth of these bacterial species was supported and enhanced by arginine and/or lysine enriched to culture media, but not by the other amino acids. Arginine deiminase, ornithine carbamoyltransferase and carbamate kinase activity were detected in the cell-free extract of E. minutum, suggesting that arginine was metabolised to citrulline initially, and subsequently to ornithine and carbamoyl phosphate. Ornithine and carbamoyl phosphate were further converted to butyrate, and carbon dioxide and ammonia, respectively. Enzymatic activity of arginine deiminase and ornithine carbamoyltransferase was not detected in Fi. alocis, indicating that Fi. alocis converted arginine to ornithine directly, not via citrulline, and further to butyrate.

Ammonia↗

A mouse model of the atopic eczema/dermatitis syndrome by repeated application of a crude extract of house-dust mite Dermatophagoides farinae.

BACKGROUND: We cultured Dermatophagoides farinae (Df), one of the most common mites in house dust and the most important allergen among natural allergens. With this material, we attempted to produce an animal model of the atopic eczema/dermatitis syndrome (AEDS). METHODS: We cultured Df mites in high density and prepared a crude extract of Df (DfE) together with the culture medium. We applied the extract to the back skin of NC/Nga and BALB/c mice three times per week for 8 weeks. RESULTS: In the NC/Nga group, dryness or scaling appeared on the skin, and scratching behavior increased at the second week in the DfE-treated group. Skin erosion and hemorrhage occurred at the fourth week. The epidermis thickened and deepened into the upper dermis, in which mast cells were highly accumulated, corresponding with the skin lesion of AEDS patients. Specific IgE and IgG to DfE and total IgE were elevated in the sera. Mice treated with an extract of mite culture medium did not develop skin lesions. In the BALB/c group, mice developed specific IgE and IgG to DfE, however, no typical skin lesions appeared. Mast cells in the upper dermis did not increase. CONCLUSIONS: Repeated painting of Dermatophagoides extract produced IgE-associated AEDS-like lesions on the skin of NC mice.

Allergens↗

Protective effect of sesamin administration on exercise-induced lipid peroxidation.

To investigate the mechanism of antioxidative effects of sesamin in vivo, 32 male ddY mice were administered with 10 mg/kg or 100 mg/kg of sesamin (S10, S100), 100 mg/kg of vitamin E (VE100) or control sample (C). They were subjected to 30 min of swimming exercise 2 h after the sample administration by using a new forced-swimming apparatus, i. e. an adjustable-current swimming pool. Exercise resulted in a significant increase in plasma lipid peroxides (LPO) in C and VE100 (p < 0.01), but not in S10 and S100. S100 showed significantly higher total glutathione peroxidase activity and glutathione S-transferase activity in liver compared to C (p < 0.05). In conclusion, sesamin may enhance LPO degradation in the liver resulting in the strong protective effects against exercise-induced plasma lipid peroxidation.

Animals↗

Involvement of cysteine proteinases in excystment of Paragonimus ohirai metacercariae induced by sodium cholate and A23187.

The involvement of intrinsic proteinases in the excystment of Paragonimus ohirai metacercariae was studied in in vitro excystment induced by sodium (Na) cholate, a bile salt and A23187, a Ca2+ ionophore. The effects of various proteinase inhibitors on the in vitro excystment were examined and similar inhibitory profiles were obtained. Benzyloxycarbonyl-L-leucyl-L-leucinal (Z-Leu-Leu-H), a cysteine proteinase inhibitor and 4-(2-aminoethyl)-benzenesulfonyl fluoride (Pefabloc SC), a serine proteinase inhibitor completely inhibited excystment, while L-3-carboxy-2,3-trans-epoxypropionyl-leucylamido (4-guanidino)-butane (E-64), a cysteine proteinase inhibitor and leupeptin, a cysteine/serine proteinase inhibitor permitted partial excystment at a lower rate, but inhibited it from proceeding from the partial excystment stage. In secretions released from metacercariae during excystment, proteinase activities detected towards various fluorogenic peptidyl substrates were almost completely inhibited by Z-Leu-Leu-H and E-64, but not by Pefabloc SC. Sodium cholate induced a higher secretion of cysteine proteinases and a higher rate of excystment than A23187. Profiles of cysteine proteinase activities towards five peptidyl substrates detected were markedly different among the two secretions and the lysate of newly excysted juveniles. Newly excysted juveniles released cysteine proteinases with similar activity profiles and levels to metacercariae induced by Na cholate-incubation, whereas the release of cysteine proteinases was reduced compared with metacercariae induced by A23187-incubation. These results provide valuable information about the involvement of intrinsic proteinases in metacercarial excystment.

Animals↗

Double-blind randomised trial comparing the non-steroidal aromatase inhibitors letrozole and fadrozole in postmenopausal women with advanced breast cancer.

BACKGROUND: To compare the efficacy, safety and tolerability of letrozole, an advanced non-steroidal aromatase inhibitor, and fadrozole hydrochloride, an older-generation drug in this class, we conducted a randomised double-blind trial in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: One hundred and fifty-seven postmenopausal women with advanced breast cancer were enrolled and randomly assigned to receive letrozole or fadrozole in a multicentre, randomised double-blind trial in Japan. One hundred and fifty-four eligible patients were treated with either letrozole 1.0 mg once daily (n = 77) or fadrozole 1.0 mg twice daily (n = 77), for a minimum of 8 weeks. RESULTS: Letrozole showed a significantly higher overall objective response rate [complete response (CR) + partial response (PR)] than fadrozole (31.2% and 13.0%, respectively; P = 0.011, Fisher's exact test). Clinical benefits defined as CR, PR and stable disease (no change in status for more than 24 weeks) were also higher in patients treated with letrozole (50.6%) than fadrozole (35.1%). Letrozole was significantly superior to fadrozole in terms of the dominant lesion in soft tissue, bone and viscera (P = 0.011, stratified Mantel-Haenszel test). Median time to progression was 211 days in the letrozole group and 113 days in the fadrozole group with no significant difference (P = 0.175, log-rank test). Letrozole markedly reduced the estradiol, estrone and estrone sulfate levels in peripheral blood within 4 weeks. The suppressive effect of fadrozole on these hormone levels was insufficient. Adverse drug reactions were observed in 35.9% of the patients treated with letrozole and in 39.5% of those treated with fadrozole with no significant difference between the two groups (P = 0.74, Fisher's exact test). Most of the adverse drug reactions were rated as grade 1 or 2. CONCLUSIONS: The results show letrozole at a dose of 1.0 mg once daily to be more effective in treating postmenopausal women with advanced breast cancer than fadrozole at 1.0 mg twice daily, with similar safety and tolerability profiles.

Administration, Oral↗

Decrease in serum nucleotide pyrophosphatase activity in ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is a prototype of a group of rheumatic diseases referred to as spondyloarthropathy. AS patients show marked ectopic ossification in the spine, occasionally resulting in so-called bamboo spine. Although a strong association with HLA-B27 has been reported, its aetiology remains undetermined. Another rheumatic disease, ossification of the posterior longitudinal ligament of the spine (OPLL), demonstrates ectopic ossification of the spinal ligaments very similar to that of AS. Recently, nucleotide pyrophosphatase (NPPS) was implicated in the aetiology of OPLL: an Npps mutation was found to cause OPLL in mice, and an association between a polymorphism of the human NPPS gene and OPLL was identified. The clinical similarities between AS and OPLL led us to hypothesize that NPPS may also be implicated in the aetiology of AS. To elucidate the role of NPPS in the pathogenesis of AS, we examined serum NPPS activity and the possible association of the NPPS gene with AS. METHODS: Forty-four Japanese patients with AS, 43 patients with OPLL, and age- and sex-matched normal volunteers took part in this study. We determined serum NPPS activity using high-performance liquid chromatography and examined the association between AS and NPPS using single nucleotide polymorphisms (SNPs) of the NPPS gene. RESULTS: Serum NPPS activity in AS patients was significantly decreased compared with the controls (P < 0.0001). However, there was no association between AS and NPPS gene SNPs. CONCLUSION: NPPS is implicated in the pathogenesis of AS.

Adult↗

Use of perfluorocarbon liquid during vitrectomy for severe proliferative diabetic retinopathy.

AIM: To evaluate the value of using perfluorocarbon liquid (PFCL) during vitrectomy in eyes with proliferative diabetic retinopathy (PDR). METHODS: The surgical records of eyes with PDR (291 eyes of 228 patients) that underwent vitrectomy in the vitreoretinal service of Osaka Medical College (April 1999 to October 2001) were reviewed. From these, 18 eyes of 15 patients had PFCL used during vitrectomy, and the preoperative and postoperative findings of these eyes were analysed. RESULTS: All of the 18 eyes had advanced PDR with tractional and/or rhegmatogenous retinal detachment. PFCL enabled easier flattening of the retinal folds and effective endophotocoagulation. In two cases, PFCL was used to flatten a bullous retinal detachment that developed when a tight vitreoretinal adhesion was loosened. In two other cases with combined traction/rhegmatogenous retinal detachment, PFCL was used to tamponade the detached retina which then allowed successful membrane dissection. Anatomical success was obtained in 16 of the 18 cases (mean follow up time 13.3 months) with visual acuity of 20/200 or better in nine eyes (50%). CONCLUSIONS: PFCL is considered to be a useful adjunct during vitrectomy for the treatment of severe PDR.

Adult↗

[Video-assisted thoracic surgery for the resection of pulmonary metastases].

We report the use of video-assisted thoracic surgery (VATS) as a treatment or pulmonary metastases. Between July 1994 and March 2002, 75 patients were treated for metastatic lung tumor by VATS. These patients included 45 males and 30 females with an average age of 60.6 years. Their primary diseases were Colon cancer (38), renal cell carcinoma (12), breast cancer (6), seminoma (3), thyroid carcinoma (3), parotid cancer (2), pharyngeal cancer (2) and the others (9). Tumor size ranged from 6 to 62 mm in diameter. A preoperative high resolution spiral computed tomography (CT) scan was used to locate the nodule in all patients. Ten recurrence cases were performed re-resection by VATS approach with an average period was 22 month. We conclude that VATS is a good candidate for the resection of lung metastases in the selected cases.

Adult↗

[Total aortic arch replacement with a right femur neck fracture on chronic renal dialysis; report of a successful case].

Although recent operative outcome for aortic arch aneurysm has been improved by various newly-devised assistant measures, satisfactory results have not been obtained in cases with serious preoperative complications, such as chronic renal failure. We present here an operative case of a 67-year-old woman on chronic hemodialysis with a calcified aortic arch aneurysm and a right femur neck fracture. First, we performed femur head replacement under careful hemodynamic control. After her mobilization was achieved, total aortic arch replacement was performed in "arch-first technique" using deep hypothermia plus retrograde cerebral perfusion in consideration of her calcified vessels. Her postoperative course was uneventful. We believe that early mobilization was a key for her recovery, because it was useful to prevent postoperative complications such as pulmonary infection and atelectasis. Our experience suggested that meticulous management throughout the whole perioperative course is very important for total aortic arch replacement in such complicated cases.

Aged↗

2-Amino-3-carboxy-1,4-naphthoquinone affects the end-product profile of bifidobacteria through the mediated oxidation of NAD(P)H.

Glucose metabolism of bifidobacteria in the presence of 2-amino-3-carboxy-1,4-naphthoquinone (ACNQ), a specific growth stimulator for bifidobacteria, and ferricyanide (Fe(CN)(6)(3-)) as an extracellular electron acceptor was examined using resting cells of Bifidobacterium longum and Bifidobacterium breve. NAD(P)H in the cells is oxidized by ACNQ with the aid of diaphorase activity, and reduced ACNQ donates the electron to Fe(CN)(6)(3-). Exogenous oxidation of NADH by the ACNQ/Fe(CN)(6)(3-) system suppresses the endogenous lactate dehydrogenase reaction competitively, which results in the remarkable generation of pyruvate and a decrease in lactate production. In addition, a decrease in acetate generation is also observed in the presence of ACNQ and Fe(CN)(6)(3-). This phenomenon could not be explained in terms of the fructose-6-phosphate phosphoketolase pathway, but suggests rather that glucose is partially metabolized via the hexose monophosphate pathway. This was verified by NADP(+)-induced reduction of Fe(CN)(6)(3-) in cell-free extracts in the presence of ACNQ. Effects of the ACNQ/Fe(CN)(6)(3-) system on anaerobically harvested cells were also examined. Stoichiometric analysis of the metabolites from the pyruvate-formate lyase pathway suggests that exogenous oxidation of NADH is an efficient method to produce ATP in this pathway.

Acetyltransferases↗

Accelerated reendothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide.

BACKGROUND: Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft. METHODS AND RESULTS: Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene (Ad.CNP) or Escherichia coli lac Z gene (Ad.LacZ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts both at 14 days (0.81+/-0.05 versus 0.30+/-0.14, P<0.01) and at 28 days (0.96+/-0.01 versus 0.45+/-0.08, P<0.001). The mural thrombus area was smaller in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration. CONCLUSIONS: Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.

Adenoviridae↗

Modulation of gene expression in transgenic mouse hearts overexpressing calsequestrin.

Calsequestrin (CSQ) is the major Ca2+ binding protein of the cardiac sarcoplasmic reticulum (SR). Transgenic mice overexpressing CSQ at the age of 7 weeks exhibit concentric cardiac hypertrophy, and by 13 weeks the condition progresses to dilated cardiomyopathy. The present study used a differential display analysis to identify genes whose expressions are modulated in the CSQ-overexpressing mouse hearts to provide information on the mechanism of transition from concentric cardiac hypertrophy to failure. Cardiac ankyrin repeat protein (CARP), glutathione peroxidase (Gpx1), and genes which participate in the formation of extracellular matrix including decorin, TSC-36, Magp2, Osf2, and SPARC are upregulated in CSQ mouse hearts at 7 and 13 weeks of age compared to those of non-transgenic littermates. In addition, two novel genes without sequence similarities to any known genes are upregulated in CSQ-overexpressing mouse hearts. Several genes are downregulated at 13 weeks, including SR Ca2+-ATPase (SERCA2) and adenine nucleotide translocase 1 (Ant1) genes. Further, a functionally yet unknown gene (NM_026586) previously identified in the mouse wolffian duct is dramatically downregulated in CSQ mice with dilated hearts. Thus, CARP, Gpx1, and genes encoding extracellular matrix proteins may participate in the development of cardiac hypertrophy and fibrosis, and changes in SERCA2, Ant1, and NM_026586 mRNA expression may be involved in transition from concentric to dilated cardiac hypertrophy.

Adenine Nucleotide Translocator 1↗

Altered expressions of glutamate transporter subtypes in rat model of neonatal cerebral hypoxia-ischemia.

Glutamate transporters are essential for maintaining the extracellular levels of glutamate at synaptic clefts and are regulated developmentally in a subtype-specific manner. We investigated chronological changes of immunoreactivities for glial glutamate transporters GLAST and GLT-1 and a neuronal glutamate transporter, EAAC1, in postnatal 7-day-old rat neocortices and hippocampi at 12, 24, 48 and 72 h after hypoxia-ischemia. Glutamate transporter subtypes are differentially expressed in the ischemic core and the boundary area of the neonatal rat brain with hypoxia-ischemia. Expressions of these glutamate transporters decreased in the ischemic core at 12 h, then immunoreactivities for GLAST and GLT-1 were recovered at the hippocampus. This was accompanied by a GFAP-positive gliosis at 72 h, whereas these immunoreactivities were reduced at the neocortex in the ischemic core. Glial glutamate transporters, especially GLAST, were noted in some astrocytes appearing as apoptosis as well as shrunken pyramidal neurons mainly in the boundary area of the neocortex. Increased perikaryal expression of EAAC1 was associated with that of MAP2 at the border of the boundary area. These temporal and regional expressions of glutamate transporters may contribute towards understanding the excitotoxic cell death mechanism in hypoxic-ischemic encephalopathy during the perinatal period.

Amino Acid Transport System X-AG↗