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T Sawada

Publications and source records attributed to T Sawada.

At least 73 records · Page 4Linked to original sources
PubMed2001

Colon cancer cell adhesion to endothelial E-selectin inhibits detachment of endothelial cells through activation of beta(1)-integrin.

Previous studies have implicated a role for E-selectin in carcinoma cell adhesion to vascular endothelium. We examined the role of colon cancer cell adhesion to vascular endothelium via E-selectin using adenoviral vector-mediated transfection in human umbilical vein endothelial cells (HUVECs). We found that the amount of HUVEC detachment from the gelatin matrix 24 h after LS-180 cell adhesion was inhibited only when the HUVECs were transduced with wild-type E-selectin, but not with a cytoplasmic domain truncated mutant E-selectin or the control Lac-Z vector. We also found that the adhesion of LS-180 cells to wild-type E-selectin transduced HUVEC-induced activation of beta(1)-integrin receptors without affecting MMP activity. These results indicate that colon cancer cell adhesion via E-selectin inhibits HUVEC detachment from the monolayer, at least in part by modulating beta(1)-integrin activity in HUVECs. In addition, they indicate the importance of the cytoplasmic domain of E-selectin with this phenomenon.

Adenocarcinoma↗
PubMed2001

Expression of thyroid hormone receptor betaA gene assayed by transgenic Xenopus laevis carrying its promoter sequences.

The responsiveness of thyroid hormone responsive element (TRE)-containing promoter sequence to thyroid hormone (TH) was studied utilizing Xenopus laevis carrying a transgene containing 5'-upstream region of TRbetaA1 gene and green fluorescent protein (EGFP) gene. EGFP-expression was seen first in neurulae, which continued to stage 45, then became weak, and again started to increase at the prometamorphic stage, culminating at the metamorphic climax stage. Immunohistochemistry identified eyes, viscera, and muscles as the EGFP-expressing larval tissues. The treatment of premetamorphic tadpoles with TH induced the precocious EGFP-expression. We also showed that the transgenic Xenopus adults were responsive to exogenous TH, a high responsiveness being seen in brain, small intestine, kidney, and bone. TRbeta-expression in the embryo, larva, and adult was verified by Western blotting. Thus, TH not only regulates the metamorphosis, but also might play some biological role(s) in embryos and adults.

Animals↗
PubMed2001

Alteration of collagen IV in acutely deteriorated renal allografts.

BACKGROUND: The changes in the basement membrane occurring in acutely deteriorated renal allografts (ADR) have not been extensively investigated. Our purpose is to elucidate the alteration of collagen IV, a main constituent of the basement membrane in ADR. METHODS: Fifty biopsy specimens of ADR and 10 of chronic transplant nephropathy (CTN) were examined with two monoclonal antibodies specific for collagen IV. JK199 and JK132 are monoclonal antibodies that recognize triple helical collagen IV containing the alpha1 chain. JK199 recognizes all the basement membrane containing [alpha1 (IV)]2alpha2(IV), although JK132 reacts only with a limited portion of it. In the normal kidney, JK199 reacts with the mesangial matrix, the basement membrane of Bowman's capsule (BBM), and the tubular basement membrane, as well as with the glomelular basement membrane (GBM). JK132 reacts with the mesangial matrix, BBM, and the tubular basement membrane. RESULTS: In ADR, increased intensity of JK199 was observed in GBM, the mesangial matrix, BBM, the tubular basement membrane, and the interstitium. Increased intensity of JK132 was observed in the mesangial matrix, BBM, and the tubular basement membrane, but was not remarkable in GBM or the interstitium. In contrast, biopsy specimens of CTN showed increased intensity of JK132 in GBM, the mesangial matrix, BBM, the tubular basement membrane and the interstitium. CONCLUSION: These results suggest that collagen IV is up-regulated in ADR. Differential staining of collagen IV with JK199 and JK132 in GBM and the interstitium may contribute to diagnose CTN.

Adult↗
PubMed2001

Up-regulation of calcineurin Abeta mRNA in the Alzheimer's disease brain: assessment by cDNA microarray.

Recent advances in cDNA microarray technology have made it possible to analyze expression of more than 8000 genes. Using this technology, gene expression in the hippocampus containing neurofibrillary tangle-associated lesions from an Alzheimer's disease (AD) patient was compared with expression in the parietal cortex from the same patient that lacked these lesions. We also compared gene expression using a control brain. The top 20 named genes significantly up-regulated or down-regulated only in the AD brain were determined. The most up-regulated gene proved to be calcineurin Abeta mRNA (CAbeta). In situ hybridization histochemistry revealed that CAbeta was significantly up-regulated in pyramidal neurons of the hippocampus in the AD brain. RT-PCR analysis revealed that CAbeta was up-regulated in the hippocampus from two out of three AD brains while there were no changes in three control brains. Our study suggests that CAbeta may play a crucial role in the pathophysiological mechanisms in AD.

Aged↗
PubMed2001

Determination of subyoctomole amounts of nonfluorescent molecules using a thermal lens microscope: subsingle-molecule determination.

The photothermal effect of an ultratrace amount of nonfluorescent molecules in liquid was determined by optimizing the optical arrangement for a thermal lens microscope. The optimized experimental setup could be determined from the evaluation of probing volume and the concentration of the sample solutions even when the expectation of the molecule number in the probing region was less than a single molecule. The minimum expectation, which is explained as being the time average, was 0.4 molecule of Pb(II) octaethylporphyrin (OEP) in benzene. The concentrations in the 9.7 x 10(-11)-7.8 x 10(-10) M region used in this work corresponded to the expected number of 0.4-3.4 molecules, and the calibration curve in this region showed good linearity. Taking into account the enhancement factor of solvent, the molar absorption coefficient of solute, and the optimization of the optical arrangement, the present result, which was the determination limit of 0.34, was consistent with that previously reported. The relation between molecular behavior in the probing volume and the signal was discussed. The average temperature rise in the probing volume by the photothermal effect for the single OEP molecule was estimated as 3.1 muK, and this value was detectable, based on conventional thermal lens measurements for bulk scale sample.

Journal Article↗
PubMed2001

M(R) 77 KDA factor derived from fibroblasts stimulates the invasion ability of breast-cancer cells.

Breast-cancer cells frequently invade into the skin. However, few reports have described the mechanisms responsible for this invasion. In this study, we investigated the effects of skin fibroblasts on the invasion ability of breast-cancer cells, using a modification of Boyden's chamber method, and purified an invasion-stimulating factor from fibroblasts. Conditioned medium of skin fibroblasts, DF-1, significantly stimulated the invasion ability of breast-cancer cells, OCUB-1. The invasion-stimulating factor produced from skin fibroblasts was then partially purified and characterized. The soluble invasion-stimulating factor of fibroblasts was a protein of 77 kDa, as calculated by SDS-PAGE. Although TGF-alpha and bFGF stimulated the invasion of OCUB-1, no inhibition of the 77 kDa factor was achieved with neutralizing antibodies against TGF-alpha and bFGF. These findings suggest that the 77 kDa factor derived from skin fibroblasts might be unique, might play an important role in invasion to the skin and might explain the frequent skin invasion in breast carcinoma.

Biological Factors↗
PubMed2001

Expression of xenoantigen transformed human cancer cells to be susceptible to antibody-mediated cell killing.

The carbohydrate epitope, alphaGal epitope, is known as a major xenoantigen. The epitope exists abundantly in non-primate mammals and has recently been found on C-type retroviruses. Humans and Old World monkeys have anti-alphaGal antibody, a natural antibody. The present study was performed to examine if the alphaGal epitope could be used as a new target of gene therapy against human cancer. Bovine alpha1-3 galactosyltransferase (alpha1-3 GT) cDNA which produces the alphaGal epitope was electrophoretically transfected into the human pancreatic cancer cell line, MIA PaCa-2 and the human hepatocellular carcinoma cell line, huH7. The expression of the alphaGal epitope was confirmed by flow cytometry, using specific binding with IB4 lectin conjugated with fluorescein isothiocyanate. Transfected MIA PaCa-2 cells and huH7 cells showed a positive log shift for the alphaGal epitope. Next, we examined whether human cancer cells expressing the alphaGal epitope could be lysed by natural antibodies using the complement-dependent cytotoxic cross-match test. The results showed that transfected MIA PaCa-2 cells and huH7 cells were effectively lysed by human natural antibodies, and the killing was observed with any serum irrelevant of blood type. The results indicate that transfection of the functional alpha1-3 GT gene into human cancer cells can lead to their transformation, making them susceptible to lysis by natural antibodies, and, thus, useful for gene therapy.

Animals↗
PubMed2001

Association between a single-nucleotide polymorphism in the promoter of the human interleukin-3 gene and rheumatoid arthritis in Japanese patients, and maximum-likelihood estimation of combinatorial effect that two genetic loci have on susceptibility to the disease.

Genetic variants of interleukin-3 (IL-3), a well-studied cytokine, may have a role in the pathophysiology of rheumatoid arthritis (RA); but reports on this association sometimes conflict. A case-control study was designed to investigate association between RA and a single-nucleotide polymorphism (SNP) in the IL-3 promoter region. Comparison of cases of RA versus control individuals yielded a chi(2) value of 14.28 (P=.0002), with a genotype odds ratio of 2.24 (95% confidence interval [95%CI] 1.44-3.49). When female cases with earlier onset were compared with female control individuals, the SNP revealed an even more significant correlation, with chi2=21.75 (P=.000004) and a genotype odds ratio of 7.27 (95%CI 2.80-18.89). The stronger association that we observed in this clinically distinct subgroup (females with early onset), within a region where linkage disequilibrium was not significantly extended, suggested that the genuine RA locus should locate either within or close to the IL-3 gene. Combined genotype data on SNPs on eight other candidate genes were combined with our IL-3 results, to estimate relationships between pairs of loci and RA, by maximum-likelihood analysis. The utility of combining the genotype data in this way to identify possible contributions of various genes to this disease is discussed.

Age of Onset↗
PubMed2001

Signaling pathway of ciliary neurotrophic factor in neuroblastoma cell lines.

BACKGROUND: Ciliary neurotrophic factor (CNTF) is a member of the interleukin-6 (IL-6) cytokine family and affects the survival and differentiation of several classes of neurons. For signal transduction, CNTF requires a receptor complex, composed of the IL-6 signal transducing molecule gp130, leukemia inhibitory factor receptor (LIFR)-beta, and CNTFR-alpha. There are two major independent pathways (Jak-STAT and Ras-MAPK) in cell signaling, and some recent reports show interaction between these pathways. The signal of the IL-6 family is mainly transduced to the Jak-STAT pathway through gp130. However, it has not been examined in neuroblastoma in detail. PROCEDURE AND RESULTS: Here we examine the signaling pathway of CNTF in 11 neuroblastoma cell lines. Northern blot analysis revealed that 3 of the 11 cell lines expressed c-fos mRNA after CNTF stimulation. Cell lysates were immunoprecipitated with agarose-conjugated antiphosphotyrosine antibody and blotted with anti-gp130, anti-Jak1, or anti-STAT3 antibody. Tyrosine phosphorylation of gp130, Jak1, and STAT3 was observed after CNTF stimulation in these three cell lines. Furthermore, tyrosine phosphorylation of ERK1 (one of the MAPKs) was also observed in all of them. CONCLUSIONS: These results demonstrate that CNTF signaling is conserved in some of the neuroblastoma cell lines and suggest that not only a Jak-STAT pathway but a MAPK pathway is activated by CNTF through gp130 in neuroblastoma cell lines.

Antigens, CD↗
PubMed2001

Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: a multicenter study.

Active ulcerative colitis (UC) is characterized by activation and infiltration of granulocytes and monocytes/macrophages into the colonic mucosa. The infiltrated leukocytes can cause mucosal damage by releasing degradative proteases, reactive oxygen derivatives, and proinflammatory cytokines. The aim of this trial (conducted in 14 specialist centers) was to assess safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active UC most of whom were refractory to conventional drug therapy. We used a new adsorptive type extracorporeal column (G-1 Adacolumn) filled with cellulose acetate beads (carriers) of 2 mm in diameter, which selectively adsorb granulocytes and monocytes/macrophages. Patients (n = 53) received five apheresis sessions, each of 60 minutes duration, flow rate 30 ml per minute for 5 consecutive weeks in combination with 24.4 +/- 3.60 mg prednisolone (mean +/- SE per patient per day, baseline dose). During 60 minutes apheresis, 26% of granulocytes, 19.5% of monocytes and 2% of lymphocytes adsorbed to the carriers. At week 7, 58.5% of patients had remission or improved, the dose of prednisolone was reduced to 14.2 +/- 2.25 mg (n = 37). The apheresis treatment was fairly safe, only eight non-severe side effects (in 5 patients) were reported. Based on our results, we believe that in patients with active severe UC, patients who are refractory to conventional drugs, granulocyte and monocyte adsorption apheresis is a useful adjunct to conventional therapy. This procedure should have the potential to allow tapering the dose of corticosteroids, shorten the time to remission and delay relapse.

Adult↗
PubMed2001

Randomized, controlled trial of lateral node dissection vs. nerve-preserving resection in patients with rectal cancer after preoperative radiotherapy.

PURPOSE: The effectiveness of preoperative radiation therapy for advanced lower rectal carcinoma to preserve the function of pelvic organs and reduce local recurrences was examined in a prospective, randomized, controlled study. METHODS: Fifty-one patients with a diagnosis of localized and resectable adenocarcinoma of the lower rectum undergoing 50 Gy of preoperative radiotherapy were recruited into the trial between April 1993 and March 1995. The patients were randomly allocated to complete autonomic nerve-preserving surgery without lateral node dissection (D1), or surgery with dissection of the lateral lymph nodes including autonomic nerves (D2) followed by oral administration of carmofur for one year. RESULTS: No difference was observed in either survival or disease-free survival between D1 and D2 groups. There was no difference between the two groups in terms of recurrence rate. A significant difference was observed in urinary and sexual function (P = 0.02 and 0.02, respectively) one year after surgery between D1 and D2 groups. CONCLUSION: This study suggests that lateral node dissection is not necessary in terms of curability for patients with advanced carcinoma of the lower rectum who undergo preoperative radiotherapy.

Adenocarcinoma↗
PubMed2001

A case of undifferentiated glioma in a 70-year-old woman.

The present case involved a 70-year-old woman who was diagnosed with a right cerebral hemorrhage. Excisional surgery of the hematoma was performed. Grossly, a whitish, solid tumor (1 x 1 x 0.8 cm in size) was recognized in the hematoma. Histologically, the tumor was composed of large, polygonal cells and small undifferentiated cells in a jumbled architectural arrangement with a cartilage component. The large, polygonal cell component was conspicuous and somewhat rhabdoid in appearance and appeared to be an astrocytic tumor showing glial differentiation. The small, undifferentiated cell component resembled tumor cells of a primitive neuroectodermal tumor (PNET). Clinical follow-up of the patient for 2 months after the first operation revealed recurrence with rapid growth. A second operation was performed, but the patient died 8 months after the first operation (2 months after the second). Immunohistochemically, the tumor cells suggesting glial differentiation were positive for glial fibrillary acidic protein (GFAP), S-100, neuron-specific enolase (NSE), and vimentin. PNET-like components in the primary tumor were positive for NSE, GFAP, and S-100, and weakly positive for vimentin and synaptophysin. Each tumor cell was negative for epithelial membrane antigen (EMA), keratin, desmin, actin, myoglobin, neurofilament (NF), and MIC2 protein. The recurrent tumor revealed predominantly PNET-like components; however, only a few tumor cells were positive for GFAP. This appearance suggested that this brain tumor might originate from a common multipotential stem cell. Considering its histopathological and immunohistochemical characteristics, the primary tumor was finally regarded as an undifferentiated glioma with dedifferentiation of the glial component in the recurrent tumor.

Aged↗
PubMed2001

Prevalence of Helicobacter pylori infection in gastric remnant after distal gastrectomy for primary gastric cancer.

BACKGROUND: The development of a second primary cancer in the gastric remnant after gastrectomy for early gastric carcinoma is a problem, and eradication of Helicobacter pylori after the operation has been recommended. However, to date, practical indications for H. pylori eradication after gastric cancer surgery have not yet been reported. METHODS: We examined H. pylori infection in the gastric remnant after distal gastrectomy for primary gastric cancer. One hundred and nine patients who had had a gastrectomy were studied. Endoscopic findings and results from the urease test, bacteriologic assessment, serological test, and histopathological examination were analyzed. RESULTS: Seventy-one patients (65.1%) were judged to be positive for H. pylori infection. The prevalence of H. pylori infection was found to be significantly decreased in older patients, patients in whom the operation had been performed a long time before examination, patients with symptoms, and patients with severe reflux gastritis. On the other hand, histologically, chronic and acute gastritis correlated significantly with H. pylori infection. H. pylori prevalence was highest in mildly atrophic mucosa and decreased with more extensive atrophic changes of the mucosa. CONCLUSIONS: The persistence of H. pylori-related active gastritis in the gastric remnant after gastric cancer surgery was suggested in younger patients with mild atrophic gastritis and without reflux gastritis. These patients may be the best candidates for H. pylori eradication therapy.

Adult↗
PubMed2001

Assessment of left ventricular diastolic function from quantitative electrocardiographic-gated 99mTc-tetrofosmin myocardial SPET.

We have developed new software which can evaluate left ventricular (LV) diastolic functional parameters from a quantitative gated SPET (QGS) program. To examine its accuracy, we compared these findings with the LV diastolic functional indices obtained from gated radionuclide ventriculography (RNV). Twenty-four patients were selected for this study. Gated SPET with technetium-99m tetrofosmin was performed and the QGS program was used with a temporal resolution of 32 frames per R-R interval. The LV volume of each frame was calculated and four harmonics of Fourier series were retained for the analysis of the LV volume curve. From this fitted curve and its first derivative curve, we derived LV systolic functional indices, e.g. ejection fraction (EF), peak ejection rate (PER) and time to PER (TPER), as well as LV diastolic functional variables, e.g. 1/3 filling fraction (1/3 FF), peak filling rate (PFR) and time to PFR (TPFR). Within 5+/-2 days, gated RNV was performed and diastolic functional parameters were determined by the same method. No significant difference was observed between the variables calculated by gated SPET and by gated RNV. There was a good correlation between EF, PER, TPER, 1/3 FF, PFR and TPFR determined by these two methods (EF: r=0.95, P<0.0001; PER: r=0.87, P<0.0001; TPER: r=0.84, P<0.0001; 1/3 FF: r=0.87, P<0.0001; PFR: r=0.92, P<0.0001; TPFR: r=0.89, P<0.0001). Bland-Altman plots did not reveal any significant degree of directional measurement bias in any of the comparisons of gated SPET data and RNV data. It is concluded that, in addition to the conventional LV systolic functional indices, our program accurately provides LV diastolic functional parameters from gated SPET. Also, this program will be useful for detecting LV diastolic dysfunction in various cardiac diseases before LV systolic dysfunction becomes evident.

Diastole↗
PubMed2001

The importance of peripheral blood leukocytes and macrophage infiltration on bronchial wall wound healing in rats treated preoperatively with anticancer agents.

Preoperative chemotherapy is commonly used for small cell lung cancer or advanced non-small cell lung cancer. This study was conducted to investigate the effects of preoperative antineoplastic agents on the postoperative would healing of bronchial anastomoses in a rat model. Cisplatin (CDDP), doxorubicin (ADM), or cyclophosphamide (CPA) was administered either 3 days preoperatively (experiment 1) or 7 days preoperatively (experiment 2). Wound healing was assessed on postoperative days (POD) 3, 5, and 7 after anastomosis of the bronchus, by examining the bursting strength and hydroxyproline tissue content. In experiment 1, significant impairment of wound healing was seen on POD 3 in the CPA-treated rats, but no significant changes were seen in the other groups. Severe leukopenia and marked reduction of macrophage infiltration into the wound were also observed in the CPA-treated rats. The impairment of wound healing coincided with the time of leukopenia and reduced macrophage infiltration into the wounds. In experiment 2, induction chemotherapy did not impair wound healing. Our experimental results suggest that preoperative chemotherapy producing mild leukopenia, or when followed by a sufficient interval to allow for the recovery of myelosuppression, did not impair wound healing of the bronchial anastomoses. The findings of this study also showed that the depletion of macrophages at the anastomotic site is one of the most important causes of impaired wound healing.

Anastomosis, Surgical↗
PubMed2001

Ultrastructure and composition of basement membranes in the tooth.

The tooth, the hardest organ in the body, is known to be formed through highly elaborate, unique processes of differentiation and development. Basement membranes play critical roles in fundamentally important biological processes such as growth and differentiation, and for better understanding of the mechanism of development and maintenance of the tooth, specializations of tooth basement membranes are reviewed in detail in relation to their roles. The basement membrane at such diverse locations in the tooth as the inner enamel epithelium, maturation-stage ameloblasts, and junctional epithelium at the dentogingival border are specialized in their own highly unique ways for anchoring, firm binding, or mediation in the transport of substances. Thus, the role of basement membranes in the developing and mature tooth is manifold and for these roles individual basement membranes are specialized in their own specific ways which are rare or not seen in nondental tissues, and these specializations are essential for successful development and maintenance of the tooth.

Animals↗
PubMed2001

Oligodendroglial cell death with DNA fragmentation in the white matter under chronic cerebral hypoperfusion: comparison between normotensive and spontaneously hypertensive rats.

We investigated the neuropathological and biochemical changes in the white matter of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) after bilateral carotid artery ligation (BCAL). One week after BCAL, both WKY and SHR showed white matter rarefaction and vacuolation with reduced oligodendrocytes, but there was no difference between WKY and SHR. On the other hand, vacuoles formed by oligodendroglial cell death were increased significantly from 2 to 4 weeks in the optic tract and fimbria fornix of hypoperfused SHR. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP in situ nick end labeling (TUNEL)-positive cells and lectin-positive microglia increased in number and intensities of staining more markedly in SHR than in WKY. In situ cell death detection ELISA supported these results quantitatively. RT-PCR represented the expression of TNF-alpha, TNF receptor 1 (p55), caspase-2 (Ich-1) and -3 (CPP32) mRNAs in both WKY and SHR brains after BCAL. Immunohistochemical analyses revealed that TNF-alpha, TNF receptor 1 (p55), Ich-1 and CPP32 immunoreactive cells could also be detected in the white matter regions of hypoperfused SHR. These results suggested that local production of TNF-alpha by the activated microglia might selectively induce oligodendroglial cell death through the death domain-containing TNF receptor 1 (p55), caspase-2 or -3 activation, resulting in white matter changes as a primary pathological feature.

Animals↗