Biomedical subjects

T Tada

Publications and source records attributed to T Tada.

At least 127 records · Page 7Linked to original sources

PubMed1998

Lymphoma arising in mucosa-associated lymphoid tissue of the duodenal bulb.

We report a case of low-grade B-cell lymphoma of the duodenal bulb arising from mucosa-associated lymphoid tissue. A barium swallow and an endoscopic examination showed multiple elevated, irregularly contoured lesions limited to the duodenal bulb. Endoscopic biopsy specimens were highly suggestive of non-Hodgkin's lymphoma. The resected specimen showed a gyriform mucosal elevation measuring 3 x 2cm in extent, with multiple small polypoid elevations scattered around it. Histologically, the small lymphocytes constituting the tumor infiltrated the duodenal mucosa and submucosa. The neoplastic centrocyte-like cells tended to grow around reactive lymphoid follicles and to invade epithelial structures, forming characteristic lymphoepithelial lesions. Monoclonal proliferation of the lymphoid tissue was demonstrated by the polymerase chain reaction method. The histologic appearance and the demonstration of monoclonality fulfilled the criteria for malignant lymphoma arising from mucosa-associated lymphoid tissue, which is extremely rare in the duodenum.

Duodenal Neoplasms↗

PubMed1998

Altered expression of membrane inhibitors of complement in human gastric epithelium during Helicobacter-associated gastritis.

AIMS: Membrane inhibitors of complement are thought to protect bystander cells from complement mediated damage. Expression of these proteins is enhanced in the colonic mucosa of patients with ulcerative colitis. Our aim was to investigate the regulation of complement activity in Helicobacter-associated chronic gastritis. METHODS AND RESULTS: We immunohistochemically assayed expression of three membrane inhibitors of complement, decay accelerating factor (DAF; CD55), 20 kDa homologous restriction factor (HRF20; CD59) and membrane cofactor protein (MCP; CD46), in 55 biopsy specimens of the human gastric mucosa. DAF, expressed in 33 (60%) of biopsy specimens, and HRF20, expressed in 45 (82%) of the samples, were located mainly on the apical surface of the epithelial cells, whereas MCP, expressed in 48 (87%) of the biopsies, was found on the basolateral surface. We found strong correlation between expression of DAF on gastric mucosal epithelium and the severity of mucosal infiltration of neutrophils (rs = 0.875, P < 0.0001) and mononuclear cells (rs = 0.773, P < 0.0001). No significant correlation was observed between HRF20 expression and neutrophil or mononuclear cell infiltration, while there was a weak negative correlation between MCP expression and these cellular infiltrations. When we assayed immunostaining of Helicobacter pylori (H. pylori) in these biopsy specimens, strong correlation with the degree of neutrophil (P < 0.0001) and mononuclear cell (P < 0.0001) infiltration were observed. The expression of DAF and H. pylori infection in these biopsies were also significantly (P < 0.0001) correlated. No correlation between HRF20 expression and H. pylori infection was observed, but we did find a significant negative correlation (P < 0.005) between the expression of MCP and H. pylori infection. CONCLUSIONS: Our results, demonstrating altered expression of membrane inhibitors of complement in gastric mucosa during inflammation and/or H. pylori infection, suggest that complement may significantly participate in the pathology of gastric inflammation. Moreover, DAF and MCP may play an important role in the regulation of complement activation in the alimentary tract.

Antigens, CD↗

PubMed1998

An allogeneic microenvironment influences the phenotype of intermediate T-cell receptor cells expanding in MRL-lpr/lpr mice.

MRL-lpr/lpr (lpr) mice fall victim to autoimmune disease owing to a lymphoproliferative disorder mainly of double-negative (DN) CD4- CD8- alpha beta T cells expressing a low density of interleukin-2 receptor beta-chain (IL-2R beta). It was previously revealed that the lpr gene is a defective Fas gene, into which an early transposon (ETn) of retrovirus is transfected. As a result of the failure of apoptosis, intermediate T-cell receptor (TCR) cells (i.e. TCRint cells) with DN phenotype abnormally accumulate in the periphery of lpr mice. We investigated herein how these TCRint cells are selected in terms of CD4, CD8 and TCR in lpr mice. When a whole fraction of mononuclear cells (MNC) in various immune organs of lpr mice was injected into scid mice (allogeneic circumstance), CD8+ TCRint cells mainly expanded. They had a high density of IL-2R beta. This was true when bone marrow cells of lpr mice were injected into scid mice. On the other hand, when MNC of the spleen and bone marrow in lpr mice were injected into irradiated (9 Gy) lpr mice (syngeneic circumstance), the major expanding cells were DN TCRint cells expressing a low density of IL-2R beta. A cell-sorting experiment for purified fractions demonstrated that only CD8- cells reconstituted TCRint cells in scid mice. Namely, DN CD4- CD8- cells as well as CD4+ cells which once acquired the mature phenotype, no longer switched their phenotype. These results suggest that the phenotype of TCRint cells is influenced by the surrounding microenvironment.

Animals↗

PubMed1998

Regulation of T cell autoreactivity to MHC class II by controlling CD80 (B7-1) expression on B cells.

Regulatory mechanisms of T cell autoreactivity to MHC class II molecules were studied in transgenic (Tg) mice with auto-I-Ak-reactive TCR alphabeta transgenes (designated as MS Tg mice). Our previous study revealed that the T cell tolerance established in autoreactive MS Tg mice was not due to either clonal deletion in the thymus, anergy or an active suppression in the periphery. We proposed a novel form of self tolerance termed 'clonal insufficiency', where autoreactive T cells were conditionally rendered unresponsiveness to self antigen in vivo, although retaining full potential reactivity in in vitro conditions. Here, we investigated the role of co-stimulatory molecules for the induction of self tolerance with 'clonal insufficiency'. MS Tg mice were mated with CD80 (B7-1) Tg mice in which B cells exclusively and constitutively expressed CD80 molecules. Both MS Tg mice and CD80 Tg mice by themselves showed no evidence for activation of T cells and B cells, whereas MS x CD80 double-Tg mice with a H-2k background revealed an abnormal increase in the number of splenocytes and in the expression of activation markers (CD69 and CD25) on CD4 T cells in the spleen. These results indicated that the self tolerance established in MS Tg mice involved a down-regulation of CD80 molecules on B cells in vivo, resulting in a failure of sufficient T-B interactions. In addition, the serum concentration of IL-10, one of the down-regulators of CD80 expression, was found to be increased significantly in MS Tg mice. The autoreactivity of MS Tg T cells detected in vitro was significantly blocked by recombinant IL-10. Thus, IL-10-mediated down-regulation of CD80 on B cells was suggested to be involved in the clonal insufficiency in MS Tg mice in vivo.

Animals↗

PubMed1998

Requirement for p56(lck) tyrosine kinase activation in Th subset differentiation.

The lymphocyte-specific protein tyrosine kinase p56(lck) (Lck) is well documented with regard to its role in regulating T cell activation and thymocyte development through delivery of signals via the mature alphabeta TCR as well as the pre-TCR. Little is known, however, about the role of Lck in Th cell subset differentiation in the periphery. Here, we assess the requirement for tyrosine kinase activation of Lck in Th1 and Th2 cell differentiation by using a dominant-negative Lck (DLGKR) transgenic (Tg) mice under the control of a lck distal promoter that directs high expression in mature T cells, in which splenic CD4 T cells developed normally. This Tg mouse provides a good experimental model system to investigate the roles of Lck in mature T cell function in vivo. We show that the catalytically inactive Lck protein at about twice-normal concentrations inhibits Th2 subset differentiation in vivo and in vitro, whilst leaving the maturation of the other T cell subset, Th1, intact. These data indicate a requirement for Lck activity in Th2 cell differentiation, and a differential dependence for Lck activity between Th2 and Th1 cell differentiation.

Amino Acid Sequence↗

PubMed1998

Participation of NK1.1+ T cells in the rejection of lpr alphabetaT cells when bone marrow cells of lpr mice are transplanted into B6 mice.

When C57BL/6 (B6) mice were irradiated (9 Gy) and received bone marrow (BM) cells of B6-lpr/lpr mouse origin (i.e., lpr-->B6), all mice died within 6 days. In the irradiated B6 mice, radioresistant CD3 IL-2Rbeta+ NK cells and IL-2Rbeta+ CD3int cells (i.e., CD3int cells of extrathymic origin) remained, especially in the liver. There were two subsets, NK1.1+ and NK1.1-, among the IL-2Rbeta+ CD3int cells. However, the NK1.1+ subset (i.e., NK1.1- T cells) was much more radioresistant, and the majority of CD3int cells belonged to this subset in irradiated mice. The expansion of lymphocytes from injected BM cells did not occur in the irradiated B6 mice. However, such expansion did take place in irradiated B6-lpr/lpr mice injected with both BM cells of B6-lpr/lpr and B6 origin. As a result, the mice subjected to BM cells survived. Irradiated B6 mice were treated in vivo with anti-NK1.1 mAb or anti-asialoGM1 antibody to eliminate NK cells alone or both NK cells and NK1.1+ T cells. When irradiated B6 mice were pretreated with anti-NK1.1 mAb, the mice could survive. These results suggest that intact NK1.1+ T cells of extrathymic origin may recognize abnormal BM cells with the lpr gene and inhibit the expansion of lymphocytes, including abnormal double-negative CD4 8 cells, in B6-lpr/lpr mice. To inhibit the expansion of lymphocytes, mechanisms other than Fas ligand/Fas molecules on extrathymic T cells may be responsible.

Animals↗

PubMed1998

Lung cancer: intermittent irradiation synchronized with respiratory motion--results of a pilot study.

PURPOSE: To test the feasibility of a system for intermittent irradiation synchronized with respiratory motion in a clinical setting. MATERIALS AND METHODS: A newly developed gate pulse controller that starts and stops irradiation at a chosen phase of the respiratory cycle by controlling a linear accelerator was used in six patients with lung cancer. A laser displacement sensor was used for the detection of respiratory motion. Three patients underwent radiation therapy during the cycles between 50% expiration and 50% inspiration (step 1), and three patients underwent radiation therapy during the cycles between 70% expiration and 30% inspiration (step 2). RESULTS: The system functioned well; irradiation was verified with portal verification radiography in all six patients. The range of the tumor position during synchronized irradiation was detectable with fast portal localization radiography. The treatment times for steps 1 and 2 were 1.38-1.71 and 2.03-2.18 times longer, respectively, than those for conventional irradiation. CONCLUSION: Synchronized irradiation with the authors' system allowed convenient and reliable reduction of the target volume. Further study is needed to standardize the system for clinical use.

Clinical Protocols↗

PubMed1998

Limited-stage small cell lung cancer: local failure after chemotherapy and radiation therapy.

PURPOSE: To evaluate radiation therapy regimens for improvement in local control in patients with limited-stage small cell lung cancer. MATERIALS AND METHODS: Radical radiation therapy results in 117 patients with limited-stage small cell lung cancer were retrospectively reviewed. The protocols in 90 patients were 40 Gy in 20 fractions (n = 28), 50 Gy in 25 fractions (n = 32), and 45 Gy in 30 fractions (accelerated hyperfractionation, n = 30). The other 27 patients received thoracic irradiation (dose range, 20-60 Gy; median dose, 54 Gy). All patients underwent systemic chemotherapy. RESULTS: The 5-year Kaplan-Meier survival rates in the patients with N0, N1, N2, and N3 disease were 26%, 34%, 18%, and 0%, respectively; the rates of in-field relapse were 25%, 36%, 26%, and 25%, respectively; and the rates of marginal relapse were 0%, 9%, 15%, and 29%, respectively. In 56% of patients with marginal relapse, the relapse site was at the upper margin. The 4-year in-field control rates for the patients who underwent 40, 50, and 45 Gy were 51%, 70%, and 56%, respectively. CONCLUSION: Patients with N3 limited-stage small cell lung cancer should undergo a separate protocol, and the upper margin should be extended in patients with N2 or N3 disease.

Adult↗

PubMed1998

Combination of irinotecan and etoposide for treatment of refractory or relapsed small-cell lung cancer.

PURPOSE: To determine the response rate, survival, and toxicity of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, in refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Twenty-five patients with refractory or relapsed SCLC were entered onto the trial. All 25 patients had been pretreated with some form of cisplatin-based combination chemotherapy and had also received previous etoposide- or anthracyclinecontaining chemotherapy. The median time off chemotherapy was 6.7 months (range, 0.9 to 23.5). Patients were treated at 4-week intervals using CPT-11 (a starting dose of 70 mg/m2 intravenously on days 1, 8, and 15) plus etoposide (80 mg/m2 intravenously on days 1 to 3), with a subsequent dose based on toxicity. In addition, recombinant human granulocyte colony-stimulating factor (rhG-CSF; 2 microg/kg/d) was given from day 4 to day 21, except on the days of CPT-11 administration. RESULTS: All patients were assessable for toxicity and survival. Twenty-four patients were assessable for response. There were 14 partial responses (PRs) and three complete responses (CRs), for an overall response rate of 71% (95% confidence interval, 53% to 89%). The median response duration was 4.6 months. Median survival was 271 days. Major toxicities were myelosuppression (predominantly leukopenia) and diarrhea. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 56% and 20% of patients, respectively. Grade 3 to 4 diarrhea was observed in 4%. There was one treatment-related death due to severe myelosuppression. CONCLUSION: A combination of CPT-11 and etoposide with rhG-CSF support is an active therapy against refractory or relapsed SCLC and deserves to be studied more extensively in a phase III trial.

Adult↗

PubMed1998

The effect of Kampo formulae on bone resorption in vitro and in vivo. I. Active constituents of Tsu-kan-gan.

Four water extracts of Kampo formulae (Yi-kkan-sen, Dai-ho-in-gan, Ni-chi-gan, Tsu-kan-gan) were screened for their inhibitory activities on bone resorption induced by parathyroid hormone (PTH) in organ culture using neonatal mouse parietal bones. Among the Kampo formulae, Tsu-kan-gan (TKG) showed the most potent inhibitory activity. We further fractionated the TKG water extract by monitoring the inhibitory activity on bone resorption stimulated by PTH in vitro. The MeOH fraction of the water extract inhibited PTH-stimulated bone resorption, and its inhibitory activity was more potent than those of other fractions. The MeOH fraction was then subjected to Sephadex LH-20 column chromatography to give fractions I, II and III, which were examined for bone resorption activity. Fraction I inhibited PTH-stimulated bone resorption, and its inhibitory activity was more potent than those of the other fractions. Upon oral administration of the three fractions (100 mg/kg/d) to ovariectomized (OVX) mice, fractions I and III prevented the decrease of bone mineral density (BMD) of the lumbar vertebra. Eleven compounds isolated from the MeOH fraction were examined for their inhibitory effect on PTH-stimulated bone resorption. Among them, berberine (1), syringin (3), limonin (4) and mangiferin (10) showed a significant inhibitory effect on bone resorption. In the formation assay of osteoclast-like cells, these compounds decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs). The inhibitory effect of TKG on bone resorption may be at least partly due to the inhibitory action of these compounds.

Animals↗

PubMed1998

Antiosteoporotic activity of the stems of Sambucus sieboldiana.

We previously found that a methanolic extract of the stems of Sambucus sieboldiana inhibited bone resorption in organ culture. In this study, we further fractionated the methanol extract guided by the activity towards bone resorption stimulated by parathyroid hormone (PTH) in vitro. The ethyl acetate fraction (EtOAc Fr.) of the methanolic extract inhibited PTH-stimulated bone resorption of neonatal mouse bones, and the inhibitory activity was more potent than those of other fractions. Oral administration of the EtOAc Fr. (50 and 100 mg/kg/d) to ovariectomized (OVX) rat prevented the decrease in bone mineral density (BMD) of the lumbar (L2-4) vertebra, indicating that the EtOAc Fr. is effective in vivo. Furthermore, the EtOAc Fr. (50, 100 and 150 mg/kg/d) decreased the serum calcium level elevated in low calcium dietary rats. The phenolic constituents of the EtOAc fraction were examined for their inhibitory effect on bone resorption stimulated by PTH in neonatal mouse bone. Among them, vanillic acid, vanillin and coniferyl alcohol showed significant inhibitory effects on bone resorption. Of the compounds examined, vanillic acid was found to have a significant inhibitory effect on the decrease of BMD in OVX mice. Therefore, the EtOAc Fr. of S. sieboldiana showed a suppressive effect on bone resorption in vitro and in vivo. In addition, the inhibitory effects of the EtOAc Fr. on bone resorption may be at least partly due to the inhibitory action of vanillic acid.

Acetates↗

PubMed1998

Suppression by water extracts of Sophora plants of sucrose-induced hyperglycemia in rats and inhibition of intestinal disaccharidases in vitro.

Partially purified hot-water extracts of the roots of plants of the Sophora family suppressed the increase in blood glucose concentration of rats in the oral sugar tolerance test. The extracts also inhibited rat intestinal sucrase and maltase. The most potent sample was about 15 times more active than catechin, a positive control, in these experiments.

Animals↗

PubMed1998

Ultramicroscopic structures of the leptomeninx of mice with communicating hydrocephalus induced by human recombinant transforming growth factor-beta 1.

An experimental model of communicating hydrocephalus was developed based on intrathecal injection of human recombinant transforming growth factor-beta 1 (hrTGF-beta 1) in the mouse. To clarify the mechanism of this hydrocephalus model, the ultrastructure of the leptomeninx in the process of ventricular dilation was examined in C57/BL6 mice injected intrathecally with 60 ng of hrTGF-beta 1. The leptomeninx was examined at various periods after injection by light and electron microscopy. Immunostaining for fibroblasts and macrophages was also performed. Leptomeninx within a week after injection showed that the thin cytoplasmic processes of leptomeningeal cells formed a laminated structure with a meshwork, which was almost the same as the controls. In the second week, many cells with a round nucleus appeared in the leptomeninx. Immunohistochemically, these cells were positive for anti-fibroblast antibody and negative for anti-Mac-1 and anti-macrophage BM-8 antibodies. Three weeks later, the laminated structure was disrupted and abundant deposition of collagen fibers was found in the inter-cellular space of the leptomeninx. Such inter-meningeal fibrosis would disturb cerebrospinal fluid flow in the mouse leptomeninx and cause slowly progressive ventricular dilation.

Animals↗

PubMed1998

Aneurysm surgery in Asia--Japanese situation.

This report is based on the results of the questionnaires conducted for the Japan Stroke Surgery Meeting 1996 (President: S. Kobayashi). The questionnaires were sent to all neurosurgical training institutions approved by The Japan Neurosurgical Society, numbering 959. The response rate was 54.2% (520 institutions). All statistics dealt with cases from January 1995 to December 1995. The total number of aneurysm surgery performed was 13,166. The average operative case number per institution during the year was 25. About 20% of the institutions exceeded 35 cases. Of all operative cases, 76.3% were ruptured aneurysms and 23.7% were nonruptured. Giant aneurysms were 2.9%; dissecting aneurysms 2.4%. Surgical procedures performed were clipping in 90.3%, wrapping in 5.2%, proximal ligation 1.6%, and bypass in 0.7%. Intravascular surgery was performed for 2.3% of the cases. Sugita clips were mainly used in 80.5% of the institutions, Yasargil clips in 6.6%, and both in 12.9%. For anterior communicating artery aneurysms pterional approach was mainly used in 81.0% of the institutions, interhemispheric in 7.2%, and both in 11.7%. For basilar terminal aneurysms, pterional approach was mainly used in 88.3% of the institutions, subtemporal approach in 6.6%, and both in 5.1%. The nonoperative cases included 24.9% of the ruptured aneurysms, 31.7% of the unruptured aneurysms, 38.4% of the giant aneurysms, and 52.1% of the dissecting aneurysms. The above statistics suggest that aneurysms are treated in Japan in most training institutions and that open surgical treatment is still the main procedure of choice.

Humans↗

PubMed1998

Structure and expression of activin genes in rainbow trout.

Activins are dimeric members of the transforming growth factor-beta (TGF-beta) superfamily. By using the polymerase chain reaction (PCR), we have cloned and sequenced activin beta A and beta B genes encoding the mature region of the peptides from the rainbow trout genomic DNA. Two forms of beta A and a single form of beta B-subunits were found. There is high identity with mammalian counterparts; the two rainbow trout beta A-subunits have more than 75% nucleotide sequence identity with the human beta A-subunit, and the beta B-subunit had 82% sequence identity with the human beta B-subunit. Expression of rainbow trout activin genes was examined by reverse transcription-PCR (RT-PCR). The major expression tissue of rainbow trout activin was ovary and brain at the messenger RNA level, and the major expression subunit of rainbow trout activin was the beta B subunit.

Activins↗

PubMed1998

Differentiative potential of a mouse parthenogenetic embryonic stem cell line revealed by embryoid body formation in vitro.

The in vitro differentiative potential of mouse parthenogenetic (PG) embryonic stem (PGES) cells were investigated in the formation of embryoid bodies (EBs). EBs derived from PGES cells retarded in growth and showed restricted differentiation compared to their fertilized counterpart. In chimeric EBs from the aggregation of PGES and fertilized ES cells, morphological examination revealed that PGES cells were reduced in their population and distributed in endodermal layer as culture periods proceeded. These findings were comparable to those in aggregation chimeras of fertilized and PG embryos, and suggest that the differentiation of PGES cells in vitro is restricted in the formation of EBs.

Animals↗

PubMed1998

Trisomy 8 does not affect differentiative potential in a murine parthenogenetic embryonic stem cell line.

Murine parthenogenetic embryonic stem (ES) cell lines expressing lac Z reporter gene were isolated after co-transfection with lac Z reporter gene (pENL) and neo gene (pSTneo) to TMA-48P cell line of 129/Sv origin. Karyotype analyses showed that all of four transfected cell lines examined contained 41 chromosomes with trisomy 8. Bacterial neo transgene required for G418 selection were integrated into several chromosomes including chromosome 8. Histological studies of teratomas formed in syngenic mice and embryoid bodies grown in vitro showed that the differentiative potential remained almost identical in chromosomally normal parental cell line and its derivative cell lines trisomic for chromosome 8.

Animals↗

PubMed1998

Effects of prefixation and fixation times on apoptosis detection by in situ end-labeling of fragmented DNA.

OBJECTIVE: Apoptosis is considered to play an important role in the pathogenesis and progression of neoplasia. An in situ 3'-end DNA labeling (TUNEL) method was recently developed and has been widely used to identify apoptotic cells in tissue sections. However, sometimes the TUNEL method labels many more cells than expected. We investigated the effects of prefixation time and fixation time on the apoptotic index detected by this method. MATERIALS AND METHODS: Using the spleen and thymus of rats, the effects of prefixation time (0, 1, 2, 4, 6, 12, 24, 48, and 72 hours) at 4 degrees C and fixation time (6, 12, 24, 48, 72, and 96 hours; 1, 2, and 3 weeks) on the apoptotic index were examined by the TUNEL method. Agarose gel electrophoresis of extracted DNA from the specimens of each prefixation time was also performed. RESULTS: In comparison with control tissue (no prefixation time), which showed scattered positive cells with distinct staining restricted to the nucleus, the splenic tissue unfixed for 2 hours or more and the thymic tissue unfixed for 4 hours or more showed cytoplasmic staining in the positive cells. Moreover, as the prefixation time was prolonged, the number of positive cells gradually increased. Agarose gel analysis of DNA extracted from tissue sections left unfixed longer than 24 hours showed a ladder pattern consisting of multiples of about 200 base pairs. CONCLUSIONS: Two hours was the limit of prefixation time for the precise identification of apoptosis by the TUNEL method. The false-positive cells in tissue sections left unfixed for longer time intervals may have been due to internucleosomal DNA cleavage following necrosis. In contrast, the length of fixation time in buffered formalin seemed to have no effect on the results obtained by this method.

Animals↗