Biomedical subjects

O Taguchi

Publications and source records attributed to O Taguchi.

At least 37 records · Page 2Linked to original sources

PubMed2000

Autologous dendritic cells or cells expressing both B7-1 and MUC1 can rescue tumor-specific cytotoxic T lymphocytes from MUC1-mediated apoptotic cell death.

We attempted to induce MUC1-specific cytotoxic T lymphocytes (CTLs) by mixed-lymphocyte tumor cell culture (MLTC) using two allogeneic MUC1-positive cancer cell lines, T-47D and MCF7. The induced CTLs exhibited MUC1-specific cytotoxicity 16 days after the initial stimulation. However, these CTLs underwent apoptotic death within 16 days. To examine whether the B7-1 molecule is required for the expansion of the responder cells, a B7-1(+)/MUC1(-) cell line was transfected with MUC1 cDNA, and the resulting transfectant was employed as a stimulator in an autologous MLTC. The CTLs exhibited MUC1 specificity but also continued to propagate. In parallel, autologous dendritic cells (DCs) were added to an MLTC containing peripheral blood lymphocytes (PBLs) and the allogeneic MUC1-positive stimulators. The CTLs demonstrated MUC1 specificity and their number increased. This suggests that the B7-1 molecule is required for rescuing CTLs from MUC1-mediated apoptotic death, but not for the induction of MUC1-specific responsiveness. This strategy to obtain the CTLs efficiently may be useful for adoptive immunotherapy against cancer.

Antigen Presentation↗

PubMed1999

A binding site for the transcription factor Grainyhead/Nuclear transcription factor-1 contributes to regulation of the Drosophila proliferating cell nuclear antigen gene promoter.

The Drosophila proliferating cell nuclear antigen promoter contains multiple transcriptional regulatory elements, including upstream regulatory element (URE), DNA replication-related element, E2F recognition sites, and three common regulatory factor for DNA replication and DNA replication-related element-binding factor genes recognition sites. In nuclear extracts of Drosophila embryos, we detected a protein factor, the URE-binding factor (UREF), that recognizes the nucleotide sequence 5'-AAACCAGTTGGCA located within URE. Analyses in Drosophila Kc cells and transgenic flies revealed that the UREF-binding site plays an important role in promoter activity both in cultured cells and in living flies. A yeast one-hybrid screen using URE as a bait allowed isolation of a cDNA encoding a transcription factor, Grainyhead/nuclear transcription factor-1 (GRH/NTF-1). The nucleotide sequence required for binding to GRH was indistinguishable from that for UREF detected in embryo nuclear extracts. Furthermore, a specific antibody to GRH reacted with UREF in embryo nuclear extracts. From these results we conclude that GRH is identical to UREF. Although GRH has been thought to be involved in regulation of differentiation-related genes, this study demonstrates, for the first time, involvement of a GRH-binding site in regulation of the DNA replication-related proliferating cell nuclear antigen gene.

Animals↗

PubMed1999

Type I collagen metabolites as tumor markers in patients with lung carcinoma.

BACKGROUND: Components of the extracellular matrix play a fundamental role in the process of tumor invasion. The objective of this study was to evaluate the value of Type I collagen metabolites as tumor markers in patients with lung carcinoma. METHODS: In this study, the serum concentrations of the cross-linked carboxyterminal telopeptide of Type I collagen (ICTP) and the aminoterminal propeptide of Type I collagen (PINP) were measured in 59 consecutive patients with lung carcinoma. The blood concentrations of neuron-specific enolase (NSE), carcinoembryogenic antigen (CEA), sialyl Le-1 antigen (SLX), squamous cell carcinoma antigen (SCC), and D-dimer were also evaluated. Data obtained on 18 age-matched healthy subjects and 12 age-matched patients with benign lung disease were available for comparison. RESULTS: The serum concentrations of PINP were significantly higher in patients with lung carcinoma than in age-matched controls. Prechemotherapy values of PINP and ICTP were significantly increased in patients who did not respond to chemotherapy compared with those who did respond. PINP and ICTP were significantly correlated with clinical stage, extent of bone metastasis, survival time, and D-dimer. PINP was also significantly correlated with tumor size. ICTP was significantly correlated with CEA, SLX, SCC, and NSE. PINP also tended to correlate with these tumor-associated glycoproteins. PINP had a better receiver operating characteristic curve than ICTP. The specificity of PINP (79%) for the diagnosis of bone metastasis was superior to that of ICTP (58%). CONCLUSIONS: The results of this study showed that, in addition to the important information that ICTP and PINP provide about the tumor cell-extracellular matrix interaction, they appear to be of great value as adjunct tools for the diagnosis of bone metastasis and as markers of the clinical response to therapy, clinical progression, and prognosis in lung carcinoma patients. However, more studies must be conducted to evaluate further the utility of these markers before their application in clinical practice.

Adult↗

PubMed1999

Protective effects of 5,6,7,8-tetrahydroneopterin against X-ray radiation injury in mice.

The protective effects of 5,6,7,8-tetrahydroneopterin (NH4) against radiation injury in mice were studied. (C57BL/6xA/J)F1 (B6A) mice received a single whole-body irradiation dose of 200, 400, 700 or 800 cGy of X-rays. NH4 (30 mg/kg body weight) or phosphate-buffered saline (PBS) was injected intraperitoneally into irradiated mice 10 min before and after the irradiation and again after 6 h. All mice which received the 800 cGy radiation+PBS died between 8 and 11 days after the treatment. In contrast, those which also received NH4 demonstrated a significantly prolonged survival time and 40% lived more than 5 months. Total numbers of thymocytes and spleen cells on day 5 post-irradiation were dramatically reduced in line with the radiation dose. The survival was significantly enhanced by NH4 in treated mice. The proliferation of spleen cells in mice stimulated by concanavalin A (Con A) or lipopolysaccharide (LPS) was also greater in NH4 treated mice. The immune response of survivors 5 months after 800 cGy+NH4 treatments, against Con A, LPS, allogenic mouse, and sheep red blood cells had essentially recovered to the levels of normal mice. These results indicate that NH4 had an important role in modifying radiation injury.

Animals↗

PubMed1999

Autoimmune diseases developed in athymic nude mice grafted with embryonic thymus of xenogeneic origin.

Reconstitution of T cell functions in athymic BALB / c nude mice was investigated after transplantation of embryonic thymus grafts under the renal capsule (TG nude mice). Thymi were obtained from mice, rats, rabbits, hamsters, guinea pigs, swine and cows. All of the grafted thymi grew and formed proper thymic structures with host CD90(+) cells. The TCRalpha beta expression pattern of the lymphocytes in the grafted thymi was quite similar to that of normal mouse thymocytes. Sufficient CD4(+) populations were observed in the peripheral lymphoid organs of all groups of TG nude mice. Plaque-forming cell assay revealed that the TG nude mice had acquired considerable helper T cell functions. Histological and serological studies, however, showed multiple organ-localized inflammatory diseases in TG nude mice of all xenogeneic thymus groups, but not with syngeneic or allogeneic thymi. The organs affected were the thyroid, the lacrimal, submandibular and sublingual glands, the eyes, stomach and ovaries. The incidence of lesions was variable depending on the species of origin of the grafted thymus. Lesions from TG nude mice were successfully transferred into naive nude mice by host CD4(+) cells. These results together suggested that the microenvironment of grafted thymi, even if xenogeneic, is able to educate host T cell precursors. However, this reconstitution of functions does not always induce tolerance to certain autoantigens, resulting in development of multiple autoimmune lesions.

Animals↗

PubMed1999

Thrombin in the airways of asthmatic patients.

The mechanism of airway remodeling in asthmatic patients is poorly understood. Thrombin is a multifunctional protease that, in addition to its critical role in thrombotic processes, has also been described as inducing cellular and molecular events relevant to tissue remodeling. The present investigation was undertaken to evaluate the activity of thrombin in the sputum of asthmatic patients and its potential role in airway remodeling. The study population comprised 8 healthy subjects and 14 stable patients with bronchial asthma. The concentrations of thrombin, thrombin-antithrombin complex (TAT), and tissue factor were measured in the sputum of all subjects. The concentrations of thrombin (p = 0. 007), TAT (p = 0.01), and tissue factor (p = 0.02) in sputum were significantly higher in asthmatic patients than in healthy controls. The proliferative effects that sputum from asthmatic patients (p = 0. 01) and thrombin (p = 0.03) have on cultured human smooth muscle cells was inhibited significantly in the presence of recombinant hirudin, a specific thrombin inhibitor. Significant statistical correlation was observed between the degree of bronchial responsiveness and the sputum concentrations of thrombin (r = -0.8; p = 0.02) and TAT (r = -0.9; p = 0.01). The results of this study showed that increased thrombin generation occurs in the airway of patients with asthma and that it may play a role in the pathogenesis of airway remodeling. Further studies should be carried out to assess whether these findings are also observed in other airway diseases.

Antithrombin III↗

PubMed1999

Syndecan-4 expression is associated with follicular atresia in mouse ovary.

Ovarian granulosa cells synthesize heparan sulfate proteoglycans (HSPGs), that have anticoagulant properties. Moreover, HSPGs greatly increase in the granulosa cells during follicular atresia. However, the species of ovarian HSPGs have not yet been identified. Syndecan-4 (ryudocan, amphiglycan) is a membrane-spanning HSPG and a member of the syndecan family. Herein, we demonstrate that syndecan-4 is expressed in the granulosa cells of type 4-5b follicles and, most intensely, in those of the atretic follicles in the mouse ovary, as revealed by in situ hybridization. There is no relationship between syndecan-4 expression and age or sexual cycle stage. Compared with syndecan-4 expression, syndecan-1 and -3 are expressed more abundantly in postovulatory follicles and the corpora lutea, but less in the type 4-5b follicles and much less in the atretic follicles. Immunohistochemistry also demonstrates syndecan-4 expression in atretic follicles with apoptosis. The present study has revealed the distinct modes of expression of the syndecan family members, and the association of syndecan-4 expression and apoptosis in ovarian atretic follicles.

Animals↗

PubMed1999

Successful transfer of localized autoimmunity with positively selected CD4+ cells to scid mice lacking functional B cells.

T-cell function of athymic BALB/c-nu/nu (nude) mice can be corrected by implantation of a embryonic rat thymus graft (TG) under the renal capsule (TG nude mice). However, multiple organ-localized autoimmune diseases, such as oophoritis, Sjögren's syndrome like disease and gastritis, develop spontaneously in TG nude mice. Transfer of spleen cells from TG nude mice with such diseases leads to multiple localized autoimmune lesions with appearance of the corresponding autoantibodies in the recipient C.B-17-scid (SCID) mice. In the present study, removal of CD90+ or CD4+, but not CD8+ cells eliminated the transfer activity. Positively selected CD4+ cells proved capable of inducing lesions without the appearance of organ-specific autoantibodies, although the grade of lesions was lower than that in recipient mice that received untreated or CD8-depleted spleen cells. Target organs demonstrating CD4+ cell infiltration, generally expressed major histocompatibility complex (MHC) class II antigen (Ia) on their parenchymal cells. Injection of sera from TG nude mice with autoantibodies to SCID mice did not induce any pathogenic features in the autoantibody-target organs, although deposition of immunoglobulins in the corresponding target organs was observed. In such cases, no Ia antigens were expressed on the parenchymal cells. The data thus indicate that effector CD4+ cells can induce autoimmunity without B-cell help but that cooperation with functional B cells induces more severe tissue damage.

Animals↗

PubMed1999

[Pulmonary involvement in ulcerative colitis].

Pulmonary involvement has been described to be a very rare complication of inflammatory bowel disease. However, recent studies reported the occurrence of airway diseases (bronchiectasis) or interstitial lung diseases (BOOP) in patients with this disorder. Pulmonary involvement in inflammatory bowel disease is responsive to steroid therapy. Because asymptomatic cases of inflammatory bowel disease with abnormal pulmonary function test has also been reported, the occurrence of pulmonary complications must be evaluated in these patients even in the absence of clinical symptoms.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

A null mutation in basigin, an immunoglobulin superfamily member, indicates its important roles in peri-implantation development and spermatogenesis.

Basigin is a highly glycosylated transmembrane protein with two immunoglobulin-like domains. We generated mutant mice lacking the basigin gene (Bsg) by gene targeting. Bsg (-/-) embryos developed normally during preimplantation stages. However, the majority of Bsg (-/-) embryos died around the time of implantation. At this time, basigin mRNA was strongly expressed in the trophectoderm, embryo proper, and uterine endometrium of Bsg (+/+) mice. These results suggest that basigin is involved in intercellular recognition during implantation. Embryos which survived the critical period yielded Bsg (-/-) mutant mice. Half of the mutant mice died before 1 month after birth, due to interstitial pneumonia. The surviving adult mutant mice were small and sterile. Spermatogenesis was arrested in the mutant mice. Most of the spermatocytes in the Bsg (-/-) mouse were arrested and degenerated at the metaphase of the first meiosis, and only a small number differentiated to step 1 spermatids. In the female mutants, the ovaries and genital tract were morphologically normal, and the defect was probably in the capability of implantation of the uterus. In conclusion, basigin is an important cell-surface molecule involved in early embryogenesis and reproduction.

Animals↗

PubMed1998

Suppression of spontaneous uveoretinitis development by non-immunopathogenic peptide immunization.

BALB/c nude mice which are grafted with thymus tissue from fetal F344 rats beneath the renal capsule (hereafter referred to as TG nude mice) spontaneously develop uveoretinitis as well as other organ-localized autoimmune diseases. Active immunization with an interphotoreceptor retinoid-binding protein (IRBP)-derived peptide, amino acids 518-529 (P518-529), induced rapid development and high incidence of uveoretinitis, whereas immunization with another amino acid fragment, 1182-1194 (P1182-1194), inhibited the disease process. P1182-1194- or P518-529-specific T cell lines were established from TG nude mice. Although both were of CD4+ type, P518-529-specific T cells expressed Vbeta8 TCR while Vbeta6 expression was evident in the P1182-1194-specific cells. P518-529-specific T cells produced IL-2 and IFN-gamma, but not IL-4 or IL-10, whereas P1182-1194-specific T cells produced IL-4 and IL-10, but not IL-2 or IFN-gamma Adoptive transfer of these peptide-specific T cells into naive BALB/c nude mice resulted in development of uveoretinitis only in the P518-529 case. Furthermore, mice receiving both T cell types simultaneously did not exhibit uveoretinitis. The results indicate that the amino acid fragment of IRBP, P518-529, is uveitogenic and immunogenic in TG nude mice and induces Th1-type T cells related to uveoretinitis, whereas the amino acid fragment 1182-1194 is immunogenic but not uveitogenic, inducing Th2-type T cells which are involved in inhibition of this pathological response in TG nude mice.

Adoptive Transfer↗

PubMed1998

Establishment of an IL-2-dependent cell line derived from 'nasal-type' NK/T-cell lymphoma of CD2+, sCD3-, CD3epsilon+, CD56+ phenotype and associated with the Epstein-Barr virus.

A novel interleukin-2 (IL-2)-dependent cell line, HANK1, was established from a patient with CD56+ NK/T-cell lymphoma arising in the retroperitoneum. Morphologically, HANK1 is a pleomorphic large cell line with irregular nuclei, which contains azurophilic granules in the cytoplasm. Immunophenotypic analysis showed that HANK1 expressed CD2, CD3epsilon, CD56, TIA-1, granzyme B, and HLA-DR, but no other T-lineage markers. These features were the same as seen in the original tumour, and are highly characteristic of nasal and 'nasal-type' NK/T-cell lymphoma as described in the proposed W.H.O. classification. Genotypically, this cell line also demonstrated the germline configuration of the T-cell receptor beta, gamma and the immunoglobulin heavy chain genes and clonal integration of the Epstein-Barr virus (EBV) together with antigen expression with a type II latency pattern (LMP-1+ and EBNA2-). Furthermore, Southern blot analysis using the EBV termini as probes confirmed its derivation from the original lymphoma, and revealed that it contained multiple copies of the EBV genome. Dose-dependent growth on IL-2 was observed in an in vitro study with a doubling time of 3 d at maximal stimulation. These data indicate that HANK1 seemed to preserve the biological characteristics of the original tumour and therefore may serve as a good model for the further analysis of unusual 'nasal-type' NK/T-cell lymphoma.

Blotting, Southern↗

PubMed1998

Protein C anticoagulant system in patients with interstitial lung disease.

Excessive procoagulant activity in the alveolar space may play a relevant role in the pathogenesis of pulmonary fibrosis. Hypercoagulability results from the disruption of the balance between the procoagulant and anticoagulant factors. The aim of this study was to assess the levels of molecular markers of the anticoagulant protein C (PC) pathway in the bronchoalveolar lavage fluid (BALF) and plasma of 11 patients with idiopathic pulmonary fibrosis (IPF), 14 with sarcoidosis and 16 with collagen vascular disease (CVD)-associated interstitial lung disease (CVD-ILD). Six healthy nonsmoking volunteers served as control subjects. BALF concentrations of the marker of clotting activation, thrombin- antithrombin III complex (TAT), in patients with sarcoidosis and CVD-ILD were significantly greater than those in control subjects. PC levels in BALF were markedly higher in patients with IPF (610 +/- 150 ng/ml), sarcoidosis (680 +/- 170 ng/ml), and CVD-ILD (1,580 +/- 600 ng/ml) than in control subjects (230 +/- 140 ng/ml). BALF concentrations of activated PC-PC inhibitor (APC-PCI) complex were significantly decreased in IPF (0.46 +/- 0.16 ng/ml), sarcoidosis (0. 43 +/- 0.11 ng/ml), and CVD-ILD (0.50 +/- 0.15 ng/ml) patients as compared with control subjects (1.08 +/- 0.23 ng/ml). APC-PCI/PC ratios were significantly lower in patients with IPF (2.70 +/- 1.74 ng/microg), sarcoidosis (1.94 +/- 0.82 ng/microg), and CVD-ILD (1.89 +/- 0.68 ng/microg) than in control subjects (15.91 +/- 8.45 ng/microg). Plasma levels of APC- PCI and the APC-PCI/PC ratio were also significantly decreased in patients with CVD-ILD as compared with control subjects. Overall, these findings suggest that decreased PC activation with increased procoagulant activity occurs in patients with ILD.

Antithrombin III↗

PubMed1998

[Relapsing pneumothorax secondary to thin-walled cavitary pulmonary metastasis from angiosarcoma of the scalp].

A 79-year-old woman was given a diagnosis of scalp angiosarcoma. Treatment with interleukin-2 and radiotherapy aclieved a complete response. However, a few months later, the patient presented with multiple thin-walled cavitary metastases in the right lung and pneumothorax. The pneumothorax was successfully treated but soon relapsed. The patient died of respiratory failure at home. Lung metastasis of malignant tumors should be considered one cause of relapsing pneumothorax.

Aged↗

PubMed1997

NF-kappa B RelA-deficient lymphocytes: normal development of T cells and B cells, impaired production of IgA and IgG1 and reduced proliferative responses.

To investigate the function of NF-kappa B RelA (p65), we generated mice deficient in this NF-kappa B family member by homologous recombination. Mice lacking RelA showed liver degeneration and died around embryonic day 14.5. To elucidate the role of RelA in lymphocyte development and function, we transplanted fetal liver cells of 13.5-day embryos from heterozygote matings into irradiated SCID mice. Within 4 weeks, both T and B cells had developed in the SCID mice receiving relA-/- fetal liver transplants, similar to the relA+/+ and +/- cases. T cells were found to mature to Thy-1+/TCR alpha beta +/CD3+/CD4+ or CD8+, while B cells had the ability to differentiate to IgM+/B220+ and to secrete immunoglobulins. However, the secretion of IgG1 and IgA was reduced in RelA-deficient B cells. Furthermore, both T and B cells lacking RelA showed marked reduction in proliferative responses to stimulation with Con A, anti-CD3, anti-CD3 + anti-CD28, LPS, anti-IgM, and PMA + calcium ionophore. The results indicate that RelA plays a critical role in production of specific Ig isotypes and also in signal transduction pathways for lymphocyte proliferation.

Animals↗

PubMed1997

Prognostic significance of plasma D-dimer levels in patients with lung cancer.

BACKGROUND: The peripheral blood concentrations of several proteases of the clotting system have been shown to predict survival in patients with malignancy. A study was undertaken to investigate the independent value of the plasma levels of the D-dimer degradation product of fibrin before treatment for predicting prognosis in patients with lung cancer. METHODS: The study comprised 70 patients with lung cancer (49 non-small cell lung cancer and 21 small cell lung cancer). Plasma levels of D-dimer were measured using an enzyme immunoassay kit. Multivariate statistical analysis was carried out using the Cox's proportional hazards model. RESULTS: The median value of the plasma level of D-dimer differentiated two groups of patients with different outcomes: a group with a D-dimer level of < 150 ng/ml (low DD group) and those with D-dimer levels of > or = 150 ng/ml (high DD group). Survival time was significantly better in patients in the low DD group than in those in the high DD group in all patients (hazard ratio for high DD group = 4.7; 95% confidence interval (CI) 1.8 to 11.7). The plasma levels of D-dimer predicted survival independently from the clinical stage of disease, histological type, performance status, and tumour size (hazard ratio = 3.9; 95% CI 1.6 to 9.2). CONCLUSIONS: These results suggest that plasma levels of D-dimer might be useful for predicting the clinical outcome in patients with lung cancer. However, further prospective studies are needed in a larger population to confirm these findings.

Adult↗

PubMed1997

Lack of ventilatory threshold in patients with chronic obstructive pulmonary disease.

We investigated whether the ventilatory threshold (VET) could be detected in 25 patients with severe chronic obstructive pulmonary disease (COPD). Exercise on a treadmill was performed until symptom-limited maximum oxygen uptake (VO2SL) was obtained. VET was absent in 14 patients (56%, VET(-) group) and present in the others (44%, VET(+) group). Basal pulmonary functions and dyspnea index (VE,SL/MVV) were not different between the two groups. Endurance time and exercise tolerance (VO2SL/bw) were significantly less in VET(-) than in VET(+). In the former group, PaO2 and pH at maximal exercise decreased and PaCO2 increased significantly, but HCO3- did not change compared with the corresponding values before exercise. In the latter group, PaCO2 at maximal exercise increased significantly, and pH and HCO3- decreased significantly compared with the values before exercise, but PaO2 did not. The changes in PaO2 and PaCO2 were not different between the two groups, but changes in pH and HCO3- in VET(+) were greater than those in VET(-). These results suggest that the absence of VET in some COPD patients indicates a lower exercise capacity without producing metabolic acidosis. This may be caused by rapidly developing dyspnea.

Aged↗

PubMed1997

Combined inhalation of nitric oxide and oxygen in chronic obstructive pulmonary disease.

Inhaled nitric oxide (NO) has been shown to reduce the mean pulmonary artery pressure (mPAP) and to improve PaO2 in patients with acute respiratory failure undergoing oxygen (O2) therapy. However, inhaled NO reduced pulmonary hypertension without improving PaO2 in patients with chronic obstructive pulmonary disease (COPD). This study was intended to compare the hemodynamic and gas exchange responses during inhalation of NO or O2 with those observed during the combined inhalation of NO and O2 in 10 spontaneously breathing COPD patients. Hemodynamic and blood gas parameters were measured after breathing: (1) room air; (2) NO added to room air; (3) O2 (1 L/min); or (4) NO and O2. During inhalation of 2 ppm NO added to room air, the mPAP (23.1 +/- 2.5 versus 20.6 +/- 2.2 mm Hg) and the pulmonary vascular resistance (PVR) (434 +/- 70 versus 378 +/- 50 dyne s/cm5) were significantly (p < 0.05) lower than those measured with room air. However, the values of PaO2 did not improve. The combined inhalation of NO and O2 was associated not only with a significant (p < 0.05) decrease of mPAP (21.4 +/- 2.3 versus 19.7 +/- 1.8 mm Hg) and PVR (431 +/- 72 versus 370 +/- 44 dyne s/cm5), but also with a remarkable improvement (p < 0.05) in the values of PaO2 (91.4 +/- 6.6 versus 111.5 +/- 7.8 mm Hg) as compared with values obtained during the inhalation of O2 alone. These findings suggest that combined therapy with NO and O2 may constitute an alternative approach to treating patients with COPD and pulmonary hypertension.

Administration, Inhalation↗