Biomedical subjects

T Ohno

Publications and source records attributed to T Ohno.

At least 163 records · Page 9Linked to original sources

PubMed1999

Induction of antitumor immunity using intercellular adhesion molecule 1 (ICAM-1) transfection in mouse glioma cells.

We investigated the role of intercellular adhesion molecule 1 (ICAM-1) expression in tumorigenicity of gliomas and the antitumor effects of glioma cells genetically engineered to express ICAM- 1. Mouse glioma cells transfected with ICAM-1 grew in T-cell deficient mice but not in syngeneic mice. Vaccination with ICAM-1-transfected tumor cells markedly inhibited the growth of subcutaneously inoculated gliomas but not gliomas located in the brain. In vivo antibody ablation study revealed that CD4+ T, CD8+ T and NK cells were all required to produce the antitumor effect of SR/ICAM- 1. In this study, we demonstrated the therapeutic potential of vaccination with ICAM-1-overexpressing tumor cells for the control of the tumor growth.

Animals↗

PubMed1999

Interferon-alpha repressed telomerase along with G1-accumulation of Daudi cells.

The implications of telomerase on senescence and human carcinogenesis are widely accepted, but the changes of telomerase activity along with cell cycle modulation by anticancer treatment still remain obscure. In this paper, we issued whether the telomerase activity fluctuated along with cell cycle of cultured cancer cells using the antiproliferative effect of interferon-alpha (IFN-alpha). Daudi Burkitt lymphoma cells, treated with IFN-alpha, showed proliferation inhibition and cell cycle arrest at G1. The telomerase activity at 72 h was repressed to about 20% of control cells. Furthermore, after 72 h IFN-alpha treatment, the cells in G1 phase showed the marked decrease of telomerase activity, while cells in S and G2/M still possessed it. Among expressions of telomerase-related genes, only the catalytic subunit of telomerase (hTERT) decreased from 48 h, while the template RNA component (hTERC) and telomerase-associated protein 1 (TEP-1) were not affected. The downregulation of c-Myc preceded the change of hTERT. Moreover, the analysis of cells treated with IFN-alpha for 24 h revealed that cells in G1-to-S transition mainly expressed high hTERT, while S and G2/M cells had higher level of telomerase activity than that of G1 cells. These results indicate that (i) the expression of hTERT precedes the telomerase activity which is higher in S and G2/M phases than G1 phase, (ii) IFN-alpha repressed the telomerase activity in a cell cycle-dependent manner with the downregulation of hTERT.

Antineoplastic Agents↗

PubMed1999

Chlorophyll b and phycobilins in the common ancestor of cyanobacteria and chloroplasts.

Photosynthetic organisms have a variety of accessory pigments, on which their classification has been based. Despite this variation, it is generally accepted that all chloroplasts are derived from a single cyanobacterial ancestor. How the pigment diversity has arisen is the key to revealing their evolutionary history. Prochlorophytes are prokaryotes which perform oxygenic photosynthesis using chlorophyll b, like land plants and green algae (Chlorophyta), and were proposed to be the ancestors of chlorophyte chloroplasts. However, three known prochlorophytes (Prochloron didemni, Prochlorothrix hollandica and Prochlorococcus marinus) have been shown to be not the specific ancestors of chloroplasts, but only diverged members of the cyanobacteria, which contain phycobilins but lack chlorophyll b. Consequently it has been proposed that the ability to synthesize chlorophyll b developed independently several times in prochlorophytes and in the ancestor of chlorophytes. Here we have isolated the chlorophyll b synthesis genes (chlorophyll a oxygenase) from two prochlorophytes and from major groups of chlorophytes. Phylogenetic analyses show that these genes share a common evolutionary origin. This indicates that the progenitors of oxygenic photosynthetic bacteria, including the ancestor of chloroplasts, had both chlorophyll b and phycobilins.

Amino Acid Sequence↗

PubMed1999

Enhancing effect of tumor necrosis factor (TNF)-alpha, but not IFN-gamma, on the tumor-specific cytotoxicity of gammadeltaT cells from glioblastoma patients.

Adoptive immunotherapy using tumor-specific killer cells can be beneficial in inducing regression of advanced cancer. The roles of cytokines on effector cells in inducing maximal killing activity and the accompanying side-effects should be investigated in vitro and fully understood prior to their clinical use. The present study indicates that the gammadeltaT cells involved in autologous tumor-specific killing consist of several populations in terms of their T cell receptor (TCR) repertoire, but predominantly express the products of the Vgamma9/Vdelta2 gene locus of the TCR. We then examined the effect of TNF-alpha and IFN-gamma on these tumor-specific gammadeltaT cells for possible clinical use in cancer patients. TNF-alpha alone, at concentrations of 0.01-1.0 microg/ml, caused increased gammadeltaT cell cytotoxicity against autologous glioblastoma cells, whereas IFN-gamma alone had no effect. The combination of TNF-alpha (1 microg/ml) with IL-2 (50 units/ml) resulted in further enhancement of cytotoxicity. TNF-alpha, but not IFN-gamma, marginally inhibited the proliferative response of gammadeltaT cells; a similar result was seen when the cytokines were combined. TNF-alpha may, therefore, be one cytokine capable of inducing increased autologous tumor-specific activity in gammadeltaT cells, bearing mainly Vgamma9/Vdelta2 chains, which can be enhanced when combined with other cytokines.

Cell Division↗

PubMed1999

Demonstration of the interaction of thioredoxin with p40phox, a phagocyte oxidase component, using a yeast two-hybrid system.

Thioredoxin (TRX) has disulfide reducing activity and is reported to be involved in various cellular functions including the promotion of cell growth and apoptosis. To help understand the molecular mechanism through which TRX is involved in immunological systems, we screened a cDNA library derived from a B-cell population of Epstein-Barr virus-transformed human peripheral blood lymhocyte for TRX binding proteins by use of a yeast two-hybrid system. Among plasmids from positive clones, a plasmid contained an insert which has homology with human p40phox, a cytosolic component of phagocyte oxidase. This insert sequence extended from the base + 181 to the stop codon of p40phox. The entire coding region of p40phox was shown to interact with TRX both in assays of histidine prototrophy and beta-galactosidase activity; in contrast, no interaction was observed with substituted mutant TRX (C32S/C35S), which lacks reducing activity. These results showed that p40phox interacts with TRX and indicated the possibility of TRX-dependent regulation of phagocyte oxidase activity.

Amino Acid Sequence↗

PubMed1999

Relationship between p21/WAF-1/CIP-1 and apoptosis in cervical cancer during radiation therapy.

PURPOSE: P21/WAF-1/CIP-1 was not considered to be involved in the regulation of apoptosis, an important indicator of radiosensitivity. However, it has been reported recently that apoptosis was suppressed when p21 expressed. The purpose of this study was to clarify the relationship between p21 and apoptosis and to evaluate the role of p21 in cervical cancer during radiation therapy (RT). METHODS AND MATERIALS: Twenty-one patients with cervical cancer were treated by RT. Tissue samples were obtained from cervical tumors of all patients before RT, and 6 hours after the fifth dose of 1.8 Gy (5th Dose). Samples were subjected to nick end labeling for apoptosis and immunohistochemical staining for p21 and p53 antigen expression. RESULTS: The mean apoptotic index, p21 labeling index and p53 labeling index were 0.27%, 9.24% and 6.60%, respectively, before RT and increased significantly to 1.20%, 17.5% and 13.9%, respectively, after 5th Dose. The apoptotic index at 5th Dose was inversely correlated with the p21 labeling index (r = -0.50, p = 0.025). Furthermore, a positive correlation was observed between the p21 and p53 labeling indices both before RT and at 5th Dose (r = 0.52, p = 0. 02; r = 0.63, p < 0.01, respectively). CONCLUSION: Our results demonstrate that apoptosis and expression of p21 and p53 were induced in cervical cancer during RT. p21 expression was dependent on p53 expression and moreover, it is suggested-that p21 might be a potential suppressor of radiation-induced apoptosis in cervical cancer during RT.

Aged↗

PubMed1999

Anti-tumor activity of interleukin-2-producing tumor cells and recombinant interleukin 12 against mouse glioma cells located in the central nervous system.

Interleukin 12 (IL-12) exhibits anti-tumor activity in a variety of laboratory models. Although IL-12 itself activates strong anti-tumor activity, the combination of vaccine therapy with IL-2-transduced tumor cells and systemic rIL-12 has been shown to cure tumor-bearing mice more effectively than either rIL-12 or IL-2-transduced tumor vaccines alone. In the present study, regression of brain tumors established in naive mice was obtained by combined administration of an intratumoral injection of a single dose of IL-2-producing glioma cells (SR/IL-2 cells) and recombinant IL-12. Intraperitoneal rIL-12 administration substantially delayed the growth of s.c. inoculated gliomas, but not of gliomas located in the brain. Although vaccination with SR/IL-2 cells alone was not effective against s.c. inoculated gliomas, the combination therapy of vaccination with irradiated SR/IL-2 cells and systemic rIL-12 was more effective than rIL-12 alone. In our brain-tumor model, intratumoral administration of irradiated SR/IL-2 cells and of rIL-12 remarkably prolonged survival as compared with untreated mice. Efficacy was reduced when studies were performed in mice depleted of CD8+ cells or NK cells. Mice cured of their intracerebral tumors by combined administration of SR/IL-2 cells and rIL-12 demonstrated protective immunity upon rechallenge. In summary, the therapeutic potential for control of tumor growth by intratumoral administration of IL-2-producing glioma cells and rIL-12 may be useful in the development of treatment for patients with glioma.

Animals↗

PubMed1999

Antitumor activity of interleukin 12 against interleukin 2-transduced mouse glioma cells.

We subcutaneously inoculated parental and glioma cells genetically engineered to express interleukin-2 (SR/IL-2) into syngeneic mice. The tumor growth of the transfectants was slower than that of the parental cells. We then stereotactically inoculated transfectants into the brains of mice. The survival of the mice injected with parental cells was shorter than that of the mice inoculated with transfectants. SR/IL-2 cells were inoculated subcutaneously into the flank of mice, after which rmIL-12 was administered intraperitoneally (i.p.). The resultant transient tumor growth was followed by regression. rmIL-12 or saline were then injected i.p. into mice that had been inoculated in the brain with SR/IL-2 cells. There was no significant difference in survival time between the treated and control groups.

Animals↗

PubMed1999

A new genotype of TT virus (TTV) infection among Colombian native Indians.

Serum TTV DNA was assayed in 140 native Indians and 40 members of the general population in Colombia to determine the prevalence of TT virus (TTV) infection among Colombian native Indians. Of the 140 native Indians, 23 (16.4%) were positive for TTV DNA, compared to 4 (10.0%) of 40 from the general population (P = not significant). The prevalence of TTV DNA among native Indians was much higher than that of HBsAg and anti-HCV. Comparison of subjects with and without TTV DNA revealed no significant differences in all characteristics between the two groups. A phylogenetic tree, using the open reading frame 1 sequence (222 bp), indicated that the virus could be classified into four different genotypes, including three previously reported ones. The results show that TTV infection is common in Colombian native Indians without liver disease and also indicate the existence of a novel genotype of TTV.

Adolescent↗

PubMed1999

Metabolism of coenzyme Q10: biliary and urinary excretion study in guinea pigs.

Biliary and urinary metabolites were examined after intravenous administration of 14C-coenzyme Q10 (14C-CoQ) to guinea pigs. Cumulative recovery of administered radioactivity for up to 8 hours by bile drainage was 4.8%. The greater part of radioactivity was detected in conjugate form. After hydrolyzing with beta-glucuronidase, aglycone fragments were subjected to methylation and reductive acetylation. The main metabolite was demonstrated to be Q acid-1 1,4-hydroquinone diacetate methyl ester (M-1) on HPLC. Then, the main metabolite was assumed to be glucuronide of 2,3-dimethoxy-5-methyl-6-(3'-methyl-5'-carboxy-2'-pentenyl)-1, 4-benzohydroquinone [Q acid-I hydroquinone]. The cumulative urinary recovery of the administered radioactivity over 48 hours was 8.3%. The labeled samples were treated similarly to bile. The urinary metabolites of CoQ10 consisted of unconjugated and conjugated forms. Lyophilized urine was treated as a bile sample and analyzed. The two major metabolites were assigned to be M-1 and Q acid-II 1,4-hydroquinone diacetate methyl ester (M-2). Then, the two metabolites were assumed to be composed of Q acid-I and 2,3-dimethoxy-5-methyl-6-(3'-carboxypropyl)-1,4-benzoquinone (Q acid-II) in free and corresponding hydroquinone conjugate forms. To investigate the effect of exogenous labeled CoQ10 on unlabeled CoQ10 (endogenous) metabolites in urine, simultaneous quantitative determination was performed using deuterium labeled CoQ10 (CoQ10-d5). Urine collected over a 72-hour period after intravenous administration of CoQ10-d5 was processed similarly to that described above and two derivatized metabolites (M-1 and M-2) were quantified by gas chromatography-mass fragmentography with the multi-ion detection method. The analytical results showed that the addition of exogenous labeled CoQ10 did not influence the metabolism (or breakdown) of unlabeled (endogenous) CoQ10.

Animals↗

PubMed1999

Deletion of a large genomic segment in tobacco varieties that are resistant to potato virus Y (PVY).

Recessive alleles (va, va1, va2, etc) of the tobacco Va locus confer resistance to potato virus Y (PVY). To elucidate the mechanism underlying this resistance, we attempted to identify randomly amplified polymorphic (RAPD) markers that reveal polymorphism between two nearly isogenic lines (NILs) that differ in their susceptibility to PVY. Using each of 500 primers and 800 pairs of primers, we identified over 100 RAPD fragments that differed between the NILs. We applied these RAPD primers or primer combinations to an F2 population obtained from a cross between the susceptible line BY4 and the resistant va2-bearing NIL, F55. It was found that only 10 RAPD markers were polymorphic between resistant and susceptible plants. Unexpectedly, these markers were all linked to Va. All 10 RAPD markers were present in all 8 susceptible varieties tested. At least one RAPD marker was not detected in 8 out of 10 resistant varieties. Southern analysis revealed that the sequences of markers were not present in the genomes of resistant varieties, and the markers were found in individually distinct positions on the chromosomes of susceptible tobacco varieties. These results strongly suggest that the resistance conferred by va is due to deletions at the Va locus governing susceptibility to PVY.

Base Sequence↗

PubMed1999

Human ovary and placenta express messenger RNA for multiple activin receptors.

In the present study, we examined the expression of activin receptor (ActR) mRNAs in human ovary and placenta. Primers specific for two type I and two type II activin receptors (ActR-I, ActR-IB, ActR-II, and ActR-IIB) were used in polymerase chain reaction (PCR) to amplify cDNAs prepared from granulosa-luteal cells, placental tissues and isolated trophoblast cells. PCR products with the expected sizes for ActR-I, ActR-IB, ActR-II, and ActR-IIB mRNAs were detected in freshly dissociated and 5-day cultured granulosa-luteal cells; and in trophoblast cells from both first trimester and term placentas. The identity of these PCR products were confirmed by Southern blot hybridization, as well as cloning and sequencing. These results suggest that multiple activin receptors are present in human ovary and placenta and may mediate activin function in these tissues. The demonstration of activin receptor mRNAs in granulosa-luteal and trophoblast cells further supports the notion that activin is an important local regulator in the human ovary and placenta.

Activin Receptors↗

PubMed1999

TT virus infection among blood donors and patients with non-B, non-C liver diseases in Korea.

BACKGROUND/AIMS: A novel virus, designated the TT virus (TTV), was isolated from the serum of a patient with posttransfusion hepatitis of unknown etiology, in Japan. Subsequently, TTV was suggested to be a causative agent in a proportion of cases with cryptogenic hepatitis in Japan. This study aimed to elucidate the significance of TTV infection in cases with cryptogenic liver disease in Korea, a neighbor of Japan. METHODS: The prevalence of TTV infection was studied in 120 patients with liver diseases, including 85 patients diagnosed as having non-B, non-C liver diseases. As controls, 220 blood donors were also examined. TTV DNA was detected by polymerase chain reaction, and the sequence was analyzed by phylogenetic analysis. RESULTS: Fourteen (14.0%) of 100 accepted blood donors, 23 (19.2%) of 120 rejected blood donors, and 15 (17.6%) of 85 patients with non-B, non-C liver diseases were positive for TTV DNA. The prevalences of TTV infection among these groups were not significantly different. Phylogenetic analysis suggested the existence of four major genotypes of TTV The proportions of each genotype among patients with non-B, non-C liver diseases were not different from those among accepted blood donors. CONCLUSIONS: TTV exists in Korea, but the prevalence among patients with non-B, non-C liver diseases was almost the same as that among blood donors. TTV may not be the main causative agent of cryptogenic liver disease in Korea. The relationship between non-B, non-C liver diseases and TTV genotype remains unclear, although TTV can be classified into four genotypes.

Adolescent↗

PubMed1999

Radiation therapy for roentogenographically occult lung cancer by external beam irradiation and endobronchial high dose rate brachytherapy.

PURPOSE: We investigated the clinical usefulness of radiation therapy by external beam irradiation and endobronchial brachytherapy for the treatment of roentogenographically occult lung cancer. PATIENTS AND METHODS: From 1995 to 1996, five patients were treated with radiation therapy. We analyzed their treatment outcomes. The follow-up period varied from 3.0 to 3.8 years or until death. External beam radiation (40 Gy/20 fractions/4 weeks) was delivered to the tumor site alone, and not prophylactically given to the mediastinum. Endobronchial brachytherapy using high dose rate iridium (Ir)-192 was concurrently administered principally to a total dose of 18 Gy on the bronchial mucosa in three weekly fractions of 6 Gy each. RESULTS: Complete remission was obtained in all patients. Two patients died of intercurrent diseases at 12 and 21 months without any evidence of recurrence. The disease has been also controlled in the other three cases. With the above doses, three small tumors < 1 cm were controlled without adverse effect. In two tumors, the dose reference points were set 2-7 mm beneath the mucosa, and larger doses were administered by brachytherapy. An applicator acting as a spacer was not used in these cases. The tumors were controlled, although the irradiated bronchi showed severe stenosis in 6 months following the treatment. However, the patients were asymptomatic and did not need further intervention. CONCLUSION: External beam irradiation combined with endobronchial brachytherapy was useful for the treatment of roentogenographically occult lung cancer as an alternative to surgery. Further investigation is needed to determine the optimal doses of radiation therapy.

Aged↗

PubMed1999

Limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer.

The outcome of limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer (NSCLC) was analyzed to discuss the elective irradiation of regional lymph nodes. From 1976 through 1994, 36 patients with peripheral stage I NSCLC were treated with definitive radiation therapy (RT) alone at Gunma University hospital. The total dose ranged from 60 to 81 Gy with a 2 Gy-daily standard fractionation, although only one patient received 48 Gy. Ten patients received elective irradiation of the regional lymph nodes with a total dose of 40 Gy or more. The overall response rate was 97% with 31% complete responses. The overall survival rates at 3 and 5 years were 42 and 23%, and disease-specific survival rates were 56 and 39% at 3 and 5 years, respectively. In 26 patients without the elective regional irradiation, disease-specific survival rates at 3 and 5 years were 53 and 40%, respectively, whereas they were 64 and 39% in 10 patients with the regional nodal irradiation. The cumulative 5-year local progression rate was 28%, and the overall progression rate was 60% at 5 years. Four patients had a local recurrence as the only site of initial tumor progression. Combined local and regional progression was seen in two patients, and one patient had a local recurrence in combination with distant metastasis. Twelve patients had distant failure without evidence of local or regional progression. Only one patient without regional nodal irradiation developed an isolated regional failure. No patient had serious complications related to RT. High-dose limited field RT is justified for medically inoperable patients with peripheral stage I NSCLC. The regional nodal irradiation can be omitted in these pulmonary compromised patients because of the low regional relapse rate. Dose-escalation by a conformal RT with a small target volume can be expected to provide a better local control rate and better survival.

Aged↗

PubMed1999

Dilatation and constriction of rat gastric mucosal microvessels through prostaglandin EP2 and EP3 receptors.

BACKGROUND: Prostaglandin (PG)E2 has both a vasodilating action and a protective function in the gastric mucosa. There are four subtypes of PGE2-sensitive, or EP, receptors. AIM: To identify the subtype of EP receptors in the microvessels of the rat gastric mucosa using EP2 and EP3 receptor agonists. METHODS: The posterior wall of the anaesthetized rat stomach was secured in a chamber and superfused with Tyrode's solution, and the gastric microcirculation of the mucosal base was observed through a window with transillumination. PGE2 and its derivatives (20 microL) were applied topically in the window. RESULTS: PGE2 (0.001-10 micromol/L), misoprostol (EP2/EP3 receptor agonist; 0.01-100 micromol/L) and butaprost (EP2 receptor agonist; 1-1000 micromol/L) dilated the arterioles dose-dependently, but M&B 28 767 (EP3 receptor agonist; 0.001-10 micromol/L) did not alter their diameters. M&B 28 767 constricted the venules and collecting venules dose-dependently whereas butaprost dilated them. PGE2 and misoprostol had bell-shaped dose-response curves: constriction by low doses of PGE2 and misoprostol (0.001-0.1 micromol/L and 0.01-1 micromol/L) and dilation by high doses of PGE2 and misoprostol (0.1-100 micromol/L and 1-100 micromol/L). CONCLUSIONS: These results suggest that PGE2 dilated both arterioles and venules in the rat gastric mucosa through the EP2 receptors and constricted the venules through the EP3 receptors.

Alprostadil↗

PubMed1999

De novo CD5-positive diffuse large B-cell lymphoma: clinical characteristics and therapeutic outcome.

To determine the clinical significance of CD5 expression in diffuse large B-cell lymphoma (DLBL) without a clinical history of low-grade B-cell lymphoma, we have reviewed the clinical features and therapeutic outcome of 25 patients with de novo CD5-positive DLBL, and compared the results with those of 87 patients with CD5-negative DLBL and 22 patients with mantle cell lymphoma (MCL). The patients with de novo CD5-positive DLBL had clinical characteristics of elderly onset (median age 63, range 37-91), and female predominance (male/female 10/15). 21 (84%) of these patients had extranodal involvement at presentation, with great variation in the sites. In comparison with the patients with CD5-negative DLBL, the treatment outcome for the patients with de novo CD5-positive DLBL was very poor with frequent relapse. The failure-free survival curve was almost identical to that of patients with MCL, showing that standard chemotherapy for DLBL was not effective for most of the patients with de novo CD5-positive DLBL. These findings suggest that de novo CD5-positive DLBL forms a distinct subgroup of DLBL.

Adult↗

PubMed1999

Bone marrow transplantation attenuates murine IgA nephropathy: role of a stem cell disorder.

BACKGROUND: The pathogenesis of IgA nephropathy is still obscure. The aim of this study was to investigate whether the fundamental pathogenesis of IgA nephropathy lies in bone marrow stem cells (BMCs). METHODS: We used donors of two different strains for bone marrow transplantation (BMT) into mice with a high content of serum IgA (ddY strain, HIGA mice), a murine model of IgA nephropathy. One group (B6-->HIGA, N = 5) received BMCs of C57BL/6j (B6) mice, and the other (HIGA-->HIGA, N = 8) were reconstituted with BMCs of HIGA mice. RESULTS: Twenty-six weeks after BMT, in B6-->HIGA mice, mesangial deposits of IgA and C3 were statistically milder than those in HIGA-->HIGA mice. Light microscopic observations disclosed that glomerular sclerosis and mesangial matrix expansion in B6-->HIGA mice were decreased compared with those in HIGA-->HIGA mice. These B6-->HIGA mice also excreted less urinary albumin than HIGA-->HIGA mice. Furthermore, serum levels of IgA in B6-->HIGA mice were markedly lower than those in HIGA-->HIGA mice. Size analysis of serum IgA revealed that macromolecular IgA were notably lower in B6-->HIGA mice than in HIGA-->HIGA mice. CONCLUSIONS: Our results suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells, and that BMT from normal donors can attenuate glomerular lesions in HIGA mice. This approach may offer a new avenue to study the pathogenesis of IgA nephropathy.

Age Factors↗