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Biomedical subjects

K Ando

Publications and source records attributed to K Ando.

At least 199 records · Page 11Linked to original sources
PubMed1998

Cytotoxic effect of accelerated carbon beams on glioblastoma cell lines with p53 mutation: clonogenic survival and cell-cycle analysis.

PURPOSE: The cytotoxic effect of high-LET carbon beams was analysed on p53 mutant and wild-type glioblastoma cell lines. MATERIALS AND METHODS: Three glioblastoma (U251MG, TK-1, A-172) cell lines, one medulloblastoma (ONS-76) and one fibroblast cell line (NB1RGB) were used. U251MG and TK-1 have mutated p53, A-172, ONS-76 and NB1RGB have wild-type p53. Gamma-ray and 290 MeV/u carbon mono-peak beams with average LET values of 20, 40, 81 and 105keV/microm were used. Cytotoxicity was measured by clonogenic survival assay and DNA histograms were analysed by flow cytometry. RESULTS: The RBE values for carbon beams at D10 ranged from approximately 1.5-1.7 (20keV) to 2.9-3.1 (105keV). Although p53 mutants were more resistant than wild-types for all radiation qualities, carbon beams yielded a higher RBE in p53 mutants than in wild-types. Alpha values were significantly smaller in p53 mutants than wild-types for gamma- and 20 keV/microm radiations, while no significant difference was noticed for LET greater than 40 keV/microm. A G1 block was noticed after irradiation with gamma-rays and carbon beams of 20 and 40keV/microm in p53 wild-types. A more pronounced G2 block occurred in p53 mutants than wild-types in proportion to LET up to 105 keV/microm. CONCLUSION: Accelerated carbon beams can yield higher RBE in gamma-resistant glioblastoma cell lines with p53 mutations. High-LET irradiation induces not only disappearance of the p53-dependent G1 block but also a greater G2 block in glioblastoma cell lines.

Cell Cycle↗
PubMed1998

Mouse skin reactions following fractionated irradiation with carbon ions.

PURPOSE: Skin reactions in the mouse leg following various daily doses given with 290 MeV/u carbon ions were investigated. MATERIALS AND METHODS: Seven different LET (linear energy transfer) values ranging from 14 to 100keV/microm were selected. The fractionation schedules were 1-, 2-, 4- and 8-daily fractions. The isoeffect doses to produce moist desquamation on the dose-response curves were calculated with 95% confidence limits. RESULTS: The isoeffect doses for carbon ions of 14 and 20 keV/microm increased with an increase in the number of fractions up to 4 fractions, but became constant when the number of fractions further increased to 8 fractions. This leveling off in isoeffect dose was more prominent for 40 keV/microm. Recovered dose per fraction was largest for 2 fractions of the 14keV/microm carbon beam. The isoeffect doses for 50, 60, 80 and 100keV/microm consistently increased with an increase in the number of fractions and did not show saturation up to 8 fractions. RBE (relative biological effectiveness) increased linearly with LET for all fractionation schedules. CONCLUSIONS: These results suggest that daily fractionation with carbon ions could spare radiation damage in patients, and that changes the fractionation schedule affect clinical outcome.

Animals↗
PubMed1998

Ex vivo evidence for asymmetric tyrosine phosphorylation of ZAP-70 on double-positive thymocytes in the positive selection process.

Antigen stimulation via TCR in mature T cells provides rapid induction of tyrosine phosphorylation of intracellular substrates including ZAP-70. To study the potential involvement of tyrosine phosphorylation in CD4+CD8+ [double-positive (DP)] thymocytes in the positive selection process in vivo, we isolated and analyzed them in the presence of phosphatase inhibitor. DP thymocytes were obtained from TCR transgenic mice (TCR-Tg) expressing MHC class I- or class II-restricted TCR in selecting and non-selecting MHC backgrounds respectively. The phosphorylation of ZAP-70 in DP thymocytes of class I-restricted TCR-Tg was significantly higher in the positively selecting background than in the non-selecting one. However, such a phosphorylation difference between selecting and non-selecting TCR-Tg was found to be considerably less in class II-restricted TCR-Tg. A similar bias for ZAP-70 phosphorylation was also observed on selecting DP thymocytes when I-A(beta) deficient- and beta2-microglobulin-deficient mice were compared. These ex vivo studies suggest that TCR-mediated signaling on DP thymocytes induces ZAP-70 phosphorylation under a different manner of engagement of TCR to class I and class II molecules in the positive selection process.

Animals↗
PubMed1998

The activities of the Tokyo Center.

The main World Health Organization (WHO) activities of the Tokyo Center are as follows: (1) It performed the research project entitled 'A Bio-Psycho-Social Study on Children with Emotional and Behavioral Problems' in cooperation with the Beijing and Seoul Centers from 1985 to 1987. These results suggested that the deviant behavior of children in the general population had no biological background, but presumably stemmed from psychosocial disadvantages. (2) It has participated in a field trial for the proposed draft for chapter V of the ICD-10 as the Field Trial Coordinating Center in Japan since 1986 and the first Japanese edition of the ICD-10 Classification of Mental and Behavioral Disorders: Clinical Descriptions and Diagnostic Guidelines were published in 1993. (3) It proposed the collaborative project exploratory eye movements in patients with schizophrenia in 1989 and has promoted the project with the cooperation of six centers that included Beijing, Casablanca, Montreal, Munich, Prague and Sapporo. The findings of the present project indicated that exploratory eye movements may be specific to schizophrenia and can be practically used to discriminate schizophrenia without significantly depending on language.

Adolescent↗
PubMed1998

A simple and efficient purification of transduced cells by using green fluorescent protein gene as a selection marker.

BACKGROUND: Simple and efficient method for the selection of transduced cells would greatly facilitate the clinical utilization of retrovirus vectors. We developed a therapeutic bicistronic retrovirus vector for Gaucher disease, MFG-GC-GFP, which contains the human glucocerebrosidase (GC) gene and the green fluorescent protein (GFP) gene of the jellyfish Aequorea victoria as a vital selection marker, and investigated its applicability as gene therapy for Gaucher disease. METHODS AND RESULTS: A packaging cell line, GP + envAM12, was transfected with MFG-GC-GFP and, thus, produced a high titer recombinant virus (1.0 x 10(6) c.f.u./mL) in the culture supernatant. The expression level of GFP was correlated with the virus production in cells. The recombinant virus infected skin fibroblasts from a Gaucher patient and a sorted fraction of the cells expressing GFP by flow cytometry exhibited almost a six-fold higher activity of GC than normal fibroblasts. CONCLUSIONS: These data indicate that MFG-GC-GFP enables the one-step purification of a transduced fraction of target cells and is, therefore, considered to be a useful therapeutic vector for the experimental gene therapy of Gaucher disease.

Animals↗
PubMed1998

Oxidative stress increases adrenomedullin mRNA levels in cultured rat vascular smooth muscle cells.

We investigated the effect of oxidative stress on the expression of adrenomedullin (AM) mRNA in cultured rat vascular smooth muscle cells (VSMCs), using diethyldithiocarbamate (DDC), which is known to inhibit endogenous Cu, Zn superoxide dismutase (SOD) and to increase superoxide (O2-). DDC (10 mM) increased O2- levels produced from rat VSMCs in a time-dependent fashion. Concomitantly, DDC increased the expression of AM mRNA for up to 24 h, although it did not affect the expression of beta-actin mRNA. Thus, oxidative stress enhanced AM production in rat VSMCs, which may compensate for oxidative-stress-induced vasoconstriction.

Actins↗
PubMed1998

Immune function and lifestyle of taxi drivers in Japan.

Many studies have reported that stress affects the immune system. It is known that professional drivers are exposed to various forms of job-related stress. The aim of the present study was to investigate the job stress of taxi drivers based on the mitogen responses and cytokine production of peripheral blood lymphocytes (PBMC), combined with interviews on lifestyles and income. We examined randomly selected male taxi drivers aged 40-59 years who were members of the Kansai District Union of Private Railway, Hire, and Taxi at the end of 1992 and 1993. At the end of 1993, they were struck by a severe economic depression. The lymphocyte proliferative responses to phytohemagglutinin (PHA), concanavalin A (ConA), poke weed mitogen (PWM), and PHA-induced interleukin-2 (IL-2) and IL-4 production of the taxi drivers were at the same level as those of the control subjects as measured in 1992. The mitogen responses and IL-2 production of taxi drivers were found to have significantly decreased in 1993, while their IL-4 production was significantly elevated. Lifestyles of normal PHA respondents were significantly different from those of low-PHA respondents in 1992. However, in 1993, these differences were unclear. The immune alterations of taxi drivers who were prohibited from working overtime were more profound than those of the drivers who were allowed to do so. These results indicate that in addition to driving stress, the daily earnings affect taxi drivers as a strong stress or that induces immunological changes.

Adult↗
PubMed1998

Serum soluble CD44 levels for monitoring disease states in acute leukemia and myelodysplastic syndromes.

To determine the clinical implications of soluble CD44 (sCD44) levels in hematologic neoplasias, we developed an enzyme-linked immunosorbent assay for sCD44 using two monoclonal antibodies to the standard 90 kDa form, and assessed the serum concentration of sCD44 in normal healthy volunteers, patients with acute leukemia, myelodysplastic syndromes (MDS), and those with chronic myeloid leukemia (CML). Compared to that in normal individuals (n=51; 145. 1 24.6 ng/ml), the serum sCD44 level was significantly elevated in patients with acute myeloid leukemia (AML; n=18; 331.9 99.0 ng/ml, P=0.0001), acute lymphoid leukemia (ALL; n=16; 551.3 427.8 ng/ml, P=0.0001) and CML (n=18; 262.0 97.5 ng/ml, P=0.0001). The sCD44 level was slightly elevated in patients with MDS (n=43; 173.8 54.9 ng/ml, P=0.0071). In patients with acute leukemia, serum sCD44 concentrations decreased significantly in response to treatment and reached nearly normal levels after complete remission (P=0.0005 in AML and P=0.0032 in ALL). The sCD44 levels in patients with MDS increased after they developed acute leukemia, whereas no significant difference in sCD44 levels was observed between the chronic and the blastic phases in patients with CML. Our results indicate that serum sCD44 levels may be a useful marker for monitoring response to treatment and disease progression, especially in acute leukemia.

Acute Disease↗
PubMed1998

S19159, a modulator of neurite outgrowth produced by the ascomycete Preussia aemulans. I. Producing strain, fermentation, isolation and biological activity.

A modulator of neurite outgrowth, designated S19159, was isolated from the fermentation broth of fungal strain 19159. This fungus was identified as the loculoascomycete, Preussia aemulans (Rehm) von Arx. In the presence of S19159, the number of neurites extending from the cell bodies of cerebral cortical neurons was markedly reduced. The effect of S19159 was observed specifically in neurons from the central nervous system. The compound exhibited similar activities on cultured cortical, hippocampal and cerebeller neurons but was without detectable effect on dorsal root ganglion neurons and PC12 cells.

Animals↗
PubMed1998

Delayed administration of low-dose NPC18915 ameliorates lung ischemia-reperfusion injury.

BACKGROUND: NPC18915, a member of new antiinflammatory agent called nactins (neutrophil activation inhibitors), has been shown to reduce reperfusion injury in rat lung transplantation at high dosage. In vitro studies have demonstrated effectiveness of this compound even at low dosage. We hypothesized that this compound ameliorates lung ischemia reperfusion injury even at low dosage levels if administration is optimally timed. The aim of this study was to determine the efficacy and the best timing for administration of low-dose NPC18915. METHODS: Forty syngeneic rat left lung transplantations were performed. All isografts were flushed with low-potassium dextran-1% glucose solution 20 ml and preserved for 18 hours at 4 degrees C. Animals were divided into four groups. Group I animals (n = 10) served as control subjects. In groups II (n = 10), III (n = 10), and IV (n = 10), NPC18915 (0.04 mg) was added to the flush solution and was administered intravenously (0.4 mg/kg) immediately before reperfusion (group II) and 60 minutes (group III) and 120 minutes (group IV) after reperfusion. Pulmonary function was assessed 24 hours after reperfusion. RESULTS: In group III, oxygenation improved in comparison to group I (247.2 +/- 59.8 versus 76.6 +/- 16.0 mm Hg, p < 0.002). Wet-to-dry weight ratio and graft myeloperoxidase activity were significantly improved (group III versus group I, 6.02 +/- 0.21 versus 7.19 +/- 0.41, p = 0.013) (group III versus group I, 0.093 +/- 0.019 versus 0.207 +/- 0.023 delta optical density/min/mg, p < 0.002). There were no significant differences in CD11b expression. CONCLUSION: These data suggest that delayed administration of NPC18915, 60 minutes after reperfusion, dramatically improves pulmonary graft function.

Animals↗
PubMed1998

[Evaluation by MR imaging of neoadjuvant intra-arterial infusion chemotherapy in uterine cervical cancer].

Eight patients with uterine cervical cancer received two or three courses of neoadjuvant chemotherapy, including 254-S i.v. and CDDP i.a. Transcatheter arterial embolization (TAE) was added for seven patients. The therapeutic efficacy was evaluated by MR imaging and postoperative histopathological examination. Three patients achieved a complete response (CR) and five others were evaluated as a partial response (PR) on MR imaging. On postoperative histology, three of eight showed CR or PR, which coincided with MR findings. Viable cancer cells were shown in five patients. To detect these viable tumors, dynamic MR imaging was indispensable. However, because of limited spatial resolution, the detection of small residual tumors was not easy using dynamic MR imaging.

Adenocarcinoma↗
PubMed1998

[Diagnosis and prognosis of reactive lymphoreticular hyperplasia (RLH) or mucosa-associated lymphoid tissue (MALT) lymphoma].

We studied the diagnostic significance of immunohistolochemical staining and immunoglobuline gene rearrangement of jumbo-biopsy specimen from 14 patients with stomach lesions which were difficult to distingwish between reactive lymphoreticular hyperplasia (RLH) and mucosa-associated lymphoid tissue lymphoma (MALT lymphoma). We also investigated Helicobacter pylori (HP) infection in the patients and followed their clinical courses from a mean observation period of 3 years and 4 months following initial diagnosis. As a result, 7 of the 14 cases were diagnosed as having MALT lymphoma. All of them were resected, and then the diagnosis was confirmed. Metastasis was found in 2 cases. The other 7 cases were diagnosed as RLH. A favorable prognosis during follow up without any treatment supported the belief that they were non-malignant lesions. HP infections were observed on 83% of the RLH cases and 57% of MALT lymphoma cases. In one of the case of RLH, the lesion disappeared after eradication of HP.

Aged↗
PubMed1998

Rebamipide prevents recurrence of gastric ulcers without affecting Helicobacter pylori status.

Rebamipide, a gastroprotective drug developed in Japan, accelerates ulcer healing and reduces recurrence of experimental gastric ulcers. We examined the effects of rebamipide, given during healing of human gastric ulcers infected with Helicobacter pylori, on the quality of ulcer healing and ulcer recurrence. Sixty H. pylori-positive patients with gastric ulcers were randomly allocated to three treatment groups: group O (N = 20) received 20 mg of omeprazole every day for eight weeks, group OR (N = 20) received the same dose of omeprazole and 300 mg of rebamipide three times a day for eight weeks, and group OA (N = 20) received the same dose of omeprazole for eight weeks and 1500 mg of amoxicillin three times a day for the first two weeks. After this treatment was completed no other medication was given. Endoscopic examinations were performed at the end of therapy (for healing rate), one month later (for rate of H. pylori eradication) and every three months for follow-up (for ulcer recurrence rate). At the end of therapy, biopsy specimens were taken from the gastric ulcer scar and examined under the microscope for neutrophil and mononuclear cell infiltration. The ulcer healing rate of the three groups was almost the same; H. pylori in group OA was 65% and that of the other two groups was 0%. The number of patients with a flat ulcer scar pattern (good quality of ulcer healing) was increased and the neutrophil infiltration was significantly improved in groups OR and OA compared to group O. The ulcer recurrence rate was significantly lower in group OA and group OR than in group O. In conclusion, rebamipide is almost equipotent to amoxicillin plus omeprazole for the reduction of ulcer recurrence. The decreased recurrence rate by rebamipide may be due to improvement of the quality of ulcer healing, reflected as in the suppression of inflammatory cell infiltration in the scar, which results from either cure of H. pylori infection and/or treatment with a gastroprotective drug such as rebamipide.

Aged↗
PubMed1998

Effect of rebamipide on Helicobacter pylori infection in patients with peptic ulcer.

This study was designed to assess whether the gastroprotective drug, rebamipide, aids in eradication of H. pylori. One hundred twenty patients, endoscopically diagnosed with gastric or duodenal ulcers and H. pylori infection, were randomly allocated to two treatment groups. Sixty patients received 40 mg of omeprazole twice a day, 1500 mg of amoxicillin three times a day, and 300 mg of rebamipide three times a day (group OAR); the other 60 patients received the same dosage of omeprazole and amoxicillin but no rebamipide for two weeks (group OA). All patients subsequently received an H2-receptor antagonist for six weeks. At the end of the treatment, endoscopy was performed to assess the status of the ulcers as well as the extent of H. pylori infection. In the intent-to-treat (73.3 vs 51.7%, P = 0.014) and per-protocol analyses (75.9 vs 55.3%, P = 0.021) the cure rates for H. pylori infection in group OAR were found to be significantly higher than those in group OA. Our findings suggest that rebamipide aids in curing H. pylori infection. This drug does not induce formation of resistant colonies and has few side effects.

Adult↗
PubMed1997

Proadrenomedullin N-terminal 20 peptide (PAMP) inhibits proliferation of human neuroblastoma TGW cells.

We investigated the effects of proadrenomedullin N-terminal 20 peptide (PAMP) and adrenomedullin (AM) on the growth of human neuroblastoma TGW cells. Both PAMP and AM inhibited growth and DNA synthesis in neuroblastoma cells. Calcitonin gene-related peptide (CGRP)(8-37), an antagonist to CGRP, abolished the inhibitory effect of AM on growth and DNA synthesis of neuroblastoma cells but did not affect that of PAMP. AM(22-52), an antagonist to AM, also reversed the effect of AM. On the other hand, pertussis toxin (PTX) and omega-conotoxin GIVA blocked the effect of PAMP alone. Thus, PAMP inhibits the growth of neuroblastoma cells by inhibiting N-type Ca2+ channels through PTX-sensitive G protein-coupled receptors, which is different mechanism of AM-induced inhibition of the cell growth.

Adrenomedullin↗
PubMed1997

Perforin, Fas/Fas ligand, and TNF-alpha pathways as specific and bystander killing mechanisms of hepatitis C virus-specific human CTL.

In chronic hepatitis C, Fas expression is up-regulated in the hepatocytes, especially near liver-infiltrating lymphocytes, and Fas ligand is expressed on the lymphocytes. The presence of hepatitis C virus (HCV)-specific CTLs has been demonstrated both in peripheral blood and among liver-infiltrating lymphocytes of patients with chronic hepatitis C. We studied the killing mechanisms of HCV-specific human CTLs using target cells that were sensitive or resistant to agonistic anti-Fas Abs and TNF-alpha. We show that HCV-specific CTL clones kill non-Ag-bearing bystander cells as well as Ag-bearing cells, although the bystander killing is less efficient than the specific target cell killing, and the efficacy of the bystander killing of anti-Fas- and soluble TNF-alpha-sensitive cells is greater than that of resistant cells. We also show that the killing of Ag-presenting, sensitive cells is mediated by Fas ligand and TNF-alpha as well as perforin, although the latter plays a major role in the killing at a low E:T ratio, and that the killing of sensitive bystander cells is primarily mediated by Fas ligand and TNF-alpha on CTLs expressed upon specific Ag stimulation, which may be relevant to the bystander lysis by HCV-specific CTLs of uninfected hepatocytes, in which Fas expression is up-regulated. Activated CTLs also kill bystander cells by the perforin-based mechanism, although it requires a high E:T ratio. The effective bystander killing requires a close intercellular contact between CTLs and target cells, although TNF-alpha released from the CTLs mediates lysis of the bystander cells without a close cell-cell contact.

Antigen Presentation↗
PubMed1997

Fas-mediated apoptosis of the hematopoietic progenitor cells in mice infected with murine cytomegalovirus.

The effects of cytomegalovirus (CMV) infection on hematopoietic progenitor cells in vivo were investigated to elucidate the pathogenesis of CMV-induced myelosuppression. BALB/c mice were inoculated with 0.2LD50 of murine CMV (MCMV). Lineage marker negative, c-kit positive (Lin-c-kit+) and Lin-CD34+ cells, which are both phenotypically defined as hematopoietic progenitor cells, showed a significant reduction in number on day 3 postinfection (pi). Moreover, the reduction in the number of day-14 colony-forming units-spleen (CFU-S), another indicator to identify hematopoietic progenitor cells, was noted on day 3 pi. To clarify the mechanism of such depletion, we examined the cells undergoing apoptosis in the Lin- populations and found a 15-fold increase in the apoptosis-induction of these cells. Furthermore, an increase in the expression level of Fas, which mediates apoptosis, was observed in such Lin-c-kit+ and Lin-Sca-1+ cells on day 3 pi. In vitro treatment with the anti-Fas antibody accelerated the apoptosis in Lin- cells, but not in the uninfected control cells, thus indicating that the upregulated Fas on Lin- cells is directly related to the acceleration of apoptosis found in these cells in vivo. These results suggest that MCMV infection reduces the number of hematopoietic progenitor cells in bone marrow at least in part due to Fas-mediated apoptosis, and this phenomenon is thus considered to contribute to CMV-induced myelosuppression.

Animals↗