K Kawashima

The Graduate University for Advanced Studies, Миура, Kanagawa, Japan

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Publications (131)201.91 Total impact

  • Norio Sakuragawa · Mohamed A Elwan · Saiko Uchida · Takeshi Fujii · Koichiro Kawashima ·
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    ABSTRACT: Human amniotic epithelial cells (HAEC) are formed from epiblasts on the 8th day after fertilization. Because they lack major histocompatibility complex (MHC) antigen, human amniotic tissue transplantation has been used for allotranplantation to treat patients with lysosomal diseases. We have provided evidence that HAEC have multiple functions such as synthesis and release of acetylcholine (ACh) and catecholamine (CA) as well as expressing mRNA coding for dopamine receptors and dopamine (DA) transporter (DAT). On the other hand, we showed that monkey amniotic epithelial cells (MAEC) synthesize and release CA and posses DA receptors and DAT. Detection of muscarinic actylcholine receptors indicates the presence of an autocrine mechanism in HAEC. Recently, we found that HAEC have neurotrophic function in conditioned medium from HAEC, indicating the presence of a novel neurotrohpic factor that is synthesized and released from HAEC. The amniotic membrane may have a significant role in supplying neurotrophic factors as well as neurotransmitters to the amniotic fluid, suggesting an important function in the early stages of neural development of the embryo. This review will focus on the neuropharmacological aspects of HAEC and MAEC in relation to the physiology of amniotic membrane.
    The Japanese Journal of Pharmacology 02/2001; 85(1):20-3. DOI:10.1254/jjp.85.20
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    ABSTRACT: To obtain background information on elderly acute myeloid leukemia (AML), unselected data covering 159 patients aged 60 years or over with AML from 14 hospitals in Nagoya, Japan was analyzed retrospectively. Among these patients, 119 had de novo acute AML, 32 had AML which evolved from myelodysplastic syndrome (MDS-AML), and 8 had other types of leukemia. The survey showed that MDS-AML tended to be more prevalent in patients aged 70 years and older and that MDS-AML showed a significantly more severe degree of leukopenia and anemia than de novo AML. MDS-AML also showed a significantly lower complete remission (CR) rate than that of de novo AML [6.9% (2/29) vs 58.3% (67/11), P < 0.01] and significantly shorter survival times than those of de novo AML [median: 3.6 months vs 9.6 months, P < 0.01 (generalized Wilcoxon test; GW]. In de novo AML, the proportion of patients treated with conventional therapy (CT group) decreased significantly, and that of those with attenuated therapy (AT group) increased significantly as age elevated (P < 0.01). The CT group showed a significantly higher CR rate (65.4% vs 41.2%, P < 0.05) and a significantly longer survival period than those of the AT group [median: 11.6 months vs 4.8 months, P < 0.05 (GW)]. Overall survival rates of the older age groups became significantly shorter with aging [P < 0.01 (GW)].
    Nagoya journal of medical science 11/1999; 62(3-4):135-44. · 0.75 Impact Factor
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    ABSTRACT: We investigated the effect of the histone deacetylase inhibitors (HDIs), trichostatin A and trapoxin A on leukemia cells and cell lines from the viewpoint of differentiation induction. TSA induced differentiation in erythroid cell lines by itself, whereas it synergistically enhanced the differentiation that was directed by all-trans retinoic acid (ATRA) or vitamin D3 in U937, HL60 and NB4 cells. The combined treatment of HDI with ATRA induced differentiation in ATRA-resistant HL60 and NB4 cells. The transcriptional expression during the treatment with HDI was examined in HL60, U937 and MEG-O1. Cell cycle-regulator genes (p21waf1 and p16INK4A) were upregulated or constantly expressed, erythroid-specific genes (GATA-1, beta-globin) were silent or downregulated, and housekeeping genes (beta-actin and GAPDH) were constantly expressed. Twelve of 35 (34%) clinical samples from AML patients ranging from M0 to M7 also displayed both phenotypical and morphological changes by the treatment with TSA alone. HDIs are thus the potent inducer or enhancer of differentiation in acute myeloid leukemia and regulate transcription in an ordered manner.
    Leukemia 10/1999; 13(9):1316-24. DOI:10.1038/sj.leu.2401508 · 10.43 Impact Factor
  • N Emi · A Abe · M Kasai · A Kohno · M Tanimoto · H Kimura · K Kawashima · M Ito · N Mori · H Saito ·
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    ABSTRACT: We have established a T-cell line, MTA, from the peripheral blasts of a patient with natural killer (NK)-like T-cell leukemia/lymphoma. The MTA cell displays a T-cell and NK-cell phenotype (CD2+, CD3+, CD4+, CD56+) identical to freshly isolated leukemic blasts from the patient. This cell line shows clonal T-cell receptor rearrangement and a distinguishable character by light microscopy with May-Grünwald Giemsa staining. G-banding analysis showed that the MTA cells had a karyotype of 94(4N), XXXX, add (1) (p36), del (5) (q14q23), add (17) (p11), add (19) (q13). However, unlike NK malignancy, we could not show a direct pathogenic role for Epstein-Barr virus (EBV) with EBV-encoded small RNA and polymerase chain reaction analysis. The MTA cell line is a novel cell line with which to study NK-like T-cell ontogenecity.
    International Journal of Hematology 05/1999; 69(3):180-5. · 1.92 Impact Factor
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    N Sakuragawa · MA Elwan · T Fujii · K Kawashima ·
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    ABSTRACT: Human amniotic epithelial cells express makers of glial and neural stem cells. These cells also synthesize and release acetylcholine and catecholamines. This study of amniotic fluid demonstrated that acetylcholine and catecholamines can be readily identified in the fluid. Norepinephrine was the major catecholamine present, although dopamine and DOPAC could also be detected. The physiologic role of these amniotic fluid neurotransmitters in fetal-placental interactions and nervous system development is currently under investigation.
    Journal of Child Neurology 05/1999; 14(4):265-6. DOI:10.1177/088307389901400410 · 1.72 Impact Factor
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    ABSTRACT: In the present study 142 patients with myeloma (102 with IgG M-protein and 40 with IgA) treated with either VMCP (65 patients) or MMCP (77 patients) as remission induction therapy were retrospectively analyzed. Response to treatment was evaluated in terms of a more-than-50% fall of pretreatment M-protein and the posttreatment M-protein nadir. Though significantly more patients treated with MMCP achieved partial response (PR) as compared with those treated with VMCP (P=0.019) and though patients achieving PR showed a significantly longer survival than those with less responsiveness (P=0.0091), the difference in survival curves between the two treatment groups was not significant (P=0.1871). The difference in response between the treatment groups evaluated in terms of posttreatment nadir was not significant (P=0.507). Multivariate analysis identified posttreatment M-protein nadir as a significant prognostic factor associated with survival, along with 3 other factors: sex, performance status, and hemoglobin. The lack of difference between the survival curves for patients treated with the 2 regimens despite the significantly different response rates evaluated in terms of percent fall of pretreatment M-protein levels was considered to be due to the lack of a difference in the ability to induce a deep posttreatment nadir between the regimens. Posttreatment M-protein nadir is an important prognostic factor associated with survival and should be included in the evaluation of the efficacy of chemotherapy.
    Japanese journal of cancer research: Gann 04/1999; 90(3):355-60.
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    ABSTRACT: We report here the results of polymerase chain reaction (PCR) for bcr-abl transcript and clinical details derived from 64 chronic myelogenous leukemia (CML) patients after allogeneic bone marrow transplantation (BMT). A total of 139 samples (2 to 220 weeks after BMT) were analyzed and bcr-abl transcript was detected in 99 samples from 52 patients. Patients were defined as bcr-abl early negative (EN) if they had > or = 1 negative PCR result < or = 1 year post-BMT (n = 13), and bcr-abl late positive (LP) if they had > or = 1 positive PCR result > or = 1 year post-BMT (n = 21). Among LP patients, only two patients had hematologic/cytogenetic (clinical) relapse. Another 19 LP patients remained in clinical remission 7 to 130 weeks after positive analysis for bcr-abl transcript, including 5 patients who had persistent bcr-abl transcript detectable even 2 years after BMT. To estimate the relationship between clinical data and residual bcr-abl transcript, EN patients are compared with LP patients. However, no clinical data studied were significantly associated with the persistent PCR positivity. If only patients in chronic phase are compared, the t-test showed significant correlation between leukocyte count just before BMT and sustained bcr-abl transcript (P < .05). These results suggest that PCR positivity is frequently observed in CML patients who sustain clinical remission after BMT, without being predictive of imminent clinical relapse. Tumor burden at the time of BMT may play an important role in the latency of bcr-abl positivity after BMT.
    Blood 02/1993; 81(4):1089-93. · 10.45 Impact Factor
  • L N Ding · T Yoshida · K Isobe · S M Rahman · F Nagase · T Yokochi · K Kawashima · I Nakashima ·
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    ABSTRACT: The specificities of the antisera raised in the CDF1 mice that had been immunized with the P1.HTR tumor cells xenogenized by transfection with recombinant H-2Kb-erbB gene were studied. The antisera cross-reacted with a broad range of tumor cell lines maintained either in vitro or in vivo in an immunofluorescence assay. However, they did not react at all with syngeneic normal tissue cells from thymus, spleen, bone marrow and fetal liver. Even though antigens related to the murine leukemia virus and murine mammary tumor virus (MuMTV) were demonstrated in many of the tumor cell lines tested with specific antibodies, these antigens did not seem to be primarily involved in the anti-P1.HTR antibody activity. The 74 kDa molecule, which was precipitated by the anti-P1.HTR anti-serum from the surface radiolabeled cell extract of P1.HTR tumor and was discriminated from the 70 kDa molecule precipitated by the anti-MuMTV serum, was widely distributed among various tumor cell lines tested, but was absent in normal tissue cells. In contrast to the extensive cross-reaction by the antibody, the cytotoxic T lymphocyte generated in the P1.HTR immune mice were shown to be specific to the P1.HTR tumor, and the 98 kDa molecule was precipitated by the anti-P1.HTR serum from the P1.HTR tumor but not from other tumors tested. It is suggested from these results that the 98 kDa molecule is a candidate for an individual tumor-specific transplantation antigen, and is immunodominant for inducing cytotoxic T lymphocytes to coexisting intrinsic retroviral antigens and other serologically cross-reactive tumor antigens.
    Japanese journal of cancer research: Gann 08/1991; 82(7):841-7.
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    J Hatazawa · K Hatano · K Ishiwata · M Itoh · T Ido · K Kawashima · K Meguro · S Watanuki · S Seo ·
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    ABSTRACT: Carbon-11-YM-09151-2 binds highly selectively to D2 dopamine receptors in the brain. Using this ligand, D2 dopamine receptor density (Bmax) and affinity (Kd) in canine striatum were measured. After administering various doses of the ligand in nine experiments, regional uptake was followed by repeated PET scanning for up to 80 min. D2 dopamine receptor specific binding at equilibrium was defined as striatal minus occipital activity after partial volume correction. Bmax and Kd were estimated by Scatchard analysis to be 40.3 pmole/ml of tissue and 22.9 nM, respectively. When a low mass dose of the ligand was administered, the bound-to-free ligand ratio in the striatum at equilibrium was consistent with the Bmax/Kd value obtained from the Scatchard analysis. The present study demonstrates the importance of partial volume correction and the Bmax/Kd measurement in a single PET study with carbon-11-YM-09151-2.
    Journal of Nuclear Medicine 05/1991; 32(4):713-8. · 6.16 Impact Factor
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    ABSTRACT: A cooperative randomized clinical trial to compare the effectiveness of multi-drug combination chemotherapy (VMCP), vincristine-melphalan-cyclophosphamide-prednisolone) with CP (cyclophosphamide-prednisolone) for the treatment of multiple myeloma was performed. When the whole group of patients was evaluated, the choice of chemotherapy (VMCP or CP) was not a significant prognostic factor associated with response or survival by uni- or multivariate analysis, and the difference between the survival curves of the treatment groups was only marginally significant. However, when the analysis was confined to stage III patients, the choice of chemotherapy became a significant prognostic factor associated with both response rate and survival, and the statistical difference between survival curves was significant. Taking the disease characteristics of multiple myeloma into consideration, the better result obtained with multi-drug combination chemotherapy in the treatment of stage III patients is consistent with other studies supporting the superiority of multi-drug combination chemotherapy for patients with overt systemic disease.
    Japanese journal of cancer research: Gann 01/1991; 81(12):1320-7.
  • Haruo Nagasawa · Kyuya Kogure · Koichiro Kawashima · Tatsuo Ido · Masatoshi Itoh · Jun Hatazawa ·
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    ABSTRACT: Three female patients aged from 74 to 79 with multi-infarct dementia were studied using positron emission tomography (PET) to assess the effect of co-dergocrine mesylate (Hydergine) on cerebral glucose metabolism. The cerebral glucose utilization (CMRGlc) of each patient was evaluated by PET scan using 2-deoxy-[18F]-2-fluoro-D-glucose (FDG). Following the first PET study, 0.04 mg/kg of co-dergocrine mesylate was injected intravenously with 250 ml saline solution, and then the second PET study was performed. The CMRGlc was determined from the images of the PET scan and the radioactivity of 18F in the plasma. After the administration of co-dergocrine mesylate, the value of CMRGlc increased significantly in the cerebral cortex (p less than 0.01 and p less than 0.05) and basal ganglia (p less than 0.05) compared with values before the administration, but no significant increase was found in the centrum semiovale. These results suggest that co-dergocrine mesylate stimulates glucose metabolism of neurons in the human brain.
    The Tohoku Journal of Experimental Medicine 12/1990; 162(3):225-33. DOI:10.1620/tjem.162.225 · 1.35 Impact Factor
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    M Towatari · Y Ito · Y Morishita · M Tanimoto · K Kawashima · Y Morishima · T Andoh · H Saito ·
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    ABSTRACT: The effect of recombinant human granulocyte colony-stimulating factor (G-CSF) on DNA topoisomerase II (topo II) expression was studied in two human acute myelogenous leukemia cell lines, NKM-1 and NOMO-1, which express G-CSF receptor and proliferate in response to exogenous G-CSF. Northern blot analysis revealed that the level of topo II mRNA in 16-h stimulated cells in serum-free medium with G-CSF (10 ng/ml) was approximately 2-fold higher than that in cells without G-CSF. Enhanced topo II mRNA expression was detectable within 3 h after the addition of G-CSF. Topo II activity in crude nuclear extracts from 16-h G-CSF-stimulated cells was also found to be approximately 2-fold greater than that from unstimulated cells. According to in vitro cytotoxic assay, the sensitivity of G-CSF-stimulated cells to intercalating (daunorubicin) and nonintercalating (etoposide) topo II-targeting drugs increased significantly, whereas no enhancement of sensitivity was observed with an alkylating agent (4-hydroperoxycyclophosphamide). The augmented drug sensitivity observed was not due to the increased level of drug transport, as suggested by the similar extent of [3H]etoposide uptake between G-CSF-stimulated and unstimulated cells. By measuring the topo II mRNA and the cytotoxicity of the above mentioned drugs, we obtained essentially the same results in G-CSF-responsive leukemia cells isolated from three acute myeloblastic leukemia patients, as observed in the cultured cell lines. These findings strongly suggest that the sensitivity to "topo II-targeting drugs" could be augmented by exogenous G-CSF through elevated topo II activity in G-CSF-responsive leukemia cells.
    Cancer Research 12/1990; 50(22):7198-202. · 9.33 Impact Factor
  • K Kogure · K Kawashima · R Iwata · T Ido ·
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    ABSTRACT: Regional water distribution in the rat brain was obtained autoradiographically by activation analysis. The autoradiogram obtained for the normal rat brain showed high accumulation of water in the areas of sensory-motor cortex, hippocampus, thalamus, and amygdaloid cortex, whereas corpus callosum and internal capsule showed low water contents as expected. The estimated values of water content were 78.6 +/- 4.9 weight % for gray matter, and 73.5 +/- 4.9 weight % for white matter, respectively. The mean values of the water content were consistent with those obtained by a conventional drying-weighing method.
    Advances in neurology 02/1990; 52:81-4. · 1.05 Impact Factor
  • L Ding · K Isobe · T Iwamoto · T Yoshida · F Nagase · K Kawashima · I Nakashima ·
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    ABSTRACT: The chimeric mouse MHC class I gene derived from a recombinant H-2Kb gene, in which the coding region for a large part of alpha 1 and alpha 2 extracellular domains was replaced with a partial avian erythroblastosis virus erbB gene segment encoding the kinase domain, was successfully introduced into a mouse mastocytoma line P1.HTR (H-2d) and transcribed to mRNA. The transfectant cells expressed the chimeric gene product, which was reactive to a phosphotyrosine-specific antibody. When the chimeric gene transfectant was inoculated into CDF1(H-2d) or BDF1(H-2d/b) mice, it grew at an early time but regressed thereafter. Transfectant-specific as well as parental P1.HTR-specific antibody activities were demonstrated in the sera of these mice. Transfectant-specific cytotoxic T lymphocytes (CTL) were generated in the antigen-sensitized culture of spleen cells from the transfectant-immune mice. The CTL-mediated lysis of target chimeric gene transfectant cells was poorly inhibited by anti-H-2d antiserum, which blocked the lysis of parental P1.HTR cells by anti-tumor CTL developed in parallel. The former was, however, inhibited by either anti-transfectant antiserum or anti-phosphotyrosine antibody, which was ineffective for blocking the latter. Target cell lysis by either anti-transfectant or anti-tumor CTL was blocked by anti-CD8 monoclonal antibody but not by anti-CD4 antibody. It was suggested from these results that the H-2K-erbB hybrid gene product, which lacks complete three-domain class I structure, was recognized by CTL in a manner that was endogenous H-2 class I-independent but CD8-dependent.
    International Immunology 02/1990; 2(1):91-7. DOI:10.1093/intimm/2.1.91 · 2.54 Impact Factor
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    ABSTRACT: Two [18F]fluoroalkyl analogs of a neuroleptic YM-09151-2 were synthesized via nucleophilic [18F]fluorination of methanesulfonyloxy- or p-toluenesulfonyloxyalkyl derivatives using no-carrier-added [18F]fluoride. Although 3-[18F]fluoropropylaminobenzamide was obtained in good yield, the yield of 2-[18F]fluoroethyl derivative was severalfold lower. The product, N-[(2RS,3RS)-1-benzyl-2-methylpyrrolidin-3-yl]-5- chloro-2-methoxy-4-(3-[18F]fluoropropyl)-aminobenzamide, was shown to have a striatum-to-cerebellum ratio comparable to that of 11C labeled YM-09151-2 and thus to be a good candidate for measuring D2-receptors in vivo.
    International Journal of Radiation Applications and Instrumentation Part A Applied Radiation and Isotopes 02/1990; 41(6):551-5. DOI:10.1016/0883-2889(90)90038-I
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    ABSTRACT: To clarify the clinical and pathological determinants affecting the sensitivity of urinary cytology, we reviewed cytological findings from 119 patients with bladder cancer who were initially treated between January 1982 and March 1988. Cytological specimens obtained from voided urine were stained by the Giemsa and Papanicolaou techniques, and were classified into three categories of malignant cells: positive, suspicious, and negative. Of 311 specimens examined, 114 (37%) were positive, 81 (26%) were suspicious, and the remaining 116 (37%) were negative. The overall positive rate, or sensitivity, was 50% (60 out of 119 patients). The sensitivities were 7% for patients with grade 1 tumors, 42% for grade 2 tumors, and 97% for grade 3 tumors. Univariate analysis by logistic regression analysis revealed that grade, stage, histological pattern of growth, size and number of tumors, and patient age were significantly related with the positivity of voided urinary cytology. The logistic regression model, as a multivariate analysis, demonstrated that grade was the most important determinant affecting the positive cytologic finding, followed by number of tumors with statistical significance. We conclude that the lower sensitivity in conventional urinary cytology for low-grade tumors necessitates new adjuncts, including immunocytochemistry and flow cytometry, to lower the false-negative rate.
    Hinyokika kiyo. Acta urologica Japonica 02/1990; 36(1):7-11.
  • K.-i. Isobe · Y Hasegawa · T Iwamoto · T Hasegawa · K Kawashima · L N Ding · I Nakashima ·
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    ABSTRACT: An allo-major histocompatibility complex class I gene (H-2Kb) was transfected to murine mastocytoma P1.HTR (P815 subline) cells, after which several transfectant clones were obtained. Two clones, which expressed a low level of H-2Kb antigen, grew well and killed the syngeneic DBA/2 mice when they were inoculated ip. These mice lived longer than the mice given injections of the parental P1.HTR tumor. However, one clone, which expressed a high level of H-2Kb antigen, was rejected completely by the syngeneic DBA/2 mice and induced a generation of H-2Kb-specific cytotoxic T cells. Interestingly, the mice that had rejected the clone with high H-2Kb expression received strong anti-tumor immunity for rejection of the parental P1.HTR tumor challenged at the high dose.
    JNCI Journal of the National Cancer Institute 01/1990; 81(23):1823-8. DOI:10.1093/jnci/81.23.1823 · 12.58 Impact Factor
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    K Hatano · K Ishiwata · K Kawashima · J Hatazawa · M Itoh · T Ido ·
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    ABSTRACT: The in vivo D2-receptor specific brain uptake of N-[(2RS,3RS)-1-benzyl-2- methyl-3-pyrrolidinyl]-5-chloro-2-methoxy-4-[11C]methylaminobenzamide ([11C]YM-09151-2), was investigated. In rat brain the high uptake of [11C]YM-09151-2 in striatum was displaced with sulpiride, spiroperidol, and YM-09151-2. SCH-23390 and ritanserin, D1-dopamine and S2-serotonin antagonists, showed no effect on the distribution of [11C]YM-09151-2. In the striatum at 60 min, 95% of the radioactivity was detected as [11C]YM-09151-2 by high performance liquid chromatography. On the other hand, 41% of 11C in the plasma at 60 min was observed as metabolites. In vivo autoradiography showed a high uptake of [11C]YM-09151-2 in the striatum and in the nucleus accumbens of rat brain. A high uptake of radioactivity was also found in the canine basal ganglia with positron emission tomography. The uptake was reduced by pretreatment with spiroperidol. The present results demonstrate that [11C]YM-09151-2 is a D2 receptor specific compound and is a potential in vivo tracer for measuring D2 receptors.
    Journal of Nuclear Medicine 05/1989; 30(4):515-22. · 6.16 Impact Factor
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    ABSTRACT: The feasibility of 2-deoxy-2-[18F]fluoro-D-galactose ([ 18F]FdGal) for imaging galactose metabolism in tumors with positron emission tomography (PET), was investigated using two hepatomas, Yoshida sarcoma, or glioma in rats, and mouse mammary carcinoma. In hepatoma-bearing rats the highest uptake of [18F]FdGal was observed in the liver followed by the kidney and tumor. The tumor uptake increased with time, and the high uptake ratios of tumor to organ were observed except for the liver and kidney. Tumor uptake was also measured in all tumors. As main metabolites in all tumors, [18F]FdGal 1-phosphate and UDP-[18F]FdGal were found by HPLC. Two hepatomas showed a slightly higher uptake and a larger percentage of UDP derivative than the other three tumors. By autoradiography the brain tumor was visualized clearly. These results indicate that [18F]FdGal has potential as a tracer for imaging galactose metabolism in tumors with PET.
    International Journal of Radiation Applications and Instrumentation Part B Nuclear Medicine and Biology 02/1989; 16(3):247-54. DOI:10.1016/0883-2897(89)90005-6
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    K I Ando · K I Isobe · T Hasegawa · T Iwamoto · R N Ding · J Rahman · Y Muro · T Yoshida · F Nagase · K Kawashima ·
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    ABSTRACT: By adding IL-2 (supernatant of culture of concanavalin A-activated rat spleen cells) on Day 3 of mixed leucocyte cultures (MLC) we managed to fully activate multiple minor histocompatibility antigen (MIHA)-specific cytotoxic T-lymphocyte precursors (CTLp). In this newly developed system we studied genetic and stimulator cell requirements for the generation and activation of MIHA-specific memory CTLp. Memory CTLp were activated to generate effector CTL in MLC only when major histocompatibility complex (MHC)-compatible MIHA-allogeneic cells were used as stimulators. In contrast, memory CTLp were generated in mice that were primed by injection of either MHC-compatible or incompatible MIHA-allogeneic spleen cells. A surprisingly small number (10(4] of MHC-disparate cells cross-primed mice effectively. For priming, no special accessory cell types were required as stimulators, and 10(4) adherent cell-depleted spleen cells primed mice as well. These results contrasted to another finding that sonication-disrupted 10(6) stimulator cells did not prime mice effectively, and antigens shed from 10(7) live stimulator cells failed to sensitize host antigen-presenting cells for priming. It is suggested from these results that the mode of recognition of MIHA by virgin CTLp is unique or that an as yet unknown unusual stimulation pathway works for the priming.
    Immunology 09/1988; 64(4):661-7. · 3.80 Impact Factor

Publication Stats

585 Citations
201.91 Total Impact Points


  • 1999
    • The Graduate University for Advanced Studies
      Миура, Kanagawa, Japan
    • Yokkaichi Municipal Hospital
      Yokkaiti, Mie, Japan
  • 1990-1999
    • Nagoya University
      • • Clinical Laboratory
      • • Division of of Internal Medicine
      Nagoya, Aichi, Japan
  • 1984-1991
    • Tohoku University
      • • Cyclotron and Radioisotope Center (CYRIC)
      • • Department of Pharmaceutical Chemistry
      Sendai-shi, Miyagi, Japan
  • 1988
    • Sendai University
      Sendai, Kagoshima, Japan

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