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We present nowcasts of sudden heavy rains on meso-γ-scales (2–20 km) using the high spatio-temporal resolution of a Multi-Parameter Phased-Array Weather Radar (MP-PAWR) sensitive to rain droplets. The onset of typical storms is successfully predicted with 10-minute lead time, i.e., the current predictability limit of rainfall caused by individual convective cores. A supervised recurrent neural network based on Long Short-Term Memory with 3D spatial convolutions (RN3D) is used to account for the horizontal and vertical changes of the convective cells with a time resolution of 30 sec. The model uses radar reflectivity at horizontal polarization (ZH) and the differential reflectivity. The input parameters are defined in a volume of 64×64×8 km3 with the lowest level at 1.9 km and a resolution of 0.4×0.4×0.25 km3. The prediction is a 10-minute sequence of ZH at the lowest grid level. The model is trained with a large number of observations of summer 2020 and an adversarial technique. RN3D is tested with different types of rapidly evolving localized heavy rainfalls of summers 2018 and 2019. The model performance is compared to that of an advection model for 3D extrapolation of PAWR echoes (A3DM). RN3D better predicts the formation and dissipation of precipitation. However, RN3D tends to underestimate heavy rainfall especially when the storm is well developed. In this phase of the storm, A3DM nowcast scores are found slightly higher. The high skill of RN3D to predict the onset of sudden localized rainfall is illustrated with an example for which RN3D outperforms the operational precipitation nowcasting system of Japan Meteorological Agency (JMA).

This overview, based on the categorization by Mark Dyreson at Pennsylvania State University of researchers into “historians of sports” and “sports historians” reveals that, in the United States, a close relationship between the two groups that originated in the 1970s is now facing a critical moment. In Japan, both groups have maintained a steady relationship since the 1980s, while historians of sports have taken a leading position as reflected in their dominant role in writing the Japan Journal of Sport History (JJSH)’s articles. In China, a gradual shift to sport history seems to be taking place, as its academia, having started from the orthodox historical discipline, is currently giving ground to social and natural sciences. It is high time for scholars of the United States, Japan, and China to meet together in one place to look back on their pasts and carve out new horizons. This is an important step in developing a global history of sports.

The relationship between sports and medicine in Japan has remained largely unexplored by historians. This paper aims to clarify the historical context in which the relationship became closer and th...

Under the Japanese Cross Strategic Innovation Promotion Program (SIP), studies are conducted to perform very short-term predictions of local torrential rains based on a new multi-parameter phased-array weather radar (MP-PAWR) and deep neural networks (DNNs). The association of the two methods is expected to overcome the limitations of the conventional rains observation systems and numerical models that are not well suited to handle the rapid non-linear processes inherent in heavy convective rains. The unique spatio-temporal resolution of the observations allows us to train supervised DNNs to extrapolate the fast evolution of 3D convective cells. We compared two DNNs (CLM3D and CGRU3D) designed to fully exploit the information in the vertical dimension. Both methods use new techniques involving spatial convolutions in temporal recurrent iterations such as Long Short-Term Memory (LSTM) or Gated Recurrent Units (GRU) ones. The core of CLM3D is a stack of convLTSM2D layers, each of which is applied to a single altitude. CGRU3D uses a multilayer encoderdecoder with convGRU3D layers, each layer is associated with a size of 3D spatial features. Forecasts with a lead-time of 10 min at an altitude of 600 m with a horizontal resolution of about 500 m are compared. The models are tested with different types of heavy precipitation: localized short-lived rains on July 24, 2018 and wide-spread ones on the 29 of the same month. The models are evaluated with respect to a 3D linear advection nowcast model (OF3D) and a persistent one. We found that the DNN and OF3D models perform better on July 24 with similar scores that are significantly higher than those of the persistent model. Considering all rain events, critical success indexes (CSI) of 0.62, 0.53, 0.55 are found for CGRU3D, CLM3D and OF3D, respectively, and 0.43 for the persistent model. Regarding only heavy precipitation, the CSIs show a great variability between 0 and 0.4 on the predictions made that day. These results clearly illustrate the great challenge of nowcasting heavy precipitation. On July 29, none of the models have significantly higher scores than those obtained with the persistent nowcast. The interesting result of this study is that the two DNNs show similar nowcasting skills whatever the intensity and the type of rain, and this despite their architectures and training strategies being different. This may indicate that optimizing the tunning of the hyperpameters and the training dataset could not bring significant improvements and, the key, could be by feeding the models with more comprehensive information on the atmospheric state.

The People’s Republic of China (PRC) has appeared to be inattentive towards the globally lobbied Sport for Development and Peace (SDP) movement that endeavors to leverage sport for non-sporting development, currently subscribing to the United Nations’ 17 Sustainable Development Goals (SDGs). By adopting the concept of ‘tiyu (体育)’—the supposed Chinese counterpart of ‘sport’—which also seeks to achieve wider objectives grounded on its premise of ‘body cultivation’, this paper proceeds with a text-based qualitative study incorporating document analysis and literature review to examine its current links to SDP. The findings suggest that: (1) While the national development foci of the PRC have demonstrated alignment with the SDGs, its tiyu policies have not. (2) Mainstream SDP projects have failed to be accommodated in the PRC, although some non-SDP tiyu practices have shown a commitment to SDP-desired outcomes. (3) The relative lack of interest in SDP in the PRC has not prevented some tiyu scholars from heeding this movement. Accordingly, this paper assesses the prospects of changing attitudes in the PRC toward SDP.

This study is to analyse how the Japanese have traditionally received and currently perceive the Super Bowl, and for this purpose, it aims to locate the position of American football in Japanese history, society, and culture. It explores the game’s history and then examine the degree of its spread among Japan’s sporting population. A two-dimensional approach of historical study and inter-game comparison gives context to the analyses of reference frequency and contents of news media, followed by speculative discussions of what the near future of Japan’s American football would be like. To conclude, it clarifies the ways the Super Bowl has been received and is now being perceived by two groups: The first group is the general people who see the Super Bowl as the convenient and useful medium by which they could learn effectively about American culture through the one-night mania for ‘conspicuous consumption’. The second group comprises American football experts and enthusiasts, including 13,000 athlet...

全身麻酔後に発生する，耳下腺の浮腫はanesthesia mumpsとして報告されているが，同じ唾液腺に含まれる顎下腺に腫脹をきたした症例の報告はない．今回，顎下腺腫脹をきたした症例を経験したので報告する．67歳の女性．全身麻酔下に開頭腫瘍摘出術が行われた．術後，十分な自発呼吸を確認し手術室で抜管した．退室時，顔面や頚部の腫脹は認めなかった．術後2時間から頚部腫脹を認め，術後4時間で呼吸困難感が出現した．CT上，顎下腺の浮腫が原因と考えられた．気道閉塞の危険性を考慮し，手術翌日に外科的気道確保を行った．全身麻酔後の顎下腺の浮腫は非常にまれと思われるが，外科的気道確保を必要とする可能性もあり留意すべきと考えられる．

Objective A newly designed combination chemotherapy for multiple myeloma, MMCP [ranimustine (MCNU), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL)], was analyzed and compared with the results of our previous randomized trial of VMCP [vincristine, MPH, CPM and PSL] and MMPP [MCNU, MPH, procarbazine and PSL]. Methods MCNU (33.3 nig/m2, div) on day 1 and MPH (4 mg/m2, po), CPM (66.7 mg/m2, po) and PSL (30 mg/m2, po) from day 1 to 4, were administered. Each cycle was repeated every 3 weeks. Patients or materials From January 1991 until August 1995, 104 patients with multiple myeloma diagnosed at 10 hospitals of Nagoya Cooperative Study Group were enrolled. Results Of the 87 evaluable patients, partial response rate for MMCP was 65.5% and was significantly higher than that of VMCP (13/47=27.7%, p

We conducted a retrospective study of patients with IgG or IgA myeloma who attained plateau to evaluate the relationships between survival and posttreatment nadir M-protein levels and between survival and the response to treatment evaluated by the percent reduction in M-protein. Of the 127 patients comprising 92 IgG and 35 IgA myeloma patients with disease stages II or III, 51 (40.2%) attained plateau. For IgG myeloma patients who attained plateau, survival time was not affected by the percent reduction in M-protein (median survival, 59.5 months for responding patients versus 54.4 months for non-responding patients,P = .6910). Posttreatment nadir M-protein level, however, did affect survival time (median survival, 61.2 months for >3000 mg/dL versus 25.7 months for

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.

In order to obtain the realistic background information on clinical features, and the present status of treatment and outcome in elderly patients with acute lymphoblastic leukemia (ALL), we carried out random survey of patients with ALL aged 60 or over who had been admitted to 13 general hospitals in the Nagoya region from January 1990 through December 1995. Among the 20 cases collected, ages ranged from 60 to 88 (median age 68), and the male to female ratio was 11:9. Nineteen cases were L2 subtype in FAB classification. Among 17 patients, 13 had B cell series surface phenotypes (76%), 2 had T cell series (12%), one had stem cell type (6%) and one had an undetermined phenotype (6%). Ph chromosomes were detected in 4 cases among 15 analyzed (27%), whereas 5 were found to have no chromosomal abnormality. Half of the patients had some concurrent disease at diagnosis, including two with treatment-limiting complications. Common induction regimens were the combination of adriamycin (ADM) + vincristine (VCR) + cyclophosphamide (CPM) + mitoxdn trone + L-asparaginase [4 patients]. ADM + VCR + PSL [4 patients]. VCR + PSL [4 patients] and others [8 patients]. The overall remission rate was 55.0% (11/20) without any significant difference according to age. The median survival time (MST) for all cases was 205 days. (1-year survival rate:17.9%, 2-year survival rate:10.8%). There was no significant difference in survival times among patients with the Ph chromosome, those with other chromosomal abnormalities and those without them. All the patients aged 75 or over were treated with attenuated induction therapy, and they had a shorter survival than those aged less than 75, but with no statistical significance [MST:121 days versus 276 days, p = 0.307 (generalized Wilcoxon test)].

Emergency surgery itself induces high risk for postoperative mortality and morbidities; however, it remains unknown which concomitant pathological conditions of emergency surgeries are causative factors of deteriorating outcomes. This study examined the causal factors of postoperative mortality and morbidity in cases of emergency surgery.Patients undergoing emergency surgery from January to December 2007 were enrolled in this retrospective cohort study. Causal relationships were analyzed by stepwise multivariate logistic regression analysis between possible independent factors (sex, age, kind of surgical department, timing of surgery, duration of surgery, blood transfusion, deteriorated consciousness level, shock state, abnormal coagulate state, and history of hypertension, diabetes, ischemic heart disease, chronic obstructive pulmonary disease, renal failure, and anemia) and postoperative mortality or morbidities (failure of removal of tracheal tube after operation, tracheotomy, cerebral infarction, massive hemorrhage, severe hypotension, severe hypoxemia, and severe arrhythmia during or after surgery).Shock, deteriorated consciousness level, chronic obstructive lung disease, and ischemic heart disease were significant risk factors for mortality (OR 14.2, 7.9, 6.4, and 3.8, respectively), and deteriorated consciousness level, blood transfusion, shock, chronic obstructive lung disease, diabetes, cardiovascular surgery, and operation longer than 2 h were significant risk factors for morbidity (OR 19.1, 3.3, 3.0, 2.5, 2.4, 2.4, and 1.8, respectively).State of shock, deteriorated consciousness level, chronic obstructive lung disease, ischemic heart disease, hemorrhage requiring blood transfusion, age over 80 years, cardiovascular surgery, surgeries at night, and surgeries of duration more than 2 h cause patients to be strongly susceptible to postoperative mortality or morbidity in emergency surgeries.

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.

We established one transgenic mouse line which developed pre-B leukemic lymphomas by introducing ret cDNA driven by the SV40 promoter and the mouse immunoglobulin (Ig) enhancer. Lymphomas developed not only in the lymph nodes and the spleen but also in the thymus between the ages of 7 and 21 weeks. Analyses of cell surface phenotypes and Ig gene rearrangement revealed that these tumors were surface IgM-B220+ pre-B lymphomas. The rearrangement pattern of the Ig heavy chain locus indicated that the tumor cells were mono- or oligoclonal. Northern blot analysis showed that the ret transgene was expressed at a high level not only in the tumors but also in the prelymphomatous lymphoid tissues. We found that the expression of N-myc was dramatically down-regulated in the tumor cells, while the expression of c-myc was rather stable. Further experiments demonstrated that ret gene product did not directly down-regulate the expression of N-myc in transformed pre-B cell lines by in vitro transfection assay. From these results, we conclude that under the control of Ig enhancer, the ret transgene affected B lymphocytes at the early maturation stage as a prerequisite for transformation, preferentially generating a unique maturation stage of pre-B lymphomas whose N-myc expression was developmentally down-regulated.

The specificities of the antisera raised in the CDF4 mice that had been immunized with the Pl. 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 thynms, 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-Pl. HTR antibody activity. The 74 kDa molecule, which was precipitated by the anti-Pl. HTR anti-serum from the surface radiolabeled cell extract of Pl. 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 Pl. HTR immune mice were shown to be specific to the Pl. HTR tumor, and the 98 kDa molecule was precipitated by the anti-Pl. HTR serum from the Pl. 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.

Two patients with hematological malignancies were successfully treated with mono methoxypolyethylene glycol-conjugated Escherichia coli l -asparaginase (PEG 2 -ASP), which reportedly lacks both antigenicity and immunogenicity but retains catalytic activity as well as slow clearance in an experimental animal model. A 20-year-old male patient with leukemic lymphoma was refractory to conventional chemotherapy but responsive to l -asparaginase ( l -ASP) followed, however, by severe adverse effects. On relapse, an intravenous infusion of 100–200 IU/day dose of PEG 2 -ASP alone led to a complete remission 2 months later without hypersensitivity or other significant adverse reactions. Surprisingly, he remained in a complete remission for over one year with a regular weekly infusion of PEG 2 -ASP, combined with a weekly small dose of Ara-C. During this period, blood asparagine was not detectable. The other patient, a 64-year-old woman with chronic myelogenous leukemia in blast crisis achieved, within 6 weeks, a complete remission with twice-weekly infusions of PEG 2 -ASP. Thus, PEG 2 -ASP is a highly effective antitumor agent overcoming the limitations in therapeutic use of l -ASP.

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.

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.

The actual utility of a new classification system of acute myeloid leukemia (AML) recently introduced by the World Health Organization (WHO) has not been thoroughly investigated yet. In this study, we evaluated long-term outcomes of unselected AML patients categorized according to the new WHO classification. Between 1990 and 2002, 109 adult AML cases were referred to our hospital. For the entire population, the median survival duration was 1.2 yr with a 5-yr survival rate of 31%. AML with recurrent genetic abnormalities accounted for 26%, AML with multilineage dysplasia for 29%, therapy-related AML for 13%, and AML not otherwise categorized for 32% of classifiable cases. Among the four groups, a significant difference was observed in terms of overall survival (P < 0.0001). Univariate analysis showed that six variables affected survival: cytogenetic risk, age, multilineage dysplasia, prior chemo/radiotherapy, type of treatment (intensive or palliative), and transplantation. However, in multivariate analysis no adverse prognostic impact of multilineage dysplasia and prior chemo/radiotherapy was detected (P = 0.4979 and 0.8702), whereas cytogenetic risk and patient age maintained their prognostic value (P = 0.0005 and 0.0100). These results indicate that outcomes for AML patients appear to be distinguished on the basis of the WHO classification, but the prognostic significance of multilineage dysplasia and prior therapy is lost after adjusting for cytogenetic risk and age. Our findings suggest that the WHO classification may be strengthened by greater emphasis on genetic/cytogenetic information.

Purpose: To compare VMCP, a multidrug combination chemotherapy comprising vincristine (VCR), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL), with MMPP comprising MPH, ranimustine (MCNU), procarbazine, and PSL as induction, to elucidate the value of alternating combination chemotherapy, and to search for an appropriate maintenance therapy in multiple myeloma. Methods: At 16 institutions in the Nagoya City area, we carried out a randomized trial of VMCP versus MMPP as the initial treatment. Patients who were refractory or resistant to the initial therapy were crossed over into the other arm (crossover trial). For patients who achieved a partial response (PR) or a minor response (MR) and in whom the paraprotein level ceased to decrease, the maintenance therapy was randomized either to an MPH/PSL combination (MP) or to alternating combination therapy (AT) with VMCP and MMPP. Results: In the 94 evaluable patients of the 111 enrolled, the response rate (PR rate) was 27.7% (13/47) in the VMCP arm and 44.7% (21/47) in the MMPP arm (P=0.0859). The crossover trial resulted in a PR rate of 15.8% (3/19) for the VMCP→MMPP crossover and 14.3% (2/14) for the MMPP→VMCP crossover. The median survival time was 23.4 months for those initially begun in the VMCP arm and 24.9 months for those in the MMPP arm, showing a tendency for better survival during a follow-up of 2–6 years with MMPP treatment, but without statistical significance. The survival time of patients with progressive disease was significantly shorter than that of patients with PR, MR or no change (NC). However, there was no significant difference in the survival rate among those who achieved PR, MR, or NC. As to the maintenance therapy, there was no significant difference in survival between MP therapy and AT. Patients who reached a plateau phase survived significantly longer than those who did not. Except for six cases of grade 3 or 4 neurotoxicity in the VMCP arm, there was no significant difference in the hematologic or gastrointestinal toxicity between the two arms. Conclusions: We conclude that VMCP is less effective for myeloma than MMPP as the induction treatment, that alternating noncrossresistant chemotherapeutic combinations do not offer an advantage in multiple myeloma, and that patients who reach a plateau phase have a significantly longer survival time.

We present an 18-year-old woman who was diagnosed with acute myeloblastic leukemia (AML M2), and in whom chromosome analysis of bone marrow cells revealed t(7;11), an abnormality rarely found in leukemias with a differentiation potency. She relapsed 1 year after complete remission was achieved by chemotherapy. Bone marrow examination then revealed a t(7;11) abnormality in 48 of 50 metaphases examined, even when there were less than 7.5% leukemic blasts in the marrow, indicating that the morphologically normal cells were derived from leukemic blasts. The number of leukemia clones with the additional abnormalities in chromosome 5 increased, with concurrent development of eosinophilia, fever, asthma-like symptoms, erythema, itching, and hepatosplenomegaly. Elevation of interleukin 5 (IL-5) in serum and an enhanced expression of IL-5 mRNA were also detected. The increase in IL-5 may have been produced by an abnormality on chromosome 5.

Aclarubicin was evaluated in combination chemotherapy for adult acute myeloid leukemia in a randomized trial involving 58 institutions throughout Japan. Behenoyl cytosine arabinoside (BH-AC).daunorubicin, 6-mercaptopurine, and prednisolone (DMP) was compared with BH-AC.aclarubicin, 6-mercaptopurine, and prednisolone (AMP). In the 360 evaluable cases among the 433 cases enrolled, complete remission (CR) rates were 63.7% (116/182) for BH-AC.DMP and 53.9% (96/178) for BH-AC.AMP (P = 0.0587). Median survival periods and 7-year survival rates were 15.8 months and 19.3% for BH-AC.DMP and 9.5 months and 20.2% for BH-AC.AMP (P = 0.0091 according to the generalized Wilcoxon test [GW], P = 0.196 according the log-rank test [LR]). Median disease-free survival periods were 15.4 months for BH-AC.DMP and 14.1 months for BH-AC.AMP (P = 0.851 by GW, P = 0.439 by LR). Among the 346 cases of extramurally confirmed FAB subtypes, CR rates were 67.9% (19/28) with BH-AC.DMP and 31.8% (7/22) with BH-AC.AMP for subtype M3 (P = 0.011) and 63.3% (93/147) with BH-AC.DMP and 56.8% (84/148) with BH-AC.AMP (P = 0.254) for subtypes M1, M2, M4, and M5. Diarrhea, ileus, pneumonia, and renal failure were more frequent with BH-AC.AMP than with BH-AC.DMP. The results indicate, at least on the basis of the long-term outcome, that BH-AC.AMP has antileukemic effects on subtypes M1, M2, M4, and M5 that are comparable with those of BH-AC.DMP.

A randomized clinical trial of combination chemotherapy for adult acute lymphoblastic leukemia (ALL) with doxorubicin, vincristine and prednisolone with and without L-asparaginase (AdVP vs L-AdVP) was conducted, involving 58 institutions throughout Japan. After reaching complete remission (CR), patients were treated with the same regimen for more than 2 years. Among 166 evaluable cases of the 198 cases enrolled, CR rates were 63.1% (53/84) with AdVP and 64.6% (53/82) with L-AdVP (P = 0.837). Median survival times and 7-year survival rates were 12.7 months and 21.2% with AdVP, and 16.0 months and 22.3% with L-AdVP (P = 0.955 by generalized Wilcoxon test [GW], P = 0.952 by log-rank test [LR]). Median disease-free survival times and 7-year survival rates were 13.5 months and 23.8% with AdVP and 17.0 months and 30.6% with L-AdVP, showing some increments for L-AdVP but no statistical significance (P = 0.141 by GW, P = 0.300 by LR). Among the cases of extramurally confirmed FAB subtypes, CR rates were 75.9% (63/83) for the L1 subtype and 51.3% (39/76) for the L2 subtype (P = 0.001). As to adverse effects, pancreatitis was complicated more frequently in L-AdVP than in AdVP (P = 0.039). Other side effects such as hyperbilirubinemia, diabetes mellitus, diarrhea and hypofibrinogenemia were observed more frequently with L-AdVP, but with no statistical significance. Thus, addition of a single course of L-asparaginase in the induction phase of combination chemotherapy with doxorubicin, vincristine and prednisolone did not significantly enhance the effect of antileukemic treatment of adult ALL.

We analyzed the changes of frequency of bacterial positive cases on the basis of blood cultures, clinical background and administrated antibiotics for the patients with bacteremia in Nagoya University Hospital from January 1978 to December 1987. During the ten years, the number of samples increased from 330 in 1978 to 1231 in 1987. Moreover, bacterial positive cases increased from 27 (8.2%) in 1978 to 152 (12.3%) in 1987. Organisms isolated consisted of 138 strains of coagulase negative Staphylococci (CNS), 81 Staphylococcus aureus, 60 Candida sp., 58 Escherichia coli, 47 Pseudomonas aeruginosa, and other species. During the period of 1986-1987, of the 92 patients with bacteremia, 85 patients (92.4%) had underlying diseases including leukemia, solid tumor, cardiovascular disease, diabetes mellitus or other diseases. In addition, 67 patients (73.9%) underwent intravascular catheters, urethral catheters, postoperative drainages or other prosthetic insertions. Fourteen patients died of septicemia within a week after recovery of the organism in the blood culture. The recovery rate for gram positive cocci in blood culture increased in the 1980's. It may partly be due to the prevalent use of these prosthetic insertions, and the preferable use of second and third generation cephalosporin antibiotics.

The recombinant H-2Kb-erbB gene, encoding for a part of the H-2 class I antigen and the kinase domain of the V-erbB peptide, was successfully introduced into murine mastocytoma P815 variant P1.HTR cells, which resulted in low but significant cell-surface expression of the hybrid gene product. When the chimeric gene transfectant was inoculated into the CDF1 mice, it soon grew but regressed thereafter. The tumorigenicity of this transfectant was lower than the H-2Kb gene transfectant that expressed the H-2Kb antigen at a comparable level. These CDF1 mice that had received the chimeric gene transfectant obtained a high-grade anti-tumor immunity against the challenge of a high dose of parental tumor. Corresponding to these observations, anti-tumor cytotoxic T lymphocytes, which lyse parental P1.HTR cells but not syngeneic L1210 or NS-1 tumor cells, were developed in the peritoneal cavity of mice that had been inoculated with the transfectant and parental tumor. Definite antibody activity binding to parental P1.HTR tumor cells was also demonstrated in the sera of these mice, precipitating 40-kDa, 74-kDa and 98-kDa molecules from the surface of the radiolabeled P1-HTR tumor cells. The results suggested that the chimeric H-2-erbB gene transfectant efficiently triggers both cellular and humoral anti-tumor immune responses.

Ontogeny of the murine transplantation immunity for rejecting ascitic allogeneic tumors (chemically-induced RG lymphoma and L1210 leukemia) as a model of in vivo cytotoxic T cell immunity was studied. challenge by 10 6 to 10 7 allogeneic tumor cells per 20 g body weight (b.w.) of the mouse was fatal to 1–3 day-old mice, whereas 7–30 day-old mice rejected the tumor. In newborn mice however some yet undetermined mechanism worked to temporally depress the initial tumor growth. Injection of low (10 6 cells per 20 g b.w.) to moderate (10 7 ) doses of semiallogeneic spleen cells into newborn mice prepared for second set rejection of the tumor carrying the same alloantigens as the spleen cells, although injection of high dose (3 × 10 8 ) cells reduced the tumor rejecting immunity. This second set rejection occurred even against the allogeneic tumor inoculated as early as 3 days old, if the mice had been primed with the alloantigens at birth. It appears therefore that newborn and early suckling mice are protected from tumor invasion by cytotoxic immunity more powerfully than expected from earlier in vitro works.

Serum antibody responses of mice to repeatedly inhaled protein antigens such as bovine serum albumin and ovalbumin, plus or minus bacterial lipopolysaccharide (LPS) in the form of an aerosol were studied. Results showed that the levels of responses to inhaled protein antigens varied, depending on the mouse strain-antigen combination and that LPS inhaled simultaneously with the antigens definitely augmented the responses which were not otherwise very high. LPS extracted from Klebsiella O3 (LPS-K) but not LPS from Escherichia coli O55 (LPSE), which was inhaled at the time of initial inhalation of antigen, significantly intensified the priming for the secondary antibody response to the antigen subsequently inhaled. Both LPS-K and LPS-E, however, definitely acted to augment the response when they were inhaled repeatedly together with the antigen. Oral administration of antigen or antigen plus LPS-K did not induce any detectable antibody response in our experiment, ruling out the possibility that the antigen and LPS stimulated the immune system via alimentary canal rather than via lung. Tissue distribution of the radioactivity soon after inhalation of 131 I-labeled antigen and decay speed of the radioactivity were not significantly changed by LPS-K inhaled simultaneously. This suggested that the augmentation of responses was not mediated by the action of LPS to modulate the air-blood barrier against the entry of antigen via lung. All the results prove for the first time that inhaled LPS displays a definite adjuvant action on antibody responses to inhaled antigens.

During the course of immunization of (C3H × DBA/2)F 1 mice (genotype H -2 k / b ) with L cell ( H -2 k / k )/L1210 leukemia cell ( H -2 d / d ) hybrids and L1210 leukemia cells, some of them produced a good titer of anti-self-H-2 (H-2 d ) antibodies. Antigens recognized by this anti-self-H-2 antiserum were shown to be controlled by the H-2K-IA-IB-IJ-IE subregions of the H -2 d but not H -2 k nor H -2 b haplotypes of parental as well as F 1 origins and to have a tissue distribution identical to that of class 1 H-2 (H-2K/D) antigens.

Two monoclonal antibodies (anti-3–3 and anti-3–40) were produced, which identify two new leukemia-associated antigens. Both antibodies reacted with most cell lines derived from patients with T lymphoblastic leukemia (T-ALL), but were not detected on suspensions of normal hematopoietic cells (including thymocytes) by cytotoxicity, absorption, or indirect immunofluorescence assays. Analysis of fresh leukemic cells indicated that anti-3–3 only reacted with T-ALL cells, while anti-3–40 also reacted with some non-T, non-B ALL cells and a few acute myelocytic leukemia (AML) cells. The 3–40 antigen was also found histopathologically in frozen sections of several normal tissues, including the epithelial cells and a few lymphoid cells of the thymus, and some malignant tissues. The 3–3 antigen was not found in any tissue studied. A “double absorption” assay provided additional serologic evidence that the two antibodies identify different antigenic determinants. Biochemical analysis indicated that the molecules immunoprecipitated by anti-3–3 and anti-3–40 have molecular weights of 35,000–40,000 daltons. This study demonstrated that the 3–3 and 3–40 antigens are markers for human T-ALL and can be used along with the normal T-lymphocyte antigen, 3A1, to discriminate T-ALL from cutaneous T-cell lymphoma (CTCL), adult T-cell leukemia (ATL), and T-cell chronic lymphocytic leukemia (T-CLL).

The murine leukemia L1210-specific cytotoxic T-cell clone K7 was established by repeated antigenic stimulation of spleen cells of L1210-immune CD2F1 mice in long-term culture. K7 possessed L1210-specific cytolytic activity detectable by the 51Cr-release test, but lost its cytolytic activity about 100 days after initiation of culture (designated as clone K7L). Clone K7L retained its L1210-specific tumor-growth-inhibitory activity independently of culture supplementation with IL-2. K7L possessed the cell-surface antigenic phenotype of cytotoxic T cells, Thy-1+, Lyt-1-, Lyt-2+. This clone K7L displayed surprisingly strong activity in specifically inhibiting in vivo tumor growth of L1210 by day 5 in the peritoneal cavity of CD2F1 mice when injected together with 10(5) tumor cells (more than 90% inhibition at E/T = 5), and prolonged survival times of most of the mice for more than 60 days, whereas control mice inoculated with L1210 alone died on day 9-17. This unique in vivo anti-tumor activity was not correlated to the in vitro cytolytic activity. Nevertheless, bystander inhibitory effect on the growth of third-party tumor cells (P388) was not seen in mice injected with a mixture of L1210 and P388 together with K7L, suggesting that K7L inhibited L1210 growth by direct cell-to-cell interaction. Host cells such as X-irradiation (800R)-sensitive lymphocytes and Carrageenan-sensitive macrophages were not involved in the early growth inhibition of L1210 by K7L.

The dynamics of cytotoxic T lymphocyte precursors (CTL-p) in mice injected with allogeneic spleen cells (SC) was studied with special reference to changes in their radiation sensitivity. Whole-body 400 rad X-ray irradiation of allo-SC-primed and unprimed mice virtually abolished the capacity of their SC to proliferate and to generate CTL in primary or secondary mixed leucocyte culture (MLC). However, the impaired ability of SC to generate CTL in the primary MLC was restored by interleukin 2 (IL-2). This showed that helper cells whose activity was replaceable with IL-2 (IL-2-producing cells) were functionally more radiation-sensitive than CTL-p in unprimed mice. In contrast, the radiation-impaired activity in secondary MLC was not restored by IL-2, suggesting that memory CTL-p in allo-SC-primed mice were unexpectedly sensitive to radiation. The D37 values determined from the percentage of residual CTL-p activity of SC in bulk cultures 1 day after irradiation were 525 rad for virgin CTL-p and 75 rad for memory CTL-p. Further studies demonstrated that the radiation-sensitive memory CTL-p were generated from relatively radiation-resistant precursors, largely independent of radiation-sensitive IL-2-producing cells and of cellular proliferation. The mean frequency of CTL-p in SC measured by limiting dilution assay was not significantly increased by the priming. This supports our conclusion that the development of the memory CTL-p activity in allo-SC-primed mice did not depend on clonal expansion. Whole-body 400 rad-irradiation reduced the frequency of CTL-p in SC from unprimed mice to 1/2-1/3 and that in SC from allo-SC-primed mice to 1/8-1/15. This supports the view that the majority of radiation-resistant virgin CTL-p functionally mature to radiation-sensitive memory CTL-p without cellular proliferation in allo-SC-primed mice.

A highly immunogenic variant of the murine L1210 leukemia cell (L1210/LN-1) for generation of tumor immunity has been obtained from culture of L1210 cells originally fused with human Lesch-Nyhan fibroblasts. In L1210/LN-1 cells, no human chromosomes were identified and chromosomes M1 and No. 1 carried by the parent L1210 cells were missing. L1210/LN-1 cells displayed an intermediate morphology between L1210 cells and Lesch-Nyhan fibroblasts. Most of the CDF1 mice that were inoculated with less than 2 X 10(6) L1210/LN-1 cells survived over 60 days without evidence of tumor, whereas the original L1210 cells killed all the mice tested in about 2 weeks. When inoculated with more than 5 X 10(6) L1210/LN-1 cells, CDF1 mice developed tumor. The CDF1 mice which rejected 2 X 10(6) L1210/LN-1 cells were protected very effectively against challenge of otherwise highly aggressive 1-5 X 10(5) L1210 leukemia cells; 40 out of 43 primed mice tested survived for 60 days or longer after the tumor challenge. Even the CDF1 mice primed with irradiated or mitomycin-treated L1210/LN-1 cells survived against a challenge of 10(5) L1210 leukemia cells. They were, however, not protected against P388 leukemia or Meth A sarcoma, indicating that the immunity was specific to L1210 leukemia. The immunity induced by L1210/LN-1 cells was transplantable by immune spleen cells into syngeneic recipients. Thus, the L1210/LN-1 cells we obtained seem to be very useful as an immunogen for generation of high-grade tumor-specific immunity against highly malignant L1210 leukemia.

Current interpretation based on analytical in vitro works that actions of Ia antigens and accessory cells such as macrophages and dendritic cells are crucial for inducing cytotoxic T cell responses to class I major histocompatibility complex (MHC) alloantigens has been challenged by experiments performed in a newly developed system handling in vivo cytotoxic T cell immunity. We first characterized the transplantation immunity for second-set rejection of ascitic tumor allografts as principally induced by allogeneic stimulator cells via direct pathway, and as exclusively mediated by class I MHC alloantigen-specific in vivo cytotoxic T cell activity. By comparison of activities of limiting effective doses (10(4)-10(5) cells per mouse) of various stimulator cells in this defined system, we could demonstrate that genetic disparity at the D region of H-2 to the recipient is just enough for inducing the immunity, and presence of allogeneic or syngeneic Ia antigens in addition to H-2D alloantigens on stimulator cells does not give any premium effect. Further study revealed that allogeneic peritoneal cells rich in macrophages or glass-adherent spleen cells enriched for dendritic cells are not stronger stimulators than allogeneic adherent cell-depleted spleen cells and semi-allogeneic thymocytes. These results fit with the alternative concept that the physiological pathway inducing in vivo cytotoxic T cell immunity for graft rejection entirely depends on class I MHC antigens on live lymphocytes as self-supported stimulators, and does not crucially involve additional stimulator activities of Ia antigens and special accessory cell types, which must be in vivo concerned with induction of other types of transplantation immunity.

We have recently described that a variant of L1210 leukemia cell (L1210/LN-1) originally fused with Lesch-Nyhan fibroblast is highly immunogenic for inducing tumor-specific transplantation immunity in (BALB/cxDBA/2)F, mice. This finding has clearly been confirmed in the present study by in-vitro cell-mediated cytotoxicity assay. Direct cytotoxic tests and competitive inhibition tests using tumor cells such as P388, LS-1 and L5178Y as target or inhibitor cells showed that the cell-mediated immunity is specific to L1210 leukemia. In the process of this study, we found that the CD2F 1 mice hyperimmune to L1210 leukemia cells developed co-existing humoral anti-L1210 leukemia immunity. In an in vitro complement-dependent cytotoxicity test and absorption test, antisera from hyperimmune mice reacted specifically to L1210 leukemia cells, but not other tumor cells such as P388, L5178Y, LS-1, DB27C and BW5147 or normal cells from various tissues of DBA/2, BALB/c and AKR mice. In an in vitro cytotoxicity blocking test, the cytotoxic antisera specifically reactive to L1210 cells totally failed to inhibit lysis of L1210 cells by cytotoxic cells, suggesting that antigens recognized by cell-mediated cytotoxicity assays are not identical to serologically defined tumor-cell surface antigens.

Transplantation immunity for second-set rejection of an allogeneic ascites tumor was induced by sensitizing mice with H-2-identical allogeneic spleen cells, and radiation-sensitivity of this immunity was studied. The immunity was not severely affected by 400 rads whole-body X-ray irradiation given at one day before the initial antigenic stimulation. In contrast, it was totally inactivated by 300-400 rads irradiation that was given one day before tumor challenge. An adoptive cell transfer experiment showed that alloreactive memory cells responsible for the immunity were unexpectedly highly radiosensitive. The immunity (memory), however, became resistant to 400 rads irradiation soon (one day) after challenge with the allogeneic tumor, and was resistant to 1500 rads for rejection of the tumor that was challenged at the second time when the initially challenged tumor was rejected. Corresponding to these observations, cells for allospecific CTL responses in peritoneal cavity of mice showed corresponding biphasic radiation-sensitivity.

1969年より1977年までの9年間に名古屋大学第一内科および愛知県職員病院内科に入院した成人急性白血病患者179例に合併した48症例延54例の敗血症を対象とし,起炎菌の種類ならびに抗生物質療法の効果を中心に検討した.起炎菌はE. coli15例, Pseudomonas aeruginosa 12例, Pseudomonas sp. 2例, Klebsiella pneumoniae 6例, Serratia marcescens 5例, Aeromonas hydrophila 4例, Acinetobacter anitratus 3例等グラム陰性桿菌が計51例で全体の89.5%を占めた.グラム陽性菌はStaph. aureusの1例のみであり,嫌気性菌が2例,真菌が3例みられた.発症時の末梢血成熟好中球数は0であつたもの19例を含み,中央値で40/cmmであつた.これらの高度の顆粒球減少状態にある敗血症に対しcarbenicillin, sulbenicillin, cephalothin, cefazolin, gentamicin, dibekacin, amikacinを中心とする抗生物質の大量併用療法を試みた所,白血病治療開始前に発症した4例中全例,初回寛解導入期に発症した22例中18例,再発寛解導入期の5例中4例,強化療法期の1例中1例,計32例中27例(84.4%)が治療可能であつたのに比し,終末増悪期に発生した22例中治癒したのは6例のみで, 16例は死亡した. 54例中27例はショック状態におちいつたが,内15例は治癒可能であり,このような重篤な敗血症でも,抗生物質大量併用投与,白血球輸血等の積極的な治療により充分治癒可能であると考えられる.

The afferent arc of the in vivo cytotoxic T-cell immunity assessed by second set rejection of ascitic allogeneic tumors was shown to be depressed by bacterial lipopolysaccharide (LPS) that was administered simultaneously with or 1 day before injection of allogeneic spleen cells as stimulators. Two different LPSs from Escherichia coli O55 and Klebsiella O3 displayed similar activities whereas dextran sulfate, concanavalin A, or poly A:U was not effective. Stimulator activities of allogeneic cells was not directly modified by LPS. Any definite suppressor activity on afferent or efferent arc of the T-cell response was not demonstrable in mice receiving LPS and allogeneic cells. Further, the LPS effect for immune depression was not diminished by whole body X-ray irradiation to the recipient at 300 R, which ablated the B-cell reactivity to LPS for polyclonal activation, or by treatment of the recipient with carrageenan, a known toxic agent to macrophages. It was suggested from these results that LPS suppresses the cytotoxic T-cell immunity by modulating responder T cells to be temporarily refractory to the allogeneic stimulus rather than by activating suppressor cells such as radiation-sensitive lymphocytes and carrageenan-sensitive macrophages.

Antigenic requirements for inducing minor histocompatibility antigens (MIHA)-specific T cell immunity for second set rejection (SSR) of a MIHA-allogeneic tumor were studied. An intravenous injection of surprisingly small numbers (10 4 –10 5 ) of live allogenetic spleen cells (SC) effectively primed mice for SSR of the allogeneic tumor, and this immunity was developed as early as 2–3 days after injection of the SC. In contrast, sonication-disrupted allogeneic SC, which should be readily processed by host antigen presenting cells (APC), were not active as immunogens, even at a dose 1000 times higher than the minimum effective dose of live SC. The possibility that host APC preferentially receive MIHA antigens shed by live allogeneic SC for T cell activation was ruled out. These results demonstrated that antigen processing via conventional pathways is very little involved in the mechanism of T cell activation. Under such restricted experimental conditions, the induction phase but not the effector phase of the MIHA-specific T cell immunity was shown to be H-2-unrestricted.

The mode of alloantibody -mediated inhibition of allo-sensitization for tumor allograftrejection was studied. Relatively small amounts of anti-H-2 d alloantiserum administered shortly before or after injection of allogeneic spleen cells blocked the allo-sensitization for second-set tumor allograft rejection. In contrast, the alloantiserum injected shortly before inoculation of tumor barely enhanced the tumor growth. The passively administered alloantiserum inhibited the sensitization for allospecific cytotoxic T lymphocyte responses in in vitro . Further study revealed that the allo-sensitization could be blocked with antiserum specific against only one of the expressed H-2 antigens on stimulator cells. Correspondingly, H-2D d -monospecific monoclonal antibody (IgG2a) was effective in inhibiting the sensitization with cells expressing multiple H-2 alloantigens. These results suggest that antibody-mediated inactivation of stimulator cells as a whole is an important mechanism of the allograft enhancement.

Spoken dialog system is one of the most useful interface between human and machine. These systems need scenario data, which is represented by Finite State Transducer (FST). It is usually written by hand, but making it is a time-consuming job.In order to make a dialog scenario file easily, a new dialog scenario editor is developed. In dialog systems, it is important for natural communication that an agent speaks with natural gesture. However, it is difficult to make an appropriate motion for every utterance in a dialog scenario. In this paper, automatic motion assignment method is proposed.Most of motions have some meanings, and these meanings correspond to some keywords. Relationship between motions and keywords are investigated in advance, and an appropriate motion is selected based on corresponding keyword list. Moreover, the proposed motion selection method also considers sentence styles (interrogative, negative, and so on) of the main phrase in the sentence. Naturalness evaluation experiment was carried out for combinations between motions and utterances, and motion selection rules (keyword list and conditions) were made based on the results. Totally 83 keywords were listed for 31 motions.The performance of the motion selection method was evaluated. From this experiment, only 13.3% of input sentences were given an appropriate motion. However, many errors could be corrected by modifying the motion selection rules, and finally 80.0% of assigned motions were evaluated as “appropriate.”The dialog scenario editor with automatic motion assignment was developed. It deals with FST-based dialog system. In particular, it outputs a dialog scenario file for MMDAgent. This editor operated correctly, and a scenario file could be created easily.