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本稿は， 福祉社会学でのケアをめぐる研究において， ケアの場に対する相互行為分析の応用可能性， 有効性について検証することを目的とした方法論的考察であり， とくにエスノメソドロジーに焦点をあててその確認を行った． まず， ケアを 「ケア」 として成立せしめている状況は， その場における人びとの相互行為によってつくられることを確認した上で， 社会福祉の近接領域での比較的数少ない先行研究のうち， 2 つを検討した． その結果まず第 1 には， 科学的理論化の態度が他者理解の本質とはなりえず， それが根ざす他者と共にある社会的場面での実践においてケア （療育） が問われるべきで， そのための経験的研究が促されることについて確認しえた． また第 2 に， エスノメソドロジーの観点に基づくビデオエスノグラフィーを用いた研究について検討し， この方法がケアの場のように言葉を介さないような空間においても分析が有効であること， さらに社会福祉領域でのケアに関しても応用可能であるとみなされ， ケアという相互行為の社会学的解明にとって有効であることが確認できた．

Accumulating evidence indicates that VEGF and matrix metalloproteinase-9 (MMP-9) play a central role in the development of peritumoral brain edema (PTBE) associated with human brain tumors. However, the roles of these proteins, particularly of MMP-9, in PTBE associated with benign meningiomas have not been elucidated. We investigated the association between clinical features and biological factors, such as VEGF and MMP-9, and the incidence of PTBE and edema index (EI) in 60 patients with benign meningiomas. In this study, supratentorial lesions were examined for evaluating the extent of PTBE in the surrounding normal brain tissue. VEGF and MMP-9 expression was immunohistochemically examined. Multivariate analysis revealed that the presence of pial blood supply (odds ratio [OR] 12.250; P = 0.0096) and VEGF (OR 7.683; P = 0.0155), but not MMP-9 (OR 1.178; P = 0.8113), expression are significant factors that independently predict the incidence of PTBE and influence EI. VEGF (P = 0.0397) and MMP-9 (P = 0.0057) expression correlates with the presence of pial blood supply. Moreover, tumors with high VEGF and MMP-9 expression had higher EIs than those with high expression of either (P = 0.030). Our findings suggest that MMP-9 expression was positively related to VEGF expression and pial blood supply and promoted the occurrence of PTBE by inducing the disruption of the arachnoid membrane and formation of pial blood supply.

It is important to understand how long-term geological phenomena such as uplift and erosion influence deep hydrogeological and hydrochemical environments, and to predict the influence of such long-term geological phenomena in the future for the geological disposal of nuclear wastes. From the viewpoint of groundwater flow, it is necessary to estimate long-term topographic changes, and to evaluate their influence on deep groundwater flow conditions. In this study, the influence of long-term topographic change on deep groundwater flow conditions was numerically assessed. The general paleotopographic features of a wide area were estimated and groundwater flow simulations were carried out around the Tono area. As a result, the effects of long-term topographic changes and hydraulic features of faults on groundwater flow conditions, such as hydraulic gradient, velocity distribution, flow paths, and lengths, were confirmed. In general, if topographic characteristics such as locations of major mountains and valleys around the site have not changed, the groundwater flow paths will not significantly change. The methodology, which is proposed in this study, used to understand groundwater flow evolutions due to long-term topographic changes is efficient for identifying detailed assessment areas and is recommended based on the results of this study.

本稿では援助の実践場面で経験される、どちらが「援助者」でどちらが「被援助者」かが、当事者自身さえ認め難いような関係が成り立ち、福祉的な行為と感情との享受が同時的・相互的になされている状態としての「福祉的」について考察することを目的とした。そこでまず心理的経験、とくに「同一化」と「同一性」の関係との比較、次いで知覚的経験における「イマージュ」概念あるいは「相貌」の知覚と「客観的世界」の関係との比較を行った。その結果「福祉的化」は、両経験とは転倒した方向性をもっていることがわかり、これには近代市民社会における集合表象としての「個人主義」の関わりがあることを述べた。最後に、「福祉的」の経験は、人と人との支え合いの始点へ実感を伴うかたちで経験させ、客体化された援助関係のあり方から援助当事者を解放させ、主体性を回復させる瞬間でもあること、その結果としてクライエントとの関係の再構成を促す基盤ともなりうるものと考察された。さらに、援助する側の専門性、援助される側の対象論的規定という、従来の制度的な捉え方を超える可能性を見出す契機になりうることを指摘した。

In order to evaluate the load on the low back of care workers in nursing homes for the elderly, basic activities and working postures were analyzed for six care workers using the 30-s snap reading method. The trunk inclination angle (TIA) was also measured continuously using an inclination monitor. The analysis of basic activities showed that 22.5% and 21.1% of the workshift were spent on 'bathing and ablution' and 'meal', respectively, and 9.3%, 8.7% and 8.3% were spent on 'assistance with elimination', 'assistance with moving and repositioning' and 'exchange of bed sheet', respectively. Total of the assistance activity was 43.7% of the workshift. The analysis of working posture showed that 'standing' and 'standing bent forward' accounted for 36.1% and 29.5%, respectively, of the workshift. Total of three postures loading the low back ('standing bent forward', 'squatting', 'kneeling') accounted for 39.0%. The time spent in TIA of 20 degrees or more was 45.7%. The postures loading the low back during 'bathing and ablution', 'exchange of bed sheet' and 'assistance with elimination' account for 68.3%, 58.2% and 49.6%, respectively, which suggests that these activities load the low back of the care workers considerably.

地下空洞掘削に伴う空洞周辺岩盤中の間隙水の挙動変化を評価することを目的として, 東濃鉱山 (核燃料サイクル開発機構東濃地科学センター: 岐阜県土岐市) に分布する第三紀堆積岩盤において空洞壁からのボーリングにより岩石コアを採取し, 得られた岩石コアから間隙水を抽出し, 水素・酸素安定同位体比および電気伝導度の測定を行った.結果として, 空洞壁からの距離と安定同位体比および電気伝導度の関係に関しては, 空洞壁に近い地点の間隙水ほど空洞掘削に伴う蒸発の影響を受けやすいことが示唆され, 同一地点の間隙水における最大抽出圧力と安定同位体比および電気伝導度の関係に関しては, 岩石との吸着力が強い間隙水ほど空洞掘削に伴う蒸発の影響を受け難いことが示唆された. また, これらの間隙水の挙動は岩質の相違により異なることが示唆された.後者の岩質に伴う空洞周辺の地下水流動特性の違いは, 岩質の違いを考慮した鉛直2次元の飽和地下水流動解析結果から判断される地下水流動状況とも整合することが示唆された.本研究において適用された堆積岩中の間隙水を抽出し, 安定同位体比を測定する手法は, 空洞掘削に伴う周辺岩盤中の地下水挙動の把握, とりわけこれまで実態の把握が困難であった空洞周辺の不飽和領域の把握に有効な手法であることが示された.

Objectives: In order to clarify the effect of lead on higher cerebral functions, lead-exposed workers (Pb group) and controls were examined for event-related potentials. Subjects and Methods: Fourteen lead-exposed workers with a mean age of 57.1 yr (SD=4.27, range 48-64; lead concentration of whole blood ranged from 33 to 106 μg/dl with a mean of 58.6 and SD 28.6 μg/dl) and 19 agematched control workers with a mean age of 57.3 yr (SD=4.80, range 48-65) were examined. Visual P300 was recorded by button pushing to the target image (minute checkerboard pattern, 20%), and the NO-GO potential by no button pushing to the target image (same as above, 50%). Results: Latencies of P300 in the Pb group (475 ± 46.0 ms) were significantly delayed compared with those in controls (407 ± 42.4 ms, p

PM2.5測定用の47mmφテフロンフィルターと一般的な大気サンプリング用の110mmφ石英フィルターを用いて, 秤量時の相対湿度変化が秤量値に及ぼす影響を, 秤量室の相対湿度を50%に調節した場合としなかった場合を比較することによって調べた.テフロンフィルターの秤量精度は, 秤量室の相対湿度を調節した場合としない場合で大きな差はなかった.秤量室の相対湿度を50%に調節したときのPM2.5質量の標準偏差は15μg, PM2.5質量濃度の定量下限値は6.3μg/m3となり, 低濃度のPM2.5測定は精度が不十分であることが分かった.一方, 石英フィルターの秤量精度は, 秤量室の相対湿度を50%に調節したときの方が調節しないときより2～5倍も良く, 秤量室の相対湿度を一定に保つことは, 石英フィルターを精度よく秤量する上で非常に重要なファクターであることが分かった.秤量室の相対湿度を50%に調節したときのSPM質量の標準偏差は36μgとなり, 2週間で約400m3の大気サンプリングの場合, SPM質量濃度の定量下限値は0.89μg/m3となった.

Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell disorder in which clonal cells defective in glycosylphosphatidylinositol (GPI) biosynthesis are expanded, leading to complement-mediated hemolysis. PNH is often associated with bone marrow suppressive conditions, such as aplastic anemia. One hypothetical mechanism for the clonal expansion of GPI(-) cells in PNH is that the mutant cells escape attack by autoreactive cytotoxic cells that are thought to be responsible for aplastic anemia. Here we studied 2 model systems. First, we made pairs of GPI(+) and GPI(-) EL4 cells that expressed major histocompatibility complex (MHC) class II molecules and various types of ovalbumin. When the GPI-anchored form of ovalbumin was expressed on GPI(+) and GPI(-) cells, only the GPI(+) cells presented ovalbumin to ovalbumin-specific CD4(+) T cells, indicating that if a putative autoantigen recognized by cytotoxic cells is a GPI-anchored protein, GPI(-) cells are less sensitive to cytotoxic cells. Second, antigen-specific as well as alloreactive CD4(+) T cells responded less efficiently to GPI(-) than GPI(+) cells in proliferation assays. In vivo, when GPI(-) and GPI(+) fetal liver cells, and CD4(+) T cells alloreactive to them, were cotransplanted into irradiated hosts, the contribution of GPI(-) cells in peripheral blood cells was significantly higher than that of GPI(+) cells. The results obtained with the second model suggest that certain GPI-anchored protein on target cells is important for recognition by T cells. These results provide the first experimental evidence for the hypothesis that GPI(-) cells escape from immunologic attack.

A homeodomain containing transcription factor PDX-1 can induce beta-cell-specific gene expressions in some non-beta-cells and may therefore be useful for future diabetes gene/cell therapy. Among the potential target organs or tissues for transcription factor-mediated induction of beta-cell-like differentiation are the intestinal epithelial cells. They have certain merits over other tissues and organs in terms of accessibility for gene delivery and of similarity in developmental background to the pancreatic primordium. In this study, we used an intestinal epithelium-derived cell line, IEC-6 cells, and investigated the possible effects of PDX-1 expression in those cells. By exogenous expression of the PDX-1 gene, IEC-6 cells started expressing multiple beta-cell-specific genes such as amylin, glucokinase, and Nkx6.1, which were not found in the original IEC-6 cells. Insulin gene expression, which was missing initially even in the PDX-1-transfected IEC-6 cells, became detectable when the cells were transplanted under the renal capsule of a rat. When the PDX-1(+) IEC-6 cells were kept in vitro, treatment with betacellulin could also confer insulin gene expression to them. Although insulin secretory granules became visible by electron microscopy, they were secreted regardless of glucose concentration. The in vivo or in vitro inductions of the insulin gene expression were not observed in the PDX-1(-) IEC-6 cells. Thus, our present observations demonstrate the potency of intestinal epithelial cells as a tool for diabetes gene/cell therapy and provide further support for the potency of PDX-1 in driving beta-cell-like differentiation in non-beta-cells.

A novel IFN-like molecule, limitin, was recently identified and revealed to suppress B lymphopoiesis through the IFN-αβ receptor, although it lacked growth suppression on myeloid and erythroid progenitors. Here we have studied diverse effects of limitin on T lymphocytes and compared limitin with previously known IFNs. Like IFN–α and -β, limitin modified immunity in the following responses. It suppressed mitogen- and Ag-induced T cell proliferation through inhibiting the responsiveness to exogenous IL-2 rather than suppressing the production of IL-2. In contrast, limitin enhanced cytotoxic T lymphocyte activity associated with the perforin-granzyme pathway. To evaluate the effect of limitin in vivo, a lethal graft-versus-host disease assay was established. Limitin-treatment of host mice resulted in the enhancement of graft-versus-host disease. Limitin did not influence thymocyte development either in fetal thymus organ cultures or in newborn mice injected with limitin-Ig, suggesting that limitin is distinguishable from IFN-α and -β. From these findings, it can be speculated that the human homolog of limitin may be applicable for clinical usage because of its IFN-like activities with low adverse effects on, for example, T lymphopoiesis, erythropoiesis, and myelopoiesis.

A methanol extract from Belamcanda chinensis showed a suppressive effect on umu gene expression of the SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide). The methanol extract from B. chinensis was re-extracted with hexane, dichloromethane, ethyl acetate and butanol. A suppressive compound in the dichloromethane extract fraction was further fractionated by SiO2 column chromatography. EI-MS and 1H and 13C NMR spectroscopy were then used to delineate the structure of the compound that confers the observed suppressive effect. Comparison of the obtained spectrum with that found in the literature indicated that iristectorigenin B (1) is the suppressive compound. Iristectorigenin B and its methylated derivative (7, 4’-di-O-methyliristectorigenin B(2)) had the suppressive effects on umu gene expression of the SOS response in Salmonella typhimurium TA1535/pSK1002 against furylfuramide, 4NQO, MNNG, and activated Trp-P-1, which do not require liver metabolic activation by S9. These compounds also showed the suppression of SOS-inducing activity against Trp-P-1 and AfB1, which require liver metabolizing enzymes. In addition to the antimutagenic activities of these compounds against furylfuramide, Trp-P-1 and activated Trp-P-1 were also assayed by an Ames test using S. typhimurium TA100.

Patients with paroxysmal nocturnal hemoglobinuria (PNH) have one or a few clones of mutant hematopoietic stem cells defective in glycosylphosphatidylinositol (GPI) synthesis as a result of somatic mutation in the X-linked gene PIG-A. The mutant stem cell clone dominates hematopoiesis by a mechanism that is unclear. To test whether a lack of multiple GPI-anchored proteins results in dysregulation and expansion of stem cells, we generated mice in which GPI-anchor negative cells are present only in the hematopoietic system. We transplanted lethally irradiated mice with female fetal liver cells bearing one allele of the Piga gene disrupted by conditional gene targeting. Because of the X-chromosome inactivation, a significant fraction of the hematopoietic stem cells in fetal livers was GPI-anchor negative. In the transplanted mice, cells of all hematopoietic lineages contained GPI-anchor negative cells. The percentage of GPI-anchor negative cells was much higher in T lymphocytes including immature thymocytes than in other cell types, suggesting a regulatory role for GPI-anchored proteins at an early stage of T-lymphocyte development. However, the proportions of GPI-anchor negative cells in various blood cell lineages were stable over a period of 42 weeks, indicating thatPiga mutation alone does not account for the dominance of the mutant stem cells and that other phenotypic changes are involved in pathogenesis of PNH.

Respiratory uptake was investigated for 10 polar organic solvents with high blood/air partition coefficients (lambda(blood/air)): ethyl acetate (lambda(blood/air), 77), methyl iso-butyl ketone (90), methyl acetate (90), methyl propyl ketone (150), acetone (245), iso-pentyl alcohol (381), iso-propyl alcohol (848), methyl alcohol (2590), ethylene glycol monobutyl ether (EGBE, 7970), and propylene glycol monomethyl ether (PGME, 12380). Test-air concentrations (Cinh) were 25 to 200 ppm. Four healthy male volunteers inhaled the test air for 10 min at rest and then room air for 5 min. The percentage of solvent in the end-exhaled air and in the mixed-exhaled air increased after the start of the test-air respiration, and reached a quasi-steady-state level within a few min. The speeds of these increases at the start of the test-air respiration became lower as lambda(blood/air) increased. The mean uptakes (U) for the last five min of the test air respiration were 67.3, 52.9, 60.4, 53.0, 52.6, 63.0, 60.3, 60.8, 79.7, and 81.3%, respectively, for ethyl acetate, methyl iso-butyl ketone, methyl acetate, methyl propyl ketone, acetone, iso-pentyl alcohol, iso-propyl alcohol, methyl alcohol, EGBE and PGME. Thus, U values of the alcohols were higher than those of the ketones and lower than the glycol ethers. The overall view, except for esters, showed that U increased with lambda(water/air) increases. This tendency can be explained by a hypothesis that solvent absorbed in the mucus layer of the respiratory tract is removed by the bronchial blood circulation. U values of ethyl acetate and methyl acetate were higher than those of methyl iso-butyl ketone and methyl propyl ketone, though the lambda(blood/air) values of these esters were nearly equal to those of the ketones. For the respiration of the esters, their metabolites, ethyl alcohol and methyl alcohol, were detected in the exhaled air. The exhalation percentage of the metabolites increased after the start of test-air respiration and reached a quasi-steady-state level of 2 and 3%, respectively, by the 5th min. These data suggest that removal of the solvent via metabolism in the wall tissue of the respiratory tract plays an important role for the esters.

Recently, we demonstrated that major histocompatibility complex class I–restricted cross-presentation of exogenous self-antigens can induce peripheral T cell tolerance by deletion of autoreactive CD8+ T cells. In these studies, naive ovalbumin (OVA)-specific CD8+ T cells from the transgenic line OT-I were injected into transgenic mice expressing membrane-bound OVA (mOVA) under the control of the rat insulin promoter (RIP) in pancreatic islets, kidney proximal tubules, and the thymus. Cross-presentation of tissue-derived OVA in the renal and pancreatic lymph nodes resulted in activation, proliferation, and then the deletion of OT-I cells. In this report, we investigated the molecular mechanisms underlying this form of T cell deletion. OT-I mice were crossed to tumor necrosis factor receptor 2 (TNFR2) knockout mice and to CD95 (Fas, Apo-1) deficient mutant lpr mice. Wild-type and TNFR2-deficient OT-I cells were activated and then deleted when transferred into RIP-mOVA mice, whereas CD95-deficient OT-I cells were not susceptible to deletion by cross-presentation. Furthermore, cross-presentation led to upregulation of the CD95 molecule on the surface of wild-type OT-I cells in vivo, consistent with the idea that this is linked to rendering autoreactive T cells susceptible to CD95-mediated signaling. This study represents the first evidence that CD95 is involved in the deletion of autoreactive CD8+ T cells in the whole animal.

In order to evaluate the load on the low back of teachers in kindergartens, basic activity and working posture were analyzed for four teachers by means of video recording. The trunk inclination angle (TIA) was also measured continuously during full workshifts for 12 kindergarten teachers by means of an inclination monitor. The kindergarten teachers spent 67% of the workshift on activities in contact with children, "indoor group childcare", "indoor free playing", "outdoor childcare", "preparation and clearing away" and "help and care", and did not take a recess during the workshift. They spent 36% of the workshift in three working postures with the load on the low back, "standing bent forward", "squatting" and "kneeling". Cumulative time at a TIA of 20 degrees or more represented 43% of the workshift. The frequency of trunk-lifting from severe bending forward (TIA > 45 degrees) was 95 times/hr on average. A comparison of the kindergarten teachers and nursery teachers in 4-5 year age classes showed that the time distributions of basic activities were generally similar to each other. Although the time distributions of working postures were also similar, time spent "standing bent forward", "squatting" and "kneeling" was longer in the kindergarten teachers than in the nursery teachers. Cumulative time at a TIA of 45 degrees or more was significantly longer in the kindergarten teachers. Although the frequency of trunklifting was not significantly different, the kindergarten teachers tended to lift their trunk more frequently. The present study found that the load on the low back was considerably great in the kindergarten teachers.

In this report, we show that cross-presentation of self-antigens can lead to the peripheral deletion of autoreactive CD8+ T cells. We had previously shown that transfer of ovalbumin (OVA)-specific CD8+ T cells (OT-I cells) into rat insulin promoter–membrane-bound form of OVA transgenic mice, which express the model autoantigen OVA in the proximal tubular cells of the kidneys, the β cells of the pancreas, the thymus, and the testis of male mice, led to the activation of OT-I cells in the draining lymph nodes. This was due to class I–restricted cross-presentation of exogenous OVA on a bone marrow–derived antigen presenting cell (APC) population. Here, we show that adoptively transferred or thymically derived OT-I cells activated by cross-presentation are deleted from the peripheral pool of recirculating lymphocytes. Such deletion only required antigen recognition on a bone marrow–derived population, suggesting that cells of the professional APC class may be tolerogenic under these circumstances. Our results provide a mechanism by which the immune system can induce CD8+ T cell tolerance to autoantigens that are expressed outside the recirculation pathway of naive T cells.

We found that human urine suppressed SOS-responses induced by furylfuramide (AF-2), as detected by the umu test using Salmonella typhimurium TA1535/pSK1002. In the present report, we studied the time stability of the SOS-inhibition activity in urine. The diurnal and daily changes of SOS-inhibition in the urine were also observed. Results obtained were as follows; 1) SOS-inhibition activity of the urine remained stable more than one month after the urine was frozen. 2) Individual variation was observed in the SOS-inhibition activity of the urine. 3) Total SOS-inhibition activity of per a day showed relatively small variation during experimental days. 4) The SOS-inhibition activity of urine was higher early in the morning than in the daytime. The activity fell gradually with time in the daytime and showed the lowest value in the evening. Then, it rose again at night. Therefore, it is necessary to collect urine at specific times to avoid the differences caused by diurnal changes in SOS-inhibition activity.

Tolerance of CD8+ cells was examined in parent-->F1 bone marrow chimeras (BMC) prepared with supralethal irradiation; host class I expression in the chimeras was limited to non-BM-derived cells. In terms of helper-independent proliferative responses in vitro and induction of graft-vs.-host disease on adoptive transfer, CD8+ cells from long-term chimeras showed profound tolerance to host antigens irrespective of whether the cells were prepared from the thymus or from spleen or lymph nodes. By limiting dilution analysis, cytotoxic T lymphocyte (CTL) precursors specific for host antigens were rare in the extrathymic lymphoid tissues. In the thymus, by contrast, host-specific CTL precursors were only slightly less frequent than in normal parental strain mice. These host-specific CD8+ cells survived when BMC thymocytes were transferred intravenously to a neutral environment, i.e., to donor strain mice. When transferred to further BMC hosts, however, most of the host-reactive cells disappeared. Collectively, the data suggest that tolerance of CD8+ cells in BMC hosts occurs in both the intrathymic and extrathymic environments. In the thymus, contact with host antigens on thymic epithelial cells deletes CD8+ cells controlling helper-independent proliferative responses and in vivo effector functions but spares typical helper-dependent CTL precursors. After export from the thymus, most of the CTL precursors are eliminated after contacting host antigens on stromal cells in the extrathymic environment.

Information was sought on the features of epithelial cells in the murine thymic medulla. The expression of major histocompatibility complex (MHC) molecules on medullary epithelium was defined by light microscopy with the aid of bone marrow chimeras and MHC-transgenic mice. A proportion of medullary epithelial cells was found to show conspicuously high expression of conventional MHC (H-2) class I (K, D, L) and class II (I-A, I-E) molecules. These cells express a high density of the Y-Ae epitope, a complex of an E alpha peptide and I-Ab molecules found on typical bone marrow-derived cells. MHC+ medullary epithelial cells show limited expression of I-O molecules, a class of atypical nonpolymorphic MHC-encoded class II molecules present on B cells. Other medullary epithelial cells express a high density of I-O molecules but show little or no expression of typical MHC class I or II molecules. MHC and I-O expression thus appear to subdivide medullary epithelial cells into two phenotypically distinct subsets. This applies in adults. In the embryonic thymus most medullary epithelial cells express both types of molecules.

To test whether unprimed CD8+ cells can recognize class I alloantigens presented selectively on non-bone marrow (BM)-derived cells, unprimed parental strain CD8+ cells were transferred to long-term parent-->F1 BM chimeras prepared with supralethal irradiation. Host class I expression in the chimeras was undetectable on BM-derived cells and, in spleen, was limited to low-level staining of vascular endothelium and moderate staining of follicular dendritic cells (a population of nonhemopoietic cells in germinal centers). Despite this restricted expression of antigen, acute blood-to-lymph recirculation of parental strain T cells through the chimeras led to selective trapping of 95% of CD8+ cells reactive to normal F1 spleen antigen presenting cells (APC) in vitro. Subsequently, a small proportion of the trapped cells entered cell division and gave rise to effector cells expressing strong host-specific CTL activity. The activation of host-specific CD8+ cells was also prominent in double-irradiated chimeras, and cell separation studies showed that the effector cells were generated from resting precursor cells rather than from memory-phenotype cells. It is suggested that the non-BM-derived cells in the chimeras acted as semiprofessional APC. These cells were nonimmunogenic for most host-reactive CD8+ cells but were capable of stimulating a small subset of high-affinity T cells. The possible relevance of the data to the prolonged immunogenicity of vascularized allografts in humans is discussed.

The effects of cyclosporin A (CsA) on influencing the intrathymic clonal deletion were investigated by using our established thymic stromal cell clone with capacities to express Ia antigens and to produce a unique T cell growth factor. The following were revealed: (a) T cell clone with a given specificity was killed on the Ia+ stromal cell monolayer in the presence of the relevant antigens, a process depending on T cell receptor (TCR) stimulation; and (b) CsA allowed the T cell clone to continuously proliferate even during TCR stimulation by virtue of the stromal cell-derived T cell growth factor. This paper describes an in vitro model of a mechanism by which CsA is responsible for the generation of normally "forbidden" T cell clones.

In the present study, SOS-inducing activity of 76 basic dyes was investigated by umu test using Salmonella typhimurium TA1535/pSK1002 under the condition of absence and presence of rat liver microsomal fraction. The test was carrid out with five doses of basic dyes (400, 120, 40, 12, and 4 μg/ml). The samples showing β-galactosidase activity more than 1.5-fold over the background level were reexamined and the dose-response curves were prepared at various doses. Thereafter, samples showing β-galactosidase activity unit more than 1.5-fold of the background level were defined as genotoxic. Among the basic dyes examined, 13 compounds induced umu gene expression. The potent genotoxic compounds without metabolic activation were Blue 40, Blue 47, Brown 14, Orange 30, Red 24, Violet 30, Violet 31, Yellow 13 (h), Yellow 19, Yellow 25, Yellow 67, and Yellow 73 and in the presence of S9, Orange 47 was judged as genotoxic in addition to the aforementioned dyes. An evident dose-response relationship between the doses of the dye and umu gene expression was observed in these 13 dyes.

The umu test system is a newly developed method to evaluate genotoxicities of a wide variety of environmental carcinogens and mutagens (Oda et al., 1985; Nakamura et al., 1987). In the present study, SOS-inducing activity of 142 synthetic dyes was investigated by the umu test using Salmonella typhimurium (TA1535/pSK1002) under the condition of absence and presence of rat liver microsomal fraction. The samples showing a beta-galactosidase activity of more than 1.5 fold over the background level were reexamined and the dose-response curves were prepared at various doses. Then, the samples showing beta-galactosidase activity of more than 1.5-fold of the background level were defined as genotoxic. Among the synthetic dyes examined, 11 compounds induced umu gene expression. The potent genotoxic compounds without metabolic activation were Acid Black 26, Acid Black 50, Acid Brown 2, Disperse Red 73, Disperse Red 145, Disperse Red 157, Disperse Violet 52, Reactive Red 110, Reactive Yellow 13 and Reactive Yellow 75, and in the presence of S9, Reactive Blue 147 was judged to be genotoxic. An evident dose-response relationship was observed between the doses of the dye and umu-gene expression in these 11 dyes.

The aims of the present study were to clarify the work environment contamination by antineoplastic drugs in a hospital ward and to assess the genotoxic risks to nurses who routinely handle antineoplastic drugs in Japan. The exposed group consisted of 19 female nurses who routinely handled antineoplastic drugs. The control group consisted of 18 female nurses who did not handle antineoplastic drugs in the same hospital as the exposed group. The genotoxicity of the 19 antineoplastic drugs used in the hospital ward and 8 wipe samples of the workbench after handling of antineoplastic drugs were measured using the umu assay. Lymphocyte DNA damage (tail length) was measured with alkaline methods of the single cell gel electrophoresis assay (comet assay). Of the 19 antineoplastic drugs, dacarbazine, bleomycin, daunorubicin, doxorubicin, pirarubicin, carboplatin, cisplatin and etoposide induced genotoxicity. Of the 8 sampling d, the umu activity of the wipe sample was positive on 3 d. Contamination of the workbench was found when the nurses handled more drugs than on other days. The medians of the tail length in the comet assay were 8.5 and 5.1 microm, respectively, for the exposed and control groups, with a significant difference (p=0.004 by Mann-Whitney's U-test). In the present study, the nurses of the exposed group were considered to have been exposed to antineoplastic drugs and lymphocyte DNA damage of the exposed group was suggested to be induced by antineoplastic drugs.

The number of those who need nursing care and the workers who provide it have been increasing year after year. In April 2000, the public nursing care insurance system was enacted by the Japanese government. After its enaction, care equipment came under scrutiny, but the situation regarding the installation of equipment is not fully understood. In order to understand the present state of care equipment in nursing facilities for the elderly, we conducted a workplace and interview survey. The surveyed facilities were 10 special nursing homes for the elderly in Osaka Prefecture which were established after April 2002. The average number of elderly residents was 79.0, the average value of degree of care was 3.52, and the average number of caregivers was 28.3 per facility. We found all facilities had installed some kinds of bathing equipment: stretcher type, 9 facilities; bath-chair type, 8 facilities. In the facilities with bath-chairs, 6 facilities had special bathtubs, and 6 facilities had general bathtubs. However, all facilities had the working principle that transfer should be done manually, and the equipment for transfer such as a lifts, a transfer and roller board were not be installed. In changing diapers, bed height adjustment was not possible. And the Japanese standard type of wheelchair has a non-detachable armrest, creating a structural barrier when transferring elderly people from a wheelchair to a toilet seat. At all facilities the basis of care was that caregivers should do it manually. In particular, all facilities had only a weak recognition of the risks of transfer. This investigation shows that facilities for the elderly should rethink elderly care based on a reduction of care load and most importantly protection of caregivers' health.

Relationships between concentrations of polychlorodibenzo-p-dioxins (PCDDs) and polychlorodibenzofurans (PCDFs) in deposited dust and those in the serum of incinerator workers were examined at 13 municipal incineration plants. The following results were found. 1) Dust analysis showed that dominant constituents were octachlorodibenzo-p-dioxin (OCDD) and 1, 2, 3, 4, 6, 7, 8-heptachlorodibenzo-p-dioxin (HpCDD) among PCDDs, and 1, 2, 3, 4, 6, 7, 8-heptachlorodibenzofuran (HpCDF) and octachlorodibenzofuran (OCDF) among PCDFs. The toxicity equivalents (TEQs) of total PCDDs and PCDFs in the deposited dust were 0.54 to 33 ngTEQ/g, which were about 1,000 to 10,000 times as high as those in general soil. 2) The mean of serum TEQ of PCDDs, that of PCDFs and that of total PCDDs and PCDFs in the incinerator workers were 16, 12 and 28 pg TEQ/g lipid, respectively, for all the incinerator workers. Concentrations of hexachlorodibenzofurans (HxCDFs) and HpCDFs in the serum were significantly higher in the incinerator workers than the general population, which suggests that these workers had inhaled these chemicals during their work. 3) The concentration of 1, 2, 3, 4, 6, 7, 8-HpCDF and the TEQ value of PCDFs and in the serum were positively correlated with those in dust except for three plants where large-scale remodeling of the equipment was conducted within the past seven years. Consequently, deposited dust analysis may be useful for judging whether health examination containing blood dioxin measurement is necessary or not.

Transgenic mice were generated to establish an animal model for T-cell-mediated autoimmune skin disease. A membrane-bound form of OVA (mOVA) was specifically expressed under the control of the keratin 5 (K5) promoter in the epidermal and hair follicular keratinocytes of mice. Syngeneic, wild-type mice rejected the skin grafts of K5-mOVA mice with the generation of OVA-specific CTL. To study the CTL response against K5-mOVA skin, we used OT-I transgenic mice, which produce K(b)-restricted, OVA-specific CD8+ T cells. Accelerated rejection of K5-mOVA skin was demonstrated when transplanted onto OT-I mice. Furthermore, OT-I cells, when adoptively transferred into K5-mOVA mice, underwent activation and vigorous proliferation in the skin-draining lymph nodes. A bone-marrow-reconstitution assay demonstrated that K(b) presentation by bone-marrow-derived cells, but not epithelial cells, was required for this response, indicating that cross-priming was the basis for immunity in this model. Finally, transferred OT-I cells, activated by cross-priming, targeted the skin of K5-mOVA mice, resulting in development of skin lesions that were reminiscent of toxic epidermal necrolysis. We conclude that our system provides a useful model for autoimmune skin diseases and will aid understanding of the pathomechanism of drug eruption, viral exanthema, and graft-versus-host disease.

This study describes abnormalities of the thymus in mice in which the Stat3 gene has been specifically disrupted behind the keratin 5 promoter. In these mice, virtually all of the thymic epithelial cells (TEC) were deficient for Stat3 activation. Adult mutant mice developed severe thymic hypoplasia, which included alterations in the cortical TEC architecture that coincided with the loss of thymocytes. Even during the asymptomatic period of preadolescence, these mice exhibited a higher susceptibility of the thymus to suboptimal doses of dexamethasone or γ-irradiation, while their thymocytes per se were no more sensitive than controls. These results indicate that Stat3 in TEC plays an essential role in maintaining thymic architecture and thymocyte survival.

Ovalbumin (OVA)-specific CD8+ T cells from the T cell receptor-transgenic line OT-I (OT-I cells) were injected into unirradiated transgenic RIP-mOVA mice, which express a membrane-bound form of OVA (mOVA) in the pancreatic islet beta cells and the renal proximal tubular cells. OT-I cells accumulated in the draining lymph nodes (LN) of the kidneys and pancreas and in no other LN. They displayed an activated phenotype and a proportion entered cell cycle. Unilateral nephrectomy 7-13 d before inoculation of OT-I cells into RIP-mOVA mice allowed the injected T cells to home only to the regional LN of the remaining kidney (and pancreas), but when the operation was performed 4 h before injecting the T cells, homing to the LN of the excised kidney was evident. When the bone marrow of RIP-mOVA mice was replaced with one of a major histocompatibility haplotype incapable of presenting OVA to OT-I cells, no homing or activation was detectable. Therefore, OT-I cells were activated by OVA presented by short-lived antigen-presenting cells of bone marrow origin present in the draining LN of OVA-expressing tissue. These results provide the first evidence that tissue-associated "self" antigens can be presented in the context of class I via an exogenous processing pathway. This offers a constitutive mechanism whereby T cells can be primed to antigens that are present in nonlymphoid tissues, which are not normally surveyed by recirculating naive T cells.

With unseparated mouse spleen cells as responders, Drosophila cells expressing MHC class I (L d ) molecules alone lead to peptide-specific responses of CD8 + cells in the absence of exogenous cytokines. Under these conditions, DNA released from dying cells stimulates the B cells in spleen to up-regulate costimulatory molecules; these activated B cells then provide bystander costimulation for CD8 + cells responding to class I–peptide complexes on the Drosophila APCs. By stimulating B cells and presenting antigen to T cells, Drosophila cells thus serve two different functions in promoting primary responses of CD8 + cells in vitro. With this system, we show that L d -transfected Drosophila cells are able to induce autologous spleen cells to respond to a tumor-specific peptide in vitro and, after transfer, cause tumor rejection in vivo.

To clarify the chronic effect of lead exposure on the central and peripheral nervous systems (CNS and PNS), we performed neurophysiological tests on 41 lead-exposed male workers. Unexposed workers (controls, N = 39) were examined for auditory brain stem response (ABR), and their ABR parameters were compared with those of 15 lead-exposed workers age-matched to the controls. Neurophysiological tests included those of motor and sensory nerve conduction velocity of the radial nerve (MCV, SCVwa and SCVfw), electroretinograms, pattern reversal visual evoked potential (VEP), ABR, and short-latency somatosensory evoked potentials (SLSEP). Neurophysiological parameters were analyzed by regression analysis [independent parameters: age, exposure duration, and current and time-weighted average lead concentration in whole blood (PbB and TWA-PbB)]. ABR parameters were also tested by Student's t test. Significant negative correlations were found between radial MCV and TWA-PbB and SCVwa and PbB, while significant positive correlations were found between the latency of component N145 of VEP and exposure duration and between the latency of component N20 of SLSEP and PbB. The mean of interpeak latency between component III and V of ABR of 15 lead-exposed workers was significantly prolonged compared with that of the control group. These results suggested that lead exposure has a greater effect on the conduction function in the PNS than in that of the CNS in somatosensory and auditory pathways, and inversely in visual pathway.

A thymic stroma-derived cell clone, MRL104.8a produced a T cell growth factor designated as thymic stroma-derived T cell growth factor (TSTGF). This factor that is distinct from previously described T cell growth factors such as interleukin (IL) 2 or 4 was capable of promoting the growth of IL2-dependent, antigen-specific helper T cell clones. While such growth promotion was induced without requirement of the relevant antigen and exogenous IL2, we further investigated whether it depended on activation of an IL2- or IL4-dependent autocrine mechanism. Helper T cell clones, 8-E and 8-5, were able to proliferate in response to stimulation with either antigen or TSTGF. 8-E and 8-5 produced IL2 and IL4, respectively, in cultures following antigenic stimulation, whereas neither IL2 nor IL4 activity was detected in cultures during TSTGF-induced proliferation. The proliferation of these helper T cell clones by antigenic stimulation was almost completely inhibited when anti-IL2 receptor or anti-IL4 antibody was added to the cultures. The addition of cyclosporin A (CsA) to cultures of 8-E and 8-5 clones together with antigen also resulted in the complete inhibition of cellular proliferation in association with the suppression of IL2 and IL4 production. In contrast, TSTGF-induced proliferation was not affected by addition of either type of antibody or CsA. These results indicate that TSTGF is a novel T cell growth factor that can exert its own growth-promoting effect without depending on an IL2- or IL4-operating autocrine mechanism.

A thymic stromal cell clone, MRL104.8a, expresses class I as well as class II H-2k antigens after exposure to gamma-interferon. This clone also produces thymic stroma-derived T-cell growth factor (TSTGF), which is distinct from other known interleukins and is capable of promoting the growth of various antigen-specific helper T cell (Th) clones without requiring a specific antigen or interleukin 2. When the keyhole limpet hemocyanin (KLH)-specific, I-Ek-restricted Th clone 9-16 was cultured on an Ia (I-Ak and I-Ek)-expressing MRL104.8a monolayer, potent proliferation of the 9-16 cells was induced by TSTGF produced by the monolayer. In contrast, the addition of KLH resulted in lethal growth inhibition of Th clone 9-16 cells. Another Th clone that is KLH-specific but I-Ab-restricted was capable of proliferating on the Iak-expressing MRL104.8a monolayer whether or not KLH was present. More importantly, death of Th clone 9-16 cells cultured on a MRL104.8a monolayer in the presence of KLH was almost completely prevented by the addition of anti-I-Ek or anti-CD3 monoclonal antibodies, which are capable of blocking antigen recognition by the T-cell receptor. However, when Th clone 9-16 cells were cultured in the presence of KLH but on a monolayer of MRL28.8a cells, another thymic stromal clone that expresses a comparable amount of I-Ek antigen but produces a marginal amount of TSTGF, cells did not die; a lethal effect was induced by adding TSTGF. These results indicate that the TSTGF-producing and Ia-expressing thymic stromal cells induce the continuous proliferation or selective elimination of each T-cell clone, depending on whether the T-cell receptor is stimulated by the relevant antigen associated with Ia molecules expressed on the stromal cell surface.

Thymic stromal cell lines, termed MRL104 and MRL28, have been isolated from long-term liquid cultures of thymic stromal cells from MRL/1 mice. The capacities of these parental lines and derived clones to express la antigens and to produce cytokines involved in T-cell proliferation and/or differentiation were investigated. Parental lines and their clones did not exhibit a typical fibroblastic, macrophage-like, or epithelial appearance in electron as well as phase-contrast micrographs. These thymic stromal cells seemed to differ from established fibroblast lines in that these thymic stromal cells expressed la antigens after exposure to interferon-γ (IFN-γ), whereas fibroblast lines did not They also appeared to differ from macrophage cell lines in that they lacked the expression of Mac-1 antigens on their cell surface and produced no detectable level of interteukin-1 (IL1) before or even after exposure to lipopolysaccharide. When these parental lines and its clones were tested for their ability to produce various types of cytokines, it was revealed that they were capable of producing colony-stimulating factor (CSF), IL6, and thymic stroma-derived T cell growth factor (TSTGF). which was recently described, but were unable to generate other lymphokines and IFNs. Thus these cell lines and clones represent unique features in that they have potentials to express la antigens and to produce CSF, IL6, and TSTGF. The biological significance for the expression of these features is discussed in the context of intrathymic T-cell maturation and T-cell repertoire selection.