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21.
Hiraoka S Takeuchi N Bian Y Nakahara H Kogo M Dunussi-Joannopoulos K Wolf S Ono S Fujiwara H 《International immunology》2005,17(8):1071-1079
The B7/CD28 co-stimulatory pathway plays a critical role in T cell activation and differentiation. Our previous study demonstrated that administration of B7.2-Ig fusion proteins to tumor-bearing mice elicits IL-4-dependent, CD8+ T cell-mediated tumor regression. Here, we investigated whether B7.2-Ig stimulation of tumor-sensitized CD8+ CTL precursors during in vitro antigen re-sensitization actually results in their differentiation into mature CTLs and if so, whether such a process depends on IL-4 signals. Splenocytes from tumor-sensitized (tumor-bearing or tumor-immunized) mice exhibited low levels of anti-tumor CTL responses upon culturing alone, but induced strikingly enhanced CTL responses when stimulated in vitro with B7.2-Ig fusion proteins. Because CTLs were not generated from normal splenocytes even by B7.2-Ig stimulation, the expression of the B7.2-Ig effect required the in vivo tumor sensitization of CD8+ CTL precursors. Administration of anti-CD4 or anti-CD40 ligand (CD40L) to mice before tumor sensitization resulted in almost complete inhibition of CTL responses generated in the subsequent culture containing B7.2-Ig. In contrast, anti-IL-4 did not influence in vivo tumor sensitization required for CTL induction. However, B7.2-Ig stimulation of tumor-sensitized splenocytes enhanced IL-4 production and neutralization of this IL-4 with anti-IL-4 potently down-regulated CTL responses. These results indicate that B7.2-Ig enhances IL-4-dependent differentiation of anti-tumor CD8+ CTL precursors that can be sensitized in vivo depending on collaboration with CD4+ T cells involving CD40L function. 相似文献
22.
We evaluated human physiological responses and the performance of manual tasks during exposure to severe cold (–25°C) at
night (0300–0500 hours) and in the afternoon (1500–1700 hours). Thirteen male students wearing standard cold protective clothing
occupied a severely cold room (–25°C) for 20 min, and were then transferred to a cool room (10°C) for 20 min. This pattern
of exposure was repeated three times, for a total time of exposure to extreme cold of 60 min. The experiments were started
either at 1500 hours or 0300 hours and measurements of rectal temperature, skin temperature, blood pressure, performance in
a counting task, hand tremor, and subjective responses were made in each condition. At the end of the experiment at night
the mean decrease in rectal temperature [0.68 (SEM 0.04)°C] was significantly greater than that at the end of the experiment
in the afternoon [0.55 (SEM 0.08)°C, P<0.01]. After the second cold exposure at night the mean increase in diastolic blood pressure [90 (SEM 2.0) mmHg] was significantly
greater than that at the end of the second cold exposure in the afternoon [82 (SEM 2.8) mmHg, P<0.01]. At the end of the second cold exposure at night, mean finger skin temperature [11.8 (SEM 0.8)°C] was significantly
higher than that at the comparable time in the afternoon [9.0 (SEM 0.7)°C, P<0.01]. Similarly for the toe, mean skin temperature at the start of the second cold exposure at night [25.6 (SEM 1.5)°C]
was significantly higher than in the afternoon [20.1 (SEM 0.8)°C, P<0.01]. The increased skin temperatures in the periphery resulted in increased heat loss. Since peripheral skin temperatures
were highest at night, the subjects noted diminished sensations of thermal cold and pain at that time. Manual dexterity at
the end of the first cold exposure at night [mean 83.7 (SEM 3.6) times·min–1] had decreased significantly more than at the end of the first cold exposure in the afternoon [mean 89.4 (SEM 3.5) times·min–1, P<0.01]. These findings of a lowered rectal temperature and diminished manual dexterity suggest that there is an increased
risk of both hypothermia and accidents for those who work at night.
Electronic Publication 相似文献
23.
Jo EK Wang Y Kanegane H Futatani T Song CH Park JK Kim JS Kim DS Ahn KM Lee SI Park HJ Hahn YS Lee JH Miyawaki T 《Journal of human genetics》2003,48(6):322-326
Mutations in the Bruton's tyrosine kinase (BTK) gene are responsible for X-linked agammaglobulinemia (XLA). We identified BTK mutations in six patients with presumed XLA from unrelated Korean families. Four out of six mutations were novel: two missense
mutations (P565T, C154Y), a point mutation in a splicing donor site (IVS11+1G>A), and a large deletion (a 6.1-kb deletion
including BTK exons 11–18). The large deletion, identified by long-distance PCR, revealed Alu-Alu mediated recombination extended from an Alu sequence in intron 10 to another Alu sequence in intron 18, spanning a distance of 6.1 kb. The two known mutations consisted of one missense (G462D) mutation,
and a point mutation in a splicing acceptor site (IVS7−9A>G). This study suggests that large genomic rearrangements involving Alu repeats are few but an important component of the spectrum of BTK mutations. 相似文献
24.
Koyama C Matsumoto H Sakai T Wakabayashi K Ito A Couch EF Inoue K 《Endocrine pathology》1995,6(1):67-75
A new cell line (TtT/GF) established from a murine pituitary thyrotropic tumor having characteristics similar to those of
pituitary folliculo-stellate cell (FS cell) was implanted into nude mice together with cells from a rat pituitary somatotrophic
tumor cell line (MtT/S) to determine whether the former enhances pituitary tumor growth. For as long as 2-3 mo after implantation,
MtT/S cells implanted either alone or together with fibroblasts formed either no tumors or only very small tumors in the nude
mice. In contrast all of the nude mice that had received MtT/S cells implanted together with TtT/GF cells developed large
tumors. Furthermore, the mice bearing the MtT/S and TtT/GF implants showed a significantly higher body weight and serum growth
hormone level than those bearing only MtT/S cells or a combination of MtT/S cells and fibroblasts. The TtT/GF cell line itself
had no tumorigenicity during the experimental period. Therefore, the TtT/GF cell line as a model of FS cells enhanced pituitary
endocrine cell tumor formation. Additionally, immunocytochemistry showed that TtT/GF cells positive for glial fibrillary acidic
protein (GFAP) or S-100 protein were present in the parenchymatous tissue elements or connective tissue surrounding the tumor
nests. In the parenchymatous tissue, the TtT/GF cells exhibited a stellate appearance and surrounded neighboring tumor cells
with their long cell processes. These results suggest that TtT/GF cells can serve as a model for pituitary FS cells, and are
capable of stimulating pituitary tumor growth either by modifying the microenvironment or producing growth factors. 相似文献
25.
Kanegane H Taneichi H Nomura K Futatani T Miyawaki T 《Journal of clinical immunology》2005,25(5):491-495
X-linked agammaglobulinemia (XLA) is clinically characterized by recurrent bacterial infections during early infancy. Although it is not a phagocytic disorder, XLA is sometimes associated with neutropenia. We conducted a nation-wide survey to determine the frequency of neutropenia among Japanese XLA patients. Responses were received from 87 (86%) of 101 patients in which BTK mutations were previously identified, and of these, 16 (18%) had neutropenia. All episodes of neutropenia occurred before initiation of intravenous immunoglobulin (IVIG) replacement therapy. Two XLA patients died of multiple organ failure caused by severe neutropenia and Pseudomonas sepsis before initiation of IVIG replacement therapy. These results suggest that, in some cases, severe bacterial infections in XLA patients might be caused not only by antibody deficiencies but also by neutropenia. 相似文献
26.
Hirokazu Taniguchi Kenjiro Hamamoto Takahiro Nagano Yuji Kishimoto Takashi Kimura Hideki Fujitake Kojiro Yasunaga 《Medical Electron Microscopy》1993,26(1):13-18
Ultrastructural myeloperoxidase (MPO) activity and myeloid-associated antigen (MyAg) expression were investigated in 12 adult
patients with acute lymphoblastic leukemia (ALL). Ultrastructural MPO was detected by 3 different methods. Immunophenotyping
was performed by flow cytometry, using a series of monoclonal antibodies. Ultrastructural MPO-positive blast cells were detected
in 6 patients (50%). In 5 of these 6 patients, the methods detecting both MPO and platelet peroxidase (PPO) activities found
MPO-positive blast cells more frequently than those detecting MPO activity alone. In 2 patients (17%), at least one kind of
MyAg was positive. Ultrastructural MPO activity was detected more frequently than MyAg expression in ALL patients. This method
of detecting PPO and MPO is recommended for detection of ultrastructural MPO-positive ALL. 相似文献
27.
Tadashi Yasuda Hirokazu Imai Yasushi Nakamoto Akira B. Miura Shiegki Inomata 《Virchows Archiv : an international journal of pathology》1992,421(4):297-303
Summary The pathogenesis of the nodular lesion in diabetic glomerulosclerosis is described in association with fibrils. Thirteen diabetic patients with glomerular nodular lesions and 9 diabetics without the nodules were examined by electron microscopy using periodic acid-thio-carbohydrazide-silver proteinate staining. In cases of nodular glomerulosclerosis, abundant fibrillar structures mixed with electron-dense material were detected within the nodule and the mesangial matrix. They were also occasionally observed along the subendothelial space of the glomerular capillary walls. On the cross-section, these fibrils, including the lucent periphery, were 34 nm wide. Immunohistologically, collagen V and collagen VI were detected in nodular lesions. In contrast, in cases of the diffuse type of glomerulosclerosis, the widened mesangium was composed of dense material, which resembled the original mesangial matrix. The above fibrils were not detected in the mesangium. These findings suggest that the accumulation of the peculiar fibrils in the glomerular mesangium is a major pathogenic factor in the formation of Kimmelstiel-Wilson nodules. 相似文献
28.
Terao K Nagasawa N Nishida H Furusawa K Mori Y Yoshii F Dobashi T 《Journal of biomaterials science. Polymer edition》2003,14(11):1197-1208
In order to obtain a gelatin hydrogel crosslinked by a reagent-free method, gamma-ray and electron beam radiation was applied to porcine, bovine and fish gelatin gels and the products were characterized by measuring the gel fraction, the swelling ratio and the enzymatic degradability. On increasing the radiation dose, the gel fraction increased and both the swelling ratio and the enzymatic degradability decreased. The transition temperature from gel to sol of the hydrogel containing more than 5% mammal gelatins increased up to more than 90 degrees C when gamma-ray or electron beam were irradiated by more than 10 kGy. The results show that the degree of crosslinking of irradiated gelatin hydrogels increases with increasing irradiation dose and with decreasing concentration. It is suggested that the radiation crosslinking occurs around the physical crosslinking point or multiple helix structure of gelatin gel. 相似文献
29.
Nishimura H Tokuyama K Arakawa H Ohki Y Sato A Kato M Mochizuki H Morikawa A 《International archives of allergy and immunology》2002,129(4):320-326
BACKGROUND: Chronic exposure to fenoterol (FEN), a beta(2)-adrenergic receptor (beta(2)-AR) agonist, was shown to induce both airway hyperresponsiveness and airway remodeling in experimental animals. OBJECTIVE: We wanted to know the effects of chronic exposure to procaterol (PRO), a beta(2)-AR agonist, on airway function and structure, because this agent is widely used as a bronchodilator in Japan. For comparison, the effects of FEN were also examined. METHODS: Aerosolized PRO (0.1 or 1 mg/ml), FEN (1 mg/ml) or vehicle (0.9% NaCl) was given to guinea pigs 3 times a day for 6 weeks. Sublaryngeal deposition of these agents was calculated using radioisotopes. At 72 h after the last inhalation of PRO, FEN or vehicle, the dose-response relationship between lung resistance (R(L)) and intravenously administered acetylcholine (ACh) was measured. After measuring R(L), histological changes in noncartilaginous airway dimensions were evaluated. RESULTS: The amount of sublaryngeal deposition of 0.1 mg/ml PRO in the present study was speculated to be 100 times larger than that of therapeutic dose. ACh concentrations causing 2-fold, 10-fold and maximal increases in R(L) were not different in 4 groups tested. In the smaller membranous airways (<0.4 mm in diameter), but not the larger ones, thickening of adventitial areas was significantly greater in animals treated with beta(2)-AR agonists than in control animals (23 and 25, and 96% higher in animals treated with 0.1 and 1 mg/ml PRO or 1 mg/ml FEN, respectively). The degree of the increase was significantly less in PRO-treated animals than in FEN-treated animals (p < 0.01). CONCLUSION: Our results did not provide any evidence that regular inhalation of PRO at the therapeutic dose might induce bronchial hyperresponsiveness. In addition, huge amounts of PRO only caused a mild thickening of the adventitial areas, suggesting that PRO may be a weak inducer of airway remodeling compared with FEN. 相似文献
30.
Tatsuo Yamazaki Shigeki Tomita Kazuhito Ichikawa Yuko Ono Fujiyuki Inaba Ichio Fukasawa Yasuo Imai Johji Imura Hirokazu Fukui Takahiro Fujimori Noriyuki Inaba 《Pathobiology》2006,73(4):176-182
OBJECTIVES: We investigated the relationship between P16-immunostaining patterns and clinicopathological factors in early uterine cervix cancers and assessed whether P16-immunostaining patterns predict the prognosis of the patients with early uterine cervix cancers. METHODS: Twenty-nine early squamous cell carcinoma (SCC) specimens of the uterus were examined using immunohistochemistry for P16 expression. The P16-immunostaining pattern was classified into two groups: the homogeneous type and the heterogeneous type. P16-immunostaining patterns were evaluated in different parts of the carcinoma in situ (CIS): the center of the tumor and the front interface of the infiltrating tumor. RESULTS: All specimens were of the homogeneous type in CIS. The P16-immunostaining pattern was significantly of the heterogeneous type in the front interface of the infiltrating tumor with lymphatic invasion, vascular invasion, lymph node metastasis, and recurrence. Regarding the P16-immunostaining patterns in the front interface of the infiltrating tumor, the patients with the heterogeneous type showed a significantly worse prognosis than the patients with the homogeneous type. CONCLUSIONS: The prognosis of patients with early uterine cervical SCC may be predicted by evaluating the P16-immunostaining pattern in the front interface of the infiltrating tumor. 相似文献