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91.
Yoram Shechter Marina Mironchik Shimon Amir Ben-Ami Sela Haim Tsubery Hailin Zheng Mati Fridkin 《International journal of peptide research and therapeutics》2006,12(2):121-129
Polymyxin B (PMXB) blocks the action of insulin on glucose uptake in vitro. In vivo, it reverses hypoglycemia induced by exogenous insulin. Here we have treated mature male rats daily with PMXB over a period of two weeks. This therapy has decreased body weight by 11%, adipose fat mass by 46% and triglyceride levels by 39%, with no indication of liver or kidney toxicity. Two suboptimal parameters, however, were a decrease in food intake in the first week of treatment and some increase in fasting glucose levels. We have screened for PMXB-analogs having less associating affinity with rat-muscle phospholipids, and revealed that the same therapy using PMXB-derived peptide (nona-PMXB) is most optimal. This PMXB-analog is devoid of antibacterial activity and is four times less toxic than PMXB. Nona-PMXB therapy lower by 10, 32, 35 and 6% body weight gain, fat mass, circulating triglycerides and fasting glucose levels, respectively, in spite of normal or even elevated food intake in nona-PMXB treated rats. In summary, we found that nona-PMXB therapy is capable if inducing leanness in mature rats, particularly at the expense of decreasing fat-mass in adipose tissue. By and large, we suggest that lowering the action of insulin, on fat build-up solely, may be a therapeutically feasible task to fight with human adiposity in the future. 相似文献
92.
Shimon Slavin Aliza Ackerstein Reuven Or Michael Y. Shapira Benjamin Gesundheit Nadir Askenasy Shoshana Morecki 《Cancer immunology, immunotherapy : CII》2010,59(10):1511-1519
The feasibility and safety of immunotherapy mediated by intentionally mismatched rIL-2 activated killer lymphocytes (IMAK)
with no prior stem cell engraftment was investigated in patients with advanced chemotherapy-resistant hematological malignancies
and metastatic solid tumors. Our goals were to maximize anti-cancer activity by using intentionally mismatched donor lymphocytes;
amplify killing of target cancer cells by rIL-2 activation of killer cells in vitro and in vivo, and avoid the risk of graft-versus-host
disease (GVHD) by anticipated rejection of alloreactive donor lymphocytes. Conditioning consisted of 5 days of fludarabine
25 mg/m2 or a single dose of cyclophosphamide 1,000 mg/m2, 2 subcutaneous injections of alpha interferon (IFN) 3 × 106 and COX2 inhibitors, followed by administration of IMAK (65 ± 5 CD3+CD56−; 17 ± 5 CD3−CD56+) in conjunction with low dose subcutaneous rIL-2 (6 × 106 IU/m2/day) for 5 days for continuous activation of alloreactive donor lymphocytes prior to their anticipated rejection. Here, we
present our phase 1 clinical study data in a cohort of 40 high-risk patients with metastatic solid tumors and hematological
malignancies. Treatment was accompanied by some malaise and occasional self-limited fever but otherwise well tolerated on
an outpatient basis. Transient engraftment of donor cells was documented in two patients and only one developed self-limited
grade 1 GVHD. Among patients with chemotherapy-resistant disease, long-term progression-free survival was recorded in 5 of
21 evaluable patients with metastatic solid tumors and in four of five patients with hematological malignancies. We conclude
that the proposed procedure is feasible, safe, and potentially effective, with some otherwise resistant cancer patients long-term
disease-free, thus justifying larger Phase II studies in patients with hematological malignancies and metastatic solid tumors,
preferably at a stage of minimal residual disease with the goal in mind to eradicate all malignant cells at an early stage
of the disease. 相似文献
93.
Root respiratory characteristics associated with plant adaptation to high soil temperature for geothermal and turf-type Agrostis species 总被引:1,自引:0,他引:1
Respiration is a major avenue of carbohydrates loss. The objective of the present study was to examine root respiratory characteristics associated with root tolerance to high soil temperature for two Agrostis species: thermal Agrostis scabra, a species adapted to high-temperature soils in geothermal areas in Yellowstone National Park, and two cultivars ('L-93' and 'Penncross') of a cool-season turfgrass species, A. stolonifera (creeping bentgrass), that differ in their heat sensitivity. Roots of thermal A. scabra and both creeping bentgrass cultivars were exposed to high (37 degrees C) or low soil temperature (20 degrees C). Total root respiration rate and specific respiratory costs for maintenance and ion uptake increased with increasing soil temperatures in both species. The increases in root respiratory rate and costs for maintenance and ion uptake were less pronounced for A. scabra than for both creeping bentgrass cultivars (e.g. respiration rate increased by 50% for A. scabra upon exposure to high temperature for 28 d, as compared with 99% and 107% in 'L-93' and 'Penncross', respectively). Roots of A. scabra exhibited higher tolerance to high soil temperature than creeping bentgrass, as manifested by smaller decreases in relative growth rate, cell membrane stability, maximum root length, and nitrate uptake under high soil temperature. The results suggest that acclimation of respiratory carbon metabolism plays an important role in root survival of Agrostis species under high soil temperatures, particularly for the thermal grass adaptation to chronically high soil temperatures. The ability of roots to tolerate high soil temperatures could be related to the capacity to control respiratory rates and increase respiratory efficiency by lowering maintenance and ion uptake costs. 相似文献
94.
Kim J Choi WS Kang H Kim HJ Suh JH Sakaguchi S Kwon B 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(9):5223-5231
In this study, we investigated the effect of an agonistic mAb (DTA-1) against glucocorticoid-induced TNF receptor (GITR) in a murine model of systemic lupus erythematosus-like chronic graft-vs-host disease (cGVHD). A single dose of DTA-1 inhibited the production of anti-DNA IgG1 autoantibody and the development of glomerulonephritis, typical symptoms of cGVHD. DTA-1-treated mice showed clinical and pathological signs of acute GVHD (aGVHD), such as lymphopenia, loss of body weight, increase of donor cell engraftment, and intestinal damage, indicating that DTA-1 shifted cGVHD toward aGVHD. The conversion of cGVHD to aGVHD occurred because DTA-1 prevented donor CD8+ T cell anergy. Functionally active donor CD8+ T cells produced high levels of IFN-gamma and had an elevated CTL activity against host Ags. In in vitro MLR, anergic responder CD8+ T cells were generated, and DTA-1 stimulated the activation of these anergic CD8+ T cells. We further confirmed in vivo that donor CD8+ T cells, but not donor CD4+ T cells, were responsible for the DTA-1-mediated conversion of cGVHD to aGVHD. These results indicate that donor CD8+ T cell anergy is a restriction factor in the development of aGVHD and that in vivo ligation of GITR prevents CD8+ T cell anergy by activating donor CD8+ T cells that otherwise become anergic. In sum, our data suggest GITR as an important costimulatory molecule regulating cGVHD vs aGVHD and as a target for therapeutic intervention in a variety of related diseases. 相似文献
95.
Terrestrial ecosystems influence climate by affecting how much solar energy is absorbed by the land surface and by exchanging climatically important gases with the atmosphere. Recent model analyses show widespread qualitative agreement that terrestrial ecological processes will have a net positive feedback effect on 21st-century global warming, and, therefore, cannot be ignored in climate-change projections. However, the quantitative uncertainty in the net feedback is large. The uncertainty in 21st-century carbon dioxide emissions resulting from terrestrial carbon cycle-climate feedbacks is second in magnitude only to the uncertainty in anthropogenic emissions. We estimate that this translates into an uncertainty in global warming owing to the land surface of 1.5 degrees C by 2100. We also emphasise the need to improve our understanding of terrestrial ecological processes that influence land-atmosphere interactions at relatively long timescales (decadal-century) as well as at shorter intervals (e.g. hourly). 相似文献
96.
Claus JA Brady MT Lee J Donohue KA Sait SN Ferrone S Wetzler M 《Cancer immunology, immunotherapy : CII》2006,55(2):160-165
Dendritic-like cells from t(9;22) acute lymphoblastic leukemia (ALL) blasts can activate T cells, while the original unmodified
leukemic blasts cannot. To determine whether these functional differences were associated with differences in antigen-processing
machinery (APM) component expression, we have measured the level of APM component expression in unmodified blasts and ALL-derived
dendritic-like cells. Seven t(9;22) ALL patient samples and one cell line were studied for APM component expression utilizing
a unique panel of recently developed monoclonal antibodies and a recently developed intracellular staining technique. In addition,
the HLA class I antigen cell surface expression was measured. HLA class I antigens were similarly expressed on the unmodified
blasts and on the autologous dendritic-like cells. Intracellular HLA class I antigen and tapasin expression (P=0.03 for both) were upregulated in all t(9;22) ALL-derived dendritic-like cells, in comparison to the unmodified blasts.
These results provide a potential mechanism for the ability of t(9;22) ALL-derived dendritic-like cells to induce T-cell activation
and, suggest that tapasin upregulation may serve as a marker to standardize and monitor the quality of the dendritic-like
cells used in immunotherapy.
Supported partially by The Heidi Leukemia Research Fund, Buffalo, NY, and by PHS grants CA 67108 and CA 16056 awarded by the
National Cancer Institute, DHHS. 相似文献
97.
Abdul-Hai A Ben-Yehuda A Galsky H Slavin S Or R 《Cancer immunology, immunotherapy : CII》2006,55(11):1330-1336
Success of allogeneic and autologous bone marrow transplantation (BMT) is hampered by susceptibility to infection during the first two post-treatment years. Further, in treating malignant diseases, impaired anti-host reactivity for donor cells may contribute to a high rate of relapse. Both complications are a consequence of immune deficiency involving B and T lymphocytes. The present study evaluates several key parameters of the immunologic reconstitution mechanism in mice subjected to myeloablative total body irradiation following semi-allogeneic (parental) BMT. This resulted in a gradual reduction of splenic CD3, CD4 and CD8 cells until day 45 post-BMT. Concomitantly, there was an increase in monocytes and CD4+/CD8+ (double positive) cells, accompanied by a persistent elevation in the percentage of B lymphocytes. The total thymic and splenic T cell populations were reduced until day +30. The cellular reduction correlated with the poor proliferative response of the thymic and splenic cells. A decrease occurred in IL-2 mRNA expression in thymic cells during days 15–20 post-transplant, corresponding with the low level of IL-2 secretion in the spleen and thymus of the transplanted mice. In conclusion, following semi-allogeneic BMT, there was an overall immune down-regulation in the cells, gene and protein levels. Reduced immunological responsiveness following BMT reinforces the need for improving the immune dysfunction by immunotherapy post-BMT. 相似文献
98.
We studied whether changes in the assimilation and allocation of carbon and nitrogen are associated with plant tolerance to high soil temperatures. Two Agrostis species, thermal Agrostis scabra, a species adapted to high-temperature soils in geothermal areas in Yellowstone National Park (USA), and two cultivars of a cool-season species, Agrostis stolonifera, L-93 and Penncross, were exposed to soil temperatures of 37 or 20 degrees C, while shoots were exposed to 20 degrees C. Net photosynthesis rate, photochemical efficiency, NO(3) (-)-assimilation rate and root viability decreased with increasing soil temperatures in both species. However, the decreases were less pronounced for A. scabra than for both A. stolonifera cultivars. Carbon investment in growth of plants exposed to 37 degrees C decreased more dramatically in both A. stolonifera cultivars than in A. scabra. Nitrogen allocation to shoots was greater in A. scabra than in both creeping bentgrass cultivars at 37 degrees C soil temperature. Our results demonstrate that plant tolerance to high soil temperature is related to efficient expenditure and adjustment of C- and N-allocation patterns between growth and respiration. 相似文献
99.
100.
New Rapid and Simple Methods for Detection of Bacteria and Determination of Their Antibiotic Susceptibility by Using Phage Mutants
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Three new methods applying a novel approach for rapid and simple detection of specific bacteria, based on plaque formation as the end point of the phage lytic cycle, are described. Different procedures were designed to ensure that the resulting plaques were derived only from infected target bacteria (“infectious centers”). (i) A pair of amber mutants that cannot form plaques at concentrations lower than their reversion rate underwent complementation in the tested bacteria; the number of plaques formed was proportional to the concentration of the bacteria that were coinfected by these phage mutants. (ii) UV-irradiated phages were recovered by photoreactivation and/or SOS repair mediated by target bacteria and plated on a recA uvrA bacterial lawn in the dark to avoid recovery of noninfecting phages. (iii) Pairs of temperature-sensitive mutants were allowed to coinfect their target bacteria at the permissive temperature, followed by incubation of the plates at the restrictive temperature to avoid phage infection of the host cells. This method allowed the omission of centrifuging and washing the infected cells. Only phages that recovered by recombination or complementation were able to form plaques. The detection limit was 1 to 10 living Salmonella or Escherichia coli O157 cells after 3 to 5 h. The antibiotic susceptibility of the target bacteria could also be determined in each of these procedures by preincubating the target bacteria with antibiotic prior to phage infection. Bacteria sensitive to the antibiotic lost the ability to form infectious centers. 相似文献