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CD4+ T-depleted spleen cells (CD8+ T cells) activated by anti-CD3 antibodies (aCD3) suppressed proliferation of CD8+ T-depleted spleen cells (CD4+ T cells) and fresh normal T cells in response to aCD3. Antigen-nonspecific cytolytic activity was induced in splenic CD8+ T cells by stimulation with aCD3 and showed the peak level on day 3, whereas cytolytic activity induced in CD4+ T cells was weak. Intact Ig but not F(ab')2 of aCD3 induced and mediated cytolytic activity. Correspondingly, the cytolytic activity induced by aCD3 was directed against target cells bearing Ig-binding Fc-receptor activity and cytolysis was inhibited by the addition of free Ig into the assay system. We showed that aCD3-activated T cells carried a high level of aCD3 on their surface at the time after the peak proliferation when they attained high cytolytic activity. This raised the possibility that the anti-CD3-induced aCD3-redirected cytolytic activity eliminated Fc-receptor-bearing costimulatory cells in the culture for down-regulation of the T-cell proliferation. This view was supported by partial restoration of anti-CD3-induced low responsiveness of CD8+ T cells by the addition of fresh costimulatory cells. These results suggested a new pathway of down-regulation of T-cell proliferation by aCD3-activated cytolytic CD8+ T cells. 相似文献
3.
Yu-Chi Liu Yan Peng Nyein Chan Lwin Subbu S. Venkatraman Tina T. Wong Jodhbir S. Mehta 《PloS one》2013,8(8)
Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA)-loaded poly (d,l-lactide-co-ε-caprolactone) (PLC) microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK) using a rat model. The drug release profiles of the microfilms were characterized (group 1). Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2), allogeneic control grafts (group 3), allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4), and allogeneic grafts with PA eye drops (group 5; n = 12 in each). PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006–0.009 mg/day, with a consistent aqueous drug concentration of 207–209 ng/ml. The mean survival days was >28 days in group 2, 9.9±0.8 days in group 3, 26.8±2.7 days in group 4, and 26.4±3.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3). Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P<0.001). There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loaded microfilm effectively prolongs corneal allograft survival. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation. 相似文献
4.
Verena I. Carrara Khin Maung Lwin Aung Pyae Phyo Elizabeth Ashley Jacher Wiladphaingern Kanlaya Sriprawat Marcus Rijken Machteld Boel Rose McGready Stephane Proux Cindy Chu Pratap Singhasivanon Nicholas White Fran?ois Nosten 《PLoS medicine》2013,10(3)
Background
The Shoklo Malaria Research Unit has been working on the Thai–Myanmar border for 25 y providing early diagnosis and treatment (EDT) of malaria. Transmission of Plasmodium falciparum has declined, but resistance to artesunate has emerged. We expanded malaria activities through EDT and evaluated the impact over a 12-y period.Methods and Findings
Between 1 October 1999 and 30 September 2011, the Shoklo Malaria Research Unit increased the number of cross-border (Myanmar side) health facilities from two to 11 and recorded the number of malaria consultations. Changes in malaria incidence were estimated from a cohort of pregnant women, and prevalence from cross-sectional surveys. In vivo and in vitro antimalarial drug efficacy were monitored. Over this period, the number of malaria cases detected increased initially, but then declined rapidly. In children under 5 y, the percentage of consultations due to malaria declined from 78% (95% CI 76–80) (1,048/1,344 consultations) to 7% (95% CI 6.2–7.1) (767/11,542 consultations), p<0.001. The ratio of P. falciparum/P. vivax declined from 1.4 (95% CI 1.3–1.4) to 0.7 (95% CI 0.7–0.8). The case fatality rate was low (39/75,126; 0.05% [95% CI 0.04–0.07]). The incidence of malaria declined from 1.1 to 0.1 episodes per pregnant women-year. The cumulative proportion of P. falciparum decreased significantly from 24.3% (95% CI 21.0–28.0) (143/588 pregnant women) to 3.4% (95% CI 2.8–4.3) (76/2,207 pregnant women), p<0.001. The in vivo efficacy of mefloquine-artesunate declined steadily, with a sharp drop in 2011 (day-42 PCR-adjusted cure rate 42% [95% CI 20–62]). The proportion of patients still slide positive for malaria at day 3 rose from 0% in 2000 to reach 28% (95% CI 13–45) (8/29 patients) in 2011.Conclusions
Despite the emergence of resistance to artesunate in P. falciparum, the strategy of EDT with artemisinin-based combination treatments has been associated with a reduction in malaria in the migrant population living on the Thai–Myanmar border. Although limited by its observational nature, this study provides useful data on malaria burden in a strategically crucial geographical area. Alternative fixed combination treatments are needed urgently to replace the failing first-line regimen of mefloquine and artesunate. Please see later in the article for the Editors'' Summary 相似文献5.
The mechanisms by which molecular motors associate with specific cargo is a central problem in cell organization. The kinesin-like protein Smy1 of budding yeast was originally identified by the ability of elevated levels to suppress a conditional myosin-V mutation (myo2-66), but its function with Myo2 remained mysterious. Subsequently, Myo2 was found to provide an essential role in delivery of secretory vesicles for polarized growth and in the transport of mitochondria for segregation. By isolating and characterizing myo2 smy1 conditional mutants, we uncover the molecular function of Smy1 as a factor that enhances the association of Myo2 with its receptor, the Rab Sec4, on secretory vesicles. The tail of Smy1—which binds Myo2—its central dimerization domain, and its kinesin-like head domain are all necessary for this function. Consistent with this model, overexpression of full-length Smy1 enhances the number of Sec4 receptors and Myo2 motors per transporting secretory vesicle. Rab proteins Sec4 and Ypt11, receptors for essential transport of secretory vesicles and mitochondria, respectively, bind the same region on Myo2, yet Smy1 functions selectively in the transport of secretory vesicles. Thus a kinesin-related protein can function intimately with a myosin-V and its receptor in the transport of a specific cargo. 相似文献
6.
Charles M. Peters Andrew Henderson U Myint Maung U Saw Lwin U Tin Maung Ohn U Kyaw Lwin U Tun Shaung 《Economic botany》2007,61(1):3-13
Although Myanmar exports millions of dollars of rattan cane each year, the last systematic treatment of rattans in this country
was done over 100 years ago, and virtually nothing has been written about the collection and trade of this important forest
resource. Here we report the results from a study of rattans in the Hukaung Valley Tiger Reserve in northern Myanmar. A total
of 15 species of rattan were encountered; seven species are new records for Myanmar and two species are new to science. Inventory
transects revealed that the density of commercial rattans in local forests averages 40.5 canes ≽4m long/hectare. Populations
of all species appear to be actively regenerating. The current pattern of rattan exploitation, however, is largely uncontrolled
and will eventually lead to resource depletion unless some form of management is implemented. 相似文献
7.
Large-scale search of SNPs for type 2 DM susceptibility genes in a Japanese population 总被引:5,自引:0,他引:5
Daimon M Ji G Saitoh T Oizumi T Tominaga M Nakamura T Ishii K Matsuura T Inageda K Matsumine H Kido T Htay L Kamatani N Muramatsu M Kato T 《Biochemical and biophysical research communications》2003,302(4):751-758
The etiology of type 2 diabetes (DM) is polygenic. We investigated here genes and polymorphisms that associate with DM in the Japanese population. Single-nucleotide polymorphisms (SNPs) of 398 derived from 120 candidate genes were examined for association with DM in a population-based case-control study. The study group consisted of 148 cases and 227 controls recruited from Funagata, Japan. No evident subpopulation structure was detected for the tested population. The association tests were conducted with standard allele positivity tables (chi(2) tests) between SNP genotype frequency and case-control status. The independent association of the SNPs from serum triglyceride levels and body mass index was examined by multiple logistic regression analysis. A value of P<0.01 was accepted as statistically significant. Six genes (met proto-oncogene, ATP-binding cassette transporter A1, fatty acid binding protein 2, LDL receptor defect C complementing, aldolase B, and sulfonylurea receptor) were shown to be associated with DM. 相似文献
8.
Carbon catabolite repression (CCR) of the Bacillus megateriumxyl operon is dependent on the catabolite responsive element cre, the catabolite control protein (CcpA) and the histidine-containing phosphocarrier protein phosphorylated at the serine 46 residue (HPrSer46P). The latter is formed in the presence of glucose and mediates CCR via CcpA. We present evidence for the presence of HPrSer46P in a ternary complex with CcpA and cre. We also demonstrate increased stability of this complex compared to the CcpA-cre complex by electrophoretic mobility shift analysis (EMSA). This stabilization by HPrSer46P is the same for the xyl cre and an improved cre. Thus, HPrSer46P is a co-repressor for CcpA. In addition, surface plasmon resonance (SPR) experiments yielded binding constants of CcpA and the CcpA-HPrSer46P complex with cre. HPrSer46P stimulated CcpA binding to cre 50-fold. The binding constant is 4.9(+/- 0.5) x 10(6) M(-1). Non-phosphorylated HPr did not affect the complex formation between CcpA and cre. Previously proposed effects by glucose-6-phosphate, fructose-1,6-diphosphate and NADP on CcpA-cre or CcpA-HPrSer46P-cre formation were not found in EMSA and SPR experiments. 相似文献
9.
Sumalika Biswas Krishna Prasad Vadrevu Zin Mar Lwin Kristofer Lasko Christopher O. Justice 《PloS one》2015,10(4)
Fire is an important disturbance agent in Myanmar impacting several ecosystems. In this study, we quantify the factors impacting vegetation fires in protected and non-protected areas of Myanmar. Satellite datasets in conjunction with biophysical and anthropogenic factors were used in a spatial framework to map the causative factors of fires. Specifically, we used the frequency ratio method to assess the contribution of each causative factor to overall fire susceptibility at a 1km scale. Results suggested the mean fire density in non-protected areas was two times higher than the protected areas. Fire-land cover partition analysis suggested dominant fire occurrences in the savannas (protected areas) and woody savannas (non-protected areas). The five major fire causative factors in protected areas in descending order include population density, land cover, tree cover percent, travel time from nearest city and temperature. In contrast, the causative factors in non-protected areas were population density, tree cover percent, travel time from nearest city, temperature and elevation. The fire susceptibility analysis showed distinct spatial patterns with central Myanmar as a hot spot of vegetation fires. Results from propensity score matching suggested that forests within protected areas have 11% less fires than non-protected areas. Overall, our results identify important causative factors of fire useful to address broad scale fire risk concerns at a landscape scale in Myanmar. 相似文献
10.
Nang Thu Thu Kyaw Anthony D. Harries Palanivel Chinnakali Annick Antierens Kyi Pyar Soe Mike Woodman Mrinalini Das Sharmila Shetty Moe Khine Lwin Zuu Pyae Sone Htwe Marcelo Fernandez 《PloS one》2015,10(8)