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901.
In vitro generation of tumor-specific cytotoxic lymphocytes. Secondary allogeneic mixed tumor lymphocyte culture of normal murine spleen cells
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In vivo or in vitro immunity to murine leukemia virus (MuLV)-induced leukemia cells which do not effectively produce virus, has been difficult to demonstrate. Because immunizations with allogeneic murine leukemia cells have been used to confer syngeneic tumor immunity to virus- producing cells, we attempted to generate lymphocytes, cytotoxic to syngeneic nonproducer leukemia cells, by stimulating normal murine spleen cells with allogeneic nonproducer leukemia cells in mixed tumor lymphocyte culture (MTLC) reactions in vitro. Secondary allogeneic MTLC of normal C57BL/6 or DBA/2 spleen cells effectively produced syngeneic tumor-specific cytotoxic lymphocytes. Target cells lysed in lymphocyte- mediated cytolysis (LMC) assays, included both Friend and Rauscher virus- induced syngeneic murine leukemia cells and chemically-induced hematopoietic tumor cells. Syngeneic tumor cells were lysed regardless of whether they produced infectious MuLV or expressed viral antigens gp-71, p-30, or p-12 at the cell surface. Syngeneic normal cells (thymus, lymph node, or Concanavalin A-stimulated spleen cells) used as targets in LMC assays were uneffected by lymphocytes harvested from secondary allogeneic MTLC. Several other in vitro culture treatments including secondary syngeneic MTLC and repetitive mixed lymphocyte culture stimulations were incapable of generating tumor-specific cytotoxic lymphocytes. Based upon these results, we propose that secondary MTLC stimulation of normal spleen cells with allogeneic nonproducer leukemia cells selects for the proliferation of two subpopulations of antigen-specific cytotoxic lymphocytes. The population capable of effecting syngeneic tumor cell lysis is directed against tumor-associated cell surface antigens which may be distinct from viral structural proteins or glycoproteins. The growth of these tumor-specific cytotoxic lymphocytes may be enhanced by a soluble allogeneic effect factor produced by the proliferation of the second subpopulation of lymphocytes generated in repetitive allogeneic MTLC, namely those lymphocytes with specificities directed against differing histocompatibility antigens. 相似文献
902.
903.
S O'Regan R W Chesney A Hamstra J A Eisman A M O'Gorman H F Deluca 《Acta paediatrica Scandinavica》1979,68(1):109-111
The serum levels of 1,25-(OH)2 vitamin D3 were assayed in samples from 12 adolescent patients with SLE. Subnormal levels were observed in 7 of these 12 patients. Low levels of the metabolically active polar metabolite of vitamin D3 may contribute to the development of osteopenia observed in this disease. The cumulative effects of the osteoporotic and anti vitamin D effects of long term steroid therapy in children with SLE may require the cautious administration of supplemental vitamin D. 相似文献
904.
Contemporary alcoholics often use multiple substances, but there is little systematic research on this. This study examines the drug use comorbidity of alcoholics (DSM diagnosis, frequency and quantity of drug use); the relationship between drinking and drug use; the relative severity of alcohol- and drug-related problems; and the validity of reports of illicit drug use. Data on substance use were collected from 248 treatment-seeking alcoholics using an expanded Time-line Follow-Back (TLFB) interview. Self-reports of substance use were validated with data from biological specimens (urine and hair). Lifetime diagnosis of joint alcohol and drug dependence/abuse was 64%. Two-thirds (68%) reported using drugs in the past 90 days: 33% powder cocaine; 29% crack cocaine; 15% heroin, and 24% cannabis. The mean proportions of exposed days on which users reported consuming a substance were 57% (alcohol), 26% (powder cocaine), 46% (crack cocaine), 47% (heroin), and 29% (cannabis). Subjects reported consuming an average of 14 standard drinks on a drinking day and $67 worth of drugs on a using day. Drug users reported drinking less than nonusers on a drinking day. Frequency of drinking and drug use were positively correlated; almost all drug users reported simultaneous drinking and drug use; and they rated drugs as the bigger problem. Considerable under-reporting of drug use occurred for the previous 3-4 days, but was more accurate for the previous month. 相似文献
905.
HE Hsu CE Rydzak KL Cotich B Wang PE Sax E Losina KA Freedberg SJ Goldie Z Lu RP Walensky for the CEPAC Investigators 《HIV medicine》2011,12(2):97-108
Objectives
The aim of the study was to quantify the benefits (life expectancy gains) and risks (efavirenz‐related teratogenicity) associated with using efavirenz in HIV‐infected women of childbearing age in the USA.Methods
We used data from the Women's Interagency HIV Study in an HIV disease simulation model to estimate life expectancy in women who receive an efavirenz‐based initial antiretroviral regimen compared with those who delay efavirenz use and receive a boosted protease inhibitor‐based initial regimen. To estimate excess risk of teratogenic events with and without efavirenz exposure per 100 000 women, we incorporated literature‐based rates of pregnancy, live births, and teratogenic events into a decision analytic model. We assumed a teratogenicity risk of 2.90 events/100 live births in women exposed to efavirenz during pregnancy and 2.68/100 live births in unexposed women.Results
Survival for HIV‐infected women who received an efavirenz‐based initial antiretroviral therapy (ART) regimen was 0.89 years greater than for women receiving non‐efavirenz‐based initial therapy (28.91 vs. 28.02 years). The rate of teratogenic events was 77.26/100 000 exposed women, compared with 72.46/100 000 unexposed women. Survival estimates were sensitive to variations in treatment efficacy and AIDS‐related mortality. Estimates of excess teratogenic events were most sensitive to pregnancy rates and number of teratogenic events/100 live births in efavirenz‐exposed women.Conclusions
Use of non‐efavirenz‐based initial ART in HIV‐infected women of childbearing age may reduce life expectancy gains from antiretroviral treatment, but may also prevent teratogenic events. Decision‐making regarding efavirenz use presents a trade‐off between these two risks; this study can inform discussions between patients and health care providers. 相似文献906.
目的 应用网络药理学分析金藤清痹颗粒治疗急性痛风性关节炎(acute gouty arthritis,AGA)的作用机制,并建立AGA大鼠模型进行验证。方法 在清热解毒、活血止痛治法指导下,通过TCMSP数据库搜集金藤清痹颗粒的活性成分及靶点,利用GeneCards、NCBI数据库等搜集AGA相关靶点,与金藤清痹颗粒作用靶点整合后,构建共有靶点蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络和“金藤清痹颗粒-中药-活性成分-靶点-AGA”网络,并进行基因本体(gene ontology,GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。雄性SD大鼠随机分为空白组、模型组、秋水仙碱(0.3 mg/kg)组和金藤清痹颗粒低、中、高剂量(1.05、2.10、4.20 g/kg)组,每组6只,踝关节注射单钠尿酸盐(monosodium urate,MSU)晶体建立AGA大鼠模型。采用游标卡尺测量大鼠踝关节直径,计算踝关节肿胀度;采用全自动生化仪检测血清尿酸(serum uric acid,SUA)、C反应蛋白(C-reactive protein,CRP)水平;采用苏木素-伊红(HE)染色观察踝关节组织病理变化;采用qRT-PCR、ELISA和Western blotting检测踝关节组织及血清中关键靶点和信号通路的表达。结果 共检索到金藤清痹颗粒110种活性成分、212个作用靶点,272个AGA治疗靶点,共有靶点29个,关键靶点有白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子(tumor necrosis factor,TNF)及IL-6,涉及TNF信号通路、IL-17信号通路和NOD样受体信号通路等。大鼠踝关节注射MSU晶体后明显肿胀(P<0.01),SUA及CRP显著升高(P<0.05、0.01),滑膜组织增生明显、结构紊乱,有大量炎症细胞浸润,NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)、NIMA相关蛋白激酶7(NIMA-related kinases 7,NEK7)、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a CARD,ASC)、半胱氨酸天冬氨酸蛋白酶-1(cystein-asparate protease-1,Caspase-1)、消皮素D(gasdermin D,GSDMD)、IL-18、IL-1β、IL-6及TNF-α表达水平明显升高(P<0.01);秋水仙碱或金藤清痹颗粒治疗后,有效缓解踝关节肿胀(P<0.05、0.01),SUA及CRP均显著降低(P<0.05、0.01),关节滑膜增生、炎症细胞浸润均得到改善,同时显著抑制IL-1β、TNF-α及IL-6等靶点和NOD样受体信号通路的表达(P<0.05、0.01)。结论 金藤清痹颗粒对AGA大鼠具有明显的保护作用,其机制可能与抑制NOD样受体信号通路的异常激活,降低炎症因子水平,改善关节滑膜增生、炎症细胞浸润有关。 相似文献
907.
Fabrizio Romano Marisa Molinaro Susanne Schibli Philipp KA Agyeman Ruth Mari Lllgen 《Clinical Case Reports》2021,9(8)
Jaundice should be considered as a first clinical sign preceding severe invasive bacterial infection or sepsis in patients of all ages including childhood and adolescence. Early laboratory investigations and MR imaging studies for osteomyelitis or myositis are paramount to avoid progression to life‐threatening sepsis and significant morbidity and mortality. 相似文献
908.
909.