An analysis of T cell responsiveness in Indian kala-azar

The inability of most untreated patients with Kala-azar to control their visceral infections with Leishmania donovani has been attributed to a defective cell-mediated immune response to leishmanial antigens. We examined the in vitro response of T cells, including Leu-2+-depleted T cell populations, to determine whether unresponsiveness could be reversed. These studies on patients with visceral leishmaniasis in Bihar, north India, support previous observations regarding T cell unresponsiveness in patients with active disease: it is profound, it is specific, and it is reversible after successful chemotherapy. However, these studies also indicate that the specific unresponsiveness cannot be reversed by depletion of "suppressor" Leu-2+ T lymphocytes, nor by the addition of exogenously supplied human IL 2 to the cultures. One interpretation of these results is that in active cases of Kala-azar, there is an absence of Leishmania-specific T cells in the periphery. The possibility that reactive cells can be found in situ cannot be excluded. The observation that 13 of 25 family members of active cases were able respond to L. donovani in vitro or by skin testing suggests that the frequency of infection within an endemic area in Bihar is very high, and that assays for T cell responsiveness are far better epidemiologic tools for the detection of asymptomatic infection than is ELISA. Identification of such an exposed, Kala-azar-resistant population will be required to study host factors which influence the development of disease in infected individuals.     

Identification of immune complex antigens in sera of Indian kala-azar patients

Level of circulating immune complex (IC) in visceral leishmaniasis is much higher than that in control sera. In immunoblot experiment, treatment of kala-azar IC with patient sera showed at least 6 bands of which the band around 55 kDa region was most prominent. The band at 55 kDa is primarily due to the presence of an antigen recognized by its corresponding antibody present in the patient sera. This was confirmed by using radiolabelled antibody from kala-azar patient serum and antipromastigote serum. The heavy chain of IgG originating from IC is also present in the same region which was detected by its recognition with antihuman IgG. The IC gave a band at 55 kDa region with sea-urchin antitubulin. Kala-azar sera also reacted with purified rat brain tubulin. The present results suggest that a tubulin like protein is present at 55 kDa region along with the heavy chain of IgG.     

Antibodies in the study of multiple drug resistance

Multidrug resistance (MDR) is a major problem in cancer chemotherapy. As P-glycoprotein is the key molecule in MDR, many investigators have constructed anti-P-glycoprotein monoclonal antibodies (MAbs). Those antibodies, including MRK16 and C219, were used for elucidation of the mechanism of MDR and for overcoming of MDR. This article describes the characterization of the antibodies against the P-glycoprotein and other proteins of multidrug-resistant tumor cells, and discusses the therapeutic implication of the antibodies.Abbreviation ADCC antibody-dependent cell-mediated cytotoxicity     

Imported and autochthonous kala-azar in France.

OBJECTIVE--To study the epidemiological, clinical, and biological features of imported and autochthonous kala-azar in France. DESIGN--Prospective survey of all patients in France with kala-azar diagnosed over the two years 1986-7. Information was obtained from parasitology laboratories in regional hospitals and all hospital laboratories and haematology departments capable of diagnosing leishmaniasis in the south of France. SETTING--107 public hospitals in France. PATIENTS--89 patients with kala-azar. INTERVENTIONS--All patients were treated with drugs. In the first instance meglumine antimonate was given to all but two patients. MAIN OUTCOME MEASURES--Prevalence of the various clinical and biological features of kala-azar; proportion of patients with HIV infection. RESULTS--Half (44) of the patients were children under 8 years old. Seventy patients acquired the disease in France. Imported kala-azar was acquired mainly in Mediterranean countries (9/18 cases). Only 46 (52%) of the patients had all three of the classic associated clinical features of fever, splenomegaly, and hepatomegaly. Anaemia was the commonest biological sign, and the association of the four usual biological signs--anaemia, leucopenia, thrombocytopenia, and hypergammaglobulinaemia--was present in only 14 (33%) of the children under 8 and 26 (60%) adults. Fourteen of the patients over 8 years old were infected with HIV. CONCLUSION--Doctors must be aware of kala-azar in Mediterranean areas, especially as patients often present without the characteristic features and the disease affects young children preferentially.     

凝固酶阴性葡萄球菌临床耐药性的连续性研究

目的了解凝固酶阴性葡萄球菌的耐药性情况。方法分析2008年至2010年沈阳军区总医院临床分离的484株凝固酶阴性葡萄球菌的药敏结果。结果 2008年至2010年凝固酶阴性葡萄球菌的分离率分别为4.7%、3.6%和3.1%。耐甲氧西林凝固酶阴性葡萄球菌（MRSCN）分别为76.6%、78.5%和79.9%。青霉素G、红霉素和苯唑西林的耐药率较高,平均分别为91.2%、87.5%和82.6%。万古霉素、替考拉宁和利奈唑胺的耐药率均为0。结论 2008年至2010年凝固酶阴性葡萄球菌检出率相对稳定,对常用抗菌药物的耐药率相对稳定,这为临床用药选择及加强感染控制提供了有力指导。     

肿瘤细胞耐药性研究的最新进展

肿瘤细胞的耐药性是化疗成功的主要障碍,细胞内mdr基因高表达引起的P-糖蛋白增多是产生耐药性的主要原因。谷胱甘肽系统和DNA修复、基因扩增系统也与耐药性密切相关。     

Apoptosis and anticancer drug resistance.

Anticancer agents induce cancer cell death through apoptosis or necrosis. As anticancer agents at low and high concentrations cause apoptosis and necrosis, respectively, cancer cells may be merely injured by an anticancer agent in apoptosis, and cell death may result from an activation of the internal constituents to induce apoptosis. Therefore, an alternation of apoptotic pathway must change the efficacy of anticancer agents. As an escape of cancer cells from apoptosis seems to be closely associated with the development of anticancer resistance, this report focuses on mechanisms of apoptosis and its association with anticancer resistance. A Bax induces apoptosis mitochondria-dependently, whereas Fas can induce apoptosis mitochondria-independently. An interaction of Bax and Bcl-2 is very important to decide cell life or death, and Bcl-2 phosphorylation may control this interaction: Paclitaxel treatment induced Bcl-2 phosphorylation and typical apoptosis, whereas hyperthermia induced not Bcl-2 phosphorylation but nuclear translocation and failed to induce apoptosis. Moreover, Fas was localized in the cytoplasm of exponentially growing cells and on the cell membrane of confluent cells. We would like to emphasize that it is very important to check the localization of constituents of apoptosis in order to evaluate the susceptibility of cancer cells to apoptosis.     

耳念珠菌耐药机制研究进展

耳念珠菌感染及其耐药问题已愈演愈烈,其临床耐药机制的研究已刻不容缓。本文整理了国内外耳念珠菌临床菌株对三大类抗真菌药物的耐药情况,并从外排泵异常表达、靶标蛋白突变、生物被膜和基因组可塑性4个方面总结了耳念珠菌已报道的或潜在的耐药机制,并与其他念珠菌耐药机制进行了对比。     

铜绿假单胞菌的临床分布和耐药性变迁

目的调查温州医学院附属第一医院铜绿假单胞菌的临床分布和耐药性及其变迁情况,指导临床合理用药和控制耐药菌的产生。方法对该院2003年至2005年437株铜绿假单胞菌进行回顾性分析,用17种抗菌药物进行体外药敏试验。结果铜绿假单胞菌分布以呼吸道感染和创口分泌物感染为主。细菌对第3代头孢菌素耐药率高,对头孢他啶、亚胺培南、头孢哌酮/舒巴坦和氟喹诺酮类药物的耐药率均有逐年增加的趋势。耐药率增加与临床广谱抗菌药物用药量增加有关。结论铜绿假单胞菌的耐药性十分突出,应在药敏指导下合理选用抗菌药物,应该适当控制碳青霉烯类和第3代头孢菌素的使用,减缓耐药菌株的产生。     

Three-dimensional culture models to study drug resistance in breast cancer

Despite recent advances in breast cancer treatment, drug resistance frequently presents as a challenge, contributing to a higher risk of relapse and decreased overall survival rate. It is now generally recognized that the extracellular matrix and cellular heterogeneity of the tumor microenvironment influences the cancer cells' ultimate fate. Therefore, strategies employed to examine mechanisms of drug resistance must take microenvironmental influences, as well as genetic mutations, into account. This review discusses three-dimensional (3D) in vitro model systems which incorporate microenvironmental influences to study mechanisms of drug resistance in breast cancer. These bioengineered models include spheroid-based models, biomaterial-based models such as polymeric scaffolds and hydrogels, and microfluidic chip-based models. The advantages of these model systems over traditionally studied two-dimensional tissue culture polystyrene are examined. Additionally, the applicability of such 3D models for studying the impact of tumor microenvironment signals on drug response and/or resistance is discussed. Finally, the potential of such models for use in the development of strategies to combat drug resistance and determine the most promising treatment regimen is explored.