大鼠单克隆抗体与博来霉素A6偶联物治疗人大肠癌实验研究

用Dextran T-40为中介体偶联大鼠抗人大肠癌单克隆抗体R19和博来霉素A6。体外实验显示R19与A6偶联物对人盲肠癌细胞Hce-8693抑制50%克隆生成浓度(IC₅₀)为0.019μmol/L;游离A6及无关单抗与A6偶联物M3-A6分别为1.05和1.00μmol/L;对人结肠HT-29细胞IC₅₀为0.078μmol/L,而游离A6为4.0μmol/L。同时加入R19单抗能阻断R19-A6偶联物的细胞毒性。体内实验显示:R19-A6偶联物对裸鼠移植的人盲肠癌生长的抑制率达90%,而同等剂量的游离A6,R19与A6混合物和M3-A6的抑制率分别为52,34和48%。结果表明单抗R19与A6偶联物对人大肠癌的抑制作用明显比游离A6强。     

人单克隆抗体与平阳霉素偶联物治疗乳腺癌实验研究

抗乳腺癌人单抗CMI用DextranT-40为中介体的方法与平阳霉素(PYM)偶联,体外实验显示CMI-PYM偶联物对人乳腺癌细胞的IC₅₀(抑制50%克隆生成浓度)为0.35μmol·L^-1;游离PYM为4.0μmol·L^-1。裸鼠体内实验证明,局部给予CMI-PYM偶联物(2.5mg·kg^-1)对移植的人乳腺癌抑制率达95%,等剂量平阳霉素为58%。结果表明人单抗CMI-平阳霉素偶联物对乳腺癌有显著疗效,偶联物对肿瘤的抑制作用比游离平阳霉素更强。     

Invasive cervical carcinoma: comparison of MR imaging and surgical findings

The accuracy of magnetic resonance (MR) imaging in staging invasive carcinoma of the cervix was determined retrospectively in 57 consecutive patients in whom the extent of disease was surgically confirmed. MR images were analyzed for (a) location and size of the primary tumor; (b) tumor extension to the uterine corpus, vagina, parametria, pelvic sidewall, bladder, or rectum; and (c) pelvic lymphadenopathy. The accuracy of MR imaging in determination of tumor location was 91% and for determination of tumor size within 0.5 cm, 70%. Its accuracy was 93% for vaginal extension and 88% for parametrial extension. Pelvic sidewall, bladder, and rectal involvement were accurately excluded in all patients, but the positive predictive values were 75%, 67%, and 100%, respectively. Overall, the accuracy of MR imaging in staging was 81%. MR imaging is valuable because it can accurately demonstrate tumor location, tumor size, degree of stromal penetration, and lower uterine segment involvement. It is also valuable for ruling out parametrial, pelvic sidewall, bladder, and rectal involvement.     

单克隆抗体与平阳霉素偶联物对肿瘤的区域性导向实验治疗

以小鼠H22肝癌腹腔内移植和胸腔内移植肿瘤为模型,观察3A5-PYM偶联物对腔内肿瘤的治疗作用,并以裸鼠移植结肠癌为模型,观察局部注射的治疗作用。结果表明,于小鼠肝癌H22皮下肿瘤局部给药,3A5-PYM在肿瘤的浓度较游离PYM高,滞留时间也较长。对小鼠腹腔内或胸腔内移植的肿瘤,腔内注射3A5-PYM比游离PYM具有更显著的延长动物生存期的作用。裸鼠皮下移植HT-29人结肠癌,在肿瘤周围注射3A5-PYM比iv或ip给予3A5-PYM显示更高的抑瘤率。提示单抗与平阳霉素偶联物在肿瘤的区域性导向治疗中有较好的疗效。     

Schistosoma mansoni excretory circulating cathodic antigen shares Lewis- x epitopes with a human granulocyte surface antigen and evokes host antibodies mediating complement-dependent lysis of granulocytes

Parasitic worms of the genus Schistosoma excrete relatively large amounts of immunogenic glycoproteins (circulating cathodic antigen [CCA]) that contain polysaccharide side chains with the trisaccharide Lewis-x (L(ex)) as a repeating unit. These carbohydrates evoke high titers of specific IgM antibodies that cross-react with the repeating L(ex) units on the surface of granulocytes. Consequently this might lead, in the presence of complement, to lysis of the granulocytes. In the present study, this hypothesis was investigated using anti-CCA mouse monoclonal antibodies (MoAbs) and polyclonal antibodies purified from sera of infected humans. By flow cytometry, it was demonstrated that the mouse MoAbs directed against CCA strongly recognized the granulocytes. It could also be shown that these MoAbs, as well as anti- CCA IgM antibodies purified from infected human sera, caused lysis of granulocytes in a complement-dependent cytotoxicity assay. Sera from healthy controls or from patients with other helminth infections resulted in negligible granulocytotoxicity. These in vitro observed phenomena may explain the mild to moderate neutropenia that occurs in schistosomiasis patients.     

Rp-HPLC法测定血清中的抗生育甾体药物利洛司酮

以RU₄₈₆为内标,建立了血清样品中新型抗孕激素甾体药物利洛司酮(lilopristone)的反相高效液相色谱法。色谱分析条件为μBondapakC₁₈柱10μm,300mm×3.9mmID;流动相为甲醇-二氯甲烷-10mmol·L^-1磷酸盐缓冲液(pH4.0)(67:5:28v/v);紫外检测波长为302nm。利洛司酮的检测限为1ng(S/N≥4:1)。血清样品经二次液一液超声振荡萃取后,得到了较好的净化。血清样品中利洛司酮的方法回收率为103.3%,日内精密度及日间精密度平均RSD为3.51%及2.92%。在浓度为10～1000ng·ml^-1血清范围内呈线性关系。     

Presence of Porphyromonas gingivalis and plasma cell dominance in gingival tissues with periodontitis

Oral Diseases (2010) 16 , 375–381 Objective: Porphyromonas gingivalis can invade and survive within its host epithelial cells. The aim of this study was to test our hypothesis that persistent presence of intracellular periodontal pathogens in gingival tissue causes the chronic inflammation and that an inappropriate immune response is a risk factor for periodontitis. Methods: Together with the presence of P. gingivalis, the distribution of B cells, plasma cells, and CD4⁺, CD8⁺, and FOXP3⁺ regulatory T cells was evaluated in gingival tissues from healthy (n = 7) and periodontitis (n = 8) sites by in situ hybridization and immunohistochemistry, respectively. Results: Porphyromonas gingivalis was detected in proximity to inflammatory infiltrates in three and seven biopsies from the healthy and periodontitis sites, respectively. Compared with healthy sites, periodontal lesions contained a significantly increased number of each immune cell studied with a relative dominance of plasma cells over T cells. Conclusions: Persistent bacterial invasion of gingival tissues in combination with a plasma cell‐dominant immune response may be involved in the pathogenesis of periodontitis.     

Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder

Kulkarni S, Jain S, Janardhan Reddy YC, Kumar KJ, Kandavel T. Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder.
Bipolar Disord 2010: 12: 647–656. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Impairments in executive function and memory have been reported in relatives of patients with bipolar disorder, suggesting that they could be potential endophenotypes for genetic studies, but the findings are inconsistent. In this study, neuropsychological performance in unaffected siblings of probands with family loading for bipolar disorder is compared to that of individually matched healthy controls. We hypothesized that performance on tests of executive functions and memory would be impaired in unaffected siblings of probands with bipolar disorder compared to matched healthy controls. Methods: We evaluated 30 unaffected siblings of probands with bipolar I disorder and 30 individually matched healthy controls using tests of attention, executive function, and memory. Unaffected siblings and healthy control subjects did not differ with respect to gender, age, and years of education. Results: Unaffected siblings performed poorly on the Tower of London test (TOL), the Rey’s auditory verbal learning test (RAVLT), and the Rey’s complex figure test. In the multivariate analysis, significance was noted for the TOL, total number of moves (p = 0.007) and the RAVLT total learning score (p = 0.001). Conclusions: Our study suggests that the deficits in verbal learning and memory and executive functions (planning) could be potential endophenotypes in bipolar disorder. These deficits are consistent with the proposed neurobiological model of bipolar disorder involving the frontotemporal and subcortical circuits. Future studies could couple cognitive and imaging strategies and genomics to identify neurocognitive endophenotypes in bipolar disorder.