Molecular characterization of the variable domains of an alphaIIbbeta3-specific immunoglobulin M kappa platelet cold agglutinin in a follicular lymphoma patient with treatment refractory autoimmune thrombocytopenia: idiotypic overlap between alphaIIbbeta3 integrin antibodies

BACKGROUND: Cold hemagglutinins are generally immunoglobulin M (IgM) kappa antibodies reactive at temperatures below 37 degrees C and if of high titer may cause hemolysis. Platelet (PLT) cold agglutinins (CAs) are rare and poorly characterized. A detailed molecular characterization of the variable domains of a pathologic, PLT-reactive, CA is presented. CASE REPORT: A 70-year-old woman was admitted with rectal bleeding accompanied by widespread petechiae, bruising, tongue and buccal mucosa bleeding, and epistaxes and proved refractory to HLA- and HPA-matched PLTs. Detailed investigation showed monoclonal heavy-chain gene rearrangement with an IgM paraprotein of 3.3 g per L and a trace of kappa Bence Jones protein in the urine, compatible with a diagnosis of secretory B-cell non-Hodgkin's lymphoma (B-NHL). PLT antibody (PAIg) investigations revealed a potent IgM kappa PLT CA. Sequencing of the rearranged variable domain genes of the malignant clone together with idiotype-specific antibodies obtained by DNA-based immunization of rabbits and matrix-assisted laser desorption/ionization-time-of-flight analysis of the PAIgM provided a irrefutable link between the thrombocytopenia, the IgM paraprotein, and the PAIgM against alphaIIbbeta3. The thrombocytopenia and bleeding were refractory to standard treatment and PLT transfusion, but treatment with rituximab resulted in a recovery of the PLT count and a complete remission of B-NHL. CONCLUSION: The IgM kappa paraprotein derived from the malignant B-cell clone was a potent and clinically significant CA against alphaIIbbeta3. The testing for PLT CAs in patients with a paraprotein and refractory to matched PLTs may aid the selection of appropriate treatment.     

β-casomorphin-7对小鼠的免疫调节作用

目的：通过体外和体内方法研究β-casomorphin-7对小鼠脾脏淋巴细胞和腹腔巨噬细胞的作用.方法：利用脾细胞增殖试验和腹腔巨噬细胞中NO浓度的变化来研究体外不同的β-casomorphin-7浓度对脾脏淋巴细胞的增殖和腹腔巨噬细胞中NO浓度变化的影响,以及腹腔注射β-casomorphin-7和饮用β-casomorphin-7溶液对上述两个指标的影响.结果：体外试验表明,β-casomorphin-7在不同浓度对脾脏淋巴细胞的增殖显示了刺激和抑制的双向作用,而对NO的产生显示了明显的抑制作用（P＜0.01）.体内试验表明,β-casomorphin-7通过腹腔注射和饮用两种给药方式对脾淋巴细胞和腹腔巨噬细胞的作用是一致的.β-casomorphin-7显著地增强了脾淋巴细胞的增殖反应（P＜0.01）,且抑制了腹腔巨噬细胞NO的产生.结论：当前的试验表明,β-casomorphin-7具有免疫调节作用,且小鼠在2～3周龄时,可吸收入血发挥免疫调节作用.     

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

Factors affecting frequency of communication about family health history with family members and doctors in a medically underserved population

Objective

Family history contributes to risk for many common chronic diseases. Little research has investigated patient factors affecting communication of this information.

Methods

1061 adult community health center patients were surveyed. We examined factors related to frequency of discussions about family health history (FHH) with family members and doctors.

Results

Patients who talked frequently with family members about FHH were more likely to report a family history of cancer (p = .012) and heart disease (p < .001), seek health information frequently in newspapers (p < .001) and in general (p < .001), and be female (p < .001). Patients who talked frequently with doctors about FHH were more likely to report a family history of heart disease (p = .011), meet physical activity recommendations (p = .022), seek health information frequently in newspapers (p < .001) and in general (p < .001), be female (p < .001), and not have experienced racial discrimination in healthcare (p < .001).

Conclusion

Patients with a family history of some diseases, those not meeting physical activity recommendations, and those who do not frequently seek health information may not have ongoing FHH discussions.

Practice implications

Interventions are needed to encourage providers to update patients’ family histories systematically and assist patients in initiating FHH conversations in order to use this information for disease prevention and control.     

慢性乙型肝炎患者肝组织中HBV抗原表达特征及其临床意义

目的探讨慢性乙型病毒性肝炎肝活检组织中检测乙肝表面抗原(HBsAg)和乙肝核心抗原(HBcAg)表达强度及表达方式的必要性。方法采用EnVision免疫组织化学法检测196例慢性乙型肝炎患者肝穿组织中HBsAg和HBcAg的表达水平,并用荧光定量PCR检测其血清中的HBV DNA的含量。对肝组织进行炎症活动度分级和纤维化分期。结果肝组织中的HBsAg表达强度和表达方式与炎症分级、纤维化分期和血清乙肝病毒载量均无相关性(P>0.05)。HBcAg表达强度与炎症分级无相关性(r=-0.02,P>0.05);与纤维化分期呈负相关(r=-0.28,P<0.01);与血清乙肝病毒载量呈正相关(r=0.53,P<0.01)。HBcAg表达方式与炎症分级为负相关(r=-0.27,P<0.01),其中浆型组炎症活动度分级高于核型组和混合型组(P<0.01),混合型组高于核型组(P<0.01)。HBcAg表达方式与纤维化分期亦呈较弱的负相关(r=-0.23,P<0.01),其中浆型组纤维化分期高于核型组和混合型组(P<0.05)。HBcAg表达方式与血清乙肝病毒载量呈正相关(r=0.22,P<0.01)。结论区分肝组织中的HBsAg表达强度和表达方式无益于了解慢性乙型肝炎患者肝损害的程度,而检测肝组织中的HBcAg则有助于临床抗病毒治疗。     

Dynamic chemical shift imaging for image-guided thermal therapy: analysis of feasibility and potential

A fast chemical shift imaging (CSI) technique based on a multiple gradient-recalled acquisition using a small number of echoes with intentional aliasing of the reference lipid peak is studied to determine its feasibility for temperature monitoring. Simulations were implemented to find parameters where the lipid and water peaks can be measured using a Fourier-based peak fitting approach as well as using an innovative autoregressive moving average technique. A phantom consisting of 50% mayonnaise/50% lemon juice was calibrated to temperature and compared to literature values. A porcine kidney was treated ex vivo with an external laser and imaged with the CSI technique with comparisons to temperature readings from a fluoroptic monitoring system and complex phase difference (CPD) calculations. To demonstrate the technique in vivo, a Balb/c mouse with a CT26 xenograft in the subcutaneous lower back was treated using gold-coated, silica-core nanoshells heated with an 808 nm interstitial laser. Compared to standard CPD techniques using a two-dimensional fast spoiled gradient recalled echo, this technique maintains spatiotemporal resolution, has high signal-to-noise ratio and accuracy over a wide range of T2* tissue values, can separate water and lipid signals, and additionally can use the lipid peak, when present, as an internal reference.