Model of Epstein-Barr virus infection of human thymocytes: expression of viral genome and impact on cellular receptor expression in the T- lymphoblastic cell line, HPB-ALL

Infection of B lymphocytes and epithelial tissue by Epstein-Barr virus (EBV) is associated with malignancy and autoimmunity. The cellular receptor for EBV has been identified as CD21 (CR2). A molecule, which is biochemically and immunologically similar to B-cell CD21, has been identified on a subpopulation of immature thymocytes, suggesting a role for this molecule in the regulation of T-cell development and further suggesting that immature T cells might be susceptible to EBV infection. A growing body of literature now documents the presence of EBV in tumors of T-cell origin. We have evaluated the susceptibility of the human immature T cell line, HPB-ALL, to infection by EBV. Electron microscopy studies showed a rapid internalization of virus by HPB cells. Southern blotting showed the intracellular presence of linear EBV genomes, and components of the virus replicative cycle were identified. Expression of the BamHI Z region of the genome, encoding the nuclear protein, ZEBRA, which is strictly associated with productive infection in B cells, was detected in HPB-ALL cells. A spliced variant of Z, RAZ, was also identified. Cell surface expression of EBV late antigens was observed to occur transiently. Infection of HPB cells was also accompanied by altered expression of T-cell surface molecules involved in antigen recognition, a process critical to normal development of the T-cell repertoire. Delineation of the outcome of T- cell infection by EBV may lead to a better understanding of the role of this virus in autoimmune processes and malignancy.     

4-O-卤代酰基-4′-去甲基表鬼臼毒素类似物的合成与抗肿瘤活性

为考察4′-去甲表鬼臼毒素C₄位上联结含卤素原子的酯化侧链时对化合物抗肿瘤活性的影响,设计并采用选择性酯化方法合成了9个新的4′-去甲基表鬼臼毒素酯化产物。其中标题化合物在L₁₂₁₀白血病肿瘤细胞与KB细胞的体外生长抑制试验中普遍表现出显著的抑制活性,大部分化合物活性超过依托泊甙。而普通脂酸酯的活性较弱。     

Hemodynamic assessment of transluminal angioplasty for lower extremity ischemia

Seventy-two patients underwent hemodynamic testing before and after treatment for occlusive disease of their lower extremities. Percutaneous transluminal angioplasty (PTA) was used to treat lesions in 26 iliac segments and produced 23 initially improved ankle or upper thigh indices, two hemodynamic failures, and one technical failure; PTA for 54 femoropopliteal lesions produced initial hemodynamic improvement in 41 cases, three hemodynamic failures, and ten technical failures. Hemodynamic follow-up of the iliac segments showed improvement in 25 (92%) as measured by the systolic pressure index of the ankle; follow-up of the femoropopliteal segments showed continued patency of 41 (65.9%). The authors analyze these hemodynamic data.     

Small-bowel malabsorption and gastrointestinal malignancy

In addition to lymphoma, there is an increased incidence of gastrointestinal carcinoma in patients with malabsorption due to celiac disease. This is frequently manifested by a loss of response to gluten withdrawal. Four such cases are described: one patient had lymphoma and the other three had cancer of the esophagus, jejunum, and pancreas, respectively. The literature indicates that carcinoma of the esophagus and small bowel is particularly common in patients with celiac disease. These findings suggest that celiac disease should be considered a premalignant condition and that such patients should undergo a regular radiographic survey to detect early cancer.     

Shear-induced platelet aggregation requires von Willebrand factor and platelet membrane glycoproteins Ib and IIb-IIIa

Different types of platelets in various types of plasma were subjected to levels of shear stress that produce irreversible platelet aggregation in normal platelet-rich plasma (PRP). At shear stresses of 90 or 180 dyne/cm2 applied for 30 seconds or five minutes, aggregation was either absent or only transient and reversible using severe von Willebrand's disease (vWD) PRP (less than 1% von Willebrand factor, vWF); Bernard-Soulier syndrome (BSS) PRP (platelets deficient in the membrane glycoprotein Ib, GPIb); normal PRP plus monoclonal antibody (MoAb) to GPIb; thrombasthenic PRP (platelets deficient in membrane glycoprotein IIb-IIIa complex, GPIIb-IIIa); and normal PRP plus MoAb to GPIIb-IIIa. Shear-induced aggregation was inhibited under the above conditions, even though the platelets were activated to release their granular contents. Sheared normal platelets in vWD plasma aggregated in response to added vWF. These studies demonstrate that the formation of stable platelet aggregates under conditions of high shear requires vWF and the availability of both GPIb and GPIIb-IIIa on platelet membranes. The experiments demonstrate that vWF-platelet interactions can occur in the absence of artificial agonists or chemical modification of vWF. They suggest a possible mechanism for platelet aggregation in stenosed or partially obstructed arterial vessels in which the platelets are subjected to relatively high levels of shear stress.     

PreCimp: Pre‐collapsing imputation approach increases imputation accuracy of rare variants in terms of collapsed variables

Imputation is widely used for obtaining information about rare variants. However, one issue concerning imputation is the low accuracy of imputed rare variants as the inaccurate imputed rare variants may distort the results of region‐based association tests. Therefore, we developed a pre‐collapsing imputation method (PreCimp) to improve the accuracy of imputation by using collapsed variables. Briefly, collapsed variables are generated using rare variants in the reference panel, and a new reference panel is constructed by inserting pre‐collapsed variables into the original reference panel. Following imputation analysis provides the imputed genotypes of the collapsed variables. We demonstrated the performance of PreCimp on 5,349 genotyped samples using a Korean population specific reference panel including 848 samples of exome sequencing, Affymetrix 5.0, and exome chip. PreCimp outperformed a traditional post‐collapsing method that collapses imputed variants after single rare variant imputation analysis. Compared with the results of post‐collapsing method, PreCimp approach was shown to relatively increase imputation accuracy about 3.4–6.3% when dosage r² is between 0.6 and 0.8, 10.9–16.1% when dosage r² is between 0.4 and 0.6, and 21.4 ～ 129.4% when dosage r² is below 0.4.     

Measuring arterial blood pressure

Accurate arterial blood pressure measurement is crucial in order to provide safe and appropriate care to patients in both theatre and the intensive care setting. Blood pressure is a measure of haemodynamic status and stability. This article will review the physical principles of both non-invasive and invasive methods of blood pressure measurement. We will cover historical measurement, commonly used techniques in clinical practice and more recent developments in blood pressure monitoring.