sPLA2-V inhibits EPCR anticoagulant and antiapoptotic properties by accommodating lysophosphatidylcholine or PAF in the hydrophobic groove

The endothelial protein C receptor (EPCR) plays an important role in cardiovascular disease by binding protein C/activated protein C (APC). EPCR structure contains a hydrophobic groove filled with an unknown phospholipid needed to perform its function. It has not been established whether lipid exchange takes place in EPCR as a regulatory mechanism of its activity. Our objective was to identify this phospholipid and to explore the possibility of lipid exchange as a regulatory mechanism of EPCR activity driven by the endothelially expressed secretory group V phospholipase A(2) (sPLA(2)-V). We identified phosphatidylcholine (PCh) as the major phospholipid bound to human soluble EPCR (sEPCR). PCh in EPCR could be exchanged for lysophosphatidylcholine (lysoPCh) and platelet activating factor (PAF). Remarkably, lysoPCh and PAF impaired the protein C binding ability of sEPCR. Inhibition of sPLA(2)-V, responsible for lysoPCh and PAF generation, improved APC binding to endothelial cells. EPCR-dependent protein C activation and APC antiapoptotic effect were thus significantly enhanced. In contrast, endothelial cell supplementation with sPLA(2)-V inhibited both APC generation and its antiapoptotic effects. We conclude that APC generation and function can be modulated by changes in phospholipid occupancy of its endothelial cell receptor.     

A new genetic abnormality leading to TP53 gene deletion in chronic lymphocytic leukaemia

The analysis of chromosomal abnormalities provides significant prognostic information in patients with chronic lymphocytic leukaemia (CLL), a disease with a highly heterogeneous clinical course. Chromosomal abnormalities commonly found are trisomy 12, del(13)(q14), del(11)(q22-23), del(17)(p13) and del(6)(q21). Translocations are present in some patients and affect regions recurrently involved in CLL. This report describes the clinical and pathological characteristics of four CLL patients showing a new recurrent chromosomal abnormality dic(8;17)(p11;p11), that implied loss of the TP53 gene in all cases. In addition, TP53 gene was mutated in three out of four patients. Mechanically, Low Copy Repeats (LCR) in 17p12 and 8p11 may explain the origin of the translocation by non-allelic homologous recombination (NAHR). Isolated dic(8;17)(p11;p11) in patients with mutated IGHV genes status may not have the same prognostic impact as other mutations or deletions affecting the TP53 gene. Larger series are needed to better evaluate the clinical impact of this chromosomal aberration during the course of the disease.     

Prooxidant-Antioxidant Balance and Antioxidized LDL Antibody Level Values and Cardiac Function in Patients with Coronary Artery Disease

Objectives: We studied the association between the prooxidant-antioxidant balance (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox-LDL) IgG antibody and indices of cardiac function (systolic and diastolic function) in patients with coronary artery disease (CAD). Methods: Fifty-five patients with established CAD were selected, and serum levels of anti-ox-LDL IgG and PAB values were measured and compared with 40 matched healthy controls. Systolic and diastolic functions were determined for all patients. Results: PAB values were significantly higher in patients than in controls (p < 0.001), whilst serum anti-ox-LDL concentrations were not statistically different between the 2 groups (p = 0.821). However, after adjustment for high-density lipoprotein cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB values were inversely associated with ejection fraction (r = -0.326, p = 0.031), but this was not the case for anti-ox-LDL in either group (p > 0.05). Conclusion: Serum concentrations of a marker of oxidative stress (PAB values) are inversely associated with cardiac function. PAB is a relatively simple index that could be incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody concentration does not appear to reflect total oxidative stress as assessed by PAB.     

Histopathology of surgically treated renal tumours in young adults: a developing country perspective

Background  

There is no data on the histopathological characteristics of renal tumours in young adults in Pakistan.     

<Emphasis Type="Italic">PTEN</Emphasis>-mediated AKT activation contributes to the reduced apoptosis among Indian oral squamous cell carcinoma patients

Purpose  

The tumor suppressor gene PTEN negatively regulates Akt, a downstream mediator phosphoinositol 3-kinase. Several studies have reported the role of PTEN gene in Akt downregulation and apoptosis induction in different cancers and cell lines. However, the role of loss of PTEN expression in Akt activation and spontaneous apoptosis in oral squamous cell carcinoma clinical specimens is not well established.     

Effect of anti-TNF treatment on sleep problems in ankylosing spondylitis

Sleep disturbances and problems are increased in ankylosing spondylitis (AS). But much is not known in a quantitative way about sleep problems and effect of treatments on AS. This study is aimed first, to investigate sleep disturbances in AS and secondly, to evaluate the effects of anti-TNF treatment on SD in AS. One hundred seventy-one (Female/male: 90/81) AS patients fulfilling modified New York criteria and 86 (F/M: 56/30) age- and gender-matched controls without inflammatory diseases were included into the study. Demographic data and disease activity and treatments were recorded using The Bath Ankylosing Spondylitis Functional Index (BASFI) and The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The Medical Outcomes Study (MOS) Sleep Questionnaire was used for evaluating sleep and problems of sleep. AS patients had higher sleep disturbance scale (SDS) and sleep problem index (SPI) II scores. Group A (patients using NSAID and/or DMARD, 53.2% of patients) had higher BASDAI and BASFI compared with Group B (Patients using anti-TNF treatments) (4.29?±?2.38 vs. 2.46?±?2.32, p?<?0.001; 1.95?±?2.15 vs. 0.93?±?1.31, p?<?0.001, respectively). Whereas Group A had higher scores of SDS, awaken short of breath or headache, somnolence, and SPI-II than controls, none of the sleep parameters were statistically different between patients on anti-TNF treatments and controls. BASDAI was positively correlated with SPI-I, SPI-II, SDS, and somnolence scale. AS patients had increased sleep problems and disturbances compared with controls. Anti-TNF agents improve significantly these problems. Sleep problems are significantly correlated with the disease activity.     

The relationship between tender point count and disease severity in patients with primary fibromyalgia

Objective of this study is to asses the relationship between tender point count (TPC) and the severity of disease in patients with primary fibromyalgia (FM). One hundred and seven female patients with FM diagnosis according to ACR criteria were included to the study. Main outcome measures were fibromyalgia impact questionnaire (FIQ), Beck depression inventory (BDI), visual analog scale (VAS) and tender point assessment. Mean TPC was 14.66 ± 2.50 and mean VAS was 6.6 ± 1.2 cm. Mean total FIQ score and BDI was 62.75 ± 15.57 and 16.17 ± 7.12, respectively. TPC was correlated positively with FIQ and VAS scores. There was no correlation between TPC and age and duration of symptoms. In conclusion, TPC is a simple and noninvasive examination finding that can supply information about the disease severity and the depression in FM.