A bi-functional hepatitis B virus core antigen (HBcAg) chimera activates HBcAg-specific T cells and preS1-specific antibodies

A major problem in chronic hepatitis B virus (HBV) infection is that treatment with specific antivirals is life-long since they rarely induce a sustained response. An attractive option is therefore to combine antiviral therapy with some type of immune stimulator, such as a therapeutic vaccine. Several lines of evidence suggest that a key target for the cellular immune response is the HBV core antigen (HBcAg). However, it may also be of advantage to simultaneously improve the neutralizing antibody response to the surface (S) region of HBV. We therefore generated chimeric HBcAg particles expressing preS1 residues 1-42 at the tip of the spike region. We could show that this chimeric HBcAg-preS1 protein primed both HBcAg-specific T cells and antibodies to preS1. This strongly suggests that this may be a viable approach to develop an effective bi-functional therapeutic vaccine as an add-on for the treatment of chronic HBV infections.     

Concomitant inhibition of DNA methyltransferase and BCL-2 protein function synergistically induce mitochondrial apoptosis in acute myelogenous leukemia cells

DNA methylation and BLC-2 are potential therapeutic targets in acute myeloid leukemia (AML). We investigated pharmacologic interaction between the DNA methyltransferase inhibitor 5-azacytidine (5-AZA) and the BCL-2 inhibitor ABT-737. Increased BCL-2 expression determined by reverse phase protein analysis was associated with poor survival in AML patients with unfavorable cytogenetics (n?=?195). We found that 5-AZA, which itself has modest apoptotic activity, acts synergistically with ABT-737 to induce apoptosis. The 5-AZA/ABT-737 combination enhanced mitochondrial outer membrane permeabilization, as evidenced by effective conformational activation of BAX and ?ψ_m loss. Although absence of p53 limited apoptotic activities of 5-AZA and ABT-737 as single agents, the combination synergistically induced apoptosis independent of p53 expression. 5-AZA down-regulated MCL-1, known to mediate resistance to ABT-737, in a p53-independent manner. The 5-AZA/ABT-737 combination synergistically induced apoptosis in AML cells in seven of eight patients. 5-AZA significantly reduced MCL-1 levels in two of three samples examined. Our data provide a molecular rationale for this combination strategy in AML therapy.     

Atherosclerotic disease of the abdominal aorta and its branches: prognostic implications in patients with heart failure

Aortic atherosclerosis reduces compliance in the systemic circulation and increases peripheral resistance, afterload and left ventricular wall stress. In patients with heart failure, these changes can impair left ventricular systolic function and energy efficiency, which could reduce exercise capacity. Though the interaction and the impact of aortic atherosclerosis on left ventricular function have been investigated, its prognostic implications in patients with heart failure are unclear. We used cardiac magnetic resonance imaging and gadolinium-enhanced abdominal aortography to investigate the prevalence and prognostic impact of atherosclerotic disease of the abdominal aorta and its side branches in 355 patients with heart failure. Sclerotic abdominal aortic disease was defined as a luminal narrowing >50% of the aorta and its side branches or the presence of abdominal aortic aneurysm. Patients with disease of the aorta and its branches were older (P?相似文献   

A decoupler-free simple paper microchip capillary electrophoresis device for simultaneous detection of dopamine,epinephrine and serotonin

This paper demonstrates a new and simplified configuration for capillary electrophoresis-amperometric detection (CE-AD) using a paper microfluidic chip incorporating inexpensive wax printing and screen printing based methods and then used for electrophoretic separation and simultaneous in-channel amperometric detection of three clinically relevant neurochemicals in a single run without using any decouplers. Detection of neurochemicals e.g., dopamine, epinephrine and serotonin is crucial for early prediction of neurological disorders including Parkinson''s, Alzheimer''s, dementia, as well as progressive neuro-psychiatric conditions such as depression, anxiety, as well as certain cardiovascular diseases. The plasma concentrations of such neurochemicals are as important as those present in cerebrospinal fluid (CSF) and can be useful for rapid and convenient biosensing. However, simultaneous detection of such neurochemicals in a complex mixture such as human serum requires their separation prior to detection. With the developed microchip, separation and detection of the neurochemicals were exhibited within 650 seconds without pre-treatment and the procedure was validated with spiked fetal bovine serum samples. Beside this, the developed paper microfluidic chip has potential to be integrated in point-of-care diagnosis with onsite detection ability. Moreover, the use of a straight channel capillary, a screen-printed carbon electrode without decoupler, in-channel amperometric detection and low sample volume requirements (2 μL) are shown as additional advantages.

This paper demonstrates a simplified configuration for capillary electrophoresis-amperometric detection using paper microfluidic chip for separation and simultaneous detection of three clinically relevant neurochemicals without using any decouplers.     

Transient Granulomatous Inflammation of the Hand

We present a granulomatous inflammatory tumour of the hand in a fit 26-year-old man. The lesion resolved spontaneously within a month of presentation. Whilst the true nature of this inflammatory lesion remains unknown the case highlights the importance of thorough investigation of all deep-seated soft tissue tumours of the hand prior to committing a patient to surgery.