Propulsion of African trypanosomes is driven by bihelical waves with alternating chirality separated by kinks

Trypanosoma brucei, a parasitic protist with a single flagellum, is the causative agent of African sleeping sickness. Propulsion of T. brucei was long believed to be by a drill-like, helical motion. Using millisecond differential interference-contrast microscopy and analyzing image sequences of cultured procyclic-form and bloodstream-form parasites, as well as bloodstream-form cells in infected mouse blood, we find that, instead, motility of T. brucei is by the propagation of kinks, separating left-handed and right-handed helical waves. Kink-driven motility, previously encountered in prokaryotes, permits T. brucei a helical propagation mechanism while avoiding the large viscous drag associated with a net rotation of the broad end of its tapering body. Our study demonstrates that millisecond differential interference-contrast microscopy can be a useful tool for uncovering important short-time features of microorganism locomotion.     

Physiology of rate-responsive pacing.

The search for a pacemaker that accurately and easily mimics normal physiology is a continuing effort. There have been many achievements in the past, including sensing of the pacing chamber and programming of the pacing rate, sensitivity, and output. Present pacing developments include atrioventricular synchrony and rate adaptiveness. Results of studies on activation sequence and circadian variations will impact future pacing. The usefulness, cost effectiveness, and clinical value of some of the new pacing features remain unclear. Further clinical trials are necessary to clarify the value of new pacing techniques.     

Immunocapture reverse transcription-polymerase chain reaction combined with nested PCR greatly increases the detection of Prunus necrotic ring spot virus in the peach

A detection system based on nested PCR after IC-RT-PCR (IC-RT-PCR-Nested PCR) was developed to improve indexing of Prunus necrotic ringspot virus in peach trees. Inhibitory effects and inconsistencies of the standard IC-RT-PCR were overcome by this approach. IC-RT-PCR-Nested PCR improved detection by three orders of magnitude compared with DAS-ELISA for the detection of PNRSV in leaves. Several different tissues were evaluated and equally consistent results were observed. The main advantages of the method are its consistency, high sensitivity and easy application in quarantine programs.     

Fusion Viewer: A New Tool for Fusion and Visualization of Multimodal Medical Data Sets

Digital medical images are very easy to be modified for illegal purposes. For example, microcalcification in mammography is an important diagnostic clue, and it can be wiped off intentionally for insurance purposes or added intentionally into a normal mammography. In this paper, we proposed two methods to tamper detection and recovery for a medical image. A 1024 × 1024 x-ray mammogram was chosen to test the ability of tamper detection and recovery. At first, a medical image is divided into several blocks. For each block, an adaptive robust digital watermarking method combined with the modulo operation is used to hide both the authentication message and the recovery information. In the first method, each block is embedded with the authentication message and the recovery information of other blocks. Because the recovered block is too small and excessively compressed, the concept of region of interest (ROI) is introduced into the second method. If there are no tampered blocks, the original image can be obtained with only the stego image. When the ROI, such as microcalcification in mammography, is tampered with, an approximate image will be obtained from other blocks. From the experimental results, the proposed near-lossless method is proven to effectively detect a tampered medical image and recover the original ROI image. In this study, an adaptive robust digital watermarking method combined with the operation of modulo 256 was chosen to achieve information hiding and image authentication. With the proposal method, any random changes on the stego image will be detected in high probability.     

Influence of amiodarone on QT dispersion in patients with life-threatening ventricular arrhythmias and clinical outcome

Increased QT dispersion, defined as the difference between the maximum and minimum QT interval on the standard 12-lead electrocardiogram, is assumed to reflect regional inhomogeneity of ventricular repolarization and has been shown to be associated with an increased risk of arrhythmic events. The purpose of the present study is to examine the influence of amiodarone on QT dispersion in patients with life-threatening ventricular arrhythmias and to evaluate the predictive value of QT dispersion after amiodarone therapy for further arrhythmic events. ECG's were obtained in 47 patients 1–2 days before and 6–8 weeks after amiodarone was started. All patients had coronary artery disease with a mean EF of 34±14%. The QT interval was measured in each lead of a digitized ECG displayed on a high resolution monitor (250 mm s⁻¹). Amiodarone therapy resulted in a significant increase in the maximal QT_c interval (476±44 to 505±44 ms, p<0.001). However, measurement of QT dispersion (70±34 vs 73±29 ms) and Qtc dispersion (78±37 vs 77±31 ms) revealed no significant difference before and after amiodarone. During a one year follow-up period 26 patients were free of arrhythmic events and 7 patients developed further arrhythmic events. The remaining 14 patients were excluded from the one year follow-up analysis because of drug discontinuation (n=8), death due to heart failure (n=1), medical intervention (n=3) and incomplete follow-up (n=2). No measure of QT dispersion was predictive of recurrent arrhythmic events during treatment with amiodarone.

Conclusion: Treatment with amiodarone results in significant QT prolongation without altering QT dispersion. Measurements of QT dispersion were not predictive of amiodarone efficacy in this patient population.     

A chaperone protein-enriched tumor cell lysate vaccine generates protective humoral immunity in a mouse breast cancer model

We have documented previously that a multiple chaperone protein vaccine termed chaperone-rich cell lysate (CRCL) promotes tumor-specific T-cell responses leading to cancer regression in several mouse tumor models. We report here that CRCL vaccine generated from a mouse breast cancer (TUBO, HER2/neu positive) is also capable of eliciting humoral immunity. Administration of TUBO CRCL triggered anti-HER2/neu antibody production and delayed the progression of established tumors. This antitumor activity can be transferred through the serum isolated from TUBO CRCL-immunized animals and involved both B cells and CD4(+) T lymphocytes. Further evaluation of the mechanisms underlying TUBO CRCL-mediated humoral immunity highlighted the role of antibody-dependent cell-mediated cytotoxicity. These results suggest that tumor-derived CRCL vaccine has a wider applicability as a cancer vaccine because it can target both T-cell- and B-cell-specific responses and may represent a promising approach for the immunotherapy of cancer.     

Cytokines fused to antibodies and their combinations as therapeutic agents against different peritoneal HER2/neu expressing tumors

We have previously generated antihuman HER2/neu-humanized IgG3 fused to interleukin-2 (IL-2), IL-12, or granulocyte macrophage colony-stimulating factor (GM-CSF) [monofunctional fusion proteins (mono-AbFP)] or fused to IL-2 and IL-12 or IL-12 and GM-CSF [bifunctional fusion proteins (bi-AbFP)]. These AbFPs retained cytokine and antigen-binding activities. We have now further characterized the AbFPs and determined the heparin-binding activity of the fused cytokines, their ability to trigger IFN-gamma secretion and natural killer (NK) activation, and their direct antitumor efficacy. Flow cytometry revealed heparin-binding activity in the AbFPs containing IL-12 and IL-2, although this activity seems to be decreased in the bi-AbFPs. However, both bi-AbFPs retained the capacity to stimulate IL-12-dependent IFN-gamma secretion in the NK cell line KY-1, and IL-12/IL-2 bi-AbFP induced NK activity in splenocytes. The antitumor effectiveness of bi-AbFPs and mono-AbFP combinations was studied in mice challenged i.p. with three different human HER2/neu murine syngeneic models (D2F2/E2, CT26-HER2/neu, and MC38-HER2/neu). Although a significant variability in the profile of antitumor response was observed in the different tumor models, the combination of IL-12 and GM-CSF mono-AbFPs protected 100% of D2F2/E2-challenged and 75% of CT26-HER2/neu-challenged mice. In contrast, bi-AbFPs protected less than the combination of mono-AbFPs and, in some models, even less than mono-AbFPs alone. However, in all cases, most of long-term survivors showed protection after s.c. rechallenge with the tumors and later with the parental tumors not expressing HER2/neu. These results show that, although the pattern of protection is tumor model dependent, treatments with AbFPs can effectively generate high levels of protection against peritoneal tumors expressing HER2/neu, which may be relevant in patients with primary or metastatic peritoneal carcinomatosis that may be observed in ovarian, colon, stomach, bladder, lung, and breast cancers.