Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for Hodgkin's disease

CD40 was originally described as a B-cell-restricted antigen and was subsequently found to be a member of the tumor necrosis factor (TNF) receptor superfamily. CD40 is also expressed on dendritic cells, thymic epithelium, monocytes, and some carcinoma cell lines, and plays a critical role in cell contact-dependent activation. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the presumed malignant cells of Hodgkin's disease (HD); were found to express high levels of cell surface CD40. We found that recombinant CD40 ligand (CD40L) induced interleukin-8 (IL-8) secretion and enhanced IL-6, TNF, and lymphotoxin-alpha (LT-alpha/TNF-beta) release from cultured H-RS cells. These cytokines play a significant role in the clinical presentation and pathology of HD, a tumor of cytokine-producing cells. CD40L had no mitogenic activity for HD-derived cell lines. In contrast, CD40L enhanced expression of costimulatory molecules intracellular adhesion molecule-T and B7-1 on cultured H-RS cells, both of which are overexpressed on primary H-RS cells. In addition, CD40L induced a 40% to 60% reduction of the expression of the HD-associated CD30 antigen, another member of the TNF receptor superfamily. Primary and cultured H- RS cells express not only CD30, but also CD40. CD40L has pleiotropic biologic activities on H-RS cells, and the CD40-CD40L interaction might be a critical element in the deregulated cytokine network and cell contact-dependent activation cascade typical for HD.     

Pulmonary embolectomy with use of pediatric bronchoscope for the detection of residual emboli: an innovative surgical technique

Pulmonary embolectomy in the treatment of massive pulmonary embolus has been in doubt since the introduction of thrombolytic therapy. Recent indications for surgical intervention are- contraindication to thrombolysis, failed medical treatment and severe Right Ventricular (RV) dysfunction. A 54-year male came to us with complaints of palpitation, tachypnea and repeated syncope . Transthoracic echocardiography and Computed Tomography pulmonary angiogram demonstrated- Biatrial mass with right atrial mass extending into right ventricle and main pulmonary artery. Pulmonary embolectomy was performed. Residual emboli of bilateral pulmonary arteries were detected with a fiberoptic pediatric bronchoscope and removed. Bronchoscopic evaluation appears to be safe and useful for direct visual detection of emboli.     

Automated volume analysis of head and neck lesions on CT scans using 3D level set segmentation

The authors have developed a semiautomatic system for segmentation of a diverse set of lesions in head and neck CT scans. The system takes as input an approximate bounding box, and uses a multistage level set to perform the final segmentation. A data set consisting of 69 lesions marked on 33 scans from 23 patients was used to evaluate the performance of the system. The contours from automatic segmentation were compared to both 2D and 3D gold standard contours manually drawn by three experienced radiologists. Three performance metric measures were used for the comparison. In addition, a radiologist provided quality ratings on a 1 to 10 scale for all of the automatic segmentations. For this pilot study, the authors observed that the differences between the automatic and gold standard contours were larger than the interobserver differences. However, the system performed comparably to the radiologists, achieving an average area intersection ratio of 85.4% compared to an average of 91.2% between two radiologists. The average absolute area error was 21.1% compared to 10.8%, and the average 2D distance was 1.38 mm compared to 0.84 mm between the radiologists. In addition, the quality rating data showed that, despite the very lax assumptions made on the lesion characteristics in designing the system, the automatic contours approximated many of the lesions very well.     

Magnetic resonance imaging of perineural spread of head and neck malignancies

Perineural invasion is a common mechanism of spread of head and neck cancers. Imaging plays an important role in detection of this condition because a large number of patients with perineural spread (PNS) are clinically asymptomatic. Accurate detection of PNS requires an understanding of anatomy of commonly involved neural pathways. High level of suspicion on the part of the radiologist, awareness of common imaging signs of PNS and careful attention to imaging technique can aid in earlier detection of this condition.     

Investigation of dual-bend serpentine/spiral waveguides coupled to a microchannel system for competent,evanescent-wave-absorption-based,on-chip,biological-/chemical-sensing applications

U or C-shaped waveguides, coupled to analyte microchannels, have been shown to be very responsive to evanescent-wave-absorption-based sensing. However, due to only having a single C-bend length, for analyte interaction in earlier devices, there was always an opportunity to advance their evanescent-absorbance sensitivity, by including multiple C-bend structures (interfaced with the analyte microchannel system) in the device design. To achieve this objective, two different types of waveguide probes (having a different orientation of two C-bends), i.e. S-bend and spiral-bend, were theoretically analyzed and further, experimentally tested for their comparative sensitivity to evanescent wave absorption, in this pioneering study. A novel single-step fabrication procedure (using an SU-8 photoresist), was executed to fabricate these waveguide structures interfaced (both at their inner and outer bend surfaces) with a microchannel system, along with fiber-to-waveguide coupler structures. Experimentally, the sensitivity of the S-bend waveguides was found to be ∼25% higher compared to that of spiral waveguides of similar dimensions, which corroborated the results from numerical modeling. Compared to our earlier embedded C-bend waveguides, the overall evanescent-wave-absorption-based detection sensitivity of the embedded spiral and S-bend waveguides were found to be improved by ∼7.5 times and ∼9 times respectively. Finally, these devices were found to be ideally suited for more sensitive biological-, as well as, chemical-sensing applications, provided a suitable surface alteration process is performed to these waveguide probes. Further, the proposed device has a possible capability for: facile continuous (real-time) analysis, a fixed sample volume interaction, and control over the evaporation of analyte samples introduced in to the device.

The reported device is a versatile sensing-platform, with high sensitivity, for any chemical/biological-sensing applications, if suitable surface adaptation is first performed to the microchannel-system-embedded duel-bend waveguide-probe.