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Background. Epithelioid, foam, and multinucleated giant cells (MNGCs) are characteristics of tuberculosis granulomas, yet the precise genesis and functions of these transformed macrophages are unclear. We evaluated the role of platelets as drivers of macrophage transformation in mycobacterial infection.Methods. We employed flow cytometry and microscopy to assess cellular phenotype and phagocytosis. Immune assays allowed quantification of cytokines and chemokines, whereas gene microarray technology was applied to estimate global transcriptome alterations. Immunohistochemical investigations of tuberculosis granulomas substantiated our findings at the site of infection.Results. Monocytes differentiated in presence of platelets (MP-Macs) acquired a foamy, epithelioid appearance and gave rise to MNGCs (MP-MNGCs). MP-Macs up-regulated activation markers, phagocytosed mycobacteria, and released abundant interleukin 10. Upon extended culture, MP-Macs shared transcriptional features with epithelioid cells and M2 macrophages and up-regulated CXCL5 transcripts. In line with this, CXCL5 concentrations were significantly increased in airways of active tuberculosis patients. The platelet-specific CD42b antigen was detected in MP-Macs, likewise in macrophages, MNGCs, and epithelioid cells within tuberculosis granulomas, along with the platelet aggregation-inducing factor PDPN.Conclusions. Platelets drive macrophage differentiation into MNGCs with characteristics of epithelioid, foam, and giant cells observed in tuberculosis granulomas. Our data define platelets as novel participants in tuberculosis pathogenesis.

Active tuberculosis (TB) has been associated with imbalance of Th1 and Th2 cytokine pattern. Activation of Th1 lymphocytes, gamma interferon (IFN-␥) production and macrophage activation are crucial in defense against mycobacteria, while Th2 activation and interleukin-4 (IL-4) production are associated with TB progressing and with poor clinical outcome after treatment (6).After being secreted, IFN-␥ and IL-4 are rapidly bound by their receptors and/or inactivated by proteases, which leads to difficulty in detecting these two typical Th1/Th2 cytokines in plasma or serum (26). Therefore, other markers have been investigated as alternative indicators of preferential Th1 or Th2 activity in vivo.CCL17 (thymus and activation-regulated chemokine [TARC]) and CCL22 (macrophage-derived chemokine [MDC]) are two specific chemotactic factors for Th2 cells (12). CD30, a tumor necrosis factor (TNF) receptor II family member, is also correlated with Th2 activation (3). sCD30 is a soluble form of CD30, which is generated by proteolytic cleavage of the extracellular portion of this transmembrane molecule and can be measured in serum or plasma by enzyme-linked immunosorbent assay (ELISA). Previous reports indicate increasing expression of these factors in patients with Th2 bias status, such as asthma (27), arthritis (7), and lymphoma (2); however, very few reports examine the changes in these Th2 factors in TB patients (16).For screening of new Th2 markers in active TB patients, we compared the serum levels of CCL17/TARC, CCL22/MDC, and sCD30 in HIV-negative TB patients with samples obtained from community healthy controls in China. The results indicate that CCL17/TARC and sCD30 might be more suitable as serum Th2 marker than CCL22/MDC in active TB patients. The correlation of these Th2 markers and the platelet and eosinophil counts in peripheral blood were also analyzed. MATERIALS AND METHODSStudy subjects. Peripheral blood was obtained from 103 normal healthy subjects, 101 active pulmonary TB patients, and 18 TB patients in recovery. The age and sex information of patients and controls are presented in Table 1. The patients included were clinically and radiologically diagnosed for pulmonary TB, and diagnoses confirmed by sputum smear and culture for Mycobacterium tuberculosis. The patients were recruited from the clinics of Shanghai Pulmonary Hospital. All of the patients were HIV negative; none of them presented with other infectious diseases or immunosuppressive conditions. All of the active TB patients received anti-TB therapy for less than 1 week and were classified into three categories (5): mild TB was defined by the presence of scattered and nonconfluent pulmonary infiltrates of slight to moderate density in one or both lungs, with the total volume less than one lung, without cavities. Moderate TB was defined by scattered and nonconfluent pulmonary infiltrates present in one or both lungs and/or with dense and confluent lesions but not involving more than one-third of the volume of one lung, with or without cavities with a...

Purpose: To evaluate the potential of proton therapy in sparing cardiac/coronary structures when compared with 3-dimensional conformal radiation therapy (3DCRT), helical tomotherapy (HT), and intensity-modulated radiation therapy using volumetric modulated arc therapy (VMAT). Materials and Methods: Comparative treatment planning was performed using computed tomography scans of 10 patients with left-sided stage III breast cancer after mastectomy, targeting the chest wall, axilla levels I to III, and the supraclavicular and internal mammary nodes (IMN) to 50.4 Gy (radiobiologic equivalent [RBE]) in 28 fractions. Organs at risk were heart, lungs, contralateral breast, unspecified healthy tissues, and coronary arteries. Plans were also compared that included IMNs for protons, but not for photons. Results: Mean heart dose of 1.2 Gy (RBE) was lowest with protons when compared with 6.8, 10.2, and 8.2 Gy for 3DCRT, HT, and VMAT, respectively (P , .05). The mean left anterior descending artery (LAD) dose was 7.0 Gy (RBE) for protons and lowest compared with 20.9, 14.8, and 15.6 Gy, respectively (P , .05). Total lung V5 Gy (RBE) was significantly lower with protons at 19.5% compared with 31.5%, 45.3%, and 54.0%, respectively (P , .05). Mean contralateral breast dose of 0.6 Gy (RBE) for protons was similar to 0.5 Gy for 3DCRT (P value not specified) but was significantly lower than 5.1 and 3.8 Gy for HT and VMAT (P , .05). Proton plans with IMN inclusion compared favorably to 3DCRT, intensity-modulated radiation therapy, and HT without IMN inclusion, with mean heart and mean LAD artery doses of 1.2 and 7.0 Gy (RBE) for protons versus 4.0 and 12.8 Gy for 3DCRT, 6.6 and 17.2 Gy for VMAT, and 7.4 and 11.4 Gy HT (P , .05). Conclusions: Proton therapy provided maximum cardiac and coronary sparing, even when compared with photon plans not including IMNs, thus, allowing treatment of the IMNs without increased risks to heart and coronary arteries. Reduced dose to lungs, contralateral breast, and healthy tissues indicates a reduced risk for development of second malignancy.

We consider the problem of detecting the presence of pneumoconiosis in a patient on the basis of evidence found in chest radiographs. Abnormalities pertaining to pneumoconiosis appear in the form of opacities of various sizes; the profusion of these opacities determines the stage of the disease. We present a multiresolution approach whereby we segment regions of interest (ROIs) from the X-Ray image at two levels -lung field and lung zone. We characterize each of these regions using a set of features and build support vector machine (SVM) classifiers that can predict whether or not the region contains any abnormalities. We combine these ROI-level predictions with a second stage SVM in order to get a prediction for the entire chest. Experimental validation shows that this approach provides good results.

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