OBJECTIVE: To evaluate the capacity of a computer-aided detection (CAD) system to detect lung nodules in clinical chest CT. MATERIALS AND METHODS: A total of 210 consecutive clinical chest CT scans and their reports were reviewed by two chest radiologists and 70 were selected (33 without nodules and 37 with 1-6 nodules, 4-15.4 mm in diameter). The CAD system (ImageChecker (R) CT LN-1000) developed by R2 Technology, Inc. (Sunnyvale, CA) was used. Its algorithm was designed to detect nodules with a diameter of 4-20 mm. The two chest radiologists working with the CAD system detected a total of 78 nodules. These 78 nodules form the database for this study. Four independent observers interpreted the studies with and without the CAD system. RESULTS: The detection rates of the four independent observers without CAD were 81% (63/78), 85% (66/78), 83% (65/78), and 83% (65/78), respectively. With CAD their rates were 87% (68/78), 85% (66/78), 86% (67/78), and 85% (66/78), respectively. The differences between these two sets of detection rates did not reach statistical significance. In addition, CAD detected eight nodules that were not mentioned in the original clinical radiology reports. The CAD system produced 1.56 false-positive nodules per CT study. The four test observers had 0, 0.1, 0.17, and 0.26 false-positive results per study without CAD and 0.07, 0.2, 0.23, and 0.39 with CAD, respectively. CONCLUSION: The CAD system can assist radiologists in detecting pulmonary nodules in chest CT, but with a potential increase in their false positive rates. Technological improvements to the system could increase the sensitivity and specificity for the detection of pulmonary nodules and reduce these false-positive results.
*Diagnosis, Computer-Assisted ; False Positive Reactions ; Humans ; Lung Diseases/*radiography ; Lung Neoplasms/radiography ; Radiography, Thoracic/*methods ; Sensitivity and Specificity ; Tomography, X-Ray Computed/*methods

Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin super-family receptor ILT2 (synonyms: LIR1, MIR7, CD85j), we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex (MHC) class I molecules. Produced in a dimeric form, either by chemical cross-linking with bivalent polyethylene glycol (PEG) derivatives or as a genetic fusion with human IgG Fc-fragment, the mutants exhibited a further increase in ligand-binding strength due to the avidity effect, with resident half-times (t(1/2)) on the surface of MHC I-positive cells of many hours. The novel compounds antagonized the interaction of CD8 co-receptor with MHC I in vitro without affecting the peptide-specific binding of T-cell receptors (TCRs). In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8(+) cytotoxic T lymphocytes (CTLs) in the presence of their target cells, with subnanomolar potency and in a dose-dependent manner. As a selective inhibitor of CD8(+) CTL responses, the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.
Amino Acid Sequence ; Antigens, CD ; chemistry ; genetics ; pharmacology ; Autoimmunity ; Biological Assay ; Cell Line ; Cytotoxicity, Immunologic ; genetics ; immunology ; Dose-Response Relationship, Immunologic ; Humans ; Immunoglobulins ; immunology ; metabolism ; Immunologic Factors ; chemistry ; genetics ; pharmacology ; Kinetics ; Leukocyte Immunoglobulin-like Receptor B1 ; Lymphocyte Activation ; genetics ; immunology ; Major Histocompatibility Complex ; genetics ; immunology ; Molecular Sequence Data ; Molecular Targeted Therapy ; Mutagenesis, Site-Directed ; Peptide Library ; Polyethylene Glycols ; Protein Binding ; genetics ; immunology ; Receptors, Immunologic ; chemistry ; genetics ; Recombinant Fusion Proteins ; genetics ; metabolism ; T-Lymphocytes, Cytotoxic ; immunology ; metabolism