The Rho GTPase, Rac2, is expressed only in hematopoietic cell lineages, suggesting a specific cellular function in these cells. Genetic targeting studies in mice showed that Rac2 is an essential regulator of neutrophil chemotaxis, L-selectin capture and rolling, and superoxide production. Recently, a dominant negative mutation of Rac2, D57N, has been reported to be associated with a human phagocytic immunodeficiency. To understand further the cellular phenotypes associated with this D57N Rac2 mutant we examined its biochemical characteristics and functional effects when expressed in primary murine bone marrow cells. When compared with wild type (WT) Rac2, D57N Rac2 displayed ϳ10% GTP binding ability resulting from a markedly enhanced rate of GTP dissociation and did not respond to the guanine nucleotide exchange factors. These results suggest that D57N Rac2 may act in a dominant negative fashion in cells by sequestering endogenous guanine nucleotide exchange factors. When expressed in hematopoietic cells, D57N Rac2 reduced endogenous activities of not only Rac2, but also Rac1 and decreased cell expansion in vitro in the presence of growth factors due to increased cell apoptosis. Unexpectedly, D57N expression had no effect on proliferation. In contrast, expansion of cells transduced with WT Rac2 and a dominant active mutant, Q61L, was associated with significantly increased proliferation. Transplantation of transduced bone marrow cells into lethally irradiated recipients showed that the percentage of D57N-containing peripheral blood cells decreased markedly from 40% at 1 month to <5% by 3 months postinjection. Neutrophils derived in vitro from the transduced progenitor cells containing D57N demonstrated markedly impaired migration and O 2 Ϫ responses to formyl-methionyl-leucyl-phenylalanine, reflecting the same cellular phenotype in these differentiated cells as those described previously in patient cells. These data suggest that the phenotypic abnormalities associated with D57N Rac2 may involve not only neutrophil cellular functions, but also abnormal cell survival in other hematopoietic cells and that overexpression of Rac leads to increased proliferation of normal cells in vitro, whereas deficiency of Rac leads to increased apoptosis.

F-18 FDOPA scan is superior to both F-18 FLT and F-18 FDG for visualization of primary and recurrent low grade gliomas. F-18-FLT should not be considered for evaluation of recurrent low grade gliomas.

Fluorodeoxyglucose-PET performed at the time of initial referral for parkinsonism is useful for the differential diagnosis of IPD, PSP, MSA, and CBS. Computer-assisted methods can be used for objective evaluation especially when expert readers are not available.

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Rac proteins, members of the Rho-related small GTPase family, play important roles in multiple cellular events, including actin cytoskeletal organization, cell proliferation and survival, cell cycle progression, and gene transcription regulation (24,45,53,70,75). The Rac subfamily of Rho GTPases comprises three members, Rac1, Rac2, and Rac3, which show Ͼ80% sequence identity (14,22). The primary difference between Rac1 and Rac2, which are over 92% homologous, is in the carboxy-terminal region, where Rac1 but not Rac2 contains a six-amino-acid polybasic domain. Unlike Rac1 and Rac3, which are widely expressed, Rac2 expression is restricted to cells of hematopoietic lineages (15,44,57). With respect to regulation of gene expression, Rac1 can induce the activation of transcription factors such as serum response factor and nuclear factor B (NF-B) to stimulate transcription of multiple genes (26, 59).

Correct staging is the most crucial for the treatment outcome in cancer management. Molecular imaging with 18F-fluoroestradiol (FES) positron emission tomography-computed tomography (PET-CT) targets estrogen receptor (ER) and may have a higher incremental value in diagnosis by aiding specificity. We enrolled 12 female breast cancer patients prospectively and did 18F-FES PET-CT and 18F-fluorodeoxyglucose (FDG) PET-CT within 1 week interval time. Lesion detection sensitivity was compared for a total number of lesions and for nonhepatic lesions only by McNemar test. 18F-FES PET-CT was taken as reference in case of indeterminate lesions. The incremental value reported by identifying 18F-FES exclusive lesions and by characterization of 18F-FDG indeterminate lesions. Spearman rank test was used to correlate ER expression and maximum standardized uptake value (SUVmax). Two ER-negative patients with no 18F-FES uptake were excluded. Ten ER-positive patients with 154 disease lesions were finally analyzed. 18F-FDG picked-up 142 lesions (sensitivity 92.21%), whereas 18F-FES picked-up 116 lesions (sensitivity 75.32%) and this difference was statistically significant. For nonhepatic lesions (n = 136) detectability, 18F-FDG picked-up 124 (sensitivity 91.18%), whereas 18F-FES picked-up 116 (sensitivity 85.29%) lesions and this difference was not statistically significant. Beside 12 exclusive lesions, 18F-FES characterized 41 (27.5%) 18F-FDG indeterminate lesions. Overall 18F-FES impacted 20% patient management. The positive trend was also seen with 18F-FES SUVmax with ER expression and negative with 18F-FDG SUVmax. We conclude, 18F-FDG has overall better sensitivity than 18F-FES PET-CT, however for nonhepatic metastasis difference was not significant. 18F-FES PET-CT better-characterized lesions and impacted 20% patient management. Therefore, 18F-FES PET-CT should be used with 18F-FDG PET-CT in strongly ER expressing patients for better specificity.

Both 11C-MET PET/CT and MRI (with the inclusion of advanced MRI techniques) demonstrated a high diagnostic performance in the identification of tumor residual/recurrence in high-grade gliomas posttherapy. Although 11C-MET PET/CT seemed to be more sensitive, whereas advanced MRI seemed more specific, there was no statistically significant difference in the diagnostic performance of either modality in the present study. Further studies with a larger group of patients are warranted.

Aim:The aim of the present study is to evaluate diffusion tensor tractography (DTT) as a tool for detecting diffuse axonal injury in patients of acute, mild, and moderate traumatic brain injury (TBI), using two diffusion variables: Fractional anisotropy (FA) and mean diffusivity (MD). The correlation of these indices with the severity of post-concussive symptoms was also assessed.Materials and Methods:Nineteen patients with acute, mild, or moderate TBI and twelve age- and sex-matched healthy controls were recruited. Following Magnetic Resonance Imaging (MRI) on a 3.0-T scanner, DTT was performed using the ‘fiber assignment by continuous tracking’ (FACT) algorithm for fiber reconstruction. Appropriate statistical tools were used to see the difference in FA and MD values between the control and patient groups. In the latter group, the severity of post-concussive symptoms was assessed six months following trauma, using the Rivermead Postconcussion Symptoms Questionnaire (RPSQ).Results:The patients displayed significant reduction in FA compared to the controls (P < 0.05) in several tracts, notably the corpus callosum, fornix, bilateral uncinate fasciculus, and bilateral superior thalamic radiations. Changes in MD were statistically significant in the left uncinate, inferior longitudinal fasciculus, and left posterior thalamic radiation. A strong correlation between these indices and the RPSQ scores was observed in several white matter tracts.Conclusion:Diffusion tensor imaging (DTI)-based quantitative analysis in acute, mild, and moderate TBI can identify axonal injury neuropathology, over and above that visualized on conventional MRI scans. Furthermore, the significant correlation observed between FA and MD indices and the severity of post-concussive symptoms could make it a useful predictor of the long-term outcome.