Avid 18F-FDG uptake of pectoralis major muscle: an equivocal sequela of strenuous physical exercise

Avid functional 18F-FDG uptake of skeletal muscle is a known false positive finding of PET-CT study especially after involuntary muscle exercise just prior to the study. We describe the case of a 50-year-old man in whom the finding of avid 18F-FDG uptake of pectoralis major muscle was encountered during investigation of metastatic melanoma

A fuzzy decision‐making approach for portfolio management with direct real estate investment

This study incorporated expert knowledge into the classical quadratic programming approach, i.e., Modern Portfolio Theory (MPT), through fuzzy set theory; in obtaining portfolio return optimization involving direct real estate investment. Two fuzzy mathematical programming models were uniquely specified and estimated in this study, namely, Zimmer‐mann's (2001) fuzzy tactical asset allocation (FTAA) flexible programming model and Ramik and Rimanek's (1985) FTAA robust programming model. These approaches try to overcome the drawbacks of traditional asset allocation models by including expert adjustment in the presence of imprecise information. The findings suggest that the fuzzy tactical asset allocation (FTAA Flexible Model), with the inclusion of expert judgments which contain information usually not found in historical data, is able to produce a portfolio just as efficient as traditional asset allocation models while minimizing the potential issues due to imprecision and vagueness of information. Meanwhile, the FTAA Robust Model proffers a more evenly‐distributed, yet with higher risks and lower returns, portfolio. Aside from the lack of emphasis on portfolio risks minimization, one reason attributed to such anomaly is the low level of returns of high‐risk stocks that are not selected by MPT and FTAA Flexible Models. It results in a unique situation where portfolio diversification does not necessarily guarantee an efficient investment decision. Santruka Šis tyrimas itraukia ekspertines žinias i klasikine kvadratinio programavimo metodika, pavyzdžiui, moderniaja portfelio valdymo teorija, per neapibrežtuju aibiu teorija, siekiant optimizuoti portfelio graža, apimant tiesiogines nekilnojamojo turto investicijas. Šiame tyrime išsamiai aprašomi ir ivertinami du neapibrežtojo matematinio programavimo modeliai. Tai Zimmermann (2001) neapibrežtasis aktyvu paskirstymo lankstusis programavimo modelis ir Ramik bei Rimanek (1985) neapibrežtasis aktyvu paskirstymo robustinis programavimo modelis. Juos taikant bandoma pašalinti tradiciniu aktyvu paskirstymo metodu trūkumus itraukiant ekspertu siūlomus pakeitimus nesant tikslios informacijos. Nustatyta, kad neapibrežtasis aktyvu paskirstymas (neapibrežtasis aktyvu paskirstymo lankstusis programavimo modelis) kartu su ekspertu vertinimais, paprastai apimančiais informacija, kurios negalima rasti tarp istoriniu duomenu, leidžia sudaryti toki pati efektyvu portfeli, kaip ir tradiciniai aktyvu paskirstymo modeliai, tačiau minimizuojant potencialius nesutarimus, kuriu atsiranda del netikslios ir neapibrežtos informacijos. Neapibrežtasis aktyvu paskirstymo robustinis programavimo modelis siūlo tolygiau paskirstyta, tačiau rizikingesni ir ne toki pelninga portfeli. Be portfelio rizikos minimizavimo trūkumo, dar viena priežastis, priskiriama prie šios anomalijos, yra maža dideles rizikos akciju graža, kuri nera pasirenkama moderniojoje portfelio valdymo teorijoje ir neapibrežtuju aktyvu paskirstymo lanksčiuosiuose programavimo modeliuose. Kaip rezultatas gaunama unikali situacija, kai portfelio diversifikavimas nebūtinai garantuoja efektyvu investavimo sprendima. First Publish Online: 18 Oct 201

Potential of 3'-fluoro-3' deoxythymidine as a cellular proliferation marker in PET oncology examination

Development of the positron emission tomography (PET) diagnostic radiopharmaceutical (18F) fluoro-2-deoxy-D-glucose (18F-FDG) subsequently facilitated the discovery and clinical evaluation of several new tracers as imaging markers for cancer. While 18F-FDG is a widely employed marker forenhanced intracellular glycolysis and metabolic function, one of the newer tracers, (18F)-3'-fluoro-3'deoxythymidine (18F-FLT), has been developed as a biomarker for cell proliferation. In this review, the potential of 18F-FLT as a biomarker for cancer imaging is discussed

Human Cytomegalovirus Long Non-coding RNA1.2 Suppresses Extracellular Release of the Pro-inflammatory Cytokine IL-6 by Blocking NF-κB Activation.

Long non-coding RNAs (lncRNAs) are transcripts of >200 nucleotides that are not translated into functional proteins. Cellular lncRNAs have been shown to act as regulators by interacting with target nucleic acids or proteins and modulating their activities. We investigated the role of RNA1.2, which is one of four major lncRNAs expressed by human cytomegalovirus (HCMV), by comparing the properties of parental virus in vitro with those of deletion mutants lacking either most of the RNA1.2 gene or only the TATA element of the promoter. In comparison with parental virus, these mutants exhibited no growth defects and minimal differences in viral gene expression in human fibroblasts. In contrast, 76 cellular genes were consistently up- or down-regulated by the mutants at both the RNA and protein levels at 72 h after infection. Differential expression of the gene most highly upregulated by the mutants (Tumor protein p63-regulated gene 1-like protein; TPRG1L) was confirmed at both levels by RT-PCR and immunoblotting. Consistent with the known ability of TPRG1L to upregulate IL-6 expression via NF-κB stimulation, RNA1.2 mutant-infected fibroblasts were observed to upregulate IL-6 in addition to TPRG1L. Comparable surface expression of TNF receptors and responsiveness to TNF-α in cells infected by the parental and mutant viruses indicated that activation of signaling by TNF-α is not involved in upregulation of IL-6 by the mutants. In contrast, inhibition of NF-κB activity and knockdown of TPRG1L expression reduced the extracellular release of IL-6 by RNA1.2 mutant-infected cells, thus demonstrating that upregulation of TPRG1L activates NF-κB. The levels of MCP-1 and CXCL1 transcripts were also increased in RNA1.2 mutant-infected cells, further demonstrating the presence of active NF-κB signaling. These results suggest that RNA1.2 plays a role in manipulating intrinsic NF-κB-dependent cytokine and chemokine release during HCMV infection, thereby impacting downstream immune responses

18[F] FDG-PET/CT is a useful molecular marker in evaluating thymoma aggressiveness.

A 54 year-old-man presented with chest fullness and difficulty of breathing for 3 months. CT thorax revealed a heterogeneously enhancing mediastinal mass for which CT-guided biopsy results were initially inconclusive. The patient underwent 18F-FDG-PET/CT study for further metabolic characterisation and staging of the disease. 18F-FDG -PET/CT showed heterogeneous FDG-avid mediastinal mass with adjoining multiple FDG-avid hilar lymph nodes, pulmonary and bone metastasis. Final diagnosis of malignant thymoma was confirmed after a successful PET/CT-guided needle biopsy

Localization and prediction of malignant potential in recurrent pheochromocytoma/paraganglioma (PCC/PGL) using 18F-FDG PET/CT

Background: To our knowledge, data are lacking on the role of 18F-FDG PET/CT in the localization and prediction of neuroendocrine tumors, in particular the pheochromocytoma/paraganglioma (PCC/PGL) group. Purpose: To evaluate the role of 18F-FDG PET/CT in localizing and predicting the malignant potential of PCC/PGL. Material and Methods: Twenty-three consecutive patients with a history of PCC/PGL, presenting with symptoms related to catecholamine excess, underwent 18F-FDG PET/CT. Final confirmation of the diagnosis was made using the composite references. PET/CT findings were analyzed on a per-lesion basis and a per-patient basis. Tumor SUVmax was analyzed to predict the dichotomization of patient endpoints for the local disease and metastatic groups. Results: We investigated 23 patients (10 men, 13 women) with a mean age of 46.43±3.70 years. Serum catecholamine levels were elevated in 82.60% of these patients. There were 136 sites (mean SUVmax: 16.39±3.47) of validated disease recurrence. The overall sensitivities for diagnostic CT, FDG PET, and FDG PET/CT were 86.02%, 87.50%, and 98.59%, respectively. Based on the composite references, 39.10% of patients had local disease. There were significant differences in the SUVmax distribution between the local disease and metastatic groups; a significant correlation was noted when a SUVmax cut-off was set at 9.2 (P<0.05). Conclusion: In recurrent PCC/PGL, diagnostic 18F-FDG PET/CT is a superior tool in the localization of recurrent tumors. Tumor SUVmax is a potentially useful predictor of malignant tumor potential

Suppression of costimulation by human cytomegalovirus promotes evasion of cellular immune defenses.

CD58 is an adhesion molecule that is known to play a critical role in costimulation of effector cells and is intrinsic to immune synapse structure. Herein, we describe a virally encoded gene that inhibits CD58 surface expression. Human cytomegalovirus (HCMV) UL148 was necessary and sufficient to promote intracellular retention of CD58 during HCMV infection. Blocking studies with antagonistic anti-CD58 mAb and an HCMV UL148 deletion mutant (HCMV∆UL148) with restored CD58 expression demonstrated that the CD2/CD58 axis was essential for the recognition of HCMV-infected targets by CD8+ HCMV-specific cytotoxic T lymphocytes (CTLs). Further, challenge of peripheral blood mononuclear cells ex vivo with HCMV∆UL148 increased both CTL and natural killer (NK) cell degranulation against HCMV-infected cells, including NK-driven antibody-dependent cellular cytotoxicity, showing that UL148 is a modulator of the function of multiple effector cell subsets. Our data stress the effect of HCMV immune evasion functions on shaping the immune response, highlighting the capacity for their potential use in modulating immunity during the development of anti-HCMV vaccines and HCMV-based vaccine vectors

The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome

BACKGROUND: Cytokines play important roles in antiviral action. We examined whether polymorphisms of IFN-γ,TNF-α and IL-10 affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). METHODS: A case-control study was carried out in 476 Chinese SARS patients and 449 healthy controls. We tested the polymorphisms of IFN-γ,TNF-α and IL-10 for their associations with SARS. RESULTS: IFN-γ +874A allele was associated with susceptibility to SARS in a dose-dependent manner (P < 0.001). Individuals with IFN-γ +874 AA and AT genotype had a 5.19-fold (95% Confidence Interval [CI], 2.78-9.68) and 2.57-fold (95% CI, 1.35-4.88) increased risk of developing SARS respectively. The polymorphisms of IL-10 and TNF-α were not associated with SARS susceptibility. CONCLUSION: IFN-γ +874A allele was shown to be a risk factor in SARS susceptibility

ADAM17 targeting by human cytomegalovirus remodels the cell surface proteome to simultaneously regulate multiple immune pathways

Human cytomegalovirus (HCMV) is a major human pathogen whose life-long persistence is enabled by its remarkable capacity to systematically subvert host immune defenses. In exploring the finding that HCMV infection up-regulates tumor necrosis factor receptor 2 (TNFR2), a ligand for the pro-inflammatory antiviral cytokine TNFα, we found that the underlying mechanism was due to targeting of the protease, A Disintegrin And Metalloproteinase 17 (ADAM17). ADAM17 is the prototype ‘sheddase’, a family of proteases that cleaves other membrane-bound proteins to release biologically active ectodomains into the supernatant. HCMV impaired ADAM17 surface expression through the action of two virally-encoded proteins in its UL/b’ region, UL148 and UL148D. Proteomic plasma membrane profiling of cells infected with an HCMV double-deletion mutant for UL148 and UL148D with restored ADAM17 expression, combined with ADAM17 functional blockade, showed that HCMV stabilized the surface expression of 114 proteins (P < 0.05) in an ADAM17-dependent fashion. These included reported substrates of ADAM17 with established immunological functions such as TNFR2 and jagged1, but also numerous unreported host and viral targets, such as nectin1, UL8, and UL144. Regulation of TNFα-induced cytokine responses and NK inhibition during HCMV infection were dependent on this impairment of ADAM17. We therefore identify a viral immunoregulatory mechanism in which targeting a single sheddase enables broad regulation of multiple critical surface receptors, revealing a paradigm for viral-encoded immunomodulation