Systemic Biomarkers of Neutrophilic Inflammation, Tissue Injury and Repair in COPD Patients with Differing Levels of Disease Severity

The identification and validation of biomarkers to support the assessment of novel therapeutics for COPD continues to be an important area of research. The aim of the current study was to identify systemic protein biomarkers correlated with measures of COPD severity, as well as specific protein signatures associated with comorbidities such as metabolic syndrome. 142 protein analytes were measured in serum of 140 patients with stable COPD, 15 smokers without COPD and 30 non-smoking controls. Seven analytes (sRAGE, EN-RAGE, NGAL, Fibrinogen, MPO, TGF-α and HB-EGF) showed significant differences between severe/very severe COPD, mild/moderate COPD, smoking and non-smoking control groups. Within the COPD subjects, univariate and multivariate analyses identified analytes significantly associated with FEV1, FEV1/FVC and DLCO. Most notably, a set of 5 analytes (HB-EGF, Fibrinogen, MCP-4, sRAGE and Sortilin) predicted 21% of the variability in DLCO values. To determine common functions/pathways, analytes were clustered in a correlation network by similarity of expression profile. While analytes related to neutrophil function (EN-RAGE, NGAL, MPO) grouped together to form a cluster associated with FEV1 related parameters, analytes related to the EGFR pathway (HB-EGF, TGF-α) formed another cluster associated with both DLCO and FEV1 related parameters. Associations of Fibrinogen with DLCO and MPO with FEV1/FVC were stronger in patients without metabolic syndrome (r  =  −0.52, p  = 0.005 and r  =  −0.61, p  = 0.023, respectively) compared to patients with coexisting metabolic syndrome (r  =  −0.25, p  = 0.47 and r  =  −0.15, p  = 0.96, respectively), and may be driving overall associations in the general cohort. In summary, our study has identified known and novel serum protein biomarkers and has demonstrated specific associations with COPD disease severity, FEV1, FEV1/FVC and DLCO. These data highlight systemic inflammatory pathways, neutrophil activation and epithelial tissue injury/repair processes as key pathways associated with COPD

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd

APOBEC3G-Augmented Stem Cell Therapy to Modulate HIV Replication: A Computational Study

PMC3661658The interplay between the innate immune system restriction factor APOBEC3G and the HIV protein Vif is a key host-retrovirus interaction. APOBEC3G can counteract HIV infection in at least two ways: by inducing lethal mutations on the viral cDNA; and by blocking steps in reverse transcription and viral integration into the host genome. HIV-Vif blocks these antiviral functions of APOBEC3G by impeding its encapsulation. Nonetheless, it has been shown that overexpression of APOBEC3G, or interfering with APOBEC3G-Vif binding, can efficiently block in vitro HIV replication. Some clinical studies have also suggested that high levels of APOBEC3G expression in HIV patients are correlated with increased CD4+ T cell count and low levels of viral load; however, other studies have reported contradictory results and challenged this observation. Stem cell therapy to replace a patient's immune cells with cells that are more HIV-resistant is a promising approach. Pre-implantation gene transfection of these stem cells can augment the HIV-resistance of progeny CD4+ T cells. As a protein, APOBEC3G has the advantage that it can be genetically encoded, while small molecules cannot. We have developed a mathematical model to quantitatively study the effects on in vivo HIV replication of therapeutic delivery of CD34+ stem cells transfected to overexpress APOBEC3G. Our model suggests that stem cell therapy resulting in a high fraction of APOBEC3G-overexpressing CD4+ T cells can effectively inhibit in vivo HIV replication. We extended our model to simulate the combination of APOBEC3G therapy with other biological activities, to estimate the likelihood of improved outcomes.JH Libraries Open Access Fun

Untersuchung hyperfunktioneller Dysphonien auf Basis des Einschwingens der Stimmlippen

Stimmstörungen können funktionelle oder organische Ursachen haben. Funktionelle Stimmstörungen gehören zu den häufigsten Stimmstörungen. Sie sind Krankheiten, die durch die Störung des Stimmklangs und der stimmlichen Leistungsfähigkeit gekennzeichnet sind, ohne dass sich klinisch primär organische Veränderungen der an der Stimmgebung beteiligten Strukturen zeigen. Sie können Folge falschen Stimmgebrauchs, von Überlastung oder Umwelteinflüssen sein. Es wird zwischen hyper- und hypofunktionellen Störungen unterschieden. Das Einschwingverhalten kann mit Hilfe der Hochgeschwindigkeits-Videotechnik (HVT) untersucht werden. Unter Zuhilfenahme eines Modells war es möglich ein objektives Diagnoseverfahren zu entwickeln, welches die Anforderungen des klinischen Alltags weitestgehend erfüllt. Normale Stimmen und hypofunktionelle Stimmstörungen unterscheiden sich in den beiden untersuchten Hauptparametern signifikant . Breite Streuungen bezüglich der Hauptparameter zeigen hyperfunktionelle Dysphonien. Die unterschiedliche Einbeziehung supraglottischer Strukturen scheint hier eine wesentliche Rolle zu spielen. Es werden die Ergebnisse einer Untersuchung vorgestellt, die nach einem Zusammenhang zwischen dem Einfluss der supraglottischen Strukturen und dem Einschwingverhalten der Stimmlippen sucht. In die Studie wurden 80 Patientinnen einbezogen