Chest CT texture analysis for response assessment in systemic sclerosis.

PURPOSE: To evaluate the role of CT-textural features for monitoring lung involvement in subjects with systemic sclerosis(SSc) undergoing autologous stem cell transplantation(SCT) by comparison with semi-quantitative chest-CT, pulmonary function tests(PFT) and clinical parameters (modified Rodnan skin score[mRSS]). METHODS: In a retrospective single centre analysis, we identified 23 consecutive subjects(11male) with SSc between 07/2005 and 11/2016 that underwent chest CTs before, 6 and 12 months post-SCT. Response to therapy was defined at 6 months after transplantation as stabilisation or improvement in FVC > 10% and DLCOSB > 10%. CT-texture analysis(CTTA) including mean, entropy and uniformity were calculated. RESULTS: PFT classified the subjects into responders(18/23;78%) and non-responders(5/23;22%). mRSS improved in responders from 28.46 ±â€¯9.53 to 15.70 ±â€¯10.07 6 months after auto-SCT(p = .001) whereas in non-responders no significant improvement was registered. Fibrosis score increased significantly(mean2.33 ±â€¯1.23 vs.1.41 ±â€¯0.78; p = .005) in non-responders after 6 and 12months. Significant lower mean intensity and entropy of skewness and higher uniformity of skewness was found in responders vs. non-responders at baseline. Significant changes in CTTA-parameters were found in both responders and non-responders at 6months and only in responders also at 12months post-SCT. CONCLUSIONS: Changes in CT-textural features after SCT are associated with visual CT evaluation of SSc-related lung abnormalities, but complementary provide information about therapy-induced, structural pulmonary changes.

Genetic inactivation of prohormone convertase (PC1) causes a reduction in cholecystokinin (CCK) levels in the hippocampus, amygdala, pons and medulla in mouse brain that correlates with the degree of colocalization of PC1 and CCK mRNA in these structures in rat brain.

Prohormone convertase (PC1) is found in endocrine cell lines that express cholecystokinin (CCK) mRNA and process pro CCK to biologically active products. Other studies have demonstrated that PC1 may be a one of the enzymes responsible for the endoproteolytic cleavages that occur in pro CCK during its biosynthesis and processing. Prohormone convertase 1 (PC1) has a distribution that is similar to cholecystokinin (CCK) in rat brain. A moderate to high percentage of CCK mRNA-positive neurons express PC1 mRNA. CCK levels were measured in PC1 knockout and control mice to assess the degree to which loss of PC1 changed CCK content. CCK levels were decreased 62% in hippocampus, 53% in amygdala and 57% in pons-medulla in PC1 knockout mice as compared to controls. These results are highly correlated with the colocalization of CCK and PC1. The majority of CCK mRNA-positive neurons in the pyramidal cell layer of the hippocampus express PC1 mRNA and greater than 50% of CCK mRNA-positive neurons in several nuclei of the amygdala also express PC1. These results demonstrate that PC1 is important for CCK processing. PC2 and PC5 are also widely colocalized with CCK. It may be that PC2, PC5 or another non-PC enzyme are able to substitute for PC1 and sustain production of some amidated CCK. Together these enzymes may represent a redundant system to insure the production of CCK.