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It is frequently stated that high fat diets are harmful with respect to nutrition and disease development. Herein, (NZB/NZW)F1 autoimmune-prone mice were compared under the influence of different calorie intakes and different calorie sources. Decreased calorie intake prolonged life and delayed onset of glomerulonephritis. This influence of restriction of energy intake was greater than any influences of dietary energy source. Parameters affected strictly by restricted calorie intake were: 1) longevity, 2) delayed onset of glomerulonephritis, 3) greatly decreased circulating immune complexes, 4) decreased production of anti-DNA antibodies, 5) increased thymocyte proliferation in response to exogenous Interleukin-2 (IL-2), 6) increased IL-2 production by spleen cells stimulated by concanavalin A and 7) marked increase of mixed lymphocyte reaction of spleen cells. Parameters affected both by restriction of calorie intake and by high sucrose content in full-fed mice and not obviously related to longevity and protection from glomerulonephritis were: 1) plaque-forming cell response to sheep red blood cells in vitro and 2) cytotoxic cell-mediated immune response generated by in vitro exposure to allogenic antigen.

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The use of rCBV as a response metric in clinical trials has been hampered, in part, due to variations in the biomarker consistency and associated interpretation across sites, stemming from differences in image acquisition and post-processing methods. This study leveraged a dynamic susceptibility contrast magnetic resonance imaging digital reference object to characterize rCBV consistency across 12 sites participating in the Quantitative Imaging Network (QIN), specifically focusing on differences in site-specific imaging protocols (IPs; n = 17), and PMs (n = 19) and differences due to site-specific IPs and PMs (n = 25). Thus, high agreement across sites occurs when 1 managing center processes rCBV despite slight variations in the IP. This result is most likely supported by current initiatives to standardize IPs. However, marked intersite disagreement was observed when site-specific software was applied for rCBV measurements. This study's results have important implications for comparing rCBV values across sites and trials, where variability in PMs could confound the comparison of therapeutic effectiveness and/or any attempts to establish thresholds for categorical response to therapy. To overcome these challenges and ensure the successful use of rCBV as a clinical trial biomarker, we recommend the establishment of qualifying and validating site- and trial-specific criteria for scanners and acquisition methods (eg, using a validated phantom) and the software tools used for dynamic susceptibility contrast magnetic resonance imaging analysis (eg, using a digital reference object where the ground truth is known).