Pansclerotic Morphea with Features of Eosinophilic Fasciitis: Distinct Entities or Part of a Continuum?

Scleroderma is a highly complex disorder in its clinical manifestations and pathogenesis. It has a wide range of clinical manifestations due to varying degrees of vasculopathy, autoimmunity, altered endothelium function, and abnormal fibrosis. The most widely used classification system grouped eosinophilic fasciitis and disabling pansclerotic morphea of childhood into the category of deep morphea. This previous classification does not include a category for overlapping conditions. A proposed new classification includes a new mixed subtype in which a combination of two or more of the previous subtypes is present in the same individual, although eosinophilic fasciitis has been excluded. We present the case of a 4‐year‐old boy who presented with features of disabling pansclerotic morphea and eosinophilic fasciitis simultaneously, which to our knowledge has not been previously reported. This suggests that these diseases are part of a more closely related continuum rather than separate disorders, as currently classified.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106686/1/pde12279.pd

Lost at Sea in Search of a Diagnosis: A Case of Unexplained Bleeding

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134475/1/pbc25980_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134475/2/pbc25980.pd

Connecting the Dots: A Rare Cause of Pulmonary Nodules in a 13-Year-Old Boy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140177/1/ped.2014.0392.pd

The effect of aging and caloric restriction on murine CD8+ T cell chemokine receptor gene expression

Abstract Background The mechanism explaining the increased disease susceptibility in aging is not well understood. CD8+ T cells are crucial in anti-viral and anti-tumor responses. Although the chemokine system plays a critical role in CD8+ T cell function, very little is known about the relationship between aging and the T cell chemokine system. Results In this study we have examined the effect of aging on murine CD8+ T cell chemokine receptor gene expression. Freshly isolated splenic CD8+ T cells from old C57BL/6 mice were found to have higher CCR1, CCR2, CCR4, CCR5 and CXCR5, and lower CCR7 gene expression compared to their younger cohort. Anti-CD3/anti-CD28 stimulation elicited a similar robust chemokine receptor response from young and old CD8+ T cells. Western blot analyses confirmed elevated protein level of CCR4 and CCR5 in aged CD8+ T cells. Increases in T cell CCR1 and CCR5 expression also correlate to increased in vitro chemotaxis response to macrophage-inflammatory protein-1 α(MIP-1α). Finally, caloric restriction selectively prevents the loss of CD8+ T cell CCR7 gene expression in aging to the level that is seen in young CD8+ T cells. Conclusion These findings are consistent with the notion that aging exists in a state of low grade pro-inflammatory environment. In addition, our results provide a potential mechanism for the reported aging-associated impaired T cell lymphoid homing and allograft response, and reduced survival in sepsis.http://deepblue.lib.umich.edu/bitstream/2027.42/112328/1/12979_2007_Article_43.pd

Multilevel simulation and numerical optimization of complex engineering designs

Multi-level representations have been studied extensively by arti cial intelligence researchers. We utilize the multi-level paradigm to attack the problem of performing multidiscipline engineering design optimization in the presence of many local optima. We use amultidisciplinary simulator at multiple levels of abstraction, paired with a multi-level search space. We tested the resulting system in the domain of conceptual design of supersonic transport aircraft, and found that using multilevel simulation and optimization can decrease the cost of design space search by one or more orders of magnitude

Western blot analyses of CCR4 and CCR5 protein level in aged CD8+ T cells

<p><b>Copyright information:</b></p><p>Taken from "The effect of aging and caloric restriction on murine CD8+ T cell chemokine receptor gene expression"</p><p>http://www.immunityageing.com/content/4/1/8</p><p>Immunity & ageing : I & A 2007;4():8-8.</p><p>Published online 14 Nov 2007</p><p>PMCID:PMC2200663.</p><p></p> Intracellular proteins were isolated from groups of 4–6 young and old C57Bl/6 mice. (A) Western blot analysis of CCR4 using proteins from 4 groups of young (Y1–Y4) and old (O1–O4) CD8+ T cells (total 20 young and 20 old mice). (B) Western blot analysis of CCR5 on CR8+ T cells isolated from 5 groups of young (Y1–Y5) and Old (O1–O5) mice (total 25 young and 25 old mice). (C) Histogram showing the composite results of the relative CCR4 and CCR5 protein level of old CD8+ T cells compared to young CD8+ T cells. Pairwise comparison was done for each individual sample preparation (Y1 versus O1, Y2 versus O2 etc., with the young group arbitrarily assigned the value of 1). The results are corrected for gel loading using β-actin as controls. The results are presented as mean ± SD

The effect of caloric restriction on CD8+ T cell chemokine receptor expression in aging

<p><b>Copyright information:</b></p><p>Taken from "The effect of aging and caloric restriction on murine CD8+ T cell chemokine receptor gene expression"</p><p>http://www.immunityageing.com/content/4/1/8</p><p>Immunity & ageing : I & A 2007;4():8-8.</p><p>Published online 14 Nov 2007</p><p>PMCID:PMC2200663.</p><p></p> Ribonuclease protection assays (RPAs) were done using RNA from freshly isolated splenic CD8+ T cells from young (3–4 months), old (18–20 months), and caloric restricted old (18–20 months) mice in groups of 5 animals. Density of the bands was quantified using a phosphoimager. (A) Histogram showing the composite data of 4 experiments (total 20 animals in each condition). The results represent the mean ± SEM of the relative CD8+ T cell chemokine receptor gene expression level of old and old caloric restricted mice compared to those from the young cohort (arbitrarily defined as equal to 1). (B) CCR7 expression was also determined using a custom CCR7 RPA probe. The left panel is a representative autoradiograph (lane 1 = young CD8+ T cells; lane 2 = old CD8+ T cells; lane 3 = caloric restricted old CD8+ T cells). The right panel represents the composite data of 3 RPAs with a total of 15 animals in each group. Results are presented as mean ± SEM. CR = caloric restricted. Gel loading is corrected with L32 expression

Murine CD8+ T cell chemokine receptor gene expression following T cell receptor/CD28 stimulation

<p><b>Copyright information:</b></p><p>Taken from "The effect of aging and caloric restriction on murine CD8+ T cell chemokine receptor gene expression"</p><p>http://www.immunityageing.com/content/4/1/8</p><p>Immunity & ageing : I & A 2007;4():8-8.</p><p>Published online 14 Nov 2007</p><p>PMCID:PMC2200663.</p><p></p> Autoradiographs of representative ribonuclease protection assay (RPA) showing the effect of aging and anti-CD3/anti-CD28 monoclonal antibody (mAb) stimulation on murine CD8+ T cell CCR1–5 (A) and CXCR2, 4 and 5 (B) gene expression. Lane 1 in Figure 2A and Lane 2 in Figure 2B = Young (3–4 months) unstimulated cells; Lane 2 in Figure 2A and Lane 3 in Figure 2B = Old (18–20 months) unstimulated cells; Lane 3 in Figure 2A and Lane 4 in Figure 2B = Young cells after 72 hours of anti-CD3/anti-CD28 mAb stimulation; Lane 4 in Figure 2A and Lane 5 in Figure 2B = Old cells after 72 hours of anti-CD3/anti-CD28 mAb stimulation; Lane 5 in Figure 2A and Lane 1 in Figure 2B = unprotected probe set. Composite histogram (C) of 3 RPAs using pooled RNA from a total of 15 animals in each age group is shown. Gel loading is corrected with L32 expression