Dsk5 mice have a gain of function in the epidermal growth factor receptor (EGFR), caused by a point mutation in the kinase domain. We analyzed the effect of this mutation on liver size, histology, and composition. We found that the livers of 12-wk-old male Dsk5 heterozygotes (+/Dsk5) were 62% heavier compared with those of wild-type controls (+/+). The livers of the +/Dsk5 mice compared with +/+ mice had larger hepatocytes with prominent, polyploid nuclei and showed modestly increased cell proliferation indices in both hepatocytes and nonparenchymal cells. An analysis of total protein, DNA, and RNA (expressed relative to liver weight) revealed no differences between the mutant and wild-type mice. However, the livers of the +/Dsk5 mice had more cholesterol but less phospholipid and fatty acid. Circulating cholesterol levels were twice as high in adult male +/Dsk5 mice but not in postweaned young male or female mice. The elevated total plasma cholesterol resulted mainly from an increase in low-density lipoprotein (LDL). The +/Dsk5 adult mouse liver expressed markedly reduced protein levels of LDL receptor, no change in proprotein convertase subtilisin/kexin type 9, and a markedly increased fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Increased expression of transcription factors associated with enhanced cholesterol synthesis was also observed. Together, these findings suggest that the EGFR may play a regulatory role in hepatocyte proliferation and lipid metabolism in adult male mice, explaining why elevated levels of EGF or EGF-like peptides have been positively correlated to increased cholesterol levels in human studies.

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Does the dermatology standardized letter of recommendation alter applicants' chances of matching into residency?

Immunosuppression following organ transplantation is a known risk factor for the development of lymphoproliferative disorders.Mycosis fungoides, a rare entity in pediatric patients, has seldom been reported as a post-transplant lymphoproliferative disorder.We report a case of folliculotropic mycosis fungoides in a pediatric patient following liver transplantation that was initially diagnosed as tinea capitis. | 387Pediatric Dermatology BRIEF REPORT majority are B-cell lymphomas, while primary cutaneous T-cell lymphoma (CTCL) is rare. 1 Mycosis fungoides (MF), the most common primary CTCL, typically occurs in adults over age 50. 2 Childhood MF as a post-transplant lymphoproliferative disorder (PTLD) has seldom been demonstrated.One case of classic MF in a 16-year-old following liver transplantation initially presented as a non-pruritic plaque on the back. 3 The area resolved with narrowband ultraviolet B light therapy, and no changes were made to his immunosuppression. 3 A second case of FMF in a 13-year-old following renal transplantation presented as widespread psoriasiform plaques, some ulcerated, along with alopecic patches with follicular plugging on the scalp. 4 He was on sirolimus, tacrolimus, and prednisone for immunosuppression. Sirolimus was discontinued given the presence of ulcerations and the higher incidence of wound complications compared to tacrolimus, with the patient achieving partial clinical remission. 4,5 Folliculotropic mycosis fungoides accounts for only 4% of the CTCLs, though it may be more common in post-transplant patients compared to the general population. 4,6 This variant is less responsive to typical treatments, and the prognosis is similar to that of classic tumor-stage MF. 6 In addition to topical treatments, our patient's immunosuppression regimen was altered, since reduction or cessation of immunosuppression can be effective in treating PTLDs. 7 Furthermore, the conversion of immunosuppression to sirolimus, an mTOR inhibitor, has also been shown to increase remission rates, possibly due to the additional antineoplastic effect of mTOR inhibitors. 7,8 Multiple biopsies are often needed to make the diagnosis of MF, as seen in our case and the two previously reported cases. 3,4 The presence of black dots on physical exam and fungal elements within the hair shaft were diagnostic red herrings in this case. A second set of biopsies was necessary to confirm the correct diagnosis of FMF.While rare, it is important for dermatologists to consider MF in the differential diagnosis in a child following solid organ transplantation. Repeat biopsies must be obtained if MF is suspected to prevent misdiagnosis and delay of treatment.

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