The uncoupling protein 1 gene, UCP1, is expressed in mammalian islet cells and associated with acute insulin response to glucose in African American families from the IRAS Family Study.

BACKGROUND: Variants of uncoupling protein genes UCP1 and UCP2 have been associated with a range of traits. We wished to evaluate contributions of known UCP1 and UCP2 variants to metabolic traits in the Insulin Resistance and Atherosclerosis (IRAS) Family Study. METHODS: We genotyped five promoter or coding single nucleotide polymorphisms (SNPs) in 239 African American (AA) participants and 583 Hispanic participants from San Antonio (SA) and San Luis Valley. Generalized estimating equations using a sandwich estimator of the variance and exchangeable correlation to account for familial correlation were computed for the test of genotypic association, and dominant, additive and recessive models. Tests were adjusted for age, gender and BMI (glucose homeostasis and lipid traits), or age and gender (obesity traits), and empirical P-values estimated using a gene dropping approach. RESULTS: UCP1 A-3826G was associated with AIR(g) in AA (P = 0.006) and approached significance in Hispanic families (P = 0.054); and with HDL-C levels in SA families (P = 0.0004). Although UCP1 expression is reported to be restricted to adipose tissue, RT-PCR indicated that UCP1 is expressed in human pancreas and MIN-6 cells, and immunohistochemistry demonstrated co-localization of UCP1 protein with insulin in human islets. UCP2 A55V was associated with waist circumference (P = 0.045) in AA, and BMI in SA (P = 0.018); and UCP2 G-866A with waist-to-hip ratio in AA (P = 0.016). CONCLUSION: This study suggests a functional variant of UCP1 contributes to the variance of AIR(g) in an AA population; the plausibility of this unexpected association is supported by the novel finding that UCP1 is expressed in islets.

Analysis of tumor characteristics and survival in liver transplant recipients with incidentally diagnosed hepatocellular carcinoma.

The use of orthotopic liver transplantation (OLTX) for the treatment of hepatocellular carcinoma (HCC) has generally become restricted to carefully selected cases of small oligocentric tumors. However, it is not uncommon to find previously undetected HCC within recipient cirrhotic livers at the time of hepatectomy. The impact of unsuspected HCC on patient outcomes remains unclear. A retrospective analysis of our institutional experience with adult primary OLTX was performed comparing recipients with incidental HCC (group 1), recipients with known or suspected HCC (group 2), and recipients confirmed by pathologic examination to be tumor free (group 3). Between 1984 and 2000, 27 patients in group 1, 12 patients in group 2, and 612 patients in group 3 underwent primary OLTX. Tumors were smaller (P = 0.0172) in group 1 than in group 2; however, the number of tumors and the histologic findings were similar in the groups. Incidence of bilobar involvement, vascular invasion, portal vein tumor thrombus, lymphatic involvement, and distant metastasis at the time of OLTX did not differ significantly between these groups. Four-year patient survival appeared to be lower in group 1 (70.0%) than in group 3 (79.0%) (P = 0.0546); 4-year patient survival was significantly worse in group 2 (31.0%) compared to group 3 (P = 0.0106). Thus, in our experience, incidentally diagnosed cases of HCC possess many of the same features of malignancy as preoperatively diagnosed HCC. Indeed, patient survival after OLTX appears to be adversely affected by the presence of incidental HCC.

Carcinoid tumor of the cystic duct.

A 69-year-old male was admitted to an outside institution for severe right abdominal pain radiating to the flank. An extensive work-up, including lower GI series, IVP, and ultrasound of the kidneys were normal. Ultrasound of the liver demonstrated a thickened gallbladder as well as cholelithiasis. Despite some improvement, his symptoms returned intermittently and cholecystectomy was performed. Pathologic examination of the gallbladder showed a carcinoid tumor, 5.4 mm in maximum diameter, in the cystic duct. A small metastatic focus was also found in the cystic duct lymph node. In this paper we compare the clinical presentation, pathological findings and outcome of this case to the previously reported six cases of cystic duct carcinoid. A comparison is also made between the general features of carcinoid at this rare location and the more common gastrointestinal carcinoid.

Infiltrating ductal carcinoma of the vulva.

The eleventh case of primary infiltrating ductal carcinoma of the vulva is reported with a review of the literature. The infiltrating tumor is associated with an intraductal component as well as noninvolved mammary-like glandular tissue (ectopic breast tissue) and metastases to inguinal lymph nodes. Estrogen receptor and progesterone receptor immunohistochemical staining is negative utilizing the HSCORE method. The treatment regimen is patterned after approach to node-positive breast carcinoma.