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BACKGROUND In patients with melanoma, ipilimumab (an antibody against cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4]) prolongs overall survival, and nivolumab (an antibody against the programmed death 1 [PD-1] receptor) produced durable tumor regression in a phase 1 trial. On the basis of their distinct immunologic mechanisms of action and supportive(More)
Insulin resistance is a major factor in the pathogenesis of type 2 diabetes in the elderly. To investigate how insulin resistance arises, we studied healthy, lean, elderly and young participants matched for lean body mass and fat mass. Elderly study participants were markedly insulin-resistant as compared with young controls, and this resistance was(More)
Lipodystrophy is a rare disorder that is characterized by selective loss of subcutaneous and visceral fat and is associated with hypertriglyceridemia, hepatomegaly, and disordered glucose metabolism. It has recently been shown that chronic leptin treatment ameliorates these abnormalities. Here we show that chronic leptin treatment improves(More)
Calcium is essential for homeostasis, and normocalcemia should be maintained strictly during the perioperative period. The biochemistry of calcium equilibrium results from the calcium-sensing receptors on the parathyroid glands, which detect changes in calcium concentrations and initiate the proper response. Asymptomatic hypercalcemia is a common metabolic(More)
The steady-state rate of glucose oxidation through the mitochondrial TCA cycle (V(TCA)) was measured in acid extracts of 10- and 30-day-old cerebral cortex of rats receiving [1-13C]glucose intravenously and in neocortical slices superfused in vitro with the same isotope. TCA cycle flux was determined for each age group based on metabolic modeling analysis(More)
Liver resection has become the standard treatment for metastatic colorectal cancer. 1 Such procedures are now justified by the increasing safety of hepatic resections and by documentation of long-term disease free survival. 1,2 Metastatic disease confined to the liver is now routinely resected as part of a potentially curative strategy. When patients(More)
The effect of lymph node metastasis on local tumor control and distant failure in patients with anorectal melanoma has not been fully studied. Understanding the significance of lymphatic dissemination might assist in stratifying patients for either organ preservation or radical surgery. A retrospective review of all patients with anorectal melanoma who(More)
While sentinel lymph node biopsy (SLN) is a highly accurate and well-tolerated procedure for patients with cutaneous melanoma, the role of the completion lymph node dissection (CLND) for patients with positive SLN biopsy remains unknown. This study aimed to look at the prognostic value of a positive nonsentinel lymph node (NSLN). A prospectively maintained(More)
Islet isolation is a time-consuming process. Islet yields vary, and previous in vitro studies suggest that Ficoll may be an islet toxin. Here, we describe an alternative, Ficoll-free method to purify murine islets by filtration through a cell strainer. Collagenase digestion of pancreata was carried out using standard procedures. The pancreatic digest was(More)
Imatinib mesylate targets mutated KIT oncoproteins in gastrointestinal stromal tumor (GIST) and produces a clinical response in 80% of patients. The mechanism is believed to depend predominantly on the inhibition of KIT-driven signals for tumor-cell survival and proliferation. Using a mouse model of spontaneous GIST, we found that the immune system(More)