Levamisole-induced vasculitis is a characteristic cutaneous vasculitis syndrome associated with the use of levamisole-adulterated cocaine. Patients will typically present with a painful, purpuric rash in a retiform or stellate pattern with or without central necrosis involving the extremities, trunk, nasal tip, digits, cheeks, and/or ears. A history of cocaine abuse can be elicited. Histologic features include microvascular thrombi and/or leukocytoclastic vasculitis involving small vessels of the superficial and deep dermis. Epidermal involvement is variably seen. Laboratory findings include leukopenia, neutropenia (including agranulocytosis), elevated erythrocyte sedimentation rate, normal coagulation studies, and positive autoantibodies including perinuclear and cytoplasmic antineutrophil cytoplasmic antibodies, antinuclear antibody, and lupus anticoagulant. Differential diagnosis includes other microscopic vasculitides, and clinical and laboratory correlation with histologic findings is essential. Lesions typically resolve with the cessation of cocaine use. Because of the treatment implications and rising incidence of this entity, rapid and accurate diagnosis is essential.
Poorly-differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly-differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports and pathology slides were reviewed for demographics, clinical history and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1 and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61 years old with 18 males and 19 females. The colorectum (n=20) was the most common primary site, other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%), and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly-differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease.
We recently generated an HT-1080-derived cell line called HT-AR1 that responds to dihydrotestosterone (DHT) treatment by undergoing cell growth arrest in association with cytoskeletal reorganization and induction of neuroendocrine-like cell differentiation. In this report, we show that DHT induces a dose-dependent increase in G 0 /G 1 growth-arrested cells using physiological levels of hormone. The arrested cells increase in cell size and contain a dramatic redistribution of desmoplakin, keratin 5, and chromogranin A proteins. DHTinduced cytoskeletal changes were also apparent from time lapse video microscopy that showed that androgen treatment resulted in the rapid appearance of neuronallike membrane extensions. Expression profiling analysis using RNA isolated from DHT-treated HT-AR1 cells revealed that androgen receptor activation leads to the coordinate expression of numerous cell signaling genes including RhoB, PTGF-, caveolin-2, Egr-1, myosin 1B, and EHM2. Because RhoB has been shown to have a role in tumor suppression and neuronal differentiation in other cell types, we investigated RhoB signaling functions in the HT-AR1 steroid response. We found that steroid induction of RhoB was DHT-specific and that newly synthesized RhoB protein was post-translationally modified and localized to endocytic vesicles. Moreover, treatment with a farnesyl transferase inhibitor reduced DHT-dependent growth arrest, suggesting that prenylated RhoB might function to inhibit HT-AR1 cell proliferation. This was directly shown by transfecting HT-AR1 cells with RhoB coding sequences containing activating or dominant negative mutations.
Previous research has shown that preferences for options, such as gambles, can reverse depending on the response mode. These preference reversals have been demonstrated when tasks were performed sequenfially. That is, subjects completed one task before beginning another. In an attempt to eliminate preference reversals, we asked subjects to perform tasks simulfaneously. That is, subjects made two types of responses for each pair of gambles before evaluating the next pair. In the condition with no financial incentives, preference reversal rates were slightly reduced. In another condition, subjects were paid for their participation and they were allowed to play a gamble with real monetary compensation. A gamble pair was randomly selected, and if a subject's responses in the two tasks were consistent for that pair, he or she was allowed to play the 'preferred' gamble. Otherwise, the experimenter selected the gamble from the pair. With these financial incentives, systematic preference reversals were eliminated for two of the three task combinations. Preference reversals continued to occur for attractiveness ratings versus selling prices, although, even for that pair of tasks, the reversal rate was significantly reduced. For all three task pairs, preference orders from the two tasks appeared to merge into more consistent orders. KEY WORDS preference reversals; violations of expected utility theory; change-ofprocess theory; strength of preference judgmentsDuring the past forty years, psychologists and economists have demonstrated numerous violations of expected utility theory, such as the Allais paradox (Allais, 1953), Ellsberg's paradox (Ellsberg, 1961), and framing effects (Tversky and Kahneman, 1986). Lichtenstein and Slovic (1971) discovered another violation of expected utility theory that they called the preference reversal phenomenon. They presented subjects with pairs of gambles matched on expected value. For each pair, subjects chose the gamble they preferred and then stated a selling price for each gamble separately. When asked, 'Which do you prefer?' in the choice task and 'Which do you value more?' in the pricing task, subjects shouldgive the same answer. But a surprising result occurred: stated preferences reversed depending on the response mode. That is, subjects frequently chose the gamble with the larger probability of winning (referred to as the P bet) over the gamble with the larger amount to win (referred to as the ! $ bet), but they assigned a higher selling price to the $ bet than the P bet. If both choices and selling prices reflect
HPV may have an important role in squamous lesions of the conjunctiva. In addition to positive polymerase chain reaction results, strong and diffuse p16 expression with marked Ki-67 is strongly suggestive of an HPV-driven lesion.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.