Lyme disease is a chronic inflammatory disorder caused by the spirochetal bacterium, Borrelia burgdorferi. In vitro evidence suggests that binding of spirochetal lipoproteins to CD14, a pattern recognition receptor expressed on monocytes/macrophages and polymorphonuclear cells, is a critical requirement for cellular activation and the subsequent release of proinflammatory cytokines that most likely contribute to symptomatology and clinical manifestations. To test the validity of this notion, we assessed the impact of CD14 deficiency on Lyme disease in C3H/HeN mice. Contrary to an anticipated diminution in pathology, CD14−/− mice exhibited more severe and persistent inflammation than did CD14+/+ mice. This disparity reflects altered gene regulation within immune cells that may engender the higher bacterial burden and serum cytokine levels observed in CD14−/− mice. Comparing their in vitro stimulatory activity, live spirochetes, but not lysed organisms, were a potent CD14-independent stimulus of cytokine production, triggering an exaggerated response by CD14−/− macrophages. Collectively, our in vivo and in vitro findings support the provocative notion that: 1) pattern recognition by CD14 is entirely dispensable for elaboration of an inflammatory response to B. burgdorferi, and 2) CD14-independent signaling pathways are inherently more destructive than CD14-dependent pathways. Continued study of CD14-independent signaling pathways may provide mechanistic insight into the inflammatory processes that underlie development of chronic inflammation.
Lung cancer has a predilection to widely metastasize to the liver, bone, brain and adrenal glands. Metastasis of primary lung tumors to the stomach is infrequent, with only sporadic cases reported. Most cases are asymptomatic and diagnosed post-mortem on autopsy. The incidence of symptomatic gastrointestinal metastases is extremely rare. Herein, we describe a case of gastric metastasis by squamous cell lung carcinoma, presenting as melena and diagnosed by esophagogastroduodenoscopy. To the best of our knowledge, only twenty other cases in the English literature have reported symptomatic gastric metastasis of lung cancer diagnosed by endoscopic biopsy. A brief review of the literature shows gastric metastasis of lung cancer to have a predilection to occur most frequently in male smokers with the most common type of tumor likely to be squamous cell carcinoma.
Granulomatosis with polyangiitis (GPA; formerly Wegener's) can present with clinical and histopathological features similar to those of immunoglobulin-G4 related disease (IgG4-RD), a recently described fibro-inflammatory condition. The ability of these two distinct entities to mimic each other closely creates significant pitfalls in diagnosis. We present a unique case in which GPA presented as a peri-aortic fibrotic mass in the retroperitoneum. The patient's other clinical features also overlapped with classic IgG4-RD disease manifestations, but the histopathology in two organs and the serological data confirmed the diagnosis of GPA. Rigorous histopathological review remains the gold standard for the diagnosis of GPA and the distinction of this entity from IgG4-RD and other mimickers.
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