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NF-B regulates liver cell death during development, regeneration, and neoplastic transformation. For example, we showed that oncogenic Ras-or Raf-mediated transformation of rat liver epithelial cells (RLEs) led to altered NF-B regulation through IKK complex activation, which rendered these cells more resistant to TGF-␤1-induced apoptosis. Thus, based on these findings, we sought to determine whether NF-B could also be in- NF-B was first identified as a nuclear factor specific to B cells that bound to the B site of the light chain gene enhancer. 1 NF-B is now known to be a family of dimeric transcription factors with subunits that contain an amino terminal stretch of approximately 300 amino acids termed the Rel homology domain (RHD) because it shares homology with the v-Rel oncoprotein. 2 The RHD is involved in DNA binding and dimerization of the various subunits. 3 Classical NF-B is composed of a p50 (NF-B1) and a p65 (RelA) subunit, 4,5 and is ubiquitously expressed. In non-B cells, NF-B is sequestered in the cytoplasm by specific inhibitory proteins termed IBs, 6,7 of which IB-␣ is the most well characterized.NF-B can be activated by many inducers including proinflammatory cytokines, phorbol esters, bacterial endotoxins, and oxidative stress. Recently the Akt/protein kinase B (PKB) kinase has been shown to play a role in this signaling in response to TNF-␣ or PDGF signalling. 8,9 The most well-characterized pathway leading to NF-B activation involves the IKK complex, which includes 2 catalytic kinase subunits IKK-1 (IKK-␣) and IKK-2 (IKK-␤), 10-13 and a third regulatory subunit termed IKK-␥ or NEMO. 14,15 Knock-out studies have underscored the nonoverlapping functions of IKK-1 and IKK-2 during vertebrate limb development and immune response, respectively. 16 Following signal-induced IKK activation, sequestered NF-B/IB-␣ is recruited to the IKK complex where the IB-␣ is phosphorylated on serine residues 32 and 36. As a consequence of phosphorylation, IB-␣ protein is rapidly ubiquitinated and degraded through the proteasome pathway, 17-19 allowing for migration of NF-B to the nucleus.Recently, NF-B/Rel factors have been strongly implicated in the regulation of malignant cell growth, survival, and transformed phenotype. 20,21 As we first showed, TGF-␤1-mediated cell killing of murine B cell lymphomas is mediated via inhibition of NF-B, and direct repression of this activity can lead to death of these cells. 22,23 Furthermore, we found that human and rodent breast cancer cells are typified by aberrant NF-B/Rel expression, and inhibition of this activity can similarly lead to cell death. 24 To date, constitutive activation of NF-B has been observed in a variety of tumors including Hodgkin's and T-cell lymphomas, 25,26 melanomas, 27 breast and pancreatic adenocarcinomas, 24,[28][29][30] and primary adult Tcell leukemias. 31 Inhibition of NF-B activity potentiated cell killing of human breast cancer and fibrosarcoma cell lines by TNF-␣, ionizing radiation, and daunorubicin [32][33][34][35] and led to sensitization of...

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Purpose To report a case of acute idiopathic blind spot enlargement syndrome (AIBSES) following influenza vaccination. Observations A 57-year old woman presented with a one-month history of photopsia, temporal visual field disturbance on the right eye, 11 days following the administration of the influenza virus vaccine. Visual acuity was 20/30, and color vision remained normal. Examination revealed mild venular dilation at the edge of the right optic disk and was otherwise unremarkable. Visual field testing revealed enlargement of the right physiological blind spot. Medical workup, including brain CT scan, brain MRI, RPR, Treponema pallidum antibodies, Chest X-Ray, ANA, and PPD testing, was found within normal limits. Ancillary testing was compatible with an assessment of AIBSES secondary to influenza virus vaccination. Conclusions and Importance Although direct causation may not be absolutely established by a single report, our case suggests that the influenza virus vaccine may serve as an immunological trigger for some cases of AIBSES. Thoughtful vaccination history is of the utmost importance when evaluating patients with AIBSES, as it may help elucidate the underlying precipitating factor. To our knowledge, this is the first reported case of AIBSES following influenza virus vaccination.

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