IntroductionZinc protoporphyrin (ZnPP) is an endogenous metalloporphyrin (MP) found at higher concentrations in anemia of chronic disorders, 1 iron deficiency, 2 and lead poisoning, 3 clinical circumstances where bone marrow cell proliferation is altered. Conversely, synthesis of ZnPP appeared diminished in states of increased cell proliferation such as in leukemia. 4 Furthermore, zinc porphyrins are potent inhibitors of hematopoiesis in animal and human bone marrow. 5 These observations suggest that ZnPP could serve as a signaling molecule in cell cycle regulation. One mechanism by which ZnPP could alter cell cycle is via heme oxygenase (HO-1), because ZnPP is a potent inducer of the enzyme that it competitively inhibits. 6 In fact, in an in vitro model, ZnPP resulted in the highest induction of HO-1 among many MPs tested (W. S. Zhang and colleagues, oral communication, October 2000). Because increased HO-1 is associated with increased cell proliferation in several models, 7,8 it may be that ZnPP-mediated HO-1 induction leads to alterations of cell cycle regulation or that ZnPP mediates cell cycle regulation to result in HO-1 induction. Nonetheless, the ability to induce HO-1 is not unique to ZnPP. For example, in chick embryo liver cells, different MPs resulted in varying levels of HO-1 induction. 9 More recent studies in murine NIH 3T3 cells and transgenic mice expressing the HO-1 promoter linked to a luciferase reporter demonstrated HO-1 induction by various MPs (W. A. Zhang and colleagues, oral communication, October 2000). However, the greater ability of ZnPP to induce HO-1 raises the question as to whether unique mechanisms contribute to ZnPP-mediated HO-1 induction.Although the induction of HO-1 by heme, the natural substrate, is believed to occur through a complex mechanism involving activator protein-1 (AP-1), 10 the mechanism of HO-1 induction by MPs is not clear. Diverse agents can lead to HO-1 induction, but the mechanism of the HO-1 induction that has been best described involves stress activation. The HO-1 induction by heavy metals on the mouse HO-1 gene, for example, is mediated via the stress response elements (SRE) and not the metal regulatory element (MRE). The multimerized SRE located on the distal enhancer 1 (DE1) and 2 (DE2) regions of the mouse HO-1 gene containing the core heptad AP-1 consensus sequence was also demonstrated to be responsible for HO-1 induction by heme. 10 Other inducer-response elements such as SP-1, a zinc finger protein, have also been identified on the DE2 region of the mouse HO-1 gene. 10 Although the role of SP-1 has not been extensively studied in induction of HO-1, it represents a class of transcription factors that requires zinc to form zinc finger motifs. These then bind to the SP-1 consensus sequence and lead to gene transcription. Another zinc finger protein that has similar motifs to SP-1 is early growth response-1 protein (Egr-1). MPs mediate HO-1 induction via SP-1 or Egr-1 binding sites, altered cell cycle regulation could be expected.We therefore investi...

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A 49-year-old man presented with an intralenticular metal foreign body incurred while he was sawing wood. The metal chard had violated the lens capsule and was lodged in the cortex of the lens. It was removed using a lens-preservation technique during open-globe repair. Subsequently, a dense posterior cortical cataract developed, which spontaneously resolved over the ensuing months. The cataract had a cruciate configuration with wave-like disruption of the stromal lamellae. To our knowledge, this is the first case of spontaneous resolution of a cataract after capsule violation by an intralenticular foreign body. The unique appearance of the cataract and its unusual resolution led to a new theory of lens injury by shockwave.

chorioiditis. 16,17 The granulomas in our patient contained no characteristic asteroid bodies or Schaumann bodies, which can be seen in sarcoidosis. Furthermore, the occurrence of stroke in sarcoidosis is extremely rare and the fluorescein angiogram shows a different pattern. 18 The absence of any signs of previous or present vasculitis in the choriocapillaris does not support the hypothesis that APMPPE is caused by a choroidal vasculitis of the lamina choriocapillaris. Instead, our findings indicate that APMPPE is caused by choroidal granulomas and can be part of a generalized granulomatous disease. The granulomas resemble those seen in sarcoidosis. However, its clinical presentation and the occurrence of a cerebral granulomatous vasculitis of large and medium arteries instead suggests that it may be a distinct multisystem granulomatous disease. Recognition of this syndrome is important and our case illustrates that it can be rapidly fatal. Because cerebral vasculitis associated with APMPPE usually responds well to corticosteroid therapy, 4,7,19 we propose that patients with APMPPE complicated by central nervous system manifestations should be treated immediately with intravenous corticosteroids.

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