Necroptosis is a caspase-independent form of cell death that is triggered by activation of the receptor interacting serine/threonine kinase 3 (RIPK3) and phosphorylation of its pseudokinase substrate ...mixed lineage kinase-like (MLKL), which then translocates to membranes and promotes cell lysis. Activation of RIPK3 is regulated by the kinase RIPK1. Here we analyze the contribution of RIPK1, RIPK3, or MLKL to several mouse disease models. Loss of RIPK3 had no effect on lipopolysaccharide-induced sepsis, dextran sodium sulfate-induced colitis, cerulein-induced pancreatitis, hypoxia-induced cerebral edema, or the major cerebral artery occlusion stroke model. However, kidney ischemia-reperfusion injury, myocardial infarction, and systemic inflammation associated with A20 deficiency or high-dose tumor necrosis factor (TNF) were ameliorated by RIPK3 deficiency. Catalytically inactive RIPK1 was also beneficial in the kidney ischemia-reperfusion injury model, the high-dose TNF model, and in A20(-/-) mice. Interestingly, MLKL deficiency offered less protection in the kidney ischemia-reperfusion injury model and no benefit in A20(-/-) mice, consistent with necroptosis-independent functions for RIPK1 and RIPK3. Combined loss of RIPK3 (or MLKL) and caspase-8 largely prevented the cytokine storm, hypothermia, and morbidity induced by TNF, suggesting that the triggering event in this model is a combination of apoptosis and necroptosis. Tissue-specific RIPK3 deletion identified intestinal epithelial cells as the major target organ. Together these data emphasize that MLKL deficiency rather than RIPK1 inactivation or RIPK3 deficiency must be examined to implicate a role for necroptosis in disease.
The constrained court Bailey, Michael A; Bailey, Michael A; Maltzman, Forrest
2011., 20110822, 2011, 2011-08-22
eBook
How do Supreme Court justices decide their cases? Do they follow their policy preferences? Or are they constrained by the law and by other political actors? The Constrained Court combines new ...theoretical insights and extensive data analysis to show that law and politics together shape the behavior of justices on the Supreme Court.
Soft toric lenses Maltzman, B A
Current opinion in ophthalmology,
1992-February, Volume:
3, Issue:
1
Journal Article
Astigmatism is a common refractive error found in a large percentage of patients who wear contact lenses. Since 1979, soft toric contact lenses have been available to correct for refractive ...astigmatism. Most of the original soft toric lenses had the correcting optical strength on the front surface, but more recently, soft toric lenses have been designed with the correcting optics on the back surface of the lens. Back-surface toric lenses provide much more stability, comfort, and increased visual acuity. There have been a number of research articles involving soft toric contact lenses that discuss various aspects of back-surface toric lenses and their advantages over front-surface toric lenses. These advantages are presented and discussed in this paper.
The most common complication of extracapsular cataract extraction is posterior capsule opacification, which appears to result from the proliferation of anterior lens epithelium onto the posterior ...capsule. The presence of a posterior chamber intraocular lens has been shown to decrease the incidence of posterior capsule opacification, possibly by a barrier mechanism. This retrospective clinical study compares the effect of two different lens designs (with and without a laser ridge) on posterior capsule opacification requiring Nd:YAG laser posterior capsulotomy. Twenty-one of 101 patients (20.8%) with nonridged lenses required Nd:YAG laser posterior capsulotomies versus 13 of 86 patients (15.1%) with ridged lenses. Although these data showed a clinical benefit from using a ridged lens, no statistical difference in the incidence of posterior capsulotomy was noted. Further evaluation of capsular-optic surface apposition is needed.
Two hundred sixty eyes of 195 patients having extracapsular cataract extraction (ECCE) with insertion of a posterior chamber intraocular lens were studied retrospectively. Of these cases, 160 eyes ...had preexisting glaucoma while 100 had no ocular pathology except for cataract. Intraocular pressure decreased significantly after ECCE in both groups and slowly returned to baseline within two years. The average postoperative visual acuity was better in the control group than in the glaucoma group. Patients with glaucoma were controlled with less medication after surgery. We believe that ECCE with insertion of a posterior chamber intraocular lens can be safely performed in glaucoma patients and has a beneficial effect on the control of glaucoma.
The records of 74 patients with primary angle-closure glaucoma were reviewed. Cataract formation in 103 eyes treated with argon laser were compared with eyes in an age- and sex-matched, ...randomly-selected control group to determine whether cataract formation was hastened by laser iridotomy. Twenty-three percent of eyes in the study group showed development of cataracts 29.9 months after laser treatment. This did not differ from the incidence of cataract formation (20%) in the same group before laser exposure (P = .357) and was significantly lower than the 49% incidence of cataracts observed in the age-matched control group (P less than .001). These data demonstrate the safety of laser iridotomy in the treatment of narrow-angle glaucoma.
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