In vivo analysis of CCM3, a gene involved in cerebral cavernous malformation development

IN VIVO ANALYSIS OF CCM3, A GENE INVOLVED IN CEREBRAL CAVERNOUS MALFORMATION DEVELOPMENT. Aimee Two, Angeliki Louvi, and Murat Gunel. Department of Neurosurgery, Yale University, School of Medicine, New Haven, CT. Cerebral cavernous malformations (CCMs), one of the most common vascular malformations of the central nervous system (CNS), occur due to both sporadic and familial mutations in any of the three CCM genes: CCM1, or KRIT1; CCM2, or malcavernin; and CCM3, the Programmed Cell Death 10 gene. As the most recently discovered of these genes, CCM3 remains poorly understood. In vitro analysis has suggested a role for it in apoptosis, but in vivo studies of this gene are limited and thus are the goal of the current work. Using conditional knockout mice in which Ccm3 has been inactivated in neural cells, experimental animals were created that develop lesions resembling human CCMs. In situ hybridization and immunohistochemistry were used to compare staining patterns of glial fibrillary acidic protein (GFAP) and vimentin, both expressed in astrocytes, with vimentin being expressed specifically in activated astrocytes, as well as connexin43, a gap junction protein that links astrocytic foot processes along the blood brain barrier (BBB), and aquaporin 4, a water channel expressed exclusively in astrocytes, between control and experimental brains. Results showed an increase in GFAP and vimentin expression in experimental brains, suggesting increased glial activation, but a decrease in that of connexin43 and aquaporin 4, suggesting an abnormality of these astrocytes. Given that CCMs represent endothelial cell and not astrocyte pathology, these results suggest that lesion formation may be related to disrupted communication within the neurovascular unit

Discoid lupus and human immunodeficiency virus: A retrospective chart review to determine the prevalence and progression of co-occurrence of these conditions at a single Academic Center

Context: Discoid lupus erythematosus (DLE) and human immunodeficiency virus (HIV) are both disorders of the immune system. The pathophysiology of these diseases varies greatly as DLE is characterized by an overactive immune system that attacks normal host cells, whereas HIV is characterized by an exogenous attack on the immune system that depletes it of key cell types. Although the reason is unknown, co-occurrence of DLE and HIV is rare. Aims: The goal of this study is to determine the prevalence of co-occurrence of DLE and HIV and to determine whether patients with both DLE and HIV share any clinical feature. Subjects and Methods: The medical records of all patients seen within a single academic health center over a 20-year period were reviewed to determine the prevalence of cutaneous lupus, HIV, and co-occurrence of these conditions. The charts of patients diagnosed with both conditions were further reviewed to determine similarities between them. Results: Of the 10,719 patients diagnosed with HIV and 182 patients diagnosed with cutaneous lupus, only 2 patients were diagnosed with both conditions. Both of these patients were diagnosed with DLE several years after being diagnosed with HIV. They had an undetectable HIV viral load, normal CD4 T-cell counts, and were on antiretroviral therapy when diagnosed with DLE. Conclusion: These results confirm that co-occurrence of DLE and HIV is rare. Although our study population was small, findings from these patients suggest that in HIV-positive patients, DLE manifestations occur when their HIV disease activity is minimal

Kallikrein 5-Mediated Inflammation in Rosacea: Clinically Relevant Correlations with Acute and Chronic Manifestations in Rosacea and How Individual Treatments May Provide Therapeutic Benefit

Rosacea is a chronic inflammatory condition of facial skin estimated to affect more than 16 million Americans. Although the pathogenesis of rosacea is not fully understood, recent evidence in vitro as well as in vivo has supported the role of increased levels of the trypsin-like serine protease, kallikrein 5, in initiating an augmented inflammatory response in rosacea. The increase in the quantity and magnitude of biological activity of kallikrein 5 leads to production of greater quantities of cathelicidin (LL-37), an antimicrobial peptide associated with increases in innate cutaneous inflammation, vasodilation, and vascular proliferation, all of which are characteristic features of rosacea. In this article, the authors review the literature supporting the role of kallikrein 5 in the pathophysiology of rosacea, including how therapeutic interventions modulate the effects of kallikrein 5, thus providing further support for this pathophysiological model that at least partially explains many of the clinical features of cutaneous rosacea

A case of eosinophilic dermatosis of hematologic malignancy in a patient with multiple myeloma

A 50-year-old man with eosinophilic dermatosis of hematologic malignancy is presented. His dermatosis cleared after chemotherapy produced improved control of his multiple myeloma