Three hundred and twenty-two patients (192 male and 130 female) with cystic lesions of the jaw were successfully diagnosed and treated. One hundred and fifty-five (48%) were radicular cysts, 80 (25%) were dentigerous cysts, 23 (7%) were odontogenic keratocyst (=keratocystic odontogenic tumor), 19 (6%) were eruption cysts, 16 (5%) were traumatic bone cysts, and 29 (9%) were non-odontogenic cysts.There were 95 in the pediatric age group (1 month to 16 years) and 227 in the adult age group (17 years and older). Male to female ratio was 1 in the pediatric age group and 1.7 in the adult age group. The treatment modalities were: marsupialization, enucleation, enucleation with bone grafting, or resection. The distribution and characteristics of jaw cysts in children are different from those in adults. In children there is a relatively high rate of developmental cysts, whereas in adults the inflammatory cysts are more common. Following enucleation of a cystic jaw lesion, the entire surgical specimen and not only a biopsy specimen, should be examined histopathologically to prevent any possibility of an intramural squamous cell carcinoma that may be overlooked. The differences in prevalence of each type of jaw cyst during a lifetime may point toward a multifactorial polygenic pattern rather than a monogenic pattern.

Autophagy genes' expression is upregulated in visceral fat in human obesity, associating with obesity-related cardio-metabolic risk. E2F1 (E2F transcription factor 1) was shown in cancer cells to transcriptionally regulate autophagy. We hypothesize that E2F1 regulates adipocyte autophagy in obesity, associating with endocrine/metabolic dysfunction, thereby, representing non-cell-cycle function of this transcription factor. E2F1 protein (N=69) and mRNA (N=437) were elevated in visceral fat of obese humans, correlating with increased expression of ATG5 (autophagy-related 5), MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β), but not with proliferation/cell-cycle markers. Elevated E2F1 mainly characterized the adipocyte fraction, whereas MKI67 (marker of proliferation Ki-67) was elevated in the stromal-vascular fraction of adipose tissue. In human visceral fat explants, chromatin-immunoprecipitation revealed body mass index (BMI)-correlated increase in E2F1 binding to the promoter of MAP1LC3B, but not to the classical cell cycle E2F1 target, CCND1 (cyclin D1). Clinically, omental fat E2F1 expression correlated with insulin resistance, circulating free-fatty-acids (FFA), and with decreased circulating ADIPOQ/adiponectin, associations attenuated by adjustment for autophagy genes. Overexpression of E2F1 in HEK293 cells enhanced promoter activity of several autophagy genes and autophagic flux, and sensitized to further activation of autophagy by TNF. Conversely, mouse embryonic fibroblast (MEF)-derived adipocytes from e2f1 knockout mice (e2f1−/−) exhibited lower autophagy gene expression and flux, were more insulin sensitive, and secreted more ADIPOQ. Furthermore, e2f1−/− MEF-derived adipocytes, and autophagy-deficient (by Atg7 siRNA) adipocytes were resistant to cytokines-induced decrease in ADIPOQ secretion. Jointly, upregulated E2F1 sensitizes adipose tissue autophagy to inflammatory stimuli, linking visceral obesity to adipose and systemic metabolic-endocrine dysfunction.

We describe the clinical course, complement components, and pathological findings of 10 infants with autosomal recessive hemolytic uremic syndrome (HUS). All patients were members of one extended highly inbred Bedouin kindred. The median age of presentation was 2 weeks (range 1-20 weeks). Eight patients died, 2 patients are alive, on dialysis. Renal biopsies revealed thrombotic microangiopathy with a predominant early arteriolar involvement and subsequent development of ischemic glomerular changes. Immunofluorescence was positive for C3 in glomeruli. All patients had low complement components levels during and between relapses, and in some this was evident soon after birth and prior to the onset of symptoms. This deficiency could not be normalized by repeated plasma transfusions. Biosynthetic labelling of patients' fibroblasts demonstrated normal rates of C3 protein synthesis. Serum factor H levels were greatly decreased or absent in 4 patients tested and moderately decreased in 15 of 23 healthy unaffected siblings and patients. This defect may cause complement activation and consumption, possibly at the endothelial cell level.

Cytosolic phospholipase A 2a (cPLA 2 ) plays an important role in the development of several inflammatory diseases. The aim of the present study is to determine whether inhibition of cPLA 2 expression, using specific antisense oligonucleotides against cPLA 2 (antisense), is efficient in reducing inflammation after its development. Two mouse models of inflammation were included in the study: thioglicolate peritonitis and collagen-induced arthritis (CIA). The antisense was found to be specific and efficient in inhibiting cPLA 2 expression and NADPH oxidase activity ex vivo in peritoneal phagocytes. Immunoblotting and immunohistochemistry analysis showed a significant elevation in cPLA 2 expression in the inflamed joints of collagen-induced arthritis mice localized in cell infiltrate, chondrocytes and the surrounding skin and skeletal muscle. Similarly, the cPLA 2 metabolite, leukotriene B 4 , accumulated in the peritoneal cavity of mice with peritonitis. Inhibition of elevated cPLA 2 expression after development of inflammation by intravenous administration of antisense resulted in a dramatic reduction in inflammation and a significant reduction in neutrophils recruitment to the site of inflammation in both mouse models of inflammation. Our results demonstrate the critical role of cPLA 2 for the duration of inflammation and suggest that inhibition of cPLA 2 expression by antisense oligonucleotides may serve as an efficient treatment of inflammatory diseases. IntroductionRheumatoid arthritis is an autoimmune inflammatory disease that affects 1% of the population. It is characterized by polyarticular joint inflammation with leukocytic recruitment into synovial fluid and tissue, which appears as a symmetric polyarticular arthritis and which is associated with joint deformities of the hands and feet [1]. Despite extensive efforts, its etiology and pathogenesis remain poorly understood, and effective therapies with limited side effects are still lacking. Collagen-induced arthritis (CIA) in mice is an experimental model that reproduces many of the pathogenic mechanisms of human rheumatoid arthritis, such as increased cellular infiltration, synovial hyperplasia, pannus formation and erosion of cartilage and bone in the distal joints [2]. In humans and in murine arthritis models, chemokines and other chemoattractants [11] knock-out mice suggest that both prostaglandins and LT play an important role in the onset of CIA. Furthermore, dual inhibitors of 5-lipoxygenase and COX were more effective than selective COX inhibitors in preventing arthritis [12]. We have previously provided evidence that cPLA 2 , in addition to its known role in participating in eicosanoid production [13], regulates the phagocyte NADPH oxidase-releasing superoxides [14][15][16]. Moreover, consistent with many other studies, we have demonstrated in vivo and in vitro that during inflammation, the level and activity of both cPLA 2 and NADPH oxidase enzymes are elevated in neutrophils and monocytes [17,18]. Inhibition of overexpressed cPLA 2 protein du...