Rabbit Anti-Human NOTCH4 (C-terminal) Polyclonal antibody

Objective. To determine whether the promoter polymorphism tumor necrosis factor (TNF) (-308) Is associated with susceptibility to or death from meningococcal sepsis. Design, Setting, Patients, and Participants. Association study involving 1321 patients with microbiologically proven Invasive meningococcal disease presenting to hospitals throughout United Kingdom during 1998-2001, among whom 134 died. Controls were derived from 1280 northern English blood donors. Measurements. DNA from patients and controls was genotyped at TNF (-308). After analysis, DNA was subsequently genotyped at eight other markers In strong linkage disequillbrium with TNF (-308); these markers were IKBL (-62), BAT3, LST1, NOTCH4 (+1297), NOTCH4 (+3061), CCHCR1 (+436), CCHCR1 (+2271), and LT alpha. To confirm functional relevance of TNF (-308) in the context of meningococcal disease, TNF secretion by, and TNF messenger RNA expression of macrophages derived from volunteers with known TNF (-308) genotype after exposure to Neisserie meningitidis were measured. Main Results. Among cases of meningococcal disease, likelihood of death was shown to be influenced by the age of the affected individual and also with the infecting serogroup, but was not influenced by genotype at TNF (-308) or the other linked markers. However, patients with meningococcal disease, irrespective of whether they died, were more likely to be homozygous for the rare allele at TNF (-308) (odds ratio = 1.93, 95% confidence interval 1.08-3.46), and less likely to be heterozygous for this marker (odds ratio = 0.79, 95% confidence Interval 0.64-0.97), compared with the control cohort. There was no association of susceptibility to disease with the other markers studied. Macrophages derived from volunteers homozygous for the rare allele at TNF(-308) expressed higher levels of TNF messenger RNA and secreted higher concentrations of TNF compared with common homozygotes after exposure to N. meningitidis. Conclusions, Genotype at TNF (-308) modifies cellular TNF secretion in response to N. meningitidis and may influence susceptibility to meningococcal disease, but does not Influence the likelihood of death after infection. (Crit Care Med 2009; 37: 1237-1243)

Objective. Notch signaling has been implicated in cell fate decisions during odontogenesis and tumorigenesis of some odontogenic neoplasms; however, its role in solid/multicystic (SA), unicystic (UA), and recurrent (RA) ameloblastoma remains unclear. The aim of this study was to determine Notch receptor and ligand expressions in these subtypes and to speculate on their significance. Methods. Notch receptors (Notch1, 2, 3, 4) and ligands (Jagged1, 2, and Delta1) were examined immunohistochemically in SA (n = 23), UA (n = 22), and RA (n = 19). Results. Notch4 overexpression in SA (n = 19/23; 82.6%) compared with UA (n = 1/22; 4.5%) or RA (n = 10/19; 52.6%) (P < .05) suggests positive correlation between Notch4 signaling and ameloblastomas with a solid/multicystic phenotype. Ligand (Jagged1 and Delta1) underexpression compared with their receptors (Notch1, 3, 4) (P < .05) and nonreactivity for Notch2 and Jagged2 in all 3 subsets suggests that ameloblastoma epithelium belongs to an earlier stage of differentiation (equivalent to inner enamel epithelium of developing tooth germ) before lineage commitment. Conclusion. Present findings suggest that Notch signaling molecules may play differing roles in the acquisition of different ameloblastoma phenotypes. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 110: 224-233)