Role of NADPH Oxidase versus Neutrophil Proteases in Antimicrobial Host Defense

NADPH oxidase is a crucial enzyme in mediating antimicrobial host defense and in regulating inflammation. Patients with chronic granulomatous disease, an inherited disorder of NADPH oxidase in which phagocytes are defective in generation of reactive oxidant intermediates (ROIs), suffer from life-threatening bacterial and fungal infections. The mechanisms by which NADPH oxidase mediate host defense are unclear. In addition to ROI generation, neutrophil NADPH oxidase activation is linked to the release of sequestered proteases that are posited to be critical effectors of host defense. To definitively determine the contribution of NADPH oxidase versus neutrophil serine proteases, we evaluated susceptibility to fungal and bacterial infection in mice with engineered disruptions of these pathways. NADPH oxidase-deficient mice (p47phox−/−) were highly susceptible to pulmonary infection with Aspergillus fumigatus. In contrast, double knockout neutrophil elastase (NE)−/−×cathepsin G (CG)−/− mice and lysosomal cysteine protease cathepsin C/dipeptidyl peptidase I (DPPI)-deficient mice that are defective in neutrophil serine protease activation demonstrated no impairment in antifungal host defense. In separate studies of systemic Burkholderia cepacia infection, uniform fatality occurred in p47phox−/− mice, whereas NE−/−×CG−/− mice cleared infection. Together, these results show a critical role for NADPH oxidase in antimicrobial host defense against A. fumigatus and B. cepacia, whereas the proteases we evaluated were dispensable. Our results indicate that NADPH oxidase dependent pathways separate from neutrophil serine protease activation are required for host defense against specific pathogens

Phaeochromocytoma and functioning paraganglioma in childhood and adolescence: role of iodine 131 metaiodobenzylguanidine

Phaeochromocytomas and functioning paragangliomas are rare tumours in childhood and adolescence. We review our experience of 43 cases (24 men, 19 women) who were first diagnosed at the age of ⩽ 18 years. All patients were evaluated at some point in their illness with iodine 131 metaiodobenzylguanidine ( 131 I-mIBG) scintigraphy. Eight patients (19%) had bilateral adrenal tumours, 12 (28%) had solitary extra-adrenal tumours, and 8 (19%) had multiple tumours. In 10 patients (23%), the tumours were associated with a familial neurocristopathic syndrome. Thirteen of 24 (54%) unifocal tumours which were initially considered to be benign ultimately proved to be multi-focal and/or malignant. The final prevalence of malignancy was 60% − 26 patients, of whom only 15 (57%) had obviously malignant tumours at the time of diagnosis. Primary tumour size ⋝5 cm was more commonly associated with a malignant course in adrenal but not extra-adrenal tumours. No other clinical, biochemical or morphological characteristic was significantly associated with malignancy. Although the high prevalence of malignancy in this series at least partly reflects referral bias, the need for lifelong follow-up of these patients is underscored. 131 I-mIBG scintigraphy was positive in 36 patients (84%), with a somewhat lower false-negative rate (12%) than X-ray computed tomography (20%). Eight patients with malignant tumours received therapeutic doses of 131 I-mIBG, with partial tumour responses in 3. Thus, 131 I-mIBG is an efficacious, non-invasive, localising agent and may be considered as a palliative therapeutic agent when alternatives have failed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46831/1/259_2005_Article_BF02262730.pd

Subjective Social Status and Psychological Distress in Mothers of Young Children

INTRODUCTION: Perceptions of social standing have increasingly well-documented relationships with health. Higher subjective social status (SSS) is associated with better psychological well-being among women, and mothers of newborns. The relationship between SSS and psychological distress among mothers of young children, however, is largely unknown. SSS may provide insight into aspects of maternal functioning that are relevant to parenting capacity, as well as insight into future health; in addition, SSS is brief, and may be perceived as less intrusive than other measures of socioeconomic status or mental health. We evaluated the relationship between SSS and psychological distress among mothers of 5-year-old children from diverse socioeconomic backgrounds. METHODS: 162 mothers of 5-year old children, who participated in a study of child self-regulation, completed surveys that assessed sociodemographics, mental health, and perceived social support. The MacArthur Scale of Subjective Social Status used pictures of 10-rung ladders to assess respondents’ social position in relation to the US (SES ladder) and their community (community ladder). Quantile regression models were used to assess the relationship between maternal psychological distress (perceived social support, depressive symptoms, anxiety) and the ladders (individually and together), adjusting for maternal age, race, education, and number of children. To examine whether the SSS-health relationships differed by race, the models were also stratified by race. RESULTS: Community ladder ranking was positively associated with social support (β=1.34, SE=0.33, p<.001), and negatively associated with depressive symptoms (β=−1.34, SE=0.52, p<.05). SES ladder ranking was positively associated with social support (β=1.17, SE=0.52, p<.05). Findings in the full sample were driven by more robust relationships between psychological distress and community SSS among Black/African-American mothers. DISCUSSION: The findings suggest that perceived social standing in one’s community is associated with maternal psychological well-being. Community SSS may be particularly influential for Black/African-American mothers’ well-being