Mineralocorticoid receptor antagonist monotherapy in pediatric non-classical 11β-hydroxylase deficiency.

Objectives: Congenital adrenal hyperplasia (CAH) is an uncommon genetic disorder which affects cortisol production in the adrenal glands. It is usually treated with glucocorticoids. We present a case of non-classical CAH caused by the partial deficiency of 11 beta-hydroxylase (11βOH) which was treated with aldosterone antagonist (eplerenone) monotherapy.

Biguanides and glucagon like peptide 1 receptor agonists in the amelioration of post liver transplant weight gain; a scoping review of the mechanism of action, safety and efficacy.

Weight gain post-liver transplant can lead to adverse patient outcomes in the post-transplant period. Pharmacotherapy and other measures can be utilised to reduce the burden and occurrence of weight gain in this population. We explored the mechanism of action, safety, and efficacy of these medications, specifically GLP-1 receptor agonists and metformin, focusing on liver transplant patients.

NK cells in childhood obesity are activated, metabolically stressed, and functionally deficient.

Childhood obesity is a major global concern, with over 50 million children now classified as obese. Obesity has been linked to the development of numerous chronic inflammatory diseases, including type 2 diabetes and multiple cancers. NK cells are a subset of innate effector cells, which play an important role in the regulation of adipose tissue and antitumor immunity.

The prevalence of cardiovascular risk factors in obese children.

Childhood Obesity poses a public health problem in Ireland. Complications associated include metabolic disease and cardiovascular disease risk. Our aim was to determine the prevalence of cardiovascular risk factors in a cohort of obese Irish children.

Altered distribution and increased IL-17 production by mucosal-associated invariant T cells in adult and childhood obesity.

Mucosal-associated invariant T (MAIT) cells are innate MHC-unrestricted cells that regulate inflammatory responses through the rapid production of cytokines. In this article, we show that circulating MAIT cells are depleted in obese adults, and depletion is associated with diabetic status. Circulating MAIT cells more frequently produced IL-17 upon stimulation ex vivo, a cytokine implicated in insulin resistance.

The impact of childhood obesity on inflammation, innate immune cell frequency, and metabolic microRNA expression.

Background: Obesity is characterized by chronic inflammation, immune dysregulation, and alteration of gene expression, associated with type 2 diabetes mellitus and cardiovascular disease. The degree to which these changes occur in childhood obesity is not fully defined.

Aims And Methods: The aim was to investigate the effect of childhood obesity on immune cell frequency, macrophage activation, cytokine production, and specific regulators of metabolic gene expression.

Bloody nipple discharge in a 7-month-old boy.

Isolated bloody nipple discharge is rare in infancy and is usually idiopathic. Discharge commonly resolves spontaneously, and ultrasonography is a useful diagnostic technique to detect the cause of discharge. The authors report a 7-month-old boy who presented with unilateral spontaneous bloody nipple discharge for 1 month without signs of infection or mass.

Day of surgery admission--is this safe practise?

Day of surgery admission (DOSA) describes the process whereby patients are admitted to hospital and have surgery, on the same day. This is the current admission policy in our institution, for most elective Otolaryngology Head and Neck Surgery patients. We audited 75 consecutive patients admitted on the same day as surgery within our department between May 2006 and January 2007.

A comparison of surgical outcomes and quality of life surveys in right lobe vs. left lateral segment liver donors.

Concern remains regarding the possibly higher risk to living liver donors of the right lobe (RL), as compared with the left lateral segment (LLS). We studied outcomes and responses to quality of life (QOL) surveys in the two groups. From 1997 to 2004, we performed 49 living donor liver transplants (LDLTs): 33 RL and 16 LLS.

Changes in the motility, morphology, and F-actin architecture of human dendritic cells in an in vitro model of dendritic cell development.

An in vitro model has been developed for analyzing the two developmental phases of human dendritic cell (DC) migration. Employing the age of the culture and the addition of GM-CSF, IL-4, and serum to regulate cellular phenotype, and glass coated with acid-precipitated human plasma proteins to facilitate persistent DC translocation, the model produces three sequential in vitro phenotypes with the following suggested in vivo counterparts: (1) DCs recently isolated from blood, which are highly polar and motile, and reflect the behavior of "undifferentiated" DCs that must extravasate from the blood stream and migrate into peripheral tissue; (2) large, nonmotile, stellate DCs, which reflect the highly "differentiated" signature phenotype of DCs in peripheral tissue, whose function is to capture foreign antigens; and (3) the large, motile "dedifferentiated" DCs, which reflect the behavior of "veiled cells" that have captured an antigen, retracted dendritic processes, migrated out of peripheral tissue, and are in the process of transporting a captured antigen to a proximal draining lymph node for presentation to T cells. Computer-assisted motion analysis of the three sequential phenotypes and fluorescent staining of F-actin reveal three unique behavioral states and unique cellular architecture consistent with inferred in vivo function.

Combination of IL-8 plus TNF alpha induces additive neutrophil migration.

We have previously reported that TNF alpha's ability to induce neutrophil transendothelial and transepithelial migration was largely dependent on the generation of IL-8 by the endothelial or pulmonary epithelial cells. To further explore the interrelationship of IL-8 with TNF alpha, we examined the migration of human neutrophils through noncellular barriers in response to these cytokines alone or in combination. We directly compared neutrophil migration through 3 microns-pore size polycarbonate Transwell filters in response to 10 nM TNF alpha or either 10 nM TNF alpha or buffer plus 10(-8) to 10(-11) M IL-8.

Cytokine-induced sequential migration of neutrophils through endothelium and epithelium.

Objective And Design: To better understand the mechanisms by which cytokines induced neutrophils to migrate into the airways, we constructed a novel in vitro model system.

Materials: Human umbilical vein endothelial cell (HUVE) monolayers were grown on top of permeable filters and human lung type II-like alveolar epithelial cell (A549) monolayers were grown on the undersurface of the filters.

Methods: The sequential migration of human neutrophils through the endothelium (apical to basal movement) and subsequently through the epithelium (basal to apical movement) in response to IL-1 beta or TNF alpha located basally to the epithelium was measured.

The sequential migration of neutrophils through endothelium and epithelium: a new model system.

To better understand the mechanisms by which neutrophils migrate into the airways, we constructed a novel in vitro model system with human umbilical vein endothelial cell (HUVE) monolayers grown on top of permeable filters and human lung Type II-like alveolar epithelial cell (A549) monolayers grown on the undersurface of the filters. The sequential migration of human neutrophils through the endothelium (apical to basal movement) and subsequently through the epithelium (basal to apical movement) in response to a stimulus located basally to the epithelium was measured. We found that the neutrophil chemoattractants, formylmethionylleucylphenylalanine (FMLP), leukotriene B4 (LTB4), and interleukin-8 (IL-8), induced dose-responsive migration through the double monolayer-filter complex.

T cell syncytia induced by HIV release. T cell chemoattractants: demonstration with a newly developed single cell chemotaxis chamber.

A chemotaxis chamber has been developed to analyze both the velocity and the directionality of individual T cells in gradients of high molecular mass molecules over long periods of time. Employing this chamber, it is demonstrated that syncytia induced by HIV in SUP-T1 cell cultures release two T cell chemoattractants with approximate molecular masses of 30 and 120 kDa. Neither uninfected single cells nor polyethylene glycol-induced syncytia release detectable chemoattractant, suggesting that these chemoattractants are linked to HIV infection.

Cytokine-induced neutrophil transepithelial migration is dependent upon epithelial orientation.

The mechanisms by which mediators and cytokines stimulate neutrophils to migrate across the lung epithelium are still unclear. We hypothesized that neutrophil transepithelial migration depends upon polarity of the epithelium. We therefore compared neutrophil migration through human lung Type II-like alveolar epithelial cell line (A549) monolayers grown on the upper versus lower surface of permeable filters to simulate apical-to-basal and basal-to-apical movement of neutrophils, respectively.

Neutrophil transepithelial migration is dependent upon epithelial characteristics.

To better understand the mechanisms by which neutrophils migrate to the airway lumen during an inflammatory response, we constructed an in vitro model system to examine the interactions of human neutrophils, human lung epithelial cells, mediators, and proinflammatory cytokines. We directly compared neutrophil movement through three lung epithelial cell lines, A549, H441, and 16-HBE-14o, in response to three chemoattractants, FMLP, LTB4, and IL-8, and the proinflammatory cytokines IL-1 alpha and beta and TNF alpha. While there was variation in the responses to the chemotaxins, there was no correlation between the transmonolayer electrical resistance and the ability of the neutrophils to migrate across the epithelia in response to the agents used.

Effects of neuropeptides on neutrophil migration through noncellular and endothelial barriers.

Background: Neuropeptides and neutrophils are postulated to be important immune effector molecules and cells, respectively, in a variety of lung inflammatory conditions.

Methods: We examined the effects of three lung neuropeptides, substance P, vasoactive intestinal peptide (VIP), and somatostatin and two relatively protease-resistant peptides, helodermin and sandostatin, on human neutrophil migration across 3 microns pore filters and human endothelial monolayers cultured on these filters.

Results: At concentrations of 1 to 10 mumol/L, substance P induced significant neutrophil migration that was dose-responsive and equivalent through endothelium and filters.

Effects of nedocromil sodium and WEB 2086 on chemoattractant-stimulated neutrophil migration through cellular and noncellular barriers.

Nedocromil sodium (Tilade) is an effective therapeutic agent against asthma and has been shown to exhibit antiinflammatory activity in vitro; however, its mode of action is yet to be described fully. Using an in vitro assay designed to mimic the extravasation of neutrophils from the peripheral circulation through cellular barriers to sites of inflammation, the effect of nedocromil sodium on chemoattractant-stimulated neutrophil migration was examined. We also examined the effects of WEB 2086, a platelet-activating factor (PAF) receptor antagonist, in parallel.

Degree of neutrophil chemotaxis is dependent upon the chemoattractant and barrier.

Stimulated neutrophil migration across lung endothelial and epithelial barriers is important in lung inflammatory processes. To better understand the interaction between chemoattractants, neutrophils, and endothelium and epithelium, we compared the ability of leukotriene B4 (LTB4), formylmethionylleucylphenylalanine (FMLP), and platelet-activating factor (PAF) to induce human neutrophil migration across 3-microns-pore filters alone and human umbilical vein endothelial (HUVE) cells and two different epithelial cell types, Madin-Darby canine kidney (MDCK) cells and human lung A549 cells, cultured in monolayers on these filters. LTB4, FMLP, and PAF induced neutrophil migration through naked filters, endothelial cells, and epithelial cells in a dose-related fashion.

Degree of platelet activating factor-induced neutrophil migration is dependent upon the molecular species.

Multiple molecular species of platelet activating factor (PAF) are produced as a result of inflammatory processes. PAF-induced neutrophil migration across endothelium is intrinsic to inflammatory responses. We therefore compared the ability of three naturally occurring PAF species (C16:0, C18:0, and C18:1), which only varied at carbon 1, to induce 51Cr-labeled human neutrophil migration across a naked 3-microns pore filter and human umbilical vein endothelial (HUVE) monolayers cultured on these filters.

Some murine thymic lymphocytes can form gap junctions.

Analysis of thymic lymphocytes isolated from weanling mice has revealed a minority population able to form permeable, intercellular (gap) junctions. This population is largest in mice aged between 3 and 6 weeks, much smaller in fetal and new-born mice and undetectable in mice aged 12 weeks or more. Fractionation of the thymocytes on Percoll gradients or with peanut agglutinin (PNA) shows the cells able to form junctions are enriched in lower density fractions and agglutinated by PNA, suggesting they are among the most immature.

The expression of murine Qa region gene product(s) in L cell transformants.

The cosmid H3.5, containing genes mapping to the murine H-2 Qa region, was used to transfect L cells by the calcium phosphate co-precipitation method. The resultant transfected cells expressed a Qa-like determinant as detected by an immune serum raised against the transfectant cells and Qa specific monoclonal antibodies.