In vitro assessment of electrospun polyamide-6 scaffolds for esophageal tissue engineering.

Artificial tissue-engineered grafts offer a potential alternative to autologous tissue grafts for patients, which can be traumatic. After decellularizing Papio hamadryas esophagus and studying the morphology and physical properties of the extracellular matrix (ECM), we generated electrospun polyamide-6 based scaffolds to mimic it. The scaffolds supported a greater mechanical load than the native ECM and demonstrated similar 3D microstructure, with randomly aligned fibers, 90% porosity, 29 μm maximal pore size, and average fiber diameter of 2.

Treatment of subcutaneous abscesses in children with incision and loop drainage: A simplified method of care.

Purpose: The aim of this study was to expand on our previous report of 115 patients after more than a decade-long experience using incision and loop drainage for pediatric subcutaneous abscess management. This report comprises the largest consecutive series of pediatric abscess patients from a single institution ever recorded.

Methods: A retrospective study was performed of all pediatric patients who underwent incision and loop drainage of subcutaneous abscesses at our institution between January 2002 and December 2014.

Orthotopic transplantation of a tissue engineered diaphragm in rats.

The currently available surgical options to repair the diaphragm are associated with significant risks of defect recurrence, lack of growth potential and restored functionality. A tissue engineered diaphragm has the potential to improve surgical outcomes for patients with congenital or acquired disorders. Here we show that decellularized diaphragmatic tissue reseeded with bone marrow mesenchymal stromal cells (BM-MSCs) facilitates in situ regeneration of functional tissue.

Dual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy.

Granulocyte macrophage colony stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine. Its inflammatory activity is primarily due its role as a growth and differentiation factor for granulocyte and macrophage populations. In this capacity, among other clinical applications, it has been used to bolster anti-tumor immune responses.

Pediatric obesity.

Childhood obesity is a tremendous burden for children, their families, and society. Obesity prevention remains the ultimate goal but rapid development and deployment of effective nonsurgical treatment options is not currently achievable given the complexity of this disease. Surgical options for adolescent obesity have been proven to be safe and effective and should be offered.

Selective destruction of mouse islet beta cells by human T lymphocytes in a newly-established humanized type 1 diabetic model.

Type 1 diabetes (T1D) is caused by a T cell-mediated autoimmune response that leads to the loss of insulin-producing beta cells. The optimal preclinical testing of promising therapies would be aided by a humanized immune-mediated T1D model. We develop this model in NOD-scid IL2rgamma(null) mice.

Dendritic cell-directed CTLA-4 engagement during pancreatic beta cell antigen presentation delays type 1 diabetes.

The levels of expression of alternatively spliced variants of CTLA-4 and insufficient CTLA-4 signaling have been implicated in type 1 diabetes. Hence, we hypothesized that increasing CTLA-4-specific ligand strength on autoantigen-presenting dendritic cells (DCs) can enhance ligation of CTLA-4 on T cells and lead to modulation of autoreactive T cell response. In this study, we show that DC-directed enhanced CTLA-4 engagement upon pancreatic beta cell Ag presentation results in the suppression of autoreactive T cell response in NOD mice.

New type of human blood stem cell: a double-edged sword for the treatment of type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease caused by an autoimmune destruction of pancreatic islet insulin-producing cells. Autoimmunity and shortage of insulin-producing cells are 2 key issues for the treatment of T1D. To cure T1D in a comprehensive manner, both issues need to be addressed simultaneously.

A prospective trial for laparoscopic adjustable gastric banding in morbidly obese adolescents: an interim report of weight loss, metabolic and quality of life outcomes.

Unlabelled: BACKGROUND AND MATERIALS AND METHODS: The outcome of patients completing 12 months of follow-up in a prospective longitudinal trial of the safety/efficacy of laparoscopic adjustable gastric banding (LAGB) for morbidly obese adolescents aged 14 to 17 years using a Food and Drug Administration Institutional Device Exemption for the use of the LAPBAND was analyzed. Baseline and outcome data were abstracted from a prospective database.

Results: Baseline (mean +/- SD) body mass index was 50 +/- 10 kg/m(2), and excess weight was 178 +/- 53 lb in 20 patients.

Persistent hypoglycemia in a child with a gastrocolic fistula--an unexpected presentation of leucine-sensitive hypoglycemia.

Leucine-hypersensitive hypoglycemia is a rare clinical entity that is usually diagnosed after an exhaustive search for other causes of hypoglycemia. In nonsurgical patients, an imbalance between metabolic demands and gluconeogenesis are most frequently responsible for recurrent symptomatic hypoglycemia. In the postoperative patient, hypoglycemia more commonly results from inadequate energy intake or malabsorption from functional or anatomical abnormalities.

Simultaneous costal cartilage-sparing modified Ravitch procedure and latissimus dorsi transfer for chest wall deformity repair in Poland's syndrome.

Poland's syndrome is a constellation of rare congenital anomalies that include hypoplasia of breast and underlying subcutaneous tissue, absence of the costosternal portion of the pectoralis major muscle, deformity or absence of ribs, absence of axillary hair, and syndactyly. Various surgical techniques have been described to repair such chest wall defects. We report a case of simultaneous Fonkalsrud procedure (costal cartilage-sparing version of the modified Ravitch procedure) and latissimus dorsi transfer in a 15-year-old boy with Poland's syndrome.

Human cord blood stem cell-modulated regulatory T lymphocytes reverse the autoimmune-caused type 1 diabetes in nonobese diabetic (NOD) mice.

Background: The deficit of pancreatic islet beta cells caused by autoimmune destruction is a crucial issue in type 1 diabetes (T1D). It is essential to fundamentally control the autoimmunity for treatment of T1D. Regulatory T cells (Tregs) play a pivotal role in maintaining self-tolerance through their inhibitory impact on autoreactive effector T cells.

Bilateral intrathoracic kidneys and adrenal glands associated with posterior congenital diaphragmatic hernias.

We present a case of bilateral intrathoracic kidneys and adrenal glands associated with bilateral posterior diaphragmatic defects in a symptomatic 18-month-old baby boy. The diaphragmatic defect did not appear to be the typical posterolateral diaphragmatic hernia of Bochdalek. The patient underwent primary surgical correction through an abdominal approach.

Preferential costimulation by CD80 results in IL-10-dependent TGF-beta1(+) -adaptive regulatory T cell generation.

Costimulatory ligands CD80 and CD86 have different binding preferences and affinities to their receptors, CD28 and CTLA-4. Earlier, we demonstrated that CD80 binds to CTLA-4 with higher affinity and has a role in suppressing T cell response. The current study demonstrates that not only did blockade of CD86 upon Ag presentation by bone marrow-derived dendritic cells (DC) to OVA-specific T cells result in induction of hyporesponsive T cells but also that these T cells could suppress the proliferative response of effector T cells.

Enhanced engagement of CTLA-4 induces antigen-specific CD4+CD25+Foxp3+ and CD4+CD25- TGF-beta 1+ adaptive regulatory T cells.

CTLA-4 is a critical negative regulator of T cell response and is instrumental in maintaining immunological tolerance. In this article, we report that enhanced selective engagement of CTLA-4 on T cells by Ag-presenting dendritic cells resulted in the induction of Ag-specific CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(-)TGF-beta1(+) adaptive Tregs. These cells were CD62L(low) and hyporesponsive to stimulation with cognate Ag but demonstrated a superior ability to suppress Ag-specific effector T cell response compared with their CD62L(high) counterparts.

Members of adenovirus species B utilize CD80 and CD86 as cellular attachment receptors.

Alternate serotypes of adenovirus (Ad), including Ads of species B, are being explored to circumvent the disadvantages of Ad serotype 5 gene delivery vectors. Whereas the majority of human Ads utilize the Coxsackievirus and adenovirus receptor (CAR), none of the Ad species B use CAR. Ad species B is further divided into two subspecies, B1 and B2, and utilizes at least two classes of receptors: common Ad species B receptors and B2 specific receptors.

Laparoscopic adjustable gastric banding for the treatment of adolescent morbid obesity in the United States: a safe alternative to gastric bypass.

Background: Morbid obesity (MO) has reached epidemic proportions and is a major health problem in developed nations. In the adolescent with MO, early intervention can minimize obesity-related comorbidities, avoid premature mortality, improve quality of life, and prevent obesity-related diseases as these patients mature into adulthood. The primary surgical treatment of adolescent patients meeting National Institutes of Health criteria for bariatric surgery has been the gastric bypass (GB).

Electron beam CT scan is a valuable and safe imaging tool for the pediatric surgical patient.

Purpose: Electron beam computed tomography (EBCT) is a relatively new technology that has been used primarily to detect coronary artery calcification in adult patients. EBCT has several potential advantages over traditional CT: (1) fast acquisition times resulting in less need for sedation, (2) decreased radiation exposure, and (3) robust software enabling real-time interactive 3-dimensional visualization of anatomic relationships. In this series of case reports, the authors describe their initial experience with the use of EBCT in pediatric noncardiac imaging.

Targeted CTLA-4 engagement induces CD4+CD25+CTLA-4high T regulatory cells with target (allo)antigen specificity.

CTLA-4 (CD152) is actively involved in down-regulating T cell activation and maintaining lymphocyte homeostasis. Our earlier studies showed that targeted engagement of CTLA-4 can down-modulate T cell response and suppress allo- and autoimmune responses. In this study, we report that targeted CTLA-4 engagement can induce immune tolerance to a specific target through selective induction of an Ag-specific CD4(+)CD25(+)CTLA-4(high) regulatory T cell (Treg cell) population.

Adenovirus serotype 3 utilizes CD80 (B7.1) and CD86 (B7.2) as cellular attachment receptors.

Most viruses exploit a variety of host cellular proteins as primary cellular attachment receptors in the context of successful execution of infection. Furthermore, many viral agents have evolved precise mechanisms to subvert host immune recognition to achieve persistence. Herein we present data indicating that adenovirus (Ad) serotype 3 utilizes CD80 (B7.

Modulation of dendritic cell function and cytokine production to prevent thyroid autoimmunity.

Understanding autoimmune thyroid diseases provides an unique perspective on the role of various components of the immune system in the pathogenesis of organ specific autoimmune diseases, whether the effector mechanism involves autoantibodies or T cells. Hashimoto's thyroiditis (HT) is largely mediated by thyroglobulin specific T cells, while Graves' disease (GD) is mediated by thyrotropin receptor specific autoantibodies. HT is characterized by thyroid destruction mediated by infiltrating or activated resident immune cells through a variety of mechanisms.

Costimulatory molecule immune enhancement in a plasmid vaccine model is regulated in part through the Ig constant-like domain of CD80/86.

There is great interest in understanding the role of costimulatory molecules in immune activation. In both the influenza and HIV DNA immunization models, several groups have reported that coimmunization of mice with plasmids encoding immunogen and CD86, but not CD80, effectively boosts Ag-specific T cell activation. This difference in immune priming provided an opportunity to examine the functional importance of different regions of the B.

Selective induction of dendritic cells using granulocyte macrophage-colony stimulating factor, but not fms-like tyrosine kinase receptor 3-ligand, activates thyroglobulin-specific CD4+/CD25+ T cells and suppresses experimental autoimmune thyroiditis.

Fms-like tyrosine kinase receptor 3-ligand (Flt3-L) and GM-CSF cause expansion of different subsets of dendritic cells and skew the immune response toward predominantly Th1 and Th2 type, respectively. In the present study, we investigated their effects on experimental autoimmune thyroiditis in CBA/J mice. Relative to mouse thyroglobulin (mTg) immunized controls, mTg-immunized mice treated with Flt3-L showed more severe thyroiditis characterized by enhanced lymphocytic infiltration of the thyroid, and IFN-gamma and IL-2 production.

Targeted engagement of CTLA-4 prevents autoimmune thyroiditis.

The CTLA-4-mediated signal is a critical step in the down-modulation of immune responses. The therapeutic potential of this signal to induce tissue-specific tolerance was investigated by using an anti-CTLA-4 antibody that was coupled to an antibody specific for the thyrotropin receptor. After in vivo administration, this bispecific antibody (BiAb) accumulated in the thyroid and prevented development of experimental autoimmune thyroiditis (EAT) in mice immunized with mouse thyroglobulin (mTg).

CD80 and CD86 C domains play an important role in receptor binding and co-stimulatory properties.

CD80 and CD86 expressed on the surface of antigen-presenting cells interact with cytotoxic T lymphocyte antigen-4 [CTLA-4 (CD152)] expressed on activated T cells and mediate critical T cell inhibitory signals. CD80 and CD86 are type I glycoproteins, and are made up of two extracellular (EC) Ig-like domains-a transmembrane region and a cytoplasmic tail. The N-terminal (V domain) and membrane-proximal (C) domains share homology with the variable region (V) and the constant region (C) of Ig respectively.