Role of regulatory dendritic cells in allergy and asthma

Dendritic cells (DCs) are the most efficient inducers of all immune responses, and are capable of either inducing productive immunity or maintaining the state of tolerance to self antigens and allergens. In this review, we summarize the emerging literature on DCs, with emphasis on the regulatory function of DCs in allergy and asthma. In particular, we summarize recent data regarding the relationship between DC subsets and T_H1, T_H2, and regulatory T (T_Reg) cells. The diverse functions of DCs have been attributed to distinct lineages of DCs, which arise from common immature precursor cells that differentiate in response to specific maturationinducing or local microenvironment conditions. These subsets of DCs induce different lineages of T cells, such as T_H1, T_H2, and T_Reg cells, including Th1_Reg and Th2_Reg cells, which regulate allergic diseases and asthma. Subsets of DCs regulate the induction of a variety of T-cell subtypes, which suppress the development of allergy and asthma, thus providing antiinflammatory responses and protective immunity.     

Screening for vesicoureteral reflux and renal scars in siblings of children with known reflux

The incidence of vesicoureteral reflux (VUR) in the general population is less than 1%, but it is high in families with reflux. The reported prevalence of VUR among siblings of index patients with reflux has ranged from 4.7% to 51%. Reflux carries an increased risk of pyelonephritis and long-term renal impairment. The purpose of this study was to identify the age-related incidence and severity of reflux, and the frequency of associated renal parenchymal damage in siblings of children with reflux in order to assess the use of screening at different ages. Between October 1994 and February 2003, 40 siblings of 34 index patients were screened with direct voiding cystography. 99( m ) technetium (Tc)-dimercaptosuccinic acid (DMSA) nuclear renal scans were performed in siblings with VUR to detect renal scarring. The cystograms were interpreted as showing the presence or absence of VUR and the DMSA scan as symmetrical or asymmetrical differential function, with or without renal scarring. Of 40 siblings, 17 had VUR, representing an incidence of 42.5%. The mean age at study entry of the 15 boys and 25 girls was 63 months (range 6 months to 12 years). The majority of siblings with abnormal DMSA scans were asymptomatic. Reflux was unilateral in 12 siblings and bilateral in 5. Of the 17 refluxing siblings (22 refluxing ureters), 7 (41.17%) had a history of symptomatic urinary tract infection (UTI). The frequency of VUR was nearly equal in siblings over 6 years and those younger than 6 years. Of the 17 siblings with VUR, 16 had DMSA scintigraphy. Of these, 5 were normal and 11 (68.75%) showed abnormalities (7 asymmetrical differential function and 4 parenchymal defect), which was bilateral in 7 and unilateral in 4. In conclusion, this study confirms a significant overall incidence of VUR and renal parenchymal damage in the siblings of patients with known reflux. The prevalence of reflux in older siblings is similar to that in younger siblings. Our review suggests that all siblings over 6 years should undergo a screening cystogram, even in the absence of urinary tract infection. DMSA scintigraphy of asymptomatic siblings appears to be beneficial in preventing renal injury.     

Alterations in expression of endometrial endothelial nitric oxide synthase and alpha(v)beta(3) integrin in women with endometriosis

OBJECTIVE: To determine the expression of endometrial endothelial nitric oxide synthase (eNOS) protein and alpha(v)beta(3) integrin in patients with and without endometriosis. DESIGN: Case-control cohort study. SETTING: University-based tertiary care center. PATIENT(S): Endometrial biopsy samples were obtained from 9 fertile women with regular cycles and 30 infertile women with varying severity of endometriosis. Peritoneal fluid levels of nitric oxide were determined in 13 infertile women with a normal pelvis and 12 infertile women with endometriosis. MAIN OUTCOME MEASURE(S): Expression of eNOS and alpha(v)beta(3) integrin protein in the endometrium and peritoneal fluid levels of nitric oxide. RESULTS: In patients with endometriosis, expression of eNOS was significantly increased in the glandular and luminal epithelium, with no significant changes in the stroma. Peritoneal fluid levels of nitric oxide were unchanged, and expression of alpha(v)beta(3) integrin expression in glandular and luminal epithelium was significantly decreased compared with controls. A significant negative correlation was observed between luminal expression of eNOS and alpha(v)beta(3) integrin and between glandular expression of eNOS and luminal expression of alpha(v)beta(3) integrin. CONCLUSION(S): The nitric oxide pathway may play a role in the pathogenesis of endometriosis.     

Thymoma associated with malignancies may herald a hereditary cancer syndrome

Two probands with thymoma and other primary malignancies with multiple cancer patients in the family are described. Types of malignancies, pattern of pedigree and age of the patients do not match the known familial cancer syndromes. One proband was a very rare case with five discrete primary malignancies; TP53 sequencing and karyotyping did not reveal any mutations. These cases suggest thymoma associated malignancies may herald a hereditary cancer syndrome.     

Chitosan-Alginate Scaffold Culture System for Hepatocellular Carcinoma Increases Malignancy and Drug Resistance

Purpose  

Hepatocellular carcinoma (HCC) is a prevalent solid malignancy. Critically needed discovery of new therapeutics has been hindered by lack of an in vitro cell culture system that can effectively represent the in vivo tumor microenvironment. To address this need, a 3D in vitro HCC model was developed using a biocompatible, chitosan-alginate (CA) scaffold cultured with human HCC cell lines.