Coexisting left diaphragmatic hernia and esophageal atresia

Coexisting left diaphragmatic hernia (DH) and esophageal atresia, a rare phenomenon, is described in two newborns, one with tracheoesophageal fistula (TEF) and the other without. The coexistence of DH and TEF in the one resulted in uncontrolled gastrointestinal distention with severe respiratory distress. Transabdominal division of the TEF was feasible and was performed concurrently with the diaphragmatic repair. Severe hypoplastic lungs and persistent pulmonary hypertension resulted in early postoperative death in both cases. Offprint requests to: R. Udassin     

Pro-angiogenic cytokines and their role in tumor angiogenesis

The development of solid tumors depends upon an adequate supply of blood. This can be achieved by way of co-option of preexisting blood vessels and by the induction of angiogenesis. During the past 30 years, tumor angiogenesis had been found to play a crucial role in the progression of solid tumors. Tumor angiogenesis was found to be induced by a variety of pro-angiogenic cytokines of which the best characterized is vascular endothelial growth factor (VEGF). Indeed, the first FDA approved anti-angiogenic drug for the treatment of cancer is Avastin^TM, a neutralizing antibdy directed against VEGF. This review focuses on cytokines which have been reported to induce tumor angiogenesis.     

Protective immunity to the larval stages of onchocerca volvulus is dependent on Toll-like receptor 4

Toll-like receptor 4 (TLR4) has been shown to be important for the induction of Th2-dependent immune responses in mice. Protective immunity against larval Onchocerca volvulus in mice depends on the development of a Th2 immune response mediated by both interleukin-4 (IL-4) and IL-5. In addition, O. volvulus contains the rickettsial endosymbiont Wolbachia, which has molecules with lipopolysaccharide-like activities that also signal through TLR4. We therefore hypothesized that protective immunity to O. volvulus would not develop in C3H/HeJ mice which have a mutation in the Tlr4 gene (TLR4 mutant), either because of a decreased Th2 response to the larvae or because of the absence of a response to Wolbachia. TLR4-mutant mice were immunized against O. volvulus with irradiated third-stage larvae, and it was observed that Th2 responses were elevated based on increased IL-5 production, total immunoglobulin E (IgE) levels, antigen-specific IgG1 response, and eosinophil recruitment. Protective immunity, however, did not develop in the TLR4-mutant mice. The Th1 response, as measured by gamma interferon production from spleen cells, was comparable in both wild-type and TLR4-mutant mice. Furthermore, antibody responses to Wolbachia were absent in both wild-type and TLR4-mutant mice. Therefore, the defect in the development of a protective immune response against O. volvulus in TLR4-mutant mice is not due to loss of Th2 immunity or the response to Wolbachia but is due to an unidentified TLR4-dependent larval killing mechanism.     

Immunogenicity of bioactive magnetic nanoparticles: natural and acquired antibodies

Uniform magnetic nanoparticles (MNP) were prepared by nucleation followed by controlled growth of maghemite thin films onto porcine gelatin nuclei. The formed gelatin containing MNP (Gel-MNP) were then coated with dextran (Gel-MNP-Dex) followed by human serum albumin (Gel-MNP-Dex-HSA). Since these MNP are designated for clinical applications, studies concerning the immunogenicity of their antigenic components (porcine gelatin, dextran, and HSA) have been performed in BALB-C mice. These studies demonstrated that plasma of nonimmunized mice already contains basal levels of natural antibodies against all of these antigenic components. This work also demonstrated that the conjugated gelatin is a weak immunogen: Intraperitoneal injection of the various MNP (Gel-MNP, Gel-MNP-Dex dispersed in PBS emulsified with Incomplete Freund's Adjuvant (IFA) mineral oil and Gel-MNP-Dex-HSA dispersed in PBS) did not increase significantly the acquired anti-gelatin antibody titers. Exceptional behavior was observed following immunization with Gel-MNP-Dex-HSA dispersed in PBS emulsified with IFA, which exhibited an adjuvant effect and turned gelatin into a stronger immunogen. In contrast to gelatin, the conjugated HSA and dextran were found to be strong immunogens. The possibility that the various MNP will not induce an autoimmune response as a result of their clinical use is discussed in the contest of the protective role of the natural antibodies.     

Cop9 signalosome subunit 8 (CSN8) is essential for Drosophila development

The COP9 signalosome (CSN) is a multisubunit regulator highly conserved in evolution. We show here that CSN subunit 8 (CSN8) is essential for Drosophila development. CSN8 is maternally contributed and present throughout development. Null mutants generated in this study are larval lethal, showing phenotypes associated with mutations in either CSN4 (molting defects) or CSN5 (melanotic tumors). Analysis of mitotic and germ-line csn8^null clones revealed the requirement of CSN8 for multiple developmental processes. The germ-line clones arrested at mid-oogenesis, while the mitotic clones led to deformed adult eyes or wings. CSN8 is present exclusively as part of the CSN holo-complex, and lack of CSN8 in the mutants leads to CSN instability. Consistent with this, Cullin deneddylation is impaired in the csn8^null mutants.     

Is age a risk factor for depression among the oldest old with cancer?

Introduction

Age is negatively related to depression among young and middle age patients with cancer. Nevertheless the relationship between age and depression among older patients with cancer is unclear. The goal of the current study is to assess the association of depression with increasing age among older patients with cancer.

Changes in psychological distress of women with breast cancer in long-term remission and their husbands

The purpose of this randomized, prospective study was to identify factors influencing the psychological distress of breast cancer patients and their husbands during remission. Background variables and distress levels of 172 couples in two locations (Graz, Austria, and Jerusalem, Israel) were assessed by using three standardized instruments in two interviews conducted 6-8 months apart. In both geographic-cultural groups, women whose partners refused to participate in the interview reported significantly less perceived family support. The global severity index (measuring total psychological distress) reflected minor changes in psychological distress of both patients and their husbands over time.