Summary Inflammatory myofibroblastic tumor (IMT) was thought to represent a benign post‐infectious or post‐inflammatory process cured by surgical resection. However, reports of cases with an aggressive clinical course suggest the need for caution about the prognosis. The treatment of choice is a complete surgical resection, while medical treatment options are limited. Corticosteroid therapy has been used with some success in unresectable lesion. However, rapid progression of lung IMT after prednisone treatment has been reported, raising the hypothesis that corticosteroids may favor a tumultuous proliferation of this lesion, possibly through immunosuppression. We here report a similar observation and suggest that other mechanisms may be involved. A 5‐year and 6‐month‐old boy presented with a 72 hr history of breathlessness, initially responsive to albuterol and prednisone. He represented 15 days later with increasing symptoms despite further prednisone treatment. CT chest scan showed a mass lesion in the tracheal lumen, which on biopsy was found to be an IMT. The possibility that prednisone may have an enhancing effect on IMT cell proliferation is demonstrated through IMT cell culture and discussed. Pediatr Pulmonol. 2014; 49:E109–E111. © 2013 Wiley Periodicals, Inc.
The incidence of congenital cardiac abnormalities remains high. Paediatric patients with congenital cardiac defects often require surgery at a young age. The surgeries are often long and complex, rendering this population particularly vulnerable to the deleterious effects of cardiopulmonary bypass and cardiac surgery. The search for cardioprotective strategies is ongoing in an attempt to reduce the morbidity in this population. In the post‐genomic era, it is apparent that simply determining the genomic sequences holds little diagnostic potential and means to determine progression of disease and response to treatment. The field of proteomics is expanding and application of proteomic techniques in the clinical setting holds great potential to advance our understanding of the proteomic changes involved in specific disease stages. This review will assess the application of proteomic techniques in the setting of paediatric cardiac surgery and highlight the need to obtain a clear understanding of the role of various proteins in children with cardiac conditions. The success and challenges of the available proteomic technology will be discussed as well as the future potential of proteomic methods for advancing our understanding of protein changes in children requiring cardiac surgery.
Interleukin‐8 (CXCL8, IL‐8) is a proinflammatory chemokine important for the regulation of inflammatory and immune responses via its interaction with G‐protein coupled receptors, including CXC receptor 1 (CXCR1). CXCL8 exists as both a monomer and as a dimer at physiological concentrations, yet the molecular basis of CXCL8 interaction with its receptor as well as the importance of CXCL8 dimer formation remain poorly characterized. Although several biological studies have indicated that both the CXCL8 monomer and dimer are active, biophysical studies have reported conflicting results regarding the binding of CXCL8 to CXCR1. To clarify this problem, we expressed and purified a peptide (hCXCR1pep) corresponding to the N‐terminal region of human CXCR1 (hCXCR1) and utilized nuclear magnetic resonance (NMR) spectroscopy to interrogate the binding of wild‐type CXCL8 and a previously reported mutant (CXCL8M) that stabilizes the monomeric form. Our data reveal that the CXCL8 monomer engages hCXCR1pep with a slightly higher affinity than the CXCL8 dimer, but that the CXCL8 dimer does not dissociate upon binding hCXCR1pep. These investigations also showed that CXCL8 is dynamic on multiple timescales, which may help explain the versatility in this interleukin for engaging its target receptors.
Lymphocyte function‐associated antigen‐1 (LFA‐1) is an integrin protein that transmits information across the plasma membrane through the so‐called inside‐out and outside‐in signaling mechanisms. To investigate these mechanisms, we carried out an NMR analysis of the dynamics of the LFA‐1 I‐domain, which has enabled us to characterize the motions of this domain on a broad range of timescales. We studied first the internal motions on the nanosecond timescale by spin relaxation measurements and model‐free analysis. We then extended this analysis to the millisecond timescale motions by measuring 15 N‐ 1 H residual dipolar couplings of the backbone amide groups. We analyzed these results in the context of the three major conformational states of the I‐domain using their corresponding X‐ray crystallographic structures. Our results highlight the importance of the low‐frequency motions of the LFA‐1 I‐domain in the inactive apo‐state. We found in particular that α‐helix 7 is in a position in the apo‐closed state that cannot be fully described by any of the existing X‐ray structures, as it appears to be in dynamic exchange between different conformations. This type of motion seems to represent an inherent property of the LFA‐1 I‐domain and might be relevant for controlling the access to the allosteric binding pocket, as well as for the downward displacement of α‐helix 7 that is required for the activation of LFA‐1.
BACKGROUND Filipinos with prostate cancer (CaP) are at increased risk of harboring advanced stages and lower survival rates compared to other Asians. This study aims to investigate prevalence of ETS‐related gene (ERG) oncoprotein overexpression in Filipinos as surrogate of TMPRSS2‐ERG gene fusions, using a highly specific monoclonal antibody (ERG‐MAb), and conduct the first attempt to study the role of genetic alterations in the aggressive tumor biologic behaviour of CaP among Filipinos. METHODS This case‐matched, case‐control retrospective study evaluated ERG expression in Filipino patients diagnosed with CaP and its effect on stage and Gleason grade of their disease. Men who underwent radical prostatectomy for organ‐confined disease at the University of the Philippines‐Philippine General Hospital (UP‐PGH) comprised the organ‐confined cohort. Age‐matched adults who had trans‐rectal ultrasound‐guided prostate (TRUSP) biopsy or trans‐urethral resection of the prostate (TURP) with bilateral orchiectomy for T4 or stage IV CaP composed the advanced disease cohort. RESULTS Overall ERG expression frequency of 23.08% (N = 104) was demonstrated, with a higher rate observed in the advanced disease cohort (32.69%) compared to the organ‐confined group (13.46%). Furthermore, ERG overexpression was only detected among intermediate and high‐risk tumors. A high‐specificity (98.08%) of the ERG‐MAb for malignant prostatic cells was likewise demonstrated. CONCLUSIONS In contrast to higher ERG frequency in Western countries, it is much lower in Filipino CaP, which is similar to lower rates noted from other Asian countries. The 98.08% specificity of ERG oncoprotein for prostate tumor cells combined with its increased association in advanced disease, suggests for prognostic potential of ERG that may aid clinicians in treatment decisions for Filipino CaP patients. Prostate 74:1079–1085, 2014 . © 2014 Wiley Periodicals, Inc.
BACKGROUND Benign prostatic hyperplasia (BPH) is a result of urogenital aging. Recent studies suggest that an age‐related impairment of the blood supply to the lower urinary tract plays a role in the development of BPH and thus may be a contributing factor in the pathogenesis of BPH. The canine prostate is a model for understanding abnormal growth of the human prostate gland. We studied the efficacy of pulsed electromagnetic field therapy (PEMF) in dogs to modify prostate blood flow and evaluated its effect on BPH. METHODS PEMF (5 min, twice a day for 3 weeks) was performed on 20 dogs affected by BPH. Prostatic volume, Doppler assessment by ultrasonography, libido, semen quality, testosterone levels, and seminal plasma volume, composition and pH were evaluated before and after treatment. RESULTS The 3 weeks of PEMF produced a significant reduction in prostatic volume (average 57%) without any interference with semen quality, testosterone levels or libido. Doppler parameters showed a reduction of peripheral resistances and a progressive reduction throughout the trial of the systolic peak velocity, end‐diastolic velocity, mean velocity, mean, and peak gradient of the blood flow in the dorsal branch of the prostatic artery. The pulsatility index and the resistance index did not vary significantly over time. CONCLUSIONS The efficacy of PEMF on BPH in dogs, with no side effects, suggests the suitability of this treatment in humans and supports the hypothesis that impairment of blood supply to the lower urinary tract may be a causative factor in the development of BPH. Prostate 74:1132–1141, 2014. © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc.
Nanotechnology is an expanding area of study with potentially pivotal applications in a discipline as medicine where new biomedical active molecules or strategies are continuously developing. One of the principal drawbacks for the application of new therapies is the difficulty to cross membranes that represent the main physiological barrier in our body and in all living cells. Membranes are selectively permeable and allow the selective internalization of substances; generally, they form a highly impermeable barrier to most polar and charged molecules, and represent an obstacle for drug delivery, limiting absorption to specific routes and mechanisms. Viruses provide attracting suggestions for the development of targeted drug carriers as they have evolved naturally to deliver their genomes to host cells with high fidelity. A detailed understanding of virus structure and their mechanisms of entry into mammalian cells will facilitate the development and analysis of virus‐based materials for medical applications. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
Epitaxial β‐Ga 2 O 3 layers have been grown on β‐Ga 2 O 3 (100) substrates using metal‐organic vapor phase epitaxy. Trimethylgallium and pure oxygen or water were used as precursors for gallium and oxygen, respectively. By using pure oxygen as oxidant, we obtained nano‐crystals in form of wires or agglomerates although the growth parameters were varied in wide range. With water as an oxidant, smooth homoepitaxial β‐Ga 2 O 3 layers were obtained under suitable conditions. Based on thermodynamical considerations of the gas phase and published ab initio data on the catalytic action of the (100) surface of β‐Ga 2 O 3 we discuss the adsorption and incorporation processes that promote epitaxial layer growth. The structural properties of the β‐Ga 2 O 3 epitaxial layers were characterized by X‐ray diffraction pattern and high resolution transmission electron microscopy. As‐grown layers exhibited sharp peaks that were assigned to the monocline gallium oxide phase and odd reflections that could be assigned to stacking faults and twin boundaries, also confirmed by TEM. Shifts of the layer peak towards smaller 2 θ values with respect to the Bragg reflection for the bulk peaks have been observed. After post growth thermal treatment in oxygen‐containing atmosphere the reflections of the layers do shift back to the position of the bulk β‐Ga 2 O 3 peaks, which was attributed to significant reduction of lattice defects in the grown layers after thermal treatment.
We propose schemes for generating spin currents into a semiconductor by adiabatic or non‐adiabatic pumping of electrons through interacting quantum dots. The appeal of such schemes lies in the possibility to tune the pumping characteristics via gate voltages that control the properties of the quantum dot. The calculations are based on a systematic perturbation expansion in the tunnel‐coupling strength and the pumping frequency, expressed within a diagrammatic real‐time technique. Special focus is put on the possibility of pure spin pumping, i.e., of pumping spin currents without charge currents. Setup of a device for generating a spin current into a semiconductor by adiabatic or non‐adiabatic pumping of electrons through an interacting quantum dot.