78 research outputs found
Autosomal dominant polycystic kidney disease with diffuse proliferative glomerulonephritis - an unusual association: a case report and review of the literature
<p>Abstract</p> <p>Introduction</p> <p>Autosomal dominant polycystic kidney disease is an inherited disorder that is characterized by the development and growth of cysts in the kidneys and other organs. Urinary protein excretion is usually less than 1 g/24 hours in autosomal dominant polycystic kidney disease, and an association of nephrotic syndrome with this condition is considered rare. There are only anecdotal case reports of autosomal dominant polycystic kidney disease associated with nephrotic syndrome, with focal segmental glomerulosclerosis being the most commonly reported histopathological diagnosis. Nephrotic-range proteinuria in the presence of autosomal dominant polycystic kidney disease, with or without an accompanying decline in renal function, should be investigated by open renal biopsy to exclude coexisting glomerular disease. To the best of our knowledge, this is the first case of autosomal dominant polycystic kidney disease with histologically proven diffuse proliferative glomerulonephritis presenting with nephrotic-range proteinuria. No other reports of this could be found in a global electronic search of the literature.</p> <p>Case presentation</p> <p>We report the case of a 35-year-old Indo-Aryan man with autosomal dominant polycystic kidney disease associated with nephrotic syndrome and a concomitant decline in his glomerular filtration rate. Open renal biopsy revealed diffuse proliferative glomerulonephritis. An accurate diagnosis enabled us to manage him conservatively with a successful outcome, without the use of corticosteroid which is the standard treatment and the drug most commonly used to treat nephrotic syndrome empirically.</p> <p>Conclusion</p> <p>Despite the reluctance of physicians to carry out a renal biopsy on patients with autosomal dominant polycystic kidney disease, our case supports the idea that renal biopsy is needed in patients with polycystic kidney disease with nephrotic-range proteinuria to make an accurate diagnosis. It also illustrates the importance of open renal biopsy in planning appropriate treatment for patients with autosomal dominant polycystic kidney disease with nephrotic-range proteinuria. The treatment for various histological subtypes leading to nephrotic syndrome is different, and in this modern era we should practice evidence-based medicine and should avoid empirical therapy with its associated adverse effects.</p
Targeting OLFML3 in colorectal cancer suppresses tumor growth and angiogenesis, and increases the efficacy of anti-PD1 based immunotherapy
The role of the proangiogenic factor olfactomedin-like 3 (OLFML3) in cancer is unclear. To characterize OLFML3 expression in human cancer and its role during tumor development, we undertook tissue expression studies, gene expression analyses of patient tumor samples, in vivo studies in mouse cancer models, and in vitro coculture experiments. OLFML3 was expressed at high levels, mainly in blood vessels, in multiple human cancers. We focused on colorectal cancer (CRC), as elevated expression of OLFML3 mRNA correlated with shorter relapse-free survival, higher tumor grade, and angiogenic microsatellite stable consensus molecular subtype 4 (CMS4). Treatment of multiple in vivo tumor models with OLFML3-blocking antibodies and deletion of the Olfml3 gene from mice decreased lymphangiogenesis, pericyte coverage, and tumor growth. Antibody-mediated blockade of OLFML3 and deletion of host Olfml3 decreased the recruitment of tumor-promoting tumor-associated macrophages and increased infiltration of the tumor microenvironment by NKT cells. Importantly, targeting OLFML3 increased the antitumor efficacy of anti-PD-1 checkpoint inhibitor therapy. Taken together, the results demonstrate that OLFML3 is a promising candidate therapeutic target for CRC. </p
Modulation of COUP-TF Expression in a Cnidarian by Ectopic Wnt Signalling and Allorecognition
COUP transcription factors are required for the regulation of gene expression underlying development, differentiation, and homeostasis. They have an evolutionarily conserved function, being a known marker for neurogenesis from cnidarians to vertebrates. A homologue of this gene was shown previously to be a neuronal and nematocyte differentiation marker in Hydra. However, COUP-TFs had not previously been studied in a colonial cnidarian.We cloned a COUP-TF homologue from the colonial marine cnidarian Hydractinia echinata. Expression of the gene was analysed during normal development, allorecognition events and ectopic Wnt activation, using in situ hybridisation and quantitative PCR. During normal Hydractinia development, the gene was first expressed in post-gastrula stages. It was undetectable in larvae, and its mRNA was present again in putative differentiating neurons and nematocytes in post-metamorphic stages. Global activation of canonical Wnt signalling in adult animals resulted in the upregulation of COUP-TF. We also monitored a strong COUP-TF upregulation in stolons undergoing allogeneic interactions. COUP-TF mRNA was most concentrated in the tissues that contacted allogeneic, non-self tissues, and decreased in a gradient away from the contact area. Interestingly, the gene was transiently upregulated during initial contact of self stolons, but dissipated rapidly following self recognition, while in non-self contacts high expression levels were maintained.We conclude that COUP-TF is likely involved in neuronal/nematocyte differentiation in a variety of contexts. This has now been shown to include allorecognition, where COUP-TF is thought to have been co-opted to mediate allorejection by recruiting stinging cells that are the effectors of cytotoxic rejection of allogeneic tissue. Our findings that Wnt activation upregulates COUP-TF expression suggests that Wnts' role in neuronal differentiation could be mediated through COUP-TF
Targeting Vascular NADPH Oxidase 1 Blocks Tumor Angiogenesis through a PPARα Mediated Mechanism
Reactive oxygen species, ROS, are regulators of endothelial cell migration, proliferation and survival, events critically involved in angiogenesis. Different isoforms of ROS-generating NOX enzymes are expressed in the vasculature and provide distinct signaling cues through differential localization and activation. We show that mice deficient in NOX1, but not NOX2 or NOX4, have impaired angiogenesis. NOX1 expression and activity is increased in primary mouse and human endothelial cells upon angiogenic stimulation. NOX1 silencing decreases endothelial cell migration and tube-like structure formation, through the inhibition of PPARα, a regulator of NF-κB. Administration of a novel NOX-specific inhibitor reduced angiogenesis and tumor growth in vivo in a PPARα dependent manner. In conclusion, vascular NOX1 is a critical mediator of angiogenesis and an attractive target for anti-angiogenic therapies
Are Hox Genes Ancestrally Involved in Axial Patterning? Evidence from the Hydrozoan Clytia hemisphaerica (Cnidaria)
Background: The early evolution and diversification of Hox-related genes in eumetazoans has been the subject of conflicting hypotheses concerning the evolutionary conservation of their role in axial patterning and the pre-bilaterian origin of the Hox and ParaHox clusters. The diversification of Hox/ParaHox genes clearly predates the origin of bilaterians. However, the existence of a "Hox code' predating the cnidarian-bilaterian ancestor and supporting the deep homology of axes is more controversial. This assumption was mainly based on the interpretation of Hox expression data from the sea anemone, but growing evidence from other cnidarian taxa puts into question this hypothesis. Methodology/Principal Findings: Hox, ParaHox and Hox-related genes have been investigated here by phylogenetic analysis and in situ hybridisation in Clytia hemisphaerica, an hydrozoan species with medusa and polyp stages alternating in the life cycle. Our phylogenetic analyses do not support an origin of ParaHox and Hox genes by duplication of an ancestral ProtoHox cluster, and reveal a diversification of the cnidarian HOX9-14 genes into three groups called A, B, C. Among the 7 examined genes, only those belonging to the HOX9-14 and the CDX groups exhibit a restricted expression along the oralaboral axis during development and in the planula larva, while the others are expressed in very specialised areas at the medusa stage. Conclusions/Significance: Cross species comparison reveals a strong variability of gene expression along the oral-aboral axis and during the life cycle among cnidarian lineages. The most parsimonious interpretation is that the Hox code, collinearity and conservative role along the antero-posterior axis are bilaterian innovations
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A review of advanced air distribution methods - theory, practice, limitations and solutions
Ventilation and air distribution methods are important for indoor thermal environments and air quality. Effective distribution of airflow for indoor built environments with the aim of simultaneously offsetting thermal and ventilation loads in an energy efficient manner has been the research focus in the past several decades. Based on airflow characteristics, ventilation methods can be categorized as fully mixed or non-uniform. Non-uniform methods can be further divided into piston, stratified and task zone ventilation. In this paper, the theory, performance, practical applications, limitations and solutions pertaining to ventilation and air distribution methods are critically reviewed. Since many ventilation methods are buoyancy driving that confines their use for heating mode, some methods suitable for heating are discussed. Furthermore, measuring and evaluating methods for ventilation and air distribution are also discussed to give a comprehensive framework of the review
Renewable energy sources and energy efficiency for building's greening: From traditional village houses via high-rise residential building's BPS and RES powered co- and tri-generation towards net ZEBuildings and Cities, 2011 IEEE 3rd International Symposium on Exploitation of Renewable Energy Sources (EXPRES)
As an introduction to the current approaches to building's greening and sustainability this paper outlines the intrinsic harmony of the traditional village houses encompassing efficiency and balanced use of renewable materials and energy sources. Further paper reviews technical advances in integrating energy efficiency, solar and other renewable energy sources in new and existing buildings, to approach sustainable net Zero Energy Buildings, villages and cities. Paper stresses importance of the BPS (Building Performance Simulation) and Co-simulation in developing reliable method/engineering procedures for RES co-utilization and interwoven "energy mix" scenarios optimization, including existing buildings RES integrated refurbishment. Finally, presented are study results on the technical feasibility of efficient/cost-effective use of relatively low temperature geothermal waters for co-and tri-generation of electricity and heat for heating and/or cooling by absorption refrigeration for building integration. As a result of global warming a need for air conditioning is in extreme growth in Central and Southeastern Europe, as well as in many other regions in the world rich in low temperature geothermal waters <;100°C (<;212°F), and there is a growing interest to utilize these waters in an efficient and cost effective way. It is well known that Kalina thermodynamic cycle can convert relatively low temperature energy, at relatively low temperature difference towards environment, to mechanical power and further to electricity using as a working fluid mixture comprised of at least two different components (water and ammonia). However, its co-generation efficiency at the heat source temperatures below and about 100°C is too low. That was the reason to explore technical possibilities to expand the low-temperature Kalina cycle's geo-water utilization for co-and tri-generation based on the co-utilization hybridization of geothermal with solar or other renewable energy sources (RES)
Posterior lumbar interbody fusion combined with instrumented postero-lateral fusion: 5-year results in 60 patients
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