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Articles from this Volume

Marion Frankenberger, Christiane Eder, Thomas PJ Hofer, Irene Heimbeck, Kerstin Skokann, Gudrun Kaßner, Norbert Weber, Winfried Möller, and Loems Ziegler-Heitbrock

Small sputum macrophages represent highly active cells that increase in the airways in patients with inflammatory diseases like chronic obstructive pulmonary disease (COPD). It has often been reported that levels of cytokines, chemokines and proteases are increased in sputum supernatants of these patients. In COPD the small sputum macrophages may contribute to these supernatant proteins and recruit additional cells via specific chemokine expression patterns. Frankenberger et al. investigated the expression profile of chemokines in sputum macrophages obtained from COPD patients in comparison to cells from healthy donors and cells isolated after inhalation of lipolysaccharide (LPS). Results suggest an increase in small sputum macrophages in COPD patients, in asymptomatic smokers and after LPS inhalation in healthy volunteers. This indicates that small sputum macrophages may have different properties dependent on the circumstance of their induction.

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Supplementary Data PDF

Posted by Leah Caracappa on Aug 5, 2011 12:00 AM CDT

Wenjun Z Martini

Hemorrhagic coagulopathy, a blood clotting disorder, accounts for up to 40% of deaths in both civilian and military hospitals. Coagulation involves complex interactions and the underlying mechanisms remain unclear. In this work, Dr. Martini examines coagulation function at various time points using an experimental model of hemorrhage and resuscitation. Results show hemorrhage compromises platelet counts, clot strength and fibrinogen levels. However, 24 hours after hemorrhage and resuscitation, fibrinogen levels increased and contributed to restoration of clot strength despite a sustained platelet deficit. This work demonstrates the potential role of fibrinogen in restoring coagulation function in vivo.

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Posted by Leah Caracappa on Aug 4, 2011 12:00 AM CDT

David F Bishop, Sonia Clavero, Narla Mohandas, and Robert J Desnick

Congenital erythropoietic porphyria (CEP) is an autosomal recessive disorder of heme biosynthesis resulting from insufficient uroporphyrinogen III synthase (UROS) activity. Bishop et al. generated and characterized UROS knock-in models for several UROS mutations, including the most common mutation that causes CEP, C73R/C73R. Homozygous C73R mice were characterized clinically, biochemically and hematologically. The C73R/C73R mice had less than 1% residual UROS activity and severe hemolytic anemia, whereas the C73R/V99L mice, that had 10–15% residual UROS activity, were only mildly anemic. These data suggest that improving UROS activity by 10-15% may be sufficient to reverse pathology in human CEP patients.

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Posted by Leah Caracappa on Aug 3, 2011 12:00 AM CDT

Arie J Hoogendijk, Sander H Diks, Maikel P Peppelenbosch, Tom van der Poll, and Catharina W Wiel

Pneumonia is a severe disease associated with high morbidity and mortality. A major causative pathogen of pneumonia is the Gram-negative bacterium Klebsiella pneumoniae (K. pneumoniae). In this work, Hoogendijk et al. explore the signal transduction and kinase activities of K. pneumoniae using a systems biology approach and a kinase activity array. The authors identified and validated activity patterns of classic immune related kinases, such as p38 and p42 as well as other key regulators of cellular responses. This study suggests a role for SRC kinase in pneumonia and delineates a potential link of AKT and PKA with inflammatory responses. Kinase activity profiling may reveal new functional and pathogenetic mechanisms involved during various stages of pneumonia.

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Posted by Leah Caracappa on Aug 2, 2011 12:00 AM CDT

Dionysios V Chartoumpekis, Ioannis G Habeos, Panos G Ziros, Agathoklis I Psyrogiannis, Venetsana E Kyriazopoulou, and Athanasios G Papavassiliou

Fibroblast growth factor-21 (FGF21) is a protein involved in energy homeostasis and is mainly expressed in liver and adipose tissue. Brown adipose tissue (BAT) burns fatty acids for heat production to defend the body against cold and has recently been shown to be present in humans. While FGF21 is reportedly expressed in BAT, its role in metabolism has not been investigated. In this work, Chartoumpekis et al. examine the role of FGF21 in BAT and show both short-term exposure to the cold, as well as β3-adrenergic stimulation, cause significant induction of FGF21 mRNA in BAT. These initial findings may open the door to future therapeutics targeting FGF21 expression and BAT thermogenesis.

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Posted by Leah Caracappa on Aug 1, 2011 12:00 AM CDT

Walter Pavicic, Esa Perkiö, Sippy Kaur, and Päivi Peltomäki

MicroRNAs (miRNAs) are small noncoding RNAs that contribute to tumorigenesis by acting as oncogenes or tumor suppressor genes and may be important in the diagnosis, prognosis and treatment of cancer. Many miRNA genes have associated CpG islands, suggesting epigenetic regulation of their expression. Pavicic et al. examined over 150 patients from gastrointestinal and endometrial carcinomas to examine how methylation profiles apply to miRNA loci in cancer. The authors showed both hypermethylation and hypomethylation at classical tumor suppressor promoter in the same tumors. Methylation alterations at miRNA-associated CpG islands may have widespread biological and clinical significance.

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Posted by Leah Caracappa on Jul 16, 2011 12:00 AM CDT

Constance AM Finney, Cheryl A Hawkes, Dylan C Kain, Aggrey Dhabangi, Charles Musoke, Christine Cserti-Gazdewich, Tamas Oravecz, W Conrad Liles, and Kevin C Kain

Cerebral malaria (CM) is a life-threatening complication resulting from Plasmodium falciparum infection which is associated with excessive inflammatory responses and endothelial activation. Sphingosine 1-phosphate (S1P) is a signaling sphingolipid that regulates several cellular processes affected by CM, including inflammation and vascular endothelial homeostasis. Here, Finney et al. test whether S1P signaling is affected during malarial infection in a manner that deleteriously impacts host immune responses. Median plasma S1P levels were significantly decreased in Ugandan children with CM compared to children with uncomplicated malaria. Similarly, in an experimental model, improved outcome was observed in animals with diminished S1P-degrading enzyme activity. S1P levels were associated with improved outcome. Increased survival was also observed when an S1P receptor modulator was administered. Data indicates that these treatments preserve blood-brain barrier and endothelium integrity. These results suggest treatment approaches to enhance S1P-mediated activity may have potential clinical utility as adjunctive therapeutic strategies for individuals with malaria.

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Posted by Leah Caracappa on Jul 15, 2011 12:00 AM CDT

Lei Jiang, Yiu-Kay Lai, Jinfang Zhang, Hua Wang, Marie CM Lin, Ming-liang He, and Hsiang-fu Kung

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Protein S100P has been found to be overexpressed in a number of cancers including CRC and is considered a potential target for cancer therapy. The functional role and mechanism of action of S100P are not fully understood. Here, Jiang et al. use in vitro and in vivo methods to investigate this mechanism. Their results suggest S100P plays an important role in colon tumorigenesis and metastasis, and the comprehensive and comparative analyses of proteins associated with S100P may contribute to a further understanding of the downstream signaling cascade of S100P. These findings highlight new therapeutic targets for colon cancer treatment.

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Posted by Leah Caracappa on Jul 14, 2011 12:00 AM CDT

Yang-Hee Kim, Yu-Mee Wee, Monica-Y Choi, Dong-Gyun Lim, Song-Cheol Kim, and Duck-Jong Han

Mesenchymal stem cells (MSCs) have been suggested as immune modulators because of their therapeutic potential in transplantation. MSCs have also been proposed as treatments for autoimmune diseases, such as diabetes, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. In this work, Kim et al. evaluated the therapeutic potential of autologous MSCs in the prevention of graft rejection after allogeneic islet transplantation. The authors assessed the ability of MSCs to elicit an antiproliferative response in alloreactive lymphocytes and tested the immunosuppressive effect of MSCs in allogeneic islet transplantation. Results indicate the combined use of autologous MSCs and cyclosporine A exert a synergistic immunosuppressive effect which prolongs graft survival. This suggests a role for autologous MSCs as immune modulators and may suggest a new strategy for preventing and treating rejection after transplantation.

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Posted by Leah Caracappa on Jul 13, 2011 12:00 AM CDT

Yoshitsugu Takabatake, Xiao-Kang Li, Masayuki Mizui, Kenro Miyasato, Isao Matsui, Noritaka Kawada, Enyu Imai, Thomas Hünig, Shiro Takahara, Takashi Wada, Kengo Furuichi, Hiromi Rakugi, and Yoshitaka Isaka

Regulatory T (Treg) cells play an important role in the resolution of crescentic lomerulonephritis (GN), therefore, agents that increase Treg cells appear to be ideal for suppressing T-cell-mediated renal pathology. Takabatake et al. hypothesized that a superagonistic monoclonal antibody for CD28 (CD28-SA) which has been known to preferentially expand Treg cells in vivo, could prevent nephrotoxic serum-induced crescentic GN. Administration of CD28-SA attenuated crescent formation, proteinuria, and glomerular accumulation of macrophages and CD8+ T cells. These changes were accompanied by increased infiltration of Treg cells. This study demonstrates treatment with CD28-SA has a dramatic therapeutic effect on an experimental crescentic GN, potentially due to expansion and activation of Treg cells.

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Posted by Leah Caracappa on Jul 12, 2011 12:00 AM CDT
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