Years and Volumes

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Articles from this Volume

Eric B Milbrandt, Michael C Reade, MinJae Lee, Stephanie L Shook, Derek C Angus, Lan Kong, Melinda Carter, Donald M Yealy, and John A Kellum, for the GenIMS Investigators
Although coagulation abnormalities are common in severe pneumonia and sepsis, little is known regarding the presence or significance of these aberrations in patients with lesser illness severity. In this study, Milbrandt et al. hypothesized that coagulation abnormalities would increase with illness severity and poor outcomes. They examined coagulation abnormalities in over 900 subjects hospitalized with community-acquired pneumonia and measured plasma coagulation markers at emergency department presentation and daily during the first week of hospitalization. The authors confirmed the existence of coagulation abnormalities in patients with pneumonia with severe sepsis. They also observed considerable abnormalities in community-acquired pneumonia patients who avoided organ dysfunction associated with severe sepsis. The observed heterogeneity in the coagulation response underscores the challenge of fine-tuning coagulation-based therapies to treat infection and severe sepsis.

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Posted by MolMed Editor on Dec 5, 2009 12:00 AM CST
Laila Abdullah, Cheryl Luis, Daniel Paris, Benoit Mouzon, Ghania Ait-Ghezala, Andrew P Keegan, Duolao Wang, Fiona Crawford, and Michael Mullan
Clinical studies designed to understand and treat mild cognitive impairment (MCI) and Alzheimer’s disease (AD) endure challenges such as a lack of biomarkers for therapeutic outcome. One promising avenue in this sphere is the evaluation of peripheral beta-amyloid (Aβ) levels. However, variations in Aβ levels have been linked with vascular risk factors and the medications used to treat them, a fact which could downgrade the predictive utility of this protein. Using a longitudinal study design, Abdullah et al. determine whether a) systolic blood pressure, total cholesterol, triglycerides, serum creatinine or b) APOE, statin and anti-hypertensives influenced the predictive value of serum Aβ for MCI/AD over two years. They found that, once adjusted for vascular risk factors and medications, Aβ levels and their derived ratios are sensitive predictors of conversion to MCI/AD. This work could significantly impact how Aβ is used to predict clinical outcomes in MCI and AD.

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Posted by MolMed Editor on Dec 4, 2009 12:00 AM CST
Victoria E Parera, Rita H Koole, Gardi Minderman, Annie Edixhoven, Maria V Rossetti, Alcira Batlle, and Felix WM de Rooij
Erythropoietic Protoporphyria (EPP) is an inherited disorder of porphyrin metabolism that is caused by the decreased activity of ferrochelatase (FECH) and is characterized by photosensitivity. This disorder presents in early childhood with burning, swelling, itching and painful erythema in sun-exposed areas, and chronic liver disease may become a complication. To further study the molecular underpinnings of this disorder, Parera et al. characterized five Argentinean EPP families and detected three novel mutations, one deletion and two splicing mutations. The authors also confirmed two previously described mutations: C343T and 400delA, both of which produce stop codons in the FECH gene. These molecular studies contribute to our understanding of disease and may allow the accurate diagnosis of asymptomatic carriers as well as help identify prognostic factors for EPP.

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Posted by MolMed Editor on Dec 3, 2009 12:00 AM CST
Maria Gazouli, Eleni Katsantoni, Theodoros Kosteas, and Nicholas P Anagnou
Thalassemia is a hereditary hemolytic disease that is caused by reduced production of globin proteins in the blood. Gazouli et al. set out to define the regulatory elements controlling fetal γ-globin gene expression, because exogenous activation of this gene may have therapeutic benefit for thalassemia patients. The authors found that selective deletion of the Enh and F regulatory elements in the γ-globin gene loci resulted in high levels of fetal Aγ-globin gene expression in adult mice. These results identify specific repressing elements in the globin gene locus, a finding that may assist in the development of targeted therapeutic strategies for thalassemia and related disorders.

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Posted by MolMed Editor on Dec 2, 2009 12:00 AM CST
Kavin G Shah, Rongqian Wu, Asha Jacob, Steven A Blau, Youxin Ji, Weifeng Dong, Corrado Marini, Thanjavur S Ravikumar, Gene F Cappa, and Ping Wang
Individuals exposed to radiation are likely to suffer from genetic mutations and additional injuries such as sepsis. Ghrelin, a human hormone found mostly in the stomach, is protective in models of sepsis. However, ghrelin had not been tested in a two-hit model of radiation combined injury (RCI). Shah et al. tested ghrelin in RCI and found that serum levels and gene expression in the stomach were markedly decreased 20 hours after injury. Administration of human ghrelin markedly attenuated tissue injury, reduced pro-inflammatory cytokine levels and improved survival. These results suggest that human ghrelin could be a safe and effective treatment against radiation combined injury.

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Posted by MolMed Editor on Dec 1, 2009 12:00 AM CST
Laura Bazzichi, Lorenzo Ghiadoni, Alessandra Rossi, Melania Bernardini, Mario Lanza, Francesca De Feo, Camillo Giacomelli, Ilaria Mencaroni, Katia Raimo, Marco Rossi, Anna Maria Mazzone, Stefano Taddei, and Stefano Bombardieri
Patients with rheumatoid arthritis (RA) - a chronic, progressive inflammatory disease – suffer shorter lifespans and are at greater risk for cardiovascular disease due, in part, to increased incidence of atherosclerosis. Bazzichi and colleagues explore whether osteopontin, a protein implicated in the pathogenesis of RA and a potent inhibitor of vascular calcification, could form a bridge between these related but distinct disease forms. The authors employed pulse wave velocity (PWV) to measure arterial stiffness in RA patients and compared these values against patients with systemic sclerosis and healthy individuals. This study reports that osteopontin levels are significantly greater in RA patients versus the control groups, suggesting a connection between the actions of this protein and the onset of atherosclerosis. A deeper understanding of RA complications, such as atherosclerosis, may ultimately lead to better treatments and perhaps prevention of this chronic illness.

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Posted by MolMed Editor on Nov 5, 2009 12:00 AM CST
Amalia Forte, Maria Teresa Schettino, Mauro Finicelli, Marilena Cipollaro, Nicola Colacurci, Luigi Cobellis, and Umberto Galderisi
Endometriosis is an estrogen-dependent disease that affects 5 to 10% of women of reproductive age in the Western countries. In this study, Forte et al. examined the expression of embryonic stemness-related genes in human normal endometrium and pathological endometriotic samples. The authors found increased expression profiles of several genes in endometriosis as compared with normal endometrium. Based on these observations, the authors suggest that stem cells may play a role in the pathogenesis of endometriosis.

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Posted by MolMed Editor on Nov 4, 2009 12:00 AM CST
Marcus Maier, Emanuel V Geiger, Dirk Henrich, Carolyn Bendt, Sebastian Wutzler, Mark Lehnert, and Ingo Marzi

Severe trauma induces a systemic inflammatory response that can eventually lead to remote organ dysfunction and failure. The innate immune system represents the first line of posttraumatic immune response, initiating further cellular activation. As a result of multiple traumatic injuries, two dendritic cell subtypes, myeloid (MDC) and plasmacytoid (PDC), are activated, with significant upregulation of platelet factor 4 (PF4) expression occurring during the first day. The potential clinical relevance of PF4 alteration in multiple trauma is unknown. To address this question, Maier et al. analyzed PF4 expression and phenotypic alterations of dendritic cells following multiple severe trauma. The authors found the intracellular PF4 content in MDCs and PDCs was significantly elevated in trauma patients when compared to control subjects. Further, they demonstrated that PF4 concentrations in MDCs and PDCs significantly correlated with the injury severity score (ISS). The results describe an early and enduring posttraumatic activation of PF4 in dendritic cells and shed light on the role PF4 plays in the posttraumatic immune response.

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Posted by MolMed Editor on Nov 3, 2009 12:00 AM CST
Chao Tian, Roman Kosoy, Rami Nassir, Annette Lee, Pablo Villoslada, Lars Klareskog, Lennart Hammaström, Henri-Jean Garchon, Ann E Pulver, Michael Ransom, Peter K Gregersen, and Michael F Seldin

Substantial progress has been made in using genotypes to elucidate population genetic substructure and apply this information to association testing. As such, the definition of substructures in specific populations (e.g. European) and their applications in understanding complex phenotypes is becoming increasingly important. In this study, Tian et al. examined over 4000 subjects genotyped for 300,000 SNPs to provide further insight into relationships among European population groups and identify sets of SNP ancestry informative markers (AIMs). They found that most allele frequency differences between various European groups could be effectively controlled in analyses using these AIM sets. The authors argue that these results are widely applicable to ongoing studies centered on identifying specific disease susceptibility candidate regions. This work could increase the overall efficiency of European population genetics studies by negating the need to perform additional genome-wide SNP studies in additional subject sets.

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Posted by MolMed Editor on Nov 2, 2009 12:00 AM CST
Gang Zhu, Wei Yan, Hui-chan He, Xue-cheng Bi, Zhao-dong Han, Qi-shan Dai, Yong-kang Ye, Yu-xiang Liang, Jianye Wang, and Weide Zhong
While significant advances in the diagnosis and treatment of prostate cancer (PCa) have been made in the past 20 years, existing treatments still fall short of a cure. Elongation factor-1α (EF-1α) is critical for protein translation but has also been linked with the development and progression of various cancers. Even so, its role in prostate cancer specifically (PCa) is less clear. In this article, Zhu and colleagues explore this question by determining the influence of EF-1α in a high-grade metastatic PCa cells as. The authors show differential expression of EF-1α in PCa cells as well as in human tissue samples. Furthermore, they found that RNAi mediated suppression of EF-1α led to decreased proliferation, cell migration and invasion. This work suggests that EF-1α affects multiple processes involved in tumor progression and could therefore be a target for pharmacological intervention.

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Posted by MolMed Editor on Nov 1, 2009 12:00 AM CDT