MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Annual Review of Pathology' source. Sat, 20 Mar 2010 14:59:28 +0100 http://www.medworm.com/index.php?rid=3184583&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20078216%26dopt%3DAbstract Authors: Araya J, Nishimura SL Fibrogenic lung reactions occur as a common phenotype shared among disorders of heterogeneous etiologies. Even with a common etiology, the extent and pattern of fibrosis vary greatly among individuals, even within families, suggesting complex gene-environment interactions. The search for mechanisms shared among all fibrotic lung diseases would represent a major advance in the identification of therapeutic targets that could have a broad impact on lung health. Although it is difficult to grasp all of the complexities of the varied cell types and cytokine networks involved in lung fibrogenic responses, and to predict the biologic responses to the overexpression or deficiency of individual cytokines, a large body of evidence converges on a single common them... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=3184583 Tue, 19 Jan 2010 15:54:27 +0100 3184583 http://www.medworm.com/index.php?rid=3184582&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20078217%26dopt%3DAbstract Authors: Coppé JP, Desprez PY, Krtolica A, Campisi J Cellular senescence is a tumor-suppressive mechanism that permanently arrests cells at risk for malignant transformation. However, accumulating evidence shows that senescent cells can have deleterious effects on the tissue microenvironment. The most significant of these effects is the acquisition of a senescence-associated secretory phenotype (SASP) that turns senescent fibroblasts into proinflammatory cells that have the ability to promote tumor progression. PMID: 20078217 [PubMed - as supplied by publisher] (Source: Annual Review of Pathology) Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=3184582 Tue, 19 Jan 2010 15:54:25 +0100 3184582 http://www.medworm.com/index.php?rid=3184581&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20078218%26dopt%3DAbstract Authors: Marchiando AM, Graham WV, Turner JR Epithelia form barriers that are essential to life. This is particularly true in the intestine, where the epithelial barrier supports nutrient and water transport while preventing microbial contamination of the interstitial tissues. Along with plasma membranes, the intercellular tight junction is the primary cellular determinant of epithelial barrier function. Disruption of tight junction structure, as a result of specific protein mutations or aberrant regulatory signals, can be both a cause and an effect of disease. Recent advances have provided new insights into the extracellular signals and intracellular mediators of tight junction regulation in disease states as well as into the interactions of intestinal barrier function with mucosal im... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=3184581 Tue, 19 Jan 2010 15:54:21 +0100 3184581 http://www.medworm.com/index.php?rid=3184580&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20078219%26dopt%3DAbstract Authors: Tiniakos DG, Vos MB, Brunt EM Nonalcoholic fatty liver disease (NAFLD) is recognized as the leading cause of chronic liver disease in adults and children. NAFLD encompasses a spectrum of liver injuries ranging from steatosis to steatohepatitis with or without fibrosis. Fibrosis may progress to cirrhosis and complications including hepatocellular carcinoma. Histologic findings represent the complexity of pathophysiology. NAFLD is closely associated with obesity and is most closely linked with insulin resistance; the current Western diet, high in saturated fats and fructose, plays a significant role. There are several mechanisms by which excess triglycerides are acquired and accumulate in hepatocytes. Formation of steatotic droplets may be disordered in NAFLD. Visceral adipose t... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=3184580 Tue, 19 Jan 2010 15:54:18 +0100 3184580 http://www.medworm.com/index.php?rid=3184576&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20078220%26dopt%3DAbstract Authors: Young BC, Levine RJ, Karumanchi SA Preeclampsia is a systemic syndrome that occurs in 3 to 5% of pregnant women and classically manifests as new-onset hypertension and proteinuria after 20 weeks of gestation. Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality. The only known cure is delivery of the placenta. Recent discoveries, however, have led to important advances in understanding the pathogenesis of the condition. Placental antiangiogenic factors are upregulated and disrupt the maternal endothelium. This change in the normal angiogenic balance toward an antiangiogenic state can result in hypertension, proteinuria, glomerular endotheliosis, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and cerebral edema-the clinical si... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=3184576 Tue, 19 Jan 2010 15:54:15 +0100 3184576 http://www.medworm.com/index.php?rid=3184575&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20078221%26dopt%3DAbstract Authors: Haigis MC, Sinclair DA Aging is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as type II diabetes mellitus, neurodegenerative diseases, cancer, and cardiovascular disease. Historically, researchers have focused on investigating individual pathways in isolated organs as a strategy to identify the root cause of a disease, with hopes of designing better drugs. Studies of aging in yeast led to the discovery of a family of conserved enzymes known as the sirtuins, which affect multiple pathways that increase the life span and the overall health of organisms. Since the discovery of the first known mammalian sirtuin, SIRT1, 10 years ago, there have been major advances in our understanding of ... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=3184575 Tue, 19 Jan 2010 15:54:12 +0100 3184575 http://www.medworm.com/index.php?rid=3184574&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20078222%26dopt%3DAbstract Authors: Wallace DC, Fan W, Procaccio V Mitochondrial dysfunction has been linked to a wide range of degenerative and metabolic diseases, cancer, and aging. All these clinical manifestations arise from the central role of bioenergetics in cell biology. Although genetic therapies are maturing as the rules of bioenergetic genetics are clarified, metabolic therapies have been ineffectual. This failure results from our limited appreciation of the role of bioenergetics as the interface between the environment and the cell. A systems approach, which, ironically, was first successfully applied over 80 years ago with the introduction of the ketogenic diet, is required. Analysis of the many ways that a shift from carbohydrate glycolytic metabolism to fatty acid and ketone oxidative metabolism m... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=3184574 Tue, 19 Jan 2010 15:54:09 +0100 3184574 http://www.medworm.com/index.php?rid=3184573&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20078223%26dopt%3DAbstract Authors: Crum CP, McKeon FD The p53homolog p63has emerged as a gene with an enormously complex function that is distinct from that of p53. It encodes two distinct transcript isoforms that have a dramatic impact on replenishment of cutaneous epithelial stem cells and on ovarian germ cell survival. However, although these two fundamental roles of p63 attest to its powerful place in development, its other functions-specifically the apparent capacity of p63, when induced, to supervise the emergence of new cell populations in the breast, prostate, cervix, and upper reproductive tract-are shared by embryo and adult. These observed functions may only scratch the surface of a repertoire that has been postulated to encompass a range of cellular activities, as evidenced by the fact that p63 prot... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=3184573 Tue, 19 Jan 2010 15:54:05 +0100 3184573 http://www.medworm.com/index.php?rid=2899752&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19824827%26dopt%3DAbstract Authors: Lipscomb MF, Hutt J, Lovchik J, Wu T, Lyons CR Acute viral and bacterial infections in the lower respiratory tract are major causes of morbidity and mortality worldwide. The proper study of pulmonary infections requires interdisciplinary collaboration among physicians and biomedical scientists to develop rational hypotheses based on clinical studies and to test these hypotheses in relevant animal models. Animal models for common lung infections are essential to understand pathogenic mechanisms and to clarify general mechanisms for host protection in pulmonary infections, as well as to develop vaccines and therapeutics. Animal models for uncommon pulmonary infections, such as those that can be caused by category A biothreat agents, are also very important because the infrequenc... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=2899752 Mon, 12 Oct 2009 23:00:00 +0100 2899752 http://www.medworm.com/index.php?rid=2899751&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19824828%26dopt%3DAbstract Authors: Sgroi DC Preinvasive breast cancer accounts for approximately one-third of all newly diagnosed breast cancer cases in the United States and constitutes a spectrum of neoplastic lesions with varying degrees of differentiation and clinical behavior. High-throughput genetic, epigenetic, and gene-expression analyses have enhanced our understanding of the relationship of these early neoplastic lesions to normal breast tissue, and they strongly suggest that preinvasive breast cancer develops and evolves along two distinct molecular genetic and biological pathways that correlate with tumor grade. Although unique epigenetic and gene-expression changes are not observed in the tumor epithelial compartment during the transition from preinvasive to invasive disease, distinct molecular alt... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=2899751 Mon, 12 Oct 2009 23:00:00 +0100 2899751 http://www.medworm.com/index.php?rid=2790465&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19743960%26dopt%3DAbstract Authors: Salk JJ, Fox EJ, Loeb LA Cancer recapitulates Darwinian evolution. Mutations acquired during life that provide cells with a growth or survival advantage will preferentially multiply to form a tumor. As a result of The Cancer Genome Atlas Project, we have gathered detailed information on the nucleotide sequence changes in a number of human cancers. The sources of mutations in cancer are diverse, and the complexity of those found to be clonally present in tumors has increasingly made it difficult to identify key rate-limiting genes for tumor growth that could serve as potential targets for directed therapies. The impact of DNA sequencing on future cancer research and personalized therapy is likely to be profound and merits critical evaluation. Expected final online publication d... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=2790465 Wed, 09 Sep 2009 23:00:00 +0100 2790465 http://www.medworm.com/index.php?rid=2786520&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19737105%26dopt%3DAbstract Authors: Olsen RJ, Musser JM Necrotizing fasciitis, also known as the flesh-eating disease, is a severe invasive infection associated with very high rates of human morbidity and mortality. It is most commonly caused by group A Streptococcus (GAS), a versatile human pathogen that causes diseases ranging in severity from uncomplicated pharyngitis (or strep throat) to life-threatening infections such as necrotizing fasciitis. Herein, we review recent discoveries bearing on the molecular pathogenesis of GAS necrotizing fasciitis. Importantly, the integration of new technologies and the development of human-relevant animal models have markedly expanded our understanding of the key pathogen-host interactions underlying GAS necrotizing fasciitis. For example, we now know that GAS organisms se... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=2786520 Mon, 07 Sep 2009 23:00:00 +0100 2786520 http://www.medworm.com/index.php?rid=2786519&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19737106%26dopt%3DAbstract Authors: Gladson CL, Prayson RA, Lu WM Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease Volume 5 is January 24, 2010. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates. PMID: 19737106 [PubMed - as supplied by publisher] (Source: Annual Review of Pathology) Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=2786519 Mon, 07 Sep 2009 23:00:00 +0100 2786519 http://www.medworm.com/index.php?rid=2537534&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19400691%26dopt%3DAbstract Authors: Schmitz R, Stanelle J, Hansmann ML, Küppers R Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (HL) and lymphocytic and histiocytic (L&H) cells in nodular lymphocyte-predominant HL (NLPHL) are derived from germinal-center B cells. HRS cells have, however, largely lost their B cell phenotype and aberrantly express markers and transcriptional regulators of other hematolymphoid cell types. Deregulation of multiple signaling pathways and downstream transcription factors, including receptor tyrosine kinases, nuclear factor-kappa B (NF-kappaB), and Janus kinase/signal transducer and activator of transcription (JAK/STAT), is a further hallmark of HRS cells. These cells harbor genetic lesions that contribute to or cause increases in the activity of transcr... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=2537534 Sat, 27 Jun 2009 20:24:02 +0100 2537534 http://www.medworm.com/index.php?rid=2537533&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19400692%26dopt%3DAbstract Authors: Asa SL, Ezzat S Recently there has been significant progress in our understanding of pituitary development, physiology, and pathology. New information has helped to clarify the classification of pituitary tumors. Epidemiologic analyses have identified a much higher incidence of pituitary tumors than previously thought. We review the pathogenetic factors that have been implicated in pituitary tumorigenesis and the application of novel targeted therapies that underscore the increasingly important role of the pathologist in determining accurate diagnoses and facilitating appropriate treatment of patients with these disorders. PMID: 19400692 [PubMed - indexed for MEDLINE] (Source: Annual Review of Pathology) Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=2537533 Sat, 27 Jun 2009 20:24:02 +0100 2537533 http://www.medworm.com/index.php?rid=2537532&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19400693%26dopt%3DAbstract Authors: Noffsinger AE Until recently, two major forms of colorectal epithelial polyp were recognized: the adenoma and the hyperplastic polyp. Adenomas were perceived to represent the precursor to colorectal cancer, whereas hyperplastic polyps were viewed as innocuous lesions with no potential for progression to malignancy. We now recognize, however, that the lesions formerly classified as hyperplastic actually represent a heterogeneous group of polyps, some of which have a significant risk for neoplastic transformation. These serrated polyps include not only hyperplastic polyps but also traditional serrated adenomas and sessile serrated adenomas. These polyps demonstrate characteristic molecular alterations not commonly seen in colorectal adenomas, and they probably progress to colore... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=2537532 Sat, 27 Jun 2009 20:24:02 +0100 2537532 http://www.medworm.com/index.php?rid=2537531&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19400694%26dopt%3DAbstract Authors: Lee PL, Beutler E Hepcidin, a 25-amino-acid antimicrobial peptide, is the central regulator of iron homeostasis. Hepcidin transcription is upregulated by inflammatory cytokines, iron, and bone morphogenetic proteins and is downregulated by iron deficiency, ineffective erythropoiesis, and hypoxia. The iron transporter ferroportin is the cognate receptor of hepcidin and is destroyed as a result of interaction with the peptide. Except for inherited defects of ferroportin and hepcidin itself, all forms of iron-storage disease appear to arise from hepcidin dysregulation. Studies using multiple approaches have begun to delineate the molecular mechanisms that regulate hepcidin expression, particularly at the transcriptional level. Knowledge of the regulation of hepcidin by inflammati... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=2537531 Sat, 27 Jun 2009 20:24:02 +0100 2537531 http://www.medworm.com/index.php?rid=2537530&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19400695%26dopt%3DAbstract Authors: Kinney HC, Richerson GB, Dymecki SM, Darnall RA, Nattie EE The sudden infant death syndrome (SIDS) is the sudden death of an infant under one year of age that is typically associated with sleep and that remains unexplained after a complete autopsy and death scene investigation. A leading hypothesis about its pathogenesis is that many cases result from defects in brainstem-mediated protective responses to homeostatic stressors occurring during sleep in a critical developmental period. Here we review the evidence for the brainstem hypothesis in SIDS with a focus upon abnormalities related to the neurotransmitter serotonin in the medulla oblongata, as these are the most robust pathologic findings to date. In this context, we synthesize the human autopsy data with genetic, whole-a... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=2537530 Sat, 27 Jun 2009 20:24:02 +0100 2537530 http://www.medworm.com/index.php?rid=2537529&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19400696%26dopt%3DAbstract Authors: Ibrahim N, Haluska FG Melanoma is the deadliest form of skin cancer without an effective treatment. An understanding of the genetic basis of melanoma has recently shed light on some of the mechanisms of melanomagenesis. This review explores the major genes involved in familial and sporadic cutaneous melanoma with an emphasis on CDKN2A, CDK4, MC1R, and MAPK pathway targets (e.g., RAS and BRAF), apoptosis regulators (e.g., BCL-2, AKT, and APAF-1), and the tumor-suppressor genes TP53 and PTEN. New directions for therapeutics based on our current knowledge of the genes implicated in melanoma are also discussed. PMID: 19400696 [PubMed - indexed for MEDLINE] (Source: Annual Review of Pathology) Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=2537529 Sat, 27 Jun 2009 20:24:02 +0100 2537529 http://www.medworm.com/index.php?rid=1915644&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18954285%26dopt%3DAbstract Authors: Venkitaraman AR Single-gene disorders that predispose to cancer afford a unique window into the mechanisms of carcinogenesis. I argue here that the instability in chromosome structure and number provoked by inactivation of the breast cancer-susceptibility genes BRCA1 and BRCA2 arises from the distinct functions served by their products in DNA repair or mitosis, explains many features of cancer pathogenesis in this setting, and has important implications for treatment. The chromosomal instability model proposed here suggests a conceptual framework for the connections between chromosomal aberrations and cancer. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease Volume 4 is January 24, 2009. Please see http://www.annualreviews.org/cat... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1915644 Mon, 27 Oct 2008 04:00:00 +0100 1915644 http://www.medworm.com/index.php?rid=1915643&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18954286%26dopt%3DAbstract Authors: Imboden JB Rheumatoid arthritis is a chronic inflammatory polyarthritis whose etiology remains uncertain. Recently we have learned that autoimmunity to citrullinated protein antigens has specificity for rheumatoid arthritis and defines a clinically and genetically distinct form of the disease. Multiple genes contribute to disease susceptibility, with the HLA locus accounting for 30% to 50% of overall genetic risk. Five risk loci have been identified and validated: HLA-DRB1, PTPN22, STAT4, a region in 6q23, and the TRAF1/C5 locus. Also, there is renewed interest in the contribution of T cells to ongoing inflammation in rheumatoid arthritis. Autoantibodies to citrullinated protein epitopes are specific for rheumatoid arthritis, are associated with a more aggressive disease cours... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1915643 Mon, 27 Oct 2008 04:00:00 +0100 1915643 http://www.medworm.com/index.php?rid=1915642&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18954287%26dopt%3DAbstract Authors: Hogg JC, Timens W The pathogenesis of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune response to the inhalation of toxic particles and gases. Although tobacco smoking is the primary cause of this inhalation injury, many other environmental and occupational exposures contribute to the pathology of COPD. The immune inflammatory changes associated with COPD are linked to a tissue-repair and -remodeling process that increases mucus production and causes emphysematous destruction of the gas-exchanging surface of the lung. The common form of emphysema observed in smokers begins in the respiratory bronchioles near the thickened and narrowed small bronchioles that become the major site of obstruction in COPD. The mechanism(s) that ... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1915642 Mon, 27 Oct 2008 04:00:00 +0100 1915642 http://www.medworm.com/index.php?rid=1896660&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18928408%26dopt%3DAbstract Authors: Chen G, Shaw MH, Kim YG, Nuñez G The NOD-like receptors (NLRs) are a specialized group of intracellular receptors that represent a key component of the host innate immune system. Since the discovery of the first NLR almost 10 years ago, the study of this special class of microbial sensors has burgeoned; consequently, a better understanding of the mechanism by which these receptors recognize microbes and other danger signals and of how they activate inflammatory signaling pathways has emerged. Moreover, in addition to their primary role in host defense against invading pathogens, their ability to regulate nuclear factor-kappa B (NF-kappaB) signaling, interleukin-1-beta (IL-1beta) production, and cell death indicates that they are crucial to the pathogenesis of a variety of... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1896660 Fri, 17 Oct 2008 04:00:00 +0100 1896660 http://www.medworm.com/index.php?rid=1896659&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18928409%26dopt%3DAbstract Authors: McGivern DR, Lemon SM Hepatitis C virus (HCV) is the only known RNA virus with an exclusively cytoplasmic life cycle that is associated with cancer. The mechanisms by which it causes cancer are unclear, but chronic immunemediated inflammation and associated oxidative chromosomal DNA damage probably play a role. Compelling data suggest that the path to hepatocellular carcinoma in chronic hepatitis C shares some important features with the mechanisms of transformation employed by DNA tumor viruses. Interactions of viral proteins with key regulators of the cell cycle, the retinoblastoma-susceptibility protein, p53, and possibly DDX5 and DDX3 lead to enhanced cellular proliferation and may also compromise multiple cell-cycle checkpoints that maintain genomic integrity, thus settin... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1896659 Fri, 17 Oct 2008 04:00:00 +0100 1896659 http://www.medworm.com/index.php?rid=1866239&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18842101%26dopt%3DAbstract Authors: Lu B, Vogel H Neurodegenerative diseases are progressive disorders of the nervous system that affect specific cellular populations in the central and peripheral nervous systems. Although most cases are sporadic, genes associated with familial cases have been identified, thus enabling the development of animal models. Invertebrates such as Drosophila have recently emerged as model systems for studying mechanisms of neurodegeneration in several major neurodegenerative diseases. These models are also excellent in vivo systems for the testing of therapeutic compounds. Genetic studies using these animal models have provided novel insights into the disease process. We anticipate that further exploration of the animal models will further our understanding of mechanisms of neurodegene... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1866239 Wed, 08 Oct 2008 04:00:00 +0100 1866239 http://www.medworm.com/index.php?rid=1866238&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18842102%26dopt%3DAbstract Authors: Cho KR, Shih IM Ovarian carcinomas are a heterogeneous group of neoplasms and are traditionally subclassified based on type and degree of differentiation. Although current clinical management of ovarian carcinoma largely fails to take this heterogeneity into account, it is becoming evident that each major histological type has characteristic genetic defects that deregulate specific signaling pathways in the tumor cells. Moreover, within the most common histological types, the molecular pathogenesis of low-grade versus high-grade tumors appears to be largely distinct. Mouse models of ovarian carcinoma have been developed that recapitulate many of the morphological features, biological behavior, and gene expression patterns of selected subtypes of ovarian cancer. Such models wil... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1866238 Wed, 08 Oct 2008 04:00:00 +0100 1866238 http://www.medworm.com/index.php?rid=1863612&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18840072%26dopt%3DAbstract Authors: Mitra AP, Cote RJ Despite elaborate characterization of the risk factors, bladder cancer is still a major epidemiological problem whose incidence continues to rise each year. Urothelial carcinoma is now recognized as a disease of alterations in several cellular processes. The more prevalent, less aggressive, recurrent, noninvasive tumors are characterized by constitutive activation of the Ras-MAPK pathway. The less common but more aggressive invasive tumors, which have a higher mortality rate, are characterized by alterations in the p53 and retinoblastoma pathways. Several diagnostic tests have attempted to identify these molecular alterations in tumor cells exfoliated in the urine, whereas prognostic tests have tried to identify aberrations so as to predict tumor behavior and... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1863612 Tue, 07 Oct 2008 04:00:00 +0100 1863612 http://www.medworm.com/index.php?rid=1863611&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18840073%26dopt%3DAbstract Authors: Iacobuzio-Donahue CA Cancer is as much an epigenetic disease as it is a genetic disease, and epigenetic alterations in cancer often serve as potent surrogates for genetic mutations. Normal epigenetic modifications of DNA encompass three types of changes: chromatin modifications, DNA methylation, and genomic imprinting, each of which is altered in cancer cells. This review addresses the various epigenetic modifications that are pervasive among human tumors and traces the history of cancer epigenetics from the first observations of altered global methylation content to the recently proposed epigenetic progenitor model, which provides a common unifying mechanism for cancer development. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Diseas... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1863611 Tue, 07 Oct 2008 04:00:00 +0100 1863611 http://www.medworm.com/index.php?rid=1833868&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18817506%26dopt%3DAbstract Authors: Lee YS, Dutta A Within the past few years, studies on microRNA (miRNA) and cancer have burst onto the scene. Profiling of the miRNome (global miRNA expression levels) has become prevalent, and abundant miRNome data are currently available for various cancers. The pattern of miRNA expression can be correlated with cancer type, stage, and other clinical variables, so miRNA profiling can be used as a tool for cancer diagnosis and prognosis. miRNA expression analyses also suggest oncogenic (or tumor-suppressive) roles of miRNAs. miRNAs play roles in almost all aspects of cancer biology, such as proliferation, apoptosis, invasion/metastasis, and angiogenesis. Given that many miRNAs are deregulated in cancers but have not yet been further studied, it is expected that more miRNAs wil... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1833868 Thu, 25 Sep 2008 04:00:00 +0100 1833868 http://www.medworm.com/index.php?rid=1786654&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18783329%26dopt%3DAbstract Authors: Teitell MA, Pandolfi PP Acute lymphoblastic leukemia (ALL) is mainly a disease of childhood that arises from recurrent genetic insults that block precursor B and T cell differentiation and drive aberrant cell proliferation and survival. Recurrent defects including chromosomal translocations, aneuploidies, and gene-specific alterations generate molecular subgroups of B- and T-ALL with differing clinical courses and distinct responses to therapy. Recent discoveries arising from genome-wide surveys and adoptive transfer of leukemia-initiating cells have uncovered multiple gene copy number aberrations and have yielded new insight into at least one type of ALL-originating cell. Our understanding of the pathogenesis of ALL has benefited from genetically modified mouse models that re... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1786654 Wed, 10 Sep 2008 04:00:00 +0100 1786654 http://www.medworm.com/index.php?rid=1765459&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18767981%26dopt%3DAbstract Authors: Chalhoub N, Baker SJ PI3-kinase and PTEN are major positive and negative regulators, respectively, of the PI3-kinase pathway, which regulates growth, survival, and proliferation. These key signaling components are two of the most frequently mutated proteins in human cancers, resulting in unregulated activation of PI3K signaling and providing irrefutable genetic evidence of the central role of this pathway in tumorigenesis. PTEN regulates PI3K signaling by dephosphorylating the lipid signaling intermediate PIP3, but PTEN may have additional phosphatase-independent activities, as well as other functions in the nucleus. In this review, we highlight current work showing cancer-relevant complexities in the regulation of PTEN and PI3K activity, potential novel functions for PTEN, an... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1765459 Wed, 03 Sep 2008 04:00:00 +0100 1765459 http://www.medworm.com/index.php?rid=1743836&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18754744%26dopt%3DAbstract Authors: Pober JS, Min W, Bradley JR Vascular endothelial cells normally perform several key homeostatic functions such as keeping blood fluid, regulating blood flow, regulating macromolecule and fluid exchange with the tissues, preventing leukocyte activation, and aiding in immune surveillance for pathogens. Injury or cell death impairs or prevents conduct of these activities, resulting in dysfunction. Most endothelial cell death is apoptotic, involving activation of caspases, but nonapoptotic death responses also have been described. Stimuli that can cause endothelial injury or death include environmental stresses such as oxidative stress, endoplasmic reticulum stress, metabolic stress, and genotoxic stress, as well as pathways of injury mediated by the innate and adaptive immune sys... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1743836 Thu, 28 Aug 2008 04:00:00 +0100 1743836 http://www.medworm.com/index.php?rid=1743837&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18729723%26dopt%3DAbstract Authors: Pai SI, Westra WH The prototypic head and neck squamous cell carcinoma (HNSCC) arises from the mucosal lining of the upper aerodigestive tract, demonstrates squamous differentiation microscopically, involves older men with a long history of cigarette smoking and alcohol consumption, and is treated by multimodality therapy. HNSCC has long been regarded as a uniform disease process requiring a methodical and unwavering therapeutic approach. Divergence in epidemiologic trends among HNSCCs arising from different anatomic sites has introduced a view that, morphologic repetition aside, head and neck cancers form a heterogeneous group. This view has been supported at the molecular genetic level. A more complete understanding of the molecular genetics of head and neck cancer is provid... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1743837 Tue, 26 Aug 2008 04:00:00 +0100 1743837 http://www.medworm.com/index.php?rid=1727128&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18717641%26dopt%3DAbstract Authors: Mitchell RN Graft vascular disease (GVD) is the single most important long-term limitation to solid-organ transplantation. It is a concentric vascular intimal hyperplastic lesion composed of smooth muscle-like cells and associated matrix. GVD diffusely involves allograft vessels, eventually compromising perfusion and resulting in graft ischemia and failure. Animal models and an increasing sophistication in analyzing human GVD have provided important new insights into GVD pathogenesis. Innate and specific immune responses both participate in the initial vascular injury; GVD develops as a consequence of downstream chemokineand cytokine-effector pathways. Other significant developments in the field include recognition of the central pathogenic role played by interferon-gamma as w... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1727128 Thu, 21 Aug 2008 04:00:00 +0100 1727128 http://www.medworm.com/index.php?rid=1710678&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18702604%26dopt%3DAbstract Authors: Ward PA It has been an honor for me to write the prefatory article for Volume 4 of the Annual Review of Pathology: Mechanisms of Disease. I decided to describe the first 50 years of my career in research, which started with my entry into medical school. I have tried to outline the numerous scientific mentors who played such an important role in my development as an independent scientific investigator. In general, I have tried to avoid mention in the text of the many, many colleagues who carried out the scientific work, as I would inevitably fail to cite many of them. Rather, I have cited what I think are my most important publications, which identify many of these scientific colleagues. I am now engaged nearly full-time in research and look forward to the next period of resear... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1710678 Thu, 14 Aug 2008 04:00:00 +0100 1710678 http://www.medworm.com/index.php?rid=1586334&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039125%26dopt%3DAbstract Authors: Hebner C, Weaver VM, Debnath J Three-dimensional (3D) epithelial culture systems recreate the cardinal features of glandular epithelium in vivo and represent a valuable tool for modeling breast cancer initiation and progression in a structurally appropriate context. 3D models have emerged as a powerful method to interrogate the biological activities of cancer genes and oncogenic pathways, and recent studies have poignantly illustrated their utility in dissecting the emerging role of tensional force in regulating epithelial tissue homeostasis. We review how 3D models are being used to investigate fundamental cellular and biophysical mechanisms associated with breast cancer progression that have not been readily amenable to traditional genetic or biochemical analysis. PMID: ... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586334 Mon, 07 Jul 2008 16:25:37 +0100 1586334 http://www.medworm.com/index.php?rid=1586333&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039126%26dopt%3DAbstract Authors: Aster JC, Pear WS, Blacklow SC Recent discoveries indicate that gain-of-function mutations in the Notch1 receptor are very common in human T cell acute lymphoblastic leukemia/lymphoma. This review discusses what these mutations have taught us about normal and pathophysiologic Notch1 signaling, and how these insights may lead to new targeted therapies for patients with this aggressive form of cancer. PMID: 18039126 [PubMed - indexed for MEDLINE] (Source: Annual Review of Pathology) Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586333 Mon, 07 Jul 2008 16:25:37 +0100 1586333 http://www.medworm.com/index.php?rid=1586332&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039127%26dopt%3DAbstract Authors: Gilbertson RJ, Ellison DW Childhood tumors containing cells that are morphologically and functionally similar to normal progenitor cells provide fertile ground for investigating the links between development and cancer. In this respect, integrated studies of normal cerebellar development and the medulloblastoma, a malignant embryonal tumor of the cerebellum, have proven especially fruitful. Emerging evidence indicates that the different precursor cell populations that form the cerebellum and the cell signaling pathways that regulate its development likely represent distinct compartments from which the various subtypes of medulloblastoma arise. Definitive characterization of each medulloblastoma subtype will undoubtedly improve treatment of this disease and provide important in... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586332 Mon, 07 Jul 2008 16:25:37 +0100 1586332 http://www.medworm.com/index.php?rid=1586331&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039128%26dopt%3DAbstract Authors: Marchesi VT Molecular analysis in the service of research on human disease has finally come of age, as the chapters within this volume testify. Many technical advances, among them the development of recombinant DNA and its many applications, opened the way to study cells and processes that were unapproachable in the 1960s, when I first began my research career. The state of molecular biological studies at that time limited studies of human cell membrane proteins to experimental material most available and accessible, making the human erythrocyte membrane the favored target. I describe here how studies of red blood cell membrane proteins evolved and how results from those studies still inform present-day research. PMID: 18039128 [PubMed - indexed for MEDLINE] (Source: Annua... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586331 Mon, 07 Jul 2008 16:25:37 +0100 1586331 http://www.medworm.com/index.php?rid=1586330&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039129%26dopt%3DAbstract Authors: Kundu M, Thompson CB Autophagy is a process by which cytoplasmic components are sequestered in double membrane vesicles and degraded upon fusion with lysosomal compartments. In yeast, autophagy is activated in response to changes in the extracellular milieu. Depending upon the stimulus, autophagy can degrade cytoplasmic contents nonspecifically or can target the degradation of specific cellular components. Both of these have been adopted in higher eukaryotes and account for the expanding role of autophagy in various cellular processes, as well as contribute to the variation in cellular outcomes after induction of autophagy. In some cases, autophagy appears to be an adaptive response, whereas under other circumstances it is involved in cell death. In mammals, autophagy has been... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586330 Mon, 07 Jul 2008 16:25:37 +0100 1586330 http://www.medworm.com/index.php?rid=1586329&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039130%26dopt%3DAbstract Authors: Yankner BA, Lu T, Loerch P Aging is accompanied by cognitive decline in a major segment of the population and is the primary risk factor for Alzheimer's disease and other prevalent neurodegenerative disorders. Despite this central role in disease pathogenesis and morbidity, the aging of the brain has not been well understood at a molecular level. This review seeks to integrate what is known about age-related cognitive and neuroanatomical changes with recent advances in understanding basic molecular mechanisms that underlie aging. An important issue is how normal brain aging transitions to pathological aging, giving rise to neurodegenerative disorders. Toxic protein aggregates have been identified as potential contributory factors, including amyloid beta-protein in Alzheimer's ... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586329 Mon, 07 Jul 2008 16:25:37 +0100 1586329 http://www.medworm.com/index.php?rid=1586328&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039131%26dopt%3DAbstract Authors: Esfandiarei M, McManus BM Myocarditis is a cardiac disease associated with inflammation and injury of the myocardium. Several viruses have been associated with myocarditis in humans. However, coxsackievirus B3 is still considered the dominant etiological agent. The observed pathology in viral myocarditis is a result of cooperation or teamwork between viral processes and host immune responses at various stages of disease. Both innate and adaptive immune responses are crucial determinants of the severity of myocardial damage, and contribute to the development of chronic myocarditis and dilated cardiomyopathy following acute viral myocarditis. Advances in genomics and proteomics, and in the use of informatics and biostatistics, are allowing unbiased initial evaluations that can b... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586328 Mon, 07 Jul 2008 16:25:37 +0100 1586328 http://www.medworm.com/index.php?rid=1586327&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039132%26dopt%3DAbstract Authors: Walshe TE, D'Amore PA Although the terms ischemia and hypoxia are often used interchangeably, they represent distinct processes that result in different modulatory effects at the cellular level. Hypoxia is a reduction in oxygen delivery below tissue demand, whereas ischemia is a lack of perfusion, characterized not only by hypoxia but also by insufficient nutrient supply. Hypoxia can be either acute or chronic, and both are centrally regulated by hypoxia-inducible factor, a transcription factor that governs the expression of key response genes such as vascular endothelial growth factor and erythropoietin. Whereas severe chronic hypoxia can cause cell death, less-severe hypoxia can protect against subsequent damage, a phenomenon known as hypoxic conditioning. Several important ... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586327 Mon, 07 Jul 2008 16:25:37 +0100 1586327 http://www.medworm.com/index.php?rid=1586325&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039134%26dopt%3DAbstract Authors: Hershenson MB, Brown M, Camoretti-Mercado B, Solway J Airway smooth muscle plays a multifaceted role in the pathogenesis of asthma. We review the current understanding of the contribution of airway myocytes to airway inflammation, airway wall remodeling, and airflow obstruction in this prevalent disease syndrome. Together, these roles make airway smooth muscle an attractive target for asthma therapy. PMID: 18039134 [PubMed - indexed for MEDLINE] (Source: Annual Review of Pathology) Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586325 Mon, 07 Jul 2008 16:25:37 +0100 1586325 http://www.medworm.com/index.php?rid=1586324&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039135%26dopt%3DAbstract Authors: Novack DV, Teitelbaum SL Bone is a dynamic organ constantly remodeled to support calcium homeostasis and structural needs. The osteoclast is the cell responsible for removing both the organic and inorganic components of bone. It is derived from hematopoietic progenitors in the macrophage lineage and differentiates in response to the tumor necrosis factor family cytokine receptor activator of NF kappa B ligand. alpha v beta 3 integrin mediates cell adhesion necessary for polarization and formation of an isolated, acidified resorptive microenvironment. Defects in osteoclast function, whether genetic or iatrogenic, may increase bone mass but lead to poor bone quality and a high fracture risk. Pathological stimulation of osteoclast formation and resorption occurs in postmenopausal... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586324 Mon, 07 Jul 2008 16:25:37 +0100 1586324 http://www.medworm.com/index.php?rid=1586323&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039136%26dopt%3DAbstract Authors: Maitra A, Hruban RH The past two decades have witnessed an explosion in our understanding of pancreatic cancer, and it is now clear that pancreatic cancer is a disease of inherited (germ-line) and somatic gene mutations. The genes mutated in pancreatic cancer include KRAS2, p16/CDKN2A, TP53, and SMAD4/DPC4, and these are accompanied by a substantial compendium of genomic and transcriptomic alterations that facilitate cell cycle deregulation, cell survival, invasion, and metastases. Pancreatic cancers do not arise de novo, and three distinct precursor lesions have been identified. Experimental models of pancreatic cancer have been developed in genetically engineered mice, which recapitulate the multistep progression of the cognate human disease. Although the putative cell of or... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586323 Mon, 07 Jul 2008 16:25:37 +0100 1586323 http://www.medworm.com/index.php?rid=1586322&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039137%26dopt%3DAbstract Authors: Cheang MC, van de Rijn M, Nielsen TO DNA microarray platforms for gene expression profiling were invented relatively recently, and breast cancer has been among the earliest and most intensely studied diseases using this technology. The molecular signatures so identified help reveal the biologic spectrum of breast cancers, provide diagnostic tools as well as prognostic and predictive gene signatures, and may identify new therapeutic targets. Data are best presented in an open access format to facilitate external validation, the most crucial step in identifying robust, reproducible gene signatures suitable for clinical translation. Clinically practical applications derived from full expression profile studies already in use include reduced versions of microarrays representing ke... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586322 Mon, 07 Jul 2008 16:25:37 +0100 1586322 http://www.medworm.com/index.php?rid=1586321&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039138%26dopt%3DAbstract Authors: Taubenberger JK, Morens DM Influenza viruses are significant human respiratory pathogens that cause both seasonal, endemic infections and periodic, unpredictable pandemics. The worst pandemic on record, in 1918, killed approximately 50 million people worldwide. Human infections caused by H5N1 highly pathogenic avian influenza viruses have raised concern about the emergence of another pandemic. The histopathology of fatal influenza virus pneumonias as documented over the past 120 years is reviewed here. Strikingly, the spectrum of pathologic changes described in the 1918 influenza pandemic is not significantly different from the histopathology observed in other less lethal pandemics or even in deaths occurring during seasonal influenza outbreaks. PMID: 18039138 [PubMed - in... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586321 Mon, 07 Jul 2008 16:25:37 +0100 1586321 http://www.medworm.com/index.php?rid=1586320&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039139%26dopt%3DAbstract Authors: Lin JH, Walter P, Yen TS The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins, which, collectively, represent a large fraction of the total protein output of a mammalian cell. Therefore, the protein flux through the ER must be carefully monitored for abnormalities, including the buildup of misfolded proteins. Mammalian cells have evolved an intricate set of signaling pathways from the ER to the cytosol and nucleus, to allow the cell to respond to the presence of misfolded proteins within the ER. These pathways, known collectively as the unfolded protein response, are important for normal cellular homeostasis and organismal development and may also play key roles in the pathogenesis of many diseases. This review provides backgro... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586320 Mon, 07 Jul 2008 16:25:37 +0100 1586320 http://www.medworm.com/index.php?rid=1586319&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039140%26dopt%3DAbstract Authors: Corless CL, Heinrich MC Gastrointestinal stromal tumors (GISTs) form an interesting group of sarcomas whose unique pathobiology provides a model of how molecularly targeted therapeutics can have a major impact on patient welfare. Approximately 85% of GISTs are driven by oncogenic mutations in either of two receptor tyrosine kinases: KIT or platelet-derived growth factor receptor alpha. We review the pivotal relationship between specific mutations in these kinase genes, the origin and pathologic spectrum of GISTs, and the response of these tumors to treatment with kinase inhibitors such as imatinib and sunitinib. Mechanisms of resistance to kinase inhibitor therapy are discussed, and targets for the next generation of therapeutics are considered. The rapid evolution in our unde... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586319 Mon, 07 Jul 2008 16:25:37 +0100 1586319 http://www.medworm.com/index.php?rid=1586318&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039141%26dopt%3DAbstract Authors: Karpanen T, Alitalo K The lymphatic vasculature is essential for the maintenance of tissue fluid balance, immune surveillance, and adsorption fatty acids in the gut. The lymphatic vessels are also crucially involved in the pathogenesis of diseases such as tumor metastasis, lymphedema, and various inflammatory conditions. Attempts to control or treat these diseases have drawn a lot of interest to lymphatic vascular research during the past few years. Recently, several markers specific for lymphatic endothelium and models for lymphatic vascular research have been characterized, enabling great technical progress in lymphatic vascular biology, and many critical regulators of lymphatic vessel growth have been identified. Despite these significant achievements, our understanding of ... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586318 Mon, 07 Jul 2008 16:25:37 +0100 1586318 http://www.medworm.com/index.php?rid=1586317&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039142%26dopt%3DAbstract Authors: Chaerkady R, Pandey A Detailed and comprehensive characterization of proteins is a major goal of proteomics. This goal has become more realistic today with the latest high-resolution mass spectrometers capable of faster sequencing in a high-throughput fashion and with the emergence of new techniques such as protein and peptide microarrays. A promising area for discovery is the application of these advanced mass spectrometric and other quantitative proteomic methodologies to laboratory diagnosis. This review focuses on the role of proteomics in the development of new laboratory diagnostics and the implications for routine diagnosis and monitoring of diseases. PMID: 18039142 [PubMed - indexed for MEDLINE] (Source: Annual Review of Pathology) Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586317 Mon, 07 Jul 2008 16:25:37 +0100 1586317 http://www.medworm.com/index.php?rid=1586316&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039143%26dopt%3DAbstract Authors: Rock KL, Kono H When cells die in vivo, they trigger an inflammatory response. The ensuing hyperemia, leak of plasma proteins, and recruitment of leukocytes serve a number of useful functions in host defense and tissue repair. However, this response can also cause tissue damage and contribute to the pathogenesis of a number of diseases. Given the key role of inflammation in these processes, it is important to understand the underlying mechanisms that drive this response. Injured cells release danger signals that alert the host to cell death. Some of these molecules are recognized by cellular receptors that stimulate the generation of proinflammatory mediators. Other molecules released by dead cells stimulate the generation of mediators from extracellular sources. The resulting... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586316 Mon, 07 Jul 2008 16:25:37 +0100 1586316 http://www.medworm.com/index.php?rid=1586315&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039144%26dopt%3DAbstract We describe the molecular and cellular mechanisms believed to be responsible for the rejection of renal allografts, including acute T cell-mediated rejection, acute antibody-mediated (humoral) rejection, rejection mediated by the innate immune system, and chronic rejection. We present mechanisms of graft acceptance, including accommodation, regulation, and tolerance. Studies in animals have replicated many pathologic features of acute and chronic rejection. We illuminate the pathogenesis of human pathology by reflection from experimental models. PMID: 18039144 [PubMed - indexed for MEDLINE] (Source: Annual Review of Pathology) Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586315 Mon, 07 Jul 2008 16:25:37 +0100 1586315 http://www.medworm.com/index.php?rid=1586314&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18215115%26dopt%3DAbstract Authors: Zheng XL, Sadler JE Profound thrombocytopenia and microangiopathic hemolytic anemia characterize thrombotic microangiopathy, which includes two major disorders: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). TTP has at least three types: congenital or familial, idiopathic, and nonidiopathic. The congenital and idiopathic TTP syndromes are caused primarily by deficiency of ADAMTS13, owing to mutations in the ADAMTS13 gene or autoantibodies that inhibit ADAMTS13 activity. HUS is similar to TTP, but is associated with acute renal failure. Diarrhea-associated HUS accounts for more than 90% of cases and is usually caused by infection with Shiga-toxin-producing Escherichia coli (O157:H7). Diarrhea-negative HUS is associated with complement dysregulati... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586314 Mon, 07 Jul 2008 16:25:37 +0100 1586314 http://www.medworm.com/index.php?rid=1586313&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18233951%26dopt%3DAbstract Authors: Aguzzi A, Sigurdson C, Heikenwaelder M Prion diseases are infectious neurodegenerative diseases occurring in humans and animals with an invariably lethal outcome. One fundamental mechanistic event in prion diseases is the aggregation of aberrantly folded prion protein into large amyloid plaques and fibrous structures associated with neurodegeneration. The cellular prion protein (PrPC) is absolutely required for disease development, and prion knockout mice are not susceptible to prion disease. Prions accumulate not only in the central nervous system but also in lymphoid organs, as shown for new variant and sporadic Creutzfeldt-Jakob patients and for some animals. To date it is largely accepted that prions consist primarily of PrPSc, a misfolded and aggregated beta-sheet-rich is... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586313 Mon, 07 Jul 2008 16:25:37 +0100 1586313 http://www.medworm.com/index.php?rid=1586312&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18233952%26dopt%3DAbstract Authors: Bacac M, Stamenkovic I Metastasis is the result of cancer cell adaptation to a tissue microenvironment at a distance from the primary tumor. Metastatic cancer cells require properties that allow them not only to adapt to a foreign microenvironment but to subvert it in a way that is conducive to their continued proliferation and survival. Recent conceptual and technological advances have contributed to our understanding of the role of the host tissue stroma in promoting tumor cell growth and dissemination and have provided new insight into the genetic makeup of cancers with high metastatic proclivity. PMID: 18233952 [PubMed - indexed for MEDLINE] (Source: Annual Review of Pathology) Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586312 Mon, 07 Jul 2008 16:25:37 +0100 1586312 http://www.medworm.com/index.php?rid=1586311&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18233953%26dopt%3DAbstract Authors: Serhan CN, Yacoubian S, Yang R The popular view that all lipid mediators are pro-inflammatory arises largely from the finding that nonsteroidal anti-inflammatory drugs block the biosynthesis of prostaglandins. The resolution of inflammation was widely held as a passive event until recently, with the characterization of novel biochemical pathways and lipid-derived mediators that are actively turned on in resolution and that possess potent anti-inflammatory and proresolving actions. A lipid-mediator informatics approach was employed to systematically identify new families of endogenous local-acting mediators from omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) in resolving exudates, which also contain lipoxins and aspirin-triggered lipoxins g... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586311 Mon, 07 Jul 2008 16:25:37 +0100 1586311 http://www.medworm.com/index.php?rid=1586326&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039133%26dopt%3DAbstract Authors: Aguzzi A, Sigurdson C, Heikenwalder M blacksquare, square, filled Abstract Prion diseases are infectious neurodegenerative diseases occurring in humans and animals with an invariably lethal outcome. One fundamental mechanistic event in prion diseases is the aggregation of aberrantly folded prion protein into large amyloid plaques and fibrous structures associated with neurodegeneration. The cellular prion protein (PrP(C)) is absolutely required for disease development, and prion knockout mice are not susceptible to prion disease. Prions accumulate not only in the central nervous system but also in lymphoid organs, as shown for new variant and sporadic Creutzfeldt-Jakob patients and for some animals. To date it is largely accepted that prions consist primarily of PrP(Sc), a mis... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586326 Wed, 08 Aug 2007 04:00:00 +0100 1586326 http://www.medworm.com/index.php?rid=1586366&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039093%26dopt%3DAbstract We present the current understanding of endometrial carcinoma, from a molecular vantage point, highlighting what are presently thought to be the fundamental pathways involved in the development and progression of the major types of endometrial carcinoma. PMID: 18039093 [PubMed - as supplied by publisher] (Source: Annual Review of Pathology) Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586366 Wed, 28 Feb 2007 05:00:00 +0100 1586366 http://www.medworm.com/index.php?rid=1586362&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039097%26dopt%3DAbstract We present the current scientific evidence supporting the cancer stem cell hypothesis and discuss the experimental and therapeutic implications of the discovery of human cancer stem cells. PMID: 18039097 [PubMed - as supplied by publisher] (Source: Annual Review of Pathology) Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586362 Wed, 28 Feb 2007 05:00:00 +0100 1586362 http://www.medworm.com/index.php?rid=1586360&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039099%26dopt%3DAbstract Authors: Haldar K, Murphy SC, Milner DA, Taylor TE Abstract Malaria is an ancient disease that continues to cause enormous human morbidity and mortality. The life cycle of the causative parasite involves multiple tissues in two distinct host organisms, mosquitoes and humans. However, all the clinical symptoms of malaria are a consequence of infection of human erythrocytes. An understanding of the basic mechanisms that govern parasite invasion, remodeling, growth, and reinvasion of erythrocytes and the complex events leading to tissue pathology may yield new diagnostics and treatments for malaria. This approach is revealing a more complete picture of the most serious syndrome associated with this infection-cerebral malaria. We focus on the most recent understanding of the molecular basi... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586360 Wed, 28 Feb 2007 05:00:00 +0100 1586360 http://www.medworm.com/index.php?rid=1586357&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039102%26dopt%3DAbstract Authors: Laflamme MA, Zbinden S, Epstein SE, Murry CE Abstract Cell-based cardiac repair has emerged as an attractive approach to preventing or reversing heart failure resulting from myocyte dysfunction-e.g., due to infarction-and to enhancing the development of collaterals in patients with symptoms of myocardial ischemia. These two problems involve both overlapping and differing mechanisms, and these differences must be considered in cell-based therapies. In terms of myocardial dysfunction due to infarction, only committed cardiomyocytes have been shown to form new myocardium that is electrically coupled with the host heart. Despite this, multiple cell populations appear to improve function of the infarcted heart, including many that are clearly nonmyogenic. In terms of myocardial isc... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586357 Wed, 28 Feb 2007 05:00:00 +0100 1586357 http://www.medworm.com/index.php?rid=1586368&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039091%26dopt%3DAbstract Authors: Pitot HC Abstract Neoplasia is a heritably altered, relatively autonomous growth of tissue. Hepatocarcinogenesis, the pathogenesis of neoplasia in liver, as modeled in the rat exhibits three distinct, quantifiable stages: initiation, promotion, and progression. Simple mutations and/or epigenetic alterations may result in the irreversible stage of initiation. The stage of promotion results from selective enhancement of cell replication and selective inhibition of cellular apoptosis of initiated cells dependent on the genetic and/or epigenetic alterations of the latter. The irreversible stage of progression results from initial karyotypic alterations that evolve into greater degrees of genomic instability. The initial genomic alteration in the transition from promotion to progre... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586368 Mon, 01 Jan 2007 05:00:00 +0100 1586368 http://www.medworm.com/index.php?rid=1586367&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039092%26dopt%3DAbstract Authors: Waki H, Tontonoz P Abstract Obesity is a risk factor for type 2 diabetes, dyslipidemia, and cardiovascular disease. Dissection of the molecular mechanisms underlying obesity and its relationship to insulin resistance and the metabolic syndrome are essential for developing new strategies for prevention and treatment of these disorders. Both excess adipose tissue and lack of adipose tissue cause insulin resistance and dyslipidemia, suggesting that normal fat is required for the maintenance of systemic glucose and lipid homeostasis. Recent advances in obesity research have led to the recognition that adipose tissue is an active endocrine organ that secretes multiple bioactive factors termed adipokines. Secretion of adipokines provides a link between adipose tissue lipid accumulat... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586367 Mon, 01 Jan 2007 05:00:00 +0100 1586367 http://www.medworm.com/index.php?rid=1586365&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039094%26dopt%3DAbstract Authors: McNally EM, Pytel P Abstract Dystrophic muscle disease can occur at any age. Early- or childhood-onset muscular dystrophies may be associated with profound loss of muscle function, affecting ambulation, posture, and cardiac and respiratory function. Late-onset muscular dystrophies or myopathies may be mild and associated with slight weakness and an inability to increase muscle mass. The phenotype of muscular dystrophy is an endpoint that arises from a diverse set of genetic pathways. Genes associated with muscular dystrophies encode proteins of the plasma membrane and extracellular matrix, and the sarcomere and Z band, as well as nuclear membrane components. Because muscle has such distinctive structural and regenerative properties, many of the genes implicated in these disord... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586365 Mon, 01 Jan 2007 05:00:00 +0100 1586365 http://www.medworm.com/index.php?rid=1586364&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039095%26dopt%3DAbstract Authors: Chin AC, Parkos CA Abstract Neutrophil (also known as polymorphonuclear leukocyte, or PMN) transepithelial migration and accumulation at mucosal surfaces is a hallmark of many inflammatory conditions. This process correlates directly with clinical disease activity and epithelial injury. Currently, the mechanisms that define PMN epithelial interactions during an inflammatory response are not completely understood. This review provides an overview of the consequences of PMN infiltration into epithelial tissues and highlights molecular details of PMN epithelial interactions during transmigration. A better understanding of this process will likely provide new insights into developing organ-specific treatment strategies to reduce the deleterious consequences of epithelial inflammat... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586364 Mon, 01 Jan 2007 05:00:00 +0100 1586364 http://www.medworm.com/index.php?rid=1586363&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039096%26dopt%3DAbstract Authors: Kaelin WG Abstract von Hippel-Lindau disease, which is characterized by an increased risk of hemangioblastomas, clear cell renal carcinomas, and pheochromocytomas, is caused by inactivating mutations of the VHL tumor suppressor gene. The VHL gene product, pVHL, has multiple functions, but the best documented, and the one most clearly linked to tumor development, relates to its role as the substrate recognition module of a ubiquitin ligase complex that targets hypoxia-inducible factor (HIF) for destruction. pVHL function is often compromised in sporadic kidney cancers, and inhibitors of the HIF-responsive growth factor (vascular endothelial growth factor) are active against this disease. pVHL, by inhibiting atypical protein kinase C and hence JunB, also affects neuronal surviva... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586363 Mon, 01 Jan 2007 05:00:00 +0100 1586363 http://www.medworm.com/index.php?rid=1586361&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039098%26dopt%3DAbstract Authors: McClatchey AI Abstract As familial cancer syndromes, the neurofibromatoses exhibit complex phenotypes, comprising a range of tumor and nontumor manifestations. Although the three recognized forms of neurofibromatosis (NF1, NF2, and schwannomatosis) all feature the development of nervous system tumors, their underlying genetic bases are clearly distinct. The most prominent common feature of all three is the appearance of Schwann cell-initiated tumorigenesis of the peripheral nervous system. Recent progress in delineating the molecular function of the NF1- and NF2-encoded proteins, together with the development and use of manipulable mouse models, has led to important advances in understanding the pathogenesis of many features of neurofibromatosis. An important outcome of the st... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586361 Mon, 01 Jan 2007 05:00:00 +0100 1586361 http://www.medworm.com/index.php?rid=1586359&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039100%26dopt%3DAbstract Authors: Nagy JA, Dvorak AM, Dvorak HF Abstract Tumors, wounds, and chronic inflammatory disorders generate a new vascular supply by a process known as pathological angiogenesis. Whereas formation of the normal blood vasculature requires the interaction of many different agonists and inhibitors, including vascular endothelial growth factor-A (VEGF-A) and other members of the vascular permeability factor/VEGF family, pathological angiogenesis is a cruder, simpler process that can be replicated by a single VEGF-A isoform, VEGF-A(164/5). VEGF-A(164/5) induces the formation of several distinctly different types of new blood vessels that differ from normal blood vessels with respect to organization, structure, and function. Elucidating the properties of these new vessels has led to a better... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586359 Mon, 01 Jan 2007 05:00:00 +0100 1586359 http://www.medworm.com/index.php?rid=1586358&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039101%26dopt%3DAbstract Authors: Contag CH Abstract The emerging tools of in vivo molecular imaging are enabling dynamic cellular and molecular analyses of disease mechanisms in living animal models and humans. These advances have the potential to dramatically change a number of fields of study, including pathology, and to contribute to the development of regenerative medicine and stem cell therapies. The new tools of molecular imaging, which have already had a tremendous impact on preclinical studies, hold great promise for bringing important and novel information to the clinician and the patient. These approaches are likely to enable early diagnosis, rapid typing of molecular markers, immediate assessment of therapeutic outcome, and ready measures of the extent of tissue regeneration after damage. However, ... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586358 Mon, 01 Jan 2007 05:00:00 +0100 1586358 http://www.medworm.com/index.php?rid=1586356&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039103%26dopt%3DAbstract Authors: Wilson PD, Goilav B Abstract This review focuses on the mechanisms that underlie the development of human renal cystic diseases. A pathological, clinical, and pathophysiological overview is given. Initial analysis of the cell biology of inappropriate hyperproliferation accompanied by fluid secretion of cyst-lining epithelia has been followed by the elucidation of fundamental defects in epithelial polarity, cell-matrix and cell-cell interactions, and apoptosis, all of which are discussed. Identification of the genes and proteins responsible for several renal cystic diseases has led to a more complete understanding of defects in renal developmental programming, differentiation, and morphogenesis, all of which underlie cystic diseases of the kidney. PMID: 18039103 [PubMed - i... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586356 Mon, 01 Jan 2007 05:00:00 +0100 1586356 http://www.medworm.com/index.php?rid=1586355&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039104%26dopt%3DAbstract Authors: Rabinovitch M Abstract A variety of conditions can lead to the development of pulmonary arterial hypertension (PAH). Current treatments can improve symptoms and reduce the severity of the hemodynamic abnormality, but most patients remain quite limited, and deterioration in their condition necessitates a lung transplant. This review discusses current experimental and clinical studies that investigate the pathobiology of PAH. An emerging theme is the consideration of ways in which one might reverse the advanced occlusive structural changes in the pulmonary circulation causing PAH. The current debate concerning the role of regeneration through stem cells is presented. This review also highlights investigations in a number of laboratories relating the pathobiology of PAH to mutati... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586355 Mon, 01 Jan 2007 05:00:00 +0100 1586355 http://www.medworm.com/index.php?rid=1586354&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039105%26dopt%3DAbstract Authors: Braun J, Wei B Abstract The abundant bacteria and other microbial residents of the human intestine play important roles in nutrient absorption, energy metabolism, and defense against microbial pathogens. The mutually beneficial relationship of host and commensal microbiota represents an ancient and major coevolution in composition and mutual regulation of the human mucosa and the resident microbial community. Inflammatory bowel disease (IBD) is a set of chronic, relapsing inflammatory intestinal diseases in which rules of normal host-microbial interaction have been violated. This review considers the components of this host-microbial mutualism and the ways in which it is undermined by pathogenic microbial traits and by host immune and epithelial functions that confer to them s... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586354 Mon, 01 Jan 2007 05:00:00 +0100 1586354 http://www.medworm.com/index.php?rid=1586353&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039106%26dopt%3DAbstract Authors: Karnovsky MJ PMID: 18039106 [PubMed - indexed for MEDLINE] (Source: Annual Review of Pathology) Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586353 Sun, 01 Jan 2006 05:00:00 +0100 1586353 http://www.medworm.com/index.php?rid=1586352&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039107%26dopt%3DAbstract Authors: Guidotti LG, Chisari FV Among the many viruses that are known to infect the human liver, hepatitis B virus (HBV) and hepatitis C virus (HCV) are unique because of their prodigious capacity to cause persistent infection, cirrhosis, and liver cancer. HBV and HCV are noncytopathic viruses and, thus, immunologically mediated events play an important role in the pathogenesis and outcome of these infections. The adaptive immune response mediates virtually all of the liver disease associated with viral hepatitis. However, it is becoming increasingly clear that antigen-nonspecific inflammatory cells exacerbate cytotoxic T lymphocyte (CTL)-induced immunopathology and that platelets enhance the accumulation of CTLs in the liver. Chronic hepatitis is characterized by an inefficient T cel... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586352 Sun, 01 Jan 2006 05:00:00 +0100 1586352 http://www.medworm.com/index.php?rid=1586351&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039108%26dopt%3DAbstract Authors: Atherton JC Helicobacter pylori is the main cause of peptic ulceration, distal gastric adenocarcinoma, and gastric lymphoma. Only 15% of those colonized develop disease, and pathogenesis depends upon strain virulence, host genetic susceptibility, and environmental cofactors. Virulence factors include the cag pathogenicity island, which induces proinflammatory, pro-proliferative epithelial cell signaling; the cytotoxin VacA, which causes epithelial damage; and an adhesin, BabA. Host genetic polymorphisms that lead to high-level pro-inflammatory cytokine release in response to infection increase cancer risk. Pathogenesis is dependent upon inflammation, a Th-1 acquired immune response and hormonal changes including hypergastrinaemia. Antral-predominant inflammation leads to incre... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586351 Sun, 01 Jan 2006 05:00:00 +0100 1586351 http://www.medworm.com/index.php?rid=1586350&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039109%26dopt%3DAbstract Authors: Louis DN Malignant gliomas, the most common type of primary brain tumor, are a spectrum of tumors of varying differentiation and malignancy grades. These tumors may arise from neural stem cells and appear to contain tumor stem cells. Early genetic events differ between astrocytic and oligodendroglial tumors, but all tumors have an initially invasive phenotype, which complicates therapy. Progression-associated genetic alterations are common to different tumor types, targeting growth-promoting and cell cycle control pathways and resulting in focal hypoxia, necrosis, and angiogenesis. Knowledge of malignant glioma genetics has already impacted clinical management of these tumors, and researchers hope that further knowledge of the molecular pathology of malignant gliomas will resu... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586350 Sun, 01 Jan 2006 05:00:00 +0100 1586350 http://www.medworm.com/index.php?rid=1586349&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039110%26dopt%3DAbstract Authors: Tlsty TD, Coussens LM Abstract In the past 25 years, a majority of cancer studies have focused on examining functional consequences of activating and/or inactivating mutations in critical genes implicated in cell cycle control. These studies have taught us a great deal about the functions of oncogenes and tumor suppressor genes and the signaling pathways regulating cell proliferation and/or cell death. However, such studies have largely ignored the fact that cancers are heterogeneous cellular entities whose growth is dependent upon reciprocal interactions between genetically altered "initiated" cells and the dynamic microenvironment in which they live. This review highlights the aspects of cancer development that, like organogenesis during embryonic development and tissue repa... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586349 Sun, 01 Jan 2006 05:00:00 +0100 1586349 http://www.medworm.com/index.php?rid=1586348&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039111%26dopt%3DAbstract Authors: Skovronsky DM, Lee VM, Trojanowski JQ Abstract Neurodegenerative diseases as diverse as Alzheimer's, Parkinson's, and Creutzfeldt-Jakob disease share a common pathogenetic mechanism involving aggregation and deposition of misfolded proteins, which leads to progressive central nervous system disease. Although the type of aggregated protein and the regional and cellular distribution of deposition vary from disease to disease, these disorders may all be linked by similar pathways of protein aggregation with fibril formation and amyloid deposition. This perspective on pathogenesis suggests that a wide variety of neurodegenerative diseases can be grouped mechanistically as brain amyloidoses, an outlook that yields novel insights into potential therapeutic approaches that may be app... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586348 Sun, 01 Jan 2006 05:00:00 +0100 1586348 http://www.medworm.com/index.php?rid=1586347&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039112%26dopt%3DAbstract This article defines criteria for considering an infection as truly endothelium-targeted and reviews the literature that offers insights into the pathogenesis of human endothelial-target infections. PMID: 18039112 [PubMed - indexed for MEDLINE] (Source: Annual Review of Pathology) Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586347 Sun, 01 Jan 2006 05:00:00 +0100 1586347 http://www.medworm.com/index.php?rid=1586346&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039113%26dopt%3DAbstract Authors: Srivastava D Developmental heart disorders are the most common of all human birth defects and occur in nearly one percent of the population. Survivors of congenital heart malformations are an increasing population, and it is becoming clear that genetic mutations that cause developmental anomalies may result in cardiac dysfunction later in life. This review highlights the progress in understanding the underlying molecular basis for cardiac formation and how disruption of the intricate steps of cardiogenesis can lead to congenital heart defects. The lessons learned from examining the early steps of heart formation are essential for informing the prevention of malformations and their long-term consequences, as well as for approaches to guide stem cells into cardiac lineages. ... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586346 Sun, 01 Jan 2006 05:00:00 +0100 1586346 http://www.medworm.com/index.php?rid=1586345&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039114%26dopt%3DAbstract Authors: Gao H, Neff T, Ward PA Modern techniques of cell and molecular biology have rapidly uncovered the mechanisms underlying inflammatory injury of the lung. This expanding knowledge (which includes an understanding of complement, cell surface receptors, cytokines and chemokines, transcription factors, oxidants, proteinases, and endogenous inhibitors, as well as the role of leukocyte adhesion-promoting molecules) has provided new insights into the inflammatory system in general, as well as in the context of lung injury. In this review, we summarize recent progress in understanding the regulation of lung inflammation by using immunoglobulin G (IgG) immune complex-induced lung injury as a model. These studies have provided information on the role of various inflammatory mediators and... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586345 Sun, 01 Jan 2006 05:00:00 +0100 1586345 http://www.medworm.com/index.php?rid=1586344&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039115%26dopt%3DAbstract Authors: Tomlins SA, Rubin MA, Chinnaiyan AM Prostate cancer displays considerable clinical, morphological, and biological heterogeneity. Classical genetic techniques have provided only limited information about the pathogenesis of prostate cancer progression. Nevertheless, several candidate genes and pathways have been implicated in prostate cancer development. High-throughput techniques have exponentially expanded the number of candidate genes, including some whose role in prostate cancer pathogenesis has been studied. However, the techniques used to study the prostate cancer genome, transcriptome, and proteome generate massive amounts of data that have yet to be integrated and explored. To move beyond candidate gene identification and develop a comprehensive understanding of cancer ... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586344 Sun, 01 Jan 2006 05:00:00 +0100 1586344 http://www.medworm.com/index.php?rid=1586343&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039116%26dopt%3DAbstract Authors: Ganem D Kaposi's sarcoma (KS) has long been suspected of having an infectious etiology on the basis of its unusual epidemiology, histopathology, and natural history. Nearly a decade ago, a novel herpesviral genome was discovered in KS biopsies, and since that time strong epidemiologic evidence has accumulated correlating infection with this KS-associated herpesvirus (KSHV, also known as human herpesvirus 8) with the development of the disease. Here we review the evidence linking KSHV infection to KS risk and discuss current notions of how KSHV gene expression promotes the development of this remarkable neoplasm. These studies show that both latent and lytic viral replicative cycles contribute significantly-but differently-to KS development. The studies also highlight mechanist... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586343 Sun, 01 Jan 2006 05:00:00 +0100 1586343 http://www.medworm.com/index.php?rid=1586342&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039117%26dopt%3DAbstract Authors: Hansson GK, Robertson AK, Söderberg-Nauclér C Atherosclerosis, the cause of myocardial infarction, stroke, and ischemic gangrene, is an inflammatory disease. The atherosclerotic process is initiated when cholesterol-containing low-density lipoproteins accumulate in the intima and activate the endothelium. Leukocyte adhesion molecules and chemokines promote recruitment of monocytes and T cells. Monocytes differentiate into macrophages and upregulate pattern recognition receptors, including scavenger receptors and toll-like receptors. Scavenger receptors mediate lipoprotein internalization, which leads to foam-cell formation. Toll-like receptors transmit activating signals that lead to the release of cytokines, proteases, and vasoactive molecules. T cells in lesions re... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586342 Sun, 01 Jan 2006 05:00:00 +0100 1586342 http://www.medworm.com/index.php?rid=1586341&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039118%26dopt%3DAbstract Authors: Wistuba II, Gazdar AF From histological and biological perspectives, lung cancer is a complex neoplasm. Although the sequential preneoplastic changes have been defined for centrally arising squamous carcinomas of the lung, they have been poorly documented for the other major forms of lung cancers, including small cell lung carcinoma and adenocarcinomas. There are three main morphologic forms of preneoplastic lesions recognized in the lung: squamous dysplasias, atypical adenomatous hyperplasia, and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. However, these lesions account for the development of only a subset of lung cancers. Several studies have provided information regarding the molecular characterization of lung preneoplastic changes, especially for squamous... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586341 Sun, 01 Jan 2006 05:00:00 +0100 1586341 http://www.medworm.com/index.php?rid=1586340&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039119%26dopt%3DAbstract Authors: Kwoh C, Shannon MB, Miner JH, Shaw A Nonimmune glomerulopathies are an area of significant research. This review discusses the development of focal segmental glomerulosclerosis, with particular attention to the role of the podocyte in the initiation of glomerulosclerosis and the contribution to glomerulosclerosis from capillary hypertension and soluble factors such as transforming growth factor beta, platelet-derived growth factor, vascular endothelial growth factor, and angiotensin. The effects of these factors on endothelial and mesangial cells are also discussed. In addition, we review our current understanding of the slit diaphragm (a specialized cell junction found in the kidney), slit diaphragm-associated proteins (including nephrin, podocin, alpha-actinin-4, CD2-associa... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586340 Sun, 01 Jan 2006 05:00:00 +0100 1586340 http://www.medworm.com/index.php?rid=1586339&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039120%26dopt%3DAbstract Authors: Kutok JL, Wang F The association between Epstein-Barr virus (EBV) and a large number of benign and malignant diseases is unique among DNA viruses. Within infected tissues, proteins that are expressed during the normal lytic and latent viral life cycle lead to cellular alterations that contribute to these EBV-associated diseases. Although the early events of EBV infection are poorly understood, increasing knowledge of the viral processes that govern viral latency has shed light upon the potential mechanisms by which EBV infection can lead to cellular transformation. Our current understanding of the role of EBV in the development of Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and other EBV-associated diseases is discussed. PMID: 18039120 [PubMed - indexed f... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586339 Sun, 01 Jan 2006 05:00:00 +0100 1586339 http://www.medworm.com/index.php?rid=1586338&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039121%26dopt%3DAbstract Authors: Dong Z, Saikumar P, Weinberg JM, Venkatachalam MA Loss of Ca(2+) homeostasis, often in the form of cytoplasmic increases, leads to cell injury. Depending upon cell type and the intensity of Ca(2+) toxicity, the ensuing pathology can be reversible or irreversible. Although multiple destructive processes are activated by Ca(2+), lethal outcomes are determined largely by Ca(2+)-induced mitochondrial permeability transition. This form of damage is primarily dependent upon mitochondrial Ca(2+) accumulation, which is regulated by the mitochondrial membrane potential. Retention of the mitochondrial membrane potential during Ca(2+) increases favors mitochondrial Ca(2+) uptake and overload, resulting in mitochondrial permeability transition and cell death. In contrast, dissipation of m... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586338 Sun, 01 Jan 2006 05:00:00 +0100 1586338 http://www.medworm.com/index.php?rid=1586337&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039122%26dopt%3DAbstract Authors: van de Rijn M, Fletcher JA Sarcomas form a highly diverse group of rare tumors that are derived from connective tissue. More than 100 different malignant and benign soft tissue neoplasms can be recognized by histologic examination. Few diagnostic markers exist, and the cell of origin for many soft tissue tumors is unknown. The accurate diagnosis of many of these tumors therefore remains a challenge. The study of sarcomas has yielded many insights that can be applied to other neoplasms such as carcinoma. For example, the success of the treatment of gastrointestinal stromal tumor with Imatinib has led to an increased effort to find targeted therapies for other malignancies. Here we describe the known molecular changes in a number of sarcomas and focus on novel scientific approac... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586337 Sun, 01 Jan 2006 05:00:00 +0100 1586337 http://www.medworm.com/index.php?rid=1586336&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039123%26dopt%3DAbstract Authors: Munford RS Abstract Although Gram-negative bacteria have often been implicated in the pathogenesis of severe sepsis and septic shock, how they trigger these often lethal syndromes is uncertain. In particular, the role played by blood-borne bacteria is controversial. This review considers two alternatives. In the first, circulating Gram-negative bacteria induce toxic reactions directly within the vasculature; in the second, the major inflammatory stimulus occurs in local extravascular sites of infection and circulating bacteria contribute little to inducing toxic responses. Evidence for each alternative is found in the literature. Bacteremia and severe sepsis are not so closely linked that the most striking cases can be a model for the rest. Intravascular and extravascular trig... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586336 Sun, 01 Jan 2006 05:00:00 +0100 1586336 http://www.medworm.com/index.php?rid=1586335&cid=s_37532_32_f&fid=37532&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18039124%26dopt%3DAbstract Authors: McKerrow JH, Caffrey C, Kelly B, Loke P, Sajid M Parasitic diseases represent major global health problems of immense proportion. Schistosomiasis, malaria, leishmaniasis, Chagas disease, and African sleeping sickness affect hundreds of millions of people worldwide, cause millions of deaths annually, and present an immense social and economic burden. Recent advances in genomic analysis of several of the major global parasites have revealed key factors involved in the pathogenesis of parasite diseases. Among the major virulence factors identified are parasite-derived proteases. This review focuses on the direct role of proteases in disease pathogenesis. Well-characterized examples of the roles proteases play in pathogenesis include their involvement in invasion of the host by pa... Annual Review of Pathology journals http://www.medworm.com/rss/comments.php?id=1586335 Sun, 01 Jan 2006 05:00:00 +0100 1586335