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May 16, 2008 DNA polymerases in adaptive immunity
  To cope with an unpredictable variety of potential pathogenic insults, the immune system must generate an enormous diversity of recognition structures, and it does so by making stepwise modifications at key genetic loci in each lymphoid cell. These modifications proceed through the action of lymphoid-specific proteins acting together with the general DNA-repair machinery of the cell. Strikingly, these general mechanisms are usually diverted from their normal functions, being used in rather atypical ways in order to privilege diversity over accuracy. In this Review, we focus on the contribution of a set of DNA polymerases discovered in the past decade to these unique DNA transactions.
May 15, 2008 A Common Progenitor at the Heart of Development
  Formation of the heart requires the coordinated functions of cardiac myocytes, smooth muscle cells, endothelial cells, and connective tissue elements. Several recent studies now reveal that these different cell types arise from a common progenitor (). These findings raise interesting questions about the lineage relationships of cardiovascular progenitor cell populations and suggest possibilities for cardiac repair in both congenital and acquired heart disease.
May 14, 2008 Tumor-Specific T-Cell Memory: Clearing the Regulatory T-Cell Hurdle
  Antitumor immune responses can be stimulated by interfering with regulatory T-cell (T(reg)) function. However, this effect is short lived unless T-cell memory to tumor antigens can be generated. Our recent studies show that T(reg) cells not only limit primary responses to tumor/self-antigens in tumor-bearing hosts but also prevent the natural generation of T-cell memory to such antigens. Here, we discuss the role of T(reg) cells in suppressing T-cell memory after surgical excision of tumors and the potential clinical benefits of overcoming this suppression.
May 13, 2008 Chemogenomics and biotechnology
  A robust knowledge of the interactions between small molecules and specific proteins aids the development of new biotechnological tools and the identification of new drug targets, and can lead to specific biological insights. Such knowledge can be obtained through chemogenomic screens. In these screens, each small molecule from a chemical library is applied to each cell type from a library of cells, and the resulting phenotypes are recorded. Chemogenomic screens have recently become very common and will continue to generate large amounts of data. The interpretation of this data will occupy biologists and chemists alike for some time to come. This review discusses methods for the acquisition and interpretation of chemogenomic data, in addition to possible applications of chemogenomics in biotechnology.
May 12, 2008 Integrating immunity: The immunculus and self-reactivity
  The most important theoretical contribution to autoimmunity was the clonal selection theory of Burnet. This thesis, including the unique terminology of the forbidden clone, laid the foundation for discussions and research regarding self-reactivity and remains the foundation for discussions of thymic education. There were, however, additional works which suggested that autoantibodies, coined natural autoantibodies, exist even in healthy individuals. The ontogenic appearance of the immune system was a series of events that were developed in evolution to recognize the biologic essence of complementary antigen recognition and elimination of foreign pathogens. Interestingly, microbial and host epitopes are often highly conserved in evolution and this homology has functional significance for both the microbe and the host. Further, while the immune system is a series of interconnecting pathways, in reality it is also composed of promiscuous and sometimes independent pathways. The interaction between antibodies and epitopes is determined not necessarily by a primary chemical structure, but more likely by the stereochemistry of the antigen. As such, we increasingly recognize a large repertoire of natural autoantibodies and the development of autoimmune disease requires more than an innocent bystander mimicry pathway, but rather expansion of lymphocytic populations that are either already naturally present, or derived from genetic/acquired defects in immune regulation. We suggest that discussion of loss of tolerance should not include focus on the classic terminology of peripheral versus central tolerance but must consider the integrative activity of the immune system and the balance between well-balanced self-reactivity and the processing of foreign antigens. These events, while primarily theoretical, provide a framework to understand the elements involved in genetic susceptibility to autoimmunity.
May 11, 2008 A role for microRNAs in the development of the immune system and in the pathogenesis of cancer
  MicroRNAs are a growing class of endogenous small non-coding RNAs that regulate gene expression by binding to target messenger RNAs and inducing translational repression, cleavage or destabilization of the target. Because each miRNA potentially can regulate expression of a distinct set of genes, it is conceivable that the differential expression of different miRNAs might profoundly influence the repertoire of genes that are expressed during development, differentiation or disease. Here, we provide background on the biogenesis and function of miRNAs, and discuss how miRNA-mediated regulation can influence tumorigenesis as well as normal development and function of cells of the immune system.
May 10, 2008 The Year in Cardiovascular Surgery
  The purpose of this ?fth and ?nal yearly review of cardio-vascular surgery by this author remains to highlight articles that provide new and accurate information that should guide management decisions for patients with cardiovascu- lar disease. In the past, preference has been given to review of reports that link outcomes of patients to decisions about whether an operation should be done. The large body of new evidence about how an operation should be done was considered more appropriate for discussions among cardiac surgeons.
May 9, 2008 Cell-division inhibitors: new insights for future antibiotics
  The growing problem of antibiotic resistance has been exacerbated by the use of new drugs that are merely variants of older overused antibiotics. While it is naive to expect to restrain the spread of resistance without controlling antibacterial usage, the desperate need for drugs with novel targets has been recognized by health organizations, industry and academia alike. The wealth of knowledge available about the bacterial cell-division pathway has aided target-driven approaches to identify novel inhibitors. Here, we discuss the therapeutic potential of inhibiting bacterial cell division, and review the progress made in this exciting new area of antibacterial discovery.
May 8, 2008 Severe asthma: approach and management
  Management of severe asthma remains a significant challenge. Patients with this condition do not respond adequately to inhaled corticosteroids and bronchodilators, forcing a search for alternative strategies. The clinician's initial priority is to firmly establish the diagnosis of severe asthma, as many conditions can mimic and/or aggravate this disease. Once the diagnosis is confirmed and confounding variables addressed, a variety of pharmacological and non-pharmacological approaches must be considered. Continuous use of oral corticosteroids carries a risk of significant adverse effects. Leukotriene modifiers and antibodies to IgE are effective for some patients but not for many others. Alternative anti-inflammatory drugs and novel or unconventional modalities may also be used. Although severe asthma remains a clinical dilemma, a rational diagnostic and therapeutic strategy can be used to improve patient outcomes.
May 7, 2008 The Epothilones: Translating from the Laboratory to the Clinic
  The epothilones are macrolide compounds that have been shown to stabilize microtubules. The epothilones are strong promoters of tubulin polymerization in vitro and have significant antitumor activity against human cancer cells that are taxane resistant, express the multidrug resistance gene MDR-1 (ABCB1), and have acquired tubulin mutations. Several epothilones have been evaluated in clinical trials in a variety of tumor types. Ixabepilone (aza-epothilone B) has significant antitumor activity in breast cancer resistant to an anthracycline and a taxane, and has been approved by the U.S. Food and Drug Administration for the treatment of patients with metastatic or locally advanced breast cancer. There have been sustained efforts to develop pharmacodynamic markers to monitor the pharmacologic effect of the epothilones on tumors and normal tissues. The development of predictive markers for epothilone chemotherapy is highly desired to provide more tailored therapy for patients with cancer.
May 6, 2008 Current Status of Cardiac Rehabilitation
  Cardiac rehabilitation is increasingly recognized as an integral component of the continuum of care for patients with cardiovascular disease. Its application is a class I recommendation in most contemporary cardiovascular clinical practice guidelines. Despite the documentation of substantial morbidity and mortality benefits, cardiac rehabilitation services are vastly underutilized. The core components of cardiac rehabilitation have been detailedly delineated. Implementation of newly available performance measures offers the potential to enhance referral to, enrollment in, and completion of cardiac rehabilitation.
May 5, 2008 Hypertension and Obesity
  Obesity is a common problem in much of the western world today in that is linked directly with several disease processes, notably, hypertension. It is becoming clear that the adipocyte is not merely an inert organ for storage of energy but that it also secretes a host of factors that interact with each other and may result in elevated blood pressure. Of particular importance is the putative role of leptin in the causation of hypertension via an activation of the sympathetic nervous system and a direct effect on the kidneys, resulting in increased sodium reabsorption leading to hypertension. Obesity per se may have structural effects on the kidneys that may perpetuate hypertension, leading to an increased incidence of end-stage renal disease that results in further hypertension. Adipose tissue may elaborate angiotensin from its own local renin-angiotensin system. The distribution of body fat is considered important in the genesis of the obesity-hypertension syndrome, with a predominantly central distribution being particularly ominous. Weight loss is the cornerstone in the management of the obesity-hypertension syndrome. It may be achieved with diet, exercise, medications, and a combination of these measures. Anti-obesity medications that are currently undergoing clinical trials may play a promising role in the management of obesity and may also result in lowering of blood pressure. Antihypertensives are considered important components in the holistic approach to the management of this complex problem.
May 4, 2008 IL-10: The Master Regulator of Immunity to Infection
  IL-10 is an anti-inflammatory cytokine. During infection it inhibits the activity of Th1 cells, NK cells, and macrophages, all of which are required for optimal pathogen clearance but also contribute to tissue damage. In consequence, IL-10 can both impede pathogen clearance and ameliorate immunopathology. Many different types of cells can produce IL-10, with the major source of IL-10 varying in different tissues or during acute or chronic stages of the same infection. The priming of these various IL-10-producing populations during infections is not well understood and it is not clear whether the cellular source of IL-10 during infection dictates its cellular target and thus its outcome. In this article we review the biology of IL-10, its cellular sources, and its role in viral, bacterial, and protozoal infections.
May 3, 2008 Application of Nanotechnology in Cancer Therapy and Imaging
  Recent developments in nanotechnology have provided researchers with new tools for cancer imaging and treatment. This technology has enabled the development of nanoscale devices that can be conjugated with several functional molecules simultaneously, including tumor-specific ligands, antibodies, anticancer drugs, and imaging probes. Since these nanodevices are 100 to 1,000-fold smaller than cancer cells, they can be easily transferred through leaky blood vessels and interact with targeted tumor-specific proteins both on the surface of and inside cancer cells. Therefore, their application as cancer cell-specific delivery vehicles will be a significant addition to the currently available armory for cancer therapeutics and imaging.
May 2, 2008 The hippocampus and memory: insights from spatial processing
  The hippocampus appears to be crucial for long-term episodic memory, yet its precise role remains elusive. Electrophysiological studies in rodents offer a useful starting point for developing models of hippocampal processing in the spatial domain. Here we review one such model that points to an essential role for the hippocampus in the construction of mental images. We explain how this neural-level mechanistic account addresses some of the current controversies in the field, such as the role of the hippocampus in imagery and short-term memory, and discuss its broader implications for the neural bases of episodic memory.
May 1, 2008 2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention
  A primary challenge in the development of clinical practice guidelines is keeping pace with the stream of new data upon which recommendations are based. In an effort to respond more quickly to new evidence, the American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Practice Guidelines has created a new “focused update” process to revise the existing guideline recommenda- tions that are affected by evolving data or opinion.

Apr. Mar. Feb. Jan. 2007 2006 2005 2004 2003 2002 2001