- Home
- A-Z Publications
- Annual Review of Medicine
- Previous Issues
- Volume 58, 2007
Annual Review of Medicine - Volume 58, 2007
Volume 58, 2007
-
-
The Leading Edge of Stem Cell Therapeutics
Vol. 58 (2007), pp. 313–328More LessAbstractStem cells, by virtue of their defining property of self-renewal, represent an unlimited source of potentially functional human cells for basic research and regenerative medicine. Having validated the feasibility of cell-based therapeutic strategies over the past decade, mostly through the use of rodent cells, the stem cell field has now embarked upon a detailed characterization of human cells. Recent progress has included improved cell culture conditions, long-term propagation, directed differentiation, and transplantation of both human embryonic and somatic stem cells. Continued progress in understanding basic human stem cell biology, combined with a better handle on the fundamental pathophysiology of human diseases one wishes to target (including the use of human stem cells in primate and other large animal models of human disease), should help to move this technology closer to clinical application.
-
-
-
New Reagents on the Horizon for Immune Tolerance
Vol. 58 (2007), pp. 329–346More LessAbstractRecent advances in immunology and a growing arsenal of new drugs are bringing the focus of tolerance research from animal models into the clinical setting. The conceptual framework for therapeutic tolerance induction has shifted from a “sledgehammer” approach that relies solely on cellular depletion and cytokine targeting, to a strategy directed toward restoring a functional balance across the immune system, namely the different populations of naive cells, effector and memory cells, and regulatory cells. Unlocking the key to tolerance induction in the future will likely depend on our ability to harness the functions of T regulatory cells. Also, dendritic cells are strategically positioned at the interface between innate and adaptive immunity and may be subject to deliberate medical intervention in a way that can control a chronic inflammatory response. Many reagents with tolerance-inducing potential are currently undergoing clinical testing in transplantation, autoimmune diseases, and allergic diseases, and even more that are on the horizon promise to offer enormous benefits to human health.
-
-
-
T Cell Costimulation: A Rational Target in the Therapeutic Armamentarium for Autoimmune Diseases and Transplantation
Vol. 58 (2007), pp. 347–358More LessAbstractT cells are central mediators of adaptive immunity. As such, they are involved in both normal immune responses (e.g., rejection of a transplanted organ) and abnormal ones (e.g., rheumatoid arthritis). T cells require both antigen-specific and costimulatory signals for their full activation. Advances in protein engineering and an increased understanding of the immune response have culminated in the evolution and creation of protein therapeutics that target specific costimulatory molecules. The selective costimulation modulator abatacept (CTLA-4Ig) binds to CD80 and CD86, blocking interaction with CD28, and is approved for the treatment of moderate to severe rheumatoid arthritis. Belatacept, currently enrolling phase III trials in renal transplantation, was rationally designed from abatacept to bind with more avidity to CD86, providing the more potent immunosuppressive properties required for immunosuppression in transplantation. This review describes the relevant immunology and summarizes recent clinical findings on these two molecules. Although both inhibit the CD28 costimulatory pathway, they are tailored for specific disease states—abatacept for autoimmune diseases and belatacept for transplantation.
-
-
-
A Human Monoclonal Antibody Cocktail as a Novel Component of Rabies Postexposure Prophylaxis*
Vol. 58 (2007), pp. 359–368More LessAbstractThe currently recommended treatment for individuals exposed to rabies virus is the combined administration of rabies vaccine and rabies immune globulin (RIG). This review sets out the criteria used to guide development of a cocktail of human monoclonal antibodies as a replacement for RIG. Using this process as a model, the general requirements for development of safe and efficacious monoclonal antibody alternatives to currently used polyclonal serum products are discussed.
-
-
-
Why Hasn't Eliminating Acute Rejection Improved Graft Survival?*
Vol. 58 (2007), pp. 369–385More LessAbstractAlthough patients with end-stage renal disease can be maintained with dialysis therapy, the superiority of patient survival with renal transplantation makes transplantation the preferred method of renal replacement. Potent immunosuppressive therapies, particularly calcineurin inhibitors, have greatly reduced the incidence of acute rejection. However, long-term allograft survival remains limited. We discuss the impact of acute rejection on long-term allograft survival and discuss other factors leading to late allograft loss, including calcineurin inhibitor toxicity, chronic allograft nephropathy, and BK virus nephropathy, as well as donor and recipient factors associated with long-term allograft loss.
-
-
-
End-Stage Renal Disease Measures of Quality
Vol. 58 (2007), pp. 387–399More LessAbstractDuring the past 35 years, there has been a geometric expansion of the population of patients receiving chronic dialysis therapy in the United States. As the size and associated costs of the dialysis population have grown, there has been a consistent and evolving emphasis on measuring and improving the quality of dialysis care. These efforts, aided by robust data collection vehicles, have translated into defined clinical performance measures; nevertheless, morbidity and mortality rates remain high for the dialysis population. Recently, attention has focused on whether improved outcomes could be obtained by paying physicians and dialysis providers on the basis of quality metrics. The feasibility, value, pitfalls, and appropriate quality metrics in a “payment-for-quality” program for dialysis care are currently under vigorous discussion.
-
-
-
Inflammatory Bowel Disease Genetics: Nod2
Judy H. Cho, and Clara AbrahamVol. 58 (2007), pp. 401–416More LessAbstractThe inflammatory bowel diseases (IBD) are comprised of two major subphenotypes, Crohn's disease (CD) and ulcerative colitis (UC). A significant role for genetic factors in IBD was established from epidemiologic studies and, more recently, the identification of well-established disease associations, notably the association of Nod2 (CARD15) polymorphisms with CD. The mapping to CD of Nod2 variants that alter protein function represents one of the earliest, most well-established, associations in complex genetic disorders. Since the initial discovery, genotype-phenotype correlations, definition of Nod2 expression and signaling pathways, association studies in other, related disorders, and features of Nod2 deficiency in murine models have been reported. Taken together, the Nod2 association to CD provides an illustrative model of the role of single gene variants in disease pathogenesis for common, complex multigenic disorders. Here we review general aspects of IBD genetics with particular focus on the role of Nod2 in CD.
-
-
-
New Therapeutic Approaches for Multiple Sclerosis
Vol. 58 (2007), pp. 417–432More LessAbstractAlthough several therapies exist for multiple sclerosis (MS), the most common inflammatory demyelinating disease of the central nervous system (CNS), there remains a large unmet clinical need for more effective immunomodulatory treatments in this category of diseases and for interventions that address their neurodegenerative component, which is currently untreated. Progress in our understanding of the immunology of MS over the past 30 years has recently synergized with novel computational methods and emerging high-throughput technologies that characterize variations in DNA, RNA, proteins, and metabolites to usher in a period of intense pathophysiologic investigation. These efforts are beginning to define subsets of patients with different forms of demyelinating disease. This partitioning of patients will prove valuable as we begin to tailor immunotherapy to the underlying pathophysiologic processes of individual patients using current therapies, emerging treatments, and rational combinations of all of these treatments. Preventing the entry of lymphocytes into the CNS and modifying the nature of the immune response are treatment approaches that work in the inflammatory component of MS but have little or no effect on neurodegeneration. Two challenges confront us: to develop cocktails of therapies that shift the immune homeostasis of patients with MS toward a healthy profile, and to identify and modulate the activity of targets within the neurodegenerative component of MS.
-
-
-
Cytokine Therapy for Crohn's Disease: Advances in Translational Research
Vol. 58 (2007), pp. 433–444More LessAbstractCrohn's disease (CD) and ulcerative colitis (UC), the two idiopathic inflammatory bowel diseases (IBDs), affect almost two million individuals in North America and several million worldwide. Cytokines are important in the pathogenesis of CD, and their manipulation has successfully reduced disease severity and maintained remission. Following the discovery of novel cytokines and the role they may play in gut mucosal immunity, as well as the emergence of new concepts and changing paradigms in CD pathogenesis, the roles of several cytokines have been elucidated and tested in both preclinical animal models and clinical trials of patients with IBD. Complementary to this, proof of concept for new cytokine targets is rapidly developing, with the possibility of future cytokine-based therapies that may offer greater specificity and decreased toxicity for the treatment of CD. This review discusses novel concepts in CD pathogenesis and the roles of cytokines in the initiation and perpetuation of disease. In addition, we review applications of cytokine-based therapies in human clinical trials and preclinical animal studies. Finally, we discuss novel cytokine targets not yet investigated in vivo and describe their potential contribution to CD pathogenesis.
-
-
-
Chemokine Antagonists as Therapeutics: Focus on HIV-1
Vol. 58 (2007), pp. 445–459More LessAbstractHuman immunodeficiency virus type 1 (HIV-1) entry into target cells is a multistep process involving the interaction of viral envelope proteins with cell surface receptors. Binding to CD4 is followed by engagement of specific chemokine receptors (CCR5 or CXCR4), triggering molecular rearrangements in the envelope transmembrane subunit that result in membrane fusion. Chemokine receptor antagonists that block the interaction of the HIV-1 envelope with CCR5 or CXCR4 potently inhibit HIV-1 in vitro. Pilot studies of orally bioavailable small-molecule CCR5 inhibitors in HIV-1-infected subjects have provided proof of concept for this novel drug class; phase III safety and efficacy trials are under way.
-
-
-
Current Concepts in AIDS Pathogenesis: Insights from the SIV/Macaque Model
Vol. 58 (2007), pp. 461–476More LessAbstractThe pathogenesis of AIDS has proven to be quite complex and dynamic, with most of the critical events (e.g., transmission, CD4+ T cell destruction) occurring in tissues that are not easily accessible for analysis. In addition, although the disease can progress over years, many critical events happen within the first few weeks of infection, when most patients are unaware that they are infected. The nonhuman primate model of AIDS has been used extensively to fill these gaps in our understanding of AIDS pathogenesis.
-
-
-
Macular Degeneration
Vol. 58 (2007), pp. 477–490More LessAbstractMacular degeneration is a term that describes a large group of conditions that are collectively the most common cause of irreversible vision loss in the developed world. Approximately one in three people will be affected to some degree by the time they reach 75 years of age. Many forms of macular degeneration have a significant genetic component, and a large amount of progress has recently been made in understanding the genes involved. In the future, genetic testing may allow specific preventive treatments to be delivered to individuals at risk, decades before the disease would ordinarily become manifest.
-
-
-
Targeting VEGF-A to Treat Cancer and Age-Related Macular Degeneration
Vol. 58 (2007), pp. 491–504More LessAbstractInhibiting angiogenesis is a promising strategy to treat cancer and several other disorders, including intraocular neovascular syndromes. The identification of vascular endothelial growth factor (VEGF)-A as a major regulator of normal and pathological angiogenesis has enabled significant progress toward effective treatments for such disorders. Several VEGF inhibitors have been recently approved by the U.S. Food and Drug Administration for the treatment of cancer and the neovascular form of age-related macular degeneration. This review summarizes the basic biology of VEGF-A and illustrates the clinical progress in targeting this molecule.
-
Previous Volumes
-
Volume 76 (2025)
-
Volume 75 (2024)
-
Volume 74 (2023)
-
Volume 73 (2022)
-
Volume 72 (2021)
-
Volume 71 (2020)
-
Volume 70 (2019)
-
Volume 69 (2018)
-
Volume 68 (2017)
-
Volume 67 (2016)
-
Volume 66 (2015)
-
Volume 65 (2014)
-
Volume 64 (2013)
-
Volume 63 (2012)
-
Volume 62 (2011)
-
Volume 61 (2010)
-
Volume 60 (2009)
-
Volume 59 (2008)
-
Volume 58 (2007)
-
Volume 57 (2006)
-
Volume 56 (2005)
-
Volume 55 (2004)
-
Volume 54 (2003)
-
Volume 53 (2002)
-
Volume 52 (2001)
-
Volume 51 (2000)
-
Volume 50 (1999)
-
Volume 49 (1998)
-
Volume 48 (1997)
-
Volume 47 (1996)
-
Volume 46 (1995)
-
Volume 45 (1994)
-
Volume 44 (1993)
-
Volume 43 (1992)
-
Volume 42 (1991)
-
Volume 41 (1990)
-
Volume 40 (1989)
-
Volume 39 (1988)
-
Volume 38 (1987)
-
Volume 37 (1986)
-
Volume 36 (1985)
-
Volume 35 (1984)
-
Volume 34 (1983)
-
Volume 33 (1982)
-
Volume 32 (1981)
-
Volume 31 (1980)
-
Volume 30 (1979)
-
Volume 29 (1978)
-
Volume 28 (1977)
-
Volume 27 (1976)
-
Volume 26 (1975)
-
Volume 25 (1974)
-
Volume 24 (1973)
-
Volume 23 (1972)
-
Volume 22 (1971)
-
Volume 21 (1970)
-
Volume 20 (1969)
-
Volume 19 (1968)
-
Volume 18 (1967)
-
Volume 17 (1966)
-
Volume 16 (1965)
-
Volume 15 (1964)
-
Volume 14 (1963)
-
Volume 13 (1962)
-
Volume 12 (1961)
-
Volume 11 (1960)
-
Volume 10 (1959)
-
Volume 9 (1958)
-
Volume 8 (1957)
-
Volume 7 (1956)
-
Volume 6 (1955)
-
Volume 5 (1954)
-
Volume 4 (1953)
-
Volume 3 (1952)
-
Volume 2 (1951)
-
Volume 1 (1950)
-
Volume 0 (1932)