The kidney plays a central role in our ability to maintain appropriate sodium balance, which is critical to determination of blood pressure. In this review we outline current knowledge of renal salt handling at the molecular level, and, given that Westernized societies consume more salt than is required for normal physiology, we examine evidence that the lowering of salt intake can combat hypertension.
Kevin M. O’Shaughnessy, Fiona E. Karet
West Nile virus was first detected in North America in 1999 and has subsequently spread throughout the United States and Canada and into Mexico and the Caribbean. This review describes the epidemiology and ecology of West Nile virus in North America and the prospects for effective treatments and vaccines.
L. Hannah Gould, Erol Fikrig
Since its identification nearly 30 years ago, Lyme disease has continued to spread, and there have been increasing numbers of cases in the northeastern and north central US. The Lyme disease agent, Borrelia burgdorferi, causes infection by migration through tissues, adhesion to host cells, and evasion of immune clearance. Both innate and adaptive immune responses, especially macrophage- and antibody-mediated killing, are required for optimal control of the infection and spirochetal eradication. Ecological conditions favorable to the disease, and the challenge of prevention, predict that Lyme disease will be a continuing public health concern.
Allen C. Steere, Jenifer Coburn, Lisa Glickstein
Malaria, the most prevalent and most pernicious parasitic disease of humans, is estimated to kill between one and two million people, mainly children, each year. Resistance has emerged to all classes of antimalarial drugs except the artemisinins and is responsible for a recent increase in malaria-related mortality, particularly in Africa. The de novo emergence of resistance can be prevented by the use of antimalarial drug combinations. Artemisinin-derivative combinations are particularly effective, since they act rapidly and are well tolerated and highly effective. Widespread use of these drugs could roll back malaria.
Nicholas J. White
Dengue is an expanding public health problem, and an effective vaccine remains elusive. This review discusses how the significant influence of sequential infection with different dengue virus serotypes on the severity of disease can be viewed in terms of beneficial and detrimental effects of heterologous immunity. A more complete understanding of these effects is likely to be critical for predicting optimal vaccine-induced immune responses.
Alan L. Rothman
Inability to recognize incident infection has traditionally limited both scientific and public health approaches to HIV disease. Recently, some laboratories have begun adding HIV nucleic acid amplification testing to HIV diagnostic testing algorithms so that acute (antibody-negative) HIV infections can be routinely detected within the first 1–3 weeks of exposure. In this review article, we will highlight critical opportunities for HIV treatment and prevention that are presented by these diagnostic strategies.
Christopher D. Pilcher, Joseph J. Eron Jr., Shannon Galvin, Cynthia Gay, Myron S. Cohen
Multiple sclerosis is a complex genetic disease associated with inflammation in the CNS white matter thought to be mediated by autoreactive T cells. Clonal expansion of B cells, their antibody products, and T cells, hallmarks of inflammation in the CNS, are found in MS. This review discusses new methods to define the molecular pathology of human disease with high-throughput examination of germline DNA haplotypes, RNA expression, and protein structures that will allow the generation of a new series of hypotheses that can be tested to develop better understanding of and therapies for this disease.
David A. Hafler
A revolution in the governance of global infectious disease threats is under way, accelerated by events triggered by the outbreak of SARS in 2003. This review article analyzes pre-SARS trends in the governance of infectious diseases, examines the impact of the SARS outbreak on these trends, and posits that germ governance is now a criterion of “good governance” in world affairs.
David P. Fidler
Human population growth, technological advances, and changing social behaviors lead to the selection of new microbial pathogens. Antimicrobial drugs, vaccines, diagnostics, and treatments for emerging infectious diseases must be developed. The selective forces that drive the emergence of new infectious diseases, and the implications for our survival, are just beginning to be understood.
Vincent R. Racaniello
Atopic dermatitis is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental triggers and is often the first step in the atopic march that results in asthma and allergic rhinitis. The clinical phenotype that characterizes atopic dermatitis is the product of interactions between susceptibility genes, the environment, defective skin barrier function, and immunologic responses. This review summarizes recent progress in our understanding of the pathophysiology of atopic dermatitis and the implications for new management strategies.
Donald Y.M. Leung, Mark Boguniewicz, Michael D. Howell, Ichiro Nomura, Qutayba A. Hamid
Human African trypanosomiasis (HAT), also known as sleeping sickness, is a major cause of mortality and morbidity in sub-Saharan Africa. Current therapy with melarsoprol for CNS HAT has unacceptable side-effects with an overall mortality of 5%. This review discusses the issues of diagnosis and staging of CNS disease, its neuropathogenesis, and the possibility of new therapies for treating late-stage disease.
Peter G.E. Kennedy
Helicobacter pylori are bacteria that have coevolved with humans to be transmitted from person to person and to persistently colonize the stomach. Their population structure is a model for the ecology of the indigenous microbiota. A well-choreographed equilibrium between bacterial effectors and host responses permits microbial persistence and health of the host but confers risk of serious diseases, including peptic ulceration and gastric neoplasia.
Martin J. Blaser, John C. Atherton
A set of lung diseases share the tendency for the development of progressive fibrosis ultimately leading to respiratory failure. This review examines the common pathogenetic features of these disorders in light of recent observations in both humans and animal models of disease, which reveal important pathways of lung matrix remodeling.
Harold A. Chapman
The anterior pituitary gland integrates the repertoire of hormonal signals controlling thyroid, adrenal, reproductive, and growth functions. The gland responds to complex central and peripheral signals by trophic hormone secretion and by undergoing reversible plastic changes in cell growth leading to hyperplasia, involution, or benign adenomas arising from functional pituitary cells. Discussed herein are the mechanisms underlying hereditary pituitary hypoplasia, reversible pituitary hyperplasia, excess hormone production, and tumor initiation and promotion associated with normal and abnormal pituitary differentiation in health and disease.
The congenital long QT syndrome is a rare disorder in which mutation carriers are at risk for polymorphic ventricular tachycardia and/or sudden cardiac death. Discovery and analysis of gene mutations associated with variants of this disorder have provided novel insight into mechanisms of cardiac arrhythmia and have raised the possibility of mutation-specific therapeutic intervention.
Robert S. Kass, Arthur J. Moss
Sepsis remains a serious cause of morbidity and mortality, and the pathophysiology of the disease is not clear. The definition of the clinical manifestations of sepsis is ever evolving. This review discusses the search for effective therapeutic interventions, hurdles in translational sepsis research, and new therapies in development in current clinical trials.
Niels C. Riedemann, Ren-Feng Guo, Peter A. Ward
Daniel J. Rader, Jonathan Cohen, Helen H. Hobbs
Franklin D. Lowy
Judith Korner, Louis J. Aronne
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