Improved reporting of statistical design and analysis: guidelines, education, and editorial policies.

A majority of original articles published in biomedical journals include some form of statistical analysis. Unfortunately, many of the articles contain errors in statistical design and/or analysis. These errors are worrisome, as the misuse of statistics jeopardizes the process of scientific discovery and the accumulation of scientific knowledge.

Innate immune activation and CD4+ T cell priming during respiratory fungal infection.

Aspergillus fumigatus is a mold that causes a spectrum of diseases, including lethal lung infections in immunocompromised humans and allergic asthma in atopic individuals. T helper 1 (Th1) CD4(+) T cells protect against invasive A. fumigatus infections whereas Th2 CD4(+) T cells exacerbate asthma upon inhalation of A.

Bringing order to early B cell chaos.

In the early 1990s, Richard (Randy) Hardy and colleagues divided B cell precursors into subpopulations--the Hardy fractions--based on the cells' expression of various cell surface proteins. This classification helped lay the groundwork for our present-day understanding of the molecular events that control early B cell development.

Ignoring endotoxin.

In 1947, Paul Beeson showed that rabbits repeatedly injected with certain bacteria eventually become resistant to the bacteria's fever-provoking effects-a phenomenon known as endotoxin tolerance.

Singapore's multibillion dollar gamble.

Figure 1Biopolis, Singapore's futuristic research hub.How does a country one-fourth the size of Rhode Island with little history in biomedical science become one of the world's biomedical research giants? The answer: with a pile of money and a large dose of chutzpah. Since 2000, Singapore has dumped more than US$2 billion into developing a biomedical research industry-from scratch.

Influenza: exposing the true killer.

In the early 1930s, Richard Shope isolated influenza virus from infected pigs. Shope's finding was quickly followed by the isolation of the influenza virus from humans, proving that a virus-not a bacterium, as was widely believed-caused influenza.

René Dubos: unearthing antibiotics.

In 1939, René Dubos discovered gramicidin-the first clinically tested antibiotic agent. This discovery helped revive the stalled interest in penicillin and launched the era of antibiotics.

Michael Heidelberger and the demystification of antibodies.

Having defined the protein nature of antibodies under the tutelage of Oswald Avery, Michael Heidelberger was the first to apply mathematics to the reaction of antibodies and their antigens (the "precipitin reaction"). Heidelberger's calculations launched decades of research that helped reveal the specificity, function, and origin of antibodies.

Aspergillus fumigatus triggers inflammatory responses by stage-specific beta-glucan display.

Inhalation of fungal spores (conidia) occurs commonly and, in specific circumstances, can result in invasive disease. We investigated the murine inflammatory response to conidia of Aspergillus fumigatus, the most common invasive mold in immunocompromised hosts. In contrast to dormant spores, germinating conidia induce neutrophil recruitment to the airways and TNF-alpha/MIP-2 secretion by alveolar macrophages.

How Heidelberger and Avery sweetened immunology.

In 1923, a young chemist-turned-microbiologist and his mentor made the startling discovery that bacterial sugars could be targeted by the immune system--a groundbreaking finding that helped launch the field of immunochemistry.

Macrophage activation unveiled.

In the early 1960s, George Mackaness showed that macrophages from mice infected with intracellular bacteria could launch an indiscriminate attack against unrelated bacteria. Thus began an explosion of research on the biology of what Mackaness first termed "macrophage activation."

Distinct CD4+-T-cell responses to live and heat-inactivated Aspergillus fumigatus conidia.

Aspergillus fumigatus is an important fungal pathogen that causes invasive pulmonary disease in immunocompromised hosts. Respiratory exposure to A. fumigatus spores also causes allergic bronchopulmonary aspergillosis, a Th2 CD4+-T-cell-mediated disease that accompanies asthma.

T cell traffic signals.

In 1990, Charles Mackay and colleagues combined classical physiology with modern molecular biology to provide the first concrete evidence that naive and memory T cells follow distinct migratory routes out of the bloodstream--a discovery that helped invigorate the field of lymphocyte homing.

Harry Goldblatt and the discovery of renin.

In 1934, pathologist Harry Goldblatt established the first animal model of hypertension. This model provided researchers with the tools to delineate the renin-angiotensin system of blood pressure control and, eventually, to design enzyme inhibitors for the treatment of chronic hypertension.

Peyton Rous: father of the tumor virus.

In 1910, Peyton Rous identified a transmissible avian tumor virus, a discovery that began the journey from tumor virus biology to tumor biology itself.

Discovering lymphocyte subsets.

At a scientific meeting in 1968, Jacques Miller was accused of complicating immunology. He and others suggested that there was not one but two kinds of lymphocytes--one from the thymus and one from the bone marrow. In a pair of groundbreaking articles published in the Journal of Experimental Medicine in 1968, Miller and his student Graham Mitchell proved that two subsets of lymphocytes did exist and identified which subset mediated antibody responses.

Broadening the horizons for yellow fever: new uses for an old vaccine.

The vaccine against yellow fever is one of the safest and most effective ever developed. With an outstanding record in humans, has this live attenuated vaccine been overlooked as a promising vector for the development of vaccines against pathogens outside its own genus? Recent studies, including a report by Tao et al. on page 201 of this issue, have sparked renewed interest.

Immune responses to Puumala virus infection and the pathogenesis of nephropathia epidemica.

Puumala virus, causative agent of a mild form of hemorrhagic fever with renal syndrome, also known as nephropathia epidemica, induces long-lasting humoral and cellular immunity in patients. The virus itself is not cytopathic, and the immune responses to the virus may be involved in teh pathogenesis of the disease.

Voriconazole inhibits fungal growth without impairing antigen presentation or T-cell activation.

Invasive aspergillosis (IA) is the most common life-threatening invasive mold infection worldwide. The principal therapy for IA is amphotericin B, despite its known toxicity and immunosuppressive side effects. Studies in animal models of IA suggest a role for T lymphocytes in the pathology of the disease, although the precise role for Aspergillus-specific T cells remains undefined.

Long-lived memory T lymphocyte responses after hantavirus infection.

Puumala virus (PUUV) is a hantavirus that causes hemorrhagic fever with renal syndrome (HFRS), which is an important public health problem in large parts of Europe. We examined the memory cytolytic T lymphocyte (CTL) responses in 13 Finnish individuals who had HFRS between 1984 and 1995. In seven of these donors, we detected virus-specific CTL responses against the PUUV nucleocapsid (N) protein after in vitro stimulation with PUUV.

Generation of recombinant vaccinia viruses expressing Puumala virus proteins and use in isolating cytotoxic T cells specific for Puumala virus.

Puumala (PUU) virus causes a form of hemorrhagic fever with renal syndrome (HFRS), called nephropathia epidemica (NE), in Europe. HFRS is characterized by an increased capillary permeability, which we hypothesize is caused by hyperactivation of the host immune system, especially cellular immune responses. To identify cytotoxic T lymphocytes (CTLs) specific for the PUU virus from NE patients, we have made recombinant vaccinia viruses expressing PUU virus proteins, the nucleocapsid (N) and two surface glycoproteins, G1 and G2.