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PubMed2007

Immunopathogenesis of poxvirus infections: forecasting the impending storm.

Variola virus, the causative agent of smallpox, is a member of the poxvirus family and one of the most virulent human pathogens known. Although smallpox was eradicated almost 30 years ago, it is not understood why the mortality rates associated with the disease were high, why some patients recovered, and what constitutes an effective host response against infection. As variola virus infects only humans, our current understanding of poxvirus infections comes largely from historical clinical data from smallpox patients and from animal studies using closely related viruses such as ectromelia, myxoma and monkeypox. The outcome of an infection is determined by a complex interaction between the type of immune response mounted by the host and by evasion mechanisms that the virus has evolved to subvert it. Disease pathogenesis is also a function of both host and viral factors. Poxviruses are not only cytopathic, causing host tissue damage, but also encode an array of immunomodulatory molecules that affect the severity of disease. The ability of the host to control virus replication is therefore critical in limiting tissue damage. However, in addition to targeting virus, the immune response can inadvertently damage the host to such a degree that it causes illness and even death. There is growing evidence that many of the symptoms associated with serious poxvirus infections are a result of a 'cytokine storm' or sepsis and that this may be the underlying cause of pathology.

Animals↗
PubMed2002

"Waves" vs. "particles" in the atmosphere's phase space: a pathway to long-range forecasting?

Thirty years ago, E. N. Lorenz provided some approximate limits to atmospheric predictability. The details---in space and time---of atmospheric flow fields are lost after about 10 days. Certain gross flow features recur, however, after times of the order of 10--50 days, giving hope for their prediction. Over the last two decades, numerous attempts have been made to predict these recurrent features. The attempts have involved, on the one hand, systematic improvements in numerical weather prediction by increasing the spatial resolution and physical faithfulness in the detailed models used for this prediction. On the other hand, theoretical attempts motivated by the same goal have involved the study of the large-scale atmospheric motions' phase space and the inhomogeneities therein. These "coarse-graining" studies have addressed observed as well as simulated atmospheric data sets. Two distinct approaches have been used in these studies: the episodic or intermittent and the oscillatory or periodic. The intermittency approach describes multiple-flow (or weather) regimes, their persistence and recurrence, and the Markov chain of transitions among them. The periodicity approach studies intraseasonal oscillations, with periods of 15--70 days, and their predictability. We review these two approaches, "particles" vs. "waves," in the quantum physics analogy alluded to in the title of this article, discuss their complementarity, and outline unsolved problems.

Journal Article↗
PubMedDate not supplied

Prediction of rodent carcinogenesis: an evaluation of prechronic liver lesions as forecasters of liver tumors in NTP carcinogenicity studies.

The National Toxicology Program (NTP) developed the chronic 2-year bioassay as a mechanism for predicting the carcinogenic potential of chemicals in humans. The cost and duration of these studies has limited their use to small numbers of selected chemicals. Many different short-term methods aimed at increasing predictive accuracy and the number of chemicals evaluated have been developed in attempts to successfully correlate their results with evidence of carcinogenicity (or lack of carcinogenicity) are assessed. Using NTP studies, the effectiveness of correlating prechronic liver lesions with liver cancer encompassing multiple studies using mice (83 compounds) and rats (87 compounds). These lesions include hepatocellular necrosis, hepatocellular hypertrophy, hepatocellular cytomegaly, bile duct hyperplasia, and hepatocellular degeneration, along with increased liver weight. Our results indicate that pooling 3 of these prechronic data points (hepatocellular necrosis, hepatocellular hypertrophy, and hepatocellular cytomegaly) can be very predictive of carcinogenicity in the 2-year study (p < 0.05). The inclusion of increased liver weight as an endpoint in the pool of data points increases the number of rodent liver carcinogens that are successfully predicted (p < 0.05), but also results in the prediction of increased numbers of noncarcinogenic chemicals as carcinogens. The use of multiple prechronic study endpoints provides supplementary information that enhances the predictivity of identifying chemicals with carcinogenic potential.

Administration, Oral↗