Table of Contents

August 2005; 5 (4)

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  • Among the salutary effects of aspirin (acetylsalicylic acid, ASA) are its ability to keep platelets from aggregating and blood from clotting too readily, to reduce fever, and to ameliorate inflammation. Aspirin also is beneficial in preventing colorectal cancer; however, aspirin is not without its side effects, which include gastrointestinal irritation and ulceration. Additionally, if a patient has pre-existing conditions that are exacerbated by aspirin, does a daily dose of aspirin make sense, when admittedly, the reduction of the incidence of colorectal cancer is less than 50% in those who take aspirin daily? New research on nitric oxide-modified aspirin (NO-ASA) indicates that the gastrointestinal side effects might be suppressed while keeping or enhancing the ability of the modified aspirin to prevent colorectal cancer and inhibit the proliferation of cancer cells in vitro.

  • Among tyrosine kinases, the Janus kinases (Jaks) are the only ones known to possess two kinase domains: a C-terminal functional kinase domain and a nonfunctional pseudokinase domain located just N-terminal to the functioning domain. The pseudokinase domain, or Jak homology domain 2 (JH2)—Jaks contain seven domains that are well-conserved by the four Jak family members—lacks a few key residues critical for catalytic activity. The function of the JH2 has remained a mystery, but recent results indicate that the JH2 domain of Jak2 may inhibit kinase activity. New intriguing observations reveal that the majority of individuals afflicted with polycythemia vera, essential thrombocythemia, or chronic idiopathic myelofibrosis (all members of the chronic myeloproliferative disorders family) share the V617F mutation of the Jak2 JH2 domain. Although the mutation occurs, to some degree, in the germ line, it more often presents as an acquired mutation. The mutation might cause a structural change sufficient to prevent negative regulators from binding and inhibiting the kinase, or could place the kinase in a constitutively “on” conformation. The identification of V617F now provides a molecular diagnostic indicator of several chronic myeloproliferative diseases.


  • A wide variety of crop plants have been cultivated over the millennia with the sole, human-driven objective of maximizing nutrient protein production. The plant cell endomembrane system has evolved to traffic proteins, according to many of the same mechanisms common to mammalian cells, and to accumulate them, by means unknown to mammalian cells, for storage. Today, scientists are turning to the plant cell endomembrane system as a potential source for non-nutrient (pharmaceutical) recombinant proteins. Beyond the exciting prospect of harvesting therapeutic human proteins from plants, the secretory mechanisms in plants offer a fascinating opportunity for understanding a fundamental cellular function that is, in varying forms, ubiquitous.

  • How is it that our immune cells know not to attack our own cells? In the case of natural killer (NK) cells, it’s a matter of “examining” the cells they encounter for major histocompatibility complex (MHC) class I antigens. The presence of these antigens on a cell apposed to an NK cell indicates “self,” and instructs the NK cell not to attack. Great efforts are being undertaken to identify small molecules that might bolster the immune response in immune-compromised patients, and such research includes investigations into the relevant immunogenetics. Indeed, an individual’s repertoire of MHC class I proteins and killer immunoglobulin-like receptors (KIR) on NK and other immune cells not only underlies responses to infection and the occurrence of autoimmune disease, but also can determine the outcome of malignant disease.

  • In vivo, ex vivo, or in vitro, the cells that populate a given tissue are not necessarily uniform, neither in terms of cell structure nor pharmacological responsiveness. Much of this cell-cell variability is taken for granted, and yet the inconsistency of tissue response to any of a number of pharmacological agents is often encountered in the literature. Could tissue heterogeneity be responsible? The retinal pigment epithelium is a single tissue that consists of a mosaic of distinctive cells and that may serve as a model for a variety of tissue types. This mosaicism can be characterized at the levels of gene and protein expression, as well as in terms of subcellular structures and resistance to environmental insults.

Beyond the Bench

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