STAT4 expression and activation is increased during mitosis in vitro and in vivo in skin- and mucosa-derived cell types: implications in neoplastic and inflammatory skin diseases.

BACKGROUND: The signal transducer and activator of transcription-4 (STAT4/Stat4) is a transcription factor known to convey signals from interleukin-12, interleukin-23, and interferon-alpha/beta to the nucleus, resulting in activation of dendritic cells, T-helper cell differentiation and production of interferon-gamma. OBJECTIVE: To demonstrate a novel role for STAT4 in cell mitosis. RESULTS: Phosphoserine STAT4 (pSerSTAT4) is increased in cells undergoing mitosis and is distributed throughout the cytoplasm during this stage of the cell cycle, whilst phosphotyrosine STAT4 (pTyrSTAT4) is confined to the chromosomal compartment. This distinct pattern of pSerSTAT4 during mitosis is seen in vitro in human keratinocytes and in other cell types. This is also present in vivo in cells undergoing mitosis in normal skin, psoriasis and squamous cell carcinoma. Inhibition of STAT4 phosphorylation by lisofylline and depletion of STAT4 by RNA interference results in a delay in progression of mitosis and leads to a reduction in cells completing cytokinesis. CONCLUSION: Our data demonstrate that STAT4 plays a role in enabling the normal and timely division of cells undergoing mitosis.

FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance.

The kinase inhibitor imatinib is used in the treatment of chronic myeloid leukaemia, where it targets the intracellular Bcr-Abl tyrosine kinase, and gastrointestinal stromal tumours, where it targets either the KIT or PDGF tyrosine kinase receptors. Here, we report that imatinib is also an effective inhibitor of the closely related FMS receptor for macrophage colony stimulating factor and that mutation of Asp 802 of FMS to Val confers imatinib resistance. Imatinib readily reverted the transformed phenotype of haemopoietic and fibroblast cell lines that express the oncogene v-fms and also inhibited the growth of the Bacl.2F5 macrophage cell line. The cellular IC50 value of imatinib for FMS was similar to those for Bcr-Abl and KIT. Consequently, imatinib may also prove effective for the treatment of diseases whose progression is dependent upon macrophage-colony stimulating factor, this includes certain aspects of cancer and inflammation.

Empirical, automated vocabulary discovery using large text corpora and advanced natural language processing tools.

A major impediment to the full benefit of electronic medical records is the lack of a comprehensive clinical vocabulary. Most existing vocabularies do not allow the full expressiveness of clinical diagnoses and findings that are often qualified by modifiers relating to severity, acuity, and temporal factors. One reason for the lack of expressivity is the inability of traditional manual construction techniques to identify the diversity of language used by clinicians. This study used advanced natural language processing tools to identify terminology in a clinical findings domain, compare its coverage with the UMLS Metathesaurus, and quantify the effort required to discover the additional terminology. It was found that substantial amounts of phrases and individual modifiers were not present in the UMLS Metathesaurus and that modest effort in human time and computer processing were needed to obtain the larger quantity of terms.

Automating concept identification in the electronic medical record: an experiment in extracting dosage information.

We discuss the development and evaluation of an automated procedure for extracting drug-dosage information from clinical narratives. The process was developed rapidly using existing technology and resources, including categories of terms from UMLS96. Evaluations over a large training and smaller test set of medical records demonstrate an approximately 80% rate of exact and partial matches' on target phrases, with few false positives and a modest rate of false negatives. The results suggest a strategy for automating general concept identification in electronic medical records.

Frequency and density of yeasts in the mouths of malnourished children.

The prevalence and density of yeasts and Candida albicans on the buccal mucosa and dorsum of the tongue have been assessed in 106 children in Crossroads squatter camp, South Africa. They were divided into a malnourished and a control group on the basis of an age/weight chart. No differences were found in yeast prevalence and density in the two groups. However, malnourished children more frequently had a mucosal density of yeasts, and particularly C. albicans, exceeding the upper limit normally found in health, in the absence of clinical infection. Some evidence was found to suggest that yeast density might be influenced by sex as well as nutritional status.