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Regul Toxicol Pharmacol. 2002 Jun;35(3):398-413.
Safety evaluation of monophosphoryl lipid A (MPL): an immunostimulatory adjuvant.

Baldrick P, Richardson D, Elliott G, Wheeler AW.

Covance Laboratories Ltd. Otley Road, Harrogate, North Yorkshire, HG3 1PY, England, United Kingdom.

Animal models have shown the potential use of monophosphoryl lipid A (MPL), a detoxified bacterial lipopolysaccharide, as a vaccine adjuvant. Immunostimulatory activity with diverse effects on the cellular elements of the immune system has been demonstrated and a range of vaccines incorporating MPL, including allergy vaccines, are currently under clinical evaluation. A series of preclinical safety investigations was performed to support clinical use of MPL as used in allergy vaccines and comprised cardiovascular/respiratory assessment in dog (up to 100 microg/kg/day); repeat-dose toxicity in rat, rabbit, and dog (up to 2500 and 1200 microg/kg/day in the rat and dog, respectively); reproduction toxicity in rat and rabbit (up to 100 microg/kg/day); and genotoxicity studies. Overall, repeat-dose toxicity studies in the rat and dog showed expected immunostimulatory effects and/or signs of toxicity associated with overstimulation of the immune system (notably increased spleen weight and white blood cell values). Studies in the rabbit with weekly doses of MPL produced no effects. MPL was shown to have no adverse effects on cardiovascular/respiratory function, reproduction, and genotoxicity. 2002 Elsevier Science (USA)

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12202055&dopt=Abstract

Virology. 2002 Aug 1;299(2):288-300.
The hepatitis B virus X protein binds to and activates the NH(2)-terminal trans-activation domain of nuclear factor of activated T cells-1.

Carretero M, Gomez-Gonzalo M, Lara-Pezzi E, Benedicto I, Aramburu J, Martinez-Martinez S, Redondo J, Lopez-Cabrera M.

Unidad de Biologia Molecular, Hospital Universitario de la Princesa, C/Diego de Leon 62, 28006 Madrid, Spain.

We have previously reported that the hepatitis B virus X protein (HBx) activates nuclear factor of activated T cells (NF-AT), a key regulator of the immune system, by a calcium/calcineurin-dependent pathway, involving dephosphorylation and nuclear translocation of this transcription factor. In addition, we showed that HBx synergizes with potent calcium-mobilizing stimuli to activate NF-AT-dependent transcription, suggesting that additional mechanisms might also be operative in the activation of NF-AT by HBx. Here we demonstrate that HBx activates the NH(2)-terminal transcription activation domain (TAD) of NF-AT1 by a mechanism involving protein-protein interaction. Targeting of HBx to the nucleus did not affect its ability to induce the transcriptional activity of NF-AT1. In contrast, mutations of HBx affecting its functional interaction with general transcription factors abrogated the HBx-induced activity of NF-AT1. Together these results indicate that HBx may exert its function by acting as a nuclear coactivator of NF-AT1.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12202232&dopt=Abstract

Int Immunol. 2002 Sep;14(9):1065-74.
Variable expression of Toll-like receptor in murine innate and adaptive immune cell lines.

Applequist SE, Wallin RP, Ljunggren HG.

Microbiology and Tumor Biology Center, Karolinska Institutet, 171 77 Stockholm, Sweden. steven.applequistc.ki.se

Pattern recognition receptors (PRR) play an important roll in immediate responses to different conserved molecules produced by microbes. In this paper we describe the cloning of the mouse homolog of Toll-like receptor (TLR) 3, and present an analysis of the expression of this gene in innate and adaptive immune cell lines. We also performed a broad expression study on these cells of other TLR, including TLR family members whose expression pattern is not known, i.e. TLR7. The analysis was done in order to understand, and possibly predict, how innate and adaptive immune cells respond to microbial pattern antigens. This first large-scale analysis of immune cell TLR expression in the mouse reveals that cells of the innate immune system express a broader number of TLR than cells of the adaptive immune system, supporting preconceptions concerning the hierarchy of immune cells involved in direct pathogen recognition. Additionally, the expression of TLR transcripts by mast cells, neutrophils and microglial cells observed here suggests that pathogen-associated molecular pattern molecules could induce activation of these cells through TLR. Finally, the mouse homolog of human TLR3 identified here may, like its human counterpart, be an exceptional TLR molecule due to its lack of a conserved proline residue seen to be involved in existing TLR signaling capabilities found in other TLR family members.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12202403&dopt=Abstract

Hum Reprod. 2002 Sep;17(9):2272-8.
Soluble adhesion molecules in serum throughout the menstrual cycle.

Bonello N, Norman RJ.

Reproductive Medicine Unit, Department of Obstetrics and Gynaecology, The University of Adelaide, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia. nigel.bonelldelaide.edu.au

BACKGROUND: The female reproductive and immune systems are integrally linked with respect to shared cellular and molecular mediators. Cell adhesion molecules (CAMs) involved in leukocyte-endothelial interactions, e.g. intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, are regulated by sex steroids when expressed by cultured endothelium, while uterine and ovarian CAM expression appears to be cyclically or gonadotrophin-regulated. METHODS AND RESULTS: To determine if these effects translate into changes in soluble CAMs (sICAM-1, sVCAM-1 and sE-selectin) levels in peripheral blood, normally cycling women received regular venous sampling throughout a complete menstrual cycle. Soluble ICAM-1 levels were maximal in the early and mid-follicular stages, progressively decreased throughout the remainder of the cycle and were significantly reduced in the late luteal stage (P < 0.001). Levels of sVCAM-1 fluctuated during the follicular phase and mid-cycle, but also declined in the late luteal phase (P < 0.01), whereas sE-selectin concentration did not vary markedly across the menstrual cycle. Plasma hormone and urinary hormone metabolite levels confirmed precise cycle tracking and revealed an inverse relationship between sICAM-1 and estradiol (r = -0.38, P < 0.005). A negative correlation was also apparent between sVCAM-1 and circulating monocyte cell numbers (r = -0.47, P < 0.001). CONCLUSIONS: The normal cyclic variation in peripheral sICAM-1 and sVCAM-1 levels reported here may reflect uterine and/or ovarian tissue remodelling events, and is of particular importance if soluble CAM levels are utilized as biological markers of certain disease states in women of reproductive age.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12202413&dopt=Abstract

Science. 2002 Sep 20;297(5589):2048-51. Epub 2002 Aug 29.
Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition.

Park JM, Greten FR, Li ZW, Karin M.

Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0636, USA.

The bacterium Bacillus anthracis causes the death of macrophages, which may allow it to avoid detection by the innate immune system. We found that B. anthracis lethal factor (LF) selectively induces apoptosis of activated macrophages by cleaving the amino-terminal extension of mitogen-activated protein kinase (MAPK) kinases (MKKs) that activate p38 MAPKs. Because macrophages that are deficient in transcription factor nuclear factor kappaB (NF-kappaB) are also sensitive to activation-induced death and p38 is required for expression of certain NF-kappaB target genes, p38 is probably essential for synergistic induction of those NF-kappaB target genes that prevent apoptosis of activated macrophages. This dismantling of the p38 MAPK module represents a strategy used by B. anthracis to paralyze host innate immunity.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12202685&dopt=Abstract

Hair loss is a problem in modern soceity. Examining the factors of hair growth may shed light on how hair loss might occur. How long can hair grow before it stops growing eventually if it does? Given that the hair growth rate is quite uniform and constant, somewhere between 0.3-0.5 millimeters per day, it's believed that the length of anagen, the growth phase, differs among individuals, and this is the major determinant to the maximum hair length. For some individuals, anagen may last ten years. Of course the length of the anagen is governed by genes, and the genetic background of the individuals. Non-genetic factors such as nutritional condition, weather, seasonal changes (hair may grow a bit faster during winter), taking medications, health condition may of course influence the rate of hair growth as well as The shape of the hair, straight or curly, is dependent on the shape of the follicle. A circular or round hair follicle would generate straight hair, while the follicle with oval or elliptical shapes (in its cross-section) would produce a curly hair.

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