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J Med Chem. 2002 Oct 24;45(22):4868-74.
Quantitative structure--activity relations for gammadelta T cell activation by phosphoantigens.
Gossman W, Oldfield E.
Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
gammadelta T cells help contribute to innate immunity and are activated by the natural phosphoantigens produced by the organisms responsible for causing, for example, tuberculosis, malaria, tularemia, and plague. They are also activated by synthetic phosphoantigens and are cytotoxic to tumor cells. Here, we show that it is now possible to accurately predict gammadelta T cell activation by both natural and synthetic phosphoantigens by using the quantitative structure-activity relationship (QSAR) techniques commonly used in drug design. This approach should be of use in developing novel immunotherapeutic agents as well as contributing to a better understanding of the immune system's response to infectious agents.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12383012&dopt=Abstract
Int J Exp Pathol. 2002 Jun;83(3):121-32.
Resolution of skeletal muscle inflammation in mdx dystrophic mouse is accompanied by increased immunoglobulin and interferon-gamma production.
Lagrota-Candido J, Vasconcellos R, Cavalcanti M, Bozza M, Savino W, Quirico-Santos T.
Department of Immunobiology, Fluminense Federal University, Rio de Janeiro, Brazil.
Mdx mouse, the animal model of Duchenne muscular dystrophy, develops an X-linked recessive inflammatory myopathy with an apparent sustained capacity for muscle regeneration. We analysed whether changes in the skeletal muscle during myonecrosis and regeneration would correlate with functional alterations in peripheral lymphoid tissues. Here we show that during the height of myonecrosis, mdx mice display marked atrophy of peripheral lymph nodes and extensive muscle inflammation. In contrast, enlargement of draining lymph nodes with accumulation of CD4+ CD44+, CD4+ CD25+, CD8+ CD44+ T lymphocytes and type-2 B cells was consistently observed during amelioration of the muscle lesion. In addition, regeneration of the muscular tissue was accompanied by concomitant increase of immunoglobulin-secreting cells in regional lymph nodes and bone marrow. Double immunolabelling analysis revealed intense B cell proliferation and formation of germinal centre in the follicles of dystrophic regional lymph nodes. Furthermore, lymph node cells produced large amounts of IFN-gamma but not IL-4, IL-6 or IL-10 after in vitro mitogen stimulation with Concanavalin A. As these alterations occurred mainly during the recovery period, we suggested that local activation of the immune system could be an influence which mitigates the myonecrosis of muscular tissue in the mdx dystrophic mouse.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12383191&dopt=Abstract
Exp Eye Res. 2002 Sep;75(3):285-93.
Adaptive immune responses to Acanthamoeba cysts.
McClellan K, Howard K, Mayhew E, Niederkorn J, Alizadeh H.
Department of Ophthalmology, University of Sydney, GPO BOX 4337, Sydney, NSW 2121, Australia.
Acanthamoeba cysts are not eliminated from the corneas of human subjects or experimentally infected animals. The persistence of Acanthamoeba cysts in the cornea indicates that either the cysts escape immunological elimination or are not recognized by the host's immunological elements. The aim of this study was to determine the immunogenicity and antigenicity of the Acanthamoeba cyst. Mice were immunized intraperitoneally and serum anti-Acanthamoeba IgG was measured by ELISA. Lymphoproliferative assay and delayed type hypersensitivity (DTH) responses to Acanthamoeba castellanii cyst and trophozoite antigens were used to determine the cell mediated immune responses against Acanthamoeba cysts. A. castellanii cysts were both immunogenic and antigenic, producing anti-Acanthamoeba serum IgG, T lymphocyte proliferation, and delayed type hypersensitivity responses. These results indicate that Acanthamoeba cysts are recognized by the immune system. The persistence of the organism in the human cornea means that these adaptive immune responses fail to kill Acanthamoeba cysts.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12384091&dopt=Abstract
Cancer Res. 2002 Oct 15;62(20):5835-44.
Direct detection and quantitation of a distinct T-cell epitope derived from tumor-specific epithelial cell-associated mucin using human recombinant antibodies endowed with the antigen-specific, major histocompatibility complex-restricted specificity of T cells.
Cohen CJ, Hoffmann N, Farago M, Hoogenboom HR, Eisenbach L, Reiter Y.
Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
The recent characterization of MHC-displayed tumor-associated antigens that recognize effector cells of the immune system has created new perspectives for cancer therapy. Antibodies that recognize these tumor-associated MHC-peptide complexes with the same specificity as the T-cell antigen receptor will therefore be valuable tools for immunotherapy, as well as for studying antigen presentation in human cancers. Most tumor-associated antigens are expressed in only one or a few tumor types; however, specific T-cell epitopes derived from the Mucin-1 tumor-associated antigen (MUC1) that are widely expressed in many cancers were identified and shown to be recognized by CTLs. We selected a large nonimmune repertoire of phage Fab antibodies on recombinant human class I HLA-A2 complexes displaying an antigenic T-cell epitope derived from MUC1. High frequency of anti-MHC-peptide binders was observed (84%), and surprisingly, a high percentage (80%) of antibodies was fully specific for the MUC1 epitope. We isolated a surprisingly large panel of 16 different high-affinity human recombinant Fab antibodies that exhibited peptide-specific, MHC-restricted binding characteristics of T cells. The analyzed Fabs not only recognize the cognate MHC-peptide complex in a recombinant soluble form but also the native complex as displayed on the surface of antigen-presenting cells and breast tumor cells. Therefore, these findings demonstrate the ability to transform the unique fine specificity but low intrinsic affinity of T-cell receptors on T cells into high-affinity soluble antibody molecules endowed with a T-cell antigen receptor-like specificity. These molecules may prove to be very important and widely applicable for monitoring the expression of specific MHC-peptide complexes on the surface of tumor and immune cells for structure-function studies of T-cell receptor-peptide-MHC interactions, as well as for developing new targeting agents for immunotherapy.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12384546&dopt=Abstract
Cancer Immunol Immunother. 2002 Nov;51(10):565-73. Epub 2002 Sep 13.
A functional recombinant single-chain T cell receptor fragment capable of selectively targeting antigen-presenting cells.
Epel M, Ellenhorn JD, Diamond DJ, Reiter Y.
Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Room 333, Haifa 32000, Israel.
Specificity in the immune system is dictated and regulated by specific recognition of peptide/major histocompatibility complexes (MHC) by the T cell receptor (TCR). Such peptide/MHC complexes are a desirable target for novel approaches in immunotherapy because of their highly restricted fine specificity. Recently a potent anti-human p53 CD8(+) cytotoxic T lymphocyte (CTL) response has been developed in HLA-A2 transgenic mice after immunization with peptides corresponding to HLA-A2 motifs from human p53. An alpha/beta T-cell receptor was cloned from such CTL which exhibited a moderately high affinity to the human p53(149-157) peptide. In this report, we investigated the possibility of using a recombinant tumor-specific TCR for antigen-specific elimination of cells that express the specific MHC-peptide complex. To this end, we constructed a functional single-chain Fv fragment from the cloned TCR and fused it to a very potent cytotoxic molecule, a truncated form of Pseudomonas exotoxin A (PE38). The p53 TCR scFv-P38 fusion protein was generated by in vitro refolding from bacterially-expressed inclusion bodies, and was found to be functional by its ability to bind antigen-presenting cells (APC) which express the specific p53-derived peptide. Moreover, we have shown that the p53-specific TCR scFv-PE38 molecule specifically kills APC in a peptide-dependent manner. These results represent the first time that a TCR-derived recombinant single-chain Fv fragment has been used as a targeting moiety to deliver a cytotoxic effector molecule to cells and has been able to mediate the efficient killing of the particular cell population that expresses the specific MHC/peptide complex. Similarly to antibody-based targeting approaches, TCR with tumor cell specificity represent attractive candidates for generating new, very specific targeting moieties for various modes of cancer immunotherapy.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12384808&dopt=Abstract
Natural Herbal Supplement: Hair Million
The most ostensive feature that distinguishes us human from chimps and other primates is the lack of bodily hair. During evolutionary process, we have lost the majority of hair. Hair is no longer a biologically essential part of our body, just
like appendix. The hair we still have on our scalp and a few other bodily parts is still regarded as significant for reasons other than biological necessity. Hair loss is naturally accompanied by aging process, although the extent of hair loss and the timing of onset vary widely among individuals. Thus, loss of hair and baldness is considered as a symbol of maturity or old age. Like winkles and other signs of aging, hair loss is not welcome by most people, because we don't welcome aging, and being perceived as an aging person. However, it is alopecia, or premature hair loss that especially concerns certain people.
While the hair loss and resulting baldness in general have not been proven to be related to underlying health problems, there are certain correlations between hair loss and health problems. For instance, premature hair loss could suggest premature aging or nutritional and hormonal imbalance, stressful life, use of drugs that cause hair loss as a side effect, skin disease, or heart disease. The balding appearance could also impart a subdued impression of integrity in bodily health and youthfulness.
Fortunately, in many cases, hair loss is reversible by change in lifestyle and/or nutritional supplementation. Herbal hair growth formula and other nutritional supplements have been shown to be effective in warding off hair loss and resuming hair growth. Certain prescription drugs such as Buy Propecia Online may also reverse hair loss by blocking the formation of DHT, a hormonal byproduct produced inceasingly as a person age.
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