Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intradermal injections of MER-BCG 0.1 mg or 0.2 mg at each of 10 multiple sites, led to local granuloma formation. The nodules reached approximately 10 mm in diameter, ulcerated and were accompanied by granulomatous changes in the regional lymph nodes. Six or twelve successive treatments (each including 10 injections) at 4 week intervals produced the same histopathological lesions but no changes in hematological and blood chemical parameters or general morphology and no changes in general condition with exception of occasional weight loss in a few animals. Injection with 0.01 or 0.001 mg/site produced similar, though less severe, skin lesions but no changes in the draining lymph nodes. The immunogenicity of MER-BCG was characterized by granuloma formation, a positive skin response to old tuberculin, and a positive lymphocyte transformation to PPD tuberculin, thus indicating stimulation of cell-mediated immune responses. However, there was a decreased responsiveness to PHA and PPD with continuing treatment with MER-BCG. The decreased responsiveness and accumulation of numerous depots of antigen would suggest an "immunologic paralysis" contraindicating the administration of excessive amounts of MER-BCG during immunotherapy. A specific humoral response to the administration of MER-BCG was not detected, but an MER-BCG dose independent decrease in albumin associated with a non-specific, dose related elevation in serum IgG was observed.
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PMID:MER-BCG (NSC-143769): immunogenicity and toxicity of single and repeated intradermal injections in dogs. 55 13

The mitogenic and adjuvant effect in vitro of MER (methanol extracted residue of tubercle bacilli), on Balb/C and nu/nu immunocompetent cells was examined and compared with the effect of PPD, LPS, DS, PHA and ConA. MER activated DNA synthesis in spleen cells of Balb/C and nu/nu mice and in blood cultures of Balb/C. The stimulation of DNA synthesis by MER in spleen cells was not macrophage dependent. Bone marrow and 1ymph node cells were slightly stimulated while thymus cells were not affected. Both MER and PPD enhanced the in vitro immune response of Balb/C mice to SRBC and to TNP (trinitrophenyl) hapten. MER, LPS and PPD enhanced the immune response of nude spleen cells to SRBC in vitro.
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PMID:Mitogenic and adjuvant activity of a methanol extraction residue (MER) of tubercle bacilli on mouse lymphoid cells in vitro. 77 Mar 12

The aim of this study was to compare skin reactivity to routine allergen prick test with panels of allergens, supplied by three different manufacturers. The allergens comprised ten aero-allergens commonly used for skin prick test in Northern Europe, and included pollen, dander, house dust mites, and moulds. Two hundred consecutive patients were tested. The methods for standardization of allergen extracts, declaration of allergenic potency, and recommended lancets differed. The equipment were Soluprick SQ (Allergologisk Laboratorium A/S, Denmark) (ALK), Alphatest (Dome/Hollister-Stier, U.K.) (DHS), and Phazet (Pharmacia, Sweden) (PHA). The coefficient of variation for the allergen coated PHA (same lancet was applied twice) was 0.31, and for ALK and DHS allergen extracts 0.13 and 0.18, respectively. The frequencies of patients with positive reactions to the various allergens were generally similar, although DHS appeared to elicit less positive reactions to Timothy, dog, and Dermatophagoides pteronnyssinus. For the individual physician, it may be important to know the allergenic activity of the different allergens in his routine panel compared to the activity in other similar panels.
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PMID:Skin prick testing with standardized extracts from 3 different manufacturers. A comparative randomized study. 129 67

The applicability of clinical examination was studied in women with symptoms of medium-advanced or advanced primary gestosis of subpopulation of T lymphocytes (CD3+, CD4+, CD8+) in the peripheral blood. Also studied was the usefulness of the proliferative activity of lymphocytes in in vitro cultures: spontaneous and mitogenic (PHA, ConA, PWM)--in the environment of fetal calf serum (FCS) and autologous sera: heat-inactivated and heat-non-inactivated. It has observed that the percentages of particular T Lymphocyte subpopulations and the proportion of CD4+ lymphocytes to CD8+ lymphocytes in the peripheral blood and the mitogenic activity of the heat-non in activated autologous serum in the test of lymphocyte spontaneous blastic transformation reveal a correlation with an enhancement of particular clinical symptoms of EPH gestosis and with the birth condition of newborns.
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PMID:[Certain factors of cellular immunity in clinical evaluation of women with EPH gestosis symptoms]. 130 36

We recently cloned the newest human integrin beta subunit, termed beta 7, from a cDNA library constructed from SEA-activated T lymphocytes. In this communication, we report on the structure of the human integrin beta 7 protein complex determined using a rabbit anti-beta 7 peptide antibody raised to an N-terminal 22 amino acid residue sequence deduced from the human beta 7 subunit cDNA. The beta 7 subunit (Mr 116,000) expressed on PHA lymphoblasts associates with a single major alpha subunit (alpha H) that is distinct from the prominent T cell marker, integrin alpha 4. The alpha H subunit (Mr 180,000 nonreduced) displays a distinctive shift in size on reduction to an apparent Mr of 150,000. We show that these structural properties of the integrin beta 7 complex are shared with the cell surface antigen HML-1 found highly expressed on T cells which populate the intestinal epithelium and are proposed to be involved in mucosal immunity. Sequential immunoprecipitation and Western blotting demonstrate identity or close homology between the alpha H beta 7 and HML-1 proteins.
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PMID:Immunologic and structural relatedness of the integrin beta 7 complex and the human intraepithelial lymphocyte antigen HML-1. 173 Feb 87

Much remains to be clarified the functional capacities of the two major reciprocal subsets of human CD4+ cells which we interpret to be naive and memory cells. CD4+ naive (CD45RA+, LFA-3-) and memory (CD45R0+, LFA-3+) cells were rigorously purified by immunomagnetic negative selection. Their proliferation was measured in response to four protocols of receptor-mediated activation: soluble anti-CD3 mAb, plastic-immobilized anti-CD3 mAb, activating pairs of anti-CD2 mAb, and "superantigens" staphyloccocal enterotoxins A and B (SEA and SEB). Naive cells proliferated much less than memory cells to each of these four regimens although their capacity to respond was demonstrated by strong PHA-induced proliferation. Although three of the regimens depend on autologous monocytes, poorer naive cell responses are also observed to anti-CD3 mAb immobilized on plastic in the absence of monocytes; this implies an intrinsic hyporesponsiveness of naive cells, independent of their potentially weaker interaction with monocytes. Naive cells proliferated less than memory cells to superantigens SEA and SEB over a wide dose range; this assumes particular importance because such superantigens are believed to more closely mimic antigen-specific stimulation than anti-CD3 mAb. The possibility was explored that hyporesponsiveness of naive cells reflects the fact that naive cells require additional co-stimuli to facilitate their activation. In support of this concept, we observed that proliferation of naive cells to anti-CD3 mAb and SEA or SEB (but not to anti-CD2 mAb pairs) was consistently enhanced by pre-activation of monocytes present in the culture. Naive cell proliferative responses were augmented further in cultures supplemented with interleukin (IL) 1 beta and IL 6 or exposed to the co-stimulating mAb anti-CD28 and anti-CD44. The pattern of augmentation was dependent on the specific triggering regimen: anti-CD44 mAb was particularly effective in augmenting the response to superantigens, anti-CD28 mAb for the anti-CD3 response and IL 1 beta/IL 6 for that induced by anti-CD2 mAb pairs. With particular combinations of stimulus/co-stimuli naive cell proliferation was as strong as that of memory cells. We interpret these findings to indicate that naive cells are capable of responding to antigen, but that such responses are critically dependent on the available co-stimuli in vivo.
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PMID:Hyporesponsiveness of "naive" (CD45RA+) human T cells to multiple receptor-mediated stimuli but augmentation of responses by co-stimuli. 197 79

We have examined the responses of cloned T cell lines and of normal T cells to staphylococcal enterotoxins A, B, and C1 (SEA, SEB, and SEC1). SEA, SEB, and SEC1 are all very potent mitogens for T cells in the presence of Ia+ APC. The minimal activating dose of all these SE varies from 1 to 100 ng/ml. As determined by mAb blocking of the responses of both normal T cells and cloned T cell lines, SEA required either the I-A or the I-E molecule on APC for stimulating T cells, whereas SEB required the I-E molecule predominantly over I-A molecule. The TCR:CD4 complex is also involved in the response to SE. The responses to SEB and SEC1 were inhibited by anti-V beta 8 antibody F23.1, whereas the response to SEA and to PHA was not affected by this antibody. Anti-CD4 effectively inhibited responses to all SE but not to PHA. The involvement of the TCR was also confirmed by flow microfluorimetry analysis of T cell blasts responding to SE and the responses of a panel of cloned T cell lines, both of which showed that V beta 8+ T cells preferentially responded to SEB, whereas V beta 8+ T cells failed to respond to SEA. By using fixed APC, it could be shown that processing is not required for the presentation of SE. Furthermore, pulsing experiments showed that SEB can bind to relevant sites on either B cells or T cells, whereas with conventional Ag only prepulsing of the APC has worked. In one case, SEB activates a cloned T cell line in the absence of APC, and this same clone also responds directly to anti-V beta 8 antibody. Thus, SEB appears to bring together V beta 8-expressing TCR with the I-E molecule, whereas SEA apparently has the same effect on TCR expressing different V beta with either the I-A or the I-E molecule, probably depending upon which TCR is bound. The close resemblance between T cell responses to SE and those to mixed-lymphocyte stimulating (Mls) locus suggests to us that a novel SE-like protein that binds both to class II MHC molecules on the APC surface and to V beta gene products on TCR could be the product of the Mls locus.
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PMID:Bacterial proteins that mediate the association of a defined subset of T cell receptor:CD4 complexes with class II MHC. 213 3

Human CD4+ T cells differ in their expression of the leucocyte common antigen. Antibodies detecting certain forms (CD45RA and CD45RO) of this antigen have been used to identify and isolate subpopulations of the CD4+ T cells. These isolated subsets have been shown to have different abilities concerning lymphokine production and provision of help to B cells for Ig production. When these T-cell subsets were activated in vitro with polyclonal activators, the production. When these T-cell subsets were activated in vitro with polyclonal activators, the CD45RA+ cells lost this marker and gained the expression of CD45RO. This was true for all mitogens used in this report, i.e. accessory cell-dependent stimulation with SEA and accessory cell-independent activation with PMA or PHA. A correlation between proliferation and differentiation was observed, but this was probably not causative as stimulation with PMA in the absence of DNA synthesis resulted in the acquisition of CD45RO and loss of the CD45RA antigen. Moreover, cells proliferating vigorously for long periods of time expressed both markers at significant levels, which suggests that proliferation did not automatically result in complete loss of the CD45RA marker. The phenotypical differentiation was associated with a functional differentiation which induced the stimulated cells' ability to act as helper cells for Ig production and to produce gamma interferon (IFN-gamma). The results obtained in this study support the contention that the CD45RA+ cells are precursors of the CD45RO+ cells and that the two subsets represent different maturational stages of the same lineage.
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PMID:Phenotypical and functional differentiation of CD4+ CD45RA+ human T cells following polyclonal activation. 214 7

Activities of IL-1 produced by peripheral blood monocytes stimulated with lipopolysaccharide and IL-2 released by peripheral blood mononuclear cells induced by PHA, SWAP and SEA in vitro were detected in patients with various stages of schistosomiasis japonica. It was found that the activity of IL-1 was greatly increased and positively related to the body temperature, and high level of IL-2 was induced by SWAP and SEA in the group of acute schistosomiasis. The activity of IL-1 was significantly reduced in the groups of chronic and advanced schistosomiasis, especially in the latter group. The level of IL-2 induced by SWAP and SEA in the groups of chronic and advanced schistosomiasis was significantly lower than that in the group of acute schistosomiasis, but was much higher than that in the group of normal control. The level of IL-2 induced by SWAP and SEA in the cases of acute schistosomiasis was positively related to the activity of IL-1. The results indicate that the specific cellular immunity was increased in acute cases and decreased in chronic cases of schistosomiasis japonica. Both specific and nonspecific cellular immune responses were greatly reduced in cases of advanced schistosomiasis japonica. IL-1 and IL-2 may play an important role in the immunoregulation of schistosomiasis japonica.
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PMID:[Changes in induced interleukin-1 and interleukin-2 activity and their interrelationship in patients with schistosomiasis japonica]. 217 63

Human thymocytes were fractionated to a low or high specific gravity fraction (LF or HF) by the BSA incontinuous density gradient method, and stimulated by lectin, lymphokine and mixed lymphocyte culture (MLC) in order to induce natural killer (NK)-like nonspecific killer (activated lymphocyte killer, ALK) cell activity. The results are summarized below. Thymocytes of LF induced a higher amount of interleukin 2 (IL2) by PHA stimulation than those of HF. Although PHA induced ALK activity from thymocytes of LF but not from thymocytes of HF, crude IL2 induced ALK activity from both fractions. The ALK activity induced by PHA or IL2 was abrogated by treatment of OKT3 and complement but not by OKT4 or OKT8 and complement. ALK activity and allospecific cytotoxic killer cell (allo-CTL) activity were induced from thymocytes of LF by MLC and from both fractions by MLC with IL2, but there were some differences between these two activities. Hydrocortisone suppressed the induction of ALK activity but not of allo-CTL activity. Interferon-gamma enhanced the induction of ALK activity but not of allo-CTL activity. Treatment of OKT8 and complement abrogated the ALK activity but not the allo-CTL activity. There were negligible thymocytes with NK cell markers (OKMI, Leu7, Leu11) and there was no increase of these markers or large granular lymphocytes after the induction of ALK activity. These results suggest that IL2 might be essential to induce ALK activity from human thymocytes and that this killer cell might be different from NK cells and allo-CTL.
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PMID:[Induction of nonspecific killer cell activity from human thymocyte]. 294 60


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