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)

Purified interleukins 1 and 2 (IL-1 and IL-2) were used to investigate their role in the production of gamma-interferon (gamma-IFN). Macrophage depletion from human peripheral blood mononuclear leukocytes (PBML) inhibited gamma-IFN production. Addition of purified IL-1 partially restored IFN production of macrophage-depleted PBML induced by three T cell mitogens (phytohemagglutinin, PHA; concanavalin A, con A; and staphylococcal enterotoxin A, SEA), but had no effect on induction of IFN production by undepleted PBML. Therefore endogenous IL-1 production by macrophages is probably one of the mechanisms by which they act as accessory cells for IFN production by lymphocytes. A monoclonal antibody 9.6 which binds to the sheep erythrocyte (E) receptor found on human T cells inhibited IFN production. Addition of IL-2, but not IL-1, was found to reverse this inhibition. Prostaglandin E2, a macrophage product, inhibited gamma-IFN production induced by PHA, Con A, and OKT3 but usually not SEA. This inhibitory effect was reversible by the addition of IL-2 but not IL-1. In the absence of mitogen IL-1 alone rarely induced any IFN production, although some IFN was produced by PBML from a small minority of donors. Without mitogen IL-2 induced IFN production only at very high concentrations and the added presence of IL-1 did not enhance this induction.
 ...
PMID:The regulation of gamma-interferon production by interleukins 1 and 2. 310 55

Previously it was shown that macrophages (M phi) isolated from the vigorous (Vig) or modulated (Mod) liver granulomas (Gr) of Schistosoma mansoni-infected mice restored mitogen and parasite egg antigen-induced proliferative responses to accessory cell-depleted lymphocytes. Furthermore, supraoptimal concentrations of highly activated VigGrM phi suppressed lymphoproliferation to a greater extent than did the lesser activated ModGrM phi. In this study we investigated the role of soluble mediators in GrM phi accessory/regulatory activity. Indomethacin released VigGrM phi-mediated inhibition of mitogen but not antigen-induced lymphoproliferation. Extensively dialyzed serum-free GrM phi culture supernatant nonspecifically suppressed SEA- or KLH-induced blastogenesis. Culture supernatants also reduced vesicular stomatitis virus-induced plaque formation in supernatant-pretreated L-929 fibroblasts. The 20 to 45 Kd GrM phi-derived lymphoproliferation suppressive factor (SF) and the 20 to 50 Kd viral plaque-reducing factor (PRF) were stable at low pH, but became inactivated by heat and trypsin digestion. Although freshly isolated Vig or ModGrM phi contained preformed SF and PRF, in vitro production of the factors were depressed by protein synthesis inhibitors. Moreover, SF was active only when added to cultures before day 3 of the 6-day proliferation assay. Both SF and PRF were specifically retained on rabbit anti-murine IFN-alpha/beta immunoaffinity columns. Thus, the suppressive activity of Vig or ModGrM phi is in part mediated by a monokine that shares physical, biological, and antigenic characteristics with murine IFN-alpha/beta. In contrast to the suppression of antigen-driven proliferation, GrM phi culture supernatant costimulated PHA-induced mitogenesis. The 13 to 21 Kd GrM phi-derived lymphocyte-activating factor (LAF) was stable to heat, low pH, and trypsin digestion. Freshly isolated Vig or ModGrM phi contained preformed LAF, although its in vitro production was depressed by protein synthesis inhibitors. The physical and biological characteristics of GrM phi-derived LAF appear similar to IL 1. It is concluded that both Vig and ModGrM phi secrete regulatory/accessory monokines that may contribute to the initiation and maintenance of the focal inflammatory granulomatous response.
 ...
PMID:Characterization of regulatory (interferon-alpha/beta) and accessory (LAF/IL 1) monokine activities from liver granuloma macrophages of Schistosoma mansoni-infected mice. 310 71

Direct correlation was established between changes in the activity of natural killers and capacity of lymphocytes for interferon synthesis after stress was demonstrated. Thymosin was found to enhance interferon synthesis in response to induction with NDV, PHA, and SEA in the period of marked inhibition of splenocyte function as a result of stress. The phenomenon of restoration by thymosin of the capacity of splenocytes in the post-stress phase to synthesize interferon in response to induction was also established in vivo.
 ...
PMID:[Thymosin restoration of the interferon-synthesizing capacity of the splenocytes in mice undergoing stress exposure]. 387 11

Human lymphocytes obtained by cytapheresis were stimulated in spinner culture conditions by nonpurified PHA in order to study the production of gamma interferon, and the characterization of IFN-gamma mRNA. Titers of interferon prepared in 0.6 to 4 1 batches, varied in 20 preparations from 8,000 to 32,000 units/ml. This interferon was unstable at pH 2: the residual antiviral activity after 20 h treatment was less than 3%. Antibodies raised against gamma interferon from Con A and SEA-stimulated lymphocytes neutralized the interferon induced by PHA, indicating that all three preparations are antigenically related. Poly(A)RNA from control, noncultivated lymphocytes and from lymphocytes stimulated by PHA for 18 h were translated in reticulocyte lysates and analysed by polyacrylamide gel electrophoresis. The pattern of synthesized polypeptides was different suggesting modifications in the population of mRNA. When total poly(A)RNA was inoculated into Xenopus Laevis oocytes, interferon activity was found with both, control and stimulated mRNAs although only at low levels in the control. After sucrose gradient fractionation of poly(A)RNA, each fraction was inoculated into oocytes and interferon activity measured in the oocyte bathing medium. A low level was synthesized by the RNA fractions around 28 S from control as well as from stimulated lymphocytes. These interferons were not neutralized by anti-IFN-alpha or anti-IFN-gamma sera but they were neutralized by anti-IFN-beta serum. Only the 16 S RNA fraction from PHA-stimulated lymphocytes induced high levels of interferon in oocytes. This interferon has been characterized as gamma interferon. Each fraction obtained from sucrose gradients on poly(A)RNA from control and PHA-stimulated lymphocytes was translated in reticulocyte lysate. Gel analysis of the products showed striking differences when the same fraction of both RNAs were compared. Concerning particularly the 16 S RNA from PHA-stimulated lymphocytes, where gamma interferon mRNA was present, polypeptides ranged from 15 to 55 K with a bulk around 45 K, indicating heterogeneous RNA molecules.
 ...
PMID:Translation of mRNA from phytohemagglutinin-stimulated human lymphocytes: characterization of interferon mRNAs. 612 11

The production of alpha, beta and gamma interferons (IFN) and interleukin 2 (IL-2) by Lyt-2+-dependent cytotoxic T-cell lines/clones was investigated. Cloned and uncloned T-cell lines specific for H-2Dd or the unique RL male 1 leukemia antigen were studied. After infection with Sendai virus (SV) or Newcastle disease virus (NDV) all cell lines produced IFN-alpha and -beta. Induction of IFN-gamma was attempted with the mitogens Con A, PHA, PWM, SEA, and SEB, with poly(I:C), with antibodies Lyt-1.2, -2.2, and Thy-1.2, or with the target cells Meth A (H-2Dd+) and RL male 1. All mitogens were effective inducers. However, the antibodies and poly(I:C) were not. One uncloned RL male 1-specific cell line CTLL-RP, produced IFN-gamma after induction with RL male 1. Production of IFN-alpha, beta depended on IL-2, whereas production of IFN-gamma did not, although addition of highly purified IL-2 increased IFN-gamma production even in the absence of other inducers. Crude IL-2 inhibited the production of IFN-gamma but not IFN-alpha, beta. In response to mitogens, some T-cell clones also produced IL-2. The results demonstrate that Lyt-2+ cells can produce a broad spectrum of lymphokine activities after appropriate stimulation. Their availability now affords us the opportunity to study the regulation of lymphokine production at the clonal level.
 ...
PMID:Characterization of interleukin 2-dependent cytotoxic T-cell clones. IV. Production of alpha, beta and gamma interferons and interleukin 2 by Lyt-2+ T cells. 619 26

Reduced cellular immune response is well documented in patients with advanced breast cancer. To investigate immunocompetence at the time of diagnosis, 104 patients with breast cancer staged according to the TNM classification were studied preoperatively and compared with 95 age matched healthy women. Tests of blood mononuclear leukocytes included lymphocyte and monocyte counts, determination of rosette forming T (SER +) and B (MER +) lymphocytes, T lymphocyte subsets defined with monoclonal antibodies (Leu-1, Leu-2a, Leu-3a) and with lectin fractionation (soybean agglutinin, SBA), lymphocyte transformation tests with PHA and ConA and colony formation of T cells in agar (TL-CFC). Two age groups (A: 30-50, B: 51-70 years) and the different tumor stages (I-IV) were analyzed. Patients and controls did not differ in absolute numbers of lymphocytes, T and B cells. In patients of group B the absolute number of monocytes was slightly increased in stages II and III and significantly in stage IV (p less than 0.025). Similarly, the lymphocyte response to PHA was significantly reduced in stage IV group B only (p less than 0.05). ConA induced lymphocyte proliferation and TL-CFC capacity were not different in patients and controls. In the small number of patients and age matched controls, in whom T lymphocyte subsets were determined, the relative numbers of T cells with helper or suppressor phenotype as defined with Leu-3a, Leu-2a, or SBA were similar. In conclusion, in breast cancer, at the time of diagnosis, blood T lymphocyte populations and functions are not altered except in elderly patients with disseminated disease. The monocytosis and reduced PHA responsiveness observed in the latter group may be related phenomena.
 ...
PMID:[Intact cellular immune response in patients with locally metastasizing breast carcinoma at the time of diagnosis]. 622 73

Although conditioned medium (CM) from human lymphocytes or mononuclear cells is the most readily available source of interleukin-2 (IL-2) for human T cell culture, its IL-2 activity in our experience is inconsistent. It is likely that this is, at least in part, due to the presence of toxic substances in the CM. Using CM from TPA/SEA induced human mononuclear cells, we have found that acid treatment (pH 2.0, greater than 30 min) significantly improves its ability to promote T cell growth. It is postulated that the selection process which occurs in cultures of mitogen stimulated T cells may result in cells which are sensitive to mitogen-induced lymphotoxins and that these are inactivated by the acid treatment. Since acid treatment did not similarly improve the T cell growth promoting ability of PHA induced, lectin-free commercial IL-2, there must be other differences between it and our CM, which play a role in T cell growth.
 ...
PMID:Acid treatment enhances IL-2 activity of conditioned medium. 636 68

Supernatants from 24 hr cultures of PHA-pulsed human T lymphocytes inhibit the migration of human peripheral blood T lymphocytes and guinea pig macrophages in vitro. The factor responsible for the inhibition of T lymphocytes provisionally called TIF (T cell migration inhibitory factor) was separated from MIF by preparative PAGE, had apparent molecular weight (m.w.) of 1,000-10,000 daltons and isoelectric point of 3.1. TIF activity was resistant to treatment with trypsin, chymotrypsin and neuraminidase but sensitive to PMSF (phenyl-methyl-sulfonyl-fluoride). This suggests that TIF is presumably different from human MIF and may represent a novel lymphokine which preferentially affects T cell migration in vitro.
 ...
PMID:Partial purification and physicochemical properties of human T cell migration inhibitory factor (TIF). 639 62

Intradermal, interlesional and intravenous MER/BCG have been reported to possess immunostimulatory properties and combined with chemo-radiotherapy an anti-neoplastic effect. Due to local and systemic side effects of the methanol extraction residue of BCG therapy a new approach to oral administration was investigated. Seventeen patients with inoperable non-oat cell lung cancer were given oral MER for 30 days. Skin tests to 5 recall antigens and various concentrations of MER, lymphocyte stimulation by PHA were done before and repeated during therapy. The initial group of patients received a dose of 1.25 mg per day and when no side effects were detected the dose was gradually escalated in subsequent groups of patients up to 5 mg. Oral MER was well tolerated even at the higher dose with no clinical or laboratory side effects. No regression in tumor size was seen. In 6 of 17 patients the disease remained stationary for a mean of 6 months (Range 6-14 months). In the remainder, disease progressed after a mean of 15 weeks. Two patients had cutaneous PPD reactivity converted from negative to positive, in one it became negative, while the remaining patients maintained their original responsiveness. No major changes could be observed in the in vivo immune tests performed following the course of treatment. In view of the reported relative efficacy of oral BCG administration, and considering the very low toxicity with oral MER, further studies employing considerably higher doses of this nonviable vaccine are now justified.
 ...
PMID:Oral administration of the methanol extraction residue of BCG (MER/BCG): a phase I study in non-oat cell lung cancer patients. 662 93

In vitro immunological tests showed that patients with pre-eclampsia are characterized by a greater degree of lymphocyte hyporesponsiveness to mitogens during pregnancy than normotensive controls. Thus, a relationship has been hypothesized between the hypoimmune lymphocyte response and the pathogenesis of the disease. We studied 20 non-pregnant healthy volunteers (group a), 11 women with a normal pregnancy (group b) and 13 women with EPH gestosis (group c). In all patients we determined the number of lymphocytes and the lymphocyte function (PHA, Con A, PWM responsiveness) in autologous and homologous plasma during pregnancy and 5 to 30 days after delivery. The mean values of the number of EAC and E rosettes in the three groups studied were similar. The mean values of the mitogenic response to PHA in autologous plasma were significantly reduced in both groups b and c in comparison with group a, but there was no statistical difference between groups b and c. The PHA lymphocyte responsiveness returned to normal in both homologous and autologous plasma after delivery. Our data demonstrate that no difference exists between pregnant women with and without pre-eclampsia as regards impaired cell-mediated lymphocyte response in vitro. Moreover, the diminished lymphocyte responsiveness to mitogens during pregnancy seems to be due to humoral circulating factor(s).
 ...
PMID:Lymphocyte hyporesponsiveness during edema, proteinuria and hypertension (EPH) gestosis. 729 70


<< Previous 1 2 3 4 5 6 7 8 9 Next >>