Search results for "Receptor"
showing 10 items of 6990 documents
TMS-EEG signatures of glutamatergic neurotransmission in human cortex
2019
AbstractNeuronal activity in the brain is regulated by an excitation-inhibition balance. Glutamate is the main excitatory neurotransmitter. Transcranial magnetic stimulation (TMS) evoked electroencephalographic (EEG) potentials (TEPs) represent a novel way to quantify pharmacological effects on neuronal activity in the human cortex. Here we tested TEPs under the influence of a single oral dose of two anti-glutamatergic drugs, perampanel, an AMPA-receptor antagonist, and dextromethorphan, an NMDA-receptor antagonist, and nimodipine, an L-type voltage-gated calcium channel blocker in 16 healthy adults in a pseudorandomized, double-blinded, placebo-controlled, crossover design. Single-pulse TM…
The affinities of monoclonal antibodies against core antigen of hepatitis B virus
1994
Four monoclonal antibodies generated against the recombinant core antigen of hepatitis B virus are investigated for antigen binding. All exhibit a similar affinity to polystyrene-sorbed antigen but only one of them interacts with native form of HBcAg (an assembled particle) in solution. The presence of 0.1% sodium dodecylsulphate is required for the binding of other three antibodies. The phenomenon can be interpreted as inaccessibility of the corresponding epitopes unless the multimeric antigen structure is disrupted. The core antigen coated on polystyrene is considered as a similar exposed structure.
Carcinogenic aspect of xenobiotic molecules belonging to the peroxisome proliferator family.
1999
It is known that a short-term exposure of rat, mice or incubation of hepatic cells with fibrate molecules leads to increase in peroxisome number and cell hyperplasia. Further, long-term incubation of cells (at least a year) show transformed characteristics with foci and nodules. To explain the hepatocarcinogenic effect of peroxisome proliferators in rodents we studied the effect of peroxisome proliferators on rat liver oncogenes expression. Earlier, we reported an increase in liver and kidney mRNA level of c-myc and N-myc. Since several metabolic genes are activated by PPAR (peroxisome proliferators activated receptor) through a PPRE (peroxisome proliferator response element), we suggest th…
Evaluation of a novel monoclonal antibody against tumor-associated MUC1 for diagnosis and prognosis of breast cancer
2019
There is still a great unmet medical need concerning diagnosis and treatment of breast cancer which could be addressed by utilizing specific molecular targets. Tumor-associated MUC1 is expressed on over 90 % of all breast cancer entities and differs strongly from its physiological form on epithelial cells, therefore presenting a unique target for breast cancer diagnosis and antibody-mediated immune therapy. Utilizing an anti-tumor vaccine based on a synthetically prepared glycopeptide, we generated a monoclonal antibody (mAb) GGSK-1/30, selectively recognizing human tumor-associated MUC1. This antibody targets exclusively tumor-associated MUC1 in the absence of any binding to MUC1 on health…
Mucin 1 downregulation associates with corticosteroid resistance in chronic rhinosinusitis with nasal polyps
2013
Background A number of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) are resistant to oral corticosteroids. Mucin 1 (MUC1) shows anti-inflammatory properties, and its cytoplasmic tail (CT) interacts with transcription factors, facilitating their nuclear translocation. Because glucocorticoid receptor (GR) nuclear translocation is key to the anti-inflammatory effect of corticosteroids, we hypothesized that MUC1 is involved in the effectiveness of corticosteroids. Objective To analyze the role of MUC1 in corticosteroid effectiveness in different cohorts of patients with CRSwNP and elucidate the possible mechanisms involved. Methods Seventy-three patients with CRSwNP took oral…
General considerations in the interpretation of I-J genetic restrictions: evidence that the antigen-binding chain of antigen-specific T-suppressor fa…
1987
SUMMARY (CBA × B10)F1 [(H-2k x H-2b)] mice produce two types of antigen-specific T-suppressor factor (TsF), which can be separated by affinity chromatography on anti-I-J monoclonal antibody. After reduction and alkylation, both chains of F1 TsF are required for biological activity. However, the antigen-binding chain (AgBC) of F1 TsFk (AgBCk) is only complemented by I-Jk and likewise for F1 TsFb. In other words, interchain complementation shows the same genetic restriction in interchain complementation in parental and F1 mice. F1 TsF bearing, for example, I-Jk (TsFk), interacts with haptenized ‘antigen-presenting cells’ (‘APC’) of both parental haplotypes, and may be described as showing dua…
Targeting a Targeted Drug: An Approach Toward Hypoxia-Activatable Tyrosine Kinase Inhibitor Prodrugs
2016
Tyrosine kinase inhibitors (TKIs), which have revolutionized cancer therapy over the past 15 years, are limited in their clinical application due to serious side effects. Therefore, we converted two approved TKIs (sunitinib and erlotinib) into 2-nitroimidazole-based hypoxia-activatable prodrugs. Kinetics studies showed very different stabilities over 24 h; however, fast reductive activation via E. coli nitroreductase could be confirmed for both panels. The anticancer activity and signaling inhibition of the compounds against various human cancer cell lines were evaluated in cell culture. These data, together with molecular docking simulations, revealed distinct differences in the impact of …
Demonstration of P29, an oestrogen receptor-associated tumor marker, in human term placenta.
1991
A Mr29,000 serine phosphoprotein (P29) related to oestradiol receptor was studied in human term placenta with the use of a specific monoclonal antibody (D5). D5 was used with two different methods, immunohistochemistry and immunoradiometry. For immunohistochemistry, an indirect immunoperoxidase method was chosen to detect P29 in methacarn-fixed, wax-embedded sections. P29 was mostly confined to the syncytiotrophoblast surrounding placental villi, staining being positive in both cytoplasm and nuclei. The stroma of villi was negative. Content of P29 was uniformly high in crude placental cytosol, as measured by immunoradiometry assays. Specificity of D5 against P29 in placenta was tested by an…
Structural, Thermodynamic, and Kinetic Traits of Antiestrogen-Compounds Selectively Targeting the Y537S Mutant Estrogen Receptor α Transcriptional Ac…
2019
The most frequently diagnosed cancers in women are the estrogen receptor (ER)-positive breast cancer subtypes, which are characterized by estrogen dependency for their growth. The mainstay of clinical treatment for this tumor relies on the modulation of ER action or on the suppression of estrogen biosynthesis via the administration of Selective ERα Modulators/Down-regulators (SERMs/SERDs) or aromatase inhibitors, respectively. Nevertheless, de novo and acquired resistance to these therapies frequently occurs and represents a major clinical concern for patient survival. Recently, somatic mutations affecting the hormone-binding domain of ERα (i. e. Y537S, Y537N, D538G) have been associated w…
Novel Approaches for Immunosuppression in Graves’ Hyperthyroidism and Associated Orbitopathy
2020
<b><i>Background:</i></b> Both Graves’ hyperthyroidism (GH) and Graves’ orbitopathy (GO) are associated with significant adverse health consequences. All conventional treatment options have limitations regarding efficacy and safety. Most importantly, they do not specifically address the underlying immunological mechanisms. We aim to review the latest development of treatment approaches in these two closely related disorders. <b><i>Summary:</i></b> Immunotherapies of GH have recently demonstrated clinical efficacy in preliminary studies. They include ATX-GD-59, an antigen-specific immunotherapy which restores immune tolerance to the thyrotropin…