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At least 703 records · Page 39Linked to original sources
PubMed1978

Prostaglandin-mediated hyperemia and renin-mediated hypertension during acute ureteral obstruction.

Acute elevation of ureteral pressure to 100 mm Hg in anesthetized dogs (n=7) resulted in an increase (P less than 0.005) in systemic blood pressure form 151 +/- 7 to 163 +/- 7 mm Hg, a transient (approximately 15 min) increase (P less than 0.05) in renal blood flow from 413 +/- 27 to 465 +/- 27 ml/min and a rise (P less than 0.05) in plasma renin activity from 6.0 +/- 1.6 to 10.3 +/- 2.1 ng/ml/hr. Pretreatment with a competitive inhibitor of angiotensin II, i.e. sar1gly8AII, abolished the hypertensive response to acute ureteral obstruction, and pretreatment with 2 mg/kg of either indomethacin (n=6) or meclofenamate (n=3), 15 min before obstruction, prevented the hyperemic response. These results suggest that acute ureteral obstruction leads to hypertension via activation of the renin-angiotensin system and hyperemia via a prostaglandin-initiated mechanism.

Acute Disease↗
PubMed1976

Cell-mediated immunity to herpes simplex virus in man. V. Antibody-mediated cell-dependent immune lysis of herpes virus-infected target cells.

Thirty-four patients, subject to recurrent herpes labialis, have been studied. They have all been shown to have high serum levels of an antibody to HSV1. This antibody has the property of sensitizing HSV1-infected target cells to lysis by nonimmune effector lymphocytes. Of 23 subjects who gave no history of herpes labialis, only four had antibody demonstrable by this technique. The level of antibody remains essentially unchanged despite recrudescenes of herpes labialis in the susceptible subjects. Effector cell activity was present in all of these and other subjects tested except for two who were suffering from chronic lymphatic leukemia. We have positive evidence that the effector cells in this system are neither T cells nor macrophages. Additional evidence suggests that the effector cells may be "null" cells.

Antibody Specificity↗
PubMed1989

Cytotoxicity of methotrexate and trimetrexate and its reversal by folinic acid in human leukemic CCRF-CEM cells with carrier-mediated and receptor-mediated folate uptake.

The cytotoxic effects of the antifolates methotrexate (MTX) and trimetrexate (TMQ) were investigated for two human leukemic CCRF-CEM cell lines, one expressing the "classical" reduced folate/MTX carrier (CEM-RF), another lacking this carrier but expressing a membrane associated folate binding protein (CEM-FBP). CEM-FBP cells were found to be highly resistant to MTX compared to CEM-RF cells, especially in short exposures. For example, after 4 h incubation, IC50 values for MTX were 251 microM and 0.98 microM for CEM-FBP and CEM-RF cells, respectively. On the other hand, CEM-FBP cells were much more sensitive to the lipophilic antifolate TMQ than CEM-RF cells as shown by IC50 values (after 4 h of exposure) of 0.059 microM and 7.5 microM, respectively. Finally, the reversal of TMQ cytotoxicity by folinic acid was significantly impaired for CEM-FBP cells, in contrast to CEM-RF cells. These results indicate that the nature of the membrane transport system for folates can be a critical determinant in tumor cell sensitivity or resistance to antifolates.

Biological Transport↗
PubMed1991

Tachykinin-mediated modulation of the primary antibody response in rats: evidence for mediation by an NK-2 receptor.

Evidence for the involvement of primary afferent nerves and their associated neuropeptides in in vivo immunologic responses has been based on experiments in rats in which destruction of primary afferent nerves by the sensory neurotoxin capsaicin results in a diminished ability of the animal to mount a primary antibody response to sheep red blood cell (SRBC) antigen. This effect was shown to be reversed by substance P infusion immediately following antigenic stimulation. In this report we show that neurokinin A (NKA) is 12 times more potent than substance P in its capacity to reverse the effects of neonatal capsaicin pretreatment on the antibody response. Neurokinin A has a pD2 of 6.65 compared to 5.98 for substance P. In addition, NKA was more potent than substance P in reversing the effects of surgical lesions 2 days prior to antigenic stimulation. The effects of the D- and L-Pro9 analogues of [Glp6, Pro9]-SP6-11 on the plaque-forming cell response in capsaicin-treated rats provide further support for the hypothesis that the tachykinin receptor modulating the primary antibody response is an NK-2 receptor. These results demonstrate, for the first time, a role for NKA in in vivo immunomodulation.

Animals↗
PubMed1984

Effect of orally administered food-grade carrageenans on antibody-mediated and cell-mediated immunity in the inbred rat.

Experiments were performed to investigate the immunological consequences associated with the persorption of poorly degradable carregeenans from the diet. Using an inbred strain of rat it was demonstrated histochemically, by the carrageenan-specific Alcian blue staining technique, that small quantities of food-grade carrageenans given at 0.5% in drinking-water for 90 days could penetrate the intestinal barrier of adult animals. This apparently occurred via an intact mucosa in the absence of inflammatory or pathological lesions. The carrageenan was demonstrated in macrophage-like cells present within the villi and lamina propria of the small intestine. The oral administration of kappa, lambda or iota food-grade carrageenans did not affect local (biliary) or systemic antibody responses to gut commensal microorganisms, or to orally-administered sheep erythrocytes. However, when sheep red blood cells were administered parenterally the ensuing anti-sheep red blood cell haemagglutinating antibody response was temporarily suppressed in carrageenan-fed rats. lambda-Carrageenan and iota-carrageenan both significantly (P less than or equal to 0.01 and P less than or equal to 0.05, respectively) reduced the mid-phase (14-28 days) haemagglutinin response; kappa-carrageenan (L100) was less effective but caused significant depression at day 21 (P less than or equal to 0.01). Individual responses were, however, within the control range 35 days after sheep erythrocyte administration, thus indicating the temporary nature of this effect. Although carrageenan administration depressed the anti-sheep erythrocyte antibody response, it did not affect T-cell immune competence as measured by the popliteal lymph node assay for graft-versus-host reactivity.

Administration, Oral↗
PubMed2004

Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression.

We used an experimental murine cancer metastasis model in which a colon adenocarcinoma cell line generates lung metastases, whose growth is stimulated in response to injection of bacterial lipopolysaccharide (LPS), to investigate the role of NF-kappaB in inflammation-induced tumor growth. We found that LPS-induced metastatic growth response in this model depends on both TNFalpha production by host hematopoietic cells and NF-kappaB activation in tumor cells. Inhibition of NF-kappaB in both colon and mammary carcinoma cells converts the LPS-induced growth response to LPS-induced tumor regression. The latter response is TNFalpha-independent, but depends on another member of the TNF superfamily, TRAIL, whose receptor is induced in NF-kappaB-deficient cancer cells.

Adenocarcinoma↗
PubMed2005

IgE-mediated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis.

BACKGROUND: Autoreactivity of patients with atopic dermatitis (AD) to human proteins has been postulated as a decisive pathogenetic factor for AD. OBJECTIVE: In this study, it was investigated whether the stress-inducible enzyme manganese superoxide dismutase (MnSOD) of human and fungal origin might act as an autoallergen in atopic dermatitis. METHODS: Patients with AD (n = 69; mean SCORAD [SCORing Atopic Dermatitis], 27) and other inflammatory skin diseases as well as with inhalant allergies were investigated. The presence of specific IgE against recombinant MnSOD of fungal and human origin and the fungal extracts of Aspergillus fumigatus and Malassezia sympodialis was measured by CAP, ELISA, skin prick test, and in subset of patients also by atopy patch tests (APTs) and PBMC proliferation assays. Cross-reactivity between allergens was determined by CAP inhibition. The presence of MnSOD in human skin in various inflammatory skin conditions was investigated by immunohistochemistry. RESULTS: Specific IgE antibodies against human MnSOD correlating with the disease activity were found in 29 out of 67 patients with AD. The human protein was able to induce in vitro T-cell reactivity and eczematous reactions in APT in MnSOD-sensitized patients with AD. MnSOD was upregulated in various inflammatory skin reactions and APT skin specimens. Cosensitization to structurally related and cross-reacting fungal MnSOD and the skin-colonizing yeast M sympodialis was observed in all patients sensitized against human MnSOD. CONCLUSION: Human MnSOD may play a role as an autoallergen in a subset of patients with AD, including nonatopic eczema. By molecular mimicry leading to cross-reactivity such sensitization might be induced primarily by exposure to environmental fungal MnSOD of M sympodialis .

Adult↗
PubMed2005

Cellular accumulation of tetrahydrobiopterin following its administration is mediated by two different processes; direct uptake and indirect uptake mediated by a methotrexate-sensitive process.

In our previous study on tetrahydrobiopterin (BH4) accumulation in organs of mice administered with 6RBH4, it was demonstrated that the intestinal mucosa was able to take up BH4 directly but that the liver could accomplish this only indirectly via a pathway involving the dihydrofolate reductase reaction. This observation was largely based on the fact that BH4 deposition in the liver was completely inhibited by prior treatment with methotrexate whereas deposition in the intestinal mucosa was only partially inhibited. To investigate the distinctive features of BH4 uptake in these organs, Caco-2 of intestinal epithelial origin and isolated hepatocytes were analyzed for cellular BH4 uptake in vitro. Both cell types exhibited a similar profile of BH4 accumulation but their response to methotrexate differed; the accumulation of BH4 in the hepatocytes was almost completely inhibited by methotrexate, whereas no inhibition was observed in Caco-2 cells, suggesting that the process of BH4 accumulation in Caco-2 cells, unlike hepatocytes, did not involve enzymic reduction by dihydrofolate reductase. Furthermore, 6SBH4, a synthetic diastereomer of BH4, was loaded into Caco-2 cells and the accumulated BH4 was identified as 6SBH4. These results provided strong evidence that BH4 had directly accumulated in Caco-2 cells. The distinctive features of BH4 deposition in the intestinal mucosa and liver reflected the means by which Caco-2 cells or hepatocytes, both representative cells of these tissues, took up extracellular BH4, i.e., in a direct or indirect manner, respectively.

Animals↗
PubMed2001

Aortic valve endothelial cells undergo transforming growth factor-beta-mediated and non-transforming growth factor-beta-mediated transdifferentiation in vitro.

Cardiac valves arise from endocardial cushions, specialized regions of the developing heart that are formed by an endothelial-to-mesenchymal cell transdifferentiation. Whether and to what extent this transdifferentiation is retained in mature heart valves is unknown. Herein we show that endothelial cells from mature valves can transdifferentiate to a mesenchymal phenotype. Using induction of alpha-smooth muscle actin (alpha-SMA), an established marker for this process, two distinct pathways of transdifferentiation were identified in clonally derived endothelial cell populations isolated from ovine aortic valve leaflets. alpha-SMA expression was induced by culturing clonal endothelial cells in medium containing either transforming growth factor-beta or low levels of serum and no basic fibroblast growth factor. Cells induced to express alpha-SMA exhibited markedly increased migration in response to platelet-derived growth factor-BB, consistent with a mesenchymal phenotype. A population of the differentiated cells co-expressed CD31, an endothelial marker, along with alpha-SMA, as seen by double-label immunofluorescence. Similarly, this co-expression of endothelial markers and alpha-SMA was detected in a subpopulation of cells in frozen sections of aortic valves, suggesting the transdifferentiation may occur in vivo. Hence, the clonal populations of valvular endothelial cells described here provide a powerful in vitro model for dissecting molecular events that regulate valvular endothelium.

Animals↗
PubMed1997

Bradykinin-induced knee joint incapacitation involves bradykinin B2 receptor mediated hyperalgesia and bradykinin B1 receptor-mediated nociception.

The participation of B1 and B2 types of bradykinin receptors was studied in the rat knee-joint incapacitation test. Five intra-articular successive hourly administrations of bradykinin produced progressive incapacitation, thus indicating that bradykinin induced sensitization to its own nociceptive effect. Four co-injections of bradykinin with the bradykinin B1 receptor antagonist des-Arg9-[Leu8]bradykinin were without nociceptive effect. However, a 5th injection of bradykinin alone produced intense incapacitation. The bradykinin B2 receptor antagonist HOE-140 ([D-Arg)[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), or indomethacin, prevented the bradykinin-induced incapacitation. However, successive co-injections of bradykinin with prostaglandin E2, in contrast to bradykinin alone, did induce incapacitation in animals pretreated with indomethacin or HOE-140. The injection of the bradykinin B1 receptor agonist des-Arg9-bradykinin into prostaglandin E2-treated joints did induce incapacitation, although administration of the bradykinin B1 receptor agonist or prostaglandin E2 alone did not induce incapacitation. In conclusion, in ongoing articular inflammation, it is suggested that the bradykinin B1 receptor is particularly involved with nociceptor activation, while the bradykinin B2 receptor is related to nociceptor sensitization.

Animals↗
PubMed1998

Decreased protein kinase C activation mediates inhibitory effect of norathyriol on serotonin-mediated endothelial permeability.

We examined the mechanisms of norathyriol on the serotonin-induced increased permeability of rat heart endothelial cell monolayers. The present study showed that the activation of rat heart endothelial cell protein kinase C by phorbol myristate acetate led to the dose-dependent increase in endothelial permeability to albumin, an effect that was inhibited by staurosporine (a protein kinase inhibitor). Staurosporine also attenuated the serotonin-induced increase in permeability. Norathyriol abolished both serotonin- and phorbol myristate acetate-induced permeability. We investigated whether norathyriol, by inhibiting protein kinase C activation, attenuated the serotonin-induced permeability. Immunofluorescence studies demonstrated that norathyriol prevented the redistribution of protein kinase C isozymes following stimulation with serotonin. Western blot analysis showed that norathyriol significantly inhibited the serotonin-induced translocation of the alpha protein kinase C isozyme from the cytosolic to the particulate fraction. In conclusion, norathyriol attenuates the serotonin-induced permeability of rat heart endothelial cells to macromolecules in association with inhibition of protein kinase C activation. This decrease in endothelial cell permeability may be one of the mechanisms for the protective effects of norathyriol against edema formation in response to inflammatory agonists in vivo.

Animals↗
PubMed1997

Influence of moderate physical exercise on insulin-mediated and non-insulin-mediated glucose uptake in healthy subjects.

To establish the relative importance of insulin sensitivity and glucose effectiveness during exercise using Bergman's minimal model, 12 nontrained healthy subjects were studied at rest and during 95 minutes of moderate exercise (50% maximum oxygen consumption [VO2max]). Each subject underwent two frequently sampled intravenous glucose tolerance tests (FSIGTs) for 90 minutes, at rest (FSIGTr) and during exercise (FSIGTe). Plasma glucose, insulin, and C-peptide were determined. Insulin sensitivity (S(I)), glucose effectiveness at basal insulin (S(G)), insulin action [X(t)], and first-phase (phi1) and second-phase (phi2) beta-cell responsiveness to glucose were estimated using both minimal models of glucose disposal (MMg) and insulin kinetics (MMi). Glucose effectiveness at zero insulin (GEZI), glucose tolerance index (K(G)), and the area under the insulin curve (AUC(0-90)) were also calculated. Intravenous glucose tolerance improved significantly during physical exercise. During exercise, S(I) (FSIGTr v FSIGTe: 8.5 +/- 1.0 v 25.5 +/- 7.2 x 10(-5) x min(-1) [pmol x L(-1)]-1, P < .01), S(G) (0.195 +/- 0.03 v 0.283 +/- 0.03 x 10(-1) x min(-1), P < .05), and GEZI (0.190 +/- 0.03 v 0.269 +/- 0.04 x 10(-1) x min(-1), P < .05) increased; however, no changes in phi1 and phi2 were found. Despite a significant decrease in the insulin response to glucose (AUC0-90, 21,000 +/- 2,008 v 14,340 +/- 2,596 pmol x L(-1) x min, P < .01), insulin action [X(t)] was significantly higher during the FSIGTe. These results show that physical exercise improves mainly insulin sensitivity, and to a lesser degree, glucose effectiveness. During exercise, the insulin response to glucose was lower than at rest, but beta-cell responsiveness to glucose did not change.

Adult↗