Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Integrins play an important role in lymphocyte adhesion to cellular and extracellular components of their microenvironment. The regulation of such adhesion often involves changes in the functional state of the integrins rather than alterations in their expression levels. Although the functional basis for such transitions is unknown, a possible role for disulfide exchange might be postulated based on the observations that integrin function can be activated by bifunctional reducing agents or by Abs that react with areas adjacent to predicted long-range disulfide bonds in integrins. Recently, it has been reported that enzymes that catalyze disulfide exchanges such as protein disulfide isomerase (PDI) are present on the surface of lymphoid cells, raising the possibility that such enzymes might be involved in the control of lymphocyte adhesion. A number of inhibitors of PDI function were examined for their effects on integrin-mediated adherence of T cells. The results did not support role for PDI in the regulation of integrin function, as the inhibitors somatostatin A, tocinoic acid, dithiobisnitrobenzoic acid, and anti-PDI mAb did not interfere with adherence. However, one of the PDI inhibitors, bacitracin, selectively interfered with the beta1 integrin-mediated adherence of lymphoid cells to collagen, fibronectin, laminin, and VCAM-1, and with alpha4beta7-dependent adherence to fibronectin and to VCAM-1. In contrast, alpha(v)beta3- and alpha(L)beta2-mediated adherence were not inhibited. Thus, it appears that bacitracin may be a selective inhibitor of beta1 and beta7 integrin functions by an as yet unknown mechanism.
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PMID:The selective inhibition of beta 1 and beta 7 integrin-mediated lymphocyte adhesion by bacitracin. 983 22

The aim of this prospective, randomized study was to investigate the serum levels of tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble interleukin-1 receptor antagonist (sIL-1RA) in patients with thyroid eye disease (TED) before and 1 and 3 months after treatment with somatostatin analogues (SM-a). Thirty patients, all with signs and symptoms of TED, were studied. Twenty-two patients (13 females) had active eye disease with a clinical activity score (CAS) > or = 4 (patients with active disease [PA]) and 8 patients (5 females) had inactive TED with CAS < or = 3 (patients with inactive disease [PI]). All PA patients had a positive orbital octreoscan, whereas PI patients had a negative one. Fifteen patients from the PA group were selected randomly and received SM-a (PA-S subgroup), while the remaining 7 patients were used as control subgroup (PA-C), received neither therapy, nor placebo. From the 15 patients who received SM-a (PA-S), 6 received octreotide (OCT) and 9 lanreotide (LRT). TED was reevaluated using the CAS 1 and 3 months after the initiation of SM-a treatment. Ten healthy individuals (6 females) were used as controls (group C). We found an increase in the basal levels of TNF-alpha (14.2 +/- 7.1 pg/mL), sICAM-1 (809.1 +/- 167.0 ng/mL), and sIL-1RA (542.1 +/- 259.0 pg/mL) in PA patients as a total group compared with the PI (1.6 +/- 1.9, 676.8 +/- 73.4, 267.6 +/- 152.8, respectively) group and C (1.9 +/- 1.4, 598.0 +/- 126.2, 258.6 +/- 155.1, respectively). The basal levels of TNF-alpha (13.3 +/- 8.3 pg/mL) and sIL-1RA (533.7 +/- 308.9 pg/mL) in PA-S as well as in PA-C (16.0 +/- 2.9, 560.2 +/- 107.3, respectively) subgroups were also increased compared with PI patients and C (1.9 +/- 1.4 and 258.6 +/- 155.1, respectively). The same was true for sICAM-1 when baseline levels compared with C (817.1 +/- 187.3 and 791.9 +/- 123.5, respectively vs. 598.0 +/- 126.2 ng/mL). After SM-a, serum levels of sICAM-1 and sVCAM-1 were decreased significantly 1 (781.2 +/- 205.9, 1,193.5 +/- 511.8 ng/mL) and 3 months (786.8 +/- 199.6, 1,122.1 +/- 225.3 ng/mL) after the initiation of treatment. In conclusion, serum levels of TNF-a, sICAM-1, and sIL-1RA were elevated in patients with active TED compared to controls. Furthermore, sICAM-1 and sVICAM-1 levels declined during the treatment with SM-a in patients with active TED.
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PMID:Serum levels of tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble interleukin-1 receptor antagonist in patients with thyroid eye disease undergoing treatment with somatostatin analogues. 1218 98

Increased plasma plasminogen activator inhibitor-1 (PAI-1) has been implicated in the development of vascular disease. In type 2 diabetes mellitus high PAI-1 levels are associated with increased plasma concentrations of free fatty acids (FFA) and triacylglycerol indicating an association or a causal relationship. To answer that question, the effect of FFA/triacylglycerol on plasma PAI-1 was examined. Ten healthy male volunteers were studied for 6 h during infusion of triacylglycerol [1.5 ml/min]/heparin [0.2 IU/(kg.min)] (LIP; n=10), saline only (SAL; n=10), and saline/heparin (HEP; n=5). Plasma insulin concentrations were kept constant at approximately 35 pmol/l by intravenous somatostatin-insulin infusions and there was no significant change in plasma glucose levels during any of the study protocols. LIP increased plasma triacylglycerol and FFA approximately 3- (p < 0.001) and approximately 8- (p < 0.000001) fold, respectively, within 90 min. Baseline plasma PAI-1 measured by a bio-immunoassay was similar in HEP (11.4 +/- 2.8 ng/ml), SAL (16.6 +/- 3.6 ng/ml), and LIP studies (15.2 +/- 3.4 ng/ml). Since studies were initiated in the morning, PAI-1 decreased (p < 0.025) over time following its normal diurnal variation to 6.4 +/- 2.0 ng/ml and 4.0 +/- 2.4 ng/ml at 360 min in SAL and HEP, respectively. During LIP, however, PAI-1 increased to approximately 2.6 fold higher levels than during SAL at 360 min (16.4 +/- 4.0 ng/ml, p < 0.01). While tissue plasminogen activator (tPA) and adipsin, an adipocyte derived protease, were unaffected by LIP, changes in soluble vascular cell adhesion molecule-1 (sVCAM-1) were significantly correlated (p = 0.02) with those seen for PAI-1. This suggests that hyperlipidemia independent of insulin and plasma glucose levels stimulates vascular tissue and in turn might induce an increase in plasma PAI-1. PAI-1 then could contribute to the development of atherothrombotic vascular disease.
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PMID:Increased plasma levels of plasminogen activator inhibitor-1 and soluble vascular cell adhesion molecule after triacylglycerol infusion in man. 1295 10