Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane cofactor protein (MCP or gp45-70) of the complement system is a cofactor for factor I-mediated cleavage of fluid-phase C3b and C3b-like C3, which opens the thioester bond. In the present study the activity of MCP was further characterized. Unexpectedly, in the absence of factor I, MCP stabilized the alternative- and, to a lesser extent, the classical-pathway cell-bound C3 convertases and thereby enhanced C3b deposition. Soluble MCP, if added exogenously, hardly functioned as cofactor for the cleavage of erythrocyte-bound C3b to iC3b; i.e. its activity, compared with the cofactor activity of factor H, was inefficient, since less than 10% of the bound C3b was MCP-sensitive. Further, exogenously added soluble MCP was also a weak cofactor for the cleavage of C3b bound to zymosan. Likewise, factor I, in the presence of cells bearing MCP, cleaved fluid-phase C3b inefficiently. These results imply that MCP has very little extrinsic cofactor activity for factor I. In contrast, exogenously added MCP and factor I mediated efficient cleavage of erythrocyte-bound C3b if the concentration of Nonidet P40 was sufficient to solubilize the cells. Interestingly, soluble MCP and factor I degraded C3b attached to certain solubilized acceptor membrane molecules more readily than others. The cleavage reaction of fluid-phase and cell-bound C3b by soluble MCP and factor I produced iC3b, but no C3c and C3dg. These and prior data indicate that soluble MCP has potent cofactor activity for fluid-phase C3b or C3b bound to solubilized molecules, but acts inefficiently towards C3b on other cells. This functional profile is unique for a C3b/C4b binding protein and, taken together with its wide tissue distribution, suggests an important role for MCP in the regulation of the complement system.
 ...
PMID:Functional properties of membrane cofactor protein of complement. 248 48

A case report of a mutilating injury of the hand is presented illustrating the use of a composite tendo-aponeuro-capsular autograft during primary reconstruction, with the aim to preserve the functional ability of the injured MCP joint. Some conditions necessary for such reconstruction are also mentioned.
 ...
PMID:[Use of the composite tendo-aponeuro-capsular autotransplant in the early repair of injuries of the metacarpophalangeal (MCP) joint--case report]. 248 29

Of 210 women with galactorrhea 66.2% had normal prolactin serum levels. Only in 33.4% elevated prolactin levels could be found, 0.4% were hypoprolactinemic. The TRH-stimulation test detected latent hyperprolactinemia in 13.5% of the cases, showed a normal thyroid function in 81.5%, hypothyroidism in 13.9% and hyperthyroidism in 4.6% and this is considered to be a more valuable diagnostic tool than the MCP-test. Galactorrhea was associated with the following conditions: hyperprolactinemia (34.8%), menstrual disturbances (67.4%), post-pill amenorrhea (30.2%), mastalgia (30.2%), prolactinoma (18.6%), fibrocystic disease (11.6%), hirsutism (4.6%), diabetes mellitus (2.3%).
 ...
PMID:[The value of hyperprolactinemia determination within the scope of galactorrhea]. 249 8

The pituitary and corpus luteum responses to acute gonadotropin-releasing hormone (GnRH) administration at the mid-luteal phase (LP) were studied in 24 infertile women. Patients were randomly divided into two groups. In one group (n = 12) metoclopramide (MCP, 10 mg orally 3 times daily) was administered from day 0 or 1 of the LP for 7 days. On day 7 or 8 of LP blood samples were taken every 15 min for 180 min; then 25 micrograms GnRH were acutely administered intravenously and blood samples taken at 185, 195, 210, 225, 240, 255, 270, 285 and 300 min. In the other 12 patients the same experimental design was performed on day 7 or 8 of an untreated LP. Plasma prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone and estradiol (E2) were assayed. The responsiveness of the different hormones to GnRH was evaluated as the integrated secretory area for 120 min after injection (sISA = stimulated integrated secretory area) and as the percentage increase (delta A) with respect to the area under basal conditions before GnRH administration (bISA = basal integrated secretory area). MCP-treated women showed higher basal PRL levels (p less than 0.01) and lower basal plasma concentrations and bISA (p less than 0.01) values of LH than controls. After GnRH a more marked response of LH secretion was observed in the treated group (p less than 0.01), so that the absolute values of sISA were superimposable in both groups. Basal and stimulated FSH secretion did not differ significantly in the study groups. Basal plasma and bISA values of progesterone were also decreased in MCP-treated subjects. After GnRH injection the absolute values of progesterone sISA were greater in controls (p less than 0.01), but delta A values were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of luteal metoclopramide-induced hyperprolactinemia on pituitary and luteal responsiveness to gonadotropin-releasing hormone. 250 35

The proteolytic specificity of the neutral zinc proteinase from Bacillus mesentericus strain 76 (MCP 76)/Bacillus subtilis was determined by using the alpha-chain of walrus hemoglobin as substrate. The resulting peptides were fractionated by gel filtration and than isolated by reversed-phase HPLC. The peptides were identified on the basis of their amino-acid compositions and aligned with the known sequence of the walrus alpha-chain. The proteolytic specificity of MCP 76, deduced from the experimental cleavage pattern is compared to that of thermolysin. The amino-acid residues in positions P1 and P'1 on both sides of the scissible bond are considered as most important for the cleavage. MCP 76 prefers leucine, valine, phenylalanine and threonine in position P'1 as well as lysine, threonine, leucine and alanine in position P1 and thus differs from thermolysin which shows no preference for threonine in P'1 and accepts numerous amino-acid residues of different type in P1.
 ...
PMID:Proteolytic specificity of the neutral zinc proteinase from Bacillus mesentericus strain 76 determined by digestion of an alpha-globin chain. 251 21

The aim of our studies was to examine if the baroreceptor reflex induced by intravenous injection of nitroglycerin (NG) nearly nullifies the vasodilator action of NG on the systemic capacitance vessels in dogs anesthetized with pentobarbital. We performed total spinal anesthesia (TSA) in open-chest dogs to eliminate the baroreceptor reflex. Dogs in which mean blood pressure (MBP) was maintained at about 100 mmHg by continuous intravenous infusion of epinephrine formed the TSA 100 group, and those in which MBP was maintained at about 70 mmHg formed the TSA 70 group. Dose-response curves relating 5-6 different doses (0.8 to 200 micrograms/kg) of intravenous NG, to changes in mean circulatory pressure (% delta MCP) and to changes in total peripheral resistance (% delta TPR), were constructed. These data were compared with those from untreated dogs. In addition, we also studied plasma catecholamine (CA) concentrations before and after the intravenous injection of NG. (1) There was no significant difference in the dose-response curves of NG for % delta TPR between the 3 groups. (2) There was no significant difference in the dose-response curves for % delta MCP between the 2 TSA groups. However, there was significant difference in the dose-response curves for % delta MCP between the TSA groups and the untreated dogs. The dose-response curves for % delta MCP in the TSA groups shifted upwards as compared with that of the untreated dogs. (3) In the TSA 100 group, there was no significant increase in the plasma CA concentrations with 100 micrograms/kg of NG. In the untreated group, intravenous injection of 12.5 micrograms/kg and 100 micrograms/kg of NG caused a dose-related fall in MBP and a dose-related rise in the plasma norepinephrine and epinephrine concentrations. Our results suggest that the vasodilator action of NG on the systemic capacitance vessels in the untreated dogs was counterbalanced partly by the vasoconstriction produced by the baroreceptor reflex, with its direct vasodilator effect masked when the hypotensive doses of NG were given acutely.
 ...
PMID:Differential vasodilator effect of nitroglycerin on systemic capacitance and resistance vessels in anesthetized dogs, and the mechanism of its action--a study by measuring mean circulatory pressure and total peripheral resistance. 251 38

Pre- and postoperative hypothalamic-pituitary-thyroid axis function was studied in 38 patients with pituitary adenomas (PRL, GH and ACTH tumours), of whom 35 were surgically confirmed and three diagnosed by clinical signs, CT scanning and hormone assessments. About ten days after operation, the same study was repeated in 10 patients with prolactinoma and 7 with growth hormone (GH) tumour. The preoperative abnormal serum TSH response to TRH was found in 8/20 patients with prolactinoma, 9/16 with GH tumour, and 2/2 with Cushing's disease due to ACTH microadenoma. The incidence of abnormal TSH response to TRH was not significantly increased in patients with larger adenoma in either PRL or GH tumour group. In 8 cases of prolactinoma, metoclopramide (MCP, 10 mg, P.O.) test was also performed and there was a significant positive correlation between TSH responses to TRH and to MCP. Serum TT3 in the GH tumour group was within normal ranges, but significantly higher than that of the normal and prolactinoma groups. After operation, TT3 was significantly decreased as compared with that before operation and there were marked changes in TSH response to TRH. In conclusion, there were some abnormalities in TSH control in patients with non-TSH pituitary tumour, and in serum TT3 control in patients with GH tumour. The surgical treatment of pituitary adenoma can lead to transient decrease in TSH reserve and serum TT3 level probably resulting from both stress and/or destruction of thyro-trophs by the operation.
 ...
PMID:Pre- and post-operative hypothalamic-pituitary-thyroidal axis function in patients with prolactinoma, growth hormone tumour and ACTH tumour. 255 2

Acetylcholine stimulates aldosterone secretion in bovine glomerulosa cells in vitro via specific cholinergic receptors. In this study we examined the effect of peripheral muscarinic blockade with atropine on metoclopramide-, angiotensin-II-, and ACTH-stimulated aldosterone secretion in man. Atropine (0.6 mg, iv) administered 10 min before MCP delayed the onset of the plasma aldosterone response and attenuated the mean peak response from 502 +/- 103 (+/- SE) to 322 +/- 72 pmol/L (P less than 0.05) without affecting zero time mean plasma aldosterone levels (144 +/- 28 vs. 136 +/- 36 pmol/L for control and atropine, respectively). This inhibitory effect was not mediated by changes in PRA or plasma potassium or ACTH (as reflected by cortisol) concentrations. Atropine also attenuated the plasma aldosterone response to a low dose angiotensin II infusion (2 ng/kg.min; control, 449 +/- 99 pmol/L; atropine, 297 +/- 78 pmol/L; P less than 0.05). In contrast, atropine had no effect on the plasma aldosterone response to a bolus dose (250 micrograms) of ACTH. Neither atropine (0.6 mg, iv) nor the cholinergic muscarinic agonist bethanechol (5 mg, sc) alone elicited a change in plasma aldosterone. Collectively, these data provide evidence for cholinergic modulation of aldosterone secretion in man. We conclude that cholinergic mechanisms may facilitate the aldosterone responses to angiotensin-II and metoclopramide, but not to ACTH.
 ...
PMID:Evidence for cholinergic modulation of aldosterone secretion in man. 256 95

This study was carried out using a dopaminergic agonist (carbidopa plus levodopa, CD + LD) and antagonist (metoclopramide, MCP) respectively for dynamic tests to observe the variations of serum prolactin (PRL), thyrotropin (TSH) and luteinizing hormone (LH) levels in 7 normal women and 11 women with pituitary prolactinoma. It was shown that CD + LD resulted in minimal suppression of serum PRL (18.4 +/- 3.4%) in tumor patients, with this being significantly less than that in normal women (80.7 +/- 4.6%). However, similar degrees of TSH and LH suppression were observed after CD + LD in patients (23.8 +/- 4.2% and 28.2 +/- 2.1%, respectively) and in normal women (27.9 +/- 2.4% and 34.7 +/- 9.0%, respectively). MCP greatly increased PRL levels in the normal women as compared with the patients (892.1 +/- 195.3%, 16.4 +/- 6.5%), but increased TSH and LH levels were much higher in the patients than in the normal women (291.4 +/- 36.1% vs 19.9 +/- 3.3% and 96.9 +/- 7.4% vs 24.9 +/- 5.5%, respectively). It was also found that the levels of TSH or LH after MCP strongly correlated with basal PRL levels in the patients (r = 0.858, P less than 0.001 and r = 0.737, P less than 0.01, respectively). These results indicate that synthesis, turnover and release of hypothalamic dopamine are normal and the hypothalamic tone is relatively high in patients with PRL-secreting pituitary tumors.
 ...
PMID:Evaluation of hypothalamic dopaminergic function in patients with pituitary prolactinoma. 259 32

Sixty-nine patients with malignant tumors receiving cancer chemotherapy, 90% including cis-platinum, were evaluated in a randomized crossover study for the antiemetic efficacy and the side effects of two antiemetic regimens: chlorpromazine (CPM) 2.5 mg/kg in 5 doses plus dexamethasone (DXM) 0.2 mg/kg in 2 doses, and high-dose metoclopramide (HD-MCP) 10 mg/kg in 5 doses plus the same dose of DXM. In 69% of 173 courses of chemotherapy, antiemetic response was achieved, and in 26% emesis was completely prevented. There was no statistical difference in the response to the antiemetic regimens, but 65% of the patients who completed 3 courses of chemotherapy preferred HD-MCP plus DXM. The main side effects of the treatment were drowsiness, nervousness, diarrhea and extrapyramidal reactions. HD-MCP plus DXM is recommended as a first line antiemetic treatment in patients receiving cancer chemotherapy. Patients resistant to this treatment should receive CPM plus DXM treatment.
 ...
PMID:Chlorpromazine and dexamethasone versus high-dose metoclopramide and dexamethasone in patients receiving cancer chemotherapy, particularly cis-platinum: a prospective randomized crossover study. 265 92


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>