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)

The authors, and others, clearly have established that interleukin-6 (IL-6) is the major growth factor for human myeloma cells in vitro. It is a critical conceptual point whether or not IL-6 remains involved in the final phases of disease progression in malignant plasma cell dyscrasias. To answer this question, the authors evaluated the in vitro IL-6 dependence of the proliferation of myeloma cells from the bone marrow of 13 patients with advanced multiple myeloma (MM) and from the peripheral blood of 13 patients with plasma cell leukemia (seven primary and six secondary cases). Their results show that myeloma cell growth was totally dependent on IL-6 in 25 of 26 patients. Myeloma cells of only one patient did not respond to IL-6 in vitro. Actually, the cells from this patient were not proliferating in vivo. Identical patterns of IL-6 dependence of myeloma cells were found in the peripheral blood and bone marrow from four patients with PCL. The authors conclude that, in the terminal phase of malignant plasma cell dyscrasias, tumoral growth is totally dependent on IL-6 in vitro. This observation is critical in considering the investigation of anti-IL-6 therapy in patients with advanced MM.
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PMID:Interleukin-6 dependence of advanced malignant plasma cell dyscrasias. 154 Aug 75

Pseudolatexes of the biodegradable polyesters poly(D,L-lactide) (PLA) and poly(epsilon-caprolactone) (PCL) have been developed as potential aqueous coatings for sustained release. Since PLA and PCL are known to hydrolyze, the influence of the surfactant system, temperature, pH, and particle size on the chemical stability of the polymers as aqueous colloidal dispersions was investigated. Pseudolatexes of PLA and PCL formulated with a nonionic surfactant system were the most stable. When these dispersions were stored in unbuffered media for 350 days at 5 degrees C, only small changes in the weight-average molecular weights (Mw) of the polymers were observed. At 37 degrees C there was rapid degradation of both polymers in the dispersions. Arrhenius plots for the degradation of PLA and PCL resulted in a linear relationship for PCL. The nonlinear relationship for PLA was attributed to the polymer being in two different physical states within the 5 to 37 degrees C range which was used for the Arrhenius plots. PCL was in the rubbery state at all temperatures studied. Storage of the pseudolatexes in pH 1.65 buffer at 37 degrees C catalyzed the rates of degradation of both PLA and PCL. However, refrigeration of the pseudolatexes stabilized the polymers even at pH 1.65 for up to 4 months. Particle size had an insignificant effect on PLA and PCL stability in pseudolatexes prepared with either a nonionic or an anionic surfactant system.
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PMID:Biodegradable pseudolatexes: the chemical stability of poly(D,L-lactide) and poly(epsilon-caprolactone) nanoparticles in aqueous media. 155 42

The safety and efficacy of phacoemulsification and posterior chamber lens insertion combined with the Pearce trabeculectomy (PE/PCL/P-TRX) in patients with coexistent cataract and glaucoma was evaluated retrospectively. The Pearce trabeculectomy is a form of nonfiltration glaucoma surgery in which an inner block containing trabecular meshwork is excised under a scleral-pocket incision which is closed tightly. Thirty consecutive eyes sustained a reduction of mean intraocular pressure from 21.0 +/- 4.4 mm Hg to 16.6 +/- 3.3 mm Hg after PE/PCL/P-TRX at one year (P less than .001). The average number of glaucoma medications used was reduced from 1.9 to 0.8 postoperatively. At one year, 60% (18 of 30) of eyes treated with PE/PCL/P-TRX had intraocular pressures less than 21 mm Hg without medications.
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PMID:Surgical outcome of phacoemulsification combined with the Pearce trabeculectomy in patients with glaucoma. 159 37

Complete knee dislocations are infrequent but serious injuries resulting from a wide spectrum of traumatic events. Significant soft tissue and ligamentous damage usually result. Previous experience and several reports in the literature had led us to believe that complete dislocations were associated with both ACL and PCL rupture. Three cases of documented complete knee dislocation in which the PCL is preserved intact are presented.
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PMID:Knee dislocations with intact PCL. 160 11

23 acute midsubstance ruptures of the posterior cruciate ligament were treated by primary suture. 20 patients returned for follow-up. Four of them had an isolated rupture of the PCL. The remaining 16 patients had sustained combined injuries to ligaments, including eight total ruptures of the anterior cruciate ligament. All ruptured ligaments were sutured. At follow-up (median = 5.5, range 3-10 years) median knee score according to Lysholm was 81 (range 53-100). Five were rated excellent, six good, three fair and six poor. KT-1000 arthrometer measurements revealed a posterior instability of between 5 and 10 mm in five patients and below 5 mm in 14 patients. Thus, in most patients, some instability remained in spite of operative treatment.
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PMID:[Primary suture of the posterior cruciate ligament]. 161 9

Poly(DL-lactic acid) (PLA), poly(epsilon-caprolactone) (PCL), and their copolymers (PLA-CL) with various monomer compositions were synthesized, and their properties as matrix for the sustained release of drugs were evaluated. The copolymerization technique produced very soft films which incorporated the drugs without deterioration of the elastic properties. Cisplatin and MD-805 were loaded in the films by casting the polymer solution containing the drugs. Fractions of the drugs released from the PLA-CL films were governed by the initial loading, the film thickness, and the polymer molecular weight. The drug release profiles obeyed the classical Fickian diffusion equation at least in the early stage, but significant hydrolytic degradation of the matrix polymers occurred in the later stage, influencing the kinetics of drug release. The monomer composition of copolymer affected the release profile more strongly than the initial molecular weight of the copolymer.
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PMID:In vitro evaluation of sustained drug release from biodegradable elastomer. 179 48

The described model of experimental pneumocystosis is based on the induction of natural latent infection of P. carinii in Wistar strain laboratory rats. As to pharmacological inducing agents immunosuppresive preparations such as Hydrocortisone sol. inj. (Spofa), Cyclosporin A (Merck) and Dexamethasone (Spofa) were used whereby the latter was effective in up 50%. As to non-pharmacological inducing agents, the authors used in combination with the tested inducers a low protein diet (less than 8% protein in the diet); for suppression of associated bacterial contamination tetracycline was added to drinking water. From the infected lungs by two different methods two types of antigens were prepared 1) PCL antigen (Pneumocystis carinii lavage antigen) isolated by rinsing of the lungs and 2) PCWD antigen (P. carinii whole digest antigen) isolated by digestion of the lungs with collagenase and trypsin. Cysts of P. carinii were detected by staining according to Giemsa (staining of internal structures of nuclear cysts) and by modified staining with toluidine blue O (staining of the cyst wall). For isolation of the antigen and for detection of cysts a combination of the two described methods seems to be best.
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PMID:[Induction of experimental pneumocystosis, detection and primary isolation of Pneumocystis carinii]. 182 70

Several steps implicated in platelet-derived growth factor (PDGF) receptor-coupled signaling are activated by PDGF exposure at 0-4 degrees C. These include receptor self-phosphorylation, physical association with and phosphorylation of phospholipase C gamma (PLC gamma). Reduced temperature blocks PDGF internalization, making it possible to dissociate bound PDGF after PLC gamma tyrosine phosphorylation. We addressed the functional consequences of PDGF dissociation from intact cell PDGF receptors. PDGF exposure at 0-4 degrees C for 15 min stimulated self-phosphorylation of a subpopulation of BALB/c 3T3 cell PDGF beta-type receptors (35%) and initiated subsequent inositol phosphate production. A small fraction of cellular PLC gamma (1-3%) coprecipitated with ligand-activated PDGF receptors; 3-5% of cellular PLC gamma acquired phosphotyrosine. The PLC gamma coprecipitating with PDGF receptors did not contain detectible phosphotyrosine. Phosphotyrosine antibody recovered similar amounts of PLC gamma from soluble and particulate fractions of PDGF-stimulated cells. Acid dissociation of bound PDGF from receptor caused rapid dephosphorylation of PDGF receptors and PCL gamma, and interrupted PLC gamma-PDGF receptor coprecipitation. Orthovanadate blocked tyrosine dephosphorylation of both PDGF receptors and PLC gamma and stabilized coprecipitation. Orthovanadate reversed the acid wash effect to abrogate PDGF-stimulated inositol phosphate production. PDGF receptor remains competent to coprecipitate with PLC gamma and stimulate PLC-mediated inositol phosphate production if PDGF-induced receptor phosphorylation is maintained. Formation of a coprecipitable PDGF receptor-PLC gamma complex appears required for PDGF-stimulated inositol phosphate production.
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PMID:Phospholipase C gamma complexes with ligand-activated platelet-derived growth factor receptors. An intermediate implicated in phospholipase activation. 184 94

PCL reconstruction is not often necessary. Arthroscopic techniques using autograft or allograft substitution for the PCL probably bear more physiologic and anatomic likeness to the normal ligament than to tissue transfers posteriorly. The arthroscopic procedure is exacting and technically demanding. It is advisable to supplement the PCL reconstruction with an appropriate capsulorrhaphy when the posterior capsule, arcuate complex, or oblique popliteal ligament are also injured. In combined cruciate injuries, PCL reconstruction is notably easier when staged before reconstruction of the ACL.
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PMID:Posterior cruciate ligament injuries. 186 57

The value of computed tomography (CT) in evaluating the cruciate ligaments was assessed by studying an amputated knee in order to find the most suitable position for detecting minimal defects of the ligaments. The ACL or PCL, or both, of 60 patients (61 knees) were then examined by CT and the findings were compared with those of arthroscopy. Defects 3mm in length were shown by CT. A sufficient quantity of air and an adequate amount of positive contrast medium were required to obtain an accurate picture of the ligaments. For the ACL, the sensitivity of CT was 96.6%, specificity was 95.5%, and accuracy was 96.1%. For the PCL, sensitivity was 78.6%, specificity was 91.7%, and accuracy was 84.6%. Ruptures of the cruciate ligaments shown by CT were classified into four types. Their CT images coincided significantly with their arthroscopic findings. This study shows double-contrast CT arthrography to be a valuable method for evaluating the cruciate ligaments, and especially the ACL.
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PMID:Double-contrast CT arthrography of the cruciate ligaments. 195 94


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