Gene/Protein Disease Symptom Drug Enzyme Compound
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Variable methods of dust collection may lead to uncertainty in the measurement of biomarkers. The purpose of this study was to examine the effect of two different dust collection devices on dust weight, Der p 1, Fel d 1, and endotoxin levels. We compared: (1) a nylon mesh sock inserted between the furniture attachment and the vacuum hose (the reference method) and (2) the ALK device. Duplicate dust samples were collected for 2 min from 2 m(2) of 37 living room floors and from each longitudinal half of 37 mattresses. Measurement of Der p 1 and Fel d 1 were by double monoclonal antibody enzyme-linked immunosorbent assay (ELISA) and endotoxin by a Limulus Amobocyte Lysate assay. Geometric mean ratios (95% confidence intervals) were calculated to show the differences between sampling devices for each measurement. Compared with the ALK device, the reference method collected significantly more dust from floors (sevenfold) and mattresses (threefold) and more total Der p 1, Fel d 1, and endotoxin in both sites. Floor, but not mattress, Der p 1 concentrations were also significantly higher (threefold) using our reference method. We recommend that, in order to minimize sampling device bias, allergen and endotoxin are expressed as a concentration, and that the bed is considered the major source of allergen exposure. Practical Implications Dust sampling equipment can influence the dust yield. In order to have confidence in comparisons of allergen and endotoxin reservoir levels between centers, standardization in the use of sampling equipment is important.
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PMID:Comparison of two dust collection methods for reservoir indoor allergens and endotoxin on carpets and mattresses. 1510 90

The aim of this study was to determine if the nutritive value and aerobic stability of bermudagrass (Cynodon dactylon) silage could be improved by addition of proprietary, exogenous cellulase/hemicellulase enzyme preparations at ensiling. A 5-wk regrowth of Tifton 85 bermudagrass was conserved without treatment (control) or after treatment with exogenous fibrolytic enzymes including Promote NET (Pr), Biocellulase X-20 (X20), Biocellulase A-20 (A20), and Enzyme CT. The respective enzymes were applied at half the recommended rate, the recommended rate, or twice the recommended rate corresponding to 0.65, 1.3, and 2.6 g/kg of DM, 7.3, 14.5, and 29 mg/kg of DM, at 7.3, 14.4, and 29 mg/kg of DM, and 89, 178, and 356 mg/kg of DM, for Pr, X20, A20, and CT, respectively. The enzymes were sprayed on the bermudagrass at ensiling (not added at feeding as suggested by the manufacturers) to test the objectives of the study. Six 1-kg replicates of chopped (5 cm) forage were ensiled for 145 d in 2.8-L mini silos. Three silos per treatment were used for chemical analysis and 3 for aerobic stability monitoring. The silage juice was analyzed for organic acids, pH, water-soluble carbohydrates (WSC), ammonia-N, and soluble N. Freeze-dried samples were analyzed for crude protein (CP), neutral detergent fiber (NDF), and acid detergent fiber (ADF). In vitro digestibility of DM (IVDMD), NDF (IVNDFD), and ADF (IVADFD) were determined after digesting the silages in buffered rumen fluid for 6 or 48 h in 2 ANKOM(II) Daisy Incubators. Compared with the other silages, those treated with Pr had lower DM losses, and lower pH and ammonia-N concentration than control silages. Residual WSC concentration was greater in Pr- and CT-treated silages than in control silages and greater in Pr-treated silages than CT-treated silages. Compared with control silages, NDF concentration was lower in silages treated with Pr, X20, and CT, and ADF concentration was lower in silages treated with Pr, X20, and A20. Nevertheless, Pr-treated silages contained lower ADF and NDF concentrations than silages treated with the other enzymes. Enzyme-treated silages contained less acetic acid than control silages, and Pr-treated silages had the lowest concentrations of acetic acid. Aerobic stability was increased by enzyme treatment but microbial counts were not affected. The 6-h IVDMD was increased by treatment with Pr and A20, however only Pr increased the IVDMD and IVNDFD at 48 h. The 48-h IVADFD was also increased by treatment with Pr, CT, and A20. These results show that when applied at ensiling, certain fibrolytic enzymes (particularly Promote) can improve the digestibility, fermentation, and aerobic stability of bermudagrass silage.
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PMID:Effect of fibrolytic enzymes on the fermentation characteristics, aerobic stability, and digestibility of bermudagrass silage. 1573 34

This Guidance provides information for clinicians and women considering the use of contraception outside the terms of the product licence. A key to the grades of recommendations, based on levels of evidence, is given at the end of this document. Details of the methods used by the Clinical Effectiveness Unit (CEU) in developing this Guidance and evidence tables summarising the research basis of the recommendations are available on the Faculty website (www.ffprhc.org.uk). Abbreviations (in alphabetical order) used include: CEU, Clinical Effectiveness Unit; COC, combined oral contraception/contraceptive; DMPA, depot medroxyprogesterone acetate; ENG, etonogestrel; IUD, copper-bearing intrauterine contraceptive device; LNG-IUS, levonorgestrel-releasing intrauterine system; NET-EN, norethisterone enantate; PGD, Patient Group Direction; PIL, Patient Information Leaflet; POC, progestogen-only contraception/contraceptive; POEC, progestogen-only emergency contraception; POP, progestogen-only pill; RCT, randomised controlled trial; SPC, Summary of Product Characteristics; UPSI, unprotected sexual intercourse; WHO, World Health Organization; WHOMEC, WHO Medical Eligibility Criteria for Contraceptive Use; WHOSPR, WHO Selected Practice Recommendations for Contraceptive Use.
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PMID:FFPRHC Guidance (July 2005): The use of contraception outside the terms of the product licence. 1682 21

Over the last two decades, various research protocols were applied for scintigraphic imaging, prognosis and treatment of breast cancer, using monoclonal antibodies. Monoclonal antibodies approved by the United States Food and Drug Administration (FDA) include the anti-carcinoembryonic antigen (CEA), and B72.3, prepared against the tumour-associated glycoprotein, TAG-72. The recombinant humanized "cold" anti-HER2 monoclonal antibody (trastuzumab), which targets oncogene receptor HER2 has hitherto been the only monoclonal antibody widely used for the treatment of breast cancer in the USA, with or without chemotherapy. Trastuzumab is constructed against the HER2 oncogene receptor (also known as neu or c-erb-B2), which is overexpressed in 25%-30% of breast cancer cell lines and is associated with poor prognosis. Immuno-lymphoscintigraphy is also applied to guide and monitor the effect of treatment regimes. Radiolabelled, "hot" monoclonal antibodies are currently being applied for the treatment of primary or metastatic breast cancer, in experimental, pre-clinical, or clinical trials, in combination with traditional external beam radiotherapy and/or chemotherapy. Radioimmunotherapy comprises systemically administered monoclonal antibodies, linked to high-energy, beta-emitting radionuclides. Radioactive antibodies, in the form of yttrium-90 (90Y)-BrE-3, 90Y- m170 and 131I- or 90Y- labelled L6 antibody, are applied with adjuvant autologous peripheral blood stem cells transfusion, to prevent myelotoxicity. Partial or rarely complete responses to "hot" antibody treatment, of breast cancer have been reported. Innovative strategies using this combined-modality treatment hold promise for better disease-free and survival rates.
Hell J Nucl Med
PMID:Monoclonal antibodies: old and new trends in breast cancer imaging and therapeutic approach. 1614 51

A common limitation of using polymeric nanoparticles in aqueous suspension is due to their poor chemical and physical stability when conserved for a long time. Therefore, freeze drying of these colloidal systems is an alternative method to achieve long-term stability. Nanocapsules have thin and fragile shell structure, which may not resist to the stress of such process. The aim of this study is to investigate the formulation and process parameters in order to ensure the stability of polycaprolactone nanocapsules (PCL NC) by freeze drying. In this paper, we studied the freeze drying of PCL NC prepared by the emulsion-diffusion method and stabilized by poly(vinyl alcohol) (PVA). Different parameters have been tested throughout the freeze-thawing study including PVA and PCL concentration, cooling rate, cryoprotectant concentrations, nature of encapsulated oil and NC purification. On the other hand, nanocapsules have been freeze dried both before and after purification. Freeze dried purified PCL NC were characterized by particle size measurement, collapse temperature, T'g determination, scanning electron microscope observation, environmental scanning electron microscope imaging and residual humidity quantification. Finally, the effect of annealing on the NC stability and the sublimation rate has been well explored. The results suggest that PCL NC could be freeze dried without a cryoprotectant if the concentration of PVA stabilizer is sufficient (5%), while for the purified NC the addition of 5% of cryoprotectant seems to be necessary to ensure the stability of NC. The type of cryoprotectants had practically negligible effects on the size and the rehydration of freeze dried nanocapsules. The annealing process could accelerate the sublimation with the conservation of nanocapsules size.
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PMID:A pilot study of freeze drying of poly(epsilon-caprolactone) nanocapsules stabilized by poly(vinyl alcohol): formulation and process optimization. 1632 53

Fibroblast growth factor (FGF) signals are transduced through FGF receptors (FGFRs) and FRS2/FRS3- SHP2 (PTPN11)-GRB2 docking protein complex to SOS-RAS-RAF-MAPKK-MAPK signaling cascade and GAB1/GAB2-PI3K-PDK-AKT/aPKC signaling cascade. The RAS approximately MAPK signaling cascade is implicated in cell growth and differentiation, the PI3K approximately AKT signaling cascade in cell survival and cell fate determination, and the PI3K approximately aPKC signaling cascade in cell polarity control. FGF18, FGF20 and SPRY4 are potent targets of the canonical WNT signaling pathway in the gastrointestinal tract. SPRY4 is the FGF signaling inhibitor functioning as negative feedback apparatus for the WNT/FGF-dependent epithelial proliferation. Recombinant FGF7 and FGF20 proteins are applicable for treatment of chemotherapy/radiation-induced mucosal injury, while recombinant FGF2 protein and FGF4 expression vector are applicable for therapeutic angiogenesis. Helicobacter pylori, a causative pathogen for peptic ulcer diseases, chronic atrophic gastritis and gastric cancer, injects bacterial proteins into gastric epithelial cells by using Type IV secretion system, which leads to FGF signaling activation through FGF2 upregulation as well as CagA-dependent SHP2 activation. FGFR2 gene is preferentially amplified and overexpressed in diffuse-type gastric cancer. PD173074 is a small-molecule inhibitor for FGFR, while RO4396686 and SU6668 are small-molecule inhibitors for FGFR and other tyrosine kinases. Cocktail therapy using multiple protein kinase inhibitors could enhance the therapeutic effects for gastrointestinal cancer through the reduction of recurrence associated with somatic mutations of drug-target genes. Single nucleotide polymorphism (SNP) and copy number polymorphism (CNP) of genes encoding FGF signaling molecules will be identified as novel risk factors of gastrointestinal cancer. Personalized prevention and personalized medicine based on the combination of genetic screening and novel therapeutic agents could dramatically improve the prognosis of cancer patients.
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PMID:FGF signaling network in the gastrointestinal tract (review). 1677 96

While cocaine's interaction with the dopamine (DA) transporter and subsequent increase in DA transmission are usually considered key factors responsible for its locomotor stimulatory and reinforcing properties, many centrally mediated physiological and psychoemotional effects of cocaine are resistant to DA receptor blockade, suggesting the importance of other non-DA mechanisms. To explore the role of cocaine's interaction with Na+ channels, rats were used to compare locomotor stimulatory and temperature (NAcc, temporal muscle and skin) effects of repeated iv injections of cocaine (1 mg/kg) with those induced by procaine (PRO 5 mg/kg), a short-acting local anesthetic with negligible effect on the DA transporter, and cocaine methiodide (COC-MET 1.31 mg/kg), a quaternary cocaine derivative that is unable to cross the blood-brain barrier. While PRO, unlike cocaine, did not induce locomotor activation, it mimicked cocaine in its ability to increase brain temperature following the initial injection and to induce biphasic, down-up fluctuations following repeated injections. This similarity suggests that both these effects of cocaine may be driven by its action on Na+ channels, a common action of both drugs. While COC-MET also did not affect locomotor activity, it shared with cocaine and PRO their ability to increase brain temperature but failed to induce temperature decreases after repeated injections. These findings point toward activation of peripheral Na+ channels as the primary mechanism of rapid excitatory effects of cocaine and inhibition of centrally located Na+ channels as the primary mechanism for transient inhibitory effects of cocaine. DA receptor blockade (SCH23390+eticlopride) fully eliminated locomotor stimulatory and temperature-increasing effects of cocaine, but its temperature-decreasing effects remained intact. Surprisingly, DA receptor blockade also altered the temperature fluctuations caused by PRO and COC-MET, suggesting that some of the central effects triggered via Na+ channels are in fact DA-dependent. Finally, repeated administration of PRO to animals that had previous cocaine experience led to conditioned locomotion and potentiated temperature-increasing effects of this drug. It appears, therefore, that, in addition to the central effects of cocaine mediated via interaction with the DA transporter and potentiation of DA uptake, interaction with peripheral and central Na+ channels is important for the initial physiological and, perhaps, affective effects of cocaine, likely contributing to the unique abuse potential of this drug.
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PMID:The role of peripheral and central sodium channels in mediating brain temperature fluctuations induced by intravenous cocaine. 1695 95

Dust collection by study participants instead of fieldworkers would be a practical and cost-effective alternative in large-scale population studies estimating exposure to indoor allergens and microbial agents. We aimed to compare dust weights and biological agent levels in house dust samples taken by study participants with nylon socks, with those in samples taken by fieldworkers using the sampling nozzle of the Allergology Laboratory Copenhagen (ALK). In homes of 216 children, parents and fieldworkers collected house dust within the same year. Dust samples were analyzed for levels of allergens, endotoxin, (1-->3)-beta-D-glucans and fungal extracellular polysaccharides (EPS). Socks appeared to yield less dust from mattresses at relatively low dust amounts and more dust at high dust amounts than ALK samples. Correlations between the methods ranged from 0.47-0.64 for microbial agents and 0.64-0.87 for mite and pet allergens. Cat allergen levels were two-fold lower and endotoxin levels three-fold higher in socks than in ALK samples. Levels of allergens and microbial agents in sock samples taken by study participants are moderately to highly correlated to levels in ALK samples taken by fieldworkers. Absolute levels may differ, probably because of differences in the method rather than in the person who performed the sampling. Practical Implications Dust collection by participants is a reliable and practical option for allergen and microbial agent exposure assessment. Absolute levels of biological agents are not (always) comparable between studies using different dust collection methods, even when expressed per gram dust, because of potential differences in particle-size constitution of the collected dust.
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PMID:Exposure to microbial components and allergens in population studies: a comparison of two house dust collection methods applied by participants and fieldworkers. 1710 Jun 63

Papillary and follicular carcinomas, commonly referred to as follicular cell-derived differentiated thyroid carcinomas (DTC), account for 90% of all thyroid carcinomas. The prognosis of DTC is generally good, depending on the biologic behavior of the tumor and on the appropriate initial treatment which includes total thyroidectomy and ablation by radioiodine-131. However, a considerable number of patients, approximately 30%, as shown after 30 years of follow-up, have recurrent disease. It is thus of utmost importance to evaluate the prognostic factors, as derived from retrospective studies, and identify high risk patients. Age of more than 45 years or less than 25 years is a particularly strong independent prognostic factor; on the contrary gender is a poor prognostic factor. Histological type of the cancer especially tall cancer cells and columnar cancer cells, as well as increased vascular invasion of the tumor, lymph-node and distant metastases, are all considered as risk factors that can lead to poor prognosis. Combined prognostic factors have been used to form scoring systems (SS) such as AGES, MACIS, AMES, EORTC and TNM for a more precise description of high or low risk patients. However, prognostic significance of the SS is limited, since they do not take into consideration the clinical status or the treatment procedure during the course of the disease. Molecular factors such as rearrangements of genes RET/PTC, RAS mutations and fusion of, paired box and 8/peroxisome proliferator-activated receptor gamma (PAX8/PPARgamma) are also involved in thyroid cancer prognosis, while some others: human Pituitary- Tumor Transforming Gene (e.g. MIB-1, hPTTG) have been reported as additional prognostic factors. In this review we describe the risk and the prognostic factors of DTC as related to management and the outcome of DTC.
Hell J Nucl Med
PMID:Risk and prognostic factors for differentiated thyroid cancer. 1881 68

Despite ongoing evolution in total knee arthroplasty (TKA) prosthesis design, restricted flexion continues to be common postoperatively. Compressive tibiofemoral force during flexion is generated through the interaction between soft tissues and prosthesis geometry. In this study, we compared the compressive tibiofemoral force in vitro of four commonly used prostheses: fixed-bearing PCL (posterior cruciate ligament)-retaining (PFC), mobile-bearing posterior-stabilized (PS), posterior-stabilized with a High Flex femoral component (HF), and mobile-bearing PCL-sacrificing (LCS). Fourteen fresh-frozen cadaver knee joints were tested in a passive motion rig, and tibiofemoral force measured using a modified tibial baseplate instrumented with six load cells. The implants without posterior stabilization displayed an exponential increase in force after 90 degrees of flexion, while PS implants maintained low force throughout the range of motion. The fixed-bearing PFC prosthesis displayed the highest peak force (214 +/- 68 N at 150 degrees flexion). Sacrifice of the PCL decreased the peak force to a level comparable with the LCS implant. The use of a PCL-substituting post and cam system reduced the peak force up to 78%, irrespective of whether it was a high-flex or a standard PS knee. However, other factors such as preoperative range of motion, knee joint kinematics, soft tissue impingement, and implantation technique play a role in postoperative knee function. The present study suggests that a posterior-stabilized TKA design might be advantageous in reducing soft tissue tension in deep flexion. Further research is necessary to fully understand all factors affecting knee flexion after TKA.
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PMID:Tibiofemoral force following total knee arthroplasty: comparison of four prosthesis designs in vitro. 1756 18


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