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 response to lithium prophylaxis was evaluated in a sample of bipolar patients subdivided into groups, according to the previous pattern of course for their illness: MDI (sequence mania-depression-free interval), DMI (sequence depression-mania-free interval), CC-LC (continuous circular course with long cycles), CC-RC (continuous circular course with rapid cycles), IRR (irregular course). The percentage of responders to treatment was significantly different among the five groups, and the difference could be ascribed mainly to the high response rate in the MDI group and the low response rate in the DMI and CC-RC groups. These data suggest that the classification of bipolar patients on the basis of the previous pattern of their course of illness may be useful for predicting lithium response.
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PMID:Clinical prediction of response to lithium prophylaxis in bipolar patients: the importance of the previous pattern of course of the illness. 211 28

The response to lithium prophylaxis was assessed in a sample of bipolar patients subdivided into the following groups on the basis of the previous pattern of course of their illness: MDI (sequence mania-depression-free interval), DMI (sequence depression-mania-free interval), CC-LC (continuous circular course with long cycles), CC-RC (continuous circular course with rapid cycles), IRR (irregular course). A significant reduction of the mean number of morbid episodes and of the mean total morbidity during lithium treatment was observed only in patients with a previous MDI or IRR course. The percentage of responders to prophylaxis was significantly different among the five groups, and the difference could be mainly ascribed to the high response rate in the MDI group and the low response rate in the DMI and CC-RC groups. These results suggest that the classification of bipolar patients according to the previous pattern of course of their illness may be useful for the prediction of lithium response.
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PMID:Previous pattern of course of the illness as a predictor of response to lithium prophylaxis in bipolar patients. 252 91

A digestibility trial involving 20 Hampshire ram lambs and a 2-yr grazing study using 103 mature crossbred cows were conducted to determine the effects of methionine addition to a urea-grain supplement on intake and digestibility of dormant range grasses and on cow performance. In each trial, four treatment groups were supplemented with either a urea-grain control (CON), urea-grain plus methionine (MET, 3.3% DL-methionine), urea-grain plus inorganic sulfur (SUL, 3.0% sodium sulfate), or soybean meal (SBM). Supplements were designed to provide 45 and 360 g of CP.animal-1.d-1 (lambs and cows, respectively) and were balanced for ME, Ca, P, and K. Lambs had ad libitum access to mature prairie hay, whereas cows grazed dormant winter range from mid-November until mid-February. For the grazing study, forage OM intake (OMI) was determined in late November and in late January by the fecal output/indigestibility ratio technique. Controlled-release chromic oxide boluses were used as an external marker to estimate fecal output, and acid insoluble ash was used as an internal marker to predict OM digestibility (OMD). Mean daily DMI of mature prairie hay was 1,057 g/lamb and was not affected by supplementation. Apparent DM, NDF, and ADF digestibilities and N biological value did not differ (P > .10) among treatments. Nitrogen digestibility was increased (P = .06) for lambs fed the MET or SUL compared with CON.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of methionine addition to a urea-grain supplement on intake and digestibility of mature, dormant grasses and performance of cows grazing winter range. 844 Jun 72

NIH3T3 cells transformed by mouse FGF3-cDNA (DMI cells) selected for their ability to grow as anchorage-independent colonies in soft agar and in defined medium lacking growth factors exhibit a highly transformed phenotype. We have used dominant negative (DN) fibroblast growth factor (FGF) receptor 2 (FGFR2) isoforms to block the FGF response in DMI cells. When the DN-FGFR was expressed in DMI cells, their transformed phenotype can be reverted. The truncated FGFR2(IIIb), the high affinity FGFR for FGF3, is significantly more efficient at reverting the transformed phenotype as the IIIc isoform, reaffirming the notion that the affinity of the ligand to the DN-FGFR2 isoform determines the effect. Heparin or heparan sulfate displaces FGF3 from binding sites on the cell surface inhibiting the growth of DMI cells and reverts the transformed phenotype (). However, the presence of heparin is necessary to induce a mitogenic response in NIH3T3 cells when stimulated with soluble purified mouse FGF3. We have investigated the importance of cell surface binding of FGF3 for its ability to transform NIH3T3 cells by creating an FGF3 mutant anchored to the membrane via glycosylphosphatidylinositol (GPI). The GPI anchor renders the cell surface association of FGF3 independent from binding to heparan sulfate-proteoglycan of the cell surface membrane. Attachment of a GPI anchor to FGF3 also confers a much higher transforming potential to the growth factor. Even more, the purified GPI-attached FGF3 is as much transforming as the secreted protein acting in an autocrine mode. Because NIH3T3 cells do not express the high affinity tyrosine kinase FGF receptors for FGF3, these findings suggest that FGF3 attached to GPI-linked heparan sulfate-proteoglycan may have a broader biological activity as when bound to transmembrane or soluble heparan sulfate-proteoglycan.
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PMID:FGF3 attached to a phosholipid membrane anchor gains a high transforming capacity. Implications of microdomains for FGF3 cell transformation. 1208 21

The antidepressants milnacipran and paroxetine are used clinically worldwide. In the present study, we report here the effects of treatment with milnacipran and paroxetine on the functional activity, binding sites, and mRNA of the norepinephrine (NE) transporter (NET) in cultured bovine adrenal medullary cells. In acute treatment with antidepressants for 20 min, both milnacipran and paroxetine competitively inhibited NET function in cultured adrenal medullary cells. Prolonged treatment of adrenal medullary cells with milnacipran produced time (48-96h)- and concentration (35-355 nM)-dependent increases in [3H]NE uptake and [3H]DMI binding without any increase in NET mRNA. At a high concentration (800 nM, 72 h), paroxetine suppressed [3H]NE uptake. To examine whether milnacipran-induced [3H]NE uptake is mediated by newly synthesized mRNAs or proteins, we used actinomycin D, an inhibitor of DNA-dependent RNA polymerase, and cycloheximide, an inhibitor of ribosomal protein synthesis. Cycloheximide (1 micorM, 72 h) abolished the effect of milnacipran on [3H]NE uptake, while the stimulatory effect of milnacipran was observed in actinomycin D-treated cells. The present findings suggest that prolonged exposure to milnacipran up-regulates the NET function, probably through a post-transcriptional process of NET or other proteins.
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PMID:Effect of prolonged exposure to milnacipran on norepinephrine transporter in cultured bovine adrenal medullary cells. 1615 10

Metabolic demand for sulfur-containing AA increases during inflammation in nonruminants. Therefore, Met supplementation may alleviate the negative effects of infection on N balance. Effects of gram-negative bacterial lipopolysaccharide (LPS) and supplemental dietary Met on N balance, serum hormones and haptoglobin, and plasma urea-N and AA were evaluated in 20 Angus-cross steers (BW = 262 +/- 6.3 kg). Treatments (2 x 2 factorial) were infusion of no LPS (-LPS) or a prolonged low dose of LPS (+LPS) and dietary supplementation of no (-MET) or 14 g/d (+MET) of rumen-protected Met (providing 7.9 g/d of dl-Met). Steers were adapted to a roughage-based diet (DMI = 1.4% of BW daily) and supplemental Met for 14 d, and were then infused (1 mL/min via intravenous catheter) with LPS on d 1 (2 microg/kg of BW) and 3 (1 microg/kg of BW) of a 5-d collection period. Blood was collected on d 1, before LPS infusion, and at 2, 4, 6, 8, 10, 12, and 24 h after LPS challenge. Diet samples, feed refusals, feces, and urine were collected daily for 5 d. Rectal temperature and serum concentrations of cortisol, prolactin, tumor necrosis factor-alpha, and haptoglobin increased, whereas thyroxine and triiodothyronine decreased for +LPS vs. -LPS steers (LPS x h; P < 0.01). Plasma urea-N was greater for +LPS than -LPS steers (LPS; P = 0.03), and serum IGF-1 was not affected (P > or = 0.26) by LPS or Met. Plasma concentrations of Thr, Lys, Leu, Ile, Phe, Trp, Asn, Glu, and Orn decreased, plasma Ala increased, and Gly and Ser initially increased, then declined in +LPS vs. -LPS steers (LPS x h; P < or = 0.04). Plasma Met was greater for +MET than -MET steers before LPS infusion, but declined in +MET steers after LPS infusion (LPS x Met x h; P < 0.01). By design, DMI was not different, but DM digested was less (P = 0.04) for +LPS than -LPS steers. Infusion of LPS did not affect (P > or = 0.24) N intake, fecal N excretion, or N digested, but resulted in greater (P < 0.01) urinary N excretion and less (P < 0.01) N retention. The absence of an LPS x Met interaction (P = 0.26) for N retention indicates that supplemental Met does not improve the N utilization of growing beef steers exposed to a gram-negative bacterial endotoxin. Decreases in plasma concentrations of several essential AA in +LPS steers suggest that metabolic demand for these AA likely increased in steers exposed to endotoxin.
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PMID:Effects of rumen-protected methionine supplementation and bacterial lipopolysaccharide infusion on nitrogen metabolism and hormonal responses of growing beef steers. 1884 91

The oncologist dream is to provide more benefit with lower toxicity. The increasing knowledge of molecular mechanism for survival and proliferation of cancer cells leads to the development of targeted therapies with impressive results for some cancers even if not associated with chemotherapy. These targeted treatments could be monoclonal antibodies or tyrosine kinase inhibitors. Inactivation of only one oncogene can lead to the regression of tumours as well as the inhibition of only one pathway with one or more inhibitors. This result is related to the oncogenic addiction of these tumours. Examples are imatinib in CML and GIST, trastuzumab in HER2 positive breast cancer, gefitinib in mutated EGFR, crizotinib in EML4-ALK positive lung cancer and, also, vemurafenib in BRAF 600E mutated metastatic melanoma. We shall specifically discuss HER2 positive breast cancer, which represent some 15-20% of breast cancers and the recent targeted and bi-targeted therapies. Trastuzumab, an anti-HER2 monoclonal antibody has changed the prognosis of the disease improving survival in the metastatic and adjuvant setting. Lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER2 is approved with capecitabine in trastuzumab resistant patients and in combination with letrozole in first line. Unfortunately, 20% of patients receiving adjuvant trastuzumab relapse and metastatic patients only transienly respond to trastuzumab or lapatinib combined with chemotherapy. New HER2 targeted drugs are currently in development like pertuzumab, T-DMI or mTOR and PI3K inhibitors. New strategies combining these drugs with or without chemotherapy showed interesting results in metastatic and neoadjuvant trials. The selection of patients who will most benefit from these combinations is still a challenge. Currently, chemotherapy in association with anti-HER2 therapy remains the most effective treatment option.
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PMID:[Will targeted therapies replace chemotherapy?]. 2269 Apr 83