Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellulose acetate electrophoretic pattern of the serum from patient Sik disclosed two distinct peaks, representing two monoclonal proteins. On immunoelectrophoresis the two M-components were found to differ in heavy chain class as well as in light chain type, IgG3(kappa) and IgA1(lambda). Serum immunoglobulin levels remained relatively constant over a period of 7 years and no clinical symptoms of a malignant deterioration occurred. It was found that the isolated M-components did not share idiotypic antigenicity. Bone marrow cells synthesizing the monoclonal proteins were identified by means of the immunofluorescent technique using isotypic as well as idiotypic antisera. Two distinct monoclonal cell populations were observed, containing either the IgG3(kappa) or the IgA1(lambda) monoclonal protein. The alpha 1-chain belonged to the VHIII subgroup, whereas the gamma 3-chain was found to be blocked. Subsequent sequence determination showed the gamma 3-chain to belong to the VHIII subgroup. It was concluded that the two M-components in the serum of patient Sik resulted from two independent neoplastic transformations.
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PMID:A biclonal origin of two monoclonal proteins, IgG3(kappa) and IgA1(lambda), from a single patient. 11 82

Peroxynitrite formation by rat alveolar macrophages activated with phorbol 12-myristate 13-acetate was assayed by the Cu,Zn superoxide dismutase-catalyzed nitration of 4-hydroxyphenylacetate. The inhibitor of nitric oxide synthesis N-methyl-L-arginine prevented the Cu,Zn superoxide dismutase-catalyzed nitration of 4-hydroxyphenylacetate by stimulated macrophages, while Cu-depleted Zn superoxide dismutase did not catalyze the formation of 3-nitro-4-hydroxyphenylacetate either in vitro or in the presence of activated macrophages. The rate of phenolic nitration by activated macrophages was 9 +/- 2 pmol x 10(6) cells-1 x min-1 (mean +/- STD). Only 8% of synthetic peroxynitrite was trapped by superoxide dismutase, which suggested that the rate of peroxynitrite formation may have been as high as 0.11 nmol x 10(6) cells-1 x min-1. This upper estimate was consistent with N-methyl-L-arginine increasing the amount of superoxide detected with cytochrome c by 0.12 nmol x 10(6) cells-1 x min-1. The rate of nitrite and nitrate accumulation was 0.10 +/- 0.001 nmol x 10(6) cells-1 x min-1, suggesting that the majority of nitric oxide produced by activated macrophages may have been converted to peroxynitrite. The formation of a relatively long lived, strong oxidant from the reaction of nitric oxide and superoxide in activated macrophages may contribute to inflammatory cell-mediated tissue injury.
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PMID:Peroxynitrite formation from macrophage-derived nitric oxide. 132 57

Malignancy is the result of multistep transformational changes of normal somatic cells. In the case of respiratory epithelial malignancies this process lasts for several years. Many methods have been explored to mimic this process in an extracorporal model. In the present investigation we combined several of these methods. Organ cultures were prepared from tracheal specimens and were then consecutively treated with human papilloma virus, benzo(a)pyrene, methylnitronitrosoguanine and tetradecanoyl phorbol acetate. Identical numbers of organ cultures from the same specimen were maintained without exposure to carcinogens. After 6 weeks these cultures were further cultivated either in mixed cultures (MC) with autologous isotopic fibroblasts or under the kidney capsule of the nude mouse (SRC). These two methods were combined after a few months: MC cells were transplanted under the SRC or SRC transplants were explanted in cell culture. This long-term selection procedure revealed striking differences between control and treated organ cultures. Three-dimensional structures containing epithelial cells were isolated from both organ cultures but survived more than 3 months only from treated cultures. Only MC from treated organ cultures produced nodules under SRC. The incidence and morphology of the nodules in the SRC were directly related to carcinogen treatment, with more nodules with pronounced epithelial cell atypia obtained from treated organ cultures. MC and SRC showed the importance of a time factor for selecting cells with changed growth behavior--increased time increased the incidence of such cells.
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PMID:Induction of transformation of human respiratory epithelium in vitro. Preliminary investigation. 141 47

Two appetite stimulants, megestrol acetate and cyproheptadine were administered in a randomized trial to 14 patients who had no evidence of opportunistic infection or malabsorption but were wasted (had lost more than 5 kg body weight) as a result of human immunodeficiency virus (HIV) infection. Energy intakes were calculated from a 7 day weighed dietary record. Mean energy intakes per kilogramme body weight were similar in both treatment groups (greater than 34 kcal/kg) and were higher than that in well British males. Energy intakes increased by just over 500 kcal during both treatments, but fell to pretreatment levels after therapy. Patients in both treatment groups gained a moderate amount of weight. Megestrol acetate was associated with impotence in 4 patients. Insufficient calorie intake alone is not a common cause of wasting associated with HIV and the role of appetite stimulants is likely to be limited.
Int J STD AIDS
PMID:Megestrol acetate vs cyproheptadine in the treatment of weight loss associated with HIV infection. 150 60

The expression and function of several proto-oncogenes were examined in a human acute T cell leukemia line, JURKAT, during phorbol ester-induced terminal differentiation. Treating JURKAT cells with the phorbol ester tetradecanoyl phorbol acetate (TPA) inhibited their proliferation and induced expression of the gene for the interleukin 2 receptor alpha chain (IL2R-alpha), consistent with previous reports. In unstimulated proliferating JURKAT cells, high levels of C-MYC, N-RAS, and BCL2 mRNAs were found that diminished rapidly following TPA-induced cessation of growth. In contrast, accumulation of mRNAs for the C-FOS, C-JUN, and EGR-1 genes increased markedly in TPA-treated cells and preceded the induction of IL2R-alpha mRNA. Expression of C-MYB, C-RAF-1, C-LCK, C-FYN, and C-FGR proto-oncogenes was relatively unchanged. To explore directly the function of two of these protooncogenes in regulating the growth of JURKAT T cells, we stably transferred C-MYC and BCL2 expression plasmids into these cells. Despite sustained expression of C-MYC, BCL2, or the combination of these protooncogenes, TPA continued to inhibit JURKAT cell growth and to induce IL2R expression. Thus, although C-MYC and BCL2 proto-oncogene expression correlated with proliferation in TPA-treated JURKAT cells, continuous over-expression of even the combination of these oncogenes was insufficient for abrogating the effects of TPA in these leukemic T cells. Because human lymphoid malignancies frequently contain chromosomal translocations that deregulate the expression of C-MYC and BCL2, our findings could have relevance for attempts to induce terminal differentiation of leukemic cells by in vitro exposure of patients' bone marrow cells to phorbol esters.
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PMID:Phorbol ester-mediated inhibition of growth and regulation of proto-oncogene expression in the human T cell leukemia line JURKAT. 201 1

The protein kinase C (PKC) inhibitor staurosporine was found to dramatically alter the actin microfilament cytoskeleton of a variety of cultured cells, including PTK2 epithelial cells, Swiss 3T3 fibroblasts, and human foreskin fibroblasts. For example, PTK2 cells exposed to 20 nM staurosporine exhibited a progressive thinning and loss of cytoplasmic actin microfilament bundles over a 60-min period. During this time microtubule and intermediate filament systems remained intact (as shown by immunofluorescence and at higher resolution by photoelectron microscopy), and the cells remained spread even though microfilament bundles were absent. Higher doses of staurosporine or longer exposure times at lower doses resulted in morphological alterations, but even severely arborized cells recovered normal morphology and actin patterns after a wash and an incubation for several hours in fresh medium. The actin filament disruption induced by staurosporine was distinguishable from the actin reorganization induced by exposure to the tumor promoter (and activator of PKC) phorbol myristate acetate (PMA). Swiss 3T3 cells made deficient in PKC by prolonged exposure to PMA (PKC down-regulation) exhibited actin alterations in response to staurosporine which were comparable to those in cells which had not been exposed to the phorbol ester. In a parallel control experiment, the actin cytoskeleton of PKC-deficient 3T3 cells was unaffected in response to PMA, consistent with down-regulation of this kinase. While the exact mechanism of staurosporine-induced actin reorganization remains to be determined, the observed effects of staurosporine on PKC-deficient cells make a role for PKC unlikely. These results indicate the need for care when staurosporine is employed as an inhibitor of protein kinase C in studies involving intact cells.
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PMID:Staurosporine induces dissolution of microfilament bundles by a protein kinase C-independent pathway. 218 42

Ovariectomized, adult female rats, with or without estradiol replacement, were kindled by daily amygdala stimulation. Kindling acquisition varied with the intra-amygdala site of stimulation. During stimulation of the medial (AME) or central (ACE) nucleus, the only effect of estradiol replacement (E), compared to non-replaced rats (nE), was to significantly decrease the number of trials with afterdischarge (AD) during early kindling (stage 0). In rats receiving stimulation of the cortical nucleus (ACO) or the baso-lateral group of nuclei (ABL), a similar effect of estradiol was extended through stage 1. In addition, nE rats with ACO or ABL electrodes required significantly more trials with AD and accumulated more than twice the sec of AD during the late stages of kindling, compared to E rats and regressed to lower stage responses between the first stage 4 and last stage 5 responses; regressed responses never occurred in E rats. Estradiol also significantly decreased the prekindling AD threshold of the AME and ACE. These results indicate that estradiol accelerates early stage kindling, likely by proconvulsive properties to increase excitability within immediate amygdala projections. During late kindling stages, estradiol may participate in reinforcing or sustaining the convulsive readiness of kindling circuits established during bilateral recruitment. The site of action for this latter effect of estradiol may reside within circuits accessed by stimulation of the ACO or ABL, and not the AME or ACE.
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PMID:Acquisition of amygdala-kindled seizures in female rats: relationship between the effect of estradiol and intra-amygdaloid electrode location. 368 62

The presence of new hypotensive peptides, possibly not related to ACE inhibition, has been investigated on 66 snake venoms from crotalid, viperid and elapid families. Only the venom of Crotalus atrox showed a substantial amount of a new decapeptide, called POL-236, with the following aminoacid sequence: PYR-LEU-TRP-PRO-ARG-PRO-GLN-ILE-PRO-PRO. Pharmacological assays performed on the synthesized peptide revealed effects on blood pressure, probably derived from vascular and cardiac interferences.
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PMID:A new peptide from Crotalus atrox snake venom. 383 66

A tyrosine protein kinase activity has been partially purified from calf thymus using the phosphorylation of the tyrosine-containing peptide angiotensin I as an assay. Detergent extracts of calf thymus possessed only low levels of specific peptide phosphorylating activity when assayed at low ionic strength. The inclusion of NaCl at a concentration of 2 M stimulated endogenous tyrosine protein kinase activity, while the activity of other endogenous kinases was inhibited. This sensitivity to NaCl was retained following partial purification of the enzyme. The phosphorylation of other substrates such as casein or the R-R-SRC peptide (Arg-Arg-Leu-Ile-Glu-Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Gly) by the tyrosine protein kinase was less sensitive to NaCl. Phosphorylation of the PK-1 peptide (Leu-Arg-Arg-Ala-Ser-Leu-Gly) by the purified catalytic subunit of cAMP-dependent protein kinase was inhibited by NaCl. The effect of NaCl on angiotensin I phosphorylation could be mimicked by KCl or sodium acetate. The principal effect of NaCl was to increase the Vmax of the enzyme for the phosphorylation of angiotensin I. At low ionic strength, Mn2+ and Co2+ were the preferred required divalent cations. At elevated NaCl concentrations Mg2+ was preferred, with half-maximal activation occurring at 35 mM Mg2+. By conducting peptide phosphorylation assays in the presence of elevated levels of Mg2+ and NaCl, tyrosine protein kinase activity can readily be detected in extracts from cell lines that express low levels of the enzyme.
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PMID:Properties of a tyrosine protein kinase from calf thymus. Response to ionic strength and divalent cations. 387 56

To clarify whether various nuclei of the amygdaloid complex play different roles in aggressive behavior including muricide, 4 types of aggression were experimentally induced in rats. These include olfactory bulbectomy (OB rats), midbrain raphe lesions (Raphe rats), administration of delta 9-tetrahydrocannabinol (THC rats) and long-term isolation (Iso rats). Rats which exhibited muricide following these treatments were subjected to bilateral lesions of either the medial (AME), central (ACE) or basolateral (ABL) amygdaloid nuclei. Both muricide and hyperemotionality in the OB rat were markedly inhibited by AME lesions. Those of the Iso and THC rats were moderately inhibited. However, in the Raphe rat, aggressive behavior was not inhibited by AME lesions. Furthermore, ACE or ABL lesions caused no significant changes in all 4 models of aggression. These results suggest that the AME plays a facilitatory role in aggression of OB, Iso and THC rats, but aggression in Raphe rat is independent of amygdaloid activity.
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PMID:Differential effects of medial, central and basolateral amygdaloid lesions on four models of experimentally-induced aggression in rats. 628 23


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