Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth factor(s) with a strong mitogenic effect on BALB/c3T3 cells was purified from an extract of C-Li21 cells, a human hepatocellular carcinoma line, by a combination of heparin-affinity chromatography and reversed-phase high-performance liquid chromatography (HPLC). Two major peaks of mitogenic activity were obtained by reversed-phase HPLC. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the two peaks revealed that one was composed of three proteins with relative molecular masses of 27, 24 and 23 kilodaltons (kD), whereas the other was a single 19-kD protein. Immunoblot analysis showed that all four of these molecules were immunoreactive species of human basic fibroblast growth factor (bFGF). N-Terminal sequence analysis of these molecules revealed that most of them were N-terminally blocked. However, small proportions of the 23- and 19-kD molecules were not blocked, and their respective N-terminal sequences were found to correspond to Gly-40-Gly-27 and Pro29-Phe40 of human bFGF deduced from the cDNA sequence of a human hepatoma cell line, SK-HEP-1. Expression of bFGF in hepatocellular carcinomas was then investigated by RNA blot analysis. All of the examined hepatocellular carcinoma cells expressed bFGF, and the degree of expression was higher in surgically resected hepatocellular carcinomas than in the corresponding adjacent non-cancerous liver tissue. Transcripts of bFGF were not detected in normal liver. These results suggest that C-Li21 cells produce four molecular forms of bFGF, and that bFGF may be involved in hepatocarcinogenesis. Moreover, it appears that bFGF is a potent mitogen toward primary-cultured hepatocytes, and that high-molecular-mass forms of bFGF produced by C-Li21 cells have stronger mitogenic effects on hepatocytes and are more stable under acidic conditions than the low-molecular-mass form, composed of 146 amino acids.
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PMID:Characterization of high-molecular-mass forms of basic fibroblast growth factor produced by hepatocellular carcinoma cells: possible involvement of basic fibroblast growth factor in hepatocarcinogenesis. 172 15

We investigated the nature of temperature sensitivity of the HEP strain of rabies virus. After initial incubation for appropriate period (more than 12 hr) at the permissive temperature (36-37 degrees), incubation temperature of the rabies virus infected cultures was shifted to a nonpermissive temperature (39.5-40.5 degrees). Upon the upshift, virion production was ceased, but the rate of viral RNA synthesis was greatly increased and reached almost 10 times that of 36 degrees-infection within 8-10 hr, and then the activity quickly decreased together with the onset of accelerated CPE. Little or no 42S genome-sized RNA was produced at the elevated temperature, and almost all RNAs produced in large amounts seemed to be viral mRNAs and were shown to be functional in t he cell-free translation system. Consistent with these observations, the viral ribonucleoprotein complex isolated from the temperature-upshifted culture was associated with relatively large amounts of small sized RNAs, which might reflect their increased transcriptive activity. These observations suggest that the viral RNA polymerase itself is not temperature-sensitive and the temperature-induced defect may reside in the regulatory factor which plays a role in turning on the synthesis of viral genome-sized RNA.
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PMID:Temperature-sensitivity of the replication of rabies virus (HEP-flury strain) in BHK-21 cells. I. Alteration of viral RNA synthesis at the elevated temperature. 173 1

The influence of an SPUU-PEO-Heparin (B-PEO-HEP) copolymer coated blood contacting surface on patency and platelet deposition in small diameter (4 mm i.d.) Biomer grafts was investigated using a canine model. Grafts were implanted in the bilateral carotid and femoral arteries. B-PEO-HEP coated grafts still showed patency after 3 days. Control Biomer grafts occluded before 24 hr. (postoperatively). SEM of the luminal surfaces of the Biomer grafts demonstrated large amounts of adherent platelets with distorted morphologies, while B-PEO-HEP grafts did not. In platelet studies, B-PEO-HEP grafts showed significantly less platelet adhesion than Biomer grafts. The improved blood compatibility of B-PEO-HEP graft co-polymer coatings attests to their usefulness for coating or casting.
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PMID:SPUU-PEO-heparin graft copolymer surfaces. Patency and platelet deposition in canine small diameter arterial grafts. 175 Oct 86

For the determination of LDL receptor expression on living human cells two monoclonal antibodies specific for the extracellular domain of LDL receptor were established using affinity-purified LDL receptor and carrier-conjugated LDL receptor peptide 163-174 as immunizing antigens. The 125I-labeled antibodies were used to quantify increases in LDL receptor expression on human cells grown in the presence of increasing concentrations of various growth factors. Growth factor-mediated increase of LDL receptor expression was entirely different in various cell lines with respect to a distinct growth factor and for different growth factors when tested with one and the same cell line. An increased LDL receptor expression was observed on A431 epidermoid carcinoma cells of the vulva in the presence of epidermal growth factor (EGF) or insulin but not with platelet-derived growth factor (PDGF), on HUV-EC primary endothelial cells in the presence of insulin or PDGF but not with EGF, and on MRC-5 diploid fetal lung cells only in the presence of PDGF. HEP-3B hepatoma cells did not respond to any of the three growth factors essentially maintaining the original level of LDL receptor expression.
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PMID:Expression of LDL receptor on tumor cells induced by growth factors. 185 Feb 20

Type IV collagen, a 500-kilodalton (alpha 1)2(alpha 2)1 heterotrimer with noncollagenous domains (NC1) is the major molecule in most basement membranes in the body. In addition to its structural role as scaffolding, type IV collagen is involved in promoting adhesion and migration of various cell types in vitro, including rabbit corneal epithelial cells. This study assessed the effect of purified proteolytic fragments of type IV collagen and selected synthetic peptides derived from the alpha 1 and alpha 2 chains that are related to the adhesion and directed migration of dissociated primary cultured rabbit epithelial cells. Two homologous peptides (HEP-1 and HEP-2) derived from alpha 1 and alpha 2 NC1 regions were found to promote epithelial cell adhesion. A peptide (HEP-3) derived from an interruption of the triple helix of type IV collagen was effective in promoting corneal epithelial cell migration in both chemotaxis and haptotaxis assays. The helical fragment of type IV collagen promoted both directed migration and ample adhesion, indicating that there may be at least another moiety in the helical region responsible for cell adhesion. The results with these peptides revealed to some extent how corneal epithelial cells react at the molecular level with type IV collagen. They could serve as the basis for therapeutic agents to modify corneal epithelial behavior in situations of perturbed wound healing.
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PMID:Type IV collagen and corneal epithelial adhesion and migration. Effects of type IV collagen fragments and synthetic peptides on rabbit corneal epithelial cell adhesion and migration in vitro. 189 74

Three T cell clones derived from rabies virus-immunized BALB/c mice were analysed for specificity and function. The clones proved to be broadly cross-reactive by responding to different rabies virus isolates (PM, ERA, CVS, HEP) and other representatives of the genus Lyssavirus, like the Duvenhage-6 (DUV6) and Mokola (MOK) viruses. The clones detected three different epitopes: an epitope expressed on the matrix protein (M) shared by PM, HEP, MOK and DUV6 viruses (clone AA8), an epitope expressed on the M-protein shared by PM, ERA, CVS, HEP and MOK viruses (clone 35A) and finally an epitope expressed on the glycoprotein (G-protein) shared by PM, ERA, CVS, HEP and MOK viruses (clone BG2). Antigen recognition of all clones proved to be MHC-restricted and they all displayed the CD4+ CD8- phenotype. Intravenous inoculation of the T cells in syngeneic mice, which had been injected intracutaneously in the ear with HEP virus, resulted in a localized DTH reaction characteristic for TH1 cells. In vitro, the clones were able to provide help to rabies virus-primed B cells, resulting in the production of virus-specific antibodies directed against all the four structural proteins of rabies virus. Further analysis of this antibody response revealed that part of it was directed against antigenic determinants of the G-protein which induce virus neutralizing antibody.
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PMID:Rabies virus cross-reactive murine T cell clones: analysis of helper and delayed-type hypersensitivity function. 196 28

Two hundred eleven patients with advanced breast cancer were randomized to receive either epirubicin (E) 50 mg/m2 and prednisolone (LEP) or E 100 mg/m2 and prednisolone (HEP). The intended treatment consisted of 16 courses of LEP or eight courses of HEP given at 3-weekly intervals. Reasons for stopping treatment early included progressive disease, stable disease without symptomatic improvement, or severe toxicity deemed intolerable by either the patient or physician. Toxicity was recorded at 3-weekly and response at 9-weekly intervals using the World Health Organization (WHO) criteria of response and toxicity. Two hundred nine patients were eligible for analysis, 98% of whom have been followed for more than a year. One hundred four patients received LEP and 105 HEP. Significantly worse myelosuppression, alopecia, nausea and vomiting, and mucositis were seen in the high-dose arm (P less than or equal to .001). More patients in the LEP arm stopped treatment before the fourth course than in the HEP arm, and the commonest reason for stopping was progressive disease. A similar median number of courses was given in each arm. There was a significantly higher response in the HEP arm (HEP - complete response [CR] + partial response [PR] = 41%, LEP - CR + PR = 23%). Despite this, no statistically significant differences was seen in overall survival or progression-free interval. The median survival for HEP and LEP was 44 and 46 weeks, respectively.
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PMID:Epirubicin at two dose levels with prednisolone as treatment for advanced breast cancer: the results of a randomized trial. 198 76

Cardiovascular disease in all its clinical manifestations progresses significantly as age advances and takes its heaviest toll in the elderly. Hypertension becomes the dominant risk factor for cardiovascular disease in this age group because of its high incidence. Traditionally, diastolic rather than systolic blood pressure has been regarded as the main risk factor for cardiovascular complications in hypertension, although it is becoming clearer that the risk of cardiovascular complications is likely to be associated mainly with systolic pressure in the elderly. Various intervention drug trials in elderly patients seem to indicate that hypotensive drug treatment can decrease cardiovascular mortality, mainly by decreasing cerebrovascular mortality. The EWPHE used a diuretic combination with methyldopa, and the HEP study used atenolol with a thiazide diuretic. The multicenter Systolic Hypertension in the Elderly Program (SHEPS) currently underway in the United States is likely to also provide some answers. The place of newer agents such as ACE inhibitors or calcium antagonists is still undetermined. Calcium antagonist drugs have been reported to be effective, and possibly more so in the elderly than in a younger population, although this assumption is not proven and may not be valid. Pharmacokinetic studies in the elderly are very few, although the studies reported indicate a reduced clearance. Studies also indicate that Nifedipine Retard tablets are effective, with a low incidence of adverse effects. There are no trials, however, looking at the long-term benefit of treating elderly hypertensive patients with either nifedipine tablets or other calcium-channel blockers.
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PMID:Hypertension in the elderly. 207 5

There is little information regarding the molecular mechanisms of hepatocarcinogenesis. We studied the p53 gene at the DNA, RNA, and protein level in seven human hepatocellular carcinoma (HCC)-derived cell lines; six of seven showed p53 abnormalities. By Southern blotting, the p53 gene was found to be partially deleted in Hep 3B and rearranged in SK-HEP-1 cells. Transcripts of the p53 gene were undetectable in Hep 3B as well as in FOCUS cells that had no apparent deletion or rearrangement of the p53 gene. Immunoprecipitation after [35S]methionine labeling of HCC cells demonstrated that p53 protein was absent in Hep 3B and FOCUS and reduced in concentration in PLC/PRF/5 cells. p53 synthesized by Mahlavu cells showed a slower migration on SDS/polyacrylamide gels suggesting it was an abnormal protein. In Huh7 cells, p53 protein had a prolonged half-life leading to its accumulation in the nuclei; increased levels of p53 protein were also found by immunoblotting. The p53 gene and its expression appeared to be unaltered in the hepatoblastoma-derived Hep G2 cell line. We found that the loss of p53 expression did not occur as a late in vitro event in the FOCUS cell line because p53 protein was also nondetectable at an early passage. We conclude that the loss of p53 expression or the presence of abnormal forms of the protein are frequently associated with HCC cell lines. These observations suggest that alterations in p53 may be important events in the transformation of hepatocytes to the malignant phenotype.
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PMID:Abnormal structure and expression of p53 gene in human hepatocellular carcinoma. 215 27

Hepatocytes, known as polarized epithelial cells, are composed of sinusoid, basolateral and bile canalicular domains. Each domain contains proteins specific for it. Our studies indicate that the well-differentiated human hepatoma cell lines HepG2 and HuH-7 formed bile canaliculi in tissue culture, whereas the poorly differentiated hepatoma cell lines HA22T/VGH and SK-HEP-1 did not. We also used the 9B2 monoclonal antibody, previously shown to be specific for the human bile canalicular domain, to study formation of bile canaliculi in these human hepatoma cell lines. All four cell lines synthesize the 140-kD 9B2 antigen. Studies using peroxidase-antiperoxidase staining and immunoelectron microscopy revealed that the 9B2 antigen was first detected in cytoplasm and packaged in microvilli-lined vesicles, then vectorially transported to the cell surface and eventually fused with microvilli-lined vesicles from neighboring cells to form bile canaliculi in well-differentiated hepatoma cell lines. However, the 9B2 antigen of poorly differentiated lines was synthesized in cytoplasm, then transported directly to and evenly distributed on the cell membrane. These results lead us to conclude that human hepatoma cell lines could serve as a good in vitro model to study the formation of bile canaliculi in human hepatocytes. The bile canaliculi of human hepatocytes may be preformed and assembled in the intracellular, microvilli-lined vesicles, then vectorially transported to the cell surface, where they form the bile canaliculi through vesicles fusion. Finally, formation of bile canaliculi and transport of 9B2 antigen may be related to the differentiation of hepatocytes or progression stages of human hepatoma cells.
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PMID:The formation of bile canaliculi in human hepatoma cell lines. 216 94


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