Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on our new finding that an inflammation in which tumor necrosis factor (TNF) is primed or triggered (ontogenic inflammation) can regulate the homeostasis in ontogenesis, we have identified a new lipopolysaccharide from wheat flour (LPSw) that can induce ontogenic inflammation in adult mice. LPSw can prime adult mice to produce TNF when given orally or percutaneously, suggesting that it may maintain homeostasis in adults. LPSw can cure experimental animals of diabetes, hyperlipidemia, ulcer, and herpes. It can also stimulate bone resorption and egg-laying, and shows a strong analgesic effect that is blocked by naloxone. This effect even allows a release from drug addiction. Suppression of serum cholesterol level by oral uptake of LPSw in Watanabe heritable hyperlipidemic (WHHL) rabbit was also observed. Infection of toxoplasma was prevented by oral uptake of LPSw. The realization that a single oral or percutaneous administration of LPSw may be a cure for multiple intractable diseases may lead to the presentation of a nontoxic type of Coley's toxin, which is known to be an efficient cancer treatment, but has high toxicity.
Mol Biother 1992 Dec
PMID:Oral or percutaneous administration of lipopolysaccharide of small molecular size may cure various intractable diseases: a new version of Coley's toxin. 147 70

While steroid response is generally restricted by the availability of steroid receptors, the theoretical limits of the response are not known. We have constructed a series of cell lines that stably express the estrogen receptor (ER) at levels up to 5,000,000 ERs per cell and employed these cells to explore the limits of the estrogen response. Several reporter genes with estrogen response elements upstream of the herpes thymidine kinase promoter showed hyperbolic saturation kinetics with increasing ER. Maximum response was 10 times that seen in cell lines with receptor titers comparable to physiological levels. Half-maximal responses required 500,000 receptors per cell, and cells with 5,000,000 ERs showed greater than 90% maximum induction. Estradiol dose-response studies indicated that the receptors are limiting below 500,000 ERs per cell, but at higher ER titers there are spare receptors. In contrast to most reporters, the widely used reporter pA2-CAT, which has 200 base pairs of Xenopus vitellogenin DNA between the response element and the promoter, showed squelching at ER levels beyond 500,000 per cell. Cell lines that expressed ER above this level activated pA2-CAT with a distorted hormone dependence, where saturating ligand concentrations were inhibitory. All reporters displayed squelching when the ER was provided by transient transfection at a level that we judge is 20,000,000 per cell by extrapolation from the behavior of stable cell lines. These findings suggest that saturation of the cellular capacity to mediate an estrogen response and ER-dependent squelching occur at receptor titers well above those encountered in nature. If current models of steroid hormone action are correct, the findings also imply that estrogen response elements are occupied to very small extents under normal conditions.
Mol Endocrinol 1992 Feb
PMID:The limits of the cellular capacity to mediate an estrogen response. 156 62

Eight recombinant clones were obtained by insertion of BamHI fragments of herpes simplex type I viral DNA into a vector plasmid pUC19o. Of the obtained clones 5 were found to hybridize with herpes simplex type I and 2 viral DNA while 3 clones revealed a positive reaction with the Vero cells DNA. A constructed DNA-probe possessing the highest level of activity was selected for further studies. The probe is a BamHI fragment of herpes simplex type I viral DNA labelled with 32P dTTP. Probe sensitivity in blot hybridization is 10 pg for identification of type I viral DNA and 50 pg for type 2 viral DNA. The DNAs of cytomegalovirus and herpes zoster virus do not show positive signals with the probe. The increased sensitivity of the used dot hybridization as compared with biological or IEA antigen identification of the virus was confirmed with the clinical material from 59 patients with the different clinical manifestations of the herpes viral infection.
Mol Gen Mikrobiol Virusol 1991 Oct
PMID:[Detection of herpes simplex virus by DNA-DNA hybridization method]. 166 48

A newly described herpes virus, human herpes virus 6, (HHV-6), has been linked to exanthema subitum but beyond this its pathogenetic impact remains to be determined. A large body of evidence links it to various lymphoproliferative disorders and this study was conducted to identify forms of lymphoproliferation linked to HHV-6. We studied biopsy samples from 32 patients with disorders of the lymphatic system for the presence of HHV-6, both by polymerase chain reaction (PCR) and in-situ hybridization (ISH) methods, as well as Epstein-Barr virus (EBV) viral DNA, clonal rearrangements of the antigen receptor genes and bcl-2 genes. All the specimens were studied morphologically and a clinical follow-up of up to 4 years was obtained. Seven of the 32 patients were positive for HHV-6 DNA and the remainder were negative. Two of these HHV-6 positive specimens, both from elderly persons, showed a similar distinct histological pattern diagnosed as malignant B-cell lymphoma of high grade malignancy. Two other HHV-6-positive specimens were reactive lymphadenopathies occurring in younger adults. In addition, one further specimen with evidence of EBV-involvement was from a patient who died 3 months after biopsy with fatal infectious mononucleosis (IM). These five samples had HHV-6 DNA by PCR and ISH. Two specimens without specific histologic abnormalities showed evidence of HHV-6 only by PCR but not by ISH. Both high grade malignant lymphomas showed clonal proliferations, one of monoclonal B-cells and the other of clonal T-cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Lymphadenitis and lymphoproliferative lesions associated with the human herpes virus-6 (HHV-6). 168 79

The Escherichia coli polB gene encodes DNA polymerase II and is regulated by the SOS system. We sequenced a 4081 nucleotide segment of the E. coli chromosome that contains the polB gene and its flanking regions. DNA polymerase II, as deduced from the DNA sequence, consists of 782 amino acids, has a molecular weight of 89,917, and is structurally homologous to alpha-like DNA polymerases, which include eukaryotic replicative DNA polymerases. Comparison of the sequences of the alpha-like DNA polymerases including E. coli DNA polymerase II showed that there were nine highly conserved regions, and we constructed an unrooted phylogenetic tree of the DNA polymerases based on the differences in these conserved regions. The DNA polymerases of herpes groups viruses and the DNA polymerases that use protein priming for the initiation of replication form two separate subfamilies that occupy opposite locations in the tree. Other DNA polymerases, including E. coli DNA polymerase II, human DNA polymerase alpha, and yeast DNA polymerase I, occupy the central regions between the two subfamilies and they are rather distantly related to each other. The transcription initiation site of polB was identified by analysis of in vivo transcripts, and the promoter was assigned upstream of the polB coding region. The recognition sequence of the LexA repressor (SOS box) was identified by a footprinting experiment. It overlaps the -35 sequence of the polB promoter.
Mol Gen Genet 1991 Apr
PMID:Escherichia coli DNA polymerase II is homologous to alpha-like DNA polymerases. 203 16

Steroid receptors have been reported to stimulate transcription in a manner synergistic with other transcription factors. We have examined this synergism or functional cooperativity between glucocorticoid receptors and basal transcription factors in a variety of promoter and reporter gene contexts. A fragment containing a hormone response element from mouse mammary tumor virus was fused to well characterized promoters from the herpes virus thymidine kinase and mouse beta-globin genes and to related mutant promoters altered by inactivation of transcription factor-binding sites through point mutagenesis or deletion. These constructs were transfected into glucocorticoid-sensitive fibroblasts, and reporter gene activity was assessed with or without hormonal stimulation. In contrast to previous studies, we found little indication of synergistic interaction between elements mediating a hormone response and adjacent basal promoters. In fact, we observed that inactivating basal factor-binding sites, thereby decreasing promoter strength, actually increased hormone inducibility. We suggest that the inverse relationship between basal promoter strength and the induction ratio attained upon hormonal stimulation may be due to limitation of a common factor, an "adaptor" through which glucocorticoid receptor and basal transcription factors interact with the components of the RNA polymerase II complex to stimulate rates of transcription.
Mol Endocrinol 1991 May
PMID:Concerted stimulation of transcription by glucocorticoid receptors and basal transcription factors: limited transcriptional synergism suggests mediation by coactivators/adaptors. 207 21

Fibronectin (FN) mRNA levels increased when quiescent cells (serum starved) were stimulated to undergo the G0/G1 transition by the addition of 20% given fetal calf serum to the media. The 5'-flanking region of the FN gene (position +69 to -510 base pairs (bp] was fused to the coding region of the chloramphenicol acetyltransferase (CAT), and the fusion gene was used in transfection assays. Expression of FNCAT increased on serum treatment indicating that the region of the FN gene between positions +69 and -510 bp mediated serum responsiveness. Deletion of FN gene 5'-flanking sequences from position -510 to -122 bp eliminated serum responsiveness suggesting that an element between these positions was mediating the effect. Sequences between positions -122 and -510 bp of the FN gene were able to confer serum responsiveness on a herpes virus thymidine kinase promoter-CAT fusion gene (TKCAT) when the FN gene sequences were cloned upstream of TKCAT. The ability to confer serum responsiveness on TKCAT was retained with a smaller 100-bp sequence (position -122 to -222 bp). Both a cAMP response element (position -170 bp) and a nuclear factor-1 binding site (position -155 bp) have been identified within this sequence (Dean, D. C., Blakeley, M. S., Newby, R. F., Ghazal, P., Hennighausen, L., and Bourgeois, S. (1989) Mol. Cell. Biol. 9, 1498-1506). The cAMP response element was serum-responsive when cloned upstream of TKCAT or a minimal FN promoter (deleted to position -56 bp) while the nuclear factor-1 binding site was unresponsive. Therefore, the cAMP regulatory element (CRE) is the serum-responsive element between position -122 and -222 bp. Serum-induced binding of proteins to the CRE was detected in gel retardation assays with extracts from cell lines where FN expression was serum-responsive. However, no serum-induced binding was detected with extracts from the JEG-3 cell line where FN expression was not serum-responsive. Serum-induced binding occurred rapidly, within 15 min, and did not require protein synthesis. The decay of serum-induced binding was relatively slow as increased binding was still detectable 24 h after removal of serum. The CRE also mediates transcriptional stimulation by cAMP, but unlike serum stimulation increased CRE binding activity was not detectable in extracts from cAMP-treated cells (Dean, D. C., Blakeley, M. S., Newby, R. F., Ghazal, P., Hennighausen, L., and Bourgeois, S. (1989) Mol. Cell. Biol. 9, 1498-1506).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Serum stimulation of fibronectin gene expression appears to result from rapid serum-induced binding of nuclear proteins to a cAMP response element. 213 58

Three DNA constructs, the natural human growth hormone gene (hGH-hGH) its 500 bp promoter linked to the chloramphenicol acetyl transferase reporter gene (hGH-CAT), and its structural part linked to the herpes virus thymidine kinase promoter (TK-hGH) were introduced into rat pituitary GC cells by DEAE-dextran transfection. Transient expression was followed as a function of triiodothyronine (T3) concentration. The hGH-CAT expression was specifically inhibited by T3 following a typical dose-response curve while hGH-GH gene expression was not significantly modified. The transient expression of TK-hGH increased as a function of T3 concentration. These results indicate that T3 exerts two opposite effects on hGH gene expression. First, it down-regulates expression by acting on the promoter; second, it up-regulates expression by acting on the structural part of the gene. These action could be due to regulation of transcription and mRNA stabilization, respectively.
Mol Cell Endocrinol 1990 Jul 09
PMID:Triiodothyronine inhibits transcription from the human growth hormone promoter. 221 33

The recovery of RNA from postmortem (PM) brain tissues was quantified by molecular hybridization. RNA degradation rates postmortem were faster in mice with herpes encephalitis than with uninfected mice, but clear ribosomal peaks could be seen up to 72 hr after death. In a comparison between frontal cortex samples from neurologically normal and Alzheimer's disease cases a reduction in ribosomal, poly A, preproenkephalin, and preprosomatostatin RNA levels was observed in the Alzheimer's disease group. This general reduction may be influenced by the cause of death as well as the pathology.
Exp Mol Pathol 1986 Feb
PMID:Recovery and measurement of specific RNA species from postmortem brain tissue: a general reduction in Alzheimer's disease detected by molecular hybridization. 241 56

We have obtained a mouse transformant cell line containing two herpes viral thymidine kinase (tk) genes integrated in pericentromeric heterochromatin. Restriction analysis of tk- revertant and tk+ rerevertant derivatives suggest that one of the two tk genes is repressed in tk- cells, but is reactivated in tk+ rerevertants. The results of Northern analysis indicated that repression-activation is probably controlled at the transcriptional level. To examine the molecular basis for this repression, we cloned the tk gene from a tk- revertant cell line. Then, using the cloned tk gene as donor DNA to select for tk+ transformants, we found that it has a transfection efficiency indistinguishable from the viral tk gene. This indicates that repression is probably not mediated via any DNA sequence changes within the tk gene. The results of further studies by restriction analysis, azacytidine treatments, and secondary DNA transfection assays demonstrated that tk repression is associated with changes in DNA methylation. Surprisingly, derepression of the tk gene was accompanied by rearrangements in the flanking DNA. The latter result suggests that the flanking DNA may exert cis effects on tk gene expression. Additional studies with this system may provide insights into the molecular basis underlying position effects in heterochromatin.
Mol Cell Biol 1986 Dec
PMID:Modulation of tk expression in mouse pericentromeric heterochromatin. 243 1


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