Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1851100 (MIP)
 5,054 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main intrinsic membrane protein of the lens fiber cell, MIP, has been previously shown to be phosphorylated in preparations of lens fragments. Phosphorylation occurred on serine residues near the cytoplasmic C-terminus of the molecule. Since MIP is thought to function as a channel protein in lens plasma membranes, possibly as a cell-to-cell channel protein, phosphorylation could regulate the assembly or gating of these channels. We sought to identify the specific serines which are phosphorylated in order to help identify the kinases involved in regulating MIP function. To this end we purified a peptide fragment from native membranes that had not been subjected to any exogenous kinases or kinase activators. Any phosphorylation detected in these fragments must be due to cellular phosphorylation and thus is termed in vivo phosphorylation. Purified membranes were also phosphorylated with cAMP-dependent protein kinase to determine the mobility of phosphorylated and unphosphorylated MIP-derived peptides on different HPLC columns and to determine possible cAMP-dependent protein kinase phosphorylation sites. Lens membranes, which contain 50-60% of the protein as MIP, were digested with lysylendopeptidase C. Peptides were released from the C-terminal region of MIP and a major product of 21-22 kDa remained membrane-associated. Separation of the lysylendopeptidase-C-released peptides on C8 reversed-phase HPLC demonstrated that one of these fragments, corresponding to residues 239-259 in MIP, was partially phosphorylated. The phosphorylated and nonphosphorylated forms of this peptide were separated on QAE HPLC. In vivo phosphorylation sites were found at residues 243 and 245 through phosphoserine modification via ethanethiol and sequence analysis. Phosphorylation was never detected on serine 240. The phosphorylation level of serine 243 could be increased by incubation of membranes with cAMP-dependent protein kinase under standard assay conditions. Other kinases that phosphorylate serines found near acidic amino acids must be responsible for the in vivo phosphorylation demonstrated at serine 245.
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PMID:Amino acid sequence of in vivo phosphorylation sites in the main intrinsic protein (MIP) of lens membranes. 217 1

Macrophage inflammatory protein (MIP-1) administered systemically causes a fever not blocked by a prostaglandin (PGE) synthesis inhibitor. The purpose of this study was to examine the central mechanism of pyrexic action of this cytokine in the unrestrained rat. After guide cannulae for microinjection were implanted stereotaxically just above the anterior hypothalamic preoptic area (AH/POA), the body temperature of each rat was monitored by a colonic thermistor probe. Saline control vehicle or MIP-1 was microinjected into the AH/POA in one of eight concentrations ranging from 0.0028-9.0 ng per 0.5 mu 1 volume. MIP-1 induced a biphasic or monophasic fever of short latency characterized by an inverse dose-response curve. The potency of MIP-1 was in the femtomolar (10(-15)) range with the lowest dose of 0.028 ng producing a fever of over 2.0 degrees C with a latency of 15 min or less. To determine whether a PGE mediates MIP-1 fever, indomethacin was administered either intraperitoneally in a dose of 5.0 mg/kg or directly into the MIP-1 injection site in a dose of 0.5 microgram/0.5 mu 1, both injected 15 min before MIP-1. Pretreatment of the injection site in the AH/POA with indomethacin failed to prevent the febrile response evoked by MIP-1 injected at the same locus. Further, the dose of systemic indomethacin, which blocks PGE-induced fever in the rat, attenuated only partially the MIP-1 fever. The results demonstrate that MIP-1 is the most potent endopyrogen discovered thus far, and that its action is directly in the region of the hypothalamus which contains both thermosensitive and pyrogen-sensitive neurons. The local action of MIP-1 on cells of the AH/POA in evoking fever is unaffected by the PGE inhibitor which indicates, therefore, that a cellular mechanism operates in the hypothalamus to evoke fever independently of the central synthesis of a PGE.
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PMID:Macrophage inflammatory protein-1: unique action on the hypothalamus to evoke fever. 219 77

A cDNA clone of murine macrophage inflammatory protein 2 (MIP-2) has been isolated from a library prepared from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the nucleotide sequence determined. This cDNA was used to clone cDNAs for human homologues of MIP-2 from a library prepared from phorbol myristate acetate-treated and LPS-stimulated U937 cells. Two homologues were isolated and sequenced. Human MIP-2 alpha and MIP-2 beta are highly homologous to each other and to a previously isolated gene, human gro/melanoma growth-stimulating activity (MGSA). These three human genes, MIP-2 alpha, MIP-2 beta, and gro/MGSA, constitute a sub-family within the cytokine family represented by platelet factor 4 and interleukin 8.
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PMID:Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues. 220 51

We characterized the tumorigenic and metastatic potential of a poorly differentiated, non-CEA-producing colon cancer cell line, MIP-101, after injection at different sites in athymic mice. After subcutaneous and intrasplenic injection tumor grew locally in 100 and 50%, respectively, but no metastases were found, even after intravenous injection. Intraperitoneal implantation, however, resulted in a high tumor take (10/10) and subsequent liver colonization (8/10 mice). Exogenous CEA prior to intrasplenic injection induced metastasis in 7/8 mice (in 2 mice to the liver and in 5 mice to the lung). Intrasplenic injection of CX-1, a good CEA producer, resulted in hepatic metastases in 100% of the animals. These data suggest a direct or indirect role of CEA in the metastatic process. We conclude that MIP-101 has a high tumorigenic and invasive potential but a low metastatic proclivity, except when grown in the peritoneum, and that pretreatment of tumor-bearing animals with CEA affects the metastatic proclivity.
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PMID:Characterization of the tumorigenic and metastatic potential of a poorly differentiated human colon cancer cell line. 222 14

The effect of sodium butyrate on the expression of the carcinoembryonic-antigen (CEA) gene was studied in two poorly differentiated colorectal-carcinoma cell lines (Clone-A and MIP-101) and in one well-differentiated cell line (LS-174T); A.T.C.C. no. CCL 188). Northern-blot and dot-blot analyses indicated a steady increase in CEA mRNA from day 4 to a maximal level by day 14 after these cells were exposed to 2 mM-sodium butyrate. Studies using nuclear run-off assays followed by dot-blot hybridization to a partial CEA cDNA clone demonstrated that specific increases in gene transcription rates (3-fold in MIP-101, 4-fold in LS-174T and 6-fold in Clone-A) are not sufficient to account for the observed increases in CEA mRNA abundance. Further studies showed that CEA-specific transcripts have a half-life of about 60-80 min, and treatment with sodium butyrate increased the stability of CEA-specific transcripts to about 340 min in LS-174T cells and to about 500 min in Clone-A cells. We conclude that the induction of the CEA-gene expression by sodium butyrate in colorectal-cancer cells is mediated by both transcriptional and post-transcriptional mechanisms, with CEA mRNA stability as one of the major check-points.
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PMID:Induction of carcinoembryonic-antigen-gene expression in human colorectal carcinoma by sodium butyrate. 226 82

The maximum static inspiratory and expiratory pressures (MIP and MEP, respectively) were measured in 15 normal male subjects (average age, 27.14 years) in standing and sitting position. The MIP was determined at RV and FRC and MEP was determined at TLC and FRC. No significant differences were found for these parameters between the two postures. Our study proves that the posture adopted by the subject when these two maneuvers are performed does not influence the results obtained.
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PMID:Postural variation of the maximum inspiratory and expiratory pressures in normal subjects. 229 56

Covalent attachment of fatty acids to proteins may be a means of anchoring cytoplasmic proteins to the plasma membrane. The possibility that lens membrane proteins can be fatty acid acylated was studied by incubating the lenses of young rats with 9,10-3H-palmitate. The distribution of 3H-palmitate among the lens membrane polypeptides separated by electrophoresis was determined by fluorography and by direct measurement of radiolabel in sliced gels. 3H-palmitate was found to be incorporated into membrane polypeptide fractions of approximately 19, 30, and 35 kD; the 30 kD fraction appeared to be most highly labeled. The principal lens membrane protein, the main intrinsic protein (MIP 26), was not labeled. This incorporation appeared to be due to covalent attachment rather than to noncovalent binding, and was temperature dependent, independent of protein synthesis, and resistant to displacement by beta-mercaptoethanol. Whether the acylation is enzymatic or nonenzymatic is unclear. The identity of the acylated polpeptides is unknown.
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PMID:Palmitoylation of ocular lens membrane proteins. 230 34

The haemopoietic system has three main compartments: multi-potential stem cells, intermediate stage progenitor cells and mature cells. The availability of simple reproducible culture systems has made possible the characterization and purification of regulators of the progenitor cells, including colony-stimulating factors and interleukins. In contrast, our knowledge of the regulators involved in the control of stem cell proliferation is limited. The steady-state quiescent status of the haemopoietic stem cell compartment is thought to be controlled by locally acting regulatory elements present in the stromal microenvironment, but their purification has been hampered by the lack of suitable culture systems. We have recently developed a novel in vitro colony assay that detects a primitive cell (CFU-A) which has similar proliferative characteristics, in normal and regenerating bone marrow, to the CFU-S (haemopoietic stem cells, as defined by the spleen colony assay) and which responds to CFU-S-specific proliferation regulators. We have now used this assay to purify to homogeneity a macrophage-derived reversible inhibitor of haemopoietic stem cell proliferation (stem cell inhibitor, SCI). Antibody inhibition and sequence data indicate that SCI is identical to a previously described cytokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and that SCI/MIP-1 alpha is functionally and antigenically identical to the CFU-S inhibitory activity obtained from primary cultures of normal bone marrow cells. The biological activities of SCI/MIP-1 alpha suggest that it is a primary negative regulator of stem cell proliferation and that it has important therapeutic applications in protecting haemopoietic stem cells from damage during cytotoxic therapies for cancer.
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PMID:Identification and characterization of an inhibitor of haemopoietic stem cell proliferation. 232 Jan 11

The formation of neurites in isolated neurones of the snail Lymnaea stagnalis in primary culture was studied. The insulin-related neuropeptide (MIP: Molluscan insulin-related peptide) produced by the neuroendocrine light green cells (LGCs) of Lymnaea stimulated neurite formation, both in isolated unidentified central neurons and in the LGCs. The effect of MIP was dose dependent. It was significant from the second day of culture and amounted up to an 8-fold increase in neurite outgrowth after 3 days. The results add a functional aspect to the evolutionary relationship of MIP with mammalian insulin and insulin-related peptides and suggest that the LGCs, which stimulate growth, are also involved in development of the nervous system.
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PMID:Molluscan insulin-related neuropeptide promotes neurite outgrowth in dissociated neuronal cell cultures. 233 Jan 29

Cytokines mediate many host responses to bacterial infections. We determined the inflammatory activities of five cytokines in the central nervous system: TNF-alpha, IL-1 alpha, IL-1 beta, macrophage inflammatory protein 1 (MIP-1), and macrophage inflammatory protein 2 (MIP-2). Using a rabbit model of meningeal inflammation, each cytokine (except IL-1 beta) induced enhanced blood brain barrier permeability, leukocytosis in cerebrospinal fluid, and brain edema. Homologous antibodies to each mediator inhibited leukocytosis and brain edema, and moderately decreased blood brain barrier permeability. In rabbits treated with anti-CD-18 antibody to render neutrophils dysfunctional for adhesion, each cytokine studied lost the ability to cause leukocytosis and brain edema. After intracisternal challenge with pneumococci, antibodies to TNF or IL-1 prevented inflammation, while anti-MIP-1 or anti-MIP-2 caused only a 2-h delay in the onset of inflammation. We suggest these cytokines have multiple inflammatory activities in the central nervous system and contribute to tissue damage during pneumococcal meningitis.
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PMID:The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis. 240 63


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