Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CD4+ T cell clone HA1.7 may be made specifically nonresponsive, or anergic, to its cognate Ag, an influenza hemagglutinin peptide (HA), by pretreatment with the superantigen Staphylococcus aureus enterotoxin B or with high concentrations of HA itself. We compare the patterns of mRNA expression and protein production of selected T cell cytokines during the first 24 h after treatments that induce anergy in HA1.7 and during the same period after treatments that simulate normal cellular activation. The cytokines examined include TNF-alpha, IL-8/neutrophil activating protein-1 and the RANTES/SIS cytokines, a family of small secreted proteins with inflammatory and potential antiproliferative and leukocyte regulating activities. Messenger RNA for TNF-alpha, human MIP-1 alpha, human MIP-1 beta, and IL-8 are all induced during the development of clonal anergy in HA1.7, and these levels are significantly higher than those seen during activation of the clone using an anti-CD3 antibody and IL-2. These high levels of mRNA also persist longer than those seen after anti-CD3 and IL-2 activation. However, the increased levels of mRNA are not typically accompanied by increased protein secretion. In all cases but one, the amount of cytokine secreted by HA1.7 cells was greater after anti-CD3 and IL-2 treatments than after anergy-inducing treatments. Thus, the induction of T cell anergy in HA1.7 does not appear to require a general inhibition of T cell cytokine mRNA expression, and, in fact, anergy treatments appear to superinduce certain cytokine transcripts, but anergy-specific posttranscriptional mechanisms may exist by which cytokine release is regulated.
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PMID:Uncoupling of cytokine mRNA expression and protein secretion during the induction phase of T cell anergy. 153 Aug 60

Cytokines may play an important role in the regulation of host defense against local bacterial infections. We have evaluated the local production of cytokines in a BALB/c mouse model of Escherichia coli pyelonephritis. Kidneys, draining lymph nodes, and spleens, were harvested at specific time intervals after bladder inoculation with E. coli corresponding to the stages of renal infection, infiltration, and bacterial clearance seen in this model. The presence of messenger RNA for specific cytokines (interleukins 1 through 6, chemotactic factors, granulocyte and granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor (TNF alpha) and beta, IFN gamma, transforming growth factor (TGF beta), and cytokine synthesis inhibitory factor (CSIF)/IL-10) was determined by polymerase chain reaction (PCR) amplification of reverse transcribed RNA. We have demonstrated mRNA encoding IL-1, IL-6, G-CSF, GM-CSF, TNF alpha, H400 (a protein homologous to a family of chemotactic factors and identical to MIP-1 beta), and CSIF/IL-10 in the kidney at 12 h and 1, 2, and 3 d after bacterial challenge. No signal was seen in normal animals or in mice after 5 d. This pattern of cytokine expression was observed only in renal tissues suggesting a localized response. IL-6 was present in the urine at 4 h with rapid resolution to baseline levels by 24 to 48 h. In contrast, IL-6 was not usually detectable in the serum. TNF alpha was not detectable in the serum or urine during the course of the infection. By immunohistochemical staining of kidney sections we have shown that IL-6 is produced predominantly by mesangial cells rather than by the inflammatory infiltrate. This study provides additional evidence utilizing novel techniques that specific cytokines are produced locally in response to bacterial infections. The time course of production demonstrated in this model supports the important role of cytokines in natural host resistance to local infection.
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PMID:Local cytokine production in a murine model of Escherichia coli pyelonephritis. 154 64

The gene encoding the major intrinsic protein (Mip) of eye-lens-fibre cell membranes has been assigned to region D1 of mouse Chromosome 10 by in situ hybridisation of a cDNA for rat MIP to G-banded metaphase chromosomes. The mouse Mip gene maps within or near to a segment homoeologous with human chromosome 12q and may be linked to the Cat locus at the distal end of mouse Chromosome 10.
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PMID:Localisation of the gene for the major intrinsic protein of eye-lens-fibre cell membranes to mouse chromosome 10 by in situ hybridisation. 154 29

In order to examine the central mechanism of pyrexic action of macrophage inflammatory protein-1 (MIP-1), guide cannulae for injections were implanted stereotaxically just above the anterior hypothalamic, pre-optic area of the rat. Following post-operative recovery, the body temperature (Tb) of each rat was monitored by a colonic thermistor probe over a test interval of 4 hr. Injected in a 0.5 microliter volume into the anterior hypothalamic pre-optic area, MIP-1, in a dose of 5.6 or 28 pg, evoked an intense fever with a latency of 15-30 min. Pretreatment of the anterior hypothalamic pre-optic area with 1.0 microgram cyclosporine A (CsA), delivered in a volume of 0.5 microliter, delayed the onset of the fever induced by 5.6 pg MIP-1, injected at the same site. Similar injections of CsA also attenuated significantly the magnitude of the fever, following either the 5.6 or 28 pg dose of MIP-1. As a systemic control, 15 mg/kg CsA was administered intraperitoneally, 2.0 hr before the injection of MIP-1 in the anterior hypothalamic pre-optic area. By this route, CsA also delayed the rise in temperature but the fever induced by 5.6 pg MIP-1 reached the same magnitude as that after MIP-1 alone. Conversely, intraperitoneal administration of CsA did not antagonize the pyrexic response evoked by 28 pg MIP-1, injected into the anterior hypothalamic pre-optic area, but rather enhanced the fever.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Action of cyclosporine on fever induced in rats by intrahypothalamic injection of macrophage inflammatory protein-1 (MIP-1). 155 29

We have shown previously that cleavage of a number of precursors by the mitochondrial processing peptidase (MPP) requires an intermediate octapeptide (FXXSXXXX) between the MPP cleavage site and the mature protein amino terminus. We show now that these octapeptides, present at the amino termini of the intermediates, direct recognition of these substrates by the mitochondrial intermediate peptidase (MIP), leading to formation of mature proteins. Synthetic peptides, corresponding to the intermediate octapeptides of human ornithine transcarbamylase (OTC) and of Neurospora cytochrome c reductase Fe/S subunit (Fe/S), inhibit the processing activity of purified rat liver MIP in vitro, without affecting MPP activity; this indicates that the octapeptides can be recognized by MIP independent of the presence of the corresponding mature proteins and interact with a site that is crucial for MIP activity. MIP activity is not inhibited by a peptide lacking the amino-terminal hydrophobic residue, while substitution of such a residue by a polar amino acid causes a 10-fold reduction in the efficiency of MIP inhibition. To analyze the requirements for removal of the octapeptide from the intermediate proteins by MIP, artificial intermediates were synthesized and subjected to in vitro processing by purified MIP. The octapeptide can be cleaved by MIP only when the amino-terminal hydrophobic residue is also the amino terminus of the intermediate. Further, when the OTC octapeptide is joined to the mature amino terminus of another twice-cleaved precursor (pFe/S; rat malate dehydrogenase, pMDH), the chimeric intermediate is cleaved by MIP to the corresponding mature-sized protein. When the OTC octapeptide is joined to the mature amino terminus of a once-cleaved precursor (yeast F1-beta-ATPase, pF1-beta), however, this intermediate is not cleaved by MIP; rather, it is processed by MPP to mature-sized F1-beta. Therefore, amino-terminal octapeptides can be cleaved by MIP only within the structural context of twice-cleaved precursors.
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PMID:Amino-terminal octapeptides function as recognition signals for the mitochondrial intermediate peptidase. 156 19

Phrenic nerve and diaphragmatic dysfunction has been assumed to be the cause of respiratory failure in hereditary motor and sensory neuropathy, type 1 (HMSN I). In order to determine the relationship between phrenic nerve and pulmonary function in this disease, 25 patients underwent a 4-step evaluation process consisting of: (1) bilateral phrenic nerve conduction study; (2) median, peroneal, and tibial motor conduction studies; (3) measurement of forced vital capacity (FVC) and maximal inspiratory and expiratory pressures (MIP, MEP); and (4) pulmonary-focused history and physical. Phrenic nerve motor latency was abnormally prolonged in 22 of the 23 (96%) subjects when a response was obtained. All had slowed velocity or absent peripheral motor conduction responses. Vital capacity was abnormally reduced in 6 of the 25 (24%) subjects. Eight (32%) had an abnormally reduced MIP, while 19 (76%) had an abnormally reduced MEP. Only 2 (8%) subjects had clinical evidence of pulmonary dysfunction. None of the dependent variables (FVC, MIP, MEP, peripheral nerve conduction, or clinical examination) correlated with phrenic nerve latencies. Although phrenic nerve latencies are markedly prolonged in HMSN I, these values are not useful in predicting respiratory dysfunction.
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PMID:Evaluation of phrenic nerve and pulmonary function in hereditary motor and sensory neuropathy, type I. 156 14

The proliferative status of the stem cell compartment is thought to be controlled by both positive and negative regulators of proliferation. These regulators have obvious clinical potential in manipulating the integrity and proliferative status of the stem cell in vivo during patient treatment for neoplastic disease. We have tested the ability of the human recombinant homologue of murine macrophage inflammatory protein-1 alpha (rhMIP1 alpha) to suppress the proliferation of primitive murine progenitors in vitro and in vivo. This recombinant protein (stem cell inhibitor, similar to the human homologue of MIP 1 alpha, LD78) is active in a dose-dependent manner in vitro on CFU-S measured at day 12 and to a slightly lesser extent on the more mature CFU-S that are measured at day 8. SCI/rhMIP1 alpha is also active in vivo in two separate models of bone marrow regeneration in which the high proliferative status of the CFU-S compartment is reduced to the quiescent state with a single inoculation of SCI/rhMIP1 alpha. The inhibitory activity of the recombinant protein was then tested in a relevant therapeutic model in which the observed protection of part of the stem cell compartment is reflected by a significant improvement in the kinetics of neutrophil recovery. These results establish the feasibility of testing SCI/rhMIP1 alpha in a range of chemotherapy regimes as a preliminary to clinical trials to attempt to protect the stem cell compartment during treatment for neoplastic disease.
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PMID:Demonstration of stem cell inhibition and myeloprotective effects of SCI/rhMIP1 alpha in vivo. 157 37

Two groups of cerebral dorsal cells of the pulmonate snail Planorbarius corneus stain positively with antisera raised against synthetic fragments of the B- and C-chain of the molluscan pro-insulin-related prohormone, proMIP-I, of another pulmonate snail, Lymnaea stagnalis. At the light-microscopic level the somata of the dorsal cells and their axons and neurohemal axon terminals in the periphery of the paired median lip nerves are immunoreactive with both antisera. Furthermore, the canopy cells in the lateral lobes of the cerebral ganglia are positive. In addition, MIPB-immunoreactive neurons are found in most other ganglia of the central nervous system. At the ultrastructural level, pale and dark secretory granules are found in somata and axon terminals of the dorsal cells. Dark granules are about 4 times as immunoreactive to both antisera as pale granules. Release of anti-MIPB- and anti-MIPC-immunopositive contents of the secretory granules by exocytosis is apparent in material treated according to the tannic acid method. It is concluded that the dorsal and canopy cells synthesize a molluscan insulin-related peptide that is packed in the cell body into secretory granules and that is subsequently transported to the neurohemal axon terminals and released into the hemolymph by exocytosis. Thus, MIP seems to act as a neurhormone on peripheral targets. On the basis of the analogy between the dorsal cells and the MIP-producing cells in L. stagnalis, it is proposed that the dorsal cells of P. corneus are involved in the control of body growth and associated processes.
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PMID:Light- and electron-microscopic immunocytochemistry of a molluscan insulin-related peptide in the central nervous system of Planorbarius corneus. 157 61

Macrophage inflammatory protein 1 (MIP 1), initially purified from the conditioned medium of endotoxin-stimulated macrophages, is a low m.w. heparin-binding protein doublet comprising two peptides, MIP 1 alpha and MIP 1 beta. Although native doublet MIP 1 has previously been shown to exert pyrogenic, mitogenic, and proinflammatory effects on other cell types, its actions on its cell of origin, the macrophage, have not been well catalogued. Our study reports several aspects of macrophage function that are modulated by MIP 1. MIP 1 was not directly cytotoxic for WEHI tumor cells, but MIP 1-treated macrophage exhibited enhanced antibody-independent macrophage cytotoxicity for tumor targets. MIP 1 treatment stimulated proliferation of mature tissue macrophages, and this effect was enhanced upon costimulations with either CSF-1 or granulocyte-macrophage-CSF. Thioglycollate-elicited peritoneal exudate macrophages incubated with native doublet MIP 1-secreted bioactive TNF and IL-6, as well as immunoreactive IL-1 alpha, and these effects were enhanced significantly when the cells were costimulated with IFN-gamma. Purified preparations of the recombinantly derived MIP 1 alpha peptide alone stimulated the secretion of TNF, IL-1 alpha, and IL-6 by peritoneal macrophages, but MIP 1 beta did not. In fact, as little as eightfold excess MIP 1 beta blocked TNF-induction by MIP 1 alpha to a significant degree. By contrast to these apparent "macrophage activating" properties of MIP 1, the cytokine failed to trigger the macrophage oxidative burst, or to up-regulate the expression of Ia on the macrophage surface. Taken together, these data reveal that MIP 1 peptides act as autocrine modulators of their cells of origin, and raise the possibility that MIP 1 peptides may play a role in modulating macrophage responses to inflammatory stimuli in vivo.
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PMID:Macrophage inflammatory protein 1 modulates macrophage function. 157 67

To evaluate the frequency of the causes of exercise limitation in patients with chronic pulmonary disease and to assess the relationship between the resting pulmonary functional parameters and the degree of exercise dyspnea, we reviewed the data from 88 consecutive stable patients with chronic lung disease (62 COPD, 16 interstitial lung disease [ILD]). In each patient, the intensity of dyspnea was measured by a Borg scale (BS) during an incremental symptom-limited exercise test. COPD patients stopped exercise due to fatigue (46%), dyspnea (36%), cardiac limitation (12%), and peripheral circulatory limitation (6%). ILD patients stopped exercise due to dyspnea (62%), fatigue (25%), and cardiac limitation (12%). In all patients, dyspnea severity increased linearly with exercise intensity as measured as VO2, VE, and VE/MVV. The severity of dyspnea expressed as the slope of the relationship between BS and VE/MVV (DBS/D[VE/MVV]) showed in COPD a significant inverse correlation with VC, FEV1, MIP, and a positive correlation with PaCO2 and VE/MVV at rest. In ILD, DBS/D(VE/MVV) showed a significant inverse correlation with VC, FEV1, TLC, and PaO2 and a positive correlation with VE/MVV at rest. The predicting power of all equations was very low.
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PMID:Dyspnea on exercise. Pathophysiologic mechanisms. 157 44


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