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)

Cyclosporine (CyA) therapy has been shown to be effective in some patients with aplastic anemia. In an attempt to characterize aplastic patients likely to benefit from CyA therapy, we examined bone marrow mononuclear cells (BMMC) obtained before therapy from 23 patients with aplastic anemia, who were treated with CyA alone. Expression of four myelosuppressive cytokines, including tumor necrosis factor (TNF), lymphotoxin, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and interferon-gamma (IFN-gamma) was examined using polymerase chain reaction (PCR)-assisted messenger RNA (mRNA) amplification. mRNA for TNF, lymphotoxin, and MIP-1 alpha was readily detectable at variable levels in BMMC from normal and transfused controls as well as in BMMC from aplastic patients. In contrast, IFN-gamma mRNA was only demonstrable in BMMC from some patients with aplastic anemia, irrespective of a history of transfusions. Of 13 patients who responded to CyA therapy and achieved transfusion-independence, IFN-gamma mRNA was detected in 12 patients, whereas the mRNA was only detectable in 3 of 10 patients refractory to CyA therapy (P = .003, Fisher's exact test). Follow-up examination of BMMC obtained from seven CyA-responding patients after hematologic remission showed disappearance of IFN-gamma mRNA in four patients. These results suggest that detection of IFN-gamma gene expression in pretreatment BMMC from aplastic patients using PCR may be helpful in predicting a good response to CyA therapy.
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PMID:Interferon-gamma gene expression in unstimulated bone marrow mononuclear cells predicts a good response to cyclosporine therapy in aplastic anemia. 158 5

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) has been assessed for its potential in vivo to protect hematopoietic progenitor cells from the cytotoxic effects of a cycle-specific drug--in this case hydroxyurea (HU). Two doses of HU, 7 hours apart, were administered to mice to induce spleen colony-forming unit (CFU-S) cycling and then to kill them during DNA-synthesis. MIP-1 alpha, in a variety of dose and time combinations, was injected before the second dose of HU in an attempt to prevent recruitment or maintain CFU-S quiescence, and thus protect them from the second dose of HU. Without MIP-1 alpha, recovery of the CFU-S population was complete in 7 days. In a dose-dependent manner, MIP-1 alpha either reduced the initial kill and accelerated recovery, or completely protected the CFU-S population. We conclude that MIP-1 alpha does protect multipotent progenitor cells in vivo and that these observations provide a base from which to build practical clinical applications.
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PMID:Macrophage-inflammatory protein protects multipotent hematopoietic cells from the cytotoxic effects of hydroxyurea in vivo. 158 12

The hemopoietic system represents a complex adult developmental system which allows the study of mechanisms of stem cell proliferative control and differentiation commitment. It is likely that information obtained from this model system will have implications for control processes regulating other hierarchical systems in the developing embryo as well as in the adult animal. We have recently identified and isolated a potent inhibitor of hemopoietic stem cell proliferation which we have labeled SCI/MIP-1 alpha. This inhibitor is also active on clonogenic epidermal cells and may thus be a more general stem cell inhibitor than was previously believed. The biology of this peptide is outlined in more detail below and the potential roles for such a factor in the developing embryo are also discussed.
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PMID:SCI/MIP-1 alpha: a potent stem cell inhibitor with potential roles in development. 160 Nov 73

Post-polio patients sometimes complain about the occurrence of breathing difficulties decades after the polio infection. We have examined 40 post-polio patients who have had respiratory or non-respiratory poliomyelitis for at least 30 years in an attempt to elucidate whether hypoventilation is common and to what extent certain symptoms and simple lung function tests are related to hypoventilation or incipient hypoventilation. We measured arterial blood gases, vital capacity (VC), maximal expiratory and inspiratory pressures (MEP, MIP) and CO2 rebreathing response. Symptoms were assessed by a yes/no questionnaire. Six patients required respiratory assistance at the onset of the disease. At present, two require nocturnal assisted ventilation. Two patients showed manifest hypoventilation; one of which required night-time ventilator, whereas the other patient had not required ventilatory assistance even at the onset of the disease. Significant correlation (p less than 0.05) was found between arterial carbon dioxide tension (a-PCO2) and VC, MEP and ventilation increase during CO2 rebreathing. A significantly higher a-PCO2 was found among those who required respiratory assistance at the onset of the disease, who admitted headache and who felt the cough ineffective. Low VC and low ventilatory increase during CO2 rebreathing and the presence of headache explained 45% of the variation in a-PCO2 in a multiple regression analysis. We conclude that manifest hypoventilation is rare in this unselected material of post-polio patients and that a vital capacity below 45-50% of predicted normal and the presence of frequent headaches indicate an increased risk to develop hypoventilation.
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PMID:Post-polio lung function. 160 61

The murine macrophage inflammatory proteins-1 alpha (MIP-1 alpha) and MIP-1 beta are distinct but closely related cytokines. Partially purified mixtures of the two proteins affect neutrophil function and cause local inflammation and fever. The particular properties of MIP-1 alpha have not been well studied, although it has been identified as being identical to an inhibitor of haemopoietic stem cell growth. We have expressed MIP-1 alpha in yeast cells and purified it to sequence homogeneity. Structural analysis of this biologically active material by circular dichroism and fluorescence spectroscopy confirms that MIP-1 alpha has a very similar secondary and tertiary structure to platelet factor 4 and interleukin 8 with which it shares limited sequence homology. The in-vitro stem cell inhibitory properties have been confirmed using a range of murine progenitor cells including purified bone marrow progenitor cells (FACS-1), the FDCP-mix A4 cell line, and spleen colony forming unit (CFU-S) populations. Plateau levels of inhibition of stem cell growth were achieved using concentrations of 0.15 micrograms/ml MIP-1 alpha. We have also demonstrated that MIP-1 alpha is active in vivo: 5 micrograms of MIP-1 alpha per mouse given as a bolus injection, protects stem cells from subsequent in-vitro killing by tritiated thymidine. MIP-1 alpha was also shown to enhance the proliferation of more committed progenitor granulocyte macrophage-colony forming cells (GM-CFC) in response to granulocyte macrophage-colony stimulating factor (GM-CSF).
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PMID:Biological and structural properties of MIP-1 alpha expressed in yeast. 161 59

A total of 22 MR venograms were performed in 7 volunteers and 15 patients suspected of deep vein thrombosis of the lower limb and pelvis. MR findings were compared to conventional venography in all patients. MR venography is a reliable method for the exclusion of thrombosis proximal to the popliteal vein. In the calf veins, diagnosis of thrombosis is not yet reliable. For MR venography 2D-time-of-flight-inflow-technique and secondary 3D-MIP reconstructions were used and compared to each other. With both methods there were no false negative results in comparison to conventional venography. 2D single slice MR venography showed two false positive results in iliac and one in popliteal vein. MIP 3D reconstructions led to seven false positive results (three iliac, two femoral, two popliteal). The exclusive interpretation of MIP-3D reconstruction is not reliable for decision-making in deep venous thrombosis.
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PMID:[MR venography in deep venous thromboses of the leg and pelvis. A comparison of 2D single layer images and 3D MIP reconstructions with phlebography]. 161 74

Soybean nodulin-26, a homologue of bovine eye lens major intrinsic protein (MIP-26), is an integral protein of the peribacteroid membrane in symbiotic root nodules. It comprises 271 amino acids with six potential transmembrane domains and lacks an amino-terminal signal sequence. A full-length nodulin-26 cDNA and its various deletion derivatives were transcribed in vitro after linking them to bacteriophage T3 promoter. In vitro translation of these transcripts in a rabbit reticulocyte lysate, in the presence or absence of canine pancreatic microsomal membranes, suggested that nodulin-26 is cotranslationally inserted into the microsomes without a cleavable signal peptide. The first two transmembrane domains (103 amino acids) of the protein are sufficient for microsomal membrane insertion. Membrane-translocated nodulin-26 binds to Con-A and is sensitive to endoglycosidase-H treatment, suggesting that it is glycosylated. Native nodulin-26 from root nodules retains its sugar moiety as it, too, binds to Con-A. Chemical cleavage mapping at cysteine residues, a trypsin protection assay, and the Con-A binding affinity of nodulin-26 suggested that both the NH2 and COOH termini of this protein are on the cytoplasmic surface of the peribacteroid membrane, while the glycosidic residue is on the surface of the membrane facing the bacteroids. In vitro phosphorylation experiments showed that nodulin-26 is a major phosphorylated protein in the peribacteroid membrane. This phosphorylation is mediated by a Ca(2+)-dependent, calmodulin-independent protein kinase located in the peribacteriod membrane. Externally supplied acid phosphatase dephosphorylates this protein, but alkaline phosphatase does not. Based on its homology with several eukaryotic and prokaryotic channel-type membrane proteins, nodulin-26 may form a channel translocating specific molecules to the bacteroids during endosymbiosis in legume plants.
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PMID:Topology and phosphorylation of soybean nodulin-26, an intrinsic protein of the peribacteroid membrane. 162 42

MR angiography (MRA) proved to be promising combined to MR imaging (MRI) in the assessment of intrathoracic masses. Sequential FLASH 2D angiograms were acquired in breath-hold technique using the following parameters: TR = 30 ms, TE = 10 ms, FA = 30 degrees. Section thickness was 5 mm with 1 mm overlap between sequential sections. Individual conditions of the examination were achieved by an automatized control procedure. Targeted MIP postprocessing resulted in 3D reconstructions illustrating vascular anatomy and avoiding superimposition. Presentation should be done by cine-mode for better spatial impression. This method was evaluated in a prospective study of 21 patients with malignant pulmonary and mediastinal masses in addition to spin-echo imaging. The diagnostic contribution concerning the relationship between the mass and the vasculature like displacement, stenosis, and poststenotic perfusion defect were assessed.
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PMID:[MR angiography. Its use in pulmonary and mediastinal space-occupying lesions]. 163 98

This study was carried out to evaluate time-of-flight RA in renal artery stenosis (RAS) in selected hypertensive patients (n = 41). In i.a. DSA studies, 10 unilateral, 8 bilateral RAS, and 4 unilateral RA occlusions were proven. MRA was done in coronal and axial 2D technique (FLASH), and in 3D technique (FISP) using GE-pulse sequences. DSA results were correlated with both 2D-individual slices, 2D- and 3D-MIP angiograms. Highest sensitivity and specificity was found for the axial 2D individual slice analysis (88%, 85% resp.), followed by the 3D-MIP MRA (78%, 80% resp.), and axial 2D-MIP MRA (73%, 79% resp.). MRA of renal arteries used in this study shows to be not adequate to DSA results due to many drawbacks. All MRA techniques, in particular the 3D-technique, tend to overestimate RAS occasionally pretending occlusions.
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PMID:[The evaluation of 2D- and 3D-"time of flight" magnetic resonance angiography (MRA) in the diagnosis of renal artery stenoses]. 163 7

In mycobacterial infections of mice there is a chronic, immune-mediated mobilization of neutrophils to the infectious site. In this study we evaluated the role played by cytokines in the chronic peritoneal neutrophilia which occurs in mice intraperitoneally infected with Mycobacterium bovis BCG or M. avium. Antibodies to IFN-gamma and to MIP-1 and -2 were effective in reducing peritoneal neutrophilia when given during the infection. Whereas the former antibody was only effective when given early, the latter two were effective when administered late in infection, suggesting the MIPs were direct mediators of neutrophil recruitment. Recombinant IFN-gamma given intraperitoneally induced the accumulation of neutrophils and primed the peritoneal cells for an enhanced recruitment of neutrophils. Our data show that chronic neutrophilia during mycobacterial infection is regulated by different cytokines acting at different stages and levels of neutrophil recruitment.
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PMID:Interferon-gamma (IFN-gamma) and macrophage inflammatory proteins (MIP)-1 and -2 are involved in the regulation of the T cell-dependent chronic peritoneal neutrophilia of mice infected with mycobacteria. 163 71


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