Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent data suggest that the increase in ventilation during hypoxia may be related to the release of the excitatory amino acid neurotransmitter glutamate centrally. To further investigate this, we studied the effects of MK-801, a selective noncompetitive N-methyl-D-aspartate receptor antagonist, on the hypoxic ventilatory response in lightly anesthetized spontaneously breathing intact dogs. The cardiopulmonary effects of sequential ventriculocisternal perfusion (VCP) at the rate of 1 ml/min with mock cerebrospinal fluid (CSF, control) and MK-801 (2 mM) were compared during normoxia and 8 min of hypoxic challenge with 12% O2. Minute ventilation (VE), tidal volume (VT), and respiratory frequency (f) were recorded continuously, and hemodynamic parameters [heart rate (HR), blood pressure (MAP), cardiac output (CO), pulmonary arterial pressure, and pulmonary capillary wedge pressure] were measured periodically. Each dog served as its own baseline control before and after each period of sequential VCP under the two different O2 conditions. During 15 min of normoxia, there were no significant changes in the cardiopulmonary parameters with mock CSF VCP, whereas with MK-801 VCP for 15 min, VE decreased by approximately 27%, both by reductions in VT and f (17 and 9.5%, respectively). HR, MAP, and CO were unchanged. During 8 min of hypoxia with mock CSF VCP, VE increased by 171% associated with increased VT and f (25 and 125%, respectively). HR, MAP, and CO were likewise augmented. In contrast, the hypoxic response during MK-801 VCP was characterized by an increased VE of 84%, mainly by a rise in f by 83%, whereas the VT response was abolished. The cardiovascular excitation was also inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of glutamate as the central neurotransmitter in the hypoxic ventilatory response. 135 May 80

Stimulation of hemopoietic cells with IL-3, IL-4, IL-5, granulocyte-macrophage-CSF and Steel factor-(SLF) induced tyrosine phosphorylation of a number of protein substrates. Two of these proteins, designated p42 and p44, were tyrosine phosphorylated rapidly in response to treatment with IL-3, IL-5, granulocyte-macrophage-CSF and SLF, but not IL-4. We demonstrate that these common substrates are members of the mitogen-activated protein kinase (MAP kinase) family of protein serine/threonine kinases. Ion-exchange chromatography yielded a peak of MAP kinase activity eluting at 0.3 to 0.32 M NaCl. Immunoblotting of column fractions with antiphosphotyrosine antibodies showed coelution of the peak of MAP kinase enzyme activity with the p42 and p44 tyrosine phosphorylated species, and with two proteins of 42 and 44 kDa which were immunoreactive with anti-MAP kinase antibodies. Moreover, a characteristic shift in mobility of the p42 and p44 species was observed after factor treatment. Time-course analyses and subsequent ion-exchange chromatography demonstrated SLF activation of MAP kinase activity was maximal after 2 min of factor treatment and decreased to basal levels after 30 min stimulation. By contrast, activation of MAP kinase after IL-5 treatment was not as rapid. Maximal activity was observed 15 min after stimulation and remained elevated for up to 60 min after IL-5 addition. Investigation of the role of protein kinase C in the mechanism of activation by these growth factors demonstrated that specific inhibition of protein kinase C led to a reduction, but not ablation, of the SLF and IL-3 induced stimulation of MAP kinase activity. The use of synthetic peptide substrates confirmed SLF and IL-5 activate isoforms of MAP kinases. These results demonstrate that members of the MAP kinase family are involved in common signal transduction events elicited by IL-3, IL-5, granulocyte-macrophage-CSF and Steel factor, but not those involving IL-4.
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PMID:Multiple hemopoietic growth factors stimulate activation of mitogen-activated protein kinase family members. 138 May 36

ICP control can be achieved removing the surgical masses and manipulating the intracranial compartments; in the intensive care setting that can be attempted using CSF withdrawal or changing the cerebrovascular resistances, the intracranial blood content and the cerebral water content. The reduction of the ICP and the maintenance of a good cerebral perfusion pressure are the main aims of the therapy; when any standard treatment fails to control ICP a further attempt to preserve cerebral perfusion should be done by increasing the mean arterial pressure. In 10 patients with severe brain damage (GCS on admission ranging from 3 to 7, mean 5) from subarachnoid hemorrhage (3 cases) or trauma an infusion of dopamine (25-150 mg/h) and noradrenaline (0.4-2.4 mg/h) was started in case of intractable ICP. The ICP was defined intractable when the pressure was more than 40 mmHg for more than 5 m' after maximum therapy, as evaluated using the Therapy Intensity Level score. The infusion obtained a raise of the MAP of approximately 25% and a variable response on ICP. In 9 cases ICP dropped, in one case, instead, the ICP increased together with the arterial pressure. The reduction of ICP was 20-30%, with a good improvement of the CPP. The patients with a good response survived, the only patient without control of the ICP died. The physiopathologic mechanisms of this treatment are discussed; the most suitable explanation is indicated in an autoregulatory process. The infusion of cathecolamines can be harmful, and the patients eligible for this treatment must be carefully chosen. Notwithstanding this approach deserves further studies for the cases of intractable ICP.
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PMID:[Increasing the pressure of cerebral perfusion to control intracranial pressure]. 162 Apr 43

Little is known about what influences cerebrospinal fluid pressure (CSFP) during anesthesia prior to aortic cross-clamping (AXC). Therefore, this study measured the effect of anesthetic induction, of various drugs administered during the course of surgery prior to AXC, and of hemodynamic changes on CSFP, and calculated spinal cord perfusion pressure (SCPP = mean arterial pressure [MAP] - CSFP) in 11 patients undergoing surgery on the descending thoracic aorta. A lumbar drainage catheter was placed to facilitate drainage of CSF and to measure CSFP. Anesthesia was induced with fentanyl, 50 micrograms/kg, and midazolam, 1 mg, using a pancuronium-metocurine mixture for neuromuscular blockade. Data were collected prior to and after (1) anesthetic induction, (2) mannitol to augment diuresis, (3) sequential use of sodium nitroprusside (SNP) and isoflurane (ISO) to lower MAP by 20%, (4) drainage of spinal fluid, (5) intrathecal injection of papaverine (IP), and (6) AXC. Statistical comparisons of recorded data were made using the least squares mean method and Friedman test. Linear regression was used to test for correlation between CSFP and hemodynamics. Anesthetic induction affected neither hemodynamics nor CSFP. Mannitol significantly increased heart rate, central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and CSFP (P less than 0.05). SNP or ISO altered neither CVP, PCWP, CO, nor CSFP, which remained elevated at the postmannitol infusion level. ISO, unlike SNP, caused a significant decrease in SCPP (P less than 0.005). Subsequent drainage of 20 mL of CSF improved SCPP (P less than 0.05). IP did not have any effect on hemodynamics or CSFP. CSFP showed a strong correlation with CVP (r = 0.86).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in cerebrospinal fluid pressure and spinal cord perfusion pressure prior to cross-clamping of the thoracic aorta in humans. 190 39

Central nervous system (CNS)-induced natriuresis was investigated in nonascitic rats with CCl4-induced cirrhosis (CTC rats) under pentobarbital anesthesia. At baseline, urine sodium output (UNa+V, in mumol.min-1.100 g body wt-1) (-30%, P less than 0.01) and mean arterial pressure (MAP, in mmHg) (-12%, P less than 0.001) were significantly reduced in CTC rats (n = 32) compared with matched controls (n = 34). In response to intracerebroventricular infusion of sodium-rich (349 mM) artificial cerebrospinal fluid (Na(+)-CSF infusion), UNa+V was significantly higher in CTC rats (2.8 +/- 0.3; n = 15) than in controls (1.7 +/- 0.2; n = 17; P less than 0.01); no differences were found in pressor changes (24 +/- 3 vs. 19 +/- 2). A similar but normal sodium CSF (150 mM) infusion did not influence UNa+V or MAP in any group (n = 12, both). In contrast, CTC rats (n = 5) showed, compared with controls (n = 5), significantly reduced natriuretic (UNa+V, 6.9 +/- 0.5 vs. 12.4 +/- 0.9; P less than 0.001) and pressor (+16 +/- 3 vs. +31 +/- 2; P less than 0.01) responses to an intravenous hypertonic sodium overload. Natriuresis induced by Na(+)-CSF infusion was related to increases in creatinine clearance (similar in both groups) and in fractional sodium excretion, which was significantly higher in CTC rats (5.90 +/- 0.15%) than in controls (3.65 +/- 0.14%; P less than 0.01). In summary, CNS-dependent efferent natriuretic mechanisms were preserved in CTC rats and were able to reverse renal tubular sodium retention in these animals. It is proposed that Na(+)-CSF infusion may be a useful tool for the study of renal sodium retention in experimental liver cirrhosis.
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PMID:Enhanced responsiveness to CNS-induced natriuresis in anesthetized nonascitic cirrhotic rats. 205 81

The courses of the hemodynamic and cardiometabolic effects of naloxone were evaluated in propoxyphene-induced shock in eight pentobarbital-anesthetized pigs. Circulatory shock was induced by an infusion of propoxyphene chloride 15 mg . min-1 i.v. At shock, i.e. MAP less than 60 mmHg and/or CI less than 2.0 l . min-1 . m-2, naloxone was administered at 0.75, 1.5 and 3.0 mg . kg-1 with an interval between increments of 8 min. The propoxyphene infusion of 15 mg . min-1 was continued throughout the study. Following the injection of naloxone 0.75 mg . kg-1, increases were observed (% of baseline value) in MAP (41%), i.e. deficit to baseline 59%, HR (66%), CI (67%) and SVI (108%), whereas MPAP and MPAOP were unchanged. dP/dt increased (34%). In the coronary circulation naloxone initiated the following changes: CSF increased (69%) as did MVO2 (48%) with unchanged MO2-extraction, but CVR decreased further (36%). The maximum effects of naloxone were registered 2-3 min after 0.75 mg . kg-1. Following 1.5 and 3.0 mg . kg-1, no changes in hemodynamics were observed other than those caused by progressing propoxyphene intoxication.
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PMID:The effects of naloxone on central hemodynamics and myocardial metabolism in experimental propoxyphene-induced circulatory shock. 300 Jan 25

Graded injections of argipressin (Arg, 150, 300, and 600 ng/1.5 microliters CSF, 2 min) into the medial amygdaloid body in anesthetized rats produced a dose-related increase in the mean arterial pressure and heart rate (Maximal delta MAP = 2.9 +/- 1.5 kPa, Maximal delta HR = 67 +/- 38 bpm), which lasting > 40 min at 600 ng dosage. Naloxone (15 micrograms/15 microliters CSF) injected into the lateral ventricle blocked the cardiovascular responses to Arg. These results suggest that Arg exerts a central action on the cardiovascular system via the opioid in the lateral ventricle.
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PMID:Effects of argipressin injected into medial amygdaloid body on blood pressure and heart rate in rats. 835 1

Cytosolic phospholipase A(2) (cPLA(2)) plays a critical role in various neutrophil functions including the generation of leukotrienes and platelet-activating factor release. Enzyme activity is regulated both by translocation to the membrane in a Ca(2+)-dependent manner and serine phosphorylation by members of the mitogen-activated protein kinase (MAPK) family. In this report, we have investigated the role of granulocyte/macrophage colony-stimulating factor (GM-CSF)-mediated signalling pathways in the regulation of cPLA(2). GM-CSF-induced cPLA(2) phosphorylation was not affected by pharmacological inhibition of p38 MAPK, phosphatidylinositol 3-kinase or Src. However, inhibition of extracellular signal-regulated kinase (ERK) MAPK activation resulted in a partial inhibition of cPLA(2) phosphorylation, revealed in a slower onset of phosphorylation. A cell line stably transfected with the GM-CSF receptor was used to further analyze GM-CSF-mediated cPLA(2) phosphorylation. Mutation of tyrosine residues 577 and 612 resulted in a delayed cPLA(2) phosphorylation similar to the pharmacological ERK inhibition. Furthermore, inhibition of p38 MAPK in cells bearing the double mutant betac577/612 completely abrogated GM-CSF-induced cPLA(2) phosphorylation. We conclude that GM-CSF can mediate cPLA(2) phosphorylation through the redundant activation of both p38 and ERK MAP kinases.
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PMID:Cytokine-mediated cPLA(2) phosphorylation is regulated by multiple MAPK family members. 1076 May 18

Our previous studies demonstrated that CEL-I, an N-acetylgalactosamine (GalNAc)-specific C-type lectin purified from the marine invertebrate Cucumaria echinata (Holothuroidea) showed potent cytotoxicity to several cell lines such as HeLa, MDCK and XC cells. In this study, we found that CEL-I induced increased secretion of tumour necrosis factor-alpha (TNF-alpha) and granulocyte colony stimulation factor (G-CSF) by mouse macrophage cell line RAW264.7 cells in a dose-dependent manner, whereas this cell line was highly resistant to CEL-I cytotoxicity. The cytokine-inducing activity of CEL-I was stronger than that of phytohaemagglutinin (PHA-L). A binding study using FITC-labelled CEL-I (F-CEL-I) indicated that the amount of bound F-CEL-I on RAW264.7 cells was greater than that of F-PHA-L, suggesting that the greater activity of CEL-I to induce cytokine secretion by RAW264.7 cells is partly due to the higher binding ability. Since the cell binding and cytokine-inducing activity of CEL-I were partly but significantly inhibited by the specific sugar (GalNAc), it is considered that the binding of CEL-I to cell-surface-specific saccharide moieties, which may be recognized by CEL-I with higher affinity than GalNAc, is essential for the induction of cytokine secretion. The secretion of TNF-alpha and G-CSF from CEL-I-treated RAW264.7 cells were almost completely prevented by brefeldin A (BFA), whereas increase in mRNA levels of these cytokines were not affected by BFA. Bio-Plex beads assay suggested that temporal increase in phosphorylation of extracellular-regulated kinase (ERK), c-jun NH(2)-terminal kinase (JNK) and p38 MAP kinase occurred at relatively early time following CEL-I treatment. Furthermore, the secretion of TNF-alpha and G-CSF were inhibited by specific inhibitors for these MAP kinases. These results suggest that the intracellular signal transduction through the activation of MAP kinase system is involved in CEL-I-induced cytokine secretion.
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PMID:CEL-I, an invertebrate N-acetylgalactosamine-specific C-type lectin, induces TNF-alpha and G-CSF production by mouse macrophage cell line RAW264.7 cells. 1784 63

Macrophage colony-stimulating factor (M-CSF) stimulation results in the production of reactive oxygen species (ROS) that participate in the proliferation of monocyte/macrophage. However, the molecular mechanisms whereby ROS modulate the signaling processes of M-CSF remain poorly defined. We report here that the redox-sensitive Src homology region 2 domain-containing phosphatase 1 (SHP1) is a critical regulator of M-CSF-mediated signaling in bone marrow monocyte/macrophage lineage cells (BMMs). Application of diphenylene iodonium (DPI) inhibited the responses of BMMs to M-CSF, including ROS production, cell proliferation, and phosphorylation of c-Fms as well as Akt kinase, but not of MAP kinases such as ERK, p38, and JNK. Dysregulation of SHP1 by overexpression or RNA interference in BMMs showed that SHP1 specifically regulates PI3 kinase (PI3K)/Akt signaling, but not MAP kinases in a redox-dependent manner, thereby regulating proliferation of BMMs through cyclins D1 and D2. These findings demonstrate that M-CSF-mediated ROS generation leads to SHP1 oxidation, which promotes cell proliferation through the PI3K/Akt-dependent signaling pathway.
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PMID:Reactive oxygen species regulate M-CSF-induced monocyte/macrophage proliferation through SHP1 oxidation. 2166 61


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