EC:3.4.11.18 - FACTA Search

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)

We have reevaluated and clinically tested the current concepts of shock and resuscitation on a logical, physiological, and physical basis. We have considered the currently accepted resuscitation paradigm which is based upon the thesis that early rapid resuscitation of "lost" fluid volume is mandatory and that adequacy of resuscitation can be evaluated by central venous pressure, PAP, PAWP, pulse rate, blood pressure, and/or urine volume. Such methods also accept as natural concomitants that capillary beds are "damaged by injury"; that they "leak" salt, fluid, and albumin; and that these are expected occurrences which are injury-related. We have also examined and clinically evaluated the thesis that MAP is a primary reflector of the relationships between volume and the size of the currently available functional vascular space. (Currently available functional vascular space is mediated through the baroreceptor (stretch receptor)/neuroendocrine mechanisms.) Under this hypothesis, fluid resuscitation comprises infusion of a volume per unit time given so as to replete currently measurable fluid losses and to normalize and/or sustain MAP and the normal osmolar and oncotic relationships at the capillary/tissue interface while holding hydrostatic pressure at normal. Using burn injury as a model, we compared statistically homogeneous, randomly selected groups of burn patients who were resuscitated using a hypotonic fluid (130 mOsm/liter) alone (group R: 7 patients), hypertonic fluid (240 mOsm/liter) alone group H: 5 patients), or the hypertonic fluid containing albumin (12.5 g/liter) (group A: 7 patients). The results indicate that significantly smaller volumes of fluid were needed to resuscitate the patients in group A with a significantly more rapid normalization of physical, physiological, and biochemical parameters. We conclude that the physically and physiologically appropriate method of resuscitation, demonstrated in burn injury, comprises the use of a fluid given at a rate: (1) to maintain mean arterial and hydrostatic pressures within normal range; (2) that delivers a volume per unit time which does not exceed the capacity of the currently available functional vascular space; (3) that replaces concurrent measurable fluid losses; (4) that is hypertonic (to normalize capillary/tissue osmotic gradients); and (5) that contains colloid (to normalize capillary/tissue osmotic gradients); and (5) that contains colloid (to normalize capillary/tissue oncotic gradients). We further conclude that salt, fluid, and colloid loss into the interstitium during resuscitation frequently is due to the rate delivered and/or the physical nature of the fluid used and not to capillary bed damage outside the zone of injury.
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PMID:Studies in shock and resuscitation, I: use of a hypertonic, albumin-containing, fluid demand regimen (HALFD) in resuscitation. 44 52

Published observations suggest that not everyone benefits from severe dietary NaCl restriction, since blood pressure responses appear heterogeneous and adverse metabolic effects may occur. We studied the cardiovascular, neurohumoral, and metabolic effects of 7 day periods of 20 v 200 mEq/day NaCl diets in 27 men. Twelve subjects were salt sensitive (SS), defined as mean intraarterial pressure (MAP, mm Hg) during high NaCl greater than or equal to 5% above MAP on low NaCl. Eleven subjects were salt resistant (SR), defined as MAP during the low NaCl phase greater than or equal to MAP during the high NaCl phase. The SR subset had a tendency to greater neurohumoral activity, assessed by changes in mean values for plasma norepinephrine (NE, P = .12) and plasma renin activity (PRA, P less than .001) on the low v high NaCl diet. In SR subjects the low v high NaCl diet also raised mean values for creatinine (P = .03), uric acid (P = .001), and low density cholesterol (LDL-C, P = .03), but not fasting insulin (P = .15). In SS subjects, the low v high NaCl diet did not raise NE (P = .35), although the PRA was greater (P = .002). Among SS subjects, mean values for uric acid (P = .005) and insulin (P = .02) were greater during the low v high NaCl phase, while creatinine (P = .15) and LDL-C (P = .67) were not different. The data suggest that severe, short-term NaCl restriction can be undesirable, especially in SR subjects, since potentially adverse neurohumoral and metabolic changes are not counterbalanced by the benefits of a lower MAP.
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PMID:Neurohumoral and metabolic effects of short-term dietary NaCl restriction in men. Relationship to salt-sensitivity status. 206 83

Signaling via the alpha-beta T cell Ag receptor (Ti)-CD3 complex is a complicated event that implicates several protein kinases, most notably protein kinase C (PKC). We have recently identified a serine kinase in T lymphocytes with the following characteristics: molecular mass 43 kDa, in vitro substrate affinity for microtubule associated protein 2 (MAP-2) with a preference for Mn2+ during the catalytic reaction, and elution from DEAE resin over a salt range 100 to 200 mM NaCl. This kinase is activated in a rapidly reversible fashion during ligation of CD3/Ti by a process which involves prior phosphorylation; in vitro exposure of activated 43-kDa MAP-2 kinase (MAP-K) to an immobilized phosphatase abrogated its kinase activity. We now show that a MAP-2K response could also be obtained during treatment with mAb to Ti and the specific PKC agonist, PMA. Although the kinetics of the former response was rapidly reversible, PMA elicited a more prolonged response. The dose responsiveness for PMA was similar to the requirements for PKC activation in intact lymphocytes. Moreover, as with PKC, we found that the CD3-induced MAP-2K response could be further enhanced by using a second layer cross-linking antibody. The specificity of CD3/Ti in the Jurkat cell response is demonstrated by the fact that OKT-11(CD2) and anti-CD4 mAb did not stimulate a MAP-2K response. It was also not possible to elicit a response in a Jurkat cell mutant that lacks surface expression of CD3 and Ti. The specificity of PKC in these events was further explored with the cell permeant diacylglycerol, 1-oleoyl-2-acetylglycerol, and the nonagonist phorbol ester, 4 alpha-phorbol 12,13-didecanoate: whereas the former was an effective inducer of the MAP-2K response, the latter failed to yield any stimulation. Prior exposure of Jurkat cells to 100 mM PMA for 24 h eliminated greater than 60% of the MAP-2K response during anti-CD3 treatment. This response could also be inhibited in dose-dependent fashion by prior treatment of Jurkat cells with the potent PKC inhibitor 1-(5-isoquinolinesulfonyl) 2-methylpiperazine dihydrochloride. Although a Ca2(+)-ionophore failed to synergize with PMA at inducing a MAP-2K response, depletion of extracellular Ca2+ by EGTA abrogated anti-CD3 responsiveness. The events culminating in MAP-2K activation were slightly inhibited in the presence of cholera toxin but not pertussis toxin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Stimulation of MAP-2 kinase activity in T lymphocytes by anti-CD3 or anti-Ti monoclonal antibody is partially dependent on protein kinase C. 215 31

The injection of 25 mg/kg i.p. cyclosporin (CsA) for 3 wk caused marked functional and morphological deteriorations of pancreatic islet cells in Wistar rats that were prevented by the combined administration of p-aminobenzoic acid-N-D-mannoside sodium salt (K-MAP). In this article, the toxic effect of CsA on pancreatic islet cells and the preventive effect of K-MAP on CsA-associated islet cell toxicity were investigated. Prolonged hyperglycemia and depressed insulin secretion after the glucose challenge observed in CsA-treated rats could be prevented by the combined administration of 300 and 900 mg/kg K-MAP. Cytoplasmic vacuolizations and a decrease in the number of mitochondria, intact endoplasmic reticula, secretory granules, and insulin-positive cells, as revealed by peroxidase-antiperoxidase staining, could also be prevented by the administration of 900 mg/kg K-MAP. This preventive effect of K-MAP on CsA-associated islet cell toxicity may suggest the combined use of K-MAP with CsA in pancreas transplantation and treatment of insulin-dependent diabetes.
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PMID:Modulation of prostaglandin metabolism by K-MAP and prevention of toxic effect of cyclosporin on pancreatic islet cells. 264 33

Sympathetic-adrenal medullary responses to acute footshock stress were assessed in inbred Dahl salt-sensitive (S/JR) and salt-resistant (R/JR) rats by measuring plasma levels of norepinephrine (NE) and epinephrine (EPI). Ten-week-old S/JR and R/JR rats were surgically prepared with indwelling tail artery catheters which permitted direct measurements of mean arterial pressure (MAP, mmHg) and heart rate (HR, beats/min) and remote sampling of blood. Two days after surgery, S/JR and R/JR rats were subjected to an acute stress paradigm. Blood samples were collected before and 3 minutes after transfer of rats to a shock chamber, after 1 minute of intermittent footshock, and again 5 minutes later. S/JR rats had significantly higher resting MAP's compared to R/JR rats. In contrast, baseline heart rates were similar for rats of the two strains. Basal plasma levels of NE and EPI were also similar in S/JR and R/JR rats. Upon transfer from the home cage to a shock chamber, S/JR rats exhibited significant increases in plasma levels of both catecholamines, while R/JR rats maintained circulating levels of NE and EPI that were near baseline values. However, S/JR and R/JR rats had similar increments in plasma NE and EPI following acute footshock stress. Five minutes after footshock, levels of NE and EPI returned toward baseline values for R/JR's, but remained significantly elevated above baseline in hypertensive S/JR rats. These data suggest that S/JR rats are more responsive than R/JR controls to the mild stress of transfer, but exhibit comparable responses to the more intense stress of inescapable footshock.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sympathetic-adrenal medullary responses to acute stress in Dahl hypertensive (S/JR) rats. 272 39

Axoplasmic vesicles were purified and observed to translocate on isolated microtubules in an ATP-dependent, trypsin-sensitive manner, implying that ATP-binding polypeptides essential for force generation were present on the vesicle surface. To identify these proteins [alpha 32P]8-azidoadenosine 5'-triphosphate ([alpha 32P]8-N3ATP), a photoaffinity analogue of ATP, was used. The results presented here identify and characterize a vesicle-associated polypeptide having a relative molecular mass of 292 kD that bound [alpha 32P]8-N3ATP. The incorporation of label is ultraviolet light-dependent and ATP-sensitive. Moreover, the 292-kD polypeptide could be isolated in association with vesicles or microtubules, depending on the conditions used, and the data indicate that the 292-kD polypeptide is similar to mammalian brain microtubule-associated protein 2 (MAP 2) for the following reasons: The 292-kD polypeptide isolated from either squid axoplasm or optic lobe cross-reacts with antiserum to porcine brain MAP 2. Furthermore, it purifies with taxol-stabilized microtubules and is released with salt. Based on these characteristics, the 292-kD polypeptide is distinct from the known force-generating molecules myosin and flagellar dynein, as well as the 110-130-kD kinesin-like polypeptides that have recently been described (Brady, S. T., 1985, Nature (Lond.), 317:73-75; Vale, R. D., T. S. Reese, and M. P. Sheetz, 1985b, Cell, 42:39-50; Scholey, J. M., M. E. Porter, P. M. Grissom, and J. R. McIntosh, 1985, Nature (Lond.), 318:483-486). Because the 292-kD polypeptide binds ATP and is associated with vesicles that translocate on purified MAP-free microtubules in an ATP-dependent fashion, it is therefore believed to be involved in vesicle-microtubule interactions that promote organelle motility.
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PMID:Identification of a MAP 2-like ATP-binding protein associated with axoplasmic vesicles that translocate on isolated microtubules. 309 8

In twenty-five outpatients with essential hypertension, the relevance of renal kallikrein excretion for inter-individual differences in the blood pressure response to changes in dietary sodium intake was investigated. The patients were studied during 2 weeks of high (300 mmol) and 2 weeks of low (50-100 mmol) sodium intake. In addition there were two control periods of normal sodium intake, one lasting 4 weeks at the beginning and one lasting 2 weeks at the end of the study. Blood pressure, body weight and 24 h urinary sodium and kallikrein excretion were measured at the end of all periods. At the end of the first control period, 1 mg furosemide per kg body weight was administered intravenously, and the urinary excretion of kallikrein and sodium were measured 30 and 120 min later. The difference in mean arterial pressure (delta MAP) between high and low sodium intake ranged from + 18 to -8 mmHg. The eight patients with a delta MAP greater than 10 mmHg were regarded as salt-sensitive. They were older and had a higher initial blood pressure than salt-insensitive patients. For all patients, urinary kallikrein excretion at the end of the low sodium period (123(SEM 20.3) micrograms 24 h-1) was significantly higher than at the end of the first control period (96(SEM 16.3) micrograms 24 h-1, P less than 0.01) and at the end of the high sodium period (96(SEM 23.7) micrograms 24(-1), P less than 0.01). When compared with salt-insensitive patients, salt-sensitives had lower levels of urinary kallikrein excretion and a blunted kallikrein response to dietary sodium restriction and furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is the renal kallikrein system relevant to sodium sensitivity in patients with essential hypertension. 392 10

The objective of this study was to investigate the relationship between the high activity of the renin-angiotensin-aldosterone system (RAAS) and the control of blood pressure and aldosterone in the canine puppy. The effect of the angiotensin II analog saralasin on arterial pressure (MAP), plasma renin activity (PRA), plasma renin concentration (PRC), and aldosterone (PA) was studied in unanesthetized normal, salt-loaded and salt-depleted puppies aged 9 to 30 days. Salt-loading was performed by daily intraperitoneal administration of 10 mEq sodium/kg body weight for 5 days and salt-depletion by furosemide injections. Saralasin infusion, 6 micrograms/kg/min, during 60 min significantly decreased MAP and increased PRC not only in salt-depleted puppies, as has been observed in adult salt-depleted dogs, but also in normal puppies (mean fall, 6.6 mm Hg). Although any developmental changes in the RAAS and MAP and in their relationship could not be ascertained, the fall in MAP during saralasin in normal puppies was significantly correlated to presaralasin renin values (r = 0.76, P less than 0.01, N = 11). PA did not change in both groups of puppies. In salt-loaded puppies saralasin caused no change of MAP, PRC, and PA. We conclude that the high renin levels at young age contribute to the basal arterial pressure in puppies.
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PMID:Effects of angiotensin II blockade in the canine puppy under different salt-intake. 639 82

In 25 outpatients with essential hypertension, sodium sensitivity, defined as the difference in mean arterial pressure (delta MAP) between 2 weeks of high-sodium (300 mmol per day) and 2 weeks of low-sodium (LS) intake (50-100 mmol per day), was studied in relation to the plasma norepinephrine (NE) level, NE release, and pressor response to intravenous NE. In addition, forearm blood flow (FBF) was measured by plethysmography. There were two control periods of regular sodium intake, one of 4 weeks' duration at the beginning of the study and one of 2 weeks' duration at the end. The delta MAP ranged from +18 to -8 mm Hg. The eight patients in whom delta MAP was greater than 10 mm Hg were regarded as salt-sensitive. When compared with salt-insensitive subjects, salt-sensitive patients had higher plasma NE levels in the control period (p less than 0.05) and after 2 weeks of HS intake (p less than 0.01). Sodium sensitivity was directly related to the change in plasma NE between the HS and LS periods (p less than 0.001). The NE release decreased in salt-insensitive subjects whereas it increased in salt-sensitive patients between the LS and HS periods. Changes in NE release were directly related to sodium sensitivity (p less than 0.05). The pressor response to NE was not significantly influenced by changes in sodium intake. The FBF fell in salt-sensitive patients and increased in salt-insensitive subjects between the LS and HS periods. Sodium sensitivity was directly related to the change in forearm vascular resistance (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adrenergic activity and peripheral hemodynamics in relation to sodium sensitivity in patients with essential hypertension. 651 41

Regulation of aldosterone secretion by sodium chloride is impaired in a group of essential hypertensives: high-salt diet fails to suppress aldosterone in these patients despite low renin values. The mechanism of this impaired regulation of aldosterone has not been clarified so far. We tested the sensitivity of aldosterone secretion and blood pressure to A II in 20 normotensive controls (aged 20-60, MAP 92 +/- 3 mm Hg), in ten normotensives with one or two parents with hypertension, and in 21 patients with essential hypertension (aged 17-65, MAP 119 +/- 4 mm Hg). After a period of 6 days on high-salt intake (300-320 mEq Na+/day), A II (0.1, 0.5, 1.0 and 2.0 ng/kg/min) was infused, each concentration for 30 min. According to aldosterone excretion during sodium loading, patients were divided into group A with complete suppression (n = 12, aldosterone excretion 3.6 +/- 0.4 microgram/day) and in group B with insufficient suppression (n = 9, aldosterone excretion 15.5 +/- 2.3 micrograms/day). Despite similarly low plasma renins, rise of serum aldosterone levels during A II infusion was significantly higher in group B patients than in group A patients and normotensive controls. Rise in mean arterial blood pressure, however, brought about by graded A II infusion was similar in both groups of hypertensives and in normotensive controls. The results demonstrate an increased adrenal sensitivity to A II in a subgroup of essential hypertensives only. A similar adrenal hypersensitivity to A II found by others in patients with hyperaldosteronism due to adrenal hyperplasia supports the hypothesis that the same mechanism underlies both disorders.
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PMID:Cardiovascular and adrenal sensitivity to angiotensin II in essential hypertension. 652 58

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