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)

Estramustine-phosphate (EMP), a phosphorylated conjugate of estradiol and nor-nitrogen mustard binds to microtubule-associated proteins MAP-2 and tau. It was shown that this estramustine derivative inhibits the binding of the C-terminal tubulin peptide beta-(422-434) to both MAP-2 and tau. This tubulin segment constitutes a main binding domain for these microtubule-associated proteins. Interestingly, estramustine-phosphate interacted with the synthetic tau peptides V187-G204 and V218-G235, representing two major repeats within the conserved microtubule-binding domain on tau and also on MAP-2. This observation was corroborated by the inhibitory effects of estramustine-phosphate on the tau peptide-induced tubulin assembly into microtubules. On the other hand, the nonphosphorylated drug estramustine failed to block the MAP peptide-induced assembly, indicating that the negatively charged phosphate moiety of estramustine-phosphate is of importance for its inhibitory effect. These findings suggest that the molecular sites for the action of estramustine-phosphate are located within the microtubule binding domains on tau and MAP-2.
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PMID:Estramustine-phosphate binds to a tubulin binding domain on microtubule-associated proteins MAP-2 and tau. 159 56

The effect of hypoxic hypoxia (HH) and carbon monoxide hypoxia (COH) on adrenal medullary (MQ) and cortical (CQ) blood flow (radiolabeled microsphere technique) was studied in pentobarbital sodium-anesthetized, mechanically ventilated dogs. Animals were exposed to 60 min of hypoxia (arterial O2 content 8 vol%) induced by adding either nitrogen (HH, n = 6) or carbon monoxide (COH, n = 6) to the inspired gas. Whole adrenal Q and CQ increased by 70 and 50%, respectively, with HH but were unchanged during COH. MQ, however, increased threefold during both HH and COH. HH and COH both increased arterial levels of epinephrine, corticosteroids, and adrenocorticotropic hormone (ACTH). To determine whether the increase in CQ during HH was because of HH-induced increases in mean arterial blood pressure (MAP, approximately 20 mmHg), an additional group of animals (n = 6) was exposed to HH but had MAP maintained at control levels using a pressurized-bottle system. MAP control did not alter the CQ response to HH. We conclude that MQ appears to be associated with medullary secretory activity during hypoxia and that HH and COH stimulate adrenal medullary secretion equally. In contrast, CQ increases only with HH, despite similar increases in ACTH and corticosteroid levels during HH and COH, suggesting that an alternative mechanism is responsible for increased cortical blood flow during HH.
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PMID:Regional adrenal blood flow during hypoxia in anesthetized, ventilated dogs. 253 47

The cerebral effects of alterations in plasma osmolality (Osm) and colloid oncotic pressure (COP) were examined in normocarbic, normothermic, pentobarbital-anesthetized rabbits that had been subjected to cryogenic brain injury. Monitored variables in all animals included mean arterial, right atrial, and intracranial pressures (MAP, CVP, and ICP), electroencephalographic (EEG) recordings, and cerebral blood flow (CBF). When surgical preparation was complete, a left parietal lesion was produced with liquid nitrogen. Group 1 (control, n = 8) animals subsequently received only maintenance fluids [lactated Ringer's solution (LR)]. One hour after injury, 3 other groups of animals underwent 45 minutes of plasmapheresis, carried out by arterial phlebotomy (packed red cells returned), with separated plasma being replaced by one of three fluids given in amounts sufficient to maintain MAP and CVP at baseline values. The three fluids were 1) 6% hetastarch in hypo-osmotic LR [Group 2 (Hypo-Osm), n = 6; COP = 21 mm Hg, Osm = 130 mOsm/kg]; 2) iso-osmotic LR [Group 3 (Hypo-COP), n = 8; COP = 0; Osm = 305]; and 3) 6% hetastarch in iso-osmotic LR [Group 4 (Iso-Osm/COP), n = 8; COP = 21, Osm = 310]. The animals were killed by exsanguination 25 minutes after completion of plasmapheresis. The brain was removed, the hemispheres separated, weighed, and sliced, and the specific gravities (SpGr) of the regional tissue determined. There were no differences in MAP, CVP, regional CBF, or EEG activity among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute effects of changing plasma osmolality and colloid oncotic pressure on the formation of brain edema after cryogenic injury. 271 75

Over two decades, experience with estramustine has provided limited data which support an estrogenic mechanism of action and no data which indicate the nitrogen mustard involvement in the cytotoxic properties of the drug. Consideration of the carbamate-ester portion of estramustine supports the pharmacokinetic evidence that estramustine has a long half life since enzymatic hydrolysis of the carbamate is an uncommon event. Using a variety of immunocytochemical and cellular morphology procedures, estramustine per se has been found to express anti-cytoskeletal properties through non-covalent binding to microtubule associated proteins (MAP's). In both fish erythrophores and in dividing human prostatic carcinoma cells, estramustine exerts an antimicrotubule effect at micromolar concentrations. Thus, estramustine possesses unique pharmacology and protein binding specificity. As such, it should not be classified as an alkylating agent. The estrogenic effects, while possibly of relevance to clinical administration, are not the primary mechanism by which the drug exerts cytotoxicity.
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PMID:Hormone-independent, non-alkylating mechanism of cytotoxicity for estramustine. 330 87

Ten advanced cancer patients not amendable to conventional therapy were treated with high dose (greater than 500 mg/day, for 30 days) Medroxyprogesterone Acetate (MAP) both orally and intramuscularly, in order to evaluate a possible anabolic effect of this hormone. During the treatment, mean protein intake increased from 37.2 gr/day to 58.8 gr/day (p less than 0.01), nitrogen intake from 5.8 to 9.4 gr/day (p less than 0.01) and caloric intake from 1407.9 to 2075 Kcal/day (p less than 0.01). Nitrogen balance also showed a significant increase (p less than 0.05), as well as elementary strength (p less than 0.02). Lean body mass and body weight did not show significant variations. The above data confirms what was already been documented by us in animals and proposed in man-that MAP has an anabolic effect.
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PMID:The anabolic effect of high dose medroxyprogesterone acetate in oncology. 622 31

The beneficial vs deleterious effects of hypothermia superimposed on hypoxia and hypotension have been argued and are clinically important. In this study, cerebral cytochrome a,a3 redox state and the quantity of intracerebral oxygenated hemoglobin (HbO2) were measured continuously and noninvasively in rats subjected to hemorrhagic hypotension (MAP = 30 mm Hg) and hypoxia (F1O2 = 7.5%) utilizing near infrared spectrophotometry. Prior to the experiment the rats were briefly respired on 100% oxygen to establish 100% oxidation of cytochrome a,a3 and hemoglobin, and at the conclusion of the experiment they were respired on 100% nitrogen to establish 100% reduction. Data are reported as percent oxidation within this range at baseline and after 15 and 30 min of hypoxic hypotension. Arterial blood gases were measured. Body temperature as monitored by a rectal probe was altered by placing anesthetized-paralyzed rats inside a circulating water jacket. Three groups of rats were studied: 38, 33, and 22 degrees C. Group III rats had a significantly (P less than 0.01) greater quantity of intracranial HbO2 than group I or II. Since MAP was held constant at 30 mm Hg, we assume this is largely due to the higher (P less than 0.01) arterial PO2 in group III (101.5) compared to group I and II (48.5, 51.3). Both groups II and III had a significantly (P less than 0.01) greater oxidation of cytochrome a,a3 indicating greater oxygen availability for a given metabolic rate. This was associated with improved survival inasmuch as all rats in groups II and III lived, and only one group I rat survived. It can be concluded that, as used in this study, hypothermia is beneficial and deserves further investigation.
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PMID:Effect of hypothermia during hypoxic hypotension on cerebral metabolism. 630 May 53

The effects of inhalation of oxygen, nitrous oxide/oxygen and nitrous oxide/nitrogen/oxygen on systolic time intervals (PEP (pre-ejection period) and LVET (left ventricular ejection time) were investigated in eight healthy persons. Nitrous oxide 40%, administered with oxygen or oxygen/nitrogen, prolonged PEP significantly by 25% and 22%, respectively. Inhalation of oxygen also prolonged PEP but to a significantly minor degree. LVET, heart rate and MAP were unchanged during the experiments. Derivatives from the systolic time intervals, i.e. PEP/LVET, I/PEP2 and ejection fraction changed significantly in the nitrous oxide groups. It is concluded that nitrous oxide depresses cardiac performance, to some degree, even when administered at a rather low concentration.
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PMID:Effects of nitrous oxide on systolic time intervals. 737 8

The safe use of nitrous oxide, in particular in patients with coronary artery disease, has been questioned. This study was designed to determine whether nitrous oxide directly affects global coronary hemodynamic variables and coronary arteriolar microvessels in the absence of changes of myocardial oxygen consumption. In dogs the effects of nitrous oxide were evaluated during normotension (NT, intravenous [IV] piritramid, nitrogen/oxygen; and NT/N2O, IV piritramid, nitrous oxide/oxygen) and during hypotension (MAP 60 mm Hg) (HT, IV piritramid, halothane, nitrogen/oxygen; and HT/N2O, IV piritramid, halothane, nitrous oxide/oxygen). The diameter of coronary arteriolar microvessels (range, 20-450 microns) was assessed by intravital fluorescence microscopy. Myocardial blood flow was determined by radioactive microspheres. Systemic and coronary hemodynamics, as well as arteriolar microvessel diameters, were comparable between NT and NT/N2O. During HT, nitrous oxide (HT/N2O) affected neither systemic nor coronary hemodynamics. Moreover, there was no obvious difference in the diameters of coronary microvessels between HT and HT/N2O. In conclusion, nitrous oxide, whether at normotensive or hypotensive conditions, neither influences coronary arteriolar tone nor reduces or redistributes myocardial blood flow.
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PMID:Does nitrous oxide affect coronary microcirculation? An intravital microscopic study in the canine heart. 781 9

The combined effects of water activity (aw), storage temperature, headspace oxygen and carbon dioxide concentrations on the growth of, and aflatoxin production by Aspergillus flavus on sterile peanuts were examined using a process optimization technique termed response surface methodology (RSM). Regression analysis of the data indicated that aw, storage temperature and initial headspace oxygen concentration were all significant factors (P < 0.001) affecting the growth of, and aflatoxin production by A. flavus. Extensive growth and aflatoxin production occurred during the first week of storage in most treatment combinations. Maximum growth occurred in peanuts with an aw of 0.97, a storage temperature of 25 degrees C and headspace oxygen of 10% (balance 60:40 carbon dioxide:nitrogen), after 21 days of storage while maximum aflatoxin production occurred at a lower aw of 0.94, after 21 days under similar storage/gaseous conditions. In several treatment combinations, where high levels of aflatoxin (> 20 ng/g) were initially detected, aflatoxin concentration decreased during storage to levels less than the current regulatory limit of 20 ng/g. This study has shown that A. flavus can grow and produce aflatoxin in carbon dioxide enriched atmospheres in the presence of oxygen. It also emphasizes the combined effect of several 'barriers' to inhibit and reduce aflatoxin in MAP products containing various levels of residual oxygen.
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PMID:Growth of and aflatoxin production by Aspergillus flavus in peanuts stored under modified atmosphere packaging (MAP) conditions. 807 70

The clinical pathogen Candida albicans is a budding yeast that is capable of forming a range of polarized and expanded cell shapes from pseudohyphae to true nonconstricted hyphae. Filamentous forms consist of contiguous uninucleated compartments that are partitioned by septa. It has long been held that the so-called "dimorphic transition" from a budding to a filamentous form may aid the fungus to penetrate epithelia and may therefore be a virulence factor. This review summarized new information regarding the physiology and ecology of hyphal growth in C. albicans. New evidence has demonstrated that hyphae of C. albicans have a sense of touch so that they grow along grooves and through pores (thigmotropism). This may aid infiltration of epithelial surfaces during tissue invasion. Hyphae are also aerotropic and can form helices when contacting solid surfaces. Growing evidence supports the view that hyphal growth is a response to nutrient deprivation, especially low nitrogen and that filamentous growth enables the fungus to forage for nutrients more effectively. Further insights into the growth of C. albicans have come from the analysis of genes and mutations of Saccharomyces which have begun to reveal the molecular mechanisms underlying the mechanisms of bud site selection, cell polarity and signal transduction pathways that lead to pseudohyphal development in this and other organisms. For example, it is now clear that a MAP-kinase cascade, homologous to the mating pathway in Saccharomyces, regulates filamentous growth in both fungi. However, this must be only one of several overlapping or separate signal transduction pathways for hyphal development because filamentous growth still occurs in mutants of Candida and Saccharomyces which are blocked in this pathway. Cell cycle analyses have shown that hyphal phase cell cycle of Candida is distinct from that in budding and pseudohyphal formation and so pseudohyphal growth of Saccharomyces is not a true model of germ tube growth in Candida. Pseudohyphal growth in both Candida and Saccharomyces involves synchronous division of mother cells and their daughters. In contrast, during germ tube growth of Candida, cytoplasm is unequally partitioned at cytokinesis so that apical cells inherit more cytoplasm and sub-apical cells have a single nucleus but are extensively vacuolated. As a result, apical cells grow and divide while sub-apical cells are apparently arrested in the cell cycle until they can regenerate sufficient cytoplasm to re-enter the cell cycle. Although current studies still fall short of verifying the status of yeast-hypha dimorphism as a virulence factor, they suggest that the cell biology of germ tube growth of C. albicans is well suited for the invasive growth of the fungus in vivo.
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PMID:Germ tube growth of Candida albicans. 950 66


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