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)

The antiproteinuric efficacy of angiotensin-converting-enzyme inhibitors (ACEI) has been extensively investigated in patients with several types of nephropathy, but there are few data on the use of ACEI in patients with primary glomerular disease without renal function impairment. We evaluate the effect of long-term therapy with captopril on arterial pressure and proteinuria in 13 patients with primary glomerular disease, selected on the following criteria: persistent proteinuria greater than 600 mg/day, serum creatinine less than or equal to 1.5 mg/dl, no dietary restriction or antihypertensive or immunosuppressive therapy for at least 9 months prior to enrolment. Ten of 13 patients were normotensive. The treatment with captopril induced an early and persistent decrease in proteinuria (41%), and a significant increase in serum albumin. We did not find a significant correlation between changes in MAP and changes in protein loss or between variations in serum creatinine and in proteinuria. Our results demonstrate that captopril is effective in reducing proteinuria in patients with primary glomerular disease with normal renal function. Since the antiproteinuric effect is not associated to a concomitant decrease in arterial pressure, we presume that it might be due to a specific intrarenal action of captopril.
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PMID:Antiproteinuric effect of angiotensin-converting-enzyme inhibitors in patients with primary glomerular disease and normal renal function. 212 69

The effect of volume replacement with crystalloidal and colloidal solutions was analyzed in 40 anesthetized Foxhounds subjected to a standardized traumatic-hemorrhagic shock. Following trauma and hypotension (MAP 40 mmHg; 3.0 +/- 0.5 hr) the animals were randomized to treatment with autologous blood and hydroxyethyl starch 6% (HES 450/0.7), or human serum albumin 5% (ALB), dextran-60 6% (DX), Ringer's lactate (RL), and hyperosmolar saline 1.3% (HS), respectively. While analgesia and sedation were maintained, the hemodynamic measurements were continued for a 24-hr period. Crystalloids and colloids were found equally effective in maintaining the macrohemodynamics following resuscitation from traumatic-hemorrhagic shock. To keep central hemodynamics at pre-shock level required at least four times higher volumes of crystalloids than colloids. No specific advantage for one of the substitutes tested was found with regard to accumulation of water in the lung during the first 24 hr following shock in dogs. Extravascular lung water (thermo-dye) and organ water (gravimetry) were not different between the groups. However, fluid loss into the abdominal cavity as well as albumin extravasation into lung interstitium and abdominal cavity were more pronounced in the crystalloid-treated animals, whereas albumin redelivery by the lymph was decreased. The deterioration of tissue oxygen extractions as well as the changes in acid-base balance in both crystalloid-treated groups reflect the persistent microcirculatory inhomogeneity in spite of normal macrohemodynamics.
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PMID:Long-term observation following traumatic-hemorrhagic shock in the dog: a comparison of crystalloidal vs. colloidal fluids. 321 30

Protein carboxyl methylase (PCM) and its substrate(s), methyl acceptor protein(s) (MAP), are present in the spermatozoa of rat, rabbit and man. In the present study, PCM activity and MAP capacity were measured in homogenates of hamster testes and isolated spermatozoa, and found to be similar to those of other species. Using solubilized preparations of spermatozoa from the cauda epididymis of hamster, PCM activity was twice as high in sperm tails as in heads while the reverse was true for MAP capacity. Since in this and in previous studies this enzyme reaction has been measured in broken cells, we thought it pertinent to measure methylation under physiological conditions (i.e., in motile spermatozoa). To accomplish this, an assay was developed which depends upon the conversion of [3H-methyl]methionine to S-adenoxyl-L [methyl-3H]methionine which, in turn, serves as a methyl donor for PCM. In sperm that had been labelled with [3H]methionine the MAP for the endogenous methylation reaction was not solubilized with Triton X-100, and was found primarily in sperm tails. When hamster spermatozoa were incubated in medium containing taurine, epinephrine and bovine serum albumin to induce capacitation, endogenous methylation was stimulated 8- to 9-fold; when taurine was omitted from this medium, methylation was stimulated 14-fold. Taurine, however, was essential for in vitro fertilization as the number of eggs fertilized declined from 92% in complete medium to 0% in medium minus taurine. The decrease in fertilization rate was also associated with a decrease in sperm motility. In previous studies we have demonstrated an association between PCM and sperm motility, and have suggested that this enzyme system could be involved in other functions such as the acrosome reaction. From the results in the present study we conclude that the conditions that lead to capacitation in vitro are associated with a marked change in endogenous protein carboxyl methylation.
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PMID:Endogenous protein carboxyl methylation in hamster spermatozoa: changes associated with capacitation in vitro. 665 20

The efficacy of Diaspirin Crosslinked Hemoglobin (DCLHb) as a resuscitative fluid in hemorrhagic shock was compared to another colloid solution (human serum albumin, HSA) and a crystalloid solution (Lactated Ringer's, LR). Hemorrhage (35 mL/kg) was followed by isovolemic exchange then volume replacement. This modeled the clinical situation where resuscitative fluids are administered prior to stopping the hemorrhage, the hemorrhage is stopped, then blood volume is restored. Four combinations of resuscitative fluids were evaluated during isovolemic exchange: volume replacement: DCLHb:LR, HSA:LR, HSA:HSA and LR:LR. All doses were 10 mL/kg:35 mL/kg except LR:LR which was 10 mL/kg:125 mL/kg. Volume replacement was followed by a stabilization period and reinfusion of shed blood (35 mL/kg). MAP increased most rapidly using DCLHb (from 48 to 102 mmHg after 10 min of isovolemic exchange) and was maintained for at least 2 hours. Arterial oxygen content and acid-base status were significantly improved after resuscitation with DCLHb:LR vs. other resuscitative therapies. In conclusion, DCLHb:LR was an effective resuscitative therapy in treatment of hemorrhagic shock.
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PMID:Resuscitation with Diaspirin Crosslinked Hemoglobin in a pig model of hemorrhagic shock. 771 45

Peptides with high affinities and specificities for numerous proteins and nucleic acids have been previously identified from random peptide bacteriophage display libraries. Here, random peptide bacteriophage display libraries were used to identify sequences that bound the cancer-associated Thomsen-Friedenreich glycoantigen (T antigen). The T antigen, present on most malignant cells, contains an immunodominant Gal beta1 --> 3GalNAc alpha disaccharide unmasked on the surfaces of most carcinomas. This antigen has been postulated to be involved in tumor cell aggregation and metastasis. Two 15 amino acid random peptide bacteriophage display libraries were affinity selected with glycoproteins displaying T antigen on their surfaces. Sequence analysis revealed that many of the peptides shared homology with sugar recognition sites in several carbohydrate-binding proteins. A comparison of affinity selected sequences from both libraries yielded a common motif (W-Y-A-W/F-S-P) rich in aromatic amino acids. Four peptides, corresponding to the affinity selected sequences, were chemically synthesized and characterized for their carbohydrate recognition properties. The synthetic peptides exhibited high specificities and affinities to T antigen displayed on asialofetuin or conjugated to bovine serum albumin (Kd = 5 nM for MAP-P30 binding to asialofetuin) as well as free T-antigen disaccharide in solution (Kd = 10 microM for MAP-P30, 20 microM for P10). Two peptides, P30 and P10, demonstrated high affinities and specificities for both asialofetuin and T antigen in solution. Iodination of a lone tyrosine residue in each sequence dramatically reduced their abilities to bind T antigen, suggesting that the tyrosine residue plays an important role in carbohydrate recognition. That these peptides are of functional significance is evidenced by the ability of both P30 and P10 to inhibit asialofetuin-mediated melanoma cell aggregation in vitro and to compete with peanut lectin for binding to T antigen displayed on the surface of MDA-MB-435 breast carcinoma cells in situ.
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PMID:Characterization of peptides that bind the tumor-associated Thomsen-Friedenreich antigen selected from bacteriophage display libraries. 923 4

Adhesion molecules and chemokines contribute to selective eosinophil recruitment in allergic inflammation. In this study, we examined the effects of eotaxin-2, a CCR3-specific chemokine, on integrin-mediated eosinophil adhesion to vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), or both using a parallel plate flow system. Tissue culture plates were coated with various combinations of VCAM-1, ICAM-1, and/or eotaxin-2. Human eosinophils were infused at physiologic shear stress (0.5 dyn/cm(2)) for 10 min, and the numbers of attached eosinophils were monitored using video microscopy. Cells accumulated efficiently on VCAM-1 and even better on surfaces co-coated with VCAM-1 and ICAM-1, but poorly on surfaces coated with ICAM-1 or bovine serum albumin alone. When eotaxin-2 was co-immobilized with adhesion proteins, fewer cells adhered to VCAM-1 and more adhered to ICAM-1, whereas levels of attachment to VCAM-1 plus ICAM-1 showed no net change. However, experiments with adhesion molecule blocking monoclonal antibody showed that the contribution of ICAM-1-mediated adhesion was always greater if eotaxin-2 was present. Pretreatment of cells with a CCR3-blocking mAb, or PD98059, a MAP-kinase inhibitor, prevented the eotaxin-2-induced changes in eosinophil attachment. These data suggest that eotaxin-2, acting via MAP kinases, may facilitate eosinophil recruitment at sites of allergic inflammation by shifting their adhesion molecule usage away from VCAM-1-dominated to ICAM-1-dominated pathways.
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PMID:Eotaxin-2 alters eosinophil integrin function via mitogen-activated protein kinases. 1203 62

We investigated the acute microcirculatory effects, including mesenteric lymphatic pumping, of volume replacement with different iso- or hypertonic/oncotic solutions after severe hemorrhage (mean arterial pressure [MAP] approximately 35 mmHg during 30 min) in halothane-anesthetized Wistar rats. Resuscitation was achieved 30 min after induction of shock with one of the following solutions: autologous blood (BL); 0.9% NaCl (IS), 7.5% NaCl (HS); 5% bovine serum albumin (BSA); 0.9% NaCl-6% hydroxyethyl starch (HES), or 7.5% NaCl-HES (HES 7.5). MAP was partially and transiently restored by infusion of IS or HS, whereas in the groups treated with BL, HES, HES 7.5, or BSA, there was a complete restoration of blood pressure in the 30-min period after infusion. Microvascular blood flow (MBF), measured by laser Doppler flowmetry, was reduced by 59% +/- 7% 10 min after bleeding. MBF was also transiently restored after infusion of IS, HS, BL, BSA, or HES. HES 7.5 was the only solution able to induce immediate and sustained (60 min) restoration of preshock levels of MBF. Volume replacement with IS or HES 7.5 resulted respectively in long-lasting or transient lymphatic pumping overload. On the other hand, resuscitation with all other solutions, except BSA, did not restore lymphatic activity to preshock levels. We also observed a significant reduction of the diameter of mesenteric terminal arterioles (15-30 microm) after bleeding, which was reversed temporarily in IS, BL, and HES groups, whereas resuscitation with HES 7.5 solution was able to maintain arterioles dilated until the end of the experimental period. Therefore, it is concluded that the association of hyperoncotic and hyperosmotic solutions, represented here by HES 7.5, induces positive effects with respect to the macro- and microhemodynamics accompanied by restoration and maintenance of the interstitial drainage system, being indicated for maintenance of postresuscitation cardiovascular and microvascular function.
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PMID:Effects of fluid resuscitation on mesenteric microvascular blood flow and lymphatic activity after severe hemorrhagic shock in rats. 1255 45

We developed a novel model using fluorescent intravital microscopy to study the effect of atrial natriuretic peptide (ANP) on the extrasplenic microcirculation. Continuous infusion of ANP into the splenic artery (10 ng min(-1) for 60 min) of male Long-Evans rats (220-250 g, n = 24) induced constriction of the splenic arterioles after 15 min (-7.2 +/- 6.6% from baseline diameter of 96 +/- 18.3 microm, mean +/- S.E.M.) and venules (-14.4 +/- 4.0% from 249 +/- 25.8 microm; P < 0.05). At the same time flow did not change in the arterioles (from 1.58 +/- 0.34 to 1.27 +/- 0.27 ml min(-1)), although it decreased in venules (from 1.67 +/- 0.23 to 1.15 +/- 0.20 ml min(-1)) and increased in the lymphatics (from 0.007 +/- 0.001 to 0.034 +/- 0.008 ml min(-1); P < 0.05). There was no significant change in mean arterial pressure (from 118 +/- 5 to 112 +/- 5 mmHg). After continuous ANP infusion for 60 min, the arterioles were dilated (108 +/- 16 microm, P < 0.05) but the venules remained constricted (223 +/- 24 microm). Blood flow decreased in both arterioles (0.76 +/- 0.12 ml min(-1)) and venules (1.03 +/- 0.18 ml min(-1); P < 0.05), but was now unchanged from baseline in the lymphatics (0.01 +/- 0.001 ml min(-1)). This was accompanied by a significant decrease in MAP (104 +/- 5 mmHg; P < 0.05). At 60 min, there was macromolecular leak from the lymphatics, as indicated by increased interstitial fluorescein isothiocyanate-bovine serum albumin fluorescence (grey level: 0 = black; 255 = white; from 55.8 +/- 7.6 to 71.8 +/- 5.9, P < 0.05). This study confirms our previous proposition that, in the extrasplenic microcirculation, ANP causes greater increases in post- than precapillary resistance, thus increasing intrasplenic capillary hydrostatic pressure (P(c)) and fluid efflux into the lymphatic system. Longer-term infusion of ANP also increases Pc, but this is accompanied by increased 'permeability' of the extrasplenic lymphatics, such that fluid is lost to perivascular third spaces.
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PMID:Effects of atrial natriuretic peptide on the extrasplenic microvasculature and lymphatics in the rat in vivo. 1571 60

Removal of the N-terminal methionine of a protein could be critical for its function and stability. Post-translational modifications of recombinant proteins expressed in heterologous systems may change amino-terminal regions. We studied the expression of mature proteins lacking methionine as the N-terminal amino acid in tobacco chloroplasts, using human serum albumin (HSA) as an example. Two approaches were explored. First, we fused the Rubisco small subunit transit peptide to HSA. This chimeric protein was correctly processed in the stroma of the chloroplast and rendered the mature HSA. The second approach took advantage of the endogenous N-terminal methionine cleavage by methionine aminopeptidase. Study of this protein processing reveals a systematic cleavage rule depending on the size of the second amino acid. Analysis of several foreign proteins expressed in tobacco chloroplasts showed a cleavage pattern in accordance to that of endogenous proteins. This knowledge should be taken into account when recombinant proteins with N-terminus relevant for its function are expressed in plastids.
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PMID:Expression of recombinant proteins lacking methionine as N-terminal amino acid in plastids: human serum albumin as a case study. 1702 13

This unit describes methods used for the chemical coupling of synthetic peptides to carrier proteins, required for the preparation of peptide immunogens. The carrier protein described here is keyhole limpet hemocyanin (KLH) because it is the one most commonly used. However, other proteins may be used in place of KLH, including bovine serum albumin (BSA) and ovalbumin. Coupling may be accomplished as described with MBS, which requires a Cys residue in the peptide, or with glutaraldehyde, EDCI, or BDB. Also included are an assay for detecting free sulfhydryl (SH) groups, a means of calculating coupling efficiency, an immunization schedule, an indirect ELISA, and a method for preparing a peptide affinity column. The final methodology described is the multiple antigen (MAP) system.
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PMID:Production of antipeptide antisera. 1842 5


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