Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A young man with severe multiple injuries following a motorcycle accident was admitted with head and mandible fractures, coma, fracture dislocation at C5-C6 resulting in total leg paralysis, partial paralysis of the right arm and intercostal muscles, and closed chest injury with possible pulmonary contusion. On the fourth day he developed fulminating mediastinitis and massive empyema, and was found to have a ruptured esophagus. Recovery became possible with surgical drainage of the pleural cavity and mediastinum, proximal and distal decompression of the esophagus, antimicrobial therapy, irrigation of the pleural cavity, complete intravenous hyperalimentation, and infusions of salt-poor albumin. The patient was discharged after 95 days, and 7 months after injury is neurologically intact except for a partial right wrist drop. This rare esophageal rupture should be suspected in any chest injury patients, especially those characterized by extreme cyanosis, dyspnea, shock, and prostration incompatible with thoracic cage injury.
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PMID:Rupture of the thoracic esophagus from blunt trauma. 59 47

The purpose of this study was to test the hypothesis that exercise training induces enhanced intracellular free Ca2+ (Cai) availability to the contractile elements of cardiac cells. Cai transients were directly measured in single isolated contracting ventricular myocytes from exercise-trained (EX) and sedentary control (SED) rats. Male Sprague-Dawley rats underwent 16 wk of progressive treadmill exercise (32 m/min, 8% grade, 1.5 h/day) (EX) or were cage confined (SED). EX rats had lower resting heart rate and elevated skeletal muscle oxidative capacity. Cai was measured with the fluorescent Cai indicator fura-2. Simultaneous video monitoring indicated that myocytes suspended in physiological salt solution were quiescent until stimulated electrically at a frequency of 0.2 Hz (12-36 V, 2-ms duration). Stimulated Cai transients, measured from changes in fura-2 fluorescence, were similar in cells from EX and SED groups. Peak shortening, time to peak shortening, velocity of shortening, contraction duration, and time to half-relaxation were also similar in cells from EX and SED rats. Ryanodine (10 microM) was applied to eliminate the contribution of Ca2+ release from sarcoplasmic reticulum to the Cai transient. Verapamil was applied to eliminate the contribution of voltage-gated Ca2+ channels to Cai transients. Cai transients were also similar in cells from EX and SED groups after these pharmacological interventions. These results suggest that treadmill training of rats does not alter Cai availability to the contractile elements in isolated ventricular myocytes.
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PMID:Effect of exercise training on intracellular free Ca2+ transients in ventricular myocytes of rats. 133 32

The tetradecapeptide Ac-D-F-L-A-E-G-G-G-V-R-G-P-R-V-OMe, which mimics residues 7f-20f of the A alpha-chain of human fibrinogen, has been co-crystallized with bovine thrombin from ammonium sulfate solutions in space group P2(1) with unit cell dimensions of a = 83.0 A, b = 89.4 A, c = 99.3 A, and beta = 106.6 degrees. Three crystallographically independent complexes were located in the asymmetric unit by molecular replacement using the native bovine thrombin structure as a model. The standard crystallographic R-factor is 0.167 at 2.3-A resolution. Excellent electron density could be traced for the decapeptide, beginning with Asp-7f and ending with Arg-16f in the active site of thrombin; the remaining 4 residues, which have been cleaved from the tetradecapeptide at the Arg-16f/Gly-17f bond, are not seen. Residues 7f-11f at the NH2 terminus of the peptide form a single turn of alpha-helix that is connected by Gly-12f, which has a positive phi angle, to an extended chain containing residues 13f-16f. The major specific interactions between the peptide and thrombin are 1) a hydrophobic cage formed by residues Tyr-60A, Trp-60D, Leu-99, Ile-174, Trp-215, Leu-9f, Gly-13f, and Val-15f that surrounds Phe-8f; 2) a hydrogen bond linking Phe-8f NH to Lys-97 O;3) a salt link between Glu-11f and Arg-173; 4) two antiparallel beta-sheet hydrogen bonds between Gly-14f and Gly-216; and 5) the insertion of Arg-16f into the specificity pocket. Binding of the peptide is accompanied by a considerable shift in two of the loops near the active site relative to human D-phenyl-L-prolyl-L-arginyl chloromethyl ketone (PPACK)-thrombin.
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PMID:The structure of residues 7-16 of the A alpha-chain of human fibrinogen bound to bovine thrombin at 2.3-A resolution. 156 20

A new alpha-amino acid derivative incorporating the 1,2-dicarba-closo- dodecarborane(12) cage, namely 5-(2-methyl-1,2-dicarba-closo-dodecarborane(12)-1-yl)- 2-aminopentanoic acid (2), was synthesized by the alkylation of the benzophenone Schiff's base of glycine methyl ester with 3-(2-methyl-1,2-dicarba-closo-dodecaborane(12)-1-yl)pr opyl iodide (8). This amino acid was employed in the synthesis of peptide derivatives such as 19-21 using solid-phase Merrifield methods. Dipeptide 19 was converted to a water-soluble ionic derivative by the pyrrolidine-mediated carborane cage degradation reaction followed by cation exchange to afford sodium salt 22. Dansylation of 22 with dansyl chloride yielded fluorescence-labeled dipeptide 23. Undecapeptide 21 was dansylated while still anchored to the Merrifield resin. Following its cleavage from the resin with hydrogen fluoride, product 25 was acetylated to block the free amino group on the lysine residue and then converted to water-soluble derivative 27. Trial conjugations of dipeptide 23 and undecapeptide 27 to T84.66, an anti-CEA antibody, were carried out by means of carboxyl activation with N-hydroxysulfosuccinimide and N,N-diisopropylcarbodiimide. Studies of the chemical syntheses of these and other peptide derivatives and the conjugation of 23 and 27 to the antibody are described.
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PMID:Novel carboranyl amino acids and peptides: reagents for antibody modification and subsequent neutron-capture studies. 177 6

The photosensitized monomerization of the cyclobutane dimers of 1,3-dimethylthymine by p-chloranil was investigated by means of steady-state irradiation and laser-flash photolysis. Quantum yields for the monomerization are 0.34 for the cis,syn dimer, 0.39 for the trans,syn dimer, and much less than 10(-2) for the cis,anti isomer. Formation of the chloranil anion radical associated with quenching of triplet chloranil by the dimers demonstrates that electron transfer from dimers to triplet chloranil occurs to initiate the monomerization. Kinetic analysis suggested that the syn-dimer cation radicals undergo the ring cleavage at greater than or equal to 10(9) s-1 before escaping from the solvent cage, while the reactivity of the anti-dimer cation radical is very low. The different reactivities of the syn and anti dimer cation radicals are discussed in terms of through-bond coupling between the n orbitals of N(1) and N(1') involving the cyclobutane-ring sigma orbitals. In the cases of the syn-dimers, the sensitizer-dimer ion-radical pairs undergo the rapid geminate recombination that works as a major energy dissipating channel responsible for the lower-than-unity quantum yields. It has been found that the presence of Mg(ClO4)2 at 0.1 M enhances approximately 1.5 times either the monomerization of the syn dimers or the formation of the chloranil anion radical. A laser-flash photolysis study shows that Mg2+ forms a complex with either the triplet or the anion radical of chloranil. The net salt effects are attributed to the retardation of the rapid geminate recombination by the participation of Mg2+ in the sensitizer-dimer ion-radical pairs.
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PMID:Chloranil-photosensitized monomerization of dimethylthymine cyclobutane dimers and effect of magnesium perchlorate. 196 58

A tetraphenylporphyrin bearing four dicarbollide ([B9C2H11]-) cages linked to the o-phenyl ring positions by anilide bonds, known as boronated tetraphenylporphyrin (BTPP), has been synthesized in excellent yield from tetra-(o-aminophenyl) porphyrin and carborane carbonyl chloride followed by base-assisted cage opening and ion exchange to give the highly water-soluble potassium salt. Preliminary studies showed that BTPP accumulates in liver and in a syngeneic ovarian carcinoma, but not in normal brain parenchyma, of mice infused with BTPP subcutaneously for 6 or 7 days via surgically implanted osmotic minipumps. In this study, the uptake of boron was measured in human gliomas xenografted subcutaneously to athymic nude mice in which BTPP was infused intraperitoneally or subcutaneously or both for 3 or 7 days by using similar minipumps. Immunocompetent mice bearing a syngeneic ovarian carcinoma were similarly infused to provide comparative data. Bulk concentrations of boron up to 18 micrograms/g of glioma and up to 45 micrograms/g of carcinoma were observed when up to 102 micrograms/g of tissue was present in the liver after 7 days of BTPP infusion. Glioma boron concentrations were increased by approximately 80% on the average (up to 33 micrograms/g) when correspondingly greater amounts of BTPP were infused in only 3 days. Cell counts and chemical tests on blood samples from individual mice indicate that BTPP causes moderate hepatotoxicity and thrombocytopenia. This hepatohematic toxicity syndrome should be taken into account if BTPP or a similar agent is used for boron neutron-capture therapy (BNCT) of human malignancies.
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PMID:Uptake of a nido-carboranylporphyrin by human glioma xenografts in athymic nude mice and by syngeneic ovarian carcinomas in immunocompetent mice. 240 7

As part of an effort to evaluate the toxicology of a chemically defined mixture of 25 frequently detected groundwater contaminants, we report here the formulation and analytical chemistry of this mixture. Many problems were anticipated, including limitation of solubility, chemical interactions, and extreme volatility in the aqueous solution of 25 chemicals. The final technically achievable stock solution was prepared based on EPA survey concentrations of these chemicals in groundwater around hazardous waste disposal sites, their toxicity information, and solubility of the individual compounds in the matrix of the aqueous solution of these 25 chemicals. Because the anticipated animal studies were to be conducted at various laboratories, for ease of handling and maximum stability, the stock solution was stored or shipped as two substock solutions: an organic substock with 18 neat organic chemicals in a glass vial sealed with minimum headspace and an aqueous substock solution with 6 metals of various salt forms and phenol. The concentrations of the solutions were such that direct mixing of the organic and aqueous substocks produced the desired high dose level for the animal experiments. Analyses of all 25 chemicals in the drinking water mixture required six different chromatographic and spectroscopic methods. Some loss of organic volatiles during mixing of the substocks and during the first 24 hr following preparation did occur. However, the concentrations of acetone, phenol, and all the metals remained constant during preparation. Solutions held under simulated animal cage conditions for 96 hr showed losses of the organic volatiles; the majority of which occurred within the first 24 hr. This study shows that it is possible to conduct animal experiments on an aqueous mixture containing 25 groundwater contaminants. Furthermore, a reasonable estimate of intake of individual chemicals can be achieved provided that dosing solutions are prepared fresh at frequent intervals (e.g., 48 to 72 hr) and that comprehensive analyses are carried out.
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PMID:Toxicology studies of a chemical mixture of 25 groundwater contaminants. I. Chemistry development. 261 71

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

11-Azapentacyclo[6.2.1.0.0.0]decane (6a) as well as its 6,7-dimethyl derivative 6b was synthesized by a novel, four-step sequence that holds promise for the construction of a variety of cage compounds with bridging nitrogen atoms. The hydrochloride salt of 6a was shown to possess no antiviral activity against either the influenza virus A/Victoria/3/75 or the herpes simplex viruses HSV-1 and HSV-2.
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PMID:Synthesis and antiviral activity of 11-azapentacyclo[6.2.1.0.0.0]decane. 298 19

Native chromatin aggregates under isotonic conditions so it is generally studied using higher or lower salt concentrations. This has led to different interpretations of how transcription might occur. Studies using hypertonically-isolated preparations suggest that DNA functions in close association with a skeletal nuclear substructure, the matrix or cage, but such a structure is not usually seen under hypotonic conditions (e.g., in 'Miller-spreads'). Using a novel method for preparing chromatin under isotonic conditions we have investigated the site of transcription. We find that all three constituents of the transcription complex, nascent transcripts, active RNA polymerase and genes being transcribed are all closely associated with some structure too large to be electroeluted from the nucleus. Hypotonic treatment partly disrupts this association. We suggest a model for transcription that involves the participation of a nucleoskeleton at the active site and reconcile the contradictory results obtained using different salt concentrations.
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PMID:Transcription occurs at a nucleoskeleton. 299 Sep 13


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