Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effects of angiotensin II (A-II) antagonist, propranolol and prostaglandin F2 alpha (PGF2 alpha) on arterial hypoxemia after injecting autologous muscle to induce massive pulmonary embolism. Twenty-four anesthetized paralyzed dogs were divided into four groups; control, intravenous A-II antagonist (1-sarcosine, 8-isoleucine A-II) infusion at 5 micrograms.kg-1.min-1, intravenous propranolol injection at 1.5-2.0 mg, and intravenous PGF2 alpha infusion at 1 microgram.kg-1.min-1. With FIO2 of 0.33, the administration of A-II antagonist produced an increase in arterial PO2 from 134 +/- 16 (mean +/- SE) to 155 +/- 11 mmHg during infusion, and to 160 +/- 9 mmHg 30 min after infusion. Simultaneous hemodynamic measurements demonstrated no significant changes in arterial blood pressure and heart rate, but a slight increase in cardiac output was observed. On the other hand, propranolol and PGF2 alpha did not reverse the pulmonary oxygenation. Cardiac output decreased after propranolol, and alveolar dead space and pulmonary artery pressure increased further after PGF2 alpha. We conclude that A-II antagonist may be effective in the treatment of massive pulmonary embolism, possibly by improving the ventilation-perfusion relationship. The exact mechanism of the effect of A-II antagonist has not been clarified.
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PMID:[The effectiveness of angiotensin II antagonist on experimental pulmonary embolism--comparison of propranolol with prostaglandin F2 alpha]. 224 4

A mutant antithrombin was isolated from the plasma of a patient with pulmonary embolism. The new protein, which accounted for 55% of the antithrombin, had decreased heparin affinity and contained two components when analysed on the basis of either charge or molecular mass. Sialidase and endo-beta-N-acetylglucosaminidase F treatment suggested that this heterogeneity was due to a partial glycosylation occurring at a new carbohydrate attachment sequence. Peptide mapping by reverse-phase HPLC showed that the abnormality involved the N-terminal tryptic peptide. Sequence analysis demonstrated that the underlying mutation was 7 Ile----Asn which introduces a new Asn-Cys-Thr glycosylation sequence. This new oligosaccharide attachment site occupies the base of the proposed heparin-binding site, and the finding explains the consequent decrease in heparin affinity.
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PMID:New carbohydrate site in mutant antithrombin (7 Ile----Asn) with decreased heparin affinity. 316 32

Previously, we showed that labeled bitistatin analogues possessed excellent characteristics for imaging both deep-vein thrombosis and pulmonary embolism. We hypothesized that the N-terminal amino acid sequence of bitistatin, which is different from other disintegrins, likely interacts with the binding site of platelets to confer desirable properties to bitistatin for imaging. In this study, we present the design, synthesis, and initial biological testing of a short-chain analogue of the native 83-amino-acid bitistatin sequence. Our initial molecular modeling of the binding loop of bitistatin showed that the minimal sequence that represented the binding region was a cyclic 10 amino acid sequence cyclo[Cys-Arg-Ile-Ala-Arg-Gly-Asp-Trp-Asn-Cys(S)]. Systematic modeling of a truncated N-terminal sequence of bitistatin fused with the optimized binding region having a thioether sequence through a Gaba spacer ultimately yielded the 24-amino acid peptide, cyclo-[CH(2)CO-Arg-Ile-Ala-Arg-Gly-Asp-Trp-Asn-Cys(S-)]-Gaba-Gly-Asn-Glu-Ile-Leu-Glu-Gln-Gly-Glu-Asp-Ser-Asp-Ser-Lys-OH, 1. The peptide was then coupled to the hydrazino-nicotinic acid bifunctional chelating agent and the purified adduct labeled with (99m)Tc using tricine as a coligand. Binding of the unlabeled and labeled peptide to stimulated human platelets was assayed in vitro. The (99m)Tc labeling yield was > 90%. The in vitro binding assays showed that the IC(50) for inhibition of platelet aggregation was 3694 nM, while the Kd of the (99m)Tc labeled peptide was 185 nM, indicating moderate affinity for the receptor. The (99m)Tc-labeled peptide was able to identify sites of experimental thrombi and emboli in a canine model. The results suggest initial success in attempting to mimic the behavior of bitistatin for imaging thrombi and emboli.
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PMID:Design and synthesis of a short-chain bitistatin analogue for imaging thrombi and emboli. 1536 61