ABSTRACT
Although Tl-201 rest redistribution SPECT is widely used to assess myocardial viability, there is no agreement on the best prognostic marker of left ventricle contraction improvement after revascularization. More recent data suggest that not only rest or redistribution uptake but also reverse redistribution patterns may serve to indicate the viability of myocardium. The aim of this study was to define criteria (which include reversibility and reverse redistribution) for viability testing and prediction of functional outcome in Tl-201 rest redistribution SPECT. Twenty-five patients with left ventricle dyssynergy were studied before and after revascularization with Tl-201 SPECT and echocardiography. Perfusion and contractility was assessed in a 16-segment model of the left ventricle. Out of 400 left ventricular segments, contraction disturbances of various degree of intensity (hypokinesis, akinesis and dyskinesis) were found by echocardiography in 107 segments. Revascularization was performed in 97 segments. In 57% of the segments, improvement of contraction was observed after PTCA or CABG. Perfusion was analysed in the segments between segments with and without contraction improvement. In discriminant analysis, only the modulus of difference between rest and redistribution study > or = 10% was the common parameter for hypo-, a- and dyskinetic segments to predict the functional recovery of left ventricle (LV) with the specificity of 93% and sensitivity of 78%. The modulus of segmental quantitative difference between redistribution and rest image is a new parameter adding specificity to Tl-201 rest redistribution SPECT in prediction of recovery of left ventricle function.
Subject(s)
Myocardial Contraction/physiology , Myocardial Revascularization/methods , Thallium Radioisotopes , Tomography, Emission-Computed, Single-Photon/methods , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/therapy , Adult , Aged , Angioplasty, Balloon, Coronary/methods , Coronary Angiography/methods , Coronary Artery Bypass/methods , Echocardiography, Doppler/methods , Female , Humans , Male , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/diagnosis , Preoperative Care , Probability , Sensitivity and Specificity , Severity of Illness Index , Thallium Radioisotopes/pharmacokinetics , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/etiologyABSTRACT
Cardiovascular diseases especially coronary heart diseases are responsible for high rate (about 50%) of deaths in the group of patients with irreversible renal failure treated with hemodialysis. Coronary artery bypass grafting is recommended as a method of choice in symptomatic patients with coronary heart disease being the candidate for renal transplantation. On the basis of recently observed patient successfully treated with coronary artery bypass grafting pre- and and postoperative dialysis protocol is presented and discussed with literature.
Subject(s)
Coronary Artery Bypass/methods , Coronary Disease/complications , Coronary Disease/diagnosis , Coronary Disease/surgery , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Renal Dialysis/methods , Clinical Protocols , Humans , Male , Middle Aged , Periodicity , Postoperative Care , Severity of Illness Index , Treatment OutcomeABSTRACT
The three human alpha adrenergic receptor subtypes, alpha 1a, alpha 1b, and alpha 1c, have been cloned, expressed in COS-7 cells, and characterized pharmacologically. Competition binding studies of several adrenergic ligands with the three human receptor subtypes reveals a distinct pharmacological profile for each receptor subtype. RNase protection analysis demonstrates that the three receptor subtypes have different patterns of distribution in human tissue. The availability of the three human alpha 1 receptor subtypes will facilitate the development of subtype-selective alpha 1 antagonists for a variety of therapeutic indications.
Subject(s)
Receptors, Adrenergic, alpha/genetics , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , DNA Primers/chemistry , Gene Expression , Humans , Molecular Sequence Data , RNA, Messenger/genetics , Rats , Receptors, Adrenergic, alpha/drug effects , Recombinant Proteins , Sequence Alignment , Sequence Homology, Amino Acid , Tissue DistributionABSTRACT
A human glucagon-like 1 peptide receptor has been cloned from the gastric tumor cell line HGT-1. The cDNA clone encodes a protein of 463 amino acids and is a member of the superfamily of seven transmembrane domain G protein coupled receptors. Transfection of the human GLP-1 receptor into COS-7 cells confers upon them high affinity binding for [125I] GLP-1 (7-36) amide. In membranes prepared from COS-7 cells transfected with the human GLP-1 receptor, the binding of [125I] GLP-1 (7-36) amide is inhibited with the rank order of potency GLP-1 (7-36) amide > glucagon > secretin, characteristic of a GLP-1 receptor. The human GLP-1 receptor is functionally coupled to increases in intracellular cAMP in these cells: incubation of COS-7 cells expressing the human GLP-1 receptor with GLP-1 (7-36) amide gives rise to a 4-fold increase in cyclic AMP over basal levels, with an EC50 of 25pM. Glucagon is also a full agonist but is 200-fold less potent than GLP-1 (7-36) amide in stimulating the human GLP-1 receptor.
Subject(s)
Receptors, Cell Surface/biosynthesis , Receptors, Cell Surface/genetics , Receptors, Glucagon , Amino Acid Sequence , Animals , Base Sequence , Cells, Cultured , Cloning, Molecular , DNA, Complementary/genetics , Glucagon/metabolism , Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor , Humans , Molecular Sequence Data , Peptide Fragments/metabolism , Protein Precursors/metabolism , Receptors, Cell Surface/classification , Recombinant Proteins/biosynthesis , Sequence Homology, Amino Acid , TransfectionABSTRACT
The D2 dopamine receptor is known to be functionally coupled when expressed in CHO cells, whereas the effector systems for the D3 dopamine receptor remain unclear. A chimeric, human D3/D2 receptor (hD3/D2) was constructed containing the third intracellular loop region of the D2 receptor. CHO cells stably expressing the D2, D3, or hD3/D2 receptors were created and the pharmacology of the receptors was examined. The chimeric hD3/D2 receptor retained D3-like affinities for dopaminergic ligands. However, in contrast to the D2 receptor neither the D3 receptor nor the hD3/D2 receptor could functionally couple to the adenylate cyclase or arachidonic acid release mechanisms.
Subject(s)
Receptors, Dopamine D2/metabolism , Receptors, Dopamine/metabolism , Recombinant Fusion Proteins/metabolism , Adenylyl Cyclases/metabolism , Amino Acid Sequence , Animals , Arachidonic Acid/metabolism , Base Sequence , CHO Cells , Calcimycin/pharmacology , Cell Membrane/metabolism , Colforsin/pharmacology , Cricetinae , Dopamine/pharmacology , Dopamine Agents/metabolism , Dopamine Antagonists , Haloperidol/pharmacology , Humans , Kinetics , Ligands , Molecular Sequence Data , Oligodeoxyribonucleotides , Polymerase Chain Reaction , Protein Structure, Secondary , Receptors, Dopamine/drug effects , Receptors, Dopamine/genetics , Receptors, Dopamine D2/drug effects , Receptors, Dopamine D2/genetics , Receptors, Dopamine D3 , Recombinant Fusion Proteins/drug effects , Sulpiride/metabolism , TransfectionABSTRACT
Human interleukin 4 is a 129 amino acid lymphokine secreted by activated T cells that exerts pleiotropic biological effects on B and T lymphocytes and other hematopoietic cells. Structure-function relations were studied by employing selective proteolytic cleavage of purified recombinant human interleukin 4 (rhuIL-4). Limited proteolysis with endoprotease Glu-C from Staphylococcus aureus (V8) produced two digestion products that were observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with apparent molecular weight values of 19K (I) and 15K (II), respectively. These species were isolated by reversed-phase HPLC. Amino acid sequencing indicated that species II was an 84 amino acid core fragment extending from Gln-20 to Glu-103 and containing a hydrolyzed peptide bond at Glu-26. On the basis of known disulfide bond assignments, it was concluded that species II was stabilized by two disulfide bonds (Cys-24/Cys-65 and Cys-46/Cys-99). Analysis of its secondary structure by circular dichroism revealed a high content of alpha helix. Species I was the full-length rhuIL-4 with selective cleavage at Glu-26 and Glu-103. Both species I and II were inactive in an in vitro assay based on proliferation of peripheral blood lymphocyte blasts and lacked the ability to bind to teh rhuIL-4 receptor on Daudi cells. In order to elucidate further the role of the residues removed by S. aureus V8 protease, rabbit antisera were raised to synthetic peptides corresponding to residues 1-26 at the N-terminus and 104-129 at the C-terminus. Only antisera directed to the C-terminal peptide inhibited binding of 125I-rhuIL-4 to Daudi cells.(ABSTRACT TRUNCATED AT 250 WORDS)
