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R A Lerch

Publications and source records attributed to R A Lerch.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of predicted amino acid sequences of measles virus strains in the Edmonston vaccine lineage.

Protein-encoding nucleotide sequences of the N, P, M, F, H, and L genes were determined for a low-passage isolate of the Edmonston wild-type (wt) measles virus and five Edmonston-derived vaccine virus strains, including AIK-C, Moraten, Schwarz, Rubeovax, and Zagreb. Comparative analysis demonstrated a high degree of nucleotide sequence homology; vaccine viruses differed at most by 0. 3% from the Edmonston wt strain. Deduced amino acid sequences predicted substitutions in all viral polypetides. Eight amino acid coding changes were common to all vaccine viruses; an additional two were conserved in all vaccine strains except Zagreb. Comparisons made between vaccine strains indicated that commercial vaccine lots of Moraten and Schwarz had identical coding regions and were closely related to Rubeovax, while AIK-C and Zagreb diverged from the Edmonston wt along slightly different paths. These comparisons also revealed amino acid coding substitutions in Moraten and Schwarz that were absent from the closely related reactogenic Rubeovax strain. All of the vaccine viruses contained amino acid coding changes in the core components of the virus-encoded transcription and replication apparatus. This observation, combined with identification of noncoding region nucleotide changes in potential cis-acting sequences of the vaccine strains (C. L. Parks, R. A. Lerch, P. Walpita, H.-P. Wang, M. S. Sidhu, and S. A. Udem, J. Virol. 75:921-933, 2001), suggest that modulation of transcription and replication plays an important role in attenuation.

Amino Acid Sequence↗
PubMed2001

Analysis of the noncoding regions of measles virus strains in the Edmonston vaccine lineage.

The noncoding sequence of five Edmonston vaccine viruses (AIK-C, Moraten, Rubeovax, Schwarz, and Zagreb) and those of a low-passage Edmonston wild-type (wt) measles virus have been determined and compared. Twenty-one nucleotide positions were identified at which Edmonston wt and one or more vaccine strains differed. The location of some of these nucleotide substitutions suggests that they may influence the efficiency of mRNA synthesis, processing, and translation, as well as genome replication and encapsidation. Five nucleotide substitutions were conserved in all of the vaccine strains. Two of these were in the genomic 3'-terminal transcriptional control region and could affect RNA synthesis or encapsidation. Three were found within the 5'-untranslated region of the F mRNA, potentially altering translation control sequences. The remaining vaccine virus base changes were found in one to four vaccine strains. Their genomic localization suggests that some may modify cis-acting regulatory domains, including the Kozak consensus element of the P and M genes, the F gene-end signal, and the F mRNA 5'-untranslated sequence.

5' Untranslated Regions↗
PubMed1999

Enhanced measles virus cDNA rescue and gene expression after heat shock.

Rescue of negative-stranded RNA viruses from full-length genomic cDNA clones is an essential technology for genetic analysis of this class of viruses. Using this technology in our studies of measles virus (MV), we found that the efficiency of the measles virus rescue procedure (F. Radecke et al., EMBO J. 14:5773-5784, 1995) could be improved by modifying the procedure in two ways. First, we found that coculture of transfected 293-3-46 cells with a monolayer of Vero cells increased the number of virus-producing cultures about 20-fold. Second, we determined that heat shock treatment increased the average number of transfected cultures that produced virus another two- to threefold. In addition, heat shock increased the number of plaques produced by positive cultures. The effect of heat shock on rescue led us to test the effect on transient expression from an MV minireplicon. Heat shock increased the level of reporter gene expression when either minireplicon DNA or RNA was used regardless of whether complementation was provided by cotransfection with expression plasmids or infection with MV helper virus. In addition, we found that MV minireplicon gene expression could be stimulated by cotransfection with an Hsp72 expression plasmid, indicating that hsp72 likely plays a role in the effect of heat shock.

Animals↗
PubMed1998

Estrogen receptor alpha requires no accessory factors for high-affinity binding to a consensus response element.

Estrogen receptor (ER) alpha is commonly thought to bind to a consensus estrogen response element (ERE) as a homodimer, but previous experiments have not ruled out the presence of other proteins in the ERalpha/ERE complex. To characterize this interaction in more detail, we overexpressed mouse (m) ERalpha in a baculovirus system, using the selective advantage of the apoptosis inhibitor p35. Recombinant mERalpha possesses the predicted molecular weight and binds 17beta-estradiol and an oligonucleotide containing a consensus vitellogenin ERE with high affinity. Over a wide concentration range of mERalpha protein (0.1-50 nM), only one complex was detected between mERalpha and vitellogenin ERE in gel shift assays. The ratio of E2:vitellogenin ERE bound by mERalpha was close to 2:1, and each complex contained only one ERE. The molecular weight of the complex was determined to be 160 000, very close to that predicted for two mERalpha proteins and one ERE oligonucleotide, therefore providing strong evidence that no other proteins were present. Recombinant mERalpha was purified such that it was the only protein observable by silver stain. Purified mERalpha and mERalpha in a nuclear extract behaved identically in Ferguson analysis, providing more evidence that only mERalpha was binding to the ERE. Purified mERalpha bound vitellogenin ERE with high affinity (Kd = 0. 92 +/- 0.20 nM), indicating that no other proteins are necessary for high-affinity mERalpha interaction with a consensus ERE. To determine whether ERalpha in an estrogen-responsive mammalian tissue behaves the same as the overexpressed mERalpha, we tested rat uterine cytosol by Ferguson analysis. ERalpha in rat uterine cytosol behaved identically to overexpressed mERalpha, suggesting that ERalpha in the uterine extract also binds to DNA predominantly as a homodimer with no additional proteins.

Animals↗
PubMed1993

The 35-kilodalton protein gene (p35) of Autographa californica nuclear polyhedrosis virus and the neomycin resistance gene provide dominant selection of recombinant baculoviruses.

Autographa californica nuclear polyhedrosis virus (AcMNPV) recombinants were constructed to test the effectiveness of the AcMNPV 35-kilodalton protein gene (35K gene) and the bacterial neomycin resistance gene (neo) as dominant selectable markers for baculoviruses. Insertion of the AcMNPV apoptosis suppressor gene (p35) into the genome of p35-deletion mutants inhibited premature host cell death and increased virus yields up to 1200-fold at low multiplicities in Spodoptera frugiperda (SF21) cell cultures. When placed under control of an early virus promoter, the bacterial neomycin resistance gene (neo) restored multiplication of AcMNPV in the same cells treated with concentrations of the antibiotic G418 that inhibited wild-type virus growth greater than 1000-fold. The selectivity of these dominant markers was compared by serial passage of recombinant virus mixtures. After four passages, the proportion of p35-containing virus increased as much as 2,000,000-fold relative to deletion mutants, whereas the proportion of neo-containing viruses increased 500-fold relative to wild-type virus under G418 selection. The strength and utility of p35 as a selectable marker was further demonstrated by the construction of AcMNPV expression vectors using polyhedrin-based transfer plasmids that contain p35. Recombinant viruses with foreign gene insertions at the polyhedrin locus accounted for 15 to 30% of the transfection progeny. The proportion of desired viruses was increased to greater than 90% by linearizing the parental virus DNA at the intended site of recombination prior to transfection. These results indicate that p35 and neo facilitate the selection of baculovirus recombinants and that p35, in particular, is an effective marker for the generation of AcMNPV expression vectors.

Animals↗
PubMed1992

Polylactosaminoglycan modification of the respiratory syncytial virus small hydrophobic (SH) protein: a conserved feature among human and bovine respiratory syncytial viruses.

We investigated the nature of the oligosaccharide modification of the glycosylated forms of the small hydrophobic integral membrane protein, SH (previously designated 1A), of respiratory syncytial (RS) virus. Analysis of SH protein expressed in cells infected with RS virus or with a recombinant vaccinia virus revealed two glycosylated SH protein species, SHg and SHp, which contained N-linked carbohydrate residues. SHp migrated diffusely on polyacrylamide gels, which suggested modification by polylactosaminoglycan oligosaccharides. Polylactosaminoglycan modification of SHp was established from three lines of investigation: (1) the synthesis of SHp in a cell line (IdID) conditionally defective in the ability to add specific carbohydrate residues to N- or O-linked oligosaccharide chains required the addition of galactose, which is a component of the N-acetyllactosamine repeating unit; (2) SHp was sensitive to digestion with endo-beta-galactosidase, which cleaves the beta 1-4 linkage between galactose and N-acetylglucosamine of the repeated N-acetyllactosamine subunit; and (3) SHp was selected by Datura stramonium lectin (Dsl), which has specificity for polylactosaminoglycans. The presence of SHp as a component of purified human subgroups A and B and bovine RS virus particles was demonstrated by Dsl affinity selection. In addition to SHp, nonglycosylated SHo was selected by Dsl affinity, indicating that SHp and SHo may associate to form complexes within infected cells and virus particles. To identify conserved amino acid residues among the human and bovine SH glycoproteins that may function as signals for polylactosaminoglycan modification, the nucleotide sequences of the SH protein genes of a human subgroup B virus (8/60) and a bovine virus (391-2) were determined and compared to those of a human subgroup A virus (A2), a subgroup B virus (18537), and a bovine virus (A51908). A comparison of the deduced amino acid sequences of the human and bovine RS virus SH proteins indicated that a central hydrophobic region and the presence of potential N-linked glycosylation sites on either side of the central hydrophobic region were conserved features that may be required for the polylactosaminoglycan modification of SH.

Amino Acid Sequence↗
PubMed1992

Bovine respiratory syncytial virus nucleocapsid protein: mRNA sequence analysis and expression from recombinant vaccinia virus vectors.

The nucleotide sequence of the mRNA encoding the nucleocapsid (N) protein of bovine respiratory syncytial (BRS) virus, strain 391-2, was determined. Recombinant vectors containing a cDNA of the complete N gene were constructed, and expression of the N protein in eukaryotic cells was demonstrated using two different vector systems. The BRS virus N mRNA was 1197 nucleotides in length, exclusive of poly(A), and had a single major open reading frame that encoded a polypeptide of 391 amino acids with a calculated M(r) of 42.6K. The nucleotide and amino acid sequences of the BRS virus N gene were compared to those of human respiratory syncytial (HRS) virus strains A2 and 18537, and to BRS virus strain A51908. The level of nucleic acid identity between the N mRNA of BRS virus 391-2 and both HRS virus subtypes was 80 to 81%, whereas the identity between the two BRS virus strains was 97%. A 93 to 94% level of identity was observed between the deduced amino acid sequences of the N protein of BRS virus 391-2 and the corresponding sequences of the two HRS virus strains. The two BRS virus N proteins differed in amino acid sequence at only three positions. Recombinant BRS virus N protein was expressed using two different vector systems: in cells from a plasmid using the vaccinia virus/T7 polymerase expression system or from a recombinant vaccinia virus. N proteins synthesized by the two vector systems migrated with an electrophoretic mobility identical to that of authentic BRS virus N protein, and were precipitated by anti-BRS virus antibodies.

Amino Acid Sequence↗
PubMed1992

The baculovirus-integrated retrotransposon TED encodes gag and pol proteins that assemble into viruslike particles with reverse transcriptase.

TED is a lepidopteran retrotransposon found inserted within the DNA genome of the Autographa californica nuclear polyhedrosis virus mutant, FP-D. To examine the proteins and functions encoded by this representative of the gypsy family of retrotransposons, the gag- and pol-like open reading frames (ORFs 1 and 2) were expressed in homologous lepidopteran cells by using recombinant baculovirus vectors. Expression of ORF 1 resulted in synthesis of an abundant TED-specific protein (Pr55gag) that assembled into viruslike particles with a diameter of 55 to 60 nm. Expression of ORF 2, requiring a -1 translational frameshift, resulted in synthesis of a protease that mediated cleavage of Pr55gag to generate p37, the major protein component of the resulting particles. Expression of ORF 2 also produced reverse transcriptase that associated with these particles. Both protease and reverse transcriptase activities mapped to domains within ORF 2 that contain sequence similarities with the corresponding functional domains of the pol gene of the vertebrate retroviruses. These results indicated that TED ORFs 1 and 2 functionally resemble the retrovirus gag and pol genes and demonstrated for the first time that an invertebrate member of the gypsy family of elements encodes active forms of the structural and enzymatic functions necessary for transposition via an RNA intermediate. TED integration within the baculovirus genome thus represents one of the first examples of transposon-mediated transfer of host-derived genes to an eukaryotic virus.

Animals↗
PubMed1991

Nucleotide sequence analysis of the bovine respiratory syncytial virus fusion protein mRNA and expression from a recombinant vaccinia virus.

Bovine respiratory syncytial (BRS) virus is an important cause of serious respiratory illness in calves. The disease caused in calves is similar to that caused by human respiratory syncytial (HRS) virus in children. The two viruses, however, have distinct host ranges and the attachment glycoproteins, G, have no antigenic cross-reactivity. The fusion glycoproteins, F, of the HRS and BRS viruses, however, have some antigenic cross-reactivity. To further compare the BRS virus and HRS virus fusion proteins, we determined the nucleotide sequence of cDNA clones to the BRS virus F protein mRNA, deduced the amino acid sequence, and compared these sequences with the HRS virus F protein sequences. The BRS virus F mRNA was 1899 nucleotides in length and had a single major open reading frame which could code for a polypeptide of 574 amino acids with an estimated molecular weight of 63.8 kDa. Structural features predicted from the amino acid sequence included an NH2-terminal signal sequence (residues 1-26), a site for proteolytic cleavage (residues 131-136) to generate the disulfide-linked F1 and F2 subunits, and a hydrophobic transmembrane anchor sequence (residues 522-549). The nucleic acid identity between the BRS virus and the HRS virus F mRNA sequences was 71.5%. The predicted BRS virus F protein shared 80.5% overall amino acid identity with the HRS virus F protein with 89% identity in the F1 polypeptide but only 68% identity in the F2 polypeptide. The position and number of the cysteine residues in the F1 and F2 polypeptides were conserved among all F proteins. However, BRS virus F protein had only three potential N-linked carbohydrate acceptor sites in comparison to four or five for the HRS viruses. A difference in the extent of glycosylation between the BRS and HRS virus F2 polypeptides was shown to be responsible for differences observed in the electrophoretic mobility of these proteins. A cDNA containing the complete open reading frame of the BRS virus F mRNA was inserted into the thymidine kinase gene of vaccinia virus and following homologous recombination, a recombinant virus containing the BRS virus F gene was isolated. The BRS virus F protein was expressed in recombinant virus infected cells as demonstrated by immunoprecipitation and was transported to and expressed on the surface of infected cells as shown by indirect immunofluorescence.

Amino Acid Sequence↗
PubMed1990

Nucleotide sequence analysis and expression from recombinant vectors demonstrate that the attachment protein G of bovine respiratory syncytial virus is distinct from that of human respiratory syncytial virus.

Bovine respiratory syncytial (BRS) virus causes a severe lower respiratory tract disease in calves similar to the disease in children caused by human respiratory syncytial (HRS) virus. While there is antigenic cross-reactivity among the other major viral structural proteins, the major glycoprotein, G, of BRS virus and that of HRS virus are antigenically distinct. The G glycoprotein has been implicated as the attachment protein for HRS virus. We have carried out a molecular comparison of the glycoprotein G of BRS virus with the HRS virus counterparts. cDNA clones corresponding to the BRS virus G glycoprotein mRNA were isolated and analyzed by dideoxynucleotide sequencing. The BRS virus G mRNA contained 838 nucleotides exclusive of poly(A) and had a major open reading frame coding for a polypeptide of 257 amino acid residues. The deduced amino acid sequence of the BRS virus G polypeptide showed only 29 to 30% amino acid identity with the G protein of either the subgroup A or B HRS virus. However, despite this low level of identity, there were strong similarities in the predicted hydropathy profiles of the BRS virus and HRS virus G proteins. A cDNA molecule containing the complete BRS virus G major open reading frame was inserted into the thymidine kinase gene of vaccinia virus by homologous recombination, and a recombinant virus containing the BRS virus G protein gene was isolated. This recombinant virus expressed the BRS virus G protein, as demonstrated by Western immunoblot analysis and immunofluorescence of infected cells. The BRS virus G protein expressed from the recombinant vector was transported to and expressed on the surface of infected cells. Antisera to the BRS virus G protein made by using the recombinant vector to immunize animals recognized the BRS virus attachment protein but not the HRS virus G protein and vice versa, confirming the lack of antigenic cross-reactivity between the BRS and HRS virus attachment proteins. On the basis of the data presented here, we conclude that BRS virus should be classified within the genus Pneumovirus in a group separate from HRS virus and that it is no more closely related to HRS virus subgroup A than it is to HRS virus subgroup B.

Amino Acid Sequence↗
PubMed1989

Characterization of bovine respiratory syncytial virus proteins and mRNAs and generation of cDNA clones to the viral mRNAs.

We have characterized the proteins and mRNAs of bovine respiratory syncytial (BRS) virus strain 391-2 and constructed cDNA clones corresponding to 9 of the 10 BRS virus mRNAs. The proteins of BRS virus-infected cells were compared with the proteins from human respiratory syncytial (HRS) virus-infected cells. Nine proteins specific to BRS virus-infected cells, corresponding to nine HRS virus proteins, were identified. Only a BRS virus polymerase protein remains to be identified. The BRS virus G glycoprotein showed major antigenic differences from the HRS virus G glycoprotein by immunoprecipitation and Western (immuno-) blot analysis, whereas the BRS virus F, N, M, and P proteins showed antigenic cross-reactivity with their HRS virus counterparts. Analysis of RNAs from BRS virus-infected cells showed virus-specific RNAs which had electrophoretic mobilities similar to those of mRNAs of HRS virus but which hybridized poorly or not at all with HRS virus-specific probes in Northern (RNA) blot analysis. To analyze the BRS virus RNAs further, cDNA clones to the BRS virus mRNAs were generated. Nine separate groups of clones were identified and shown to correspond to nine BRS virus mRNAs by Northern blot analysis. A 10th BRS virus large mRNA was identified by analogy with the HRS virus polymerase mRNA. These data show that like HRS virus, BRS virus has 10 genes coding for 10 mRNAs.

Antibodies, Monoclonal↗
PubMed1988

Assessment of myocardial metabolism with iodine-123 heptadecanoic acid: effect of decreased fatty acid oxidation on deiodination.

Terminally radioiodinated fatty acid analogs are of potential use for the noninvasive delineation of regional alterations of fatty acid metabolism by gamma imaging. Since radioactivity from extracted iodine-123 heptadecanoic acid [( 123I]HDA) is released from the myocardium in form of free radioiodide (123I-) the present study was performed to determine whether deiodination of [123I]HDA is related to free fatty acid metabolism. Myocardial production of free radioiodide was measured in rat hearts in vitro and in vivo both under control conditions and after inhibition of fatty acid oxidation. In isolated rat hearts perfused at constant flow with a medium containing [123I]HDA, release of 123I- was markedly reduced during cardioplegia and pharmacologic inhibition of mitochondrial fatty acid transfer with POCA by 67% (p less than 0.005) and 72% (p less than 0.005), respectively. In fasted rats in vivo, 1 min after i.v. injection of [123I]HDA, 51 +/- 5% of myocardial radioactivity was recovered in the aqueous phase, containing free iodide, of myocardial lipid extracts. Aqueous activity was significantly decreased in fed (20 +/- 2%; p less than 0.002) and POCA pretreated (30 +/- 3.7%; p less than 0.05) animals exhibiting reduced oxidation of [14C]palmitate. Thus, deiodination of [123I]HDA was consistently reduced during inhibition of fatty acid oxidation in vitro and in vivo. The results apply to the interpretation of myocardial clearance curves of terminally radioiodinated fatty acid analogs.

Animals↗
PubMed1987

Effect of acetylation on arthropathic activity of group A streptococcal peptidoglycan-polysaccharide fragments.

Purified group A streptococcal peptidoglycan-polysaccharide (PG-PS) fragments were either de-O-acylated, or acetylated and then de-O-acylated to yield N-acetylated PG-PS. Native PG-PS was poorly degraded, N-acetylated PG-PS was extensively degraded, and de-O-acylated PG-PS was only slightly degraded by hen egg white lysozyme. N-acetylated PG-PS was also extensively degraded by human lysozyme and partially degraded by rat serum or rat liver extract. After a single intraperitoneal injection of rats with a sterile, aqueous suspension, all PG-PS preparations induced acute arthritis. The acute arthritis induced by N-acetylated PG-PS was significantly more severe than that induced by native PG-PS; that induced by de-O-acylated PG-PS was of intermediate severity. After the acute reaction, rats injected with native PG-PS developed chronic relapsing erosive synovitis which remained severe for the duration of the experiment (83 days). In contrast, joint inflammation induced by N-acetylated PG-PS resolved within 6 weeks with little evidence of recurrent disease. Chronic arthritis induced by de-O-acylated PG-PS was of intermediate severity. In another assay of arthropathic activity, the arthritis in all rat ankle joints, which had been injected directly with native PG-PS, could be reactivated 3 weeks later by the intravenous injection of a small dose of PG. In contrast, only 50% of the joints initially injected with de-O-acylated PG-PS and none of the joints injected with N-acetylated PG-PS could be reactivated. These studies support the concepts that the resistance of PG-PS to muralytic digestion is crucial for chronic arthropathic activity and that the nature and degree of PG acetylation are important molecular determinants of the phlogistic activities of PG-PS polymers.

Acetylation↗
PubMed1985

Assessment of myocardial metabolism with 11C-palmitate. Comparison with 123I-heptadecanoic acid.

Carbon-11 (11C)-palmitate is chemically identical to its physiological counterpart. After intravenous injection the myocardial distribution of 11C-activity can be measured accurately by positron emission tomography. Regions of decreased 11C-palmitate uptake can be readily identified and their size quantified. Results obtained in dogs with experimental coronary thrombosis and in patients with myocardial infarction indicate that positron emission tomography with 11C-palmitate allows non-invasive assessment of the metabolic recovery of the myocardium after lysis of the occluding coronary thrombus. There is experimental evidence that the rate of clearance of 11C-palmitate activity from the myocardium is related to oxidative fatty acid metabolism. In dogs, a restriction of the oxygen supply to the myocardium results in a decrease in the rate of 11C-clearance independently of whether myocardial perfusion is concomitantly reduced or not. Similarities in myocardial uptake and clearance exist between iodine-123 (123I)-heptadecanoic acid and 11C-palmitate. However, interpretation of the kinetics of the radio-iodinated fatty acid analogue has to take into account the different intracellular fate of the iodine label compared with the fatty acid structure.

Animals↗
PubMed1983

Noninvasive detection of coronary thrombi with In-111 platelets: concise communication.

The need for rapid, definitive identification of coronary thrombosis has been intensified by the advent of thrombolytic therapy and by interest in the role of thrombosis in the etiology of coronary artery disease. To determine whether platelet thrombi can be detected noninvasively with In-111 platelets, a method was developed in which Tc-99m-tagged red blood cells were used to correct for activity within the blood attributable to platelets circulating but not associated with thrombus. In 18 dogs coronary thrombi were induced closed-chest with a copper coil introduced into the coronary artery. Indium-111 platelets and Tc-99m RBCs were administered either before or 1 hr after induction of thrombus, and serial scintigrams obtained. Coronary thrombus was identified readily in the processed scintigrams. In six dogs, thrombolysis was achieved with intracoronary streptokinase. In each case serial scintigraphy demonstrated resolution of the clot. The dual radiotracer technique should permit serial noninvasive delineation of the temporal relationship between platelet deposition and coronary heart disease in patients, and should facilitate the evaluation of interventions designed to prevent platelet aggregation or to lyse existing thrombi.

Animals↗
PubMed1982

Temporal dependence of beneficial effects of coronary thrombolysis characterized by positron tomography.

To delineate beneficial effects of intracoronary thrombolysis on myocardial metabolism in vivo and their dependence on the interval after coronary occlusion prior to reperfusion, we studied 23 closed-chest dogs. Coronary occlusion was produced with a thrombogenic copper coil to performance of cardiac positron emission tomography with 11C-palmitate. Jeopardized zones were calculated by summation by myocardial regions exhibiting less than 50 percent of the peak left ventricular wall radioactivity, and residual metabolic activity within jeopardized zones quantified based on the average counts compared with average counts in normal myocardium. After tomography, streptokinase was infused into the coronary artery (4,000 units per minute), resulting in angiographically demonstrable restoration of patency. Repeat tomography performed 90 minutes after the initial study with a second injection of 11C-palmitate demonstrated reduction of jeopardized zones by 51 +/- 6.3 percent (SE) and by 21 +/- 1.8 (p less than 0.01 based on paired comparisons) when refusion was initiated 1 to 2 (in four dogs) or 2 to 4 (in six dogs) hours after occlusion. Metabolic activity in initially jeopardized regions increased by 111 +/- 24.3 percent and 61.8 +/- 12.6 (p less than 0.01 for each). When streptokinase was infused later after occlusion, significant salutary metabolic effects did not occur. These results indicate that positron tomography may be useful in the clinical delineation of the efficacy of thrombolytic therapy in restoring myocardial metabolism and underscore the marked dependence of such efficacy on the duration of the interval of ischemia prior to the onset of reperfusion.

Animals↗
PubMed1982

Kinetics of positron emitters in vivo characterized with a beta probe.

To facilitate characterization of regional myocardial kinetics of positron-emitting tracers in vivo without distortion by activity outside the region of interest, a probe was developed and evaluated for monitoring radioactivity by detection of positrons themselves. These particles (beta particles) have a maximal range in tissue of only few millimeters rather than the larger range of gamma photons emitted as a result of positron annihiliation. Regional myocardial time-activity curves were determined in open-chest dogs after intracoronary injection of 0.5-1.5 mCi [15O]H2O, a tracer used for measurement of myocardial blood flow, or 6.0-8.0 mCi [11C]palmitate, a tracer used for noninvasive assessment of myocardial metabolism. Time-activity curves after [11C]palmitate injection clearly delineated specific components of myocardial tracer clearance previously identified in vitro in isolated perfused hearts. Myocardial washout of [15O]H2O was monoexponential for more than 2 min without distortion induced by recirculating tracer in ventricular blood. Reproducibility of measured tracer clearance rates during monoexponential clearance was high based on duplicate determinations for both tracers. The beta-detector probe developed overcomes several intrinsic limitations of gamma-probe systems or well counting of serial myocardial biopsies for studies of positron-emitting tracers in vivo and should facilitate assessment of factors of influencing tracer kinetics in vivo relevant to positron-emission tomography.

Animals↗