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Biomedical subjects

M M Goodman

Publications and source records attributed to M M Goodman.

At least 73 records · Page 4Linked to original sources
PubMed1985

Design, synthesis, and evaluation of omega-iodovinyl- and omega-iodoalkyl-substituted methyl-branched long-chain fatty acids.

The synthesis of a new methyl-branched fatty acid, (E)-19-iodo-3(RS)-methyl-18-nonadecenoic acid (19), is described. Methyl branching has been introduced at the 3-position to inhibit beta-oxidation and radioiodide has been attached as a trans-vinyl iodide. Preparation of 19 involved a 15-step sequence of reactions climaxing with formation of the methyl ester 18 by iododestannylation of methyl (E)-19-(tri-n-butylstannyl)-3(RS)-methyl-18-nonadecenoate (17) resulting from the reaction of n-Bu3SnH with methyl 3(RS)-methyl-18-nonadecynoate (16). Methyl branching was introduced at an early stage by Friedel-Crafts acylation of thiophene with 3(RS)-methyl-4-carbomethoxybutanoyl chloride (3) generated from 3-methylglutaric anhydride. The new agent, [125I]-19, showed high myocardial uptake (5 min, 4.89% dose/g; 30 min, 3.32% dose/g), good heart/blood (H/B) ratios (5 min, 5.4/1; 30 min, 4.3/1), and significantly greater myocardial retention in fasted rats than the corresponding straight-chain analogue 19-[125I]-iodo-18-nonadecenoic acid (5 min, 3.52% dose/g, H/B = 4.8/1; 30 min, 1.19% dose/g, H/B = 1.6/1). Excellent myocardial images were obtained in rats after administration of [123I]-19 and confirmed the slow myocardial washout over a 60-min period. These data suggest that 19 is a good candidate for evaluation of heart disease involving aberrations in fatty acid metabolism by use of imaging techniques such as single photon emission computerized tomography (SPECT) where redistribution or washout should be minimized.

Animals↗
PubMed1985

Radioiodinated beta-methyl phenyl fatty acids as potential tracers for myocardial imaging and metabolism.

Since fatty acids provide the majority of myocardial energy requirements under basal conditions, an alteration in the global or regional utilization of these substrates may be an early indicator of myocardial disease. To determine areas of potential clinical utility of fatty acid imaging, we synthesized a radioiodinated modified fatty acid 14-(p-iodophenyl) beta methyltetradecanoic acid IPBMTA, which cannot undergo beta-oxidation. Preliminary biodistribution and imaging studies were performed in animals and man. These studies suggest that radioiodinated beta-methyl phenyl fatty acids localized rapidly in the myocardium and had prolonged myocardial retention time. The long residence time permits the recording of high quality planar and SPECT images.

Animals↗
PubMed1984

Accumulation of radioiodinated 15-(p-iodophenyl)-6-tellurapentadecanoic acid in ischemic myocardium during acute coronary occlusion and reperfusion.

The myocardial uptake of 15-(p-iodophenyl)-6- tellurapentadecanoic acid ( TPDA ) was studied in dogs during coronary occlusion and after reperfusion. In eight dogs with a 3 hour occlusion (Group A) with (n = 5) and without (n = 3) 30 minutes of reperfusion, iodine-125 TPDA uptake correlated well with microsphere myocardial blood flow over a wide range of flow levels (n = 111, r = 0.94). In six dogs with a 20 minute occlusion of the left anterior descending coronary artery and 1 hour of reperfusion (Group B), iodine-125 TPDA uptake correlated equally well with myocardial blood flow (n = 37, r = 0.90). There was no difference between the slopes of regression lines for Groups A and B, indicating no release from the myocardium of radioiodinated TPDA . Dual radiolabeling of TPDA was employed in five Group A animals by intravenous injection of iodine-125 TPDA during coronary occlusion and iodine-131 TPDA after reperfusion. In 63 myocardial samples, microsphere reperfusion flow and iodine-131 TPDA uptake were closely correlated (r = 0.91). As with monovalent cations, at myocardial flows higher than control flows, iodine-131 TPDA uptake was flow-limited. It is concluded that: 1) radioiodinated TPDA accurately reveals severely ischemic areas of myocardium without myocardial release of the radionuclide in coronary occlusions lasting 20 to 180 minutes and followed by reperfusion, and 2) double radiolabeled TPDA allows assessment of both occlusion and reperfusion flows. This compound may find an application in the measurement of infarct size and the evaluation of interventional therapies in acute myocardial infarction.

Animals↗
PubMed1984

Synthesis and evaluation of radioiodinated (E)-18-iodo-17-octadecenoic acid as a model iodoalkenyl fatty acid for myocardial imaging.

125I-labeled (E)-18-iodo-17-octadecenoic acid (13) has been prepared and evaluated in rats to determine the myocardial uptake and retention and degree of in vivo deiodination of this model iodovinyl-substituted fatty acid, which contains no structural perturbation to inhibit metabolism. This new agent was prepared by NaI-chloramine-T treatment of (17-carbomethoxyheptadec-1-en-1-yl)boronic acid (11) prepared by catecholborane treatment of methyl 17-octadecynoate (10), followed by basic hydrolysis to the free acid (13). The pivotal substrate, 17-octadecynoic acid (9), was prepared by two new routes. The 125I-labeled acid 13 showed high myocardial uptake (1 h, 1.90-2.28% dose/g) with 45% washout after 2 h but lower heart/blood ratios in comparison to analogues containing the tellurium heteroatom. Deiodination was low for the first 2 h after injection (2 h, 61% dose/g). Excellent myocardial images were obtained in a dog with the 123I-labeled agent.

Animals↗
PubMed1984

Synthesis and evaluation of radioiodinated terminal p-iodophenyl-substituted alpha- and beta-methyl-branched fatty acids.

Methods have been developed for the preparation of terminal p-idophenyl-substituted alpha- and beta-methyl-branched long-chain fatty acids. The syntheses and physical properties of 14-(p-iodophenyl)-2(RS)-methyltetradecanoic acid and 15-p-iodophenyl)-3(RS)-methylpentadecanoic acid are described. The radioiodinated agents are of interest as a result of the expected pronounced uptake and prolonged myocardial retention that may result from the inhibition of fatty acid metabolism. Tissue distribution studies in rats with 14-(p-[125I]iodophenyl)-2(RS)-methyltetradecanoic acid and 15-(p-[125I]iodophenyl)-3(RS)-methylpentadecanoic acid show significant heart uptake and prolonged retention accompanied by low in vivo deiodination and high blood levels. A comparison of the heart uptake of the radioiodinated methyl-branched fatty acids and their unbranched analogues has demonstrated a greater myocardial retention of the methyl-branched fatty acids than the unbranched analogues. These results suggest that the mechanism of myocardial retention results from steric or chemical inhibition of the metabolism of these fatty acids by the presence of the methyl group.

Animals↗
PubMed1984

Digoxin-quinidine-spironolactone interaction.

Digoxin kinetics are substantially altered by quinidine and by spironolactone. We evaluated the effect of the combination of quinidine and spironolactone on digoxin kinetics and compared it to the effect on digoxin of each drug alone. Six normal subjects each received a 1.0-mg intravenous dose of digoxin alone, digoxin with quinidine, digoxin with spironolactone, and digoxin with both quinidine and spironolactone. Spironolactone and quinidine, alone and in combination, reduced digoxin systemic, renal, and nonrenal clearances and prolonged digoxin elimination t 1/2. A greater alteration in digoxin kinetics was induced by quinidine than by spironolactone, and an even greater effect resulted from the combination. We did not assess clinical consequences of the interaction. We advise reduction in digoxin dose, careful clinical evaluation, and measurement of serum digoxin concentrations when digoxin is used in combination with quinidine and spironolactone.

Adult↗
PubMed1983

Inheritance, intracellular localization, and genetic variation of phosphoglucomutase isozymes in maize (Zea mays L.).

Phosphoglucomutase (PGM; EC 2.7.5.1) isozyme variants were studied in a large number of inbred lines, crosses, and races of maize (Zea mays L.). Patterns of Mendelian inheritance demonstrated for PGM isozyme variants indicated that they are encoded by nuclear genes. Two unlinked loci, Pgml and Pgm2, located on the long arm of chromosome 1 and the short arm of chromosome 5, respectively, specify the observed electrophoretic variation on starch gels. No intra- or interlocus hybrid bands were found, suggesting that each isozyme band consists of a single polypeptide. PGM isozymes were present in all plant parts studied and the activity specified by both loci appears to reside in the cytoplasm. In studies of 520 racial collections of maize from Latin America, a single allele at each locus predominated in most collections. Likewise, the same alleles predominated in a set of 406 inbred lines of maize from the United States and Canada.

Genetic Variation↗
PubMed1983

New myocardial imaging agents: stabilization of radioiodine as a terminal vinyl iodide moiety on tellurium fatty acids.

To determine the myocardial uptake and retention properties of radioiodinated tellurium fatty acids, we prepared two new tellurium fatty acids in which iodine-125 has been chemically stabilized by attachment as a trans-vinyl iodide (I-CH = CH-R-Te-R'-COOH) and evaluated them in rats. Fabrication of 18-iodo-13-tellura-17-octadecenoic acid was accomplished by coupling 1,5-diiodo-1-pentene with sodium 12-(methoxycarbonyl)-n-dodecan-1-yl telluride. The [5-125I]-1,5-diiodo-1-pentene was prepared by an organoborane technique involving 125I+ treatment of 5-iodo-1-penten-1-ylboronic acid [I(CH2)3CH = CHB(OH)2]. The absolute heart uptake of this agent was moderate (1.47-2.52% dose/g after 60 min), but the heart/blood ratios were low (approximately 2.6:1). Only marginal in vivo deiodination occurred, since the thyroid uptake was low (15-18% dose/g after 60 min). The effect of tellurium in position 13 was unexpected. To determine if the low heart specificity and low heart/blood ratios were dependent upon the position of the tellurium, we prepared an analogue with the same chain length, 18-[125I]iodo-7-tellura-17-octadecenoic acid, in the same manner by reaction of [11-125I]-1,11-diiodo-1-undecene with sodium 6-(methoxycarbonyl)-n-hexan-1-yl telluride. This agent showed pronounced heart uptake (2.47-3.94% dose/g after 60 min) and prolonged retention (1.76-3.14% dose/g after 4 h) in rats. Furthermore, the heart/blood ratios remained high for several hours (13:1 after 60 min; 9:1 after 4 h). Iodine-123 labeled 18-iodo-7-tellura-17-octadecenoic acid is an attractive new compound for evaluation as a myocardial imaging agent.

Animals↗
PubMed1982

Synthesis and biological evaluation of 17-[131I]iodo-9-telluraheptadecanoic acid, a potential imaging agent.

A method has been developed for the preparation of terminal halogenated tellurium fatty acids (X-R-Te-R'-COOH). The synthesis and physical properties of 17-bromo- and 17-iodo-9-telluraheptadecanoic acid (17-iodo-9-THDA) are described. The radiohalogenated agents are of interest as a result of their expected pronounced and prolonged heart uptake and potential use for evaluation of regional myocardial fatty acid metabolism. Evaluation in rats indicates that the myocardial uptake of 17-[131I]iodo-9-telluraheptadecanoic acid (17-[131I]iodo-9-THDA) is accompanied by significant in vivo deiodination. A comparison of the heart uptake and deiodination of 17-[131I]iodo-9-THDA and 16-[131I]iodopalmitic acid has demonstrated a close similarity in blood levels of radioactivity and thyroid uptake of radioiodide after administration of these agents to rats. These data suggest that the mechanism of deiodination of terminal radioiodinated alkanoic acids primarily results from direct cleavage of the carbon-iodine bond and not from loss of radioiodine from the final catabolite.

Animals↗
PubMed1982

Unique plasmid-like mitochondrial DNAs from indigenous maize races of Latin America.

Mitochondrial DNA from 81 races of Latin American maize were examined by agarose gel electrophoresis. Twelve South American races each contained two plasmid-like mtDNA molecules similar to those of the cytoplasmic male-sterile S type (cms-S). The plasmid-like elements from all 12 races, designated RU, appear to be identical. Both molecules appear in vitro as double-stranded linear DNAs terminated by repeated sequences arranged in reverse polarity (terminal inverted repeats). The larger molecule of the pair, R-1, contains about 7460 nucleotides. It shares considerable homology with the larger plasmid-like molecule of cms-S, S-1, but is about 1000 nucleotides longer than S-1, has a unique sequence of about 2576 nucleotides, and also contains a BamHI recognition site not present in S-1, R-2, the smaller plasmid-like element, consists of about 5450 nucleotides and appears to share complete homology with S-2, the smaller plasmid-like molecule of cms-S. Neither pollen sterility nor any other trait has been associated with the R-1 and R-2 plasmid-like mtDNAs. The BamHI restriction fragments of total mtDNA from the 12 RU cytoplasms display similar patterns, which differ only slightly but vividly from that of a normal maize standard, B73 x Mo17. BamHI restriction analysis of 22 additional races produced arrays similar to those of the RU cytoplasms, but which lacked plasmid-like mtDNAs. The taxonomic significance of this digestion pattern and of the RU cytoplasms is discussed. One Mexican race, Conico Norteño, has been shown to contain the cms-S cytoplasm.

Journal Article↗
PubMed1982

A new, well-retained myocardial imaging agent: radioiodinated 15-(p-lodophenyl)-6-tellurapentadecanoic acid.

A method involving the acid-catalyzed decomposition of a piperidyltriazene intermediate in the presence of radioiodide has been developed for the synthesis of radioiodinated 15-(p-iodophenyl)-6-tellurapentadecanoic acid. The iodine-125-labeled agent shows rapid, pronounced myocardial uptake in rats (5.30-6.45% injected dose/g after 5 min) and also exhibits the prolonged retention previously observed with 9-[123mTe]telluraheptadecanoic acid (9-123mTe]HDA). After 6 hr, the heart uptake remained high (3.89-5.33%) dose/g) and decreased only to 3.02-3.41% dose/g after 24 hr. Very low blood activity was detected (0.24-0.27% dose/g at 5 min; 0.29-0.32% dose/g at 6 hr) and the heart-to-blood ratios were high (22:1 at 5 min; 15:1 at 6 hr). Minimal deiodination was demonstrated by the low thyroid uptake (1.41-1.63% dose/g at 5 min; 5.33-7.08% dose/g at 6 hr). The rapid and pronounced uptake, prolonged myocardial retention, and low in vivo deiodination make this agent attractive for further evaluation.

Animals↗
PubMed1981

Malate dehydrogenase: viability of cytosolic nulls and lethality of mitochondrial nulls in maize.

Five independently inherited loci on five distinct chromosomes encode the mitochondrial and cytosolic isozymes of NAD-dependent malate dehydrogenase (MDH; L-malate:NAD+ oxidoreductase, EC 1.1.1.37). Multiple alleles, including electrophoretic nulls, occur for each locus. However, a single allele of normal activity at one of the three loci encoding the mitochondrial MDHs is sufficient for normal development, whereas plants with essentially no cytosolic MDH activity function normally. The requirement of a normal activity allele at one of the three structural loci encoding the mitochondrial MDHs demonstrates in plants that a commonly studied dehydrogenase enzyme is essential for normal embryogenesis.

Alleles↗
PubMed1981

F-18-labeled 3-deoxy-3-fluoro-D-glucose for the study of regional metabolism in the brain and heart.

Glucose is the major physiological substrate of the brain and an important physiological substrate for the myocardium. [19F]fluoro-3-deoxy-glucose [3-FDG(F-18)] was studied to determine whether it is a suitable tracer for evaluating the metabolic function of the brain and myocardium. 3-FDG(F-18) was rapidly accumulated in the mouse myocardium (10-12% injected dose/g) and remained constant up to 120 min. Blood, liver, and lung activities exhibited a rapid accumulation of activity (4% injected dose/g) at 1 min, followed by elimination of activity up to 30 min (2% injected dose/g), and then remaining unchanged for a period of 120 min. The arterial blood curve in the dog was fit best by three exponential components (T 1/2 = 0.52 min, 2.75 min, and 142.8 min). Transverse-section images were obtained of the dog's brain and myocardium. From sequential two-dimensional images, a clearance half-time of 26.88 min was determined for the canine brain. Radiation doses for man were calculated from tissue distribution data for mice.

Animals↗
PubMed1977

Genetic control and racial variation of beta-glucosidase isozymes in maize (Zea mays L.)

beta-Glucosidase (beta-D-glucoside glucohydrolase, E.C. 3.2.1.21, beta-Glu) isozyme variants were studied in a large number of inbred lines, crosses, and races of maize (Zea mays L.). The pattern of Mendelian inheritance demonstrated for beta-GLU variants indicated that they are under nuclear gene control. Twenty-two allelic forms at a single locus were identified in the materials studied by starch gel electrophoresis. Genetic data indicate that beta-GLU in maize is functionally a dimer. Variation of beta-GLU isozymes in 51 racial collections of maize from Mexico showed little correlation with morphological or geographical data. In 39 collections from Central America, variation patterns appeared to have some association with altitude.

Alleles↗