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Biomedical subjects

M M Goodman

Publications and source records attributed to M M Goodman.

At least 55 records · Page 3Linked to original sources

A case for revising the 'weight gain during pregnancy' guidelines for Australian women.

In 1989, an average weight gain during pregnancy of 14 kg was determined for a sample of 1,253 public patients at the Royal Women's Hospital, Brisbane. This greatly exceeded the weight gain of 10 to 12 kg which was recommended by the hospital and which is based on United States of America (US) data. The finding prompted a comparison of characteristics of Brisbane mothers (weight gain during pregnancy, age, prepregnant weight, height, birth-weight of infant, etc) with the characteristics of mothers in two large US studies. Significant differences were found to exist with Brisbane women being taller, heavier in body mass, more overweight and gaining less weight during pregnancy than the US women. Unexpectedly, the birth-weight of infants was neither more nor less than reported for the American studies. Further studies to gain more information about Australian women during their pregnancies should be undertaken.

Adolescent↗

Studies of a new fatty acid analog (DMIVN) in hypertensive rats and the effect of verapamil using ARG microimaging.

Studies of myocardial utilization of fatty acids and analogs has focused on coronary heart disease. This study addresses the topic of radioiodinated fatty acid utilization in hypertensive-cardiomyopathy. The new fatty acid analog 19-iodo-3,3-dimethyl-18 nonadecenoic acid (DMIVN) was studied by autoradiographic microimaging (ARG) in salt-sensitive (S) hypertensive (salt-fed) and in salt-sensitive (S) normotensive (low-salt diet), Dahl-strain rats. A salt fed, S-strain group was treated with verapamil and the results were compared to those in a hypertensive, non-treated group. The distribution of DMIVN in the hearts of normotensive rats was uniform. In the myocardium of hypertensive rats nonuniform DMIVN concentration was seen in the subendocardial and mid-layers of the left ventricle (LV). Verapamil given to salt-fed rats prevented hypertension and uniform DMIVN uptake similar to normotensive controls was seen. The data suggest that DMIVN may be suitable for the detection of hypertension induced myocardial changes and for assessing therapy. The distribution and clearance characteristics of DMIVN indicate that DMIVN may be a useful agent for SPECT imaging in man.

Animals↗

Effect of 3-methyl-branching on the myocardial retention of radioiodinated 19-iodo-18-nonadecenoic acid analogues.

The effect of methyl-branching at the 3(beta-)-position on myocardial uptake and retention of fatty acids where radioiodide has been stabilized as a terminal trans-(E)-vinyl iodide has been evaluated in fasted rats. The syntheses of two new dimethyl-branched fatty acids, 17-iodo-3,3-dimethylheptadecanoic acid (14) and (E)-19-iodo-3,3-dimethyl-18-nonadecenoic acid (19), are described. Tissue distribution studies in fasted rats with [125I]-19 showed significant heart uptake (2 min, 4.56% dose/g), and prolonged retention (60 min 4.10% dose-g). These results suggest that [123I]-19 is a good candidate for further studies of regional myocardial fatty acid uptake patterns by SPECT.

Animals↗

Neurofollicular hamartoma: a light microscopic and immunohistochemical study.

Neurofollicular hamartoma is an unusual, previously undescribed neoplasm characterized by a proliferation of spindle cells and hyperplastic pilosebaceous units. Five cases were reviewed. The lesions presented as single, asymptomatic, smooth, flesh-colored papules. Four were on the nose, and one on the adjacent nasolabial fold. Immunoperoxidase studies performed on two cases utilizing antibodies to S-100 antigen were positive in both. These lesions share some histological and clinical features with angiofibroma and neurofibroma.

Adult↗

Earthquake urticaria.

Acute urticaria was seen in a patient following the October 1987 earthquake in Los Angeles, California. The psychological stress of earthquakes may trigger urticaria.

Adult↗

New isozyme systems for maize (Zea mays L.): aconitate hydratase, adenylate kinase, NADH dehydrogenase, and shikimate dehydrogenase.

Electrophoretic variation and inheritance of four novel enzyme systems were studied in maize (Zea mays L.). A minimum of 10 genetic loci collectively encodes isozymes of aconitate hydratase (ACO; EC 4.2.1.3.), adenylate kinase (ADK; EC 2.7.4.3), NADH dehydrogenase (DIA; EC 1.6.99.-), and shikimate dehydrogenase (SAD; EC 1.1.1.25). At least four loci are responsible for the genetic control of ACO. Genetic data for two of the encoding loci, Aco1 and Aco4, demonstrated that at least two maize ACOs are active as monomers. Analysis of organellar preparations suggests that ACO1 and ACO4 are localized in the cytosolic and mitochondrial subcellular fractions, respectively. Maize ADK is encoded by a single nuclear locus, Adk1, governing monomeric enzymes that are located in the chloroplasts. Two cytosolic and two mitochondrial forms of DIA were electrophoretically resolved. Segregation analyses demonstrated that the two cytosolic isozymes are controlled by separate loci, Dia1 and Dia2, coding for products that are functional as monomers (DIA1) and dimers (DIA2). The major isozyme of SAD is apparently cytosolic, although an additional faintly staining plastid form may be present. Alleles at Sad1 are each associated with two bands that cosegregate in controlled crosses. Linkage analyses and crosses with B-A translocation stocks were effective in determining the map locations of six loci, including the previously described but unmapped locus Acp4. Several of these loci were localized to sparsely mapped regions of the genome. Dia2 and Acp4 were placed on the distal portion of the long arm of chromosome 1, 12.6 map units apart. Dia1 was localized to chromosome 2, 22.2 centimorgans (cM) from B1. Aco1 was mapped to chromosome 4, 6.2 cM from su1. Adk1 was placed on the poorly marked short arm of chromosome 6, 8.1 map units from rgd1. Less than 1% recombination was observed between Glu1 (on chromosome 10) and Sad1. In contrast to many other maize isozyme systems, there was little evidence of gene duplication or of parallel linkage relationships for these allozyme loci.

Aconitate Hydratase↗

Effects of fasting on the myocardial subcellular distribution and lipid distribution of terminal p-iodophenyl-substituted fatty acids in rats.

The myocardial lipid pool distribution and subcellular distribution of radiolabeled methyl-branched fatty acids in rats was evaluated under conditions of fasting (24 h) and feeding. With the unbranched iodophenyl fatty acid, fasting resulted in increased myocardial extraction and clearance time with a decrease in the incorporation into triglycerides and greater radioactivity in the mitochondrial fraction. With the monomethyl-branched analogue, the effects of fasting on lipid and subcellular distribution were minor except for a decrease in triglyceride incorporation. Like the unbranched analogue, the dimethyl-branched iodophenyl fatty acid showed increased myocardial extraction with fasting, however, this structurally-modified fatty acid showed increased rather than decreased incorporation into triglycerides.

Animals↗

Detection of cardiomyopathy in an animal model using quantitative autoradiography.

A fatty acid analog (15-p-iodophenyl)-3,3 dimethyl-pentadecanoic acid (DMIPP) was studied in cardiomyopathic (CM) and normal age-matched Syrian hamsters. Dual tracer quantitative wholebody autoradiography (QARG) with DMIPP and 2-[14C(U)]-2-deoxy-2-fluoro-D-glucose (FDG) or with FDG and 201Tl enabled comparison of the uptake of a fatty acid and a glucose analog with the blood flow. These comparisons were carried out at the onset and mid-stage of the disease before congestive failure developed. Groups of CM and normal animals were treated with verapamil from the age of 26 days, before the onset of the disease for 41 days. In CM hearts, areas of decreased DMIPP uptake were seen. These areas were much larger than the decrease in uptake of FDG or 201Tl. In early CM only minimal changes in FDG or 201Tl uptake were observed as compared to controls. Treatment of CM-prone animals with verapamil prevented any changes in DMIPP, FDG, or 201Tl uptake. DMIPP seems to be a more sensitive indicator of early cardiomyopathic changes as compared to 201Tl or FDG. The trial of DMIPP and SPECT in the diagnosis of human disease, as well as for monitoring the effects of drugs which may prevent it seems to be warranted.

Animals↗

Effect of 3-methyl-branching on the metabolism in rat hearts of radioiodinated iodovinyl long chain fatty acids.

The metabolism of two new 3-methyl-branched iodovinyl fatty acids in rat hearts was evaluated by determining the subcellular and lipid pool distribution of these radiolabeled analogues after intravenous injection. Methyl branching had been introduced into the straight chain analogue, 19-iodo-18-nonadecenoic acid (IVN), to produce the monomethyl analogue, 19-iodo-3-(R,S)-methyl-18-nonadecenoic acid (BMIVN) and the dimethyl derivative, 19-iodo-3,3-dimethyl-18-nonadecenoic acid (DMIVN) in the hope of inhibiting beta oxidation. Since the presence of 3-methyl branching results in delayed myocardial clearance in rats, differences were sought in the lipid and subcellular distribution of these branched analogues that might correlate with the prolonged retention and reflect differences in metabolism. Hearts of rats injected intravenously with the radiolabeled fatty acids were removed and homogenized and the homogenates partitioned between the chloroform-methanol (organic) fraction and the aqueous fraction. Comparison of the distribution of radioactivity between the organic and aqueous fractions showed that most of the DMIVN and BMIVN activity was in the organic fraction with IVN activity initially divided equally between the two fractions. Identification of the lipid components of these organic fractions showed that there was slow incorporation of DMIVN into the triglyceride and polar lipid fractions with a slow loss from the free fatty acid fraction. With the straight chain IVN analogue which shows rapid washout from rat hearts, there was loss of activity from all 3 lipid components during the 60 min. The monomethyl branched BMIVN analogue demonstrated predominant storage in the polar lipid fraction with some incorporation into triglycerides.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of the metabolism in rat hearts of two new radioiodinated 3-methyl-branched fatty acid myocardial imaging agents.

The biological fate of two new radioiodinated 3-methyl-branched fatty acids has been evaluated in rat hearts following intravenous administration. Methyl-branching was introduced in [15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) and 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) to inhibit beta-oxidation. The goals of these studies were to correlate the effects of methyl-branching on the incorporation of these agents into the various fatty acid pools and subcellular distribution profiles, and to relate these data to the myocardial retention properties. The properties of BMIPP and DMIPP were compared with the 15-(p-iodophenyl)pentadecanoic acid straight-chain analogue (IPP). Differences in the heart retention of the analogues after intravenous administration in rats correlated with differences observed in subcellular distribution patterns. The dimethyl DMIPP analogue showed the longest retention and the highest association with the mitochondrial and microsomal fractions (34%, 38%) 30 min after injection. These data are in contrast to the rapid clearance of the straight-chain IPP analogue which showed much lower relative association with the mitochondria and microsomes (18%, 15%). The distribution patterns of each analogue in the various lipid pools appeared consistent with the expected capacity of the analogues to be metabolized by beta-oxidation. In contrast to the rapid oxidation of the straight-chain IPP analogue, the 3-monomethyl BMIPP analogue appeared to undergo slower oxidation and clearance, whereas the dimethyl-branched DMIPP analogue was apparently not catabolized by the myocardium. All three analogues showed some incorporation into triglycerides. The metabolism patterns of the branched analogues reported here may provide useful information in the description of the mechanisms by which BMIPP and DMIPP are retained in rat myocardium.

Animals↗

A model of human melanoma in cyclosporine-immunosuppressed rats.

A human malignant melanoma maintained in athymic nude mice has been successfully implanted and grown in cyclosporine (Cys)-immunosuppressed Lewis rats. Suspended melanoma cells (10(6)) or solid tumor sections measuring 2-4 mm in diameter were implanted s.c. in rats receiving parenteral Cys doses of 15-50 mg/kg each day for 1 week, and 3 times per week thereafter. Eighty-five percent of solid tumor sections implanted in animals receiving 25 mg/kg resulted in tumor growth, whereas no tumors grew from cell suspension injection sites. The average maximum tumor growth rate was 2 cm3/day, with a doubling time of 8 days. Tumors retained pretransplant gross and microscopic morphology, karyotype, and labeling index. Possible advantages of this model over the athymic nude mouse include greater longevity, larger animal and tumor size, and less stringent aseptic environmental requirements. This model may prove useful for further study of the pathophysiology of melanoma and for testing of new antimelanoma therapies.

Animals↗

New radioiodinated methyl-branched fatty acids for cardiac studies.

The effects of 3-methyl substitution on the heart retention and metabolism of 3-R,S-methyl-(BMIPP) and 3,3-dimethyl-(DMIPP) analogues of 15-(p-iodophenyl)-pentadecanoic acid (IPP) were studied in rats. Methyl substitution considerably increased the myocardial half-time values in fasted rats: IPP, 5-10 min; BMIPP, 30-45 min; DMIPP, 6-7 h. Because of the observed differences in the relative myocardial uptake and retention of these agents, an evaluation of the subcellular distribution profiles and the distribution of radioactivity within various lipid pools extracted from cell components was performed. Studies with DMIPP in food-deprived rats have shown high levels of the free fatty acid and only slow conversion to triglycerides. These data are in contrast to the rapid clearance of the straight chain IPP analogue and rapid incorporation into triglycerides, and suggest that the prolonged myocardial retention observed with DMIPP in vivo may result from inhibition of beta oxidation. Subcellular distribution studies have shown predominant association of DMIPP and BMIPP with the mitochondrial and microsomal fractions, while IPP was primarily found in the cytoplasm. Because of the unique "trapping" properties and the high heart:blood ratios, [123I]DMIPP should be useful for evaluation of aberrations in regional myocardial uptake.

Animals↗

Structurally modified fatty acids: clinical potential as tracers of metabolism.

Recently 15-p-iodophenyl-beta-methyl-pentadecanoic acid (BMPPA) was proposed for use in myocardial scintigraphy, as a possible probe of metabolic processes other than beta-oxidation. In 19 patients (CAD/15, St.p. Mi/7; control 4) myocardial scintigraphy was carried out after i.v. I-123-BMPPA (2-4 mCi). Data were collected (LAO 45 degrees/14; anterior/5) for 100 min in the fasted patients. Organ to background (BG) ratios were calculated for the heart (H) and liver (L), and the elimination (E) behaviour was analyzed from BG (vena cava region) corrected time activity curves. In 10 patients plasma and urine were examined. By CHCl3/MeOH extraction of plasma samples (90 min after injection), both in water and in organic medium soluble catabolites were found. TLC fractionation showed that those were co-migrating, compared to standards, with bencoic acid, BMPPA and triglycerides. In the urine (0-2 h after injection, 4.1% dose) hippuric acid was found. The mean t-max of BMPPA occurred at 15 min in the heart and at 9 min in the liver (P less than 0.01), with H/BG and L/BG ratios of 1.8 and 2.1, respectively. The elimination of BMPPA was slower from the heart than from the liver (P less than 0.01). It was biexponential from the liver in all cases (means: t/2 I, 11.4 min; t/2 II, 92 min; t/2 I uncor., 38 min) with the size of phase I smaller than that of phase II (means: I/II, 0.57). From the heart BMPPA turnover was biexponential in 11 patients (means: t/2 I, 13.8 min; t/2 II, 187 min; t/2 I uncor., 65 min; I/II, 0.34), but monoexponential in 8 (means: t/2, 218 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

Radioiodinated 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid: a useful new agent to evaluate myocardial fatty acid uptake.

Radioiodinated 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) has been prepared as a new terminal iodophenyl-substituted fatty acid containing dimethyl-branching at the beta position. For the synthesis of this new agent, chain homologation was accomplished by fabrication of a 2,5-disubstituted thiophene by successive Friedel-Crafts acylation and Wolff-Kishner reduction reactions, followed by thiophene ring opening. The dimethyl-branching was introduced using the monomethyl ester of dimethylglutaryl chloride. Radioiodination of the 15-phenyl-3,3-dimethylpentadecanoic acid substrate in the para position then gave DMIPP. Iodine-125-labeled DMIPP showed rapid, high myocardial uptake (min, mean % injected dose/g) in fasted rats (5, 4.67; 30, 5.06; 60, 4.79; 120, 4.37), and also exhibited good heart:blood ratios (min, heart:blood: 5, 3:1; 30, 12:1; 60, 12:1; 120, 13:1). To further evaluate the effects of dimethyl-branching, the biodistribution properties of DMIPP were compared with the 3-monomethyl-branched (15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid; BMIPP) and the unbranched (15-(p-iodophenyl)pentadecanoic acid; IPP) analogs. A triple-labeled [123I]DMIPP/[131I]BMIPP/[125I]IPP mixture was administered to groups of fasted rats. These results confirmed the greater myocardial retention and higher heart:blood ratios observed with DMIPP in comparison with both the 3-monomethyl-(BMIPP) and unbranched (IPP) analogs. These data suggest that [123I]DMIPP is an excellent candidate for clinical evaluation of regional energy substrates (fatty acid) uptake.

Animals↗

Dual tracer autoradiographic study of beta-methyl-(1-14C) heptadecanoic acid and 15-p-(131I)-iodophenyl-beta-methylpentadecanoic acid in normotensive and hypertensive rats.

The myocardial distribution of 15-p-[131I]iodophenyl-3-(R,S)-methylpentadecanoic acid (BMPDA) and 1[14C]-3-(R,S)-methylheptadecanoic acid (BMHDA) was compared in normotensive and hypertensive rats using quantitative dual tracer autoradiographic techniques. The myocardial distribution of carbon-14 [14C] BMHDA and iodine-131 [131I] BMPDA was nearly homogeneous in the normotensive rats, while both tracers showed similar, though very heterogeneous, distribution in hypertensive hearts with decreased uptake in the endocardial region. Our data demonstrate that myocardial distribution of [131I]BMPDA was essentially the same as [14C]BMHDA, and thus single photon emission computed tomographic imaging with 123I-labeled BMPDA could be useful for the detection of regional changes of myocardial fatty acid uptake in patients with prolonged and severe hypertension.

Animals↗

Regional myocardial substrate uptake in hypertensive rats: a quantitative autoradiographic measurement.

Severe hypertension causes global and regional changes in myocardial perfusion and substrate utilization. Regional perfusion and fatty acid utilization were evaluated by dual-tracer autoradiography in normotensive and hypertensive rats of the Dahl strain. The regional distributions of perfusion and fatty acid utilization were homogeneous in normotensive rats. Severe hypertension was associated with a homogeneous pattern of regional perfusion, but fatty acid utilization was focally decreased in the free wall of the left ventricle. The decrease in fatty acid uptake was associated with a concomitant increase in glucose utilization. These findings suggest that severe hypertension is associated with uniform myocardial perfusion and focal alterations in the substrates used for the performance of myocardial work.

Animals↗

Tellurium-labeled fatty-acid analogs: relationship of heteroatom position to myocardial kinetics.

To determine the effects of tellurium-heteroatom position on myocardial fatty-acid kinetics, a series of tellurium Te 123m-labeled heptadecanoic-acid analogs (123mTe-THDA) were evaluated in dogs. The left-anterior descending coronary artery was partially occluded, and 123mTe-THDA labeled at either the 5, 6, 9, 10, 11, 12, or 13 position from the carboxyl group was administered intravenously. In 24 dogs, the 123mTe activity in the ischemic and normal zones was monitored continuously for 3 h using miniature radiation detectors. There were no significant differences between the ischemic- and normal-wall 123mTe clearance rates for any of the compounds. There was minimal fractional 3-h myocardial clearance for the 123mTe-THDA labeled at the 5, 6, and 9 position (range of means, 0.02-0.05). There was significant clearance of 123mTe-THDA labeled at the 11, 12, and 13 position (range of means, 0.37-0.44). The myocardial clearance of the 123mTe-THDA labeled at the 10 position was intermediate between the two extremes. Thus, as the 123mTe heteroatom is placed further from the carboxyl portion of the molecule, there is a progressive increase in the myocardial clearance. Selection of the heteroatom position should depend on whether initial fatty-acid distribution or subsequent clearance rates are being studied.

Animals↗