17 results on '"Dac M. Dinh"'
Search Results
2. Design, Synthesis, and Evaluation of NO-Donor Containing Carbonic Anhydrase Inhibitors To Lower Intraocular Pressure
- Author
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Saurabh Mehta, Hovhannes J. Gukasyan, Morena Cobbs, Martin Paul Edwards, Dac M. Dinh, Paul F. Richardson, Jennifer Lafontaine, Rui Eugene Yuanjin, Brian Douglas Patterson, Qinhua Huang, and D.A. Rewolinski
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Male ,Intraocular pressure ,genetic structures ,Brinzolamide ,Thiazines ,Thiophenes ,Pharmacology ,No donors ,Nitric oxide ,chemistry.chemical_compound ,Dorzolamide ,Carbonic anhydrase ,Drug Discovery ,medicine ,Animals ,Nitric Oxide Donors ,Carbonic Anhydrase Inhibitors ,Intraocular Pressure ,chemistry.chemical_classification ,Sulfonamides ,biology ,Chemistry ,Glaucoma ,eye diseases ,Enzyme ,Design synthesis ,Drug Design ,biology.protein ,Molecular Medicine ,Rabbits ,sense organs ,medicine.drug - Abstract
The antiglaucoma drugs dorzolamide (1) and brinzolamide (2) lower intraocular pressure (IOP) by inhibiting the carbonic anhydrase (CA) enzyme to reduce aqueous humor production. The introduction of a nitric oxide (NO) donor into the alkyl side chain of dorzolamide (1) and brinzolamide (2) has led to the discovery of NO-dorzolamide 3a and NO-brinzolamide 4a, which could lower IOP through two mechanisms: CA inhibition to decrease aqueous humor secretion (reduce inflow) and NO release to increase aqueous humor drainage (increase outflow). Compounds 3a and 4a have shown improved efficacy of lowering IOP in both rabbits and monkeys compared to brinzolamide (2).
- Published
- 2015
3. Mitotic Checkpoint Kinase Mps1 Has a Role in Normal Physiology which Impacts Clinical Utility
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Robert Louis Hoffman, Jill Hallin, Patrick B. Lappin, Jeffery Fan, Gina M. Yanochko, Murphy Sean T, Ricardo Martinez, Isha Rymer, Zhou Zhu, Dac M. Dinh, Brion W. Murray, Matthew A. Marx, Wenyue Hu, Peiquing Sun, Sergei Timofeevski, Dusko Trajkovic, and Alessandra Blasina
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Cell cycle checkpoint ,Pyridines ,Physiology ,lcsh:Medicine ,Apoptosis ,Cell Cycle Proteins ,Mice, SCID ,Piperazines ,Histones ,Mice ,0302 clinical medicine ,Intestine, Small ,Phosphorylation ,RNA, Small Interfering ,lcsh:Science ,0303 health sciences ,Multidisciplinary ,biology ,Cell cycle process ,Protein-Tyrosine Kinases ,3. Good health ,Spindle checkpoint ,030220 oncology & carcinogenesis ,Female ,RNA Interference ,G1 phase ,Research Article ,Cell Survival ,Transplantation, Heterologous ,Mitosis ,Bone Marrow Cells ,Breast Neoplasms ,Protein Serine-Threonine Kinases ,Palbociclib ,03 medical and health sciences ,Cell Line, Tumor ,Animals ,Humans ,Protein Kinase Inhibitors ,Cell Proliferation ,030304 developmental biology ,Cyclin-dependent kinase 4 ,lcsh:R ,Cyclin-Dependent Kinase 4 ,Cyclin-Dependent Kinase 6 ,G1 Phase Cell Cycle Checkpoints ,Rats ,biology.protein ,lcsh:Q ,Cyclin-dependent kinase 6 - Abstract
Cell cycle checkpoint intervention is an effective therapeutic strategy for cancer when applied to patients predisposed to respond and the treatment is well-tolerated. A critical cell cycle process that could be targeted is the mitotic checkpoint (spindle assembly checkpoint) which governs the metaphase-to-anaphase transition and insures proper chromosomal segregation. The mitotic checkpoint kinase Mps1 was selected to explore whether enhancement in genomic instability is a viable therapeutic strategy. The basal-a subset of triple-negative breast cancer was chosen as a model system because it has a higher incidence of chromosomal instability and Mps1 expression is up-regulated. Depletion of Mps1 reduces tumor cell viability relative to normal cells. Highly selective, extremely potent Mps1 kinase inhibitors were created to investigate the roles of Mps1 catalytic activity in tumor cells and normal physiology (PF-7006, PF-3837; K i
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- 2015
4. Substituted 4-aminopiperidines having high in vitro affinity and selectivity for the cloned human dopamine D4 receptor
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J. Neil Duncan, Schlachter Sk, Arthur Glenn Romero, Mary E. Lajiness, Toni J Poel, Martin W. Smith, Dac M. Dinh, Lawson Cf, and Susan A Rees
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Pharmacology ,Adrenergic receptor ,Receptors, Dopamine D2 ,Chinese hamster ovary cell ,Receptors, Dopamine D4 ,Dopaminergic ,Aminopyridines ,Mitosis ,Biological activity ,CHO Cells ,Biology ,Recombinant Proteins ,Dopamine receptor D1 ,Piperidines ,Biochemistry ,Dopamine receptor ,Dopamine ,Cricetinae ,medicine ,Animals ,Humans ,Receptor ,Signal Transduction ,medicine.drug - Abstract
We have discovered two substituted 4-aminopiperidine compounds having high in vitro affinity and selectivity for the human dopamine D 4 receptor. Both compounds, 3-ethoxy- N -methyl- N -[1-(phenylmethyl)-4-piperidinyl]-2-pyridinylamine (U-99363E), and its 3-isopropoxy analog (U-101958), were found through a routine receptor binding screen. The determined affinities ( K i ) of these compounds for the cloned human dopamine D 4 receptor were 2.2 and 1.4 nM, respectively. They exhibited at least 100-fold lower affinities for dopamine D 2 and for other dopaminergic, serotonergic and adrenergic receptors. Both compounds were found to antagonize quinpirole-induced mitogenesis in Chinese hamster ovary cells expressing the human dopamine D 4 receptor. In spite of their poor metabolic stability and low bioavailability, U-99363E and U-101958 appear to be among the first high-affinity, highly selective dopamine D 4 receptor antagonists reported, and may have utility in in vitro investigations requiring selective tagging or blockade of dopamine D 4 sites. © 1997 Elsevier Science B.V. All rights reserved.
- Published
- 1997
5. Screening for inhibitors of the HMG-CoA reductase promoter in HepG2 cells: Identification of four non-oxysterol inhibitors
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Dac M. Dinh, Karen L. Hart, Debra J. Bevis, Keiser Bj, Y. Yagi, Charles H. Spilman, Gerard F. Hess, and Scott D. Larsen
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Reporter gene ,biology ,Biochemistry ,Enzyme inhibitor ,Cell culture ,Drug Discovery ,HMG-CoA reductase ,biology.protein ,Promoter ,Reductase ,Hydroxymethylglutaryl-CoA reductase ,Molecular biology ,Sterol - Abstract
The 4.9-kb segment of the Chinese hamster hydroxymethylglutaryl-CoA reductase promoter found in pRedCAT-3 consists of 1.4-kb of the promoter and a 3.5-kb intron. We placed this segment upstream of a reporter gene, lacZ of E. coli. The new construct pRed3lacZ was transfected into human hepatoma cells (HepG2), and a single clone, G52, was isolated. Promoter activity was monitored by measuring β-galactosidase activity in cell lysates in microtiter wells using a fluorogenic substrate, 4-methyl-umbelliferyl β-D-galactoside. The amount of β-galactosidase activity in cell lysates was directly proportional to the initial cell inoculum up to 30,000 cells per well. Fidelity of the reductase promoter in G52 was confirmed by (1) suppression of β-galactosidase synthesis (62.7%) by a sterol mixture consisting of 1.6 × 10−5 M 25-hydroxycholesterol and 3.1 × 10−6 M cholesterol, and (2) increased synthesis (51.3%) of β-galactosidase in the presence of 10−7 M mevinolin, a competitive inhibitor of HMG-CoA reductase activity. Using this cell line, we examined 5,400 compounds and found four compounds, U-9888, U-20685, U-51862, and U-71690, that inhibit the reductase promoter with IC50 values of 13.3, 12.0, 12.3, and 14.3 μM, respectively. In wild-type HepG2 cells, these compounds reduced the synthesis of HMG-CoA reductase by 37, 48, 32, and 22%, respectively. Significantly, none of these compounds inhibit the binding of LDL to its receptor, suggesting an important separation of these two coordinately regulated activities. Furthermore, all four of these inhibitors lie outside of the class of compounds typically defined as classic oxysterols, and thus represent new potential templates for the discovery of HMG-CoA reductase expression regulators. Drug Dev. Res. 40:41–47, 1997. © 1997 Wiley-Liss, Inc.
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- 1997
6. Lifibrol increases hepatic cholesterol 7?-hydroxylase activity in sprague-dawley rats
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G. Michael Funk, Charles H. Spilman, Thomas J. Vidmar, and Dac M. Dinh
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medicine.medical_specialty ,Very low-density lipoprotein ,biology ,Cholesterol ,Reductase ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Mechanism of action ,Internal medicine ,Drug Discovery ,HMG-CoA reductase ,medicine ,biology.protein ,Gemfibrozil ,Distribution (pharmacology) ,lipids (amino acids, peptides, and proteins) ,Lovastatin ,medicine.symptom ,medicine.drug - Abstract
The hypocholesterolemic drug lifibrol was administered orally to Sprague-Dawley rats to determine its effects on lipoprotein cholesterol distribution and hepatic HMG-CoA reductase and cholesterol 7α-hydroxylase activities. The effects of lifibrol on those endpoints were compared with the effects of gemfibrozil and lovastatin. When administered to either chow-fed or cholesterol-fed rats, lifibrol (25 or 50 mg/kg/day) caused a redistribution of lipoprotein cholesterol such that HDL increased and VLDL + LDL decreased significantly. Gemfibrozil (30 or 50 mg/kg/day) caused similar changes in lipoprotein cholesterol distribution. In contrast, lovastatin (10 mg/kg/day) decreased both HDL and VLDL + LDL in chow-fed animals, but had no effect in cholesterol-fed animals. Hepatic HMG-CoA reductase activity was increased in rats treated with lifibrol (50 mg/kg/day), gemfibrozil (50 mg/kg/day), and lovastatin (10 mg/kg/day). The most significant finding is that lifibrol was the only drug that increased hepatic cholesterol 7α-hydroxylase activity. This observation in rats separates the mechanism of action of lifibrol from those of the HMG-CoA reductase inhibitors and the fibrates, and suggests that one mechanism of action of lifibrol is to enhance cholesterol elimination through conversion to bile acids. © 1994 Wiley-Liss, Inc.
- Published
- 1994
7. Design and Synthesis of Seco-oxysterol Analogs as Potential Inhibitors of 3-Hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) Reductase Gene Transcription
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Karen L. Hart, Charles H. Spilman, Scott D. Larsen, Gerard F. Hess, Dac M. Dinh, and Yoshi Yagi
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Transcription, Genetic ,Oxysterol ,Reductase ,Gene Expression Regulation, Enzymologic ,Cricetinae ,Drug Discovery ,Gene expression ,Tumor Cells, Cultured ,Animals ,Humans ,Promoter Regions, Genetic ,biology ,Chemistry ,Biological activity ,Transfection ,Hydroxymethylglutaryl-CoA reductase ,Oxygen ,Sterols ,Receptors, LDL ,Biochemistry ,Enzyme inhibitor ,Drug Design ,HMG-CoA reductase ,biology.protein ,Molecular Medicine ,Hydroxymethylglutaryl CoA Reductases ,lipids (amino acids, peptides, and proteins) - Abstract
The synthesis and biological activity of a series of seco-oxysterol analogs designed to be inhibitors of transcription of the gene for 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGR) are described. The compound possessing the most significant activity, [1 alpha (E),4 beta]-3-[2-(4- hydroxy-1-methylcyclohexyl)ethenyl]-alpha,alpha-dimethylbenzenepentan ol (4, U-88156), inhibited (IC50 = 10 microM) the expression of beta-galactosidase (beta-gal) in a transfected human HepG2 cell line wherein the beta-gal gene was driven by a 5 kB segment of the promoter for hamster HMGR. Furthermore, using wild-type HepG2 cells, it was shown that 10 microM 4 reduced HMGR mRNA levels by 73% while stimulating LDL-receptor activity by 47%. In the same system, the related oxysterol, 25-hydroxycholesterol (1), at 10 microM lowered both HMGR mRNA levels and LDL-receptor activity by 58% and 64%, respectively. Overall HMGR activity in wild-type HepG2 cells was inhibited 30% by 4 at 10 microM. These findings collectively demonstrate that a seco-oxysterol analog is capable of regulating HMGR gene expression and that this regulation can occur without a concomitant attenuation of the level of LDL-receptor activity.
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- 1994
8. ChemInform Abstract: Design and Synthesis of Seco-Oxysterol Analogues as Potential Inhibitors of 3-Hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) Reductase Gene Transcription
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K. L. Hart, Scott D. Larsen, Charles H. Spilman, Dac M. Dinh, G. F. Hess, and Y. Yagi
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3-hydroxy-3-methylglutaryl-coenzyme A ,Oxysterol ,biology ,Biochemistry ,Chemistry ,HMG-CoA reductase ,biology.protein ,General Medicine - Published
- 2010
9. Spontaneous hypercholesterolemia in cynomolgus monkeys: evidence for defective low-density lipoprotein catabolism
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Dac M. Dinh, Karen L. Hart, Thomas J. Vidmar, and Charles H. Spilman
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medicine.medical_specialty ,Hypercholesterolemia ,Biophysics ,Biology ,Biochemistry ,Binding, Competitive ,chemistry.chemical_compound ,Endocrinology ,Apolipoproteins E ,Cell surface receptor ,Internal medicine ,medicine ,Animals ,Humans ,Fibroblast ,Cells, Cultured ,Apolipoproteins B ,Catabolism ,Monkey Diseases ,Fibroblasts ,Pathophysiology ,In vitro ,Lipoproteins, LDL ,Kinetics ,Macaca fascicularis ,medicine.anatomical_structure ,Cholesterol ,chemistry ,Receptors, LDL ,Low-density lipoprotein ,LDL receptor ,lipids (amino acids, peptides, and proteins) ,Clearance - Abstract
Spontaneously hypercholesterolemic (SH) cynomolgus monkeys were identified that have average plasma cholesterol of 202 mg/dl, while that in normal monkeys is 119 mg/dl. The LDL from these SH monkeys have lower affinity for fibroblast LDL receptors in vitro. The amount of LDL2 (1.030 mean value of d 1.063 g/ml) required to displace 50% of [125I]LDL was 3.8 micrograms/ml for normal LDL2 and 6.6 micrograms/ml for SH-LDL2. The binding affinity of LDL1 (1.019 mean value of d 1.030 g/ml) was the same in normal and SH animals. LDL turnover experiments showed that the SH monkeys were comprised of two populations. Normal LDL2 was cleared much slower in two of the SH monkeys than in normocholesterolemic animals, suggesting that these two animals have an LDL receptor defect. However, LDL2 isolated from these two SH monkeys was cleared normally in normal monkeys. LDL2 isolated from two other SH monkeys is cleared slower than is normal LDL2 in normal animals, suggesting that these animals have an LDL defect. Thus, the hypercholesterolemia of these SH monkeys is associated with defective LDL catabolism; two animals appear to have functionally defective LDL receptors, and two animals appear to have functionally defective LDL.
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- 1992
10. Synthesis and hypocholesterolemic activity of 6,7-dihydro-4H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8-diones, novel inhibitors of acylCoA:cholesterol O-acyltransferase
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Gracella J. Wilson, Frank P. Bell, Scott D. Larsen, Charles H. Spilman, Esther Martinborough, and Dac M. Dinh
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Male ,Pyrimidine ,Chemical Phenomena ,Stereochemistry ,Pyrimidinones ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,Animals ,chemistry.chemical_classification ,biology ,Cholesterol ,Anticholesteremic Agents ,Biological activity ,Rats, Inbred Strains ,In vitro ,Rats ,Chemistry ,Enzyme ,chemistry ,Enzyme inhibitor ,Acyltransferase ,biology.protein ,Lactam ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Sterol O-Acyltransferase - Abstract
A novel series of 6,7-dihydro-4H-pyrazolo [1,5-a] pyrrolo [3,4-d] pyrimidine-5,8-dione inhibitors of the enzyme acyl-CoA: cholesterol O-acyltransferase is described. A number of these derivatives were found to obe potent modulators of serum lipoprotein levels in cholesterol-feld rats. Further evaluation of one of the most effective analogues confirmed that it was significantly blocking the absorption of cholesterol from the gut
- Published
- 1991
11. Sterol and bile acid metabolism during development: 2. Identification of 3β-hydroxy-5-cholenoic acid (an intermediate in alternate pathway of bile acid synthesis) in newborn and fetal guinea pig
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M.T.Ravi Subbiah, Dac M. Dinh, Job R. Li, and L. Marai
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Chromatography, Gas ,Alternate pathway ,medicine.drug_class ,Guinea Pigs ,Clinical Biochemistry ,In Vitro Techniques ,Biology ,Chenodeoxycholic Acid ,Biochemistry ,Mass Spectrometry ,Bile Acids and Salts ,Guinea pig ,Feces ,chemistry.chemical_compound ,Fetus ,Endocrinology ,Chenodeoxycholic acid ,medicine ,Animals ,Intestinal Mucosa ,Molecular Biology ,Pharmacology ,Bile acid ,Organic Chemistry ,Gallbladder ,Sterol ,Cholenes ,Animals, Newborn ,chemistry ,Glycine ,Chromatography, Thin Layer - Abstract
3β-hydroxy-5-cholenoic acid was found in the bile and feces of new-born and fetal guinea pigs. The identity of this compound was confirmed by gas chromatography and mass spectrometry. This finding suggests that the formation of chenodeoxycholic acid through 3β-hydroxy-5-cholenoic acid is intermediate in the early life of guinea pigs. Thus, it provides a useful model for studying the details of regulatory factors and significance of this pathway. This study also revealed that, unlike the adult guinea pig, the newborn guinea pig has significant amounts of glycine conjugates of bile acid.
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- 1977
12. Alteration of biliary ursodeoxycholic acid in guinea pig during early stages of cholestyramine feeding
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Dac M. Dinh, Bruce A. Kottke, and Job R. Li
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Male ,medicine.medical_specialty ,Cholestyramine Resin ,Guinea Pigs ,Clinical Biochemistry ,Reductase ,Chenodeoxycholic Acid ,Biochemistry ,Bile Acids and Salts ,Guinea pig ,Feces ,chemistry.chemical_compound ,Endocrinology ,Plasma cholesterol ,Internal medicine ,Chenodeoxycholic acid ,medicine ,Animals ,Bile ,Cholesterol 7-alpha-Hydroxylase ,Molecular Biology ,Pharmacology ,Cholestyramine ,biology ,Cholesterol ,Ursodeoxycholic Acid ,Organic Chemistry ,Ursodeoxycholic acid ,Sterols ,Liver ,chemistry ,Steroid Hydroxylases ,HMG-CoA reductase ,biology.protein ,Hydroxymethylglutaryl CoA Reductases ,lipids (amino acids, peptides, and proteins) ,Deoxycholic Acid ,medicine.drug - Abstract
The effects of cholestyramine feeding on biliary ursodeoxycholic acid, fecal excretion of bile acids and neutral sterols on cholesterol 7α-hydroxylase and hepatic HMG-CoA reductase were examined in the guinea pig. In the bile there was a 57% decrease in the concentration of ursodeoxycholic acid while an increase was observed in the concentration of chenodeoxycholic acid. Cholestyramine feeding for ten days resulted in a decrease in plasma cholesterol levels and an increase in both hepatic HMG-CoA reductase and cholesterol 7α-hydroxylase activities. The fecal excretion of both bile acids and neutral sterols was significantly increased.
- Published
- 1979
13. Apolipoprotein A-I as a Marker of Angiographically Assessed Coronary-Artery Disease
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Bruce A. Kottke, James J. Maciejko, Simon J.T. Mao, David R. Holmes, Dac M. Dinh, and Alan R. Zinsmeister
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Male ,medicine.medical_specialty ,Apolipoprotein B ,Coronary Disease ,Disease ,Coronary Angiography ,Coronary artery disease ,chemistry.chemical_compound ,Text mining ,Internal medicine ,medicine ,Humans ,In patient ,Apolipoproteins B ,Analysis of Variance ,Apolipoprotein A-I ,biology ,business.industry ,Cholesterol ,Stepwise discriminant analysis ,Cholesterol, HDL ,General Medicine ,Plasma levels ,Middle Aged ,medicine.disease ,Apolipoproteins ,chemistry ,biology.protein ,Cardiology ,lipids (amino acids, peptides, and proteins) ,Lipoproteins, HDL ,business - Abstract
This study was designed to determine whether the plasma level of apolipoprotein A-I is a better discriminator of angiographically documented coronary-artery disease than the level of high-density-lipoprotein (HDL) cholesterol in male subjects. The level of plasma apolipoprotein A-I in 83 patients with coronary-artery disease was 96.7 +/- 4.2 mg per deciliter (mean +/- S.E.M.), which was significantly lower (P less than 0.0001) than the level in 25 patients without coronary-artery disease (146.9 +/- 2.1 mg per deciliter). The levels of HDL cholesterol were also lower (P less than 0.0001) in patients with coronary-artery disease (31.9 +/- 1.5 mg per deciliter) than in those without it (45.9 +/- 2.3 mg per deciliter). A stepwise discriminant analysis, however, indicated the superiority of apolipoprotein A-I over HDL cholesterol in detecting coronary-artery disease. Furthermore, a linear discriminant analysis suggested that although HDL cholesterol by itself was a discriminator of coronary-artery disease, it did not provide a substantial increase in discriminatory value over that provided by apolipoprotein A-I; in contrast, apolipoprotein A-I levels added discriminatory value to the information obtained by measuring HDL cholesterol alone. We conclude that apolipoprotein A-I by itself is more useful than HDL cholesterol for identifying patients with coronary-artery disease.
- Published
- 1983
14. Sterol and bile acid metabolism during development. 3. Occurrence of neonatal hypercholesterolemia in guinea pig and its possible relation to bile acid pool
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M.T.Ravi Subbiah, Dac M. Dinh, Ralph D. Ellefson, and Job R. Li
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Aging ,medicine.medical_specialty ,medicine.drug_class ,Lipoproteins ,Endocrinology, Diabetes and Metabolism ,Guinea Pigs ,Hypercholesterolemia ,Hepatic cholesterol ,High density ,Biology ,Bile Acids and Salts ,Guinea pig ,chemistry.chemical_compound ,Endocrinology ,Plasma cholesterol ,Pregnancy ,Internal medicine ,medicine ,Animals ,Bile ,Triglycerides ,Bile acid ,Cholesterol ,Sterol ,Animals, Newborn ,Liver ,chemistry ,Bile acid metabolism ,Female ,lipids (amino acids, peptides, and proteins) - Abstract
The relationship of the changes in plasma cholesterol to bile acid pool was studied in the newborn guinea pig. Plasma cholesterol reached the maximum on the fifth day and gradually declined to adult levels. The cholesterol concentration in the high density lipoproteins (HDL) was higher in the newborn guinea pig than in the adult. Plasma triglycerides peaked on the third day and decreased markedly. The bile acid pool increased progressively after birth with a 13-fold increase at 5 days of age. While the hepatic triglycerides decreased sharply in the newborn guinea pig, hepatic cholesterol increased in the first 5 days and then decreased to adult levels. This study has described the occurrence of “neonatal hypercholesterolemia” in the guinea pig and its possible relationship to the low level of bile acid synthesis.
- Published
- 1979
15. Apolipoprotein A-I in coronary-artery disease
- Author
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Bruce A. Kottke, Boas Gonen, Dac M. Dinh, Simon J.T. Mao, Terry J. Pundiak, Alan R. Zinsmeister, David R. Holmes, and James J. Maciejko
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medicine.medical_specialty ,Apolipoprotein B ,biology ,Apolipoprotein A-I ,business.industry ,Coronary Disease ,General Medicine ,medicine.disease ,Coronary artery disease ,Apolipoproteins ,Internal medicine ,Cardiology ,biology.protein ,Medicine ,Humans ,business - Published
- 1984
16. Regional aortic differences in atherosclerosis-susceptibility: changes in prostaglandin biosynthesis and cholesterol accumulation in response to desoxycorticosterone (DOCA)-salt induced hypertension
- Author
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Dac M. Dinh, B. A. Kottke, M. T. R. Subbiah, D. Deitemeyer, and L.K. Bale
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medicine.medical_specialty ,Arteriosclerosis ,Doca salt ,Lesion ,chemistry.chemical_compound ,ATHEROSCLEROSIS SUSCEPTIBILITY ,Internal medicine ,medicine.artery ,medicine ,Animals ,Columbidae ,Desoxycorticosterone ,Aorta ,Carneau ,biology ,Cholesterol ,biology.organism_classification ,medicine.disease ,Endocrinology ,Prostaglandin biosynthesis ,chemistry ,embryonic structures ,Hypertension ,cardiovascular system ,Prostaglandins ,lipids (amino acids, peptides, and proteins) ,medicine.symptom - Abstract
In spontaneously atherosclerosis-susceptible White Carneau pigeons, intimal cushions that appear at birth near the coeliac branch of aorta do not progress into atherosclerotic lesions. However, the area across from the intimal cushion (so called 'lesion area') a) accumulates cholesteryl esters b) synthesizes more PGE2 and c) eventually develops into complicated atherosclerotic plaques. When DOCA-salt hypertension is induced in the pigeons, the 'initimal cushion' area displays a) accumulation of increasing amounts of cholesteryl esters and b) increase in the synthesis of all prostaglandins (particularly PGE2) from C14-arachidonic acid and c) approaches similarity to the 'lesion area' in the magnitude of these changes. These results suggest that under the influence of a risk factor, the 'intimal cushion' can acquire biochemical properties of the atherogenic areas of the aorta.
- Published
- 1981
17. Arterial and metabolic changes during the critical period of spontaneous sterol accumulation in pigeon aorta
- Author
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Dac M. Dinh, Bruce A. Kottke, K.K. Unni, M.T.R. Subbiah, and Ivette A. Carlo
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medicine.medical_specialty ,Lipid accumulation ,Arteriosclerosis ,Period (gene) ,Clinical Biochemistry ,Pathology and Forensic Medicine ,Excretion ,chemistry.chemical_compound ,Species Specificity ,Internal medicine ,medicine.artery ,Extracellular ,medicine ,Animals ,Columbidae ,Molecular Biology ,Aorta ,Carneau ,biology ,Age Factors ,biology.organism_classification ,Sterol ,Oleic acid ,Sterols ,Endocrinology ,Cholesterol ,chemistry ,Biochemistry ,lipids (amino acids, peptides, and proteins) - Abstract
Age-related changes in arterial structure and sterol chemistry were investigated during spontaneous (noncholesterol fed) atherogenesis in the White Carneau pigeon and compared to the changes in atherosclerosis-resistant Show Racer breeds. The critical period of spontaneous sterol accumulation occurs at 9–12 months of age in the White Carneau pigeons. At this age there is an increase in cholesteryl esters (rich in oleic acid) in the aorta. The Show Racer pigeons, however, did not show significant changes with age. Structurally, aortas from both breeds showed intimal cushions at birth which become prominent with age, with an increase in extracellular lipid and basement membranelike structures and the presence of a few foam cells at 9–12 months of age. The Show Racers showed a slightly lesser amount of lipid material when compared to White Carneau pigeons. During the period of lipid accumulation the White Carneau pigeons showed a significantly decreased excretion of total fecal steroids P P
- Published
- 1976
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