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Biomedical subjects

J S Parks

Publications and source records attributed to J S Parks.

At least 109 records · Page 6Linked to original sources
PubMed1987

Effect of fish oil versus lard diets on the chemical and physical properties of low density lipoproteins of nonhuman primates.

Twenty-four adult male African green grivet monkeys were fed diets containing 42% of calories as lard or menhaden oil and 0.76 mg of cholesterol/kcal for a period of 8 months. Plasma samples from fasting animals were then taken and low density lipoproteins (LDL) were isolated by ultracentrifugation and agarose column chromatography. The LDL were analyzed chemically, and physical properties of the particles were studied by differential scanning calorimetry. The fish oil group had significantly smaller LDL (2.91 vs. 3.43 g/mumol), which contained fewer molecules per particle of all lipid constituents, except triglyceride, compared to the lard-fed animals. The fish oil-fed group had 15% of the total cholesteryl esters as n-3 fatty acyl species and the number of n-3, but not n-6, cholesteryl esters per LDL particle was proportional to LDL size. The numbers of saturated and monounsaturated cholesteryl ester species per LDL particle were highly correlated with LDL size for both diet groups. The LDL of the fish oil group had broad reversible thermotropic transitions that were 12-13 degrees C lower than those of the lard group. These transitions were indicative of order-disorder transitions of the LDL core cholesteryl esters. The peak transition temperature of LDL of the lard group was proportional to the ratio of saturated and monounsaturated to polyunsaturated cholesteryl ester species (CEFA ratio). However, the much lower peak transition temperature of the LDL of the fish oil group was not related to the CEFA ratio nor to the triglyceride content of the particles, but rather, to the n-3 cholesteryl ester content of the particles. Studies of cholesteryl ester model systems demonstrated that relatively small amounts of n-3 cholesteryl esters (less than 15% of total cholesteryl ester) could result in a lowering of the peak transition temperature of cholesteryl linoleate similar to that seen for intact LDL. We conclude that n-3 cholesteryl esters in small quantities have a marked disordering effect on the core cholesteryl esters of LDL, resulting in a striking depression of LDL transition temperature. In addition, we conclude that n-3 cholesteryl esters are preferentially utilized relative to n-6 cholesteryl esters to increase the number of cholesteryl esters per LDL particle with LDL enlargement in fish oil-fed animals.

Animals↗
PubMed1986

Blood pressure, body fat, and dehydroepiandrosterone sulfate variation in adolescence.

Several significant interrelations among variation in blood pressure, body fat, and adrenal androgen levels, as assessed by serum dehydroepiandrosterone sulfate concentrations, were found in black male and female adolescents, aged 12 to 16 years. In girls, high levels of dehydroepiandrosterone sulfate were associated with significantly higher levels of blood pressure (alpha = 0.05), even after adjusting for the significant association between increased levels of dehydroepiandrosterone sulfate and body fat. The increased body fat (i.e., body mass index) found with higher levels of dehydroepiandrosterone sulfate in girls was related to significantly greater (alpha = 0.05) accumulations of fat in the upper trunk, as opposed to the limb. In boys, high levels of serum dehydroepiandrosterone sulfate, low body mass index, and significantly higher blood pressure were interrelated (alpha = 0.05). In addition to the interaction of increased body mass index or body fat and increased levels of dehydroepiandrosterone sulfate in association with higher blood pressure, high levels of the adrenal androgen, even in boys with low body mass index, were associated independently with relatively higher blood pressure. Body proportion analyses for these boys indicated that they were tall and thin, in contrast to the other boys with low body mass index, who were generally short and thin.

Adipose Tissue↗
PubMed1986

Lecithin:cholesterol acyltransferase-induced modifications of liver perfusate discoidal high density lipoproteins from African green monkeys.

The role of lecithin:cholesterol acyltransferase (LCAT) in the formation of plasma high density lipoproteins (HDL) was studied in a series of in vitro incubations in which perfusates from isolated African green monkey livers were incubated at 37 degrees C with partially purified LCAT for between 1 and 13 hr. The HDL particles isolated from monkey liver perfusate stored at 4 degrees C and not exposed to added LCAT contained apoA-I and apoE, were deficient in neutral lipids, and were observed by electron microscopy as discoidal particles. Particle sizes, measured as Stokes' diameters by gradient gel electrophoresis (GGE), ranged between 7.8 nm and 15.0 nm. The properties of perfusate HDL were unchanged following incubation at 37 degrees C in the presence of an LCAT inhibitor. However, HDL subfractions derived from incubations at 37 degrees C with active LCAT contained apoA-I as the major apoprotein, appeared round by electron microscopy, and possessed chemical compositions similar to plasma HDL. The HDL isolated from perfusate incubations at 37 degrees C with low amounts of LCAT had a particle size and chemical composition similar to plasma HDL3a. In three of four perfusates incubated with higher levels of LCAT activity, the HDL products consisted of two distinct HDL subpopulations when examined by GGE. The major subpopulation was similar in size and composition to plasma HDL2a, while the minor subpopulation demonstrated the characteristics of plasma HDL2b. The data indicate that the discoidal HDL particles secreted by perfused monkey livers can serve as precursors to three of the major HDL subpopulations observed in plasma.

Animals↗
PubMed1985

Fusion of low density lipoproteins with cholesterol ester-phospholipid microemulsions. Prevention of particle fusion by apolipoprotein A-I.

Little is known about the mechanism and control of lipoprotein particle fusion, although apoproteins are presumed to be important in maintenance of particle structure. This study characterizes the interaction of apo-B-containing low density lipoproteins (LDL) with cholesterol ester microemulsions (CEME) in the presence and absence of apo-A-I to determine if a role for these apoproteins in particle integrity could be ascertained. CEME are an apoprotein-free analog of LDL formed by sonication of radiolabeled phospholipid (surface) and cholesterol ester (core). Incubation of CEME with LDL followed by precipitation of LDL with MnCl2 resulted in coprecipitation of CEME with LDL that was time-, temperature-, and concentration-, but not pH (pH 6-9)-, dependent and occurred over a wide range of CEME and LDL particle compositions. Particles from the incubation were larger than the unincubated particles and intermediate in density and electrophoretic mobility between the starting LDL and CEME. Differential scanning calorimetry experiments suggested that CEME surface and core lipids had mixed with those of LDL. When particles from incubations were exposed to an anti-apo-B column, radiolabeled surface and core molecules originating from the CEME particles bound to the column. Particles eluted at low pH from the anti-apo-B column were irregularly shaped and had excess surface material as judged by electron microscopy. Incubation of CEME with LDL in the presence of 3 M KBr or 4% bovine serum albumin did not alter the interaction of the particles. However, incubation of CEME with LDL in the presence of apo-A-I (2:1 CEME cholesterol-to-apo-A-I mass ratio) greatly reduced the interaction of the LDL and CEME particles. We conclude that the incubation of CEME with isolated LDL resulted in particle fusion that was prevented by apo-A-I.

Apolipoprotein A-I↗
PubMed1985

Chromosomal assignment of human sequences encoding arginine vasopressin-neurophysin II and growth hormone releasing factor.

Complementary DNA clones encoding bovine vasopressin and human pancreas growth hormone releasing factor have been used to map homologous sequences in the human genome. Assignment of both cloned sequences to human chromosome 20 was accomplished by hybridization of insert DNAs to a panel of human-rodent somatic cell hybrids. Both these probes have been used to examine the structure of their respective genes in DNA from various individuals. No restriction fragment variants for growth hormone releasing factor have yet been found. Analysis of populations for restriction fragment length polymorphisms associated with disease states involving arginine vasopressin is underway.

Animals↗
PubMed1985

An effect of gene dosage on production of human chorionic somatomammotropin.

The gene deletions responsible for isolated partial deficiency of fetal human chorionic somatomammotropin (hCS) production were characterized by restriction endonuclease analysis of genomic DNA prepared from the leukocytes of an affected child. The phenotypically normal child was the product of a 38-week pregnancy characterized by peak maternal hCS levels of 1.1 micrograms/microliter (normal, 3-9.2 micrograms/ml) and normal levels of other pregnancy-associated hormones. Two genes, termed hCS-A and hCS-B, specify the same mature hCS peptide and are responsible for fetal hCS production. Digestion of the child's DNA with the enzymes Hind III, Eco RI, Bam HI, Bgl II, Hinc II and Msp I disclosed absence of the restriction fragments that normally contain the hCS-A gene. However, the hCS-B gene was present in the child's DNA. The child's DNA digests contained an abnormally large Eco RI fragment of 10.0 kb containing the hCS-L gene. This abnormal fragment is a marker for a deletion that is responsible for complete deficiency of hCS when present in the homozygous state. The child's DNA restriction patterns were consistent with heterozygosity for two different deletions involving hCS genes. The paternal hGH gene cluster lacked the hCS-A, human GH variant, and hCS-B genes, while the maternal cluster lacked only the hCS-A gene. Thus, the child's DNA contained only one of the normal complement of four functional hCS genes per diploid genome. Material hCS levels approximately one fourth as great as those present at comparable stages of normal pregnancies indicated that there was no compensatory increase in expression of the remaining hCS gene.

Chromosome Deletion↗
PubMed1985

Human growth hormone gene deletion without antibody formation or growth arrest during treatment--a new disease entity?

Using restriction endonuclease analysis of genomic DNA hybridized to a human chorionic somatomammotropin (hCS) complementary (c)DNA probe, we studied four young Jewish patients with isolated growth hormone deficiency (IGHD), and 15 family members. One family originated in Iraq, two in Yemen and one in Iran. Each patient was homozygous for a deletion of approximately 7.5 kilobases, which included the hGH-N gene. Three of the deletions were associated with the same restriction fragment length polymorphism haplotype, while the deletion in the child of Iranian descent was associated with a different haplotype. All the patients were treated with three injections per week of pituitary human growth hormone (hGH) for periods of 2 1/2 to 14 1/2 years. All had a good growth response. Three reached normal and one almost normal height. Repeated serum analyses revealed absence of anti-hGH antibodies. Thus, the presently described patients differ from those previously reported from Switzerland, Argentina and Japan, all of whom developed anti-hGH antibodies during treatment, with resultant slowing or arresting of growth. Expression of heterozygosity in family members was variable with regard to stature, hGH reserve and insulin-like growth factor I (IGF-I) levels. It is hypothesized that hGH-N gene deletion is not the sole determinant of immune response during hGH treatment, and that the difference between the current series and other cases needs further investigation.

Autoantibodies↗
PubMed1985

Alteration of high density lipoprotein subfraction distribution with induction of serum amyloid A protein (SAA) in the nonhuman primate.

Overnight chair restraint results in a dramatic increase in serum amyloid A protein (apoSAA) of nonhuman primate high density lipoprotein (HDL). To determine whether apoSAA induction resulted in a displacement of indigenous HDL protein or a change in the subfraction distribution of HDL, we analyzed the characteristics of HDL subfractions in eight vervet monkeys before and 24 hr after apoSAA induction. Blood was taken from each animal before and after chair restraint to induce apoSAA. HDL was isolated from the plasma by ultracentrifugation and agarose column chromatography. The isolated HDL was subfractionated by density gradient centrifugation and five resulting subfractions were analyzed for protein and lipid content. With apoSAA induction there was a significant increase in d less than 1.09 g/ml protein, phospholipid, and free and esterified cholesterol which resulted in a 44% increase in the total mass of this subfraction. Concomitantly, there was a significant decrease in d 1.10-1.11 g/ml protein, total cholesterol, and cholesteryl ester, which resulted in a 16% decrease in the total mass of the subfraction. The response of the d 1.10-1.11 and d greater than 1.12 g/ml subfraction protein, cholesterol, and phospholipid concentrations to chair restraint for individual animals was directly proportional to their plasma HDL concentrations. Although there was a change in the HDL subfraction concentrations after chair restraint, there was no change in the lipid composition of the HDL subfractions nor in the total amount of HDL protein. However, the apoSAA/A-I ratio was significantly increased with induction while the apoA-II + C's/A-I ratio remained unchanged. The apoSAA/A-I ratio progressively increased with the density of the HDL subfraction. The protein composition of the d greater than 1.12 g/ml subfraction was changed from an average of three apoA-I and two apoA-II (or C's) molecules per particle to an average of two apoA-I, one apoA-II (or C's), and three or four apoSAA molecules per particle after chair restraint. Thus, apoSAA was predominantly associated with the denser HDL subfractions even though the lighter HDL subfractions were the most responsive in terms of changes in concentration. These data suggest that chair restraint of nonhuman primates induces apoSAA which displaces apoA-I and apoA-II or C's from HDL without altering the overall lipid and protein composition of the particle. In addition, chair restraint alters the concentration of HDL subfractions in ways that may be independent of apoSAA induction.

Amyloid↗
PubMed1985

Studies of low density lipoprotein molecular weight in human beings with coronary artery disease.

Low density lipoprotein molecular weight (LDL MW) correlates positively with coronary artery disease in cholesterol-fed nonhuman primates. To evaluate this in human beings with coronary artery disease (CAD) we measured LDL MW in 93 volunteers undergoing coronary angiography (47 controls and 46 CAD patients). LDL MW of CAD patients was less than that of controls (patients, 2.79 +/- 0.17 g/mumol; controls, 2.93 +/- 0.19 g/mumol; P less than 0.001). However, LDL MW decreased as plasma triglyceride increased and concentrations of triglyceride were greater in CAD patients than in controls. Since decreased LDL MW is likely to result, in part, from increased plasma triglyceride concentrations, we attempted to determine the effect of triglyceride on the relation of LDL MW to CAD in this study. After covariance adjustment for triglyceride, there was no LDL MW difference between CAD patients and controls. Because LDL heterogeneity has been identified in other studies and was apparent on inspection of agarose column profiles of LDL of these volunteers, we sought differences in the profiles that might distinguish coronary disease cases from controls. No differences could be found. In addition, we used density gradient ultracentrifugation to characterize LDL in more detail in a subset of volunteers who had a wide range of plasma triglyceride concentrations (50 mg/dl to 900 mg/dl). LDL mean hydrated density was inversely related to LDL MW and increased as triglyceride increased. The increase in peak density was reflected in an increase in percent of total protein in LDL found to have d greater than 1.045 g/ml and a decrease in protein in LDL of d 1.035-1.040 g/ml. These interrelationships were not apparently influenced by coronary artery status.

Centrifugation, Density Gradient↗
PubMed1984

The endocrine spectrum of septo-optic dysplasia.

Six children with septo-optic dysplasia were evaluated at the Children's Hospital of Philadelphia. There was a common history of young, nulliparous mothers. The clinical presentation of these children differed according to age of presentation and was a function of the degree and type of hypothalamic-pituitary and ophthalmologic impairment. Endocrine evaluation revealed four of six children to be growth hormone deficient, four of six to have hypothalamic hypothyroidism, and two of four to have elevated prolactin levels. One of the patients demonstrated adrenocorticotropic hormone deficiency, and one had diabetes insipidus. Neuroanatomic findings in the children were variable, but, in general, the rare syndrome did not carry as grave a morbidity as had been reported previously. Our data support a high degree of hypothalamic impairment in septo-optic dysplasia.

Adolescent↗
PubMed1983

Interactions of the carboxyl group of oleic acid with bovine serum albumin: a 13C NMR study.

The interactions of the carboxyl group of oleic acid with bovine serum albumin (BSA) were studied by 13C NMR spectroscopy at 50.3 MHz using 90% isotopically substituted [1-13C]oleic acid. 13C NMR spectra were obtained as a function of the mole ratio of oleic acid to BSA (from 0.5-10.0) and, for selected mole ratios, as a function of pH (between pH 3.0 and 10.6) and temperature (between 15 and 55 degrees C and thermally denatured at 95 degrees C). Except for spectra of highly acidic (pH less than or equal to 3.9) and denatured samples, spectra of oleic acid/BSA complexes showed multiple narrow resonances from the oleic acid carboxyl carbon in a region (179-184 ppm) downfield from protein carbonyl and carboxyl carbon resonances. At low oleic acid/BSA ratios (0.5 and 1.0), at least two oleic acid carboxyl carbon peaks were observed; at high ratios (greater than or equal to 3.0), at least four peaks were present. The intensities of individual peaks, but not their chemical shifts, varied with the oleic acid/BSA ratio. The chemical shift of individual oleic acid peaks was invariant between pH 6.0 and 10.6; below pH 6.0, one of the oleic acid resonances exhibited an NMR titration curve with an apparent pKa of approximately 4. Thus, BSA binding sites for oleic acid are heterogeneous as monitored by the magnetic microenvironment of the oleic acid carboxyl carbon. The number of different oleic acid environments and the relative population of oleic acid molecules in these environments is dependent on the mole ratio of oleic acid/BSA. Our results suggested that the anionic form of oleic acid is bound to BSA at physiological pH and that the multiplicity of NMR peaks for [1-13C]oleic acid resulted from, at least in part, different electrostatic and hydrogen bonding interactions between the oleic acid carboxyl group and specific amino acid residues of BSA.

Fourier Analysis↗
PubMed1983

1H NMR studies of lymph chylomicra and very low density lipoproteins from nonhuman primates.

1H NMR spectroscopy at 200 MHz was used to study triglyceride crystalline leads to liquid transitions which occurred on heating between 10 and 50 degrees C in very low density lipoprotein and subfractionated chylomicron particles from nonhuman primates fed a saturated fat (butter fat) diet. Model system studies of pure triglycerides (triolein, tripalmitin and a 1:1 mixture) and emulsion particles consisting of these triglycerides with a surface of egg phosphatidylcholine showed that high resolution spectra were obtained only from liquid triglycerides. In lipoprotein spectra, changes in 1H NMR peak intensities and line widths accompanied the solid leads to liquid transition of the constituent triglycerides. Peak areas of fatty acyl resonances were proportional to the percentage of melted triglyceride determined by differential scanning calorimetry. NMR peak area measurements showed that the calorimetric transition involved the melting of relatively greater numbers of saturated fatty acyl chains than unsaturated chains; at temperatures well below the solid leads to liquid transition, the lipoproteins contained a significant fraction (approximately 33%) of liquid triglycerides which were relatively enriched in unsaturated fatty acyl chains. For model systems containing mixtures of solid and liquid triglycerides, the temperature dependence of line widths of fatty acyl resonances demonstrated that solid triglycerides decreased the mobility of the liquid triglycerides. A similar temperature dependence for the lipoprotein resonances suggested that solid and liquid species are co-mixed in individual lipoprotein particles within a purified subfraction. Temperature-dependent line width and intensity changes were observed for the phospholipid-choline methyl resonance in lipoprotein spectra and were apparently independent of the core transition.

Animals↗
PubMed1983

Vasculitis, pulmonary cavitation, and anemia during antithyroid drug therapy.

Two thyrotoxic girls, aged 12 and 16 years, had a clinical picture consisting of purpuric skin rash, nephritis, pulmonary cavitation, hemoptysis, and profound anemia during antithyroid drug therapy. These major toxic manifestations prompted discontinuation of antithyroid drugs and institution of antibiotic and glucocorticoid therapy before the resolution of the severe illness. The girls eventually required ablative doses of radioactive iodine, and one of them had a thyroidectomy for the treatment of thyrotoxicosis. The skin biopsy specimen in one patient was indicative of mononuclear cell cutaneous vasculitis. After recovery, the patients had no evidence Of persistent anemia, nephritis, or pulmonary parenchymal disease.

Adolescent↗