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Biomedical subjects

R L Jackson

Publications and source records attributed to R L Jackson.

At least 73 records · Page 4Linked to original sources
PubMed1988

Inhibition by probucol of interleukin 1 secretion and its implication in atherosclerosis.

Intravenous injection of 1.5 mg of acetylated low-density lipoprotein (LDL) or 100 micrograms of lipopolysaccharide (LPS) to zymosan-primed mice induced a decrease in serum zinc levels measured 6 hours after injection, suggesting the release of interleukin 1 (IL-1). Oral administration of probucol, 100 mg/kg once daily for 14 days, inhibited the LPS-induced fall in serum zinc levels, suggesting inhibition of IL-1 release. Direct evidence for inhibition of IL-1 release by probucol was obtained with an ex vivo system in which, compared with controls, peritoneal macrophages from probucol-treated mice (100 mg/kg orally X 3, or 0.25% in the diet for 3 weeks) secreted 80 to 90% less IL-1 upon LPS stimulation, measured by the C3H/HeJ thymocyte proliferation assay. Inhibition of IL-1 secretion by probucol may contribute to the therapeutic effect of probucol in atherosclerosis since as little as 1 unit of recombinant IL-1 beta was found to induce proliferation of aortic smooth muscle cells. With regard to the endogenous stimulus for IL-1 secretion, oxidized LDL is a putative candidate because it is capable of stimulating peritoneal macrophages to secrete IL-1. Because oxidized LDL is involved in the transformation of macrophages to foam cells, our data on IL-1 induction by oxidized LDL and the mitogenic effect of IL-1 on aortic smooth muscle cells suggest that activated macrophages play an important role in atherogenesis.

Animals↗
PubMed1988

Comparison of the effects of neuropeptide Y (NPY) and 4-norleucine-NPY on isolated perfused rat hearts; effects of NPY on atrial and ventricular strips of rat heart and on rabbit heart mitochondria.

Isolated perfused rat hearts were used to compare the effects of the synthetic neuropeptide Y (NPY) and 4-norleucine-NPY on cardiac function. Each peptide exhibited both negative inotropic and chronotropic effects, and also caused coronary vasoconstriction leading to a reduction in coronary flow. A comparison of the IC50 values from dose-response curves using 10(-14) to 10(-7) M peptides (IC50 is the peptide concentration that produced a 50% decrease of the maximal effect) indicated that NPY was more potent as inhibitor of contractility and less potently inhibited coronary flow and heart rate, whereas 4-norleucine-NPY had more inhibitory influence on coronary flow and heart rate and less on cardiac contractility. This difference in potencies suggests that the inhibitory effects of NPY on contractility, coronary flow and heart rate may be independent of each other. Since NPY also decreased the contractile force of isolated left atrial and right ventricular strips of the rat heart, the coronary flow decrease cannot be the cause of the negative inotropy of isolated heart. Pretreatment of atrial and ventricular strips with NPY did not influence the positive inotropic effect produced by the cardiac glycoside ouabain indicating that sarcolemmal Na+, K+-ATPase was not involved in the inhibitory inotropic effect of NPY. Further studies towards elucidating the mechanism of the negative inotropy of cardiac muscles using isolated heart mitochondria revealed that NPY uncoupled oxidative phosphorylation and blocked mitochondrial calcium uptake; the former event fosters negative inotropy. Since these effects on mitochondria occurred at concentrations 100-fold higher than those required for negative inotropy, the two effects of NPY may not be related.

Animals↗
PubMed1988

Ecological breastfeeding and child spacing.

Until the 2nd and 3rd decades of this century, breastfeeding was essential for infant survival. In that period, spacing of children was generally about 2 years. Later, improved modified cow's milk preparations became commercially available and were well tolerated by most infants. As a result, near cessation of ecological breastfeeding occurred toward the middle of the century. The decline in ecological breastfeeding was associated with early postpartum ovulation and shortened child-spacing of about 1 year. The endocrinology of breastfeeding is now known in considerable detail. Prolactin is secreted promptly in response to nipple stimulation and is a reliable marker of the endocrine alterations occurring postpartum. Success of lactation in suppression of ovulation was found to occur when infants sucked frequently and when only small amounts of selected foods were introduced gradually after the infants were about 6 months of age.

Amenorrhea↗
PubMed1988

Monoclonal antibodies that distinguish between active and inactive forms of human postheparin plasma hepatic triglyceride lipase.

Hepatic triglyceride lipase (H-TGL) was purified from human postheparin plasma. Specific monoclonal antibodies (MAbs) were produced that discriminate between active (native) and inactive (denatured) forms of the enzyme. Mice immunized with native H-TGL resulted in MAbs that recognized only the native protein. The antibodies did not react with H-TGL treated with 1% sodium dodecyl sulfate or heated at 60 degrees C. The loss of immunoreactivity with heating correlated directly with the loss of enzyme activity and there was a corresponding increase in immunoreactivity with the MAbs prepared against the denatured enzyme. Western blot analysis of postheparin plasma with the MAbs against denatured H-TGL gave a single protein band of 65 kD; preheparin plasma showed no detectable immunoreactivity with either MAb. These immunochemical studies suggest that there are no circulating active or inactive forms of H-TGL in man. Furthermore, the MAbs provide the necessary reagents for development of immunoassays for H-TGL.

Antibodies, Monoclonal↗
PubMed1988

Effects of signaling inescapable shock on subsequent escape learning: implications for theories of coping and "learned helplessness".

The present experiments reveal that shuttle-escape performance deficits are eliminated when exteroceptive cues are paired with inescapable shock. Experiment 1 indicated that, as in instrumental control, a signal following inescapable shock eliminated later escape performance deficits. Subsequent experiments revealed that both forward and backward pairings between signals and inescapable shock attenuated performance deficits. However, the data also suggest that the impact of these temporal relations may be modulated by qualitative aspects of the cues because the effects of these relations depended upon whether an increase or decrease in illumination (Experiment 2) or a compound auditory cue (Experiment 4) was used. Preliminary evidence suggests that the ability of illumination cues to block escape learning deficits may be related to their to reduce contextual fear (Experiment 3). The implications of these data for conceptions of instrumental control and the role of fear in the etiology of effects of inescapable shock exposure are discussed.

Adaptation, Psychological↗
PubMed1987

Isolation and characterization of four heparin-binding cyanogen bromide peptides of human plasma apolipoprotein B.

Apolipoprotein B-100 (apoB-100) is the major protein constituent of human plasma low-density lipoproteins (LDL). On the basis of its amino acid sequence [Chen, S.-H., Yang, C.-Y., Chen, P.-F., Setzer, D., Tanimura, M., Li, W.-H., Gotto, A. M., Jr., & Chan, L. (1986) J. Biol. Chem. 261, 12918-12921], apo B-100 is one of the largest monomeric proteins known with a calculated molecular weight of 512937. Heparin binds to the LDL surface by interacting with positively charged amino acid residues of apoB-100, forming soluble complexes in the absence of divalent metals and insoluble complexes in their presence. The purpose of this study was to isolate and characterize the heparin-binding domain(s) of apoB-100. Human plasma LDL were fragmented with cyanogen bromide (CNBr). After delipidation and reduction-carboxymethylation, the CNBr peptides were fractionated by sequential chromatography on DEAE-Sephacel, Mono S, and high reactive heparin (HRH) AffiGel-10; HRH was purified by chromatography of crude bovine lung heparin on LDL AffiGel-10. Heparin-binding peptides were further purified by reverse-phase high-performance liquid chromatography. Heparin-binding activity was monitored by a dot-blot assay with 125I-HRH. The amino-terminal sequences of four CNBr heparin-binding peptides (CNBr-I-IV) were determined. CNBr-I-IV correspond to residues 2016-2151, 3109-3240, 3308-3394, and 3570-3719, respectively, of the amino acid sequence of apoB-100. Each CNBr peptide contains a domain(s) of basic amino acid residues which we suggest accounts for their heparin-binding activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1987

Physical-chemical interaction of heparin and human plasma low-density lipoproteins.

This study characterizes the physical-chemical interactions of heparin with human plasma low-density lipoproteins (LDL). A high reactive heparin (HRH) specific for the surface determinants of LDL was isolated by chromatography of commercial bovine lung heparin on LDL immobilized to AffiGel-10. HRH was derivatized with fluoresceinamine and repurified by affinity chromatography, and its interaction with LDL in solution was monitored by steady-state fluorescence polarization. Binding of LDL to fluoresceinamine-labeled HRH (FL . HRH) was saturable, reversible, and specific; HRH stoichiometrically displaced FL . HRH from the soluble complex, and acetylation of lysine residues on LDL blocked heparin binding. Titration of FL.HRH with excess LDL yielded soluble complexes with two LDL molecules per heparin chain (Mr 13,000) characterized by an apparent Kd of 1 microM. Titration of LDL with excess HRH resulted in two classes of heparin binding with two and five heparin molecules bound per LDL and apparent Kd values of 1 and 10 microM, respectively. At physiological pH and ionic strength, the soluble HRH-LDL complexes were maximally precipitated with 20-50 mM Ca2+. Insoluble complexes contained 2-10 HRH molecules per LDL with the final product stoichiometry dependent on the ratio of the reactants. The affinity of HRH for LDL in the insoluble complexes was estimated between 1 and 10 microM. Insoluble LDL-heparin complexes were readily dissociated with 1.0 M NaCl, and their formation was prevented by acetylation of the lysine residues on LDL.

Animals↗
PubMed1987

Human plasma lipid transfer protein catalyzes the speciation of high density lipoproteins.

The role of purified plasma lipid transfer protein complexes in determining the particle size distribution of human plasma high density lipoproteins (HDL) was examined in vitro. Incubation of HDL2 or HDL3, isolated from normolipemic subjects with very low density lipoproteins (VLDL) or VLDL-remnants and lipid transfer protein complex had little or no effect on HDL particle size. In contrast, HDL isolated from patients with hypertriglyceridemia, designated HDL3D, showed speciation of particle size distribution when incubated with VLDL-remnants and the transfer protein. Incubation of HDL3D with VLDL-remnants and lipid transfer complex resulted in the production of two particles of radius 4.3 and 3.7 nm; incubation with VLDL or in the absence of the transfer protein did not result in a redistribution of particle size. We suggest that the action of lipid transfer protein complex on triacylglycerol-rich lipoprotein remnants and HDL accounts for the low levels of HDL-cholesterol observed in subjects with severe hypertriglyceridemia.

Carrier Proteins↗
PubMed1987

Mechanism of action of lipoprotein lipase and hepatic triglyceride lipase.

Lipoprotein lipase (LPL) and hepatic triglyceride lipase (H-TGL) were isolated from human postheparin plasma, and their interfacial properties were examined with mixed monolayers of trioleoylglycerol and phosphatidylcholine. LPL showed a surface pressure optimum between 20 and 22 mN/m, whereas H-TGL activity decreased at lipid packing densities of greater than 20 mN/m. LPL activity toward monolayers containing 2 mol percent trioleoylglycerol was enhanced 2.6-fold by the addition of 5 mol percent cholesteryl oleate; cholesteryl ester had no effect on H-TGL activity. We suggest that differences in interfacial properties account for the lipoprotein specificity of these lipolytic enzymes.

Catalysis↗
PubMed1987

Rapid purification and revised amino-terminal sequence of hirudin: a specific thrombin inhibitor of the bloodsucking leech.

Hirudin is a specific polypeptide thrombin inhibitor consisting of 65 amino acids that is produced by the leech, Hirudo medicinalis. We describe a rapid method for the purification of hirudin from a leech extract. Crude hirudin, purchased from a commercial source, was first fractionated on a DEAE-HPLC column using a salt gradient. Hirudin activity was monitored by inhibition of the thrombin-mediated hydrolysis of a synthetic substrate H-D-Phenylalanyl-Pipecolyl-Arginine-p-Nitroanilide. The fractions containing antithrombin activity were pooled and further purified by reverse-phase HPLC. The homogeneity of purified hirudin was confirmed by a single amino-terminal sequence for 43 residues with Val-Val as the first two amino acids. Residue 33 was Asn rather than Asp as reported previously.

Amino Acid Sequence↗
PubMed1987

Effect of a sustained release formulation of diltiazem on the development of atherosclerosis in cholesterol-fed rabbits.

Cholesterol-fed rabbits were used to test potential anti-atherosclerotic effects of diltiazem, a calcium antagonist of the benzothiazepine type. Two groups of 7 rabbits each were fed standard laboratory chow supplemented with 1% cholesterol. One group received a 60 mg sustained release diltiazem capsule twice a day and the other group received a placebo capsule twice a day. A third group of control animals were fed an unmodified basal diet under conditions exactly the same as the experimental groups. All groups were studied over a period of 16 weeks. The cholesterol-fed animals showed a marked increase in plasma total cholesterol which was not significantly different for the diltiazem and placebo groups. Plasma calcium levels, blood pressure, and heart rate were also unchanged from the control animals. In the diltiazem-treated animals, 47.5 +/- 10.5% of the aortae showed atherosclerotic lesions; the value for the placebo group was 43.1 +/- 8.1%. Similar results were obtained for the coronary arteries. These results show that diltiazem treatment in the doses employed in this study had no effect on the reduction of atherosclerosis in this animal model.

Animals↗
PubMed1987

Characterization of high density lipoproteins from patients with severe hypertriglyceridemia.

High density lipoproteins (HDL) were isolated by zonal ultracentrifugation from 6 subjects with severe hypertriglyceridemia. Four subjects had familial endogenous hypertriglyceridemia with fasting chylomicronemia; 2 subjects were non-insulin-dependent diabetics. Plasma triglycerides ranged from 920 to 5440 mg/dl and HDL-cholesterol from 12 to 23 mg/dl. The major HDL from these hypertriglyceridemic subjects had a peak mean density of 1.153 g/ml as compared to 1.140 g/ml for HDL3 from normal subjects. None of the subjects had significant amounts of HDL corresponding to normal HDL2. The major subpopulation of hypertriglyceridemic HDL had a mean diameter of 8.4 +/- 0.1 nm (range 7.6-9.0 nm). The HDL were enriched in triacylglycerols and depleted in cholesteryl esters and the C apoproteins as compared to control HDL3. The mass ratio of triacylglycerols to cholesteryl esters ranged from 4.00 to 5.22 for the patients versus 0.41 for normal HDL3. The increased content of triacylglycerols partially explains the decreased amount of cholesterol associated with these hypertriglyceridemic HDL.

Centrifugation↗
PubMed1987

Preservation of pathology specimens by silicone plastination. An innovative adjunct to pathology education.

The authors have used the process of plastination to preserve gross anatomic specimens for teaching purposes. A specimen is fixed in 10% buffered formalin and dehydrated in increasing grades of ethanol. Thereafter it is saturated with methylene chloride and then impregnated in vacuo at -20 degrees C with silicone rubber. Final steps involve drainage and exposure to a curing agent. The total time required is approximately 16 weeks. The finished plastinated specimen is dry to the touch, odorless, and nontoxic, yet it maintains its original shape and, in many cases, is reasonably close in color and consistency. It resists deterioration and can be stored at room temperature indefinitely. The authors have found plastinated specimens to be superior to those preserved in formalin for teaching anatomic pathology to undergraduate medical students.

Costs and Cost Analysis↗