Search PubMed⌕ Search

Biomedical subjects

D M Lee

Publications and source records attributed to D M Lee.

105 records · Page 6Linked to original sources
PubMed1984

Studies of lipids, lipoproteins, and apolipoproteins in Menkes' disease.

Three patients with Menkes' disease, an inherited disorder of copper transport, were studied to determine whether the copper deficiency was associated with a lipoprotein disorder. Hypocuprinemia was documented in all three cases. Two patients had severe copper and ceruloplasmin deficiencies, whereas the third patient had a less severe deficiency. Hypertriglyceridemia was observed in the first patient, and elevations in triglyceride, cholesterol, apolipoprotein B (ApoB), and apolipoprotein C-III (ApoC-III) occurred predominantly in the very low density lipoprotein fraction (VLDL). This patient had normal lipoprotein lipase activity but mild glucose intolerance. The second patient had a borderline high cholesterol level with normal plasma triglycerides and apolipoproteins, whereas the third patient appeared to have normal total cholesterol but slightly higher triglycerides with elevated plasma apolipoprotein E (ApoE). No striking differences were observed in the chemical composition of all lipoprotein subfractions between patients and controls except that the neutral lipid content of VLDL was higher in patients than in controls. The ApoB was initially normal in molecular weight but degraded faster than the controls during storage. The appearance of the major low density lipoprotein (LDL) fraction of the first two patients was opaque white, in contrast to clear yellow in the third patient and in the age- and diet-matched controls. This abnormal appearance of LDL in these patients was associated with low plasma levels of beta-carotene and ceruloplasmin. These findings suggest that decreased serum copper levels may be associated with lipid and lipoprotein abnormalities and may enhance lipid peroxidation of LDL accounting for the color change.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein C-III↗
PubMed1982

A quick and large-scale density gradient subfractionation method for low density lipoproteins.

A quick density gradient-banding subfractionation method has been developed for d < 1.063 g/ml lipoproteins. Up to 324 ml of plasma can be resolved into five distinct layers by a single ultracentrifugation. The separation was achieved with a discontinuous density gradient formed between plasma and a layer of NaCl solution of d 1.080 g/ml in an angle-head rotor during centrifugation at 45,000 rpm for 26 hr at 5 degrees C. VLDL and LDL(1) (layer 1, d < 1.020 g/ml) were at the top. Layer 2 (apparent d 1.025-1.028 g/ml), layer 3 (apparent d 1.032-1.043 g/ml) and layer 4 (apparent d 1.046-1.054 g/ml) were subfractions of normal LDL(2). Layer 5 (d > 1.071 g/ml) contained HDL and plasma proteins. A second step centrifugation separates VLDL from LDL(1). When opaque tubes are used, additional centrifugation is needed to separate layer 4 from layer 5. The subfractionation method was reproducible and was verified by analytical ultracentrifugation, chemical analyses, agarose electrophoresis, and electron microscopy. This method has been applied to plasma of normal males and females of the same age group. The chemical composition of a given subfraction from subjects of the same category was constant. However, compositional differences were found between normal males and females. The triglyceride content was higher in layer 2 and the cholesteryl ester content was lower in layer 4 for normal females than for males. Quantitatively, cholesterol concentration was significantly higher in layer 2 for normal males than for females. Layer 4 and layer 5 were the only fractions containing Lp(a). Applicability of the subfractionation method to studies of dyslipoproteinemia was demonstrated with plasma from patients with type III and type IV hyperlipoproteinemias. Marked differences were found in VLDL and LDL(1), both qualitatively and quantitatively, between the two types of patients and between the type III patient and normal subjects. A primarily quantitative difference was found in VLDL between the type IV patient and normal subjects. This isolation method yields concentrated subfractions that reveal the heterogeneity of LDL(2) in one spin, and offers quick isolation of narrow density ranges of LDL species, thereby providing better defined molecular entities for structural and/or metabolic studies.-Lee, D. M., and D. Downs. A quick and large-scale density gradient subfractionation method for low density lipoproteins.

Adult↗
PubMed1980

Acute and chronic effects of delta 9-tetrahydrocannabinol on complex behavior of squirrel monkeys.

Squirrel monkeys were trained to press either two (phase one) or five (phase two) differently colored keys sequentially. Food presentation resulted if colors were pressed in a specific order, and high levels or accuracy were generated. Acutely, delta 9-tetrahydrocannabinol reduced accuracy and rate of responding in a dose-related fashion under both the two-key and five-key conditions. Responding, however, was more sensitive to the drug under the five-key procedure. Accuracy of responding at the beginning of a sequence tended to be more sensitive to drug effects than responding near the end. Daily (chronic) administration resulted in the development of tolerance to both the rate- and accuracy-reducing effects of the drug, although tolerance developed more rapidly to the accuracy-reducing effects. Tolerance developed more slowly under the five-key procedure than under the two-key procedure. Details of tolerance development were related to aspects of acute effects, suggesting that some facets of tolerance development may be predictable from acute drug effects.

Animals↗
PubMed1980

Schedule-dependent tolerance to behavioral effects of delta 9-tetrahydrocannabinol when reinforcement frequencies are matched.

Squirrel monkeys pressed a lever under a multiple interresponse-time greater than 28-sec, modified random-interval schedule which provided comparable frequencies and temporal distributions of food pellet presentation in the two components. Daily intramuscular administration of either 0.25 or 1.00 mg/kg delta 9-tetrahydrocannabinol resulted initially in suppression and/or disruption of responding and concomitant decreases in the frequency of food presentation in both components. Responding in both components next increased, resulting in recovery of baseline frequencies of pellet delivery during the random-interval component, but continued depression during the interresponse-time schedule. The drug-induced changes in responding under the interresponse-time schedule diminished with repeated injections, whereas response rates during the random-interval schedule sometimes remained elevated. Interresponse-time distributions under the interresponse-time schedule showed that with repeated administration of the drug only those characteristics which had the greatest effect on reinforcement frequency recovered to baseline levels. When drug injections were replaced by daily injections of the vehicle, responding was greatly disrupted only during the random-interval component. These findings are only partially consistent with other results which suggest aht tolerance development to the behavioral effects of delta 9-tetrahydrocannabinol is greatly enhanced if the drug initially produces reinforcement loss.

Animals↗
PubMed1979

A novel method for converting apolipoprotein B, the major protein moiety of human plasma low density lipoproteins, into a water-soluble protein.

We have developed a new technique to solubilize apolipoprotein B (ApoB) in aqueous solutions. The procedure involves stirring ApoB in 6 M guanidine/20 mM NH4Cl/NH4OH in the presence of cupric ammonia complexes at pH 9.7 for 20 h in N2, and then removing these reagents by a series of dialysis in N2. The resulting Cu(NH3)4(2)+-treated (Cu2+-treated) ApoB is soluble in aqueous buffers of pH above 8.3 or below 3. Parallel experiments carried out on control proteins, human albumin, alpha-lactalbumin, and insulin, indicated no change in molecular weight and no creation of a new NH2-terminal amino acid after Cu2+-treatment. By Edman degradation, the Cu2+-treated ApoB showed no detectable NH2-terminal amino acid. These results showed that the mechanism of Cu2+-solubilization of ApoB was not due to the cleavage of peptide bonds. Electrophoresis on urea-polyacrylamide gel, Cu2+-treated ApoB showed the same number of bands as the non-treated ApoB in the separating gels (7%) near the cathode, suggesting the heterogeneity of ApoB. In SDS-polyacrylamide gel (10%), the reduced and Cu2+-treated ApoB migrated with the similar mobilities to the monomer or dimer of human albumin. Antibodies raised against Cu2+-treated ApoB gave at least two immunoprecipitin lines against the Cu2+-treated ApoB as well as the non-treated guanidine-HCl-soluble ApoB, suggesting the presence of non-identical subunits.

Amino Acids↗
PubMed1974

Physiocochemical properties of low-density lipoproteins of normal human plasma. Evidence for the occurrence of lipoprotein B in associated and free forms.

1. Low-density (d 1.006-1.063g/ml) lipoproteins from normal human plasma were separated by differential preparative ultracentrifugation into six subfractions. Each low-density (LD) lipoprotein subfraction contained lipoprotein B as the major and lipoproteins A and C as the minor lipoprotein families. 2. Three lipoprotein B subfractions (LP-B), LP-B-III (d 1.019-1.030g/ml), LP-B-IV (d 1.030-1.040g/ml) and LP-B-V (d 1.040-1.053g/ml) were prepared from the corresponding LD lipoprotein subfractions by immunoprecipitating small amounts of lipoproteins A and C. 3. Determination of hydrodynamic properties indicated that LD lipoproteins consisted of three molecular segments characterized by a stepwise change in the molecular weight: LDL-I and LDL-II subfractions (d 1.006-1.019g/ml) with an average mol.wt. of 4.75x10(6), LDL-III (d 1.019-1.030g/ml) with a mol.wt. of 3.99x10(6), and LDL-IV, LDL-V and LDL-VI (d 1.030-1.063g/ml) with a mol.wt. of 2.85x10(6). 4. All three lipoprotein B subfractions had an average mol.wt. of 3.16x10(6). 5. The LDL-I and LDL-II subfractions consisted of lipoprotein B and lipoprotein C families which were present in the form of an association complex. This was isolated from serum by immunoprecipitation with antibodies to lipoprotein B. The complex had a mol.wt. of 4.35x10(6). 6. The results indicate a fundamental difference between the LD lipoprotein subfractions with d 1.006-1.019g/ml and those subfractions with d 1.030-1.063g/ml. In the former, lipoprotein B occurs as a part of an association complex, whereas in the latter it occurs as a separate entity.

Animals↗