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Biomedical subjects

D Atkinson

Publications and source records attributed to D Atkinson.

At least 109 records · Page 6Linked to original sources
PubMed1985

Structure and polymorphism of 1,2-dioleoyl-3-acyl-sn-glycerols. Three- and six-layered structures.

Triacylglycerols, which usually contain at least one unsaturated fatty acid, are the most important forms of stored biological lipids in teleosts, mammals, and most plants. Since the physical properties of such mixed-chain triacylglycerols are poorly understood, a systematic study of such compounds has been initiated. Stereospecific 1,2-dioleoyl-3-acyl-sn-glycerols were synthesized with even carbon saturated fatty acyl chains of 14-24 carbons in length. Their polymorphic behavior was examined by differential scanning calorimetry and X-ray powder diffraction. The thermal behavior revealed from one to four major polymorphic transitions depending upon saturated chain length. Plots of enthalpy of fusion and entropy vs. carbon number for melting of the most stable polymorph were linear throughout the series with slopes of 1.0 kcal/mol per carbon atom and 2.6 cal/(mol K) per carbon atom, respectively. These slopes indicate that the saturated chains are packed in a well-ordered tightly packed lattice. When the compounds were rapidly cooled to 5 degrees C, X-ray powder diffraction revealed strong beta' (ca. 3.8 and 4.2 A) reflections and weak beta (ca. 4.6 A) reflections. The beta subcell reflections intensified when the compounds were heated to within 5 degrees C of the melting temperature of the highest melting polymorph. Evidence of an alpha phase was not seen on 30-min X-ray exposures for any of the compounds. In the proposed packing arrangement the saturated and unsaturated chains are segregated into layers. The stable form of all compounds exhibits a triple layer packing mode in which a bilayer of oleoyl chains is segregated from an interdigitated layer of saturated chains.(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry↗
PubMed1985

Synthesis and polymorphism of 3-acyl-sn-glycerols.

3-Acyl-sn-glycerols with even-numbered saturated fatty acyl chains from decanoate to lignocerate were synthesized. Successful hydrolysis of the long acyl chain intermediate 1,2-isopropylidene-3-acyl-sn-glycerols from stearate to lignocerate was accomplished by applying the compounds to silica gel and exposing them to hydrogen chloride gas at -75 degrees C. The purity of the compounds was checked by boric acid impregnated thin-layer chromatography, 13C NMR, and reverse-phase high-pressure liquid chromatography. Differential scanning calorimetry and X-ray diffraction techniques were used to study the polymorphism of the compounds. In the beta phase obtained from solvent of crystallization, the acyl chain packing was in a two-dimensional oblique lattice with specific chain-chain interactions with a tilt angle of 55.4 degrees from the bilayer plane. The thickness of the region containing two glycerol head groups was 12.7 A. The phase transition enthalpy of melting for the beta phase was 1.06 kcal/mol of CH2. On being cooled these compounds crystallized reversibly to an unstable alpha phase, which on being further cooled underwent a second crystallization to a beta or beta' phase. The thermodynamic parameters and long spacings of these compounds in both beta and alpha phases were linear, indicating isostructural packing in each phase. The enthalpy of the melting transition of the alpha phase was 0.69 kcal/mol of CH2. In this phase, the chains were packed in a hexagonal lattice with nonspecific chain-chain interactions. The thickness of the head-group region (12.2 A) and the tilt angle (55 degrees) of the acyl chains in the alpha phase were very similar to those in the beta phase.

Calorimetry↗
PubMed1985

Adoptive transfer of autoimmune diabetes mellitus in biobreeding/Worcester (BB/W) inbred and hybrid rats.

Adoptive transfer of diabetes was accomplished by the injection of Con A-activated acutely diabetic BB/W rat spleen cells into immunosuppressed diabetes-resistant BB/W control rats and F1 hybrid offspring produced by BB/W X Lewis, BN, Yashida, and NEDH matings. Immune suppression methods that facilitated adoptive transfer of diabetes included neonatal thymectomy, cyclophosphamide, and splenectomy plus rabbit anti-rat lymphocyte serum injections. The successful transfer of BB/W diabetes to otherwise normal (BB/W X inbred)F1 rats and to diabetes-resistant BB/W animals suggests that antigenically normal pancreatic beta cells were destroyed by the injected effector cells. Diabetes-resistant BB/W control rats also evidenced diabetes after the injection of cyclophosphamide alone. The requirement for immunosuppression suggests that an intact immune system protects against adoptive transfer and diabetes in diabetes-resistant BB/W rats.

Animals↗
PubMed1984

Reassembled plasma low density lipoproteins. Phospholipid-cholesterol ester-apoprotein B complexes.

Reassembled low density lipoprotein (LDL) complexes have been prepared by the interaction of lipid-free sodium deoxycholate-solubilized apoprotein B (apoB) of native human LDL with preformed, 200 A in diameter, microemulsions of cholesteryl oleate (CO), surface-stabilized by either egg yolk phosphatidylcholine ( EYPC ) or dimyristoyl phosphatidylcholine (DMPC). Gel chromatography of PC/CO/apoB complexes shows co-elution of the complex at 43% PC, 43% CO, and 14% apoB. Negative stain electron microscopy shows the particles to be circular, homogeneous, and approximately 200 A in diameter. PC/CO/apoB complexes exhibit beta-migration on agarose gels and show one high molecular weight protein band on 3.0% sodium dodecyl sulfate-polyacrylamide gels. Differential scanning calorimetry and x-ray scattering show the lipids in the complexes to undergo at least two specific thermal transitions depending on lipid composition, one associated with the core-located cholesterol esters similar to LDL and the protein-free microemulsions and the other from the phospholipid forming the surface monolayer. In addition, particle disruption-protein unfolding/denaturation occur irreversibly at 80-85 degrees C. At 4 degrees C, the secondary structure of apoB on complexes of EYPC /CO/apoB is similar to that of native LDL. For complexes of DMPC/CO/apoB, the secondary structure shows less alpha-helix which correlates with the difference in surface lipid environment. The reassembled complexes of PC/CO/apoB provide a defined system in which the components may be varied systematically in order to study the molecular organization, molecular interactions, and metabolism of LDL.

Apolipoproteins↗
PubMed1984

Factor structure of the WPPSI in mental health clinic settings.

Factor analyzed the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) scores of children (N = 181) seen at several outpatient mental health clinics. A two-factor solution that approximated Wechsler's grouping into Verbal and Performance sections was extracted. The Arithmetic subtest, however, loaded strongly onto both factors. The results suggest that the structure of intelligence for emotionally disturbed children is similar to that for normal children. The results also suggest that WPPSI profile analysis that uses subtest scores may be invalid in clinical settings because the specific variance of most subtests was low and because error variance exceeded specific subtest variance for half of the subtests. Further research is needed to clarify the utility of the WPPSI in outpatient clinical settings.

Aggression↗
PubMed1984

Structural studies of plasma lipoproteins.

These studies with neutron small-angle scattering were designed to probe the location of the apoprotein of HDL on recombinant particles formed with phospholipids. The use of isotopic substitution with deuterium in the headgroup of the phospholipid allows the positions of the molecular components to be probed in more detail. These initial experiments point to the direction future structural studies must take. Reconstitution techniques together with compositional modification of native lipoproteins must be coupled with a combination of high accuracy x-ray and neutron scattering studies, the latter employing isotopic substitution with deuterium to highlight specific areas of the structure. This approach will undoubtedly provide a higher resolution picture of the molecular organization of plasma lipoproteins.

Apolipoproteins↗
PubMed1984

Physical properties of cholesteryl esters.

Cholesteryl esters, the intracellular storage form and intravascular transport form of cholesterol, can exist in crystal, liquid crystal and liquid states. The physical state of cholesteryl esters at physiologic temperatures may be a determinant of their pathogenicity. This review has surveyed saturated aliphatic cholesteryl esters of chain length 1 to 24 carbons and a series of medium-chained unsaturated cholesteryl esters from chain lengths 14 to 24 carbons. A systematic study of transition temperatures by polarizing microscopy and enthalpies by differential scanning calorimetry has provided unifying concepts concerning the phase behavior as a function of chain length and unsaturation. Neat cholesteryl esters show chain-length dependence of transition temperature and enthalpy of both the crystal and liquid crystal transitions. Double bond position along the fatty acyl chain affected stability of the liquid crystal phases; a smectic phase was not observed for any cholesteryl ester with a double bond more proximal than delta 9. 13C NMR spectroscopy in the isotropic liquid phase has provided evidence suggesting a balance of ring-ring vs. chain-chain interactions as a determinant for isotropic liquid----cholesteric vs. isotropic liquid----smectic transitions. Specifically, anisotropic molecular motions of the steroid ring are greater for cholesteryl esters forming a cholesteric phase than a smectic phase from the melt. Chain-chain interactions apparently predominate in smectic phase formation. The X-ray diffraction patterns of cholesteryl esters as a function of chain length reveal several isostructural series and known single crystal data are presented. A chain length depending on the periodicity of the smectic phase is observed which may be different for saturated vs. unsaturated esters. In summary, the phase behavior of cholesteryl ester molecules is complex and cannot be determined a priori from the phase behavior of component cholesterol and fatty acid. The data presented here should provide insight into the biological behavior of this lipid class.

Calorimetry, Differential Scanning↗
PubMed1984

Digital arthrography of the wrist: a radiographic-pathologic investigation.

An analysis of digital arthrography of the wrist was accomplished in 10 cadaveric specimens. In each case, images were obtained during a 30-sec period in which a small amount of contrast material was introduced into the radiocarpal compartment; films were reviewed with and without subtraction technique. Pathologic examination of the sectioned specimens documented the accuracy of this arthrographic method. The sequence of contrast opacification of the various compartments of the wrist and the location and size of the defects within ligamentous and cartilaginous structures were ideally seen with digital arthrography. A previously unemphasized pattern of communication, that between the midcarpal and pisiform-triquetral compartments, was seen in two instances. Digital wrist arthrography seems to represent an excellent method to evaluate the patient with suspected soft-tissue injury.

Fluoroscopy↗
PubMed1983

Solubilization of low-density lipoprotein with sodium deoxycholate and recombination of apoprotein B with dimyristoylphosphatidylcholine.

Apoprotein B (apoB) of human plasma low-density lipoprotein (LDL) (d 1.025-1.050 g/mL) has been solubilized with solid sodium deoxycholate (NaDC) above its critical micellar concentration. ApoB is isolated by gel-filtration chromatography as a mixed micellar complex of protein and detergent in high yield in a lipid-free form. A soluble apoB-dimyristoylphosphatidylcholine (DMPC) complex has been prepared by incubation of aqueous solutions of apoB-NaDC and DMPC-NaDC (2/1 w/w) at room temperature with detergent removal by extensive dialysis. A combination of gel chromatographic and density gradient fractionation of DMPC-apoB incubation mixtures demonstrates that a reasonably well-defined complex of DMPC and apoB is formed with a 4:1 w/w lipid:protein ratio. Negative-stain electron microscopy shows these particles to be single-bilayer phospholipid vesicles with a diameter of 210 +/- 20 A into which the apoB is incorporated. Circular dichroic spectra of NaDC-solubilized apoB show apoB to have similar conformation to that seen in the native LDL particle. However, apoB that has been complexed with DMPC exhibits more alpha-helix. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows a single band (apparent Mr 366000) for apoB after solubilization, purification, and interaction with phospholipid. The behavior of apoB during its reassociation with phospholipid and the structural features of the DMPC-apoB particle are similar to those observed in the interaction of solubilized membrane proteins with lipid rather than that of other apo-lipoproteins.

Apolipoproteins↗
PubMed1983

Validity of two WPPSI short forms in outpatient clinic settings.

Investigated the validity of two- and four-subtest short forms for the WPPSI in an outpatient clinic population of 116 children aged 4 and 5 years. The short forms differed in ability to approximate the Full Scale IQ. Both short forms correlated highly with the Full Scale IQ and accounted for a high percentage of variance. Both short forms misclassified a substantial percentage of Ss in relation to intelligence category. It was concluded that only the four-subtest short form was useful as a screening device in an outpatient mental health setting.

Ambulatory Care↗
PubMed1983

Thermal transitions and structural properties of synthetic cholesterol alkyl and alkenyl ethers: analogues of biological cholesterol esters.

Nine even-numbered saturated (C4 to C20) and two unsaturated (C18:1, C18:2) cholesterol alkyl ethers were studied by differential scanning calorimetry, polarizing microscopy, and X-ray powder diffraction. Seven of the nine saturated ethers examined melt into stable liquid crystal mesophases. Mesophase transition temperatures vary over a much narrower range than in cholesterol esters and are lower than those of corresponding esters. Polarizing microscopy and X-ray diffraction show structural similarities between cholesterol ethers and esters. Since cholesterol ethers behave similarly thermotropically to cholesterol esters, they may serve as suitable nonmetabolizable analogues for cholesterol esters in biological systems.

Calorimetry, Differential Scanning↗
PubMed1982

Triple endoscopy. A valuable procedure in head and neck surgery.

Synchronous carcinoma in the head and neck, lung, or esophagus may be identified in 10 percent of patients with squamous head and neck carcinoma by routinely performing triple endoscopy (direct laryngoscopy, bronchoscopy, and esophagoscopy) at the time of initial evaluation. In 5.5 percent of patients with squamous head and neck cancer, synchronous lung and/or esophageal cancer was identified. However, in only 1.5 percent of patients was it asymptomatic and would not have been suspected as a result of a thorough history, physical examination, and chest x-ray. The cost-effectiveness of routine triple endoscopy can be questioned, but we think it is indicated to identify those early carcinomas with an excellent chance of cure. The time and money expended to identify these early, asymptomatic cancers is small compared to that spent in treating patients with symptomatic cancer of the same organs, in whom there appears to be a much smaller chance of cure. Multiple superficial squamous carcinomas of head and neck mucosa may be managed by surgical excision, radiation therapy, laser destruction, or cryosurgery. If these methods cannot be applied, combination chemotherapy appears to provide a satisfactory alternative method of short-term control, which we believe merits further clinical investigation.

Carcinoma↗
PubMed1982

Physical studies of d less than 1.006 g/ml lymph lipoproteins from rats fed palmitate-rich diets.

At body temperature the stable form of triglycerides rich in saturated fatty acids is crystalline. We examined the physical state of triglyceride-rich lymph lipoproteins from rats fed saturated fat, as a function of temperature. When chylomicrons and very low density lipoproteins were collected, isolated, and examined at 37 degrees C, they were liquid as judged by differential scanning calorimetry, x-ray diffraction analysis and proton nuclear magnetic resonance spectroscopy, and they appeared spherical by electron microscopy. At 23-26 degrees C, triglyceride began to crystallize in the alpha form, which transformed to the stable beta form at lower temperatures. On cooling from 23 degrees C to 17 degrees C, considerable crystallization occurred and the particle density was increased significantly. When lipoproteins were held at 0-7 degrees C, about 75% of the triglyceride crystallized, distorting the lipoprotein shape. Reheating from 0 degrees C to 37 degrees C left 25% of the triglyceride unmelted. Heating to 58 degrees C was necessary to melt all the crystallized triglyceride and to restore the spherical lipoprotein shape. After complete melting of cooled lipoproteins, the liquid state was maintained on recooling to 37 degrees C, with formation of a metastable particle similar to the nascent lipoprotein. Isolation of lipoproteins containing highly saturated triglyceride at temperatures below 23-26 degrees C results in partial crystallization, alters their physical properties, and may affect their metabolism.

Animals↗
PubMed1981

Physical characterization of lymph chylomicrons and very low density lipoproteins from nonhuman primates fed saturated dietary fat.

Differential scanning calorimetry (DSC) and x-ray diffraction studies were performed on chylomicrons and very low density lipoproteins (VLDL), from nonhuman primates fed saturated fat, isolated from lymph at two different temperatures (15 and 39 degrees C). When heated from -10 leads to 60 degrees C, chylomicrons and VLDL isolated at 15 degrees C had two endothermic transitions resulting from the melting of triglycerides (TG). Cooling resulted in the onset of crystallization of the TG core at 16-19 degrees C; 50% of the TG in the particles remained fluid at 4 degrees C. The initial DSC pattern was reproduced not on immediate reheating, but by storing samples at 4 degrees C overnight. Chylomicrons isolated at 39 degrees C contained a metastable (undercooled) TG core until cooled to the onset of TG crystallization at 16-19 degrees C. Reheating the particles with crystalline TG to body temperature (39 degrees C) resulted in a partially crystalline TG core, not an undercooled liquid. To ascertain the effect of particle structure on the TG physical properties, intact particles were compared with heat denatured particles and extracted lipids. The onset of crystallization was lower and the time necessary for isothermal crystallization was much greater for intact versus denatured particles or lipids. Only minor differences in physical properties as a function of particle size were found. It was concluded that: 1) the physical state of chylomicrons and VLDL TG core can be modified by isolation temperature; 2) particle structure affects crystallization but not melting of chylomicrons and VLDL TG; and 3) chylomicrons particle size does not markedly influence the physical properties of the TG core.

Animals↗
PubMed1981

X-ray diffraction and calorimetric study of anhydrous and hydrated N-palmitoylgalactosylsphingosine (cerebroside).

Differential scanning calorimetry and X-ray diffraction of anhydrous and hydrated N-palmitoylgalactosylsphingosine (NPGS) show evidence of complex polymorphic behavior and interconversions between stable and metastable structural forms. Anhydrous NPGS exhibits three lamellar crystal forms (A, B, and B') at temperatures below 143 degrees C and a liquid-crystal form between 143 and 180 degrees C before melting to an isotropic liquid at 180 degrees C. The crystal B leads to liquid-crystal transition is accompanied by an enthalpy change, delta H, of 11.2 kcal/mol of NPGS, while a relatively small enthalpy change (delta H = 0.8 kcal/mol) marks the liquid-crystal leads to liquid transition. The A and B' crystal forms do not hydrate readily at room temperature. When heated, crystal form A in the presence of water undergoes an exothermic transition at 52 degrees C to produce a thermodynamically stable hydrated crystal E form. X-ray diffraction shows that this stable bilayer crystal form has a highly ordered hydrocarbon chain packing arrangement; melting to the bilayer liquid-crystal form occurs at 82 degrees C with a large enthalpy change, delta H = 17.5 kcal/mol of NPGS. A complex liquid-crystal leads to crystal transition is observed on cooling; the cooling rate independent exotherm involves the transition of the hydrated liquid crystal to an intermediate metastable crystal form identical with anhydrous crystal form A. The subsequent cooling rate dependent step involves the conversion of the metastable crystal form A to the stable crystal form E. We suggest that hydrated crystal form E is stabilized by both a highly ordered chain packing mode and a lateral intermolecular hydrogen bonding network involving the sphingosine backbone, the galactosyl group, and interbilayer water molecules. Although disruption of both the specific hydrogen chain packing and H-bonding networks occurs at the high enthalpy transition to the bilayer liquid-crystal L alpha form, these two types of interactions are not reestablished simultaneously on cooling. First, recrystallization of the hydrocarbon chain accompanies removal of water from the lipid interface, leading to "dehydrated" metastable crystal form A. This is followed by a time-dependent, temperature-dependent hydration process which allows a rearrangement of the hydrogen-bonding matrix. Alterations in the NPGS-NPGS and NPGS-water interactions accompany further changes in the hydrocarbon chain packing and lead to the formation of the stable E form.

Animals↗