Biomedical subjects

S L Cooper

Publications and source records attributed to S L Cooper.

At least 19 recordsLinked to original sources

PubMed2007

Antibodies to a novel antigen in acute hepatitis C virus infections.

BACKGROUND: Conformational viral proteins potentially play an important role in the immunobiology of acute hepatitis C virus (HCV) infection and may enable earlier antibody detection. MATERIALS AND METHODS: HCV RNA was detected using nucleic acid testing. Early antibody production was evaluated using three enzyme immunoassays (EIAs) containing antigenic proteins not present in licensed EIAs. Respectively, these contained: (1) multiple-epitope fusion antigen (MEFA) 7.1-NS3/4a, (2) F and Core, and (3) E1/E2 proteins. NS3/4a is a conformational antigen retaining protease and helicase enzymatic activities. MEFA 7.1 contains the linear epitopes used in licenced EIAs, including the latest EIA-3.0, in combination with genotype 1-3 specific epitopes. Forty-two RNA positive, EIA-3.0 negative samples, including two persistently serosilent cases, were used to evaluate these research EIAs. As controls, 54 EIA-3.0 negative/RNA negative and three HCV RNA+/antibody positive specimens were included. RESULTS: Only the MEFA 7.1-NS3/4a EIA was positive in seven (17%) of the 42 HCV RNA + specimens, in all three EIA-3.0 positive controls but in none of 54 EIA-3.0 negative/HCV RNA negative controls. Notably, six of the seven (86%) specimens had evidence of active hepatitis (ALT > 210 IU/l). The two serosilent cases were research EIA negative. CONCLUSION: A novel EIA with conformational and linear epitopes detected HCV antibodies in 17% of viraemic specimens missed by the standard reference EIA-3.0. Our research EIA appears to detect HCV antibodies closer to the initiation of acute hepatitis. Given that the average RNA-positive, antibody-negative window period is 56.4 days, this 17% yield would translate into a 10-day earlier detection of antibodies.

Blood Donors↗

PubMed2006

Field- and pressure-induced phases in Sr4Ru3O10: a spectroscopic investigation.

We have investigated the magnetic-field- and pressure-induced structural and magnetic phases of the triple-layer ruthenate Sr4Ru3O10. Magnetic-field-induced changes in the phonon spectra reveal dramatic spin-reorientation transitions and strong magnetoelastic coupling in this material. Further, we are able to deduce key magnetoelastic coupling parameters, and evidence that the magnetic moments are localized on the Ru sites. Additionally, pressure-dependent Raman measurements at different temperatures reveal an anomalous negative Gruneisen parameter associated with the B(1g) mode (approximately 380 cm(-1)) at low temperatures (T < 75 K), which can be explained consistently with the field-dependent Raman data.

Journal Article↗

PubMed2005

Optical sum rules that relate to the potential energy of strongly correlated systems.

A class of sum rules for inelastic light scattering is developed. We show that the first moment of the nonresonant response provides information about the potential energy in strongly correlated systems. The polarization dependence of the sum rules provides information about the electronic excitations in different regions of the Brillouin zone. We determine the sum rule for the Falicov-Kimball model, which possesses a metal-insulator transition, and compare our results to the light scattering experiments in SmB(6).

Journal Article↗

PubMed2004

Field-induced orbital and magnetic phases in Ca3Ru2O7.

Magnetic-field- and temperature-dependent Raman scattering studies of Ca3Ru2O7 reveal dramatic field-dependent properties arising from transitions between various complex orbital and magnetic phases, including a field-induced orbital-ordered to orbital-disordered transition (H(o) // hard axis), and a reentrant orbital-ordered to orbital-disordered to orbital-ordered transition (H(o) // easy axis). We find that the dramatic magnetic-field properties are most prevalent in a "mixed"-magnetic and -orbital phase regime, providing evidence for a strong connection between orbital phase inhomogeneity and "colossal" field effects in the ruthenates.

Journal Article↗

PubMed2004

Manipulation of the n-3 polyunsaturated fatty acid content of muscle and adipose tissue in lambs.

Fifty Suffolk-crossbred wether lambs, with an initial live weight of 29 +/- 2.1 kg, were allocated to one of five concentrate-based diets formulated to have a similar fatty acid content (60 g/kg DM), but containing either linseed oil (high in 18:3n-3); fish oil (high in 20:5n-3 and 22:6n-3); protected linseed and soybean (PLS; high in 18:2n-6 and 18:3n-3); fish oil and marine algae (fish/algae; high in 20:5n-3 and 22:6n-3); or PLS and algae (PLS/algae; high in 18:3n-3 and 22:6n-3). Lambs were slaughtered when they reached 40 kg. Growth performance and intake were similar (P > 0.35) among treatments. By contrast, gain:feed was higher (P < 0.05) in lambs fed the fish oil compared with the linseed oil or PLS/algae diets. Total fatty acid concentration (mg/100 g) in the neutral lipid of the longissimus muscle was not affected by treatment (P > 0.87) but was least (P < 0.05) in the phospholipid fraction in lambs fed the linseed oil diet. Lambs fed either diet containing marine algae contained the highest (P < 0.05) percentage of 22:6n-3 in the phospholipid (mean of 5.2%), 2.8-fold higher than in sheep fed the fish oil diet. In lambs fed the fish/algae diet, the percentage of 20:5n-3 was highest (P < 0.05), contributing some 8.7, 0.8, and 0.5% of the total fatty acids in the muscle phospholipid, neutral lipids, and adipose tissue, respectively. The percentage of 18:3n-3 in the phospholipid fraction of the LM was highest (P < 0.05) in lambs fed the linseed oil diet (6.9%), a value double that of sheep fed the PLS diet. By contrast, lambs fed the PLS diet had twice the percentage of 18:3n-3 in the muscle neutral lipids (3.8%) than those offered the linseed oil diet, and 5.5-fold greater than lambs fed the fish/algae treatment (P < 0.05), an effect that was similar in the adipose tissue. The percentage of 18:2n-6 was highest (P < 0.05) in lambs fed the PLS diet, where it contributed 33.7, 10.1, and 11.2% in the muscle phospholipid, neutral lipids, and adipose tissue, respectively. The highest (P < 0.05) muscle PUFA-to-saturated fatty acid (P:S) ratio was obtained in lambs fed the PLS diet (0.57), followed by the PLS/algae diet (0.46), and those fed the fish oil or linseed oil diets had the lowest ratios (0.19 and 0.26, respectively). The favorable P:S ratio of lambs fed the PLS/algae diet, in conjunction with the increased levels of 20:5n-3 and 22:6n-3, enhanced the nutritional qualities of lamb to more closely resemble what is recommended for the human diet.

Adipose Tissue↗

PubMed2003

Quantum melting of the charge-density-wave state in 1T-TiSe2.

We report a Raman scattering study of low-temperature, pressure-induced melting of the charge-density-wave (CDW) phase of 1T-TiSe2. Our measurements reveal that the collapse of the CDW state occurs in three stages: (i) For P<5 kbar, the pressure dependence of the CDW amplitude mode energies and intensities are indicative of a "crystalline" CDW regime; (ii) for 5 25 kbar, the absence of amplitude modes reveals a metallic regime in which the CDW has melted.

Journal Article↗

PubMed2002

Pressure-tuned collapse of the Mott-like state in Ca(n+1)Ru(n)O(3n+1) (n=1,2): Raman spectroscopic studies.

We report a Raman scattering study of the pressure-induced collapse of the Mott-like phases of Ca3Ru2O7 (T(N)=56 K) and Ca2RuO4 (T(N)=110 K). The pressure dependence of the phonon and two-magnon excitations in these materials indicate (i) a T approximately 0 pressure-induced collapse of the antiferromagnetic (AF) insulating phase above P(*) approximately 55 kbar in Ca3Ru2O7 and P(*) approximately 5-10 kbar in Ca2RuO4, (ii) a remarkable insensitivity of the exchange interaction to pressure in both systems, and (iii) evidence for persistent AF correlations above the critical pressure of Ca2RuO4, suggestive of phase separation involving AF insulator and ferromagnetic metal phases.

Journal Article↗

PubMed2002

Evolution of magnetic polarons and spin-carrier interactions through the metal-insulator transition in Eu(1-x)Gd(x)O.

Raman scattering studies as functions of temperature, magnetic field, and Gd substitution are used to investigate the evolution of magnetic polarons and spin-carrier interactions through the metal-insulator transition in Eu(1-x)Gd(x)O. These studies reveal a spin-fluctuation-dominated paramagnetic (PM) regime for T>T*>T(C), and a coexistence regime for T<T* in which spin polarons develop and coexist with remnants of the PM phase. They further show a strong connection between spin cluster formation and the dramatic field effects observed in these materials.

Journal Article↗

PubMed2001

Design, synthesis, and proposed active site binding analysis of monocyclic 2-azetidinone inhibitors of prostate specific antigen.

A homology derived molecular model of prostate specific antigen (PSA) was created and refined. The active site region was investigated for specific interacting functionality and a binding model postulated for the novel 2-azetidinone acyl enzyme inhibitor 1 (IC(50) = 8.98 +/- 0.90 microM) which was used as a lead compound in this study. A single low energy conformation structure II (Figure 2) was adopted as most likely to represent binding after minimization and dynamics calculations. Systematic analysis of the binding importance of all three side chains appended to the 2-azetidinone was conducted by the synthesis of several analogues. A proposed salt bridge to Lys-145 with 4 (IC(50) = 5.84 +/- 0.92 microM) gave improved inhibition, but generally the binding of the N-1 side chain in a specific secondary aromatic binding site did not tolerate much structural alteration. A hydrophobic interaction of the C-4 side chain afforded inhibitor 6 (IC(50) = 1.43 +/- 0.19 microM), and polar functionality could also be added in a proposed interaction with Gln-166 in 5 (IC(50) = 1.34 +/- 0.05 microM). Reversal of the C-4 ester connectivity furnished inhibitors 7 (IC(50) = 1.59 +/- 0.15 microM), 11 (IC(50) = 3.08 +/- 0.41 microM), and 13 (IC(50) = 2.19 +/- 0.36 microM) which were perceived to bind to PSA by a rotation of 180 degrees relative to the C-4 ester of normal connectivity. Incorporation of hydroxyl functionality into the C-3 side chain provided 16 (IC(50) = 348 +/- 50 nM) with the greatest increase in PSA inhibition by a single modification. Multiple copy simultaneous search (MCSS) analysis of the PSA active site further supported our model and suggested that 18 would bind strongly. Asymmetric synthesis yielded 18 (IC(50) = 226 +/- 10 nM) as the most potent inhibitor of PSA reported to date. It is concluded that our design approach has been successful in developing PSA inhibitors and could also be applied to the inhibition of other enzymes, especially in the absence of crystallographic information.

Azetidines↗

PubMed2001

Synthesis and characterization of non-leaching biocidal polyurethanes.

The biocidal activities of a series of quaternized polyurethanes were examined against Staphylococcus aureus and Escherichia coli. The percentage of dead cells on a surface was found to depend on the alkyl halide used for quaternization, the concentration of quaternized moieties in the polyurethane, the gram-type of the microorganism, and the contact time of the organism with the surface. N,N-bis(2-hydroxyethyl)isonicotinamide (BIN) was incorporated as the chain extender in a series of poly(tetramethylene oxide)-based polyurethane block copolymers. Three families of materials were synthesized that contained increasing hard segment fractions and therefore increasing concentrations of BIN. The pyridine ring in BIN was quaternized with a variety of alkyl halides to form cationic polyurethanes that possessed biocidal activity. The effect of quaternization on material properties was examined with tensile testing, water absorption analysis, and contact angle measurements. The antibacterial action of the polymers was investigated with zone of inhibition experiments and fluorescence microscopy, which was established as a reliable technique to determine the viability of organisms attached to a polymer surface.

Adsorption↗

PubMed2001

Assessment of hypercholesterolemia control in a managed care organization.

To determine the extent of achievement of goal low-density lipoprotein cholesterol (LDL) as defined by National Cholesterol Education Program-Adult Treatment Panel II (NCEP-ATP 11) and American Diabetes Association (ADA) 2000 guidelines, we conducted a retrospective study by integrating data from medical, laboratory, and pharmacy claims databases. Subjects were selected from a 232,000-member staff-model managed care organization consisting of 19 clinics in the Minneapolis-St. Paul, Minnesota, metropolitan area. A total of 124,971 members aged 18 years and older, who had been continuously enrolled from July 1, 1996-June 6, 1998, were included. Outcome measures were the extent of achievement of goal LDL as defined by NCEP-ATP II and the use of antihyperlipidemic drugs for patients with and without diabetes at various levels of risk for coronary heart disease (CHD). Of 124,971 subjects, 6538 had a history of CHD, 1523 of whom met their LDL goal. Of the population with CHD who did not achieve goal, 1141 (43%) missed by over 30 mg/dl; 621 (54%) of these patients were not receiving drug therapy A total of 17,267 had no history of CHD but had two or more risk factors; 3,298 of these achieved their LDL goal. Of those who did not achieve goal, 1,136 (35%) missed by over 30 mg/dl; 897 (79%) of these were not receiving drug therapy A total of 6,586 had a history of diabetes; 1,004 and 2,340 reached an LDL of 100 mg/dl or lower and less than 130 mg/dl, respectively Of those with diabetes who had an LDL greater than 100 mg/dl, 1,276 (49%) missed their goal by over 30 mg/dl; 898 (70%) of these were not receiving drug therapy. Inadequate use of pharmacologic agents plays a significant role in failure to achieve goal LDL for patients with CHD, without CHD, and with diabetes. Analysis of the data based on the new ADA guidelines for LDL demonstrates the need for continued vigilance. Finally, the successful merging of medical, laboratory, and pharmacy claims databases provides a benchmark for other institutions.

Adult↗

PubMed2000

Raman scattering study of anomalous spin, charge, and lattice dynamics in the charge-ordered phase of Bi1-xCaxMnO3 (x > 0.5).

We report an inelastic light scattering study of the effects of charge ordering on the spin, charge, and lattice dynamics of Bi1-xCaxMnO3 (x>0.5). We find that charge ordering results in anomalous phonon behavior, such as the appearance of "activated" modes. More significantly, however, the transition to the charge-ordered phase results in the appearance of a quasielastic scattering response with the symmetry of the spin-chirality operator ( T(1g)); this scattering response is thus indicative of magnetic or chiral spin fluctuations in the antiferromagnetic charge-ordered phase.

Journal Article↗

PubMed2000

Leukocyte adhesion on model surfaces under flow: effects of surface chemistry, protein adsorption, and shear rate.

The effect of specific chemical functionalities on the adhesion of polymorphonuclear leukocytes (PMNs) under flow was investigated using a set of well-characterized, chemically functionalized surfaces prepared by self-assembly of alkanethiolate monolayers on gold surfaces. Terminal functionalities included CH(3), CH(2)OH, COOH, and (OCH(2)CH(2))(3)OH groups. A new surface modification was used to incorporate a phosphorylcholine moiety on the hydroxyl-terminated monolayer. Surface modification was verified using contact-angle measurements, ellipsometry, and X-ray photoelectron spectroscopy. Adhesion on the surfaces was studied in the presence and absence of pre-adsorbed fibrinogen. Fibrinogen adsorption on self-assembled monolayers (SAMs) was quantified using radioisotope detection. PMN adhesion was found to be dependent on the monolayer's terminal functionality. Adhesion was higher on the hydrophobic CH(3) surface and the polar COOH monolayer. Leukocyte adhesion was least on the phosphorylcholine-rich surface, followed by the ethylene-oxide-containing monolayer. Cell adhesion also was low on the hydrophilic OH monolayer. Attachment was decreased with increasing shear rate, exhibiting a three-fold decrease between 20 and 100 s(-1). Fibrinogen adsorption was higher on the CH(3) monolayer but comparable for the other four SAMs. Preincubation of the surfaces with fibrinogen decreased adhesion on all SAMs examined.

Biocompatible Materials↗

PubMed2000

Bacterial colonization of functionalized polyurethanes.

A protocol was developed for studying the growth of bacteria upon polyurethanes subsequent to the establishment of an adherent bacterial population. An inocula of approximately 10(5) cfu S. aureus were spread on functionalized polyurethanes which included Pellethane, sulfonated Pellethane, phosphonated Pellethane, quaternized amine polyurethanes, and a zwitterionic phosphonated polyurethane. After 24 h incubation, Pellethane, sulfonated Pellethane, and phosphonated Pellethane showed bacterial growth by at least a factor of 10. In contrast, the zwitterionic phosphonated polyurethane showed a factor of 10 decrease in bacteria after 24 h and the quaternized amine polyurethanes reduced the bacteria to only a few hundred after only 1 h. When treated with bovine serum albumin, Pellethane, sulfonated Pellethane, and phosphonated Pellethane again showed bacterial growth by as much as a factor of 10 over 24 h. The quaternized amine polyurethanes and the zwitterionic phosphonated polyurethane still exhibited bactericidal abilities even when coated with bovine serum albumin, with the zwitterionic material reducing bacteria by more than a factor of 10 over 24 h and the quaternized amine polyurethane reducing the bacteria to only a few hundred after only 1 h. A zone of inhibition study suggested that the bactericidal activity of the zwitterionic phosphonated polyurethane was due to the leaching of cadmium ions. A quaternized amine polyurethane which contained chloride instead of iodide as the counterion to the amine moiety was less bactericidal than the iodide-containing polymer when treated with albumin. Thus, bacteria were able to colonize Pellethane, phosphonated sulfonated Pellethane, and phosphonated Pellethane, but the iodide-containing quaternized amine polyurethane and the zwitterionic polyurethane prevented colonization.

Albumins↗

PubMed2000

High-molecular-weight kininogen preadsorbed to glass surface markedly reduces neutrophil adhesion.

Adsorbed proteins on biomaterial surfaces determine whether cells adhere, but rheological variables are also critical. Neutrophil adhesion under well-defined radial flow conditions was studied on glass preadsorbed with plasma proteins or plasma protein domain fragments. Fibrinogen, low-molecular-weight kininogen (LK), high-molecular-weight kininogen (HK), cleaved HK (HKa), and recombinant HK domains 3 and 5 (D3 and D5H) were used. The number of adherent cells on the HK and HKa surfaces was less than 10% that found on the fibrinogen absorbed surface. The degree of spreading was minimal and detachment of adherent neutrophils was observed. HK and HKa contain binding sites for both anionic surfaces and neutrophils in the same domain (D5H). When adsorbed to surfaces, HK and HKa did not have the neutrophil binding sites available and therefore exhibited an anti-adhesive effect. Although D5H contains anionic surface binding sites, its small molecular size required a higher number of adsorbed molecules to cover the surface before a significant decrease in cell adhesion was observed. Since LK and D3 do not possess specific anionic surface binding sites, the adsorption of these proteins on glass was very low compared to HK and HKa. Thus, extensive cell adhesion and spreading were observed on the surfaces partially covered with preadsorbed LK and D3.

Adsorption↗

PubMed2000

Rapid evolution of NK cell receptor systems demonstrated by comparison of chimpanzees and humans.

That NK cell receptors engage fast-evolving MHC class I ligands suggests that they, too, evolve rapidly. To test this hypothesis, the structure and class I specificity of chimpanzee KIR and CD94:NKG2 receptors were determined and compared to their human counterparts. The KIR families are divergent, with only three KIR conserved between chimpanzees and humans. By contrast, CD94:NKG2 receptors are conserved. Whereas receptors for polymorphic class I are divergent, those for nonpolymorphic class I are conserved. Although chimpanzee and human NK cells exhibit identical receptor specificities for MHC-C, they are mediated by nonorthologous KIR. These results demonstrate the rapid evolution of NK cell receptor systems and imply that "catching up" with class I is not the only force driving this evolution.

Animals↗

PubMed2000

Quaternary ammonium functionalized poly(propylene imine) dendrimers as effective antimicrobials: structure-activity studies.

Quaternary ammonium functionalized poly(propyleneimine) dendrimers were synthesized and their antibacterial properties were evaluated using a bioluminescence method. These quaternary ammonium dendrimers are very potent biocides. The antibacterial properties depend on the size of the dendrimer, the length of hydrophobic chains in the quaternary ammonium groups, and the counteranion. Since these dendrimers are well characterized and monodisperse, they also serve as an effective system to study the structure-activity relationship. The antimicrobial properties of these dendrimer biocides have a parabolic dependence on molecular weight, which is different from the bell-shaped molecular weight dependence of conventional polymer biocides. The dependence on the hydrophobic chain of the quaternary ammonium structure is similar to conventional polymer biocides, and shows a parabolic relationship with dendrimer biocides carrying C10 hydrophobes the most potent. The antimicrobial properties of these novel biocides with bromide anions are more potent than those with chloride anions. Biocides derived from hyperbranched polymers were also synthesized and found to possess somewhat lower effectiveness.

Anti-Bacterial Agents↗

PubMed2000

The influence of thrombus components in mediating bacterial adhesion to biomaterials.

Thrombosis and infection represent the two largest limiting factors determining the long term success of implanted biomaterials. Infections associated with biomaterials are difficult to treat, and appear to evade the host defense systems. Mechanisms relating infection to thrombosis are described. Investigations into the role of receptors in mediating adhesion to thrombi are also discussed, in addition to strategies to reduce bacterial adhesion to biomaterial surfaces.

Bacterial Adhesion↗