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Biomedical subjects

D H Lee

Publications and source records attributed to D H Lee.

At least 55 records · Page 3Linked to original sources
PubMed2002

Peripheral arterial insufficiency associated with protein C deficiency.

Two patients with protein C deficiency who presented with peripheral arterial insufficiency were successfully managed. One patient was managed with bypass surgery for focal gangrene followed by full anticoagulation whilst the other patient was managed with full anticoagulation. Both patients showed characteristic arteriographic findings. Patients who present with peripheral arterial insufficiency demonstrating thrombotic occlusion of main peripheral artery without atherosclerosis and other risk factors should be evaluated for hypercoagulable states.

Adult↗
PubMed2002

Investigation of genotype x country interactions for growth traits in beef cattle.

The importance of genotype x country interactions for weaning and birth weight and postweaning gain between Argentina (AR), Canada (CA), Uruguay (UY), and the United States (US) for populations of Hereford cattle was investigated. Three sample data sets of computationally manageable sizes were formed for each trait and pairwise combination of countries to investigate possible interactions. Parameters were estimated for each sample data set via an accelerated EM-REML algorithm and multiple-trait animal models that considered either weaning or birth weight as a different trait in each country. Direct and maternal (in parentheses) weaning weight genetic correlation estimates for AR-CA, AR-UY, AR-US, CA-UY, CA-US, and UY-US were 0.82 (0.80), 0.81 (0.72), 0.81 (0.79), 0.83 (0.78), 0.85 (0.82), and 0.86 (0.81), respectively. Direct and maternal (in parentheses) birth weight genetic correlation estimates were 0.92 (0.62), 0.97, (0.85), and 0.99 (0.97) for AR-CA, AR-US, and CA-US, respectively. Birth weight was not analyzed for UY due to small amounts of data. Postweaning gain in CA and US was 160-d gain, and in AR and UY 345-d gain was used. Across-country direct genetic correlations for postweaning gain were estimated for each pairwise country data set using a model that considered weaning weight as the same trait across each country, whereas postweaning gain was treated as a different trait in each country. Direct genetic correlation estimates for postweaning gain for AR-CA, AR-UY, AR-US, CA-UY, CA-US, and US-UY were 0.64, 0.80, 0.51, 0.84, 0.92, and 0.83, respectively. The overall results indicate that weaning and birth weights of Hereford calves can be analyzed as the same trait in all countries with a common set of heritabilities and genetic correlations, after adjustment for heterogenous phenotypic variances across countries. Postweaning gain in CA and US can be considered as the same trait and analyzed using a single set of parameters. Postweaning gain in AR and UY should be considered as a separate trait from postweaning gain in CA and US, and postweaning gain in AR and UY can be considered as the same trait and analyzed using a common heritability, after adjustment for phenotypic variance differences between the two countries.

Animals↗
PubMed2001

Conformational analysis of the eight-membered ring of the oxidized cysteinyl-cysteine unit implicated in nicotinic acetylcholine receptor ligand recognition.

Nicotinic acetylcholine receptors (nAChRs) are membrane-bound, pentameric ligand-gated ion channels associated with a variety of human disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia, and pain. Most known nAChRs contain an unusual eight-membered disulfide-containing cysteinyl-cysteine ring, ox-[Cys-Cys], as does the soluble acetylcholine binding protein (AChBP) found in the snail Lymnaea stagnalis. The cysteinyl-cysteine ring is located in a region implicated in ligand binding, and conformational changes involving this ring may be important for modulation of nAChR function. We have studied the preferred conformations of Ac-ox-[Cys-Cys]-NH2 by NMR in water and computationally by Monte Carlo simulations using the OPLS-AA force field and GB/SA water model. ox-[Cys-Cys] adopts four distinct low-energy conformers at slightly above 0 degrees C in water. Two populations are dependent on the peptide omega2 dihedral angle, with the trans amide favored over the cis amide by a ratio of ca. 60:40. Two ox-[Cys-Cys] conformers with a cis amide bond (C+ and C-) differ from each other primarily by variation of the chi3 dihedral angle, which defines the orientation of the helicity about the S-S bond (+/- 90 degrees ). Two trans amide conformers have the same S-S helicity (chi3 approximately -90 degrees ), but are distinguished by a backbone rotation about phi2 and psi1 (T- and T'-). The ratio of T-/T'-/C+/C- is 47:15:29:9. The orientation of the pendant moieties from the eight-membered ring is more compact for the major trans conformer (T-) than for the extended conformations adopted by T'-, C+, and C-. These conformational preferences are also observed in tetrapeptide and undecapeptide fragments of the human alpha7 subtype of the nAChR that contains the ox-[Cys-Cys] unit. Conformer T- is nearly identical to the conformation seen in the X-ray structure of ox-[Cys(187)-Cys(188)] found in the unliganded AChBP, and is a Type VIII beta-turn.

Computer Simulation↗
PubMed2001

Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21.

Global patterns of human DNA sequence variation (haplotypes) defined by common single nucleotide polymorphisms (SNPs) have important implications for identifying disease associations and human traits. We have used high-density oligonucleotide arrays, in combination with somatic cell genetics, to identify a large fraction of all common human chromosome 21 SNPs and to directly observe the haplotype structure defined by these SNPs. This structure reveals blocks of limited haplotype diversity in which more than 80% of a global human sample can typically be characterized by only three common haplotypes.

Algorithms↗
PubMed2001

A novel anti-ischemic ATP-sensitive potassium channel (K(ATP)) opener without vasorelaxation: N-(6-aminobenzopyranyl)-N'-benzyl-N' '-cyanoguanidine analogue.

This paper describes the design, synthesis, and biological evaluation of a novel anti-ischemic compound, (2S,3S,4R)-N-(6-amino-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-benzopyranyl)-N'-benzyl-N"-cyanoguanidine (33), and the structure-activity relationships leading to the discovery of this compound. Compound 33 significantly reduced the myocardial infarct zone to area at risk (IZ/AAR) in the ischemic myocardium rat model with high cardioselectivity. Since the cardioprotective effect of compound 33 is reversed by ATP-sensitive potassium channel (K(ATP)) blockers, its anti-ischemic effect appears to be at least mediated by K(ATP) opening. In addition, compound 33 shows good protective activity on neuronal cells against oxidative stress, and therefore it is suggested that compound 33 may have therapeutic potential both in cardio- and in neuroprotection.

Adenosine Triphosphate↗
PubMed2001

Antithrombotic effects of YS-49 and YS-51--1-naphthylmethyl analogs of higenamine.

The antiplatelet and antithrombotic effects of YS-49 and YS-51--l-naphthylmethyl analogs of higenamine, which is a benzyl-tetrahydroisoquinoline alkaloid isolated from Aconitum japonicum (Ranunculaceae)--were investigated. YS-49 and YS-51 showed inhibitory activities to both human and rat platelet aggregation induced by ADP, collagen and epinephrine. They were more inhibitory to epinephrine-induced aggregation (IC(50); 3.4 and 1.7 microM of YS-49, and 6.0 and 6.3 microM of YS-51 to human and rat platelets, respectively) than ADP- or collagen-induced aggregation. The antithrombotic effects of YS-49 and YS-51 were also observed in both mouse acute thrombosis model and rat arterio-venous shunt (AV shunt) model. The oral administration of YS-49 and YS-51 (50 or 100 mg/kg) increased the recovery rates from the acute thrombotic challenge in mice and lowered the weight of thrombus formed inside the AV shunt tube in rats.

Alkaloids↗
PubMed2001

Staggered currents in the mixed state.

The current pattern in the mixed state of high-T(c) superconductors is studied in the U(1) mean-field theory of the t-J model. Assuming the absence of spin antiferromagnetism we find (1) at moderate doping staggered-current pattern exists in vortex cores and eventually percolates with increasing magnetic field. (2) The polarity of the staggered current is pinned by the magnetic field. (3) Vortex cores with (without) staggered current are slightly negatively (positively) charged. (4) Gutzwiller projection does not wash out the staggered current. We discuss the signature of staggered current in neutron scattering and scanning tunneling microscopy.

Journal Article↗
PubMed2001

Cyclobutane pyrimidine dimers are responsible for the vast majority of mutations induced by UVB irradiation in mammalian cells.

The most prevalent DNA lesions induced by UVB are the cyclobutane pyrimidine dimers (CPDs) and the pyrimidine (6-4) pyrimidone photoproducts ((6-4)PPs). It has been a long standing controversy as to which of these photoproduct is responsible for mutations in mammalian cells. Here we have introduced photoproduct-specific DNA photolyases into a mouse cell line carrying the transgenic mutation reporter genes lacI and cII. Exposure of the photolyase-expressing cell lines to photoreactivating light resulted in almost complete repair of either CPDs or (6-4)PPs within less than 3 h. The mutations produced by the remaining, nonrepaired photoproducts were scored. The mutant frequency in the cII gene after photoreactivation by CPD photolyase was reduced from 127 x 10(-5) to 34 x 10(-5) (background, 8-10 x 10(-5)). Photoreactivation with (6-4) photolyase did not lower the mutant frequency appreciably. In the lacI gene the mutant frequency after photoreactivation repair of CPDs was reduced from 148 x 10(-5) to 28 x 10(-5) (background, 6-10 x 10(-5)). Mutation spectra obtained with and without photoreactivation by CPD photolyase indicated that the remaining mutations were derived from background mutations, unrepaired CPDs, and other DNA photopoducts including perhaps a small contribution from (6-4)PPs. We conclude that CPDs are responsible for at least 80% of the UVB-induced mutations in this mammalian cell model.

Animals↗
PubMed2001

Superfluid density in the d-density-wave scenario.

Recently Chakravarty, Laughlin, Morr, and Nayak [Phys. Rev. B 62, 4880 (2000)] made an interesting proposal that the cuprate superconductors possess a hidden " d-density-wave" (DDW) order. We study the implication of this proposal for the superfluid density rho(s). We find that it predicts a temperature gradient [d rho(s)/dT](T = 0) that is strongly doping dependent near the critical doping at which the superconducting gap vanishes. This demonstrates that the DDW scenario is inconsistent with existing well-established experimental data.

Journal Article↗
PubMed2001

Salt-thermal zeolitization of fly ash.

The molten-salt method has been recently proposed as a new approach to zeolitization of fly ash. Unlike the hydrothermal method, this method employs salt mixtures as the reaction medium without any addition of water. In this study, systematic investigation has been conducted on zeolitization of fly ash in a NaOH-NaNO3 system in order to elucidate the mechanism of zeolite formation and to achieve its optimization. Zeolitization of fly ash was conducted by thermally treating a powder mixture of fly ash, NaOH, and NaNO3. Zeolitization of fly ash took place above 200 degrees C, a temperature lower than the melting points of salt and base in the NaOH-NaNO3 system. However, it was uncertain whether the reactions took place in a local molten state or in a solid state. Therefore, the proposed method is renamed the "salt-thermal" method rather than the "molten-salt" method. Mainly because of difficulty in mobility of components in salt mixtures, zeolitization seems to occur within a local reaction system. In situ rearrangement of activated components seems to lead to zeolite formation. Particle growth, rather than crystal growth through agglomeration, resulted in no distinct morphologies of zeolite phases. Following are the optimal zeolitization conditions of the salt-thermal method: temperature, 250-350 degrees C; time, 3-12 h; weight ratio of NaOH/NaNO3, 0.3-0.5; weight ratio of NaNO3/fly ash, 0.7-1.4. Therefore, it is clear from this work that the salt-thermal method could be applied to massive zeolitization of fly ash as a new alternative method for recycling this waste.

Carcinogens↗
PubMed2001

Synergistic induction of cyclooxygenase-II by bacterial lipopolysaccharide in combination with particles of medical device materials in a murine macrophage cell line J774A.1.

Corrosion and wear of implanted medical devices may produce particulate debris, leading to acute and chronic inflammatory responses in the host. In the presence of biomaterial wear particles, host monocytes/macrophages are activated to synthesize or secrete mediators of inflammation. In order to understand the mechanisms underlying the host response to particulates and device-associated infections, we have focused on the effects of medical device particles on macrophage function, because these cells play a pivotal role in the body's response to foreign bodies and their interaction with other cellular components of the immune system. In order to evaluate the effects of particles of medical device materials on functional activities of macrophages, we developed a cyclooxygenase-II (COX-II) assay system using J774A.1 macrophages. Constitutive cyclooxygenase (COX-I) is present in cells under physiological conditions, whereas inducible COX-II is induced by some cytokines, mitogens, and endotoxin, presumably in pathological conditions such as inflammation. We have evaluated the inductive effects of implant materials, i.e., particles of polymethylmethacrylate (PMMA), hydroxyapatite (HA), titanium oxide, and silica, on the activity of COX-II using thin layer chromatography of prostaglandin D(2) (PGD(2)) formed from [1-(14)C]-labeled arachidonic acid (AA). Also, we have assessed the synergistic effects of these particles on lipopolysaccharide (LPS)-mediated macrophage activation. Addition of LPS to these particles increased PGD(2) production several-fold greater than the addition of any inducer alone. Our results indicated that device-associated infections could enhance inflammatory responses to the wear particles in subjects with medical implants or in whom particulate biomaterials are used for clinical purposes. The use of this model COX-II assay system may lead to the identification of inflammatory potentials for implant materials more specifically than present in vivo assays.

Animals↗
PubMed2001

Trehalose accumulation during cellular stress protects cells and cellular proteins from damage by oxygen radicals.

The disaccharide trehalose, which accumulates dramatically during heat shock and stationary phase in many organisms, enhances thermotolerance and reduces aggregation of denatured proteins. Here we report a new role for trehalose in protecting cells against oxygen radicals. Exposure of Saccharomyces cerevisiae to a mild heat shock (38 degrees C) or to a proteasome inhibitor (MG132) induced trehalose accumulation and markedly increased the viability of the cells upon exposure to a free radical-generating system (H(2)O(2)/iron). When cells were returned to normal growth temperature (28 degrees C) or MG132 was removed from the medium, the trehalose content and resistance to oxygen radicals decreased rapidly. Furthermore, a mutant unable to synthesize trehalose was much more sensitive to killing by oxygen radicals than wild-type cells. Providing trehalose exogenously enhanced the resistance of mutant cells to H(2)O(2). Exposure of cells to H(2)O(2) caused oxidative damage to amino acids in cellular proteins, and trehalose accumulation was found to reduce such damage. After even brief exposure to H(2)O(2), the trehalose-deficient mutant exhibited a much higher content of oxidatively damaged proteins than wild-type cells. Trehalose accumulation decreased the initial appearance of damaged proteins, presumably by acting as a free radical scavenger. Therefore, trehalose accumulation in stressed cells plays a major role in protecting cellular constituents from oxidative damage.

Cell Survival↗
PubMed2001

Mitochondrial dysfunction by gamma-irradiation accompanies the induction of cytochrome P450 2E1 (CYP2E1) in rat liver.

Multiple biological effects are induced by ionizing radiation through dysfunction of cellular organelles, direct interaction with nucleic acids and production of free radical species. The expression of cytochrome P450s was assessed in the livers of 60Co gamma-irradiated rats. Three gray (G) of gamma-irradiation caused CYP2E1 induction with a 3.6-fold increase in the mRNA at 24 h, whereas the expression of CYP1A2 and CYP3A was not changed. Pharmacokinetics of chlorzoxazone, a specific substrate of CYP2E1, was studied in 3 G-irradiated rats. The area under the plasma concentration-time curve from time zero to infinity of 6-hydroxychlorzoxazone and the amount of 6-hydroxychlorzoxazone excreted in 8 h urine were both significantly greater than those in control rats. Hepatic CYP2E1 was not induced in rats exposed to 0.5-1 G of gamma-rays. Rats irradiated at 6-9 G accumulated doses of gamma-rays exhibited smaller increases in the mRNA due to liver injury than those irradiated at a single dose of 3 G gamma-rays. The plasma glucose and insulin levels were not altered in rats with 3 G of gamma-irradiation. As the exposure level of gamma-irradiation increased, the activity of hepatic aconitase, a key enzyme in energy metabolism in mitochondria, was 30-90% decreased. The amount of mitochondrial DNA per gram of wet liver was 50% decreased in rats exposed to 3 G of gamma-rays. These results demonstrated that gamma-ray irradiation at the exposure level inducing organelle dysfunction induced CYP2E1 in the liver, which might be associated with mitochondrial damage, but not with alterations in glucose or insulin levels.

Aconitate Hydratase↗
PubMed2001

A de novo designed peptide ligase: a mechanistic investigation.

A 33-residue de novo designed peptide ligase is reported which catalyzes the template-directed condensation of suitably activated short peptides with catalytic efficiencies in excess of 10(5) ([k(cat)/K(m)]/k(uncat)). The ligase peptide, derived from natural and designed alpha-helical coiled-coil proteins, presents a surface for substrate assembly via formation of a hydrophobic core at the peptide interface. Charged residues flanking the core provide additional binding specificity through electrostatic complementarity. Addition of the template to an equimolar fragment solution results in up to 4100-fold increases in initial reaction rates. Dramatic decreases in efficiency upon mutation of charged residues or increase in ionic strength establishes the importance of electrostatic recognition to ligase efficiency. Although most of the increase in reaction efficiency is due to entropic gain from binding of substrates in close proximity, mechanistic studies with altered substrates demonstrate that the system is highly sensitive to precise ordering at the point of ligation. Taken together these results represent the first example of a peptide catalyst with designed substrate binding sites which can significantly accelerate a bimolecular reaction and support the general viability of alpha-helical protein assemblies in artificial enzyme design.

Amino Acid Sequence↗
PubMed2001

The effect of lumbar sympathectomy on increased tactile sensitivity in spinal nerve ligated rats.

The aim of this study was to investigate the reason for the contradictory results following surgical sympathectomy on increased tactile sensitivity in spinal nerve ligated rats. For this purpose, firstly the results of L5 spinal nerve ligation alone and both L5 and L6 (L5/6) spinal nerve ligation were compared in Sprague-Dawley rats. Secondly, the difference in tactile sensitivity between the plantar surface (the middle glabrous area on the foot pads of the hind paw) and on the toe (the proximal half of the third and fourth toe of the hind paw) after the spinal nerve injury was studied. Third, we divided the L5 spinal nerve ligated rats into two groups, (i.e. low and high threshold groups) based on the degree of tactile sensitivity and investigated the effect of surgical lumbar sympathectomy (L2-L5) on tactile sensitivity in both the plantar and toe areas. The results show that the tactile sensitivities of L5 spinal nerve ligated rats and L5/6 spinal nerve ligated rats were not different. However, tactile sensitivities of the plantar surface were less than those of toe area suggesting that the response from toe is a better indicator of neuropathic pain. Surgical sympathectomy reduced the response from only the toe area and only in the low threshold group. These results suggest that the reason for the contradictory results of surgical sympathectomy in spinal nerve ligation models is, at least in part, the difference in the degree of mechanical allodynia in each study.

Animals↗
PubMed2001

An azophenol-based chromogenic anion sensor.

[figure: see text] A new chromogenic azophenol-thiourea based anion sensor, 2, has been developed. This system allows for the selective colorimetric detection of F-, H2PO4-, and AcO-. Selectivity trends turned out to be dependent upon guest basicity and conformational complementarity between 2 and the guest.

Journal Article↗
PubMed2001

Biochemical properties of a newly synthesized H(+)/K(+) ATPase inhibitor, 1-(2-methyl-4-methoxyphenyl)-4-.

A new compound, 1-(2-methyl-4-methoxyphenyl)-4-[(3-hydroxypropyl)amino]-6-methyl-2,3-dihydropyrrolo[3,2-c]quinoline (DBM-819), inhibited gastric H(+)/K(+) ATPase in the rabbit (EC 3.6.1.3) with an IC(50) value of 5 microM. However, DBM-819 was a weak inhibitor of kidney Na(+)/K(+) ATPase in the dog, indicating that it has selectivity for the gastric H(+)/K(+) ATPase. The inhibition was reversible and non-competitive with respect to the activating cation K(+). The presence of dithiothreitol did not protect the H(+)/K(+) ATPase from inactivation. The inhibition by DBM-819 was potentiated by acid pretreatment of the compound, suggesting that DBM-819 is converted into a more active intermediate under acidic conditions. The results suggest that DBM-819 is a potent, selective and reversible inhibitor of gastric H(+)/K(+) ATPase, and that the essential cysteine residue may not be involved in the DBM-819-mediated inactivation of gastric H(+)/K(+) ATPase.

Acids↗