Images in clinical medicine. Ischemic retinopathy caused by severe megaloblastic anemia.
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Adult↗
Biomedical subjects
K Li
Publications and source records attributed to K Li.
Neuropathogenicity and sensitivity to antibody neutralization of lactate dehydrogenase-elevating virus are determined by polylactosaminoglycan chains on the primary envelope glycoprotein.
Common strains of lactate dehydrogenase-elevating virus (LDV, an arterivirus), such as LDV-P and LDV-vx, are highly resistant to antibody neutralization and invariably establish a viremic, persistent, yet asymptomatic, infection in mice. Other LDV strains, LDV-C and LDV-v, have been identified that, in contrast, are highly susceptible to antibody neutralization and are incapable of a high viremic persistent infection, but at the same time have gained the ability to cause paralytic disease in immunosuppressed C58 and AKR mice. Our present results further indicate that these phenotypic differences represent linked properties that correlate with the number of N-glycosylation sites associated with the single neutralization epitope on the short ectodomain of the primary envelope glycoprotein, VP-3P. The VP-3P ectodomains of LDV-P/vx possess three N-glycosylation sites, whereas those of LDV-C/v lack the two N-terminal sites. We have now isolated four independent neutralization escape variants of neuropathogenic LDV-C and LDV-v on the basis of their ability to establish a high viremic persistent infection in mice. The VP-3P ectodomains of all four variants had specifically regained two N-glycosylation sites concomitant with decreased immunogenicity of the neutralization eptitope and decreased sensitivity to antibody neutralization as well as loss of neuropathogenicity.
Amino Acid Sequence↗
Validation of biomarkers in humans exposed to benzene: urine metabolites.
BACKGROUND: The present study was conducted among Chinese workers employed in glue- and shoe-making factories who had an average daily personal benzene exposure of 31+/-26 ppm (mean+/-SD). The metabolites monitored were S-phenylmercapturic acid (S-PMA), trans, trans-muconic acid (t,t-MA), hydroquinone (HQ), catechol (CAT), 1,2, 4-trihydroxybenzene (benzene triol, BT), and phenol. METHODS: S-PMA, t,t-MA, HQ, CAT, and BT were quantified by HPLC-tandem mass spectrometry. Phenol was measured by GC-MS. RESULTS: Levels of benzene metabolites (except BT) measured in urine samples collected from exposed workers at the end of workshift were significantly higher than those measured in unexposed subjects (P < 0.0001). The large increases in urinary metabolites from before to after work strongly correlated with benzene exposure. Concentrations of these metabolites in urine samples collected from exposed workers before work were also significantly higher than those from unexposed subjects. The half-lives of S-PMA, t,t-MA, HQ, CAT, and phenol were estimated from a time course study to be 12.8, 13.7, 12.7, 15.0, and 16.3 h, respectively. CONCLUSIONS: All metabolites, except BT, are good markers for benzene exposure at the observed levels; however, due to their high background, HQ, CAT, and phenol may not distinguish unexposed subjects from workers exposed to benzene at low ambient levels. S-PMA and t,t-MA are the most sensitive markers for low level benzene exposure.
Acetylcysteine↗
Isolation of lactate dehydrogenase-elevating viruses from wild house mice and their biological and molecular characterization.
Lactate dehydrogenase-elevating virus (LDV) was first identified as a contaminant of transplantable mouse tumors that were passaged in laboratory mice. It has been assumed that these LDVs originated from LDVs endemic in wild house mouse populations. In order to test this hypothesis and to explore the relationships between LDVs from wild house mice among each other and to those isolated from laboratory mice, we have isolated LDVs from wild house mice and determined their biological and molecular properties. We have screened for LDV tissues of 243 wild house mice that had been caught in various regions of North, Central and South America between 1985 and 1994. We were able to isolate LDVs from the tissues of four mice, three had been caught in Baltimore, MD and one in Montana. We demonstrate that the phenotypic properties (ability to establish a long-term viremic infection, low immunogenicity of the neutralization epitope, high resistance to antibody neutralization and lack of neuropathogenicity) of the four wild house mouse LDVs are identical to those of the primary LDVs isolated from transplantable tumors (LDV-P and LDV-vx), which are distinct from those of the neuropathogenic LDV-C. Furthermore, ORF 5 and ORF 2 and their protein products (the primary envelope glycoprotein VP-3P, and the minor envelope glycoprotein, respectively) of the wild house mouse LDVs were found to be closely related to those of LDV-P and LDV-vx. The LDVs caught in Baltimore, MD were especially closely related to each other, whereas the LDV isolated in Montana was more distantly related, indicating that it had evolved independently. The ectodomain of VP-3P of all four wild house mouse LDVs, like those of LDV-P and LDV-vx, possess the same three polylactosaminoglycan chains, two of which are lacking in the VP-3P ectodomain of LDV-C. These results further strengthen the conclusion that the three polylactosaminoglycan chains are the primary determinants of the phenotypic properties of LDV-P/vx.
Americas↗
Retention of organic and inorganic chemicals by the drainage/supply piping material.
A critical issue facing the turfgrass industry is the environmental fate and transport of organic and inorganic chemicals used on golf courses. The fate and distribution of those chemicals are strongly influenced by sorptive interactions with soil and sediment. In this study, the drainage and water supply piping material (used for construction of a prototype encapsulated golf green) was utilized to determine its potential sorption of three organic chemicals [2,4-dichloro-phenoxyacetic acid] (2,4-D), naphthalene and toluene and nitrate. Crushed piping material (small-to-large particle sizes) was evaluated. Isotherms were constructed using a batch equilibration technique. The results showed that the drainage/supply piping material at small particle sizes (<2.5 mm) has higher sorptive ability compared to soil (1.7 for 2,4-D and 13.4 for naphthalene). The K(F) value was 44, 253 and 70 for 2,4-D, naphthalene and toluene, respectively. K(oc) values were much higher than those of peat and soil at lower equilibrium concentrations. However, sorption decreased dramatically with increasing particle size (approaching zero at particle size 10 mm), due to reduction of surface areas and sorption sites. Sorption of NO(3)-N by the piping material was negligible. We concluded that sorption by intact drainage/supply piping material would not affect the recycling efficiency of pesticides and nutrients in the constructed encapsulated green. Conversely, drainage/supply piping material particles smaller than 2.5 mm in diameter can effectively be utilized as a filtering material.
Journal Article↗
Development of an enzyme-linked immunosorbent assay for the insecticide imidacloprid.
Enzyme-linked immunosorbent assays (ELISAs) were developed for imidacloprid, a neonicotinoid insecticide. Haptens were designed in such ways that spacer arms were introduced on either the pyridinyl or the imidazolidinyl ring of imidacloprid. Two sets of polyclonal antibodies were raised from rabbits immunized with two different immunogens and were characterized with an indirect ELISA format. Cross-reactivities and effects of organic solvents on the assays were evaluated. One set of antibodies shows approximately equal cross-reactivities to imidacloprid and its major metabolites with half-maximum inhibition concentrations (I(50)) of 73-88 ppb. Another is specific to imidacloprid with an I(50) of 35 ppb. The assay was initially applied to the analysis of imidacloprid in fortified water, coffee cherry, and bean extracts.
Enzyme-Linked Immunosorbent Assay↗
Rarity of microsatellite alterations in patients with paroxysmal nocturnal haemoglobinuria.
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Adult↗
Cloning of the mouse desmoglein 3 gene (Dsg3): interspecies conservation within the cadherin superfamily.
Desmoglein 3 is a cadherin-like calcium-dependent cell adhesion molecule expressed primarily in suprabasal keratinocytes of the epidermis. In this study, we have cloned the full-length cDNA and characterized the entire gene structure for the mouse desmoglein 3 gene (Dsg3). Isolation of overlapping cDNA clones, together with 5' and 3' rapid amplification of cDNA ends (RACE), allowed delineation of the entire coding sequence. The transcriptional initiation site was confirmed by primer extension and reverse transcription polymerase chain reaction analysis. The entire cDNA consisted of 6407 bp with an open reading frame of 2979 bp, and the deduced polypeptide contained 993 amino acids. Comparison of mouse and human desmoglein 3 amino acid sequences demonstrated 85.6% homology. Computer analysis suggested the presence of a transmembrane segment, 5 potential calcium binding sites, and a RAL motif which corresponds to the HAV motif, the potential site for homophilic interaction of typical cadherins. The mouse desmoglein 3 gene consisted of 15 exons in chromosome 18. Comparison of the intron-exon organization of Dsg3 with various cadherins from different species revealed remarkable conservation. This relatively high level of conservation both at the protein and genomic level suggests that desmoglein 3 plays an important role in keratinocyte cell-cell adhesion.
Amino Acid Sequence↗
Single vs twice daily G-CSF dose for peripheral blood stem cells harvest in normal donors and children with non-malignant diseases.
The optimal dose and schedule of G-CSF for mobilization of peripheral blood stem cells (PBSC) is not well defined. G-CSF mobilization was performed in a group of healthy donors and paediatric patients for autologous back-up before receiving allogeneic stem cell transplant. Seventeen consecutive subjects who received G-CSF at 5 microg/kg/dose twice daily (group A) were compared with a historical control group of 25 subjects who received a single daily dose of 10 microg/kg/day G-CSF (group B). Double blood volume apheresis for PBSC collection was started on day 5. G-CSF was continued and apheresis repeated until the targeted CD34+ cell dose was achieved. Both groups were comparable for sex, age, body weight and reason for PBSC collection. Over two-thirds of the subjects in both groups were less than 16 years of age. The G-CSF priming and apheresis were well tolerated. When the first day apheresis products were analyzed, group A resulted in significantly higher yield of total nucleated cells (5.91 vs 3.92 x 108/kg, P = 0. 013), mononuclear cells (5.73 vs 3.92 x 108/kg, P = 0.017), CD34+ cells (2.80 vs 1.69 x 106/kg, P = 0.049) and colony-forming units (107 vs 54 x 104/kg, P = 0.010) as compared with group B. We conclude that the two dose schedule is more efficient in mobilizing PBSC in normal donors and children with non-malignant diseases. This approach may reduce the number of aphereses required and thus reduce the transplant cost.
Adolescent↗
Gene transfer of virally encoded chemokine antagonists vMIP-II and MC148 prolongs cardiac allograft survival and inhibits donor-specific immunity.
Introducing immunomodulatory molecules into allografts by gene transfer may avoid the side-effects of systemic immunosuppression. vMIP-II and MC148 are two recently identified chemokine homologues encoded by human herpes virus 8 and Molluscum contagiosum, respectively, that have antagonistic activities against multiple different CC and CXC chemokine receptors. We hypothesized that introduction of these molecules into cardiac allografts may block leukocyte infiltration into the grafts and prolong survival. Vascularized and nonvascularized cardiac allografts in mice were performed and plasmid DNA encoding vMIP-II, MC148 and/or vIL-10 was transferred into the allograft at the time of transplantation. Gene transfer of either vMIP-II or MC148 into cardiac allografts markedly prolonged graft survival. Combining gene transfer of either one of these chemokine antagonists with vIL-10 gene transfer, which has a mechanistically different immunosuppressive action, further enhanced graft survival. vMIP-II and MC148 gene transfer both resulted in a marked decrease of donor-specific cytotoxic T lymphocytes (CTL) infiltrating the grafts and inhibited alloantibody production. These results demonstrate that plasmid-mediated gene transfer of virally encoded chemokine antagonists vMIP-II and MC148 can block donor-specific lymphocyte immunity within cardiac allografts and prolong graft survival. This is a new mechanistic approach to analyze, treat, and prevent graft rejection. Delivery of these or related molecules by gene transfer or conventional pharmacologic means may represent a novel therapeutic modality for alloactivation.
Animals↗
Analysis of diversity and genetic relationships between four Chinese indigenous pig breeds and one Australian commercial pig breed.
The genetic diversities and relationships of four Chinese indigenous pig breeds and one Australian commercial pig breed have been evaluated using 27 microsatellites recommended by the International Society of Animal Genetics (ISAG) and the Food and Agriculture Organization (FAO). The allele frequencies, effective numbers of alleles and the polymorphic information content have been calculated. Nei's standard genetic distances have been used to construct a UPGMA dendrogram, which has been evaluated by the Bootstrap test. The utility of microsatellites for evaluating genetic diversity of pigs is discussed.
Alleles↗
Expression of interleukin (IL) 1 type I and type II receptors in megakaryocytic cells and enhancing effects of IL-1beta on megakaryocytopoiesis and NF-E2 expression.
Megakaryocytopoiesis is regulated by thrombopoietin (TPO) and cytokines such as interleukin 3 (IL-3), IL-6 and IL-11. This study investigated the in vitro effects of IL-1beta on megakaryocytopoiesis and the expression of IL-1 type I and type II receptors (IL-1 RI and RII) on mega-karyocytic cell lines and primary cells. Our results demonstrated that IL-1beta alone or in combination with TPO induced megakaryocyte colony forming units (CFU-MK) from murine and human haematopoietic cells. Using reverse-transcription polymerase chain reaction (RT-PCR) and Southern hybridization techniques, the mRNA of IL-1beta, IL-1 RI, IL-1 RII and the transcription factor NF-E2 were detected in CD61+ CD41+ cells cultured from cord blood and four megakaryocytic cell lines, Meg-01, DAMI, CHRF-288-11 and M-07e. The expression of IL-1 RI and RII proteins was confirmed by flow cytometry and immunofluorescence staining. In Meg-01 cells, the expression of NF-E2 was increased at both mRNA and protein levels after treatment with IL-1beta for 4 h. This study demonstrated for the first time the presence of IL-1 receptors on megakaryocytic cells and the induction of NF-E2 by IL-1beta. The mitogenic effect of IL-1beta on this lineage could be mediated through IL-1 receptors and the activation of NF-E2.
Analysis of Variance↗
Ordering three microsatellites on porcine chromosome 12 by single sperm typing.
Three microsatellite loci on porcine chromosome 12 were ordered by single sperm typing to expand the limited genetic map of this region. Individual sperm cells from a Chinese indigenous Qingping boar triply heterozygous at SW874, SW1350 and SW1553 were amplified using PEP and heminesting primer design at each locus. Analysis of the sperm typing data by the SPERM.FOR program showed that the most likely order was SW1553-SW1350-SW874.
Animals↗
Cerebral glucose utilization and glucose transporter expression: response to water deprivation and restoration.
The relationship between local rates of cerebral glucose utilization (ICMRglc) and glucose transporter expression was examined during physiologic activation of the hypothalamoneurohypophysial system. Three days of water deprivation, which is known to activate the hypothalamoneurohypophysial system, resulted in increased ICMRglc and increased concentrations of GLUT1 and GLUT3 in the neurohypophysis; mRNA levels of GLUT1 and GLUT3 were decreased and increased, respectively. Water deprivation also increased ICMRglc in the hypothalamic supraoptic and paraventricular nuclei; mRNA levels of GLUT1 and GLUT3 appeared to increase in these nuclei, but the changes did not achieve statistical significance. Restoration of water for 3 to 7 days reversed all observed changes in GLUT expression (protein and mRNA): restoration of water also reversed changes in ICMRglc in both the neurohypophysis and the hypothalamic nuclei. These results indicate that under conditions of neural activation and recovery, changes in ICMRglc and the levels of GLUT1 and GLUT3 are temporally correlated in the neurohypophysis and raise the possibility that GLUT1 and GLUT3 transporter expression may be regulated by chronic changes in functional activity. In addition, increases in the expression of GLUT5 mRNA in the neurohypophysis after dehydration provide evidence for involvement of microglial activation.
Animals↗
Cokeromyces recurvatus as a human pathogenic fungus: case report and critical review of the published literature.
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Abscess↗
Redox chemistry in laccase-catalyzed oxidation of N-hydroxy compounds.
1-Hydroxybenzotriazole, violuric acid, and N-hydroxyacetanilide are three N-OH compounds capable of mediating a range of laccase-catalyzed biotransformations, such as paper pulp delignification and degradation of polycyclic hydrocarbons. The mechanism of their enzymatic oxidation was studied with seven fungal laccases. The oxidation had a bell-shaped pH-activity profile with an optimal pH ranging from 4 to 7. The oxidation rate was found to be dependent on the redox potential difference between the N-OH substrate and laccase. A laccase with a higher redox potential or an N-OH compound with a lower redox potential tended to have a higher oxidation rate. Similar to the enzymatic oxidation of phenols, phenoxazines, phenothiazines, and other redox-active compounds, an "outer-sphere" type of single-electron transfer from the substrate to laccase and proton release are speculated to be involved in the rate-limiting step for N-OH oxidation.
Acetaminophen↗
Strain-dependent association between lateralization and lipopolysaccharide- induced IL-1beta and IL-6 production in mice.
OBJECTIVE: The brain modulates the immune system in an asymmetrical way, as shown by the association between paw preference and immune response in the mouse. We predicted that the production of cytokines, which are one of the molecular pathways for brain-immune interactions, should be linked to lateralization in a strain-dependent manner. METHODS: We therefore measured plasma levels of interleukin (IL)-1beta and IL-6 after an intraperitoneal injection of lipopolysaccharide (LPS) in two strains of mice (C3H and BALB/c) that were selected for their different profiles of cytokine production. RESULTS: Plasma levels of IL-1beta and IL-6 increased after LPS injection in both strains and this increase was dependent on paw preference in BALB/c but not in C3H mice. Increased levels of IL-1beta were observed in left-pawed and ambidextrous but not in right-pawed mice. For IL-6, the LPS-induced increase was higher in ambidextrous than in left- and right-pawed animals. CONCLUSION: Cytokines may represent one of the factors responsible for interindividual differences in brain-immune interactions.
Analysis of Variance↗
Targeting RNA with small molecules.
Therapeutic targeting of RNA is not as well-developed as with DNA and proteins, and the many structures and functions of RNA suggest that it is an underutilized target. As with DNA, RNA has heterocyclic bases and base pairs with a highly anionic backbone, but as with proteins, RNA can fold into complex tertiary structures that create unique binding pockets for small molecules. Aminoglycoside targeting of ribosomal RNA is a well-known success story, and mRNAs and tRNAs have also served as therapeutic targets as well as model systems for understanding RNA-ligand interactions. The unique, species-specific structures and chemistry involved in splicing and ribozyme activity makes this RNA function an attractive target, and inhibitors of ribozyme activity have been discovered. The numerous serious human diseases caused by RNA viruses highlight the importance of developing new compounds that can target RNA structures in viral genomes. Considerable effort has been directed at finding compounds that target HIV-1 RNAs that control viral replication and frameshifting. As part of these efforts very useful new assays have been developed for small molecule-RNA interactions. The assays have led to the discovery of new inhibitors for different steps in viral replication. The next phase of research in RNA targeting will not only focus on the discovery of new compounds, but also on how to develop small molecules with high affinity and selectively for RNA that can penetrate effectively into a wide array of cell types.
Animals↗