Biomedical subjects

Q Li

Publications and source records attributed to Q Li.

At least 289 records · Page 16Linked to original sources

PubMed2000

Conversion of compatible plant-pathogen interactions into incompatible interactions by expression of the Pseudomonas syringae pv. syringae 61 hrmA gene in transgenic tobacco plants.

The hrmA gene from Pseudomonas syringae pv. syringae has previously been shown to confer avirulence on the virulent bacterium P. syringae pv. tabaci in all examined tobacco cultivars. We expressed this gene in tobacco plants under the control of the tobacco Delta0. 3 TobRB7 promoter, which is induced upon nematode infection in tobacco roots (Opperman et al. 1994, Science, 263, 221-223). A basal level of hrmA expression in leaves of transgenic plants activated the expression of pathogenesis-related genes, and the transgenic plants exhibited high levels of resistance to multiple pathogens: tobacco vein mottling virus, tobacco etch virus, black shank fungus Phytophthora parasitica, and wild fire bacterium Pseudomonas syringae pv. tabaci. However, the hrmA transgenic plants were not significantly more resistant to root-knot nematodes. Our results suggest a potential use of controlled low-level expression of bacterial avr genes, such as hrmA, in plants to generate broad-spectrum resistance to bacterial, fungal and viral pathogens.

Animals↗

PubMed2000

Bovine FcgammaRIII with a single extracellular domain.

The full length of gene encoding Fc receptor types III for bovine immunoglobulin G (boFcgammaRIII, CD16) was obtained with PCR from the c DNA library of bovine alveolar macrophages. Through molecular cloning and sequencing it is shown that the coding gene has 507 bp and codes for 168 amino acids. There are signal peptide, transmembrane spanning domain and three potential N-linked glycosylation sites in the sequence. Compared with the boFcgammaRIII cDNA sequence cloned by Collins et al, it deletes 82 amino acids and has only one extracellular domain. It is suggested that this cDNA fragment is a special form of the gene structure of bovine FcgammaRIIIA (CD16-II).

Amino Acid Sequence↗

PubMed2000

Vascularized plantaris tendon graft: anatomic study of the donor.

In order to determine new vascularized donor tendons for grafting, a detailed anatomic study of the plantaris tendon and vascular connections with the posterior tibial artery or its branches was undertaken in 20 legs of 10 fresh adult cadavers. A histologic evaluation was also undertaken. Findings demonstrated that there is a close vascular connection between the crural fascial-linked section of the plantaris tendon and the posterior tibial artery. Through its rich surrounding paratenon, the blood supply of the tendon is provided by two to four transfascial branches of the posterior artery in the lower-middle portion of the leg. Out of these branches, one or two anastomosing arteries (more than 1.0 mm in diameter), together with accompanying veins, consistently emerge 5 to 8 cm from the insertion of the plantaris tendon. Histologic observations demonstrate the reliable vascularity of the paratenon and crural fascia. The authors consider this vascularized tendon donor a good option for grafting. A composite tendofascial flap with vascularized pedicle from the posterior tibial artery or an isolated vascularized tendon graft from its branches would both be alternative techniques for clinical vascularized tendon grafting.

Adult↗

PubMed2000

Prophylactic value of preincision intra-aortic balloon pump: analysis of a statewide experience.

OBJECTIVE: The objective of this study was to determine whether preincision use of an intra-aortic balloon pump improves survival and shortens postoperative length of stay in hemodynamically stable, high-risk patients undergoing coronary artery bypass grafting. METHODS: A post hoc analysis of the Alabama CABG Cooperative Project database was performed by using propensity scores to model the likelihood of receiving a prophylactic preincision intra-aortic balloon pump. Every patient receiving a prophylactic preincision balloon pump was matched with another patient of similar propensity score who did not receive one. We then compared outcomes for matched pairs. RESULTS: There were 7581 patients of whom 592 received a prophylactic preincision balloon pump. Patients with preoperative renal insufficiency, heart failure, or left main coronary artery disease, or who had undergone previous bypass grafting were significantly more likely to receive a prophylactic preincision balloon pump. By using propensity scores, we matched 550 patients who received a prophylactic preincision balloon pump with 550 who did not. Survival did not significantly differ by whether a prophylactic preincision balloon pump was used. However, surviving patients who received a preincision balloon pump had a significantly shorter postbypass length of stay (7 +/- 7.3 days) than did matched patients not receiving a balloon pump (8 +/- 6.2 days; P <.05). CONCLUSIONS: No survival advantage was found for use of a prophylactic intra-aortic balloon pump in hemodynamically stable, high-risk patients undergoing bypass grafting, as opposed to placing a balloon pump on an "as needed" basis during or after the operation. However, the patients receiving the balloon pump had improved convalescence as shown by significantly shorter length of stay.

Aged↗

PubMed2000

Quantitative image analysis of simian immunodeficiency virus replication in macrophages coinfected with Mycobacterium avium complex.

Mycobacterium avium is the most frequent cause of disseminated bacterial infection in patients with human immunodeficiency virus type 1 infection and in rhesus macaques with simian immunodeficiency virus (SIV) infection. This animal model of AIDS was used to test the hypothesis that this frequent association is the result of reciprocal enhancement of replication of both microorganisms. The replication of M. avium and SIV was analyzed in lymphatic tissues obtained from rhesus macaques experimentally inoculated with SIVmac who developed or remained free of overt M. avium infection. In situ hybridization, quantitative image analysis, and staining of M. avium and of macrophages were used to assess the effects of coinfection on the replication of SIV and M. avium in vivo. There was no correlation between virus load and M. avium load in coinfected lymph nodes, and, with one exception, there was no evidence that M. avium coinfection of macrophages increased SIV replication.

Animals↗

PubMed2000

Preparation and characterization of mabs against different epitopes of CD226 (PTA1).

Recently the platelet and T-cell activation antigen 1 (PTA1) was assigned as CD226 at the 7th Conference and Workshop on Human Leukocyte Differentiation antigens (HLDA). PTA1 is mainly expressed on activated T cells, natural killer (NK) cells, platelets and stimulated endotheliocytes, and involved in the differentiation of cytotoxic T lymphocytes (CTL) and NK, as well as platelet activation and aggregation. We raised hybridomas secreting monoclonal antibodies (MAbs) to PTA1 by using the natural PTA1 as immunogen, which was purified from platelets via affinity chromatography. These MAbs, designated FMU1, FMU2, FMU3, FMU4, FMU5, FMU6 and FMU7, could recognize PTA1 cDNA transfected COS7 cells detected by flow cytometry (FCM), and also react with both natural PTA1 and PTA1/Ig fusion protein in indirect enzyme-linked immunoadsorbent assay (ELISA). The biosensor epitope mapping assay showed that the seven MAbs, together with previous PTA1-specific MAbs Leo A1 and New E1, could bind seven distinct epitopes of PTA1, respectively. The panel of MAbs might be new powerful tools to study the structure-function relationship of PTA1 molecule, and to search for the ligand of PTA1.

Animals↗

PubMed2000

Genetic analysis of the Drosophila DNAprim gene. The function of the 60-kd primase subunit of DNA polymerase opposes the fat facets signaling pathway in the developing eye.

The Drosophila DNAprim gene encodes the large subunit (60 kD) of DNA primase, the part of DNA polymerase alpha that synthesizes RNA primers during DNA replication. The precise function of the 60-kD subunit is unknown. In a mutagenesis screen for suppressors of the fat facets (faf) mutant eye phenotype, we identified mutations in DNAprim. The faf gene encodes a deubiquitinating enzyme required specifically for patterning the compound eye. The DNA sequences of four DNAprim alleles were determined and these define essential protein domains. We show that while flies lacking DNAprim activity are lethal, flies with reduced DNAprim activity display morphological defects in their eyes, and unlike faf mutants, cell cycle abnormalities in larval eye discs. Mechanisms by which DNA primase levels might influence the faf-dependent cell communication pathway are discussed.

Alleles↗

PubMed2000

TYRP2-mediated resistance to cis-diamminedichloroplatinum (II) in human melanoma cells is independent of tyrosinase and TYRP1 expression and melanin content.

Tyrosinase-related protein-2 (TYRP2) is a melanocyte-specific enzyme that catalyses the non-decarboxylative tautomerization of L-dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in the melanin biosynthetic pathway. We have recently demonstrated that the constitutive expression of TYRP2 in human melanoma cells positively correlates with cis-diamminedichloroplatinum (II) (CDDP) resistance, and that the ectopic expression of TYRP2 in CDDP-sensitive cells rendered them more resistant to CDDP treatment. Here, we demonstrate that this correlation between constitutive TYRP2 expression and CDDP resistance applies to a panel of distinct human melanoma cell lines obtained from patients with melanoma at various stages of disease progression. We further show that CDDP resistance correlates only with TYRP2 expression and is associated neither with tyrosinase and TYRP1 expression, nor with cellular melanin content. Together, these results further support the notion that TYRP2 is a novel mediator of CDDP resistance in melanoma cells and suggest that this function of TYRP2 is independent of cellular melanin content and of the other regulatory enzymes of the melanogenic pathway.

Cell Survival↗

PubMed2000

Procalcitonin and proinflammatory cytokine interactions in sepsis.

Immunoneutralization of procalcitonin (ProCT), a putative mediator of sepsis, has been shown to increase survival in an animal model of sepsis. To better understand the role that ProCT plays in the sepsis cascade, we studied the relationship of this hormone to the proximal proinflammatory mediators, IL-1beta and TNFalpha. Hamsters were made septic by i.p. implantation of Escherichia coli-impregnated agar pellets. A time line study of serum IL-beta, TNFalpha, and ProCT levels showed that the increase in the cytokines was transient and less than 2-fold over baseline, whereas ProCT increased >100-fold by 12 h and remains elevated through 24 h. TNFalpha (400 microg/kg) was injected into healthy animals, inducing an elevation in ProCT that was 25-fold greater than controls. ProCT (30 microg/kg) was given to healthy and septic animals. In healthy animals, there was no significant elevation in serum IL-1beta or TNFalpha levels. In septic animals, IL-1beta was modestly blunted at 3 h but not at 12 h, and there was no change in TNFalpha levels. ProCT did not initiate or enhance IL-1beta or TNFalpha expression; however, the massive and sustained elevation of this hormone seen in sepsis can be induced by the proximal cytokine, TNFalpha. This study suggests that ProCT is a secondary mediator that might augment and amplify but does not initiate the septic response. Immunoneutralization of ProCT may prove to be an important clinical strategy, in view of its sustained elevation and the difficulty in initiating therapy for sepsis during the early phases of illness.

Animals↗

PubMed2000

Therapeutic applications of antiflammin peptides in experimental ocular inflammation.

Antiflammins are synthetic peptides derived from the region of highest local similarity between uteroglobulin and lipocortin. These peptides have shown anti-inflammatory activity on carrageenan-induced rat footpad edema. They are potent inhibitors for phospholipase A2 activation both in vitro and in vivo. Previously, we have demonstrated the effectiveness of topical antiflammins in suppressing acute ocular inflammation and allergic response in rodent endotoxin-induced uveitis and murine allergic conjunctivitis. The mechanisms by which antiflammins protect against inflammation and allergy in these ocular models may involve inhibition of phospholipase A2 and inducible nitric oxide synthase (iNOS) as well as the production of proinflammatory cytokine, interleukin-6.

Animals↗

PubMed2000

Role of ECM remodeling in thyroid hormone-dependent apoptosis during anuran metamorphosis.

Programmed cell death or apoptosis is an important aspect in organogenesis and tissue remodeling. It is precisely controlled both temporally and spatially during development. Amphibian metamorphosis is an excellent model to study developmental control of apoptosis in vertebrates. This process involves the transformation of essentially every organ/tissue as tadpoles change to frogs, yet is controlled by a single hormone, thyroid hormone (TH). Although different organs and tissues undergo vastly different developmental changes, including de novo development and total resorption, most require apoptotic elimination of at least some cell types. Such properties and the dependence on TH make frog metamorphosis a unique model to isolate and functionally characterize genes participating in the regulation of tissue specific cell death during organ development in vertebrates. Indeed, molecular studies of the TH-dependent gene regulation cascade have led to the discovery of a group of genes encoding matrix metalloproteinases (MMPs) participating in metamorphosis. In vivo and in vitro studies have provided strong evidence to support a role of MMP-mediated remodeling of the extracellular matrix in regulating apoptotic tissue remodeling during metamorphosis.

Animals↗

PubMed2000

Improved contralateral subtraction images by use of elastic matching technique.

A contralateral subtraction technique has been developed to assist radiologists in the detection of asymmetric abnormalities such as lung nodules on a single chest radiograph. With this technique, a contralateral subtraction image is obtained by subtracting a right/left reversed "mirror" image from the original one. The lesions in the subtraction image may be enhanced because most of the symmetric skeletal structures, such as peripheral ribs, are eliminated. Although the quality of the previous contralateral subtraction images is relatively good, severe misregistration artifacts, mainly due to serious asymmetry of the ribs in the two lungs of the original image, were observed in some cases, and minor misregistration artifacts were also observed in many cases. In this study, we employed three image warping techniques. An initial global warping technique was applied to reduce severe misregistration artifacts in the subtraction image caused by asymmetric rib structures. Additional two iterative warping techniques based on an elastic matching technique were used for accurate registration of the local structures of ribs, so that minor artifacts present in many subtraction images obtained with the previous technique were greatly reduced. With the new technique, the percentage of chest images, which were rated as being of adequate, good, or excellent quality of subtraction images by use of a subjective evaluation method, was improved from 91% to 97%. In particular, the number of cases with excellent quality was greatly increased from 15% to 42%. The contralateral subtraction technique can be used for detection of asymmetric abnormalities, such as lung nodules, pneumothorax, pneumonia, and emphysema, on peripheral lungs in single chest radiographs, and it therefore has potential utility in a large proportion of abnormal chest images.

Algorithms↗

PubMed2000

Contralateral subtraction: a novel technique for detection of asymmetric abnormalities on digital chest radiographs.

A novel contralateral subtraction technique has been developed to assist radiologists in the detection of asymmetric abnormalities on a single chest radiograph. With this method, the lateral inclination is first corrected by rotating and shifting the original chest image so that the midline of the thorax is aligned with the vertical centerline of the original chest image. The rotated image is then flipped laterally to produce a reversed "mirror" image. Finally, the mirror image is warped and subtracted from the original image for derivation of the contralateral subtraction image. The three key techniques which are employed in this study are applied successively to the initial contralateral subtraction technique for acquisition of improved subtraction images. One hundred PA chest radiographs, including 50 normals and 50 abnormals, were used as the database for this study. The percentage of chest images, which were rated as being adequate, good, or excellent quality of subtraction images by employing a subjective evaluation method, was improved from 73% to 91% by use of the three key techniques. The contralateral subtraction technique can be used for detection of any asymmetric abnormalities, such as lung nodules, pneumothorax, pneumonia, and emphysema, on a single chest radiograph, and therefore has potential utility in a high proportion of abnormal cases.

Biophysical Phenomena↗

PubMed2000

Characterization of the UDP-glucuronosyltransferase 1A locus in lagomorphs: evidence for duplication of the UGT1A6 gene.

The UGT1 locus is felt to be highly conserved between species, as is evident from the characterization of the locus in rodents and humans. In rabbits, cDNAs encoding proteins homologous to human UGT1A4, UGT1A6, and UGT1A7 have previously been identified. Here we demonstrate by Southern blot analysis, using exon 1 divergent 5' segments from rabbit UGT1A4 and UGT1A6 cDNAs, the existence of a cluster of highly related genes that are homologous to each of these exon 1 sequences. In comparing rabbit and human, it is evident that the UGT1A4 and UGT1A6 gene clusters in rabbit have undergone gene duplication. This is particularly evident with rabbit UGT1A6. The human UGT1A6 cDNA anneals to only a single gene fragment, as displayed by Southern blot analysis, indicating that the UGT1A6 exon 1 sequence is highly conserved. However, up to six rabbit UGT1A6 genes could be predicted from Southern blot analysis. To examine the potential linkage of the rabbit UGT1A6 genes, multiple UGT1A6 exons were identified from genomic DNA by extended polymerase chain reaction techniques and cloning of the UGT1A6 exon 1 sequences. Five unique UGT1A6 exon 1 gene sequences were characterized that could be predicted to encode proteins that are 98% similar in amino acid structure. Using a conserved region of the rabbit UGT1A6 cDNA as a probe to screen cDNA libraries, we identified a second UGT1A6 cDNA, termed UGT1A6alpha. In addition, a cDNA that encodes a protein similar to human UGT1A3 was also cloned. Characterization of UGT1A6alpha demonstrated the protein to be 98.9% identical to UGT1A6. The expression of rabbit UGT1A3, UGT1A4, and UGT1A6 displayed catalytic activities similar to their human orthologs. However, UGT1A6alpha was catalytically divergent from UGT1A6, indicating that UGT1A6 and UGT1A6alpha do not arise from allelic polymorphism. These results demonstrate that lagomorphs have evolved at least five additional UGT1A6 genes, an event that is not duplicated in rodents or humans.

Amino Acid Sequence↗

PubMed2000

In vitro activity of A-192411.29, a novel antifungal lipopeptide.

A-192411.29 is a novel antifungal agent derived from the structural template of the natural product echinocandin. The in vitro activity of A-192411.29 against common pathogenic yeasts was assessed by National Committee for Clinical Laboratory Standards method M27-A. It demonstrated broad-spectrum, fungicidal activity and was active against the most clinically relevant yeasts, such as Candida albicans, Candida tropicalis, and Candida glabrata, as well as less commonly encountered Candida species; in general, its potency on a weight basis was comparable to that of amphotericin B. It maintained potent in vitro activity against Candida strains with reduced susceptibilities to fluconazole and amphotericin B. The in vitro activity of A-192411.29 against Cryptococcus neoformans was comparable to its activity against Candida spp. However, A-192411.29 did not demonstrate complete growth inhibition of Aspergillus fumigatus by the broth microdilution method used. A-192411.29 possesses an antifungal profile comparable to or better than those of fluconazole and amphotericin B against pathogenic yeasts, including strains resistant to fluconazole or amphotericin B, suggesting that it may be a therapeutically useful new antifungal drug.

Antifungal Agents↗

PubMed2000

Construction and characterization of a Mycobacterium tuberculosis mutant lacking the alternate sigma factor gene, sigF.

The alternate RNA polymerase sigma factor gene, sigF, which is expressed in stationary phase and under stress conditions in vitro, has been deleted in the virulent CDC1551 strain of Mycobacterium tuberculosis. The growth rate of the DeltasigF mutant was identical to that of the isogenic wild-type strain in exponential phase, although in stationary phase the mutant achieved a higher density than the wild type. The mutant showed increased susceptibility to rifampin and rifapentine. Additionally, the DeltasigF mutant displayed diminished uptake of chenodeoxycholate, and this effect was reversed by complementation with a wild-type sigF gene. No differences in short-term intracellular growth between mutant and wild-type organisms within human monocytes were observed. Similarly, the organisms did not differ in their susceptibilities to lymphocyte-mediated inhibition of intracellular growth. However, mice infected with the DeltasigF mutant showed a median time to death of 246 days compared with 161 days for wild-type strain-infected animals (P < 0.001). These data indicate that M. tuberculosis sigF is a nonessential alternate sigma factor both in axenic culture and for survival in macrophages in vitro. While the DeltasigF mutant produces a lethal infection of mice, it is less virulent than its wild-type counterpart by time-to-death analysis.

Animals↗

PubMed2000

Identification of echocardiographic "smoke" in a bench model with transcranial Doppler ultrasound.

BACKGROUND AND PURPOSE: Spontaneous echo contrast in cardiac chamber has been indicated as a source of cerebral embolism. The nature of the echocardiographic smokelike signal is still not fully understood. This study was designed to regenerate spontaneous echo contrast and verify its thromboembolic characters in an in vitro model. METHODS: Spontaneous echo contrast was reproduced in an expansion chamber under low flow conditions in a close circulation system. The spontaneous echo contrast was monitored and recorded with a 2-dimensional cardiosonography system and a transcranial Doppler device. Meanwhile, clinically commonly encountered embolic materials such as whole-blood clots, platelet aggregate-rich plasma, air bubbles, and 100-mL normal saline were injected into this monitored circuit. The differentiation of spontaneous echo contrast from emboli was performed by both visual observations of the echo images and offline Doppler signal intensity analysis. Average signal intensities produced by spontaneous contrast and injection of embolic materials and saline were compared. Furthermore, the effect of Doppler-detected flow velocity on generation of spontaneous contrast was also evaluated. RESULTS: Spontaneous echo contrast was reproduced at low flow settings (90 to 120 mL/min) in this model. There was no significant difference in average signal intensity between the flow with spontaneous echo contrast and that without the echo (P=0.71). However, injection of embolic materials or normal saline did not generate smokelike image but caused much higher average signal intensity than the flow with spontaneous contrast (P<0.001). Injection of normal saline also increased average signal intensity. CONCLUSIONS: Our results suggest that smokelike echo is a special echo phenomenon occurring at low flow situations and does not itself produce material capable of embolizing into the systemic circulation.

Blood Flow Velocity↗

PubMed2000

Pharmacokinetics of artemisinin-type compounds.

Various compounds of the artemisinin family are currently used for the treatment of patients with malaria worldwide. They are characterised by a short half-life and feature the most rapidly acting antimalarial drugs to date. They are increasingly being used, often in combination with other drugs, although our knowledge of their main pharmacological features (including their absorption, distribution, metabolism and excretion) is still incomplete. Such data are particularly important in the case of combinations. Artemisinin derivatives are converted primarily, but to different extents, to the bioactive metabolite artenimol after either parenteral or gastrointestinal administration. The rate of conversion is lowest for artelinic acid (designed to protect the molecule against metabolism) and highest for the water-soluble artesunate. The absolute and relative bioavailability of these compounds has been established in animals, but not in humans, with the exception of artesunate. Oral bioavailability in animals ranges, approximately, between 19 and 35%. A first-pass effect is highly probably for all compounds when administered orally. Artemisinin compounds bind selectively to malaria-infected erythrocytes to yet unidentified targets. They also bind modestly to human plasma proteins, ranging from 43% for artenimol to 81.5% for artelinic acid. Their mode of action is still not completely understood, although different theories have been proposed. The lipid-soluble artemether and artemotil are released slowly when administered intramuscularly because of the 'depot' effect related to the oil formulation. Understanding the pharmacokinetic profile of these 2 drugs helps us to explain the characteristics of the toxicity and neurotoxicity. The water-soluble artesunate is rapidly converted to artenimol at rates that vary with the route of administration, but the processes need to be characterised further, including the relative contribution of pH and enzymes in tissues, blood and liver. This paper intends to summarise contemporary knowledge of the pharmacokinetics of this class of compounds and highlight areas that need further research.

Animals↗