Biomedical subjects

A Liu

Publications and source records attributed to A Liu.

At least 55 records · Page 3Linked to original sources

PubMed2001

A computer-based simulator for diagnostic peritoneal lavage.

Diagnostic peritoneal lavage (DPL) is an emergency diagnostic procedure performed when intra-abdominal bleeding secondary to trauma is suspected. This procedure is part of the surgical skills section of the Advanced Trauma Life Support course. DPL is traditionally taught using anesthetized animals or cadavers. For reasons described below, these alternatives are not ideal. We have developed a computer-based diagnostic peritoneal lavage simulator. Our system addresses the shortcomings of the traditional method. We have used our system to teach ATLS. Preliminary results suggests that our system is effective.

Abdominal Injuries↗

PubMed2001

[Cytokines in experimental cancer cachexia].

OBJECTIVE: To investigate the relationship between cytokine IL-6, IL-1, TNF-alpha and experimental cancer cachexia as well as observe the effect of indomethacin on the cachectic mice. METHODS: T739 mice bearing lung adenocarcinoma LA795 were used as murine tumor cachexia model. In this experiment, serum IL-6, IL-1, TNF-alpha, glucose, protein and triglyceride levels and body weight in different stages of cancer cachexia were monitored. Thirty-two mice were randomized into four groups for comparison, with eight mice in each group: no tumor (NTB) group, tumor without treatment (NT) group, tumor with normal saline (NST) group and tumor with indomethacin (INDT) group. For the last group, intraperitoneal infusion of indothacin 1 microgram/gm was given once every day for six days starting from the 14 th day of tumor implantation. RESULTS: Compared with the NTB group, the NT group showed higher serum of IL-6, IL-1, TNF-alpha and lower total protein, triglyceride and glucose (P < 0.01). After treatment with indomethacin, the INDT mice gave higher serum glucose, protein and lipid levels. Meanwhile, the serum level of IL-6, TNF-alpha and IL-1 in the INDT group was found to be significantly low in comparison with the NST group. CONCLUSION: (1) IL-6, IL-1 and TNF-alpha appear to be involved in experimental cancer cachexia. (2) The positive effects of indomethacin by inhibiting the growth of these cytokines indicate that indomethacin is able to improve the condition of cancer cachexia.

Adenocarcinoma↗

PubMed2001

[Changes of the temporomandibular joint following orthognathic surgery on radiography].

OBJECTIVE: To investigate the effect of different operative techniques and fixed methods on the TMJ condylar position and remolding process. METHODS: The standard Schuller's position radiographs were used to examine the postoperative temporomandibular joint form and condylar position changes of 57 cases within one week and one year after orthognathic surgery. The form changes were divided into three types. Type I was that the joint form was normal or abnormal before the operation and no significant change was found after the operation. Type II was that the joint form was abnormal before but after the operation it was improved. Type III was that the joint form was normal before but after the operation it changed into abnormal or it was abnormal before but after the operation it worsened. RESULTS: 1. Changes of the condylar position had happened after the operations, but within one year the condyles had resumed the same position as the preoperative. The condylar displacements were not beyond the TMJ adaptabilities. Different operative techniques had different effects on the condylar positions. 2. In 86.4% of cases, TMJs had undergone adaptable remolding (Type II) or no significant changes (Type I). Only 13.6% of cases, degenerative changes were found (Type III). CONCLUSIONS: The effect of orthognathic surgery on the condylar position and TMJ form is significant, but most of the changes are within the normal adaptability of TMJ.

Adolescent↗

PubMed2001

[The relationship of low density lipoprotein receptor gene polymorphism and hyperlipidemia].

OBJECTIVE: To study the relationship of low density lipoprotein receptor gene polymorphism and hyperlipidemia in the population with essential hypertension. METHODS: People with different lipid levels including 107 hyperlipidemia, 104 at margin level and 108 normal were recruited in the study. Their polymorphisms of LDL-R gene were analyzed using PCR-RFLP. RESULTS: There were three kinds of genotype: (+/+), (+/-), (-/-). In male, the frequencies of the (+/-) in three study groups were shown as follows: 41.18% in hyperlipidemia, 46.15% in margin level, 19.05% in normal lipid. The frequency of (+) allele was significantly higher in hyperlipidemia than that in normal lipid (24.51%, 25.00% and 11.11%, respectively). In women, the differences were not statistically significant. The nonconditional univariate and multivariate logistic regression analysis demonstrated that (+) allele of Ava II polymorphism of LDL-R was a genetic marker of male's hypercholesterolemia. CONCLUSIONS: The frequency of (+/-) hyperlipidemia in males was higher than that in normal lipid group and the (+) allele in male hyperlipidemia was significantly more frequent seen than that in normal lipid group. These results suggested that polymorphisms of LDL-Rgene might play an independent role of risk factor for hyperlipidemia.

Female↗

PubMed2001

[A novel rat aplastic anemia model induced by 5-fluorouracil combined with busulfan].

OBJECTIVE: To develop an aplastic anemia model with hematopoietic stem cell failure in rats. METHODS: Normal Wistar rats were injected i.p. with 5-fluorouracil and 5 days later p.o. by busulfan once a week for 3 times. A 5-FU alone group and a busulfan alone group were as control. The parameters tested indices were as following: incidence and mortality of aplastic anemia rats, blood picture, bone marrow nucleated cell count, CFU-GM of bone marrow cells and histology of hematopoietic organs. RESULTS: In the 5-FU plus busulfan group, the incidence of acute aplastic anemia was 82.0% (40/49 rats), the average survival time was (30.0 +/- 6.5) days. The remained 9 rats developed chronic aplastic anemia (18.0%). The total incidence of aplastic anemia was 100%, and the mortality was 98%. The blood cells count of the aplastic anemia rats was gradually reduced to a level of half the premedications and no CFU-GM was detected, and the patho-morphological examination showed that the bone marrow was replaced by fat cells, and the lymphoid tissue of spleen, thymus and lymph-nodes were remarkably atrophied without extra-medullary hematopoiesis. The control group (5-FU treated) developed a transient hematopoiesis suppression, and recovered rapidly to normal. Three of 12 rats in the busulfan treated group developed aplastic anemia. CONCLUSION: 5-FU combined with busulfan could impair the hematopoietic stem cells and resulted in an irreversible aplastic anemia in rats, making a rat aplastic anemia model with hematopoietic stem cell failure.

Anemia, Aplastic↗

PubMed2000

Geranylgeranylated RhoB is sufficient to mediate tissue-specific suppression of Akt kinase activity by farnesyltransferase inhibitors.

Farnesyltransferase inhibitors (FTIs) induce apoptosis by elevating the levels of geranylgeranylated RhoB (RhoB-GG) in cells. However, the mechanism by which RhoB-GG acts is unclear. Here we report that RhoB-GG is sufficient to mediate the suppressive effects of FTIs on the activity of the survival kinase Akt-1 in epithelial cells. This mechanism is tissue-specific insofar as it does not operate in fibroblasts. We discuss how the cell survival functions of RhoB and Akt may be linked biochemically in certain cell types.

Alkyl and Aryl Transferases↗

PubMed2000

EPR evidence of two structurally different diferric sites in Mycobacterium tuberculosis R2-2 ribonucleotide reductase protein.

Mixed-valent species were generated in the diiron site of active (with tyrosyl free radical) and met (without radical) forms of protein R2-2 in a class Ib ribonucleotide reductase from Mycobacterium tuberculosis by low temperature reduction (gamma-irradiation) at 77 K. The primary mixed-valent EPR signal is a mixture of two components with axial symmetry and g(av) < 2.0, observable at temperatures up to 77 K, and assigned to antiferromagnetically coupled high spin ferric/ferrous sites. The two components in the primary EPR signal can be explained by the existence of two structurally distinct mu-oxo-bridged diferric centers, possibly related to structural heterogeneity around the iron site, and/or different properties of the two polypeptide chains in the homodimeric protein after the radical reconstitution reaction. Annealing of the irradiated R2-2 samples to 143 K transforms the primary EPR signal into a rhombic spectrum characterized by g(av) < 1.8 and observable only below 25 K. This spectrum is assigned to a partially relaxed form with a mu-hydroxo-bridge. Further annealing at 228 K produces a new complex rhombic EPR spectrum composed of at least two components. An identical EPR spectrum was observed and found to be stable upon chemical reduction of Mycobacterium tuberculosis RNR R2-2 at 293 K by dithionite.

Dithionite↗

PubMed2000

Chemical speciation of nickel in fly ash by phase separation and carbon paste electrode voltammetry

In a risk-based approach to cost-effective management of power plant emissions, chemical speciation of fly ash is required. A quantitative but indirect separation of nickel phases by sequential extraction was undertaken in conjunction with direct analysis of the sulfidic nickel phase by carbon paste electrode voltammetry (CPEV). Four ash samples produced in a laboratory combustion system from burning high- and low-sulfur residual oil at excess O(2) of 1 and 2-3 mol% were studied. The extractions yielded five phases of nickel. The CPEV analysis of sulfidic nickel in the ash and extraction residues was performed in pH 5 acetate. The anodic peak (-0.1 V) unique to Ni(3)S(2), distinguishing it from NiS and NiS(2), was found to be absent from these ash samples. The CPEV method was consistent with phase extraction, which showed NiSO(4) being predominant with very low proportions of sulfidic nickel.

Journal Article↗

PubMed2000

Electron paramagnetic resonance evidence for a novel interconversion of [3Fe-4S](+) and [4Fe-4S](+) clusters with endogenous iron and sulfide in anaerobic ribonucleotide reductase activase in vitro.

We report an EPR study of the iron-sulfur enzyme, anaerobic ribonucleotide reductase activase from Lactococcus lactis. The activase (nrdG gene) together with S-adenosyl-L-methionine (AdoMet) give rise to a glycyl radical in the NrdD component. A semi-reduced [4Fe-4S](+) cluster with an axially symmetric EPR signal was produced upon photochemical reduction of the activase. Air exposure of the reduced enzyme gave a [3Fe-4S](+) cluster. The Fe(3)S(4) cluster was convertible to the EPR-active [4Fe-4S](+) cluster by renewed treatment with reducing agents, demonstrating a reversible [3Fe-4S](+)- to-[4Fe-4S](+) cluster conversion without exogenous addition of iron or sulfide. Anaerobic reduction of the activase by a moderate concentration of dithionite also resulted in a semi-reduced [4Fe-4S](+) cluster. Prolonged reduction gave an EPR-silent fully reduced state, which was enzymatically inactive. Both reduced states gave the [3Fe-4S](+) EPR signal after air exposure. The iron-sulfur cluster interconversion was also studied in the presence of AdoMet. The EPR signal of semi-reduced activase-AdoMet had rhombic symmetry and was independent of which reductant was applied, whereas the EPR signal of the [3Fe-4S](+) cluster after air exposure was unchanged. The results indicate that an AdoMet-mediated [4Fe-4S](+) center is the native active species that induces the formation of a glycyl radical in the NrdD component.

Bacterial Proteins↗

PubMed2000

Heterocyclic bibenzimidazole derivatives as topoisomerase I inhibitors.

A series of 2'-heterocyclic derivatives of 5-phenyl-2,5'-1H-bibenzimidazoles were evaluated for topoisomerase I poisoning activity and cytotoxicity. Topo I poisoning activity was associated with 2'-derivatives that possessed a hydrogen atom capable of hydrogen bond formation, suggesting that the interatomic distances between such hydrogen atoms and the heteroatoms on the adjacent benzimidazole influence activity.

Benzimidazoles↗

PubMed2000

Molecular cloning and characterization of Pals, proteins associated with mLin-7.

In Caenorhabditis elegans, three PDZ domain proteins, Lin-2, Lin-7, and Lin-10, are necessary for the proper targeting of the Let-23 growth factor receptor to the basolateral surface of epithelial cells. It has been demonstrated that homologues of Lin-2, Lin-7, and Lin-10 form a heterotrimeric complex in mammalian brain. Using Far Western overlay assay, we have identified additional proteins that can bind to the amino terminus of mLin-7 and cloned the genes encoding these proteins using bacterial expression cloning. We call these proteins Pals, for proteins associated with Lin-7. These proteins, which include mammalian Lin-2, contain a conserved mLin-7 binding domain in addition to guanylate kinase, PDZ (postsynaptic density 95/discs large/zona occludens-1), and Src homology 3 domains. Using site-directed mutagenesis, we have identified the conserved residues among these proteins crucial for mLin-7 binding. Two of these proteins, Pals1 and Pals2, are newly described. Pals1 consists of 675 amino acids and maps to mouse chromosome 12. Pals2 was found to exist in two splice forms of 539 and 553 amino acids and maps to mouse chromosome 6. Like mLin-2, Pals1 and Pals2 localize to the lateral membrane in Madin-Darby canine kidney cells. Pals proteins represent a new subfamily of membrane-associated guanylate kinases that allow for multiple targeting complexes containing mLin-7.

Amino Acid Sequence↗

PubMed2000

Cell growth and matrix invasion of EBV-immortalized human B lymphocytes is regulated by expression of alpha(v) integrins.

alpha(v) integrins have been shown to play an important role in epithelial-derived cell migration, cell growth and tumor invasion/metastasis, however their role on cells of hematopoietic origin is less clear. Epstein-Barr virus (EBV), a human herpesvirus associated with several lymphoproliferative disorders in man, induces expression of alpha(v) integrins on transformed B lymphocytes. In the studies reported here, we show that EBV infection increases alpha(v), beta3 and beta5 integrin subunit mRNAs as well as upregulates the expression of the alphavbeta3 integrin protein on human B cells. Among the nine different EBV proteins expressed in latently infected B cells (nuclear and plasma membrane-associated), only LMP1, LMP2A and EBNA2 were shown to selectively transactivate the alpha(v) integrin promoter. Treatment of EBV-transformed B cells with alpha(v) antisense oligonucleotides specifically reduced cell surface expression of alpha(v) integrins, inhibited cell growth in low serum, reduced cell invasion in matrigels and decreased expression of metalloprotease, MMP9. These studies indicate that alpha(v) integrins play a significant role in EBV-induced B-lymphocyte proliferation and invasion. Strategies to interfere with alphav integrin expression and/or function may therefore be of potential value in the treatment of EBV-associated lymphoproliferative disorders.

Antigens, CD↗

PubMed2000

Yeast ribonucleotide reductase has a heterodimeric iron-radical-containing subunit.

Ribonucleotide reductase (RNR) catalyzes the de novo synthesis of deoxyribonucleotides. Eukaryotes have an alpha(2)beta(2) form of RNR consisting of two homodimeric subunits, proteins R1 (alpha(2)) and R2 (beta(2)). The R1 protein is the business end of the enzyme containing the active site and the binding sites for allosteric effectors. The R2 protein is a radical storage device containing an iron center-generated tyrosyl free radical. Previous work has identified an RNR protein in yeast, Rnr4p, which is homologous to other R2 proteins but lacks a number of conserved amino acid residues involved in iron binding. Using highly purified recombinant yeast RNR proteins, we demonstrate that the crucial role of Rnr4p (beta') is to fold correctly and stabilize the radical-storing Rnr2p by forming a stable 1:1 Rnr2p/Rnr4p complex. This complex sediments at 5.6 S as a betabeta' heterodimer in a sucrose gradient. In the presence of Rnr1p, both polypeptides of the Rnr2p/Rnr4p heterodimer cosediment at 9.7 S as expected for an alpha(2)betabeta' heterotetramer, where Rnr4p plays an important role in the interaction between the alpha(2) and the betabeta ' subunits. The specific activity of the Rnr2p complexed with Rnr4p is 2,250 nmol deoxycytidine 5'-diphosphate formed per min per mg, whereas the homodimer of Rnr2p shows no activity. This difference in activity may be a consequence of the different conformations of the inactive homodimeric Rnr2p and the active Rnr4p-bound form, as shown by CD spectroscopy. Taken together, our results show that the Rnr2p/Rnr4p heterodimer is the active form of the yeast RNR small subunit.

Blotting, Western↗

PubMed2000

Zebrafish wnt4b expression in the floor plate is altered in sonic hedgehog and gli-2 mutants.

The floor plate of the neural tube serves an important function as a source of signals that pattern cell fates in the nervous system as well as directing proper axon pathfinding. We have cloned a novel zebrafish wnt family member, wnt4b, which is expressed exclusively in the floor plate. To place wnt4b in the context of known regulators of midline development, its expression was analyzed in the zebrafish mutants cyclops (cyc), floating head (flh), you-too (yot), and sonic you (syu). wnt4b expression in the medial and lateral floor plate are shown to be regulated independently: medial floor plate expression occurs in the absence of a notochord, while lateral floor plate expression requires a functional notochord, sonic hedgehog and gli-2.

Amino Acid Sequence↗

PubMed2000

A polymorphic L1 retroposon insertion in the centromere of the human Y chromosome.

We have identified a novel polymorphic L1 retroposon insertion, designated LY1, in the centromeric alphoid array of the human Y chromosome. The element belongs to the transpositionally active Ta subset and its presence is compatible with normal centromere function. It was found at highest frequency in China, where it accounts for 23% of the Han sample, and was present at low frequencies in the surrounding areas, but was not found at all outside Asia. Chromosomes carrying LY1 show considerable microsatellite diversity, suggesting an ancient origin for the lineage at approximately 10 000 years ago (with wide confidence limits), but only limited subsequent migration.

Base Sequence↗

PubMed2000

Evaluating changes in stable chromosomal translocation frequency in patients receiving radioimmunotherapy.

PURPOSE: The lack of any consistent correlation between radioimmunotherapy (RIT) dose and observed hematologic toxicity has made it difficult to validate RIT radiation dose estimates to marrow. Stable chromosomal translocations (SCT) which result after radiation exposure may be a biologic parameter that more closely correlates with RIT radiation dose. Increases in the frequency of SCT are observed after radiation exposure and are highly correlated with absorbed radiation dose. SCT are cumulative after multiple radiation doses and conserved through an extended number of cell divisions. The purpose of this study was to evaluate whether increases in SCT frequency were detectable in peripheral lymphocytes after RIT and whether the magnitude of these increases correlated with estimated radiation dose to marrow and whole body. METHODS AND MATERIALS: Patients entered in a Phase I dose escalation therapy trial each received 1-3 intravenous cycles of the radiolabeled anti- carcinoembryonic antigen (CEA) monoclonal antibody, 90Y-chimeric T84.66. Five mCi of 111In-chimeric T84.66 was co-administered for imaging and biodistribution purposes. Blood samples were collected immediately prior to the start of therapy and 5-6 weeks after each therapy cycle. Peripheral lymphocytes were harvested after 72 hours of phytohemagglutinin stimulation and metaphase spreads prepared. Spreads were then stained by fluorescence in situ hybridization (FISH) using commercially available chromosome paint probes to chromosomes 3 and 4. Approximately 1000 spreads were evaluated for each chromosome sample. Red marrow radiation doses were estimated using the AAPM algorithm and blood clearance curves. RESULTS: Eighteen patients were studied, each receiving at least one cycle of therapy ranging from 5-22 mCi/m2. Three patients received 2 cycles and two patients received 3 cycles of therapy. Cumulative estimated marrow doses ranged from 9.2 to 310 cGy. Increases in SCT frequencies were observed after each cycle for both chromosomes 3 and 4 in 16 of 18 patients and in at least one chromosome for the remaining 2 patients. Cumulative increases in SCT frequencies ranged from 0.001 to 0.046 with no major differences observed between chromosomes 3 and 4. A linear correlation between cumulative marrow dose and increases in SCT frequencies was observed for chromosome 3 (R2 = 0.63) and chromosome 4 (R2 = 0.80). A linear correlation was also observed between increases in SCT frequency and whole body radiation dose or administered activity (R2 = 0.67-0.89). There was less correlation between observed decrease in wbc or platelet counts and marrow dose, whole body dose, or administered activity (R2 = 0.28-0.43). CONCLUSIONS: Increases in SCT frequency were detectable in peripheral lymphocytes after low dose-rate RIT irradiation. A linear correlation was observed between increases in SCT and marrow dose, whole body dose, and administered activity. This correlation provides one of the strongest radiation dose-response and activity-response relationships observed with RIT. The detection of SCT may therefore have application as an in situ integrating biodosimeter after RIT. This biologic parameter should prove useful in comparing effects on marrow for different therapeutic radionuclides and in comparing effects of RIT and external beam radiation doses on a cGy per cGy basis. As a result, this should allow for a more direct comparison between different methods of irradiation and in further refinement of radioimmunotherapy dose estimates and dosimetry methodology.

Bone Marrow↗

PubMed2000

Sample size calculation for planning group sequential longitudinal trials.

Procedures are developed in this paper for sample size calculations for planning a group sequential longitudinal trial with various correlation structures, using a test statistic based on generalized estimating equations (Lee, Kim and Tsiatis) and group sequential boundaries based on type I error spending functions (Lan and DeMets).

Adolescent↗

PubMed2000

The anaerobic (class III) ribonucleotide reductase from Lactococcus lactis. Catalytic properties and allosteric regulation of the pure enzyme system.

Lactococcus lactis contains an operon with the genes (nrdD and nrdG) for a class III ribonucleotide reductase. Strict anaerobic growth depends on the activity of these genes. Both were sequenced, cloned, and overproduced in Escherichia coli. The corresponding proteins, NrdD and NrdG, were purified close to homogeneity. The amino acid sequences of NrdD (747 residues, 84.1 kDa) and NrdG (199 residues, 23.3 kDa) are 53 and 42% identical with the respective E. coli proteins. Together, they catalyze the reduction of ribonucleoside triphosphates to the corresponding deoxyribonucleotides in the presence of S-adenosylmethionine, reduced flavodoxin or reduced deazaflavin, potassium ions, dithiothreitol, and formate. EPR experiments demonstrated a [4Fe-4S](+) cluster in reduced NrdG and a glycyl radical in activated NrdD, similar to the E. coli NrdD and NrdG proteins. Different from E. coli, the two polypeptides of NrdD and the proteins in the NrdD-NrdG complex were only loosely associated. Also the FeS cluster was easily lost from NrdG. The substrate specificity and overall activity of the L. lactis enzyme was regulated according to the general rules for ribonucleotide reductases. Allosteric effectors bound to two separate sites on NrdD, one binding dATP, dGTP, and dTTP and the other binding dATP and ATP. The two sites showed an unusually high degree of cooperativity with complex interactions between effectors and a fine-tuning of their physiological effects. The results with the L. lactis class III reductase further support the concept of a common origin for all present day ribonucleotide reductases.

Allosteric Regulation↗