Biomedical subjects

L Liu

Publications and source records attributed to L Liu.

At least 1,351 records · Page 75Linked to original sources

PubMedDate not supplied

Annexin II binds to the membrane of A549 cells in a calcium-dependent and calcium-independent manner.

We investigated the nature of annexin II binding to the biological membranes using a lung epithelium-derived cell line A549. The cytosolic and membrane fractions of A549 cells were separated in the presence of 5 mM EGTA. Both fractions contain annexin II monomer and tetramer as evaluated by western blots using specific monoclonal antibodies against p36 and p11 subunits of annexin II. A substantial amount of annexin II was associated with the membrane fraction even after extensive washing with EGTA buffer, indicating the presence of two pools of annexin II. The EGTA-resistant membrane-bound annexin II could be partially extracted by 1% Triton X-100 or 60 mM n-octyl-beta-D-glucopyranoside, and completely by 30 mM CHAPS or 0.1% deoxycholate. This fraction of annexin II was also extracted by 0.1 M Na2CO3, pH 11 and partitioned into the aqueous phase after being treated with Triton X-114, demonstrating that the EGTA-resistant annexin II is a peripheral membrane protein. When the cells were lysed in varying concentrations of Ca2+, annexin II translocated from cytosolic fraction to membrane fraction at 4-25 microM Ca2+. To identify proteins closely associated with annexin II the membrane fraction was treated with the bifunctional chemical cross-linker disulfosuccinimidyl tartarate, followed by western blot analysis using anti-p36 or anti-p11 antibodies. We find that both p36 and p11 were cross-linked to a 51 kDa protein. In addition, p11 also binds to several proteins with molecular mass of 91, 65, 40 and 36 kDa. Our results suggest that annexin II may bind to the A549 cell membranes via specific membrane-associated proteins.

Annexin A2↗

PubMedDate not supplied

Monte Carlo simulation for IRRMA.

Monte Carlo simulation is fast becoming a standard approach for many radiation applications that were previously treated almost entirely by experimental techniques. This is certainly true for Industrial Radiation and Radioisotope Measurement Applications--IRRMA. The reasons for this include: (1) the increased cost and inadequacy of experimentation for design and interpretation purposes; (2) the availability of low cost, large memory, and fast personal computers; and (3) the general availability of general purpose Monte Carlo codes that are increasingly user-friendly, efficient, and accurate. This paper discusses the history and present status of Monte Carlo simulation for IRRMA including the general purpose (GP) and specific purpose (SP) Monte Carlo codes and future needs--primarily from the experience of the authors.

Computer Simulation↗

PubMedDate not supplied

On the depth of penetration of photons and electrons for intravascular brachytherapy.

PURPOSE: To investigate the depth dose characteristics of various radionuclides under consideration for intravascular brachytherapy (IVB). MATERIALS AND METHODS: In the past few years, various preclinical studies have shown that 10-30 Gy of ionizing radiation delivered by a brachytherapy treatment may inhibit restenosis following angioplasty. A number of new delivery systems using various radionuclides have been developed and are being investigated for IVB. Typical target size for IVB is in the range of millimeters, in contrast to conventional brachytherapy for cancer in which the target may be 1-5 cm in size. The question addressed in this paper is: whether lower energy photon emitters and even beta emitters, which are not commonly used for intracavitary brachytherapy of cancer, may provide a depth of penetration adequate for IVB. To explore this issue, radial dose functions for photons and electrons in the range of 1-10 mm in water were calculated using Monte Carlo simulation. Reference depth for normalization of the radial dose funtion was chosen to be 2 mm. RESULTS: Radial dose functions have been calculated for monoenergetic photons with energies of 0.01, 0.02, 0.04, 0.06, 0.08, 0.10, 0.20, 0.40, and 1.00 MeV and monoenergetic electrons with energies of 0.5, 1.0, 1.5 and 2.0 MeV. Also, the same calculations have been performed for 192Ir, 125I, and 103Pd gamma or x-ray sources as well as 90Sr-90Y, 32P, and 188Re beta-emitting sources. Results are also provided for selected cases in a simulated calcified lesion in water. CONCLUSIONS: It is concluded that photons above an energy of 20 keV and electrons above an energy of 1.0 MeV are acceptable from the point of view of adequate depth of penetration for IVB in tissue.

Animals↗

PubMedDate not supplied

Cationic lipid polymerization as a novel approach for constructing new DNA delivery agents.

In vivo gene delivery mediated by cationic lipids is often compromised by aggregation due to complexation with proteins in the blood. To improve the stability of cationic lipid-DNA complexes, the present study aimed to develop a novel approach in which a poly(cationic lipid) (PCL) is utilized to form stable cationic polyplexes for gene transfection. Hydrogenation of the acrylamide analogue of betaAE-DMRI, the polymerizable precursor of PCL, provided a monomeric lipid derivative (MHL) which was used for direct comparison of corresponding lipoplex stability, toxicity, and transfection activity. Various formulations of cationic liposomes, such as MHL, MHL-cholesterol (Chol), PCL, PCL-Chol, DOTAP-Chol, and commercially available lipofectamine were generated and examined in this study. The new poly(cationic lipid) did not display any significant toxicity to rat hepatocytes or Hep G2 cells as indicated by an LDH leakage assay. Furthermore, PCL was significantly less toxic than MHL, DOTAP-Chol or lipofectamine. Suspensions of PCL were resistant to aggregation even after 24 h of exposure to solutions containing 50 and 100% fetal bovine serum (FBS). In contrast, suspensions of lipofectamine extensively aggregated after 24 h of exposure to 50% FBS. To examine the influence of lipid polymerization on gene transfer activity, liposome-mediated transfections of a luciferase vector (pGL3) were performed in Hep G2 and Alexander cell lines. The luciferase activity of the PCL formulations in Hep G2 cells were similar to those of the MHL, DOTAP-Chol and lipofectamine formulations, demonstrating that lipid polymerization does not compromise transfection activity. In comparison to the monomeric precursor MHL and to the industry transfection standards DOTAP and lipofectamine, the novel poly(cationic lipid) exhibited the lowest cytotoxicity, was the most resistant to serum-induced aggregation and had comparable transfection activity when coformulated with cholesterol. This novel polymerization approach for the development of stable and active polyplexes may prove a valuable alternative for in vivo gene delivery.

Animals↗

PubMedDate not supplied

A versatile and inexpensive apparatus for rapid parallel synthesis on solid support: description and synthesis illustration.

A new inexpensive and practical apparatus for solid-phase chemistry and parallel synthesis is described. This new apparatus fills an important void in the availability of portable tools for the synthesis of libraries of compounds in multi-milligram amounts. Individual reaction tube capacities range in size from 4 mL to 500 mL of operating liquid volume. Reaction blocks of 36 tubes x 4 mL or 24 tubes x 150 mL allow flexibility of operation. Insert tubes with frit ends function as filter sticks for resin wash and for maintenance of inert atmosphere. An electronic controller device connects to the reaction tubes for programmable entry of pulses of inert gas for resin mixing or vacuum for resin wash. The utility of this apparatus is illustrated by the synthesis of libraries based on 4-methaneamine imidazoles.

Amination↗

PubMedDate not supplied

The impact of radiation therapy on quality of life in patients with cancer.

PURPOSE: This study was conducted to evaluate the physical and mental status change during and after a course of radiation treatment in patients with cancer. DESCRIPTION OF STUDY: Twenty-four patients with various malignant diseases were enrolled, including 9 men and 15 women, whose median age was 64.5, to receive radiation therapy. All patients also received psychosocial support from nurses, social workers, and/or organized support groups. The Rand 36-item survey 1.0 (SF-36) was completed at the beginning, the second week, the completion of treatment, and 1 and 3 months after treatment for the evaluation of physical component scores and mental component scores. Karnofsky performance scale and toxicity scores were determined by the treating nurses and physicians. RESULTS: The physical component scores of evaluated patients before treatment were approximately 20% lower than those of the general U.S. population, whereas mental component scores were similar to those of the general U.S. population. After treatment started, Karnofsky performance scale decreased concurrently with an increased rate of toxicity. Both physical and mental component scores were relatively stable throughout the course of evaluation. Mental component scores were the only predictor of toxicity during the treatment. Karnofsky performance scale dropped to their lowest point at the completion of treatment and then improved at 1-month follow-up. CLINICAL IMPLICATIONS: The patients who had higher mental component scores before treatment appeared to have higher, and improving, physical component scores throughout the course of evaluation. Along with complementary social support, the implementation of psychosocial support early and throughout the course of treatment may result in physical benefits and improving overall quality of life. Care should also be taken to make psychosocial support available to patients after the completion of treatment.

Activities of Daily Living↗

PubMedDate not supplied

Recovery of respiratory function in survivors with paraquat intoxication.

The purpose of this study was to investigate chest radiograms and respiratory function changes, including pulmonary function tests and alveolar-arterial oxygen difference, in survivors with paraquat intoxication. Chest radiograms and pulmonary function tests for 21 paraquat-poisoned patients were performed 10 d after paraquat intoxication; 3 mo later, the tests were repeated in 16 patients who survived. Forced vital capacity, forced expiratory volume in 1 s, diffusing capacity of the lung, and alveolar-arterial oxygen difference were compromised after paraquat intoxication. Forced expiratory volume in 1 s and forced vital capacity correlated significantly with initial platelet counts (r = .453 and .443, respectively) 10 d after intoxication. The alveolar-arterial oxygen difference also correlated significantly with peak serum total bilirubin concentrations (r = .443) and initial platelet counts (r = .469). The follow-up data for respiratory functions forced expiratory volume in 1 s; 74.33 +/- 27.1% versus 97.89 +/- 16.39%; forced vital capacity: 71.44 +/- 26.03% versus 93.22 +/- 13.92%; diffusing capacity of lung: 60.11 +/- 27.61% versus 81.67 +/- 24.56%; alveolar-arterial oxygen difference: 37.95 +/- 24.32 mm Hg versus 7.75 +/- 9.94 mm Hg) and chest radiograms of survivors with moderate to severe paraquat poisoning showed significant improvements 3 mo after intoxication. The results demonstrated that paraquat-induced respiratory function impairments could recover significantly, at least partially, with time. In addition, pulmonary structure damage improved, as shown in the follow-up chest radiographs.

Adolescent↗

PubMedDate not supplied

Heparin binding sites are present at a higher concentration on sperm of subfertile men than donors of known fertility.

Heparin sulfate has been shown to both stimulate sperm capacitation and cause decondensation of sperm chromatin. Recent studies have shown that sperm chromatin decondensation following exposure to a low concentration of heparin sulfate is inversely correlated with penetration ability. This study shows that sperm from subfertile patients contain a higher (p < .05) concentration of heparin binding sites than sperm from donors of known fertility. No differences were observed in the binding affinity of 3H-labeled heparin to donor and patient sperm. Binding was specific for sulfated heparin and dextran. FITC-labeled heparin bound to a higher percentage (p < .01) of patient sperm (39.6 +/- 3.1) than donor sperm (12.3 +/- 1.7). A relationship is demonstrated between heparin binding sites and sperm chromatin decondensation following heparin cxposure, both of which are increased in sperm from subfertile men.

Binding Sites↗

PubMedDate not supplied

Sperm DNA fragmentation is increased in couples with unexplained recurrent pregnancy loss.

Previous studies have indicated that sperm quality may be related to unexplained recurrent pregnancy loss. This study evaluated the degree of sperm DNA fragmentation using the TUNEL assay on sperm from 24 couples with unexplained recurrent pregnancy loss (RPL) compared to sperm from 2 control groups: donors of known fertility and unscreened men from the general population. The percentage of sperm staining positive for DNA fragmentation was increased (p < .001) in the RPL group (38 +/- 4.2) compared to the donor (11.9 +/- 1.0) or general population (22 +/- 2.0) control groups. In the RPL group, no correlation was observed between semen quality parameters and the TUNEL data. These data indicate that some RPL patients have a significant increase of sperm DNA fragmentation, which may be causative of pregnancy loss in some patients.

Abortion, Habitual↗

PubMedDate not supplied

Effects of peroxynitrite on pulmonary edema and the oxidative state.

Excess nitric oxide (NO) generation in the presence of superoxide anion (O2-) leads to the formation of peroxynitrite which may result in lung injury. Oxidant-mediated lung injury has a critical role in pulmonary diseases. We therefore determined whether peroxynitrite causes lung fluid accumulation, lipid peroxidation, and formation of nitrotyrosine using an isolated perfused rat lung model. The lung weight gain during bolus peroxynitrite infusion increased in a dose-dependent manner over a range of 3 to 30 mumole. Concomitantly, bronchoalveolar lavage Ficoll also increased, indicative of increased endothelial permeability. Peroxynitrite increased the production of thiobarbituric acid reactive substances, an index of lipid peroxidation. Furthermore, nitrotyrosine levels in lung tissue rose with increased concentration of peroxynitrite, as determined by Western blot using antinitrotyrosine antibodies. These results suggest that peroxynitrite, formed from NO and O2-, leads to increased pulmonary fluid accumulation, possibly through lipid peroxidation and/or nitration of cell membrane proteins.

Animals↗

PubMedDate not supplied

Memory consolidation in Drosophila operant visual learning.

A new conditioning procedure, developed for the operant learning paradigm at the flight simulator, leads to stronger learning scores in wild-type flies. This procedure produces mean learning indices up to LI = 0.52. The heat-avoidance behavior acquired during training is very difficult to extinguish during extinction. Memory decays quickly during the first 3 hr after training and still is measurable 48 hr later. Disruption experiments demonstrate that memory can be disrupted by cold anesthesia within the first approximately 20 min after training, whereas KCl- and CXM-feeding regimens abolish memory soon after training and 3 hr later, respectively. These results initially suggest at least three distinct memory phases involved in memory consolidation in Drosophila after operant conditioning.

Animals↗

PubMedDate not supplied

HIV protease (HIV PR) inhibitor structure-activity-selectivity, and active site molecular modeling of high affinity Leu [CH(OH)CH2]Val modified viral and nonviral substrate analogs.

This report details the structure-activity relationships of the HIV gag substrate analog Val-Ser-Gln-Asn-Leu psi[CH(OH)CH2]Val-Ile-Val (U-85548E), an inhibitor exhibiting subnanomolar affinity towards HIV type-1 aspartic proteinase (HIV-1 PR). Our data show that the P1-P2' tripeptidyl sequence provides the minimal chemical determinant for HIV-1 PR binding. We describe the structure-activity properties of Leu psi[CH(OH)CH2]Val substitution in other peptidyl ligands of nonviral substrate origin (e.g., angiotensinogen, insulin and pepstatin). Furthermore, the aspartic proteinase selectivities of a few key compounds are summarized relative to evaluation against human renin, human pepsin, and the fungal enzyme, rhizopuspepsin. These studies have led to the rational design of nanomolar potent inhibitors of both HIV-1 and HIV-2 PR. Finally, a 2.5 A resolution X-ray crystallographic structure of U-85548E complexed to synthetic HIV-1 PR dimer (Jaskolski et al., Biochemistry 30, 1600 [1991]) provided a 3-D picture of the inhibitor bound to the enzyme active site, and we performed computer-assisted molecular modeling studies to explore the possible binding modes of the above series of Leu psi[CH(OH)CH2]Val substituted HIV-1 PR inhibitors.

Amino Acid Sequence↗

PubMedDate not supplied

Characterization, chromosomal mapping, and expression of different polyubiquitin genes in tissues from control and heat-shocked maize seedlings.

Polyubiquitin transcripts accumulate in plant and animal cells following a heat shock. Most species have a few to several polyubiquitin genes; within a species, the genes may differ in nucleotide (nt) sequence and (or) the number of 228-nt repeats encoding the ubiquitin monomer. This study examines three maize (inbred Oh43) polyubiquitin genes. Two of the genes, MubG9 and MubG5, possess five repeats; the third, MubG1 possesses seven repeats. Sequence analyses of the genomic clones, MubG9 and MubG1 and a cDNA clone, MubG5, reveal that they differ primarily from each other in their nt sequences 5' and 3' to their open reading frames. MubG1 contains a 1004-base pair (bp) intron in its 5' untranslated region. Using gene-specific probes, we show that the amount of polyribosome-associated mRNA transcripts from MubG9 isolated from 2- and 5-day old plumules and radicles is unchanged by heat shock. While the amount of transcript from MubG1 and MubG5 on the polyribosomes in plumules and radicles of 2-day-old seedlings is also unchanged by heat shock, the levels of these transcripts are elevated considerably in similar tissues from heat-shocked 5-day-old seedlings. Similar or identical gene-specific probes were employed to map the genes using the recombinant inbred method. MubG9 maps to chromosome 4L position 186; MubG1 maps to 5L104 and MubG5 to 4L188. The opportunity to use gene-specific probes extends the evidence for distinct modulation (time and tissue) of polyubiquitin gene expression in maize and provides the basis for locus assignment within the genome.

Base Sequence↗

PubMedDate not supplied

Validity of stroke diagnosis on hospital discharge records in Saskatchewan, Canada: implications for stroke surveillance.

This study examines the validity of the diagnosis of stroke on hospital discharge records in Saskatchewan, Canada. In total, 1,494 records with a discharge diagnosis of 'stroke' or a 'stroke-related condition' were reviewed. The clinical algorithm of the 1980 USA National Survey of Stroke was considered the 'gold standard'. The positive predictive value of a primary diagnosis of stroke in the tertiary-care hospitals was about 90%. In community hospitals the majority of stroke cases were coded as ICD9 436 in which the positive predictive value was 78%. The variation between regions would limit the use of hospital discharge data for stroke surveillance.

Cerebrovascular Disorders↗

PubMedDate not supplied

Innovative dementia care: functional status over time of persons with Alzheimer disease in a residential care centre compared to special care units.

Residential care centres (RCCs) for persons with Alzheimer disease are increasing worldwide, but there are few studies that compare the functional outcomes of RCC residents to residents of other types of continuing care settings. This study compared residents of the first Canadian RCC on physical, cognitive, behavioural and emotional functioning 6, 12 and 18 months after admission to residents of special care units (SCUs) operated by the same continuing care provider. SCU residents were initially functioning lower than RCC residents on most outcome measures and these differences persisted over time. Resident functioning declined over time regardless of care setting and, when the initial status was controlled for, the rates of decline were similar. However, RCC residents experienced greater independence/freedom of choice, fewer physical or psychotropic medication restraints and were more active, which may have enhanced their quality of life.

Accidental Falls↗

PubMedDate not supplied

Effects of human hepatocyte growth factor on the proliferation of human hepatocytes and hepatocellular carcinoma cell lines.

BACKGROUND: Hepatocyte growth factor (HGF) has been suggested to initiate both hepatocyte and tumor cell proliferation after partial hepatectomy, thereby supporting local tumor recurrence. The aim of this study was to clarify the role of HGF in the regeneration of human hepatocyte and the growth of residual hepatocellular carcinoma cells after liver resection. PATIENTS/METHODS: 36 patients who underwent partial hepatectomy for hepatocellular carcinoma (HCC) or living liver donation have been analyzed for HGF serum levels at day -1 through day 5 following surgery using an enzyme-linked immunosorbent assay. Isolated human hepatocytes and HCC cell lines (Hep 3B, Hep G2) were treated either with recombinant human (rh)-HGF, or sera from the 36 patients in the presence or absence of anti-HGF in order to measure their proliferative capacity using (3)H-thymidine incorporation. RESULTS: Basal HGF levels were significantly higher in HCC than in healthy patients (1,573 +/- 131 vs. 778 +/- 64 pg/ml; p < 0.001), however, the postoperative rise of HGF in healthy patients was higher (9,608 +/- 3111 vs. 2,060 +/- 148 pg/ml) than in HCC patients. Incubation of human hepatocytes and Hep 3B cells with rh-HGF revealed a dose-dependent increase in DNA synthesis, while anti-HGF partially abolished this effect. Sera from normal and resected HCC patients stimulated DNA synthesis only in human hepatocytes, whereas it was inhibited in HCC cell lines. CONCLUSION: HGF plays an important role in hepatocyte proliferation but contrary to in vitro results, HGF does not play a major role for the progression of hepatocarcinoma cells in vivo.

Adult↗

PubMedDate not supplied

Comparison of gastrointestinal tolerance to two enteral feeding protocols in critically ill patients: a prospective, randomized controlled trial.

BACKGROUND: The purpose of this study was to compare gastrointestinal tolerance to two enteral feeding protocols in critically ill patients. METHODS: A prospective, randomized controlled trial, that involved 96 consecutive patients expected to stay in the intensive care unit for > or =3 days and who had no contraindications to enteral feeding. The patients were randomized to either the current protocol (group I; gastric residual volume threshold, 150 mL, optional prokinetic) or proposed feeding protocol (group II; gastric residual volume threshold 250 mL, mandatory prokinetic). Gastrointestinal intolerance was recorded as episodes of high gastric residual volume, emesis, or diarrhea. The time to reach the goal rate of feeding and the percentage of nutritional requirements received during the study period were also recorded. RESULTS: Nineteen of 36 patients (19/36 = 0.53) in group I had one or more episodes of high gastric residual volume, compared with 10 of 44 patients (10/44 = 0.23) in group II (p < .005). There was no statistical difference between the two protocols with regards to emesis, diarrhea, or the total episodes of intolerance. The patients in group II reached their goal rates on average in 15 hours and received 76% of their nutritional requirements, compared with 22 hours and 70% in group I; however, these differences were not statistically significant. CONCLUSIONS: The incidence of enteral feeding intolerance was reduced by using a gastric residual volume of 250 mL along with the mandatory use of prokinetics. The study showed a trend of improved enteral nutrition provision and reduced the time to reach the goal rate in group II. These improvements support the adoption of the proposed feeding protocol for critically ill patients.

Adult↗

PubMedDate not supplied

Effect of body positions and splints in bioelectrical impedance analysis.

The objective of this study was to evaluate body composition as measured by bioelectric impedance analysis using splints and body positions differing from the standard supine position. Forty-three patients, randomized into two groups of different body positions, and 101 healthy volunteers were prospectively studied. Resistance and reactance of body tissues were measured by bioelectric impedance analysis. Body composition is described by a three-compartment model composed of body fat, body cell mass, and extra cellular mass. The patients were measured in the standard supine position and then randomized into two groups. They were then remeasured with the appropriate splinting device or position change. Volunteers were measured in the standard supine position and all four alternative positions. There was a statistically significant difference demonstrated in whole body resistance, whole body reactance, body cell mass, and the ratio of extracellular mass to body cell mass in some body positions. The percentage of change with different body positions and splints, when compared with the standard supine position, was generally below 2%, a clinically insignificant difference. We conclude that the reliability of resistance and reactance as measured by bioelectric impedance analysis is clinically valid using any of the tested body positions and/or splints. The three-compartment model may be a useful concept to measure body composition changes in both healthy and sick persons.

Body Composition↗