Biomedical subjects

J Liu

Publications and source records attributed to J Liu.

At least 343 records · Page 19Linked to original sources

PubMed2001

Graft function and survival depend primarily on host factors in compromised recipient models of orthotopic liver transplantation in the rat.

BACKGROUND: Experimental models of liver transplantation use normal recipients, although most patients undergoing liver transplantation suffer from acute or chronic liver failure. This study was designed to analyze the outcome of orthotopic liver transplantation in compromised rat hosts. METHODS: Recipient animals were either rats with D-galactosamine-induced acute or rats with chronic liver failure secondary to common bile duct ligation. Liver damage was evaluated by monitoring enzymes, bilirubin, ammonia levels, prothrombin, thrombin time, and cytokines. In vivo function of hepatocytes and sinusoidal endothelial cells were evaluated by indocyanine green and hyaluronic acid uptake. Transplantation was performed in normal, acute, and chronic liver failure rats at different time points using either freshly harvested or cold-preserved syngeneic livers. RESULTS: Survival with fresh grafts decreased significantly when transplants were performed 48 hr after the induction of acute liver failure. No rats with acute liver failure survived transplantation with grafts stored for 12 or 24 hr although in chronic failure survival was more 80%. Survival of acute liver failure rats receiving 6 hr preserved grafts was 16.6% compared with 83.3% observed with fresh grafts transplanted at the same time point after D-galactosamine injection. Elevated tumor necrosis factor-alpha and interleukin-1beta levels as well as impaired sinusoidal endothelial cell function were detected in acute liver failure rats with 6 h preserved grafts. CONCLUSION: These results suggest that preoperative status and different host factors have a significant effect on outcome and graft function after liver transplantation in rats.

Animals↗

PubMed2001

Cadmium-induced malignant transformation of human prostate epithelial cells.

Prostate cancer has become epidemic, and environmental factors such as cadmium may be partly responsible. This study reports malignant transformation of the nontumorigenic human prostatic epithelial cell line RWPE-1 by in vitro cadmium exposure. The cadmium-transformed cells exhibited a loss of contact inhibition in vitro and rapidly formed highly invasive and occasionally metastatic adenocarcinomas upon inoculation into mice. The transformed cells also showed increased secretion of MMP-2 and MMP-9, a phenomenon observed in human prostate tumors and linked to aggressive behavior. Cadmium-induced malignant transformation of human prostate epithelial cells strongly fortifies the evidence for a potential role of cadmium in prostate cancer.

Adenocarcinoma↗

PubMed2001

Hydraphile channels: models for transmembrane, cation-conducting transporters.

A completely synthetic, non-peptide channel has been prepared and shown to conduct cations across a phospholipid bilayer membrane. Studies have been undertaken to assess the compound's location within the bilayer and to better understand its function. These studies are described along with background on the design and concept of the channel.

Cations↗

PubMed2001

Antitumor activity and toxicity of novel nitroheterocyclic phosphoramidates.

A series of novel nitroheterocyclic phosphoramidates has been evaluated for antitumor activity in murine and xenograft tumor models and for toxicity in mice. Significant increases in lifespan and long-term survivors were noted in L1210 leukemia and B16 melanoma models, and both complete and partial tumor regressions were observed in the MX-1 breast cancer xenograft model. All compounds exhibited some degree of toxicity to granulocyte/macrophage progenitors in the bone marrow of mice. Two drugs were selected for further toxicologic, histopathologic, and pharmacokinetic evaluations. Toxicity of potential clinical significance was observed only in the bone marrow at the highest drug dose; otherwise no significant abnormalities in blood chemistries or organ histopathology were noted. The bone marrow lesions consisted of reduced numbers of progenitor cells in the myeloid and erythroid series; platelets were not affected. The compounds were eliminated rapidly by first-order kinetics, with half-lives in the 4-12 min range. The best of these compounds exhibits excellent antitumor activity and minimal toxicity at therapeutically effective doses in mice.

Animals↗

PubMed2001

Superoxide radical-initiated apoptotic signalling pathway in selenite-treated HepG(2) cells: mitochondria serve as the main target.

The exact role of superoxide radicals (O(2)(*)(-)) in apoptosis is still a matter of debate. The main objective of the present study is to evaluate the apoptotic signalling pathway initiated by O(2)(*)(-). The reductive reaction of sodium selenite with glutathione was used as the intracellular O(2)(*)(-)-generating system. When cells were exposed to 5 to 25 microM selenite, a temporal pattern of apoptotic events was observed following the elevation of O(2)(*)(-), in which cytochrome c release and mitochondrial depolarization preceded caspase-3 activation and DNA fragmentation. The simultaneous treatment with N-acetylcysteine and 4-hydroxy-2,2,6, 6-tetramethylpiperidine-N-oxyl markedly reduced O(2)(*)(-) level and suppressed the mitochondrial changes and the downstream apoptotic events. Moreover, pretreatment with cyclosporin A plus trifluoperazine, two mitochondrial permeability transition (MPT) inhibitors, was capable of attenuating O(2)(*)(-)-mediated cytochrome c release and mitochondrial depolarization, and subsequently inhibiting apoptosis. Thus, the present results provide convincing evidence that O(2)(*)(-) generated from the reductive reaction of selenite with GSH is capable of triggering a mitochondria-dependent apoptotic pathway. Such knowledge may not only help to obtain a better understanding of the apoptotic effect of selenite per se, but of the role of O(2)(*)(-) in initiation and execution of apoptosis.

Acetylcysteine↗

PubMed2001

Cytosolic phospholipase A2-alpha associates with plasma membrane, endoplasmic reticulum and nuclear membrane in glomerular epithelial cells.

Eicosanoids mediate complement-dependent glomerular epithelial injury in experimental membranous nephropathy. The release of arachidonic acid from phospholipids by cytosolic phospholipase A(2) (cPLA(2)) is the rate-limiting step in eicosanoid synthesis. The present study examines the association of cPLA(2) with membranes of organelles. Glomerular epithelial cells were disrupted by homogenization in Ca(2+)-free buffer; organelles were separated by gradient centrifugation. The distribution of cPLA(2) and organelles was analysed by immunoblotting with antibodies against cPLA(2) and organelle markers, or by enzyme assay. In cells incubated with or without the Ca(2+) ionophore ionomycin plus PMA, cPLA(2) co-localized with plasma membrane, endoplasmic reticulum and nuclei, but not with mitochondria or Golgi. A greater amount of cPLA(2) was associated with membranes in stimulated cells, but membrane-associated cPLA(2) was readily detectable under resting conditions. The pattern of association of cPLA(2) with membrane in cells treated with antibody and complement was similar to that in cells stimulated with ionomycin plus PMA; however, complement did not enhance the membrane association of cPLA(2) protein. To determine the functional role of membrane association of cPLA(2), phospholipids were labelled with [(3)H]arachidonic acid. Cells were then incubated with or without antibody and complement and were fractionated. Complement induced a loss of radioactivity from the plasma membrane, endoplasmic reticulum and nuclei, but not from the mitochondrial fraction. Thus the release of arachidonic acid by cPLA(2) is due to the hydrolysis of phospholipids at multiple subcellular membrane sites, including the endoplasmic reticulum, plasma membrane and nucleus.

Animals↗

PubMed2001

Expression of a truncated first exon BCR sequence in chronic myelogenous leukemia cells blocks cell growth and induces cell death.

We have shown that a deletion mutant form of Bcr [Bcr(64-413)] is a strong inhibitor of the tyrosine kinase of Bcr-Abl in vitro and also inhibits its oncogenic growth effects (Liu et al., Cancer Res., 56: 5120-5124, 1996). To determine the effects of this Bcr-Abl kinase inhibitor on chronic myelogenous leukemia (CML) cells, we cloned BCR(64-413) into a recombinant, replication-defective adenovirus to express useful quantities of Bcr(64-413) in a wide variety of cells in culture. Infection of Cos1 cells with plaque-purified virus at a multiplicity of infection of 20-40 induced high expression of Bcr(64-413) as detected by Western blotting. Infection of hematopoietic cells at modest multiplicities of infection (20-40) required special conditions involving shifting cycling cells to a nongrowing condition involving serum starvation and cell crowding. Under these conditions, both Bcr-Abl-positive and -negative hematopoietic cells can be efficiently infected by adenovirus, as demonstrated by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining of cells infected by beta-galactosidase (beta-GAL) adenovirus. We found that expression of Bcr(64-413) in Bcr-Abl-positive K562 and BV-173 cells, but not Bcr-Abl-negative SMS-SB cells, increased cell-cell clumping and inhibited cell growth. In contrast to the effects of the Bcr(64-413) adenovirus, the beta-GAL adenovirus, despite infecting both types of cells, did not block growth or increase cell-cell clumping of Bcr-Abl-positive and -negative hematopoietic cells. Expression of Bcr(64-413) protein in primary cultures of cells from CML patients with active disease interfered with cell growth, induced apoptosis (as measured by annexin staining), and increased cell-cell clumping, whereas the beta-GAL adenovirus and mock-infected cells lacked these effects. In contrast, normal marrow cells did not exhibit these effects on infection with Bcr(64-413) adenovirus. We conclude from these findings that Bcr(64-413) interferes with the oncogenic effects of Bcr-Abl and therefore has the potential for use in therapy of CML.

Adenoviridae↗

PubMed2001

Combined effect of cyclosporine and sirolimus on improving the longevity of recombinant adenovirus-mediated transgene expression in the retina.

OBJECTIVES: To reevaluate the longevity and intraocular safety of recombinant adenovirus (rAd)-mediated gene delivery after subretinal injection, and to prolong transgene expression through the combination of 2 synergistic immunosuppressants. METHODS: An rAd vector carrying green fluorescent protein (GFP) gene was delivered subretinally in the rat eye. The GFP expression was monitored in real time by fundus fluorescent photography. Intraocular safety was examined by observation of changes of retinal pigmentation, cell infiltration in virus-contacted area, immunophenotyping for CD4(+) and CD8(+) cytotoxic T lymphocytes, and CD68(+) macrophages, histologic findings, and dark-adapted electroretinography. Two synergistic immunosuppressants, cyclosporine and sirolimus, were used alone or in combination to prolong transgene expression by temporary immunosuppression. RESULTS: The GFP expression peaked on day 4, dramatically decreased on day 10, and was not detectable on day 14. The decreased GFP expression was coincident with cell infiltration in virus-contacted area. Immunostaining showed that the infiltrating cells were CD4(+) and CD8(+) cytotoxic T lymphocytes and CD68(+) macrophages. Clumped retinal pigmentation and decreased b wave of dark-adapted electroretinogram were observed at 3 to 4 weeks after injection. Histologic examination confirmed rAd-induced retinal degeneration. Transient immunosuppression by cyclosporine and sirolimus, either alone or in combination, improved transgene expression, with the combination being the most efficient. The combined immunosuppression attenuated but did not retard the rAd-induced retinal damage. CONCLUSIONS: Transgene expression mediated by rAd after subretinal delivery is short-term and toxic to the retina. Combination of cyclosporine and sirolimus may act as an immunosuppressive adjunct to prolong rAd-mediated gene transfer. CLINICAL RELEVANCE: The intraocular safety of rAd should be carefully considered before clinical trials are performed.

Adenoviridae↗

PubMed2001

Topical mitomycin application after laryngotracheal reconstruction: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To explore the effect of mitomycin treatment on the pediatric airway following laryngotracheal reconstruction. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: Children aged 2 to 17 years with subglottic or upper tracheal stenosis undergoing laryngotracheal reconstruction at a single, tertiary care, children's hospital. INTERVENTION: At the time of extubation or stent removal, the children underwent bronchoscopy and 0.4 mg/mL (2 mL of a 0.2-mg/mL solution of either mitomycin or an equal volume of isotonic sodium chloride was directly applied to the subglottic region for a single application of 2 minutes. These children then underwent interval endoscopy at 2 weeks, 6 weeks, and 3 months postoperatively for assessment of their airways. RESULTS: Granulation tissue was graded on a scale of 0 (none) to 4 (near-total or total occlusion). Videotapes of endoscopies were independently observed and graded by 3 pediatric otolaryngology fellows with a subsequent interobserver agreement of 91.6%. The results were then dichotomized to represent a single cohort in which further surgical intervention would be required and another separate cohort in which further surgery would not be required. At the 1-year mark, interim analysis was performed by a Data Safety and Monitoring Committee. At this time, 13 children had been randomized to the mitomycin-treated arm of the study and 11 children to the placebo-treated arm. A 2-tailed Fisher exact test revealed a value of 1.00. The Data Monitoring and Safety Committee advised that the trial should be stopped because the distributions between the 2 populations were almost identical. CONCLUSION: We cannot reject the null hypothesis that a single topical dose of mitomycin exerts an equal benefit as does isotonic sodium chloride when applied to the pediatric airway after laryngotracheal reconstruction.

Administration, Topical↗

PubMed2001

Genetic events associated with arsenic-induced malignant transformation: applications of cDNA microarray technology.

Arsenic is a human carcinogen. Our recent work showed that chronic (>18 wk), low-level (125-500 nM) arsenite exposure induces malignant transformation in normal rat liver cell line TRL1215. In these arsenic-transformed cells, thecellular S-adenosylmethionine pool was depleted from arsenic metabolism, resulting in global DNA hypomethylation. DNA methylation status in turn may affect the expression of a variety of genes. This study examined the aberrant gene expression associated with arsenic-induced transformation with the use of Atlas Rat cDNA Expression microarrays. Poly(A(+)) RNA was prepared from arsenic-transformed cells and passage-matched control cells, and (32)P-labeled cDNA probes were synthesized with Clontech Rat cDNA Synthesis primers and moloney murine leukemia virus reverse transcriptase. The hybrid intensity was analyzed with AtlasImage software and normalized with the sum of the four housekeeping genes. Four hybridizations from separate cell preparations were performed, and mean and SEM for the expression of each gene were calculated for statistical analysis. Among the 588 genes, approximately 80 genes ( approximately 13%) were aberrantly expressed. These included genes involved in cell-cycle regulation, signal transduction, stress response, apoptosis, cytokine production and growth-factor and hormone-receptor production and various oncogenes. These initial gene expression analyses for the first time showed potentially important aberrant gene expression patterns associated with arsenic-induced malignant transformation and set the stage for numerous further studies. Mol. Carcinog. 30:79-87, 2001. Published 2001 Wiley-Liss, Inc.

Animals↗

PubMed2001

Inhibition of forskolin-stimulated cAMP formation in vitro by paraoxon and chlorpyrifos oxon in cortical slices from neonatal, juvenile, and adult rats.

Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides, which elicit toxicity following biotransformation to the potent acetylcholinesterase inhibitors, paraoxon (PO) and chlorpyrifos oxon (CPO). Both oxons have also been shown to interact directly with muscarinic receptors coupled to inhibition of adenylyl cyclase. Immature animals are more sensitive than adults to the acute toxicity of PS and CPF but little is known regarding possible age-related differences in interactions between these toxicants and muscarinic receptors. We compared the inhibition of forskolin-stimulated cAMP formation by PO and CPO (1 nM-1 mM) in vitro in brain slices from 7-, 21-, and 90-day-old rats to the effects of well-known muscarinic agonists, carbachol and oxotremorine (100 microM). Both agonists inhibited cAMP formation in tissues from all age groups and both were more effective in adult and juvenile (20-26% inhibition) than in neonatal (12-13% inhibition) tissues. Atropine (10 microM) completely blocked agonist-induced inhibition in all cases. PO maximally inhibited (37-46%) cAMP formation similarly in tissues from all age groups, but atropine blocked those effects only partially and only in tissues from 7-day-old rats. CPO similarly inhibited cAMP formation across age groups (27-38%), but ATR was partially effective in tissues from all three age groups. Both oxons were markedly more potent in tissues from younger animals. We conclude that PO and CPO can directly inhibit cAMP formation through muscarinic receptor-dependent and independent mechanisms and that the developing nervous system may be more sensitive to these noncholinesterase actions.

Aging↗

PubMed2001

Dynamics and mechanism of ultraviolet photolysis of atrazine on soil surface.

The photolysis of atrazine in the soil surface under UV light and the factors affecting this has been studied. A rate constant of 0.09-0.17 min-1, photolytic depth of 0.1-0.3 mm and half-life of 4-8 min were determined. The results show that soil granularity, pH, humidity, organic content, humic acid and surface-active agents could affect the photolysis of atrazine in soil. GC-MS showed three photolytic products: 1-sec-butyl-4,4-diethyl-1-tetrazene, N2,N4-diethyl-6-methyl-1,3,5-triazine-2,4-diamine and 6-chloro-N2-propyl-1,3,5-triazine-2,4-diamine. The mechanism of the photolytic process is discussed.

Atrazine↗

PubMed2001

Varied ecological environment and fluorosis in Tibetan children in the nature reserve of Mount Qomolangma.

To determine the extent of brick tea consumption fluorosis in children living at elevations of 2000 and 4300 m, 519 children aged 8-15 years living in Xiege'er Town at 4300 m and Zhangmu Town at 2000 m were examined for dental fluorosis, their urinary fluoride concentration was determined, their dietary structure investigated, and the fluoride concentrations of various foods, freshwaters, soils, and fuels determined. Fifteen Tibetan families living in these two areas of the nature reserve of Mount Qomolangma were studied according to UNEP, FAO, and WHO guidelines for the study of dietary intake of chemical contaminants, Horowitz's classification and examination of dental fluorosis, and Dean's dental fluorosis index. The results demonstrated that dental fluorosis in Tibetan children living at an elevation of 2000 m was significantly lower than that of children at 4300 m (P<0.01). Higher elevation can worsen the extent of fluorosis, leading to retention of fluoride in tissues as a result of hypoxia, but fluorosis can also be associated with the deterioration of the ecological environment at high elevation and a low-level economy. Beverages and foods mixed with brick tea water are responsible for the dental fluorosis in the children.

Adolescent↗

PubMed2001

Site formation processes at Zhoukoudian, China.

Zhoukoudian is often cited for its human remains and the early evidence of fire. Yet, since its first excavations over 70 years ago, detailed studies of processes responsible for the accumulation of anthropogenic and geogenic sediments in the site have been sparse. This paper provides some details of site formation processes mainly through field observations of the extant section at Locality 1, and the use of soil micromorphology and Fourier Transform Infrared Spectrometry (FTIR) analyses of the sediments. Samples from Layers 10 through 3 show extensive water deposition of fine silt-sized material (reworked loess), including fine-grained organic matter. The dark organic-rich unit in Layer 10--often cited as one of the earliest evidence of fire--is a water-laid accumulation. Much of the fine-grained sediment was derived from outside Locality 1, implying that the site was open to varying extents throughout most of its depositional history. The 4-6 m accumulation of "ashes" in Layer 4 represents subaerial water-laid silt deposits derived from the loess-covered hillslopes surrounding the site. They presumably accumulated in an open depression that formed after the collapse of the brecciated roof deposits represented by Layer 6. Diagenesis is present in many of the Layers, and is exemplified by calcite precipitation and dissolution, and localized apatite (dahllite) replacement of calcite. In Layer 4 diagenesis is more advanced, including calcite/dahllite precipitation, subaerial weathering of the loess and associated precipitation of hematite, alteration of clay and the neoformation of quartz. Many of our conclusions concur with those of Teilhard de Chardin & Young published over 70 years ago.

Animals↗

PubMed2001

Identification of symbiotic bacteria (Photorhabdus and Xenorhabdus) from the entomopathogenic nematodes Heterorhabditis marelatus and Steinernema oregonense based on 16S rDNA sequence.

Two species of entomopathogenic nematodes, Heterorhabditis marelatus and Steinernema oregonense, were described recently from the west coast of North America. It is not known whether the bacterial symbionts of these nematodes are also unique. Here we compared partial 16S rRNA sequences from the symbiotic bacteria of these two nematodes with sequence from previously described Photorhabdus and Xenorhabdus species. The 16S sequence from the new Xenorhabdus isolate appears very similar to, although not identical to, that of X. bovienii, the common symbiont of S. feltiae. The new Photorhabdus isolate appears to be very distinct from other known Photorhabdus species, although its closest affinities are with the P. temperata group. We also verified a monoxenic association between each isolate and its nematode by amplifying and sequencing bacterial 16S sequence from crushed adult and juvenile nematodes and from bacterial cultures isolated from infected hosts.

Animals↗

PubMed2001

Significant correlation between micrometastasis in the lymph nodes and reduced expression of E-cadherin in early gastric cancer.

BACKGROUND: E-cadherin has been recognized as an important factor associated with tumor metastasis. However, the relationship between micrometastasis in the lymph nodes and the expression of E-cadherin in the primary tumor in gastric cancer remains unclear. METHODS: Two consecutive sections of 4522 lymph nodes from 162 patients with early gastric cancer were prepared for simultaneous hematoxylin and eosin (H&E) and cytokeratin (CK) staining. Sections of primary tumors from 135 of these patients were prepared for E-cadherin immunostaining. RESULTS: The incidence of lymph node involvement was significantly increased, from 6.8% (11/162 patients) by H&E staining, to 27% (43/162 patients) by CK immunostaining (P < 0.0001). Micrometastasis in the lymph node was found in 32 of 151 (21%) patients who had no lymph node metastasis evidenced by H&E staining. Micro-lymph node metastasis was frequently found in tumors with a diameter more than 1.0 cm, of those that were poorly differentiated, deeply invaded, showed lymphatic on vascular invasion, and in those that showed reduced expression of E-cadherin. Loss of expression of E-cadherin in the primary tumor was closely correlated with micro-lymph node metastasis. Patients with tumors with micro-lymph node metastasis detected by CK immunostaining had a significantly lower 5-year survival rate (P < 0.01) than those without such metastases. CONCLUSION: Tumors more than 1.0 cm in diameter and those that exhibit poor differentiation, deep invasion (i.e., to the submucosa), lymphatic or vascular invasion, and reduced expression of E-cadherin are risk factors for lymph node metastasis in early gastric cancer. Thus, it is recommended that cancers confined to the mucosa (m-cancers) that are more than 1.0 cm in diameter should not be treated with limited surgery without lymphadenectomy.

Adult↗

PubMed2001

A new method of Fourier-transform smoothing with ratio spectra derivative spectrophotometry.

A new method which combines Fourier-transform smoothing with ratio spectra derivative spectrophotometry has been developed for analysis of binary and ternary mixtures. The method proposed has been applied to the simultaneous determination of a binary mixture of 0.974-2.026 x 10(-2) g L(-1) nitrate and nitrite and to a ternary mixture of 1.840-3.888 x 10(-3) g L(-1) histidine, phenylalanine, and tryptophan. The relative standard derivations are between 0.07 and 5.3% for the former system, and between 0.5 and 7.3% for the latter. The results show that the method proposed is more accurate than multiple linear regression.

Journal Article↗

PubMed2001

Highly toxic and broad-spectrum insecticidal Bacillus thuringiensis engineered by using the transposon Tn917 and protoplast fusion.

The chromosome of the Bacillus thuringiensis strain S184 that was toxic against the third instar larvae of Spodoptera litura with the LC(50) of 9.74 microg/ml was successfully integrated into two genes of cyt1Aa and cry11Aa using the transposon Tn917, yielding the primary engineered strain TnX. The strain TnX was highly toxic to the third instar larvae of Culex pipiens fatigans with the LC(50) of 5.12 ng/ml which was 1.82-fold higher than that of B. thuringiensis subsp. israelensis, but lowly toxic to lepidopterous larvae. By the protoplast fusion of the strain TnX and the strain S184-Tet(r) (resistance to tetracycline), the target engineered strain TnY was obtained. Against the third instar larvae of S. litura, the strain TnY LC(50) was of 4.68 micro g/ml and increased by 2.08-fold in comparison with the parent strain S184. Against the third instar larvae of C. pipiens fatigans, the strain TnY LC(50) was of 103.20 ng/ml. The two target genes of cyt1Aa and cry11Aa integrated into the chromosome were extremely stable and had little possibility of a second transposition. It was unclear whether some factors existing in the parent strain, S184, contributed to the high toxicity of the strains TnX and TnY.

Animals↗