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Biomedical subjects

M Liu

Publications and source records attributed to M Liu.

At least 109 records · Page 6Linked to original sources
PubMed2001

Genomic characterization, localization, and functional expression of FGL2, the human gene encoding fibroleukin: a novel human procoagulant.

For diseases in which thrombosis plays a pivotal role, such as virus-induced fulminant hepatitis, fetal loss syndrome, and xenograft rejection, the major procoagulant has remained elusive. Here we describe the isolation and functional expression of a distinct human prothrombinase, termed FGL2. The murine fgl2 gene product has been implicated in the pathophysiology of murine fulminant hepatitis. The predicted ORF corresponds to a 439-amino-acid type II integral membrane protein that contains a carboxy-terminal Fibrinogen-related domain. Functional analysis showed that FGL2-encoded protein is indeed a prothrombinase. This enzyme is a serine protease and directly cleaves prothrombin to thrombin. The FGL2 gene is a single-copy gene in the haploid human genome and has two exons separated by a 2195-bp intron expressing two mRNA transcripts of 1.5 and 5.0 kb. The 5'-flanking region contains putative cis-elements including a TATA box, an AP1 site, CEBP sites, Sp1 site, and Ets binding domains. By both radiation hybrid analyses and fluorescence in situ hybridization, human FGL2 was localized to 7q11.23.

Amino Acid Sequence↗
PubMed2001

Invalidation of the Kelvin force in ferrofluids.

Direct and unambiguous experimental evidence for the magnetic force density being of the form MnablaB in a certain geometry-rather than being the Kelvin force MnablaH--is provided for the first time. ( M is the magnetization, H is the field, and B is the flux density.)

Journal Article↗
PubMed2001

Mannitol for acute stroke.

BACKGROUND: Mannitol is an osmotic agent and a free radical scavenger so it might decrease oedema and tissue damage in stroke. OBJECTIVES: To test whether treatment with mannitol reduces short and long-term case fatality and dependency after acute ischaemic stroke or cerebral parenchymal haemorrhage. SEARCH STRATEGY: We searched the Cochrane Stroke Group Specialised Trials Register. In addition to this, supplementary MEDLINE searches were performed. The Chinese Stroke Trials Register was checked and the Latin-American databank LILACS was searched with the search term MANNITOL and its variations in the Portuguese and Spanish languages. A search was performed of Masters and Ph.D. degree theses in the databank of Sao Paulo University, and in abstracts of medical congresses on neurology and neurosurgery from 1965 to 1997 in Brazil. SELECTION CRITERIA: Truly randomised unconfounded clinical trials comparing the effect of mannitol with placebo or open control in patients with acute ischaemic stroke or parenchymal haemorrhage were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected the trials to be included in the review. After reaching an agreement on which trials to include, two of the reviewers extracted data from the trials and performed the data analysis. Accuracy of data extraction was checked by comparing the results. Included trials were tabulated for methodological quality including the method of randomisation and blinding, and stating if CT was performed, if patients were lost to follow-up and if intention-to-treat analysis was performed. Data synthesis and analysis was performed using the Cochrane Review Manager software. MAIN RESULTS: Only one trial fulfilled the inclusion criteria. The number of included patients was small (36 treated and 41 controls) and the follow up was short. Neither beneficial nor harmful effects of mannitol could be proved. Case fatality, the proportion of dependent patients at the end of the follow up and side effects were not reported and were not available from the investigators. The planned outcome analyses and sensitivity analyses could not be performed due to lack of appropriate trials. REVIEWER'S CONCLUSIONS: There is currently not enough evidence to decide whether the routine use of mannitol in acute stroke would result in any beneficial or harmful effect. The routine use of mannitol in all patients with acute stroke is not supported by any evidence from randomised controlled clinical trials. Further trials are needed to confirm or refute the routine use of mannitol in acute stroke.

Acute Disease↗
PubMed2001

MR angiographic investigation of transient focal cerebral ischemia in rat.

Contrast agent free time-of-flight magnetic resonance angiography (TOF-MRA) was applied to the intraluminal thread occlusion model of experimental stroke in rat. It was combined with perfusion- and diffusion-weighted imaging (PWI and DWI) sequences to correlate occlusion and reopening of the middle cerebral artery with alterations in these well-established magnetic resonance sequences. Since TOF-MRA can be repeated without limitations, the time course of vascular patency is demonstrated during an experimental period of up to 8 h (2 h control, 1 h ischemia, 3-6 h reperfusion). With an acquisition time of 10 min, TOF-MRA proved to be suitable to analyze the vascular state of occlusion and reperfusion repetitively in longitudinal studies. Spatial resolution was sufficient to observe neurovascular structural details. In eight out of 10 animals complete vessel occlusion by the intraluminal thread could be validated by an entirely extinguished signal of the ipsilateral middle cerebral artery (MCA) in the angiograms. This was in accordance with a perfusion deficit in the MCA vascular territory detected by PWI (reduction to 30.4 +/- 7.4% relative to contralateral side) and a disturbance of water ion homeostasis monitored by DWI in this area. One animal showed a delayed occlusion after 30 min of MCA occlusion, in another animal vessel occlusion failed. In seven out of the eight successful occlusion experiments there was immediate reperfusion after withdrawal of the thread. One animal showed a delayed reperfusion after suture retraction. Remarkable hemispheric differences in vascular branching of the MCA could be recognized in three out of 10 animals. In conclusion, TOF-MRA is considered a helpful method to survey even in small laboratory animals the correct time course of vascular occlusion and reopening in experimental ischemia, and provides complementary information to the tissue perfusion status monitored by PWI and the ischemic lesion territory detected by DWI.

Animals↗
PubMed2001

Recovery of underwater resonances by magnetization transferred NMR spectroscopy (RECUR-NMR).

A method for detecting small molecule NMR resonances under a water peak in biological samples is presented. After high-efficiency solvent suppression using double WATERGATE, either a TOCSY- or ROESY-based coherence transfer sequence is applied to reestablish the resonances close to, or under, water through magnetization transfer using scalar or dipolar coupling, respectively. The use of the TOCSY and ROESY methods ensures an in-phase magnetization transfer, which makes the new approach readily extended for the measurement of transverse relaxation times, internuclear ROEs, and ROE buildup rates. An extension of the new approach for J-resolved spectroscopy is also presented and tested using a sample of human blood plasma.

Blood Glucose↗
PubMed2001

The Potential Energy Coefficients for Internal Rotation in CH(2)DSH and CHD(2)SH.

An internal axis method (IAM) has been used to determine the potential energy coefficients V(1), V(2), and V(3) to internal rotation in CH(2)DSH and CHD(2)SH. Two torsional differences for the gauche ground states and one torsional difference for the excited states were used to fix the V's. A fourth term, K(varsigma), 3(e(2))-2(o(2)), determines the torsional state assignment for this Q-branch series as o(2) to e(2) that was not known previously. For CH(2)DSH, the potential energy coefficients are V(1) = 4.54 cm(-1), V(2) = -9.36 cm(-1), V(3) = 440.50 cm(-1); for CHD(2)SH, V(1) = -4.12 cm(-1), V(2) = 8.23 cm(-1), V(3) = 439.65 cm(-1). Nonrigidity coefficients have also been determined for both the trans and gauche conformations of the ground state. Copyright 2001 Academic Press.

Journal Article↗
PubMed2001

Administration of plasmid DNA expressing human interleukin-6 significantly improves thrombocytopoiesis in irradiated mice.

When people are exposed to large doses of ionizing rays in a short time, hematopoiesis is impaired and hemorrhage is one of the major clinical features. Suddenly decreasing platelet counts are responsible for the life-threatening hemorrhagic complication. Therefore, some cytokines have been used to improve thrombocytopoiesis in various radiation-induced thrombocytopenia models. Current measures for this purpose involve repeated intravenous or subcutaneous injections of recombinant proteins, which are expensive and inconvenient, or gene therapy with viral vectors that could not obviate the risk of infection. We tried to determine the possibility of gene therapy with plasmid vectors for radiation-induced hematopoietic injury, which could overcome the above-mentioned problem. In this study, we describe the enhanced efficiency of radiation on gene transfer with plasmid vector in vivo and the physiological role of expressed human interleukin-6 (hIL-6) in vivo on a radiation-induced thrombocytopenia model. After a single intramuscular injection of plasmid hIL-6 DNA on 6.5-Gy-irradiated mice, the hIL-6 protein level in mouse plasma was determined with enzyme-linked immunosorbent assay (ELISA). The level of hIL-6 began to increase from the 4th day, reached the peak value on about the 11th day, and remained at a higher level on the 28th day. Meanwhile, unirradiated mice injected with the same amount of plasmid DNA showed less hIL-6 on the 11th day after administration. Further experiments demonstrated that the hIL-6 level in 7.5-Gy-irradiated mice was about three times higher than that of 5.0-Gy-irradiated mice, suggesting radiation could improve gene transfer efficiency of plasmid DNA in vivo and might be dependent on radiation doses. The expression of hIL-6 in vivo showed a significant effect on hematopoietic recovery after radiation. Not only the platelet nadir in peripheral blood, but also the number of colony-forming cells in bone marrow rose. The increased platelet counts were partially due to the increase of reticulated platelet that reflected the activity of a given population of megakaryocyte in bone marrow. We conclude that radiation could significantly enhance the gene transfer efficiency of plasmid DNA and that gene therapy with plasmid vectors for radiation-induced hematopoietic injury might be more effective than other diseases without DNA repair.

Animals↗
PubMed2001

Raffinose improves 24-hour lung preservation in low potassium dextran glucose solution: a histologic and ultrastructural analysis.

BACKGROUND: We have previously shown that the addition of raffinose to low potassium dextran (LPD) preservation solution improves transplanted rat lung function after 24 hours of storage. The mechanisms by which raffinose acts are unclear. The aim of this study was to examine the histologic and ultrastructural correlates of this enhanced pulmonary function after preservation with raffinose. METHODS: In a randomized, blinded study, rat lungs were flushed with LPD, or LPD containing 30 mmol/L of raffinose, and stored for 24 hours at 4 degrees C. Control lungs were flushed with LPD but not stored (n = 5 each group). Changes in postpreservation edema were determined. In addition, lungs were flushed with a trypan blue solution to quantify cell death, and examined using both light and electron microscopy. RESULTS: The LPD lungs gained significantly more weight (25.5%+/-5.5%) compared with raffinose-LPD lungs (5.2%+/-5.3%; p < 0.0001). There were higher percentages of dead cells in the LPD lungs (29%+/-0.3% of total cells) compared with raffinose-LPD lungs (14%+/-1.4%; p < 0.001) and control lungs (0.2%+/-5%; p < 0.001). Control lungs maintained normal ultrastructure, whereas LPD lungs showed a decreased number of intact type II pneumocytes and significant cellular necrosis. Interstitial and alveolar edema with interstitial macrophage infiltration was also observed. Alveolar capillaries were collapsed. In contrast, raffinose-LPD lungs showed only mild alterations such as minimal interstitial edematous expansion, fewer damaged cells, and minimal capillary injury. CONCLUSIONS: Raffinose exerts a cytoprotective effect on pulmonary grafts during preservation, which explains the previously documented improved function. This simple modification of LPD with raffinose may provide clinical benefit in extended pulmonary preservation.

Animals↗
PubMed2001

Orally bioavailable farnesyltransferase inhibitors as anticancer agents in transgenic and xenograft models.

The in vivo evaluation process described here was instrumental in the identification of SCH 66336 as a clinical candidate. Our lead FTI, SCH 66336, and several other FTIs are being evaluated in early-phase clinical trials to establish proof-of-principle for farnesyl transferase inhibition in human patients. The preclinical studies described here suggest that FTIs may have utility against a wide array of human cancers as a single agent and may, at least in some cases, lead to tumor regression. In addition, the results to date in combination with cytotoxic chemotherapeutic agents in animal models indicate that these combinations may enhance the clinical efficacy of FPT inhibitors. Further preclinical studies should help to guide the clinical development of this class of novel antitumor agents.

3T3 Cells↗
PubMed2001

Prediction of programmed-temperature retention values of naphthas by wavelet neural networks.

The wavelet neural network (WNN) was used to predict the programmed-temperature retention values of naphthas. In WNN, a Morlet mother wavelet was used as a transfer function, and the convergence speed was faster than other neural networks. Sixty-four compounds (selected randomly from 94) were used as a training set, and the 30 remaining compounds were used as a test set. A very satisfactory result was obtained only after about 8000 training epochs. The other two methods, the artificial neural network (ANN) and the Simpson integral method, were also used for this study. The comparison of results obtained from three methods showed that the WNN is the most suitable tool in predicting programmed-temperature retention values of naphthas, consequently this method can be used to provide reliable data for the petrochemical industry.

Journal Article↗
PubMed2001

Prediction of enthalpy of alkanes by the use of radial basis function neural networks.

A new method for the prediction of enthalpy of alkanes between C6 and C10 from molecular structures has been proposed. Thirty five calculated descriptors were selected for the description of molecular structures. The first four scores of Principle Component Analysis on the calculated descriptors were used as inputs to predict the enthalpy of alkanes. Models relating relationships between molecular structure descriptors and enthalpy of alkanes were constructed by means of radial basis function neural networks. To get the best prediction results, some strategies were also employed to optimise the learning parameters of the radial basis function neural networks. For the test set, a predictive correlation coefficient of R = 0.9913 and root mean squared error of 0.5876 were obtained.

Journal Article↗
PubMed2001

Loss of p73 gene expression in lymphoid leukemia cell lines is associated with hypermethylation.

The expression of the p73 gene and the methylation status was examined in 61 acute lymphoblastic leukemia (ALL) cell lines and lymphocytes from seven healthy individuals. p73 mRNA was not expressed in 19 (31.1%) of 61 ALL cell lines, including 11 (31.4%) of 35 B-precursor ALL cell lines, 2 (16.7%) of 12 B-ALL/Burkitt lymphoma (BL) cell lines (totally 27.7% of B-lineage cell lines), 6 (42.9%) of 14 T-ALL cell lines, and expressed in all of normal lymphocytes, by reverse transcriptase-polymerase chain reaction (RT-PCR). Restriction-enzyme related PCR (REP) and methylation-specific PCR (MSP) revealed that the cell lines lacking p73 mRNA expression were hypermethylated. In contrast, normal lymphocytes and most cell lines that expressed detectable p73 mRNA were not hypermethylated with the exception of five cell lines. Furthermore, bisulfite genomic sequencing confirmed the results obtained by REP and MSP. Our results suggest that p73 inactivation may be involved in the pathogenesis of both T- and B-ALLs, and that hypermethylation is the predominant mechanism of inactivation of the p73 gene in ALL.

CpG Islands↗
PubMed2001

Enzyme histochemical profile of immunohistochemically identified Renshaw cells in rat lumbar spinal cord.

Activity levels of cytochrome oxidase, acid phosphatase, and NADPH diaphorase were examined in the perikarya of immunohistochemically identified Renshaw cells from sections of rat lumbar spinal cord. Renshaw cell profiles were identified on the basis of their characteristic anti-gephyrin-immunofluorescent labelling. Intrasomatic densities of enzyme histochemical reaction product were employed as indicators of relative mitochondrial activity (cytochrome oxidase), intracytoplasmic digestion (acid phosphatase), or putative nitrergic signalling (NAPDH-diaphorase). Approximately half of the Renshaw cell somata examined displayed moderate levels of cytochrome oxidase reaction product (142 of 262 Renshaw cells) or low levels of acid phosphatase activity (156 of 243 Renshaw cells). A majority (160 of 202 cells) of Renshaw cells contained low intrasomatic levels of NADPH-diaphorase activity but most of these cells were closely apposed by at least one NADPH-diaphorase reactive axonal varicosity. Our findings suggest that moderate levels of perikaryal oxidative metabolism and low levels of intracytoplasmic digestion are sufficient for, and support, the unique physiological capabilities of Renshaw cells. The presence of NADPH-diaphorase containing somatic close contacts indicate that nitric oxide may have at least a minor role in the regulation of Renshaw cell activity. These results are complementary and consistent with previous morphological and pharmacological demonstrations of Renshaw cell heterogeneity.

Acid Phosphatase↗
PubMed2001

Genetic and molecular characterization of Skb15, a highly conserved inhibitor of the fission yeast PAK, Shk1.

The p21-activated kinase, Shk1, is essential for viability, establishment and maintenance of cell polarity, and proper mating response in the fission yeast, Schizosaccharomyces pombe. Here we describe the characterization of a highly conserved, WD repeat protein, Skb15, which negatively regulates Shk1 in fission yeast. A null mutation in the skb15 gene is lethal and results in deregulation of actin polymerization and localization, microtubule biogenesis, and the cytokinetic machinery, as well as a substantial uncoupling of these processes from the cell cycle. Loss of Skb15 function is suppressed by partial loss of Shk1, demonstrating that negative regulation of Shk1 by Skb15 is required for proper execution of cytoskeletal remodeling and cytokinetic functions. A mouse homolog of Skb15 can substitute for its counterpart in fission yeast, demonstrating that Skb15 protein function has been substantially conserved through evolution.

Actins↗