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Biomedical subjects

M Liu

Publications and source records attributed to M Liu.

At least 199 records · Page 11Linked to original sources
PubMed2000

Fibrinogen depleting agents for acute ischaemic stroke.

BACKGROUND: Fibrinogen depleting agents reduce fibrinogen in blood plasma, reduce blood viscosity and hence increase blood flow. This may help remove the blood clot blocking the artery and re-establish blood flow to the affected area of the brain after an ischaemic stroke. The risk of haemorrhage may be less than with thrombolytic agents. OBJECTIVES: The objective of this review was to assess the effect of fibrinogen depleting agents in people with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register, Embase (to January 1996) and the Index of scientific and technical proceedings (1982 to 1996). We handsearched 10 Chinese journals and the proceedings of the 4th Chinese Stroke Conference (1995). We contacted Chinese and Japanese researchers, and drug companies. SELECTION CRITERIA: Randomised and quasi-randomised trials of fibrinogen depleting agents started within 14 days of stroke onset, compared with control in patients with definite or possible ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria, assessed trial quality and extracted the data. MAIN RESULTS: Three trials involving 182 patients were included. All trials tested ancrod. Allocation concealment was adequate in two trials. Fibrinolytic therapy appeared to reduce the number of deaths during the scheduled treatment period (odds ratio 0.33, 95% confidence interval 0.13 to 0.85). There was no difference in death from all causes at the end of follow-up (odds ratio 0.57, 95% confidence interval 0.27 to 1.23). The risk of haemorrhage appeared to be small, but there were too few data to be conclusive. One trial in 132 people showed a statistically non-significant decrease in the odds of being dead or disabled at the end of follow-up (odds ratio 0.52, 95% confidence interval 0.26 to 1.03). REVIEWER'S CONCLUSIONS: Although ancrod appears to be promising, it is not possible to draw reliable conclusions from the available data.

Ancrod↗
PubMed2000

Anticoagulants for preventing recurrence following ischaemic stroke or transient ischaemic attack.

BACKGROUND: After a first stroke, further vascular events (especially myocardial infarction and recurrent stroke) are common and often fatal. OBJECTIVES: The objective of this review was to assess the effect of prolonged anticoagulant therapy following presumed non-embolic ischaemic stroke or transient ischaemic attack. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register. We contacted companies marketing anticoagulant agents. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing anticoagulant therapy, for at least one month, with control in people with previous non-embolic presumed ischaemic stroke or transient ischaemic attack. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Nine trials involving 1214 patients were included. The quality of all trials was poor. All pre-dated routine computerised tomography scanning and use of the International Normalised Ratio to monitor anticoagulation. Anticoagulant therapy did not significantly reduce the odds of death or dependency (two trials, odds ratio 0.83, 95% confidence interval 0.52 to 1.34). Death from any cause (odds ratio 0.95, 95% confidence interval 0.72 to 1.23), and death from vascular causes (odds ratio 0.86, 95% confidence interval 0.66 to 1.13) were not significantly different between treatment and control across all nine trials. Anticoagulant therapy did not reduce the risk of recurrent stroke (odds ratio 0.79, 95% confidence interval 0.56 to 1.13). However, fatal intracranial haemorrhage increased (odds ratio 2.54, 95% confidence interval 1.19 to 5.45), as did major extracranial haemorrhage (odds ratio 4.87, 95% confidence interval 2.50 to 9.49). This means anticoagulant therapy caused 11 additional fatal intracranial haemorrhages and 25 additional major extracranial haemorrhages per year for every 1000 patients given anticoagulant therapy. REVIEWER'S CONCLUSIONS: There appears to be no clear benefit from long-term anticoagulant therapy in people with non-embolic presumed ischaemic stroke or transient ischaemic attack. There appears to be a significant bleeding risk associated with anticoagulant therapy.

Anticoagulants↗
PubMed2000

Thrombolysis (different doses, routes of administration and agents) for acute ischaemic stroke.

BACKGROUND: Thrombolytic therapy is effective for acute myocardial infarction, a vascular disease with some similarities to acute ischaemic stroke. OBJECTIVES: The objective of this review was to assess the effect of different thrombolytic agents, and different regimens in acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register and Embase (1980 to 1997). We handsearched Japanese and Chinese journals. We contacted researchers in the field and pharmaceutical companies. SELECTION CRITERIA: Randomised and quasi-randomised trials of different doses of a thrombolytic agent, or one thrombolytic agent compared with another, or the same agent given by different routes, in people with confirmed acute ischaemic stroke. Trials were included if treatment was started within 14 days of stroke onset. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility, trial quality and extracted the data. MAIN RESULTS: Eight trials involving 1334 people were included. Concealment of allocation was generally adequate. All the trials were conducted in Japan. Different doses (of tissue plasminogen activator or urokinase) were compared in seven trials. Different agents (tissue plasminogen activator versus urokinase, or tissue-cultured urokinase versus conventional urokinase) were compared in three trials. Few data were available for functional outcomes. A higher dose of thrombolytic therapy was associated with a five-fold increase in fatal intracranial haemorrhages (odds ratio 5.02, 95% confidence interval 1.56 to 16. 18). This was based on 11 events among 369 higher-dose patients and one event among 356 lower-dose patients in six trials. There was a non-significant trend towards more early deaths or clinically significant intracranial haemorrhages. No difference in late deaths or extra-cranial haemorrhages was shown between low and higher doses. However, very few of these events occurred. No difference was shown between the different thrombolytic agents tested. REVIEWER'S CONCLUSIONS: There is not enough evidence to conclude whether lower doses of thrombolytic agents might be safer or more effective than higher doses in acute ischaemic stroke. It is not possible to conclude whether one agent might be better than another, or which route of administration might be best. No comparative data for streptokinase have been found.

Brain Ischemia↗
PubMed2000

Production of tumour necrosis factor alpha by primary cultured rat alveolar epithelial cells.

Tumour necrosis factor alpha(TNF-alpha) is one of the most important pro-inflammatory cytokines, which plays an important role in host defense and acute inflammation related to tissue injury. The major source of TNF-alpha has been shown to be immune cells such as macrophages and neutrophils. In the present study, we demonstrated that LPS-treatment on alveolar epithelial cells isolated from adult rat lungs also induced a dose- and time-dependent release of TNF-alpha. The purity and identity of these cells were examined by immunofluorescent staining and confocal microscopy with antibodies for cytokeratin and pro-surfactant protein C, markers for epithelial cells and type II pneumocytes respectively. Positive staining of TNF-alpha was observed throughout the cell layer and localized intracellularly. LPS-induced TNF-alpha production from alveolar epithelial cells was blocked not only by cycloheximide, an inhibitor of protein translation, but also by actinomycin D, an inhibitor of gene transcription. The mRNA of TNF-alpha rapidly increased within 1 h of LPS stimulation. These data suggest that LPS-induced TNF-alpha production from alveolar epithelial cells is primarily regulated at the transcriptional level, which is different from that of macrophages and neutrophils. TNF-alpha produced by alveolar epithelial cells may function as an alert signal in host defense to induce production of other inflammatory mediators.

Animals↗
PubMed2000

Multiple-quantum J-resolved NMR spectroscopy (MQ-JRES): measurement of multiple-quantum relaxation rates and relative signs of spin coupling constants.

The technique of multiple-quantum J-resolved NMR spectroscopy (MQ-JRES) is introduced and applied to the spin system SI(3)-M (such as in the example given here, the (13)CH(3)-(12)CH in alanine). The SI(3) spin system was excited to its highest quantum state (8S(y)I(x)I(y)I(y)), which consists of four coherences: quadruple quantum of (3I + S), double quantum of (3I - S), double quantum of (I + S), and zero quantum of (I - S). In the MQ spectrum generated from the projection onto the F(1) dimension, the resonances of the different multiple-quantum coherences are resolved by their coupling constants to the remote spin (M). The absorptive lineshapes in both F(1) and F(2) dimensions enable accurate measurements of transverse relaxation rates, and both amplitude and relative signs of the long-range coupling constants are to be derived from either frequency or time domain data. The selective detection of MQ-JRES spectra of the individual MQ coherences using either phase cycling or pulsed field gradients is presented.

Alanine↗
PubMed2000

Heparin interference with reverse transcriptase polymerase chain reaction of RNA extracted from lungs after ischemia-reperfusion.

The reverse transcriptase polymerase chain reaction (RT-PCR) is a rapid and sensitive method for detecting gene expression. However, when we used this technique to study gene expression of cytokines in ischemic and ex-vivo-reperfused rat lungs as a model for transplantation, significant inhibition of RT-PCR reaction was observed. To optimize RT-PCR conditions, RNA was extracted from rat lungs after flushing, preservation, and reperfusion. RNA was further purified and PCR conditions were modified with various strategies. We found that heparinase I pretreatment completely overcame the inhibitory effects of RT-PCR using RNA extracted from lung tissues after ischemia-reperfusion. With this treatment, a dramatic increase in tumor necrosis factor-a (TNF-a) mRNA was revealed from lung tissues after ischemia-reperfusion. This result suggests that residual heparin in lung tissue interferes with RT-PCR. Because heparinization is routinely used during clinical and experimental organ transplantation, we recommend the treatment of RNA samples with heparinase prior to RT-PCR.

Animals↗
PubMed2000

The farnesyl protein transferase inhibitor SCH66336 synergizes with taxanes in vitro and enhances their antitumor activity in vivo.

PURPOSE: SCH66336 is an orally active, farnesyl protein transferase inhibitor. SCH66336 inhibits ras farnesylation in tumor cells and suppresses tumor growth in human xenograft and transgenic mouse cancer models in vivo. The taxanes, paclitaxel (Taxol) and docetaxel (Taxotere) block cell mitosis by enhancing polymerization of tubulin monomers into stabilized microtubule bundles, resulting in apoptosis. We hypothesized that anticancer combination therapy with SCH66336 and taxanes would be more efficacious than single drug therapy. METHODS: We tested the efficacy of SCH66336 and taxanes when used in combination against tumor cell proliferation in vitro, against NCI-H460 human lung tumor xenografts in nude mice, and against mammary tumors in wap-ras transgenic mice. RESULTS: SCH66336 synergized with paclitaxel in 10 out of 11 tumor cells lines originating from breast, colon, lung, ovary, prostate, and pancreas. SCH66336 also synergized with docetaxel in four out of five cell lines tested. In the NCI-H460 lung cancer xenograft model, oral SCH66336 (20 mg/kg twice daily for 14 days) and intraperitoneal paclitaxel (5 mg/kg once daily for 4 days) caused a tumor growth inhibition of 56% by day 7 and 65% by day 14 compared to paclitaxel alone. Male transgenic mice of the wap-ras/F substrain [FVB/N-TgN(WapHRAS)69LlnYSJL] spontaneously develop mammary tumors at 6 9 weeks of age which have been previously shown to be resistant to paclitaxel. Paclitaxel resistance was confirmed in the present study, while SCH66336 inhibited growth of these tumors. Most importantly, SCH66336 was able to sensitize wap-ras/F mammary tumors to paclitaxel chemotherapy. CONCLUSION: Clinical investigation of combination therapy using SCH66336 and taxanes in cancer patients is warranted. Further, SCH66336 may be useful for sensitizing paclitaxel-resistant tumors to taxane treatment.

Alkyl and Aryl Transferases↗
PubMed2000

Coordinate expression of NGF and alpha-smooth muscle actin mRNA and protein in cutaneous wound tissue of developing and adult rats.

Nerve growth factor (NGF) is synthesized in cutaneous wound tissue, and its higher levels in the neonate may contribute to more efficient wound healing. We used in situ hybridization and immunohistochemistry to define NGF mRNA and protein expression in intact skin and following excision wounding in neonatal and adult rats. To determine whether NGF is associated with wound contractile fibroblasts (myofibroblasts), we also examined expression of alpha-smooth muscle actin (alpha-SMA) mRNA and protein, established markers for these cells. In intact skin, NGF mRNA and protein were present in vascular and arrector pili smooth muscle, hair follicle sheath cells, keratinocytes, and hypodermal fibroblasts. Neonatal adipocytes and Schwann cells also expressed NGF mRNA and protein, while adult adipocytes and Schwann cells displayed only NGF-ir. Following wounding, NGF mRNA expression was exuberant in these cell types, and increased similarly at both ages and appeared de novo in skeletal muscle cells. Additionally, both NGF mRNA and protein were present in macrophages and myofibroblasts, and expression in myofibroblasts was significantly greater in neonates. Wound myofibroblasts also expressed alpha-SMA. Surprisingly, after wounding alpha-SMA mRNA and protein were present in essentially all cells in which NGF mRNA was detected. We conclude that NGF expression is enhanced in many cell types after wounding, but greater NGF synthesis in neonates appears to be due to a more robust myofibroblast response. In addition, cell types which demonstrated NGF mRNA also expressed alpha-SMA, and staining for both markers increased following wounding, suggesting synthesis of both proteins is regulated in a coordinated fashion.

Actins↗
PubMed2000

Epidemiology of yeast colonization in the intensive care unit.

In order to investigate the epidemiology of colonization and possible transmission of yeasts among patients and healthcare workers in adult intensive care units (ICUs), 194 patients were followed for a mean of 9 +/- 11 days and 63 healthcare workers were followed for a mean of 132 +/- 52 days. Among the patients, 142 (73%) were colonized by yeast, with Candida albicans being the species most commonly recovered. Most patients (65%) were already colonized with yeast upon admission to the intensive care unit; only 17% became colonized after admission. Persistent colonization occurred in 51 (55%) of 92 patients who had more than three cultures performed; in 75% of them, colonization persisted with the same strain of Candida albicans or Candida glabrata. Bacterial infection in the month preceding entry into the ICU was the only risk factor significantly associated with yeast colonization. Among the healthcare workers, yeasts were isolated from 42 (67%). Candida albicans was most frequently recovered from the oropharynx (19% of occasions), and Candida parapsilosis was most frequently found on hands (8% of occasions). Persistent colonization of the oropharynx occurred in only six healthcare workers, and none had persistence of yeasts on hands. In this non-outbreak setting, 5 (4%) of 123 patient/healthcare worker interactions that were linked epidemiologically yielded the same strain of Candida albicans, providing evidence for possible cross-transmission. No similar link was found between healthcare worker-patient interactions and colonization with Candida glabrata or Candida parapsilosis.

Adult↗
PubMed2000

Molecular and functional analysis of the human prothrombinase gene (HFGL2) and its role in viral hepatitis.

In the present studies, we report the cloning and structural characterization of the HFGL2 gene and its functional role in human fulminant hepatitis. The HFGL2 gene is approximately 7 kb in length with 2 exons. The putative promoter contains cis element consensus sequences that strongly suggest the inducibility of its expression. From the nucleotide sequence of the human gene, a 439-amino acid long protein is predicted. The overall identity between the murine fgl2 and hfgl2 coded proteins is over 70%. About 225 amino acids at the carboxyl end of these molecules are almost 90% identical, and correspond to a well-conserved fibrinogen-related domain. Both HFGL2 and FGL2 encode a type II transmembrane protein with a predicted catalytic domain toward the amino terminus of the protein. Transient transfection of Chinese hamster ovary (CHO) cells with a full-length cDNA of HFGL2 coding region resulted in high levels of prothrombinase activity. Livers from 8 patients transplanted for fulminant viral hepatitis were examined for extent of necrosis, inflammation, fibrin deposition, and HFGL2 induction. In situ hybridization showed positive staining of macrophages in areas of active hepatocellular necrosis. Fibrin stained positively in these areas and was confirmed by electron microscopy. These studies define a unique prothrombinase gene (HFGL2) and implicate its importance in the pathogenesis of fulminant viral hepatitis.

Adolescent↗
PubMed2000

Raffinose improves the function of rat pulmonary grafts stored for twenty-four hours in low-potassium dextran solution.

OBJECTIVES: The perfect strategy for pulmonary graft preservation remains elusive. Experimental work supports the use of perfusates, such as Euro-Collins, University of Wisconsin, and low-potassium dextran solutions. We use low-potassium dextran solution in our clinical program, but we aim for continued improvement. The trisaccharide raffinose has been shown to be responsible for the efficacy of University of Wisconsin perfusate in lung preservation. Raffinose is superior to a variety of other saccharides for this purpose. We tested the hypothesis that the addition of raffinose to low-potassium dextran solution might further improve graft function. METHODS: In a randomized blinded study with a rat left lung transplant model, donor lungs were flushed with either standard low-potassium dextran solution or low-potassium dextran solution modified by the addition of 30 mmol/L raffinose (n = 5 for each group). Alprostadil (prostaglandin E(1), 500 microg/L) was added to the perfusates in accordance with our clinical practice. Grafts were stored inflated at 4 degrees C for 24 hours. After transplantation, recipients were ventilated with a fraction of inspired oxygen of 1 and a positive end-expiratory pressure of 2 cm H(2)O. Graft function was evaluated by measuring oxygenation at 2 hours after graft reperfusion, peak airway pressure throughout the reperfusion period, and the wet/dry lung weight ratio. RESULTS: The group receiving low-potassium dextran solution with raffinose demonstrated significantly higher oxygenation (oxygen tension, 370 +/- 45 mm Hg vs 150 +/- 64 mm Hg; P =.0025), lower peak airway pressures at 2 hours after lung reperfusion (11 +/- 2.7 mm Hg vs 16 +/- 2.4 mm Hg; P <.001), and a lower wet/dry weight ratio (4.7 +/- 1.26 vs 11 +/- 5. 0; P =.017). CONCLUSION: Modification of low-potassium dextran solution with the trisaccharide raffinose resulted in a significant improvement in graft function in this model and merits further evaluation with respect to the mechanisms involved.

Animals↗
PubMed2000

Historical record and sources of polycyclic aromatic hydrocarbons in core sediments from the Yangtze Estuary, China.

Polycyclic aromatic hydrocarbons (PAHs) in a sediment core taken from intertidal flat in the Yangtze Estuary were determined by gas chromatography-mass spectrometry. The results indicate that the total concentration of PAHs ranged from 0.08 to 11.74 microg/g. The concentration levels of total and individual PAHs changed dramatically with depth. The concentrations of PAHs were relatively high above 35 cm depth and remained constantly low below this depth. The historical record of PAHs in the core shows subsurface maximum (one or more peak values), followed by decreased levels to the surface and with depth. And, PAH sediment record in the core profile is in agreement with historically sewage discharge events during the 1980s to 1990s. The distribution of target molecule acenephthene, the fluoranthene/pyrene ratio, the proportion of 2-3-ring and 4-5-ring PAHs, and alkylated naphthalene to parent naphthalene in the core profile show that the sources in this area are characterized by petroleum-derived PAH contamination (mainly sewage discharge and the river runoff) and the incorporation of atmospheric inputs. Studies indicate the PAH profile pattern in this site in comparison with other regions appear to reflect its particular local position (near the sewage outlet). Moreover, physico-chemical conditions and sedimentation rate as well as biodegradation also affect the PAH concentration levels in the core sediments.

Journal Article↗
PubMed2000

Transplant immunosuppression increases and prolongs transgene expression following adenoviral-mediated transfection of rat lungs.

BACKGROUND: Gene therapy provides the potential to modify donor organs to better withstand transplantation, but this has yet to be realized. In vivo gene transfer using adenoviral vectors has had limited success because of host immune response that induces inflammation and limits the amount and duration of transgene expression. We hypothesize that transplantation immunosuppression can attenuate the post-transfection host-immune response to allow for improved gene transfer following adenoviral-mediated transfection. METHODS: We intratracheally transfected with adenovirus containing the beta-galactosidase gene and randomized the rats to either the immunosuppression group, receiving daily cyclosporine, azathioprine, and methylprednisolone, or the control group, receiving no immunosuppression. We evaluated transgene expression and post-transfection inflammation at time points ranging from 1 day to 5 weeks. RESULTS: Following transfection, control rats showed relatively low levels of transgene expression, which rapidly decreased to non-detectable levels. In contrast, immunosuppressed rats demonstrated significantly higher levels of transgene expression overall (p < 0.00005), peaking at almost 3 times that of the control group (p < 0.02), and showing prolonged and elevated transgene expression at 5 weeks (p < 0.02). On histologic sections of the lungs, immunosuppressed rats exhibited overall lesser grades of post-transfection inflammation. CONCLUSIONS: Transplant immunosuppression provides the means to attenuate the severe immune response to adenoviral-mediated gene transfection and thereby increase and prolong transgene expression.

Adenoviridae↗
PubMed2000

Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.

A novel sequence discovered in a computational screen appears distantly related to the p35 subunit of IL-12. This factor, which we term p19, shows no biological activity by itself; instead, it combines with the p40 subunit of IL-12 to form a novel, biologically active, composite cytokine, which we term IL-23. Activated dendritic cells secrete detectable levels of this complex. IL-23 binds to IL-12R beta 1 but fails to engage IL-12R beta 2; nonetheless, IL-23 activates Stat4 in PHA blast T cells. IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low)) T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population. Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells.

Amino Acid Sequence↗
PubMed2000

Sociable and prosocial dimensions of social competence in Chinese children: common and unique contributions to social, academic, and psychological adjustment.

A sample of 6th-grade children (N = 470), initially aged 12 years, in Shanghai, People's Republic of China, participated in this longitudinal study. Data on children's sociability and prosocial orientation were collected from peer assessments. Information on indexes of adjustment was obtained from multiple sources. The results indicated that sociable and prosocial functions were 2 overlapping, but distinct, dimensions of social competence and had common as well as unique contributions to the prediction of adjustment in specific areas. Whereas prosocial orientation was mainly predictive of social and school adjustment and externalizing problems, sociability uniquely contributed to the prediction of internalizing problems and emotional adjustment. Finally, prosocial orientation and sociability might moderate the development of adjustment difficulties.

Achievement↗
PubMed2000

Parental warmth, control, and indulgence and their relations to adjustment in Chinese children: a longitudinal study.

A sample of children, initially 12 years old, in the People's Republic of China participated in this 2-year longitudinal study. Data on parental warmth, control, and indulgence were collected from children's self-reports. Information concerning social, academic, and psychological adjustment was obtained from multiple sources. The results indicated that parenting styles might be a function of child gender and change with age. Regression analyses revealed that parenting styles of fathers and mothers predicted different outcomes. Whereas maternal warmth had significant contributions to the prediction of emotional adjustment, paternal warmth significantly predicted later social and school achievement. It was also found that paternal, but not maternal, indulgence significantly predicted children's adjustment difficulties. The contributions of the parenting variables might be moderated by the child's initial conditions.

Adaptation, Psychological↗