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Biomedical subjects

N Liu

Publications and source records attributed to N Liu.

At least 19 recordsLinked to original sources

The effect of natural killer cell killer Ig-like receptor alloreactivity on the outcome of bone marrow stem cell transplantation for severe combined immunodeficiency (SCID).

Natural killer (NK) cell alloreactions against recipient cells in the setting of bone marrow transplantation have been associated with decreased rates of graft-versus-host disease (GVHD) and improved survival in transplant recipients with myeloid leukemia. These alloreactions are predicted by the absence of recipient HLA class I ligands for donor inhibitory killer Ig-like receptors (KIR). We hypothesized that donor NK cell alloreactions against recipient cells may affect the development of T and B-cell functions and incidence of GVHD in infants with severe combined immunodeficiency (SCID). Of the 156 patients with SCID who had received related bone marrow transplants without pretransplant chemotherapy or posttransplant GVHD prophylaxis, 137 patient-donor pairs were evaluated for the absence of recipient HLA class I ligands for donor inhibitory KIR. Analysis showed that the absence of a KIR ligand had no effect on the incidence or severity of GVHD (RR [corrected] = 0.95, p = 0.84), development of T-cell function (RR [corrected] = 1.05, p = 0.69), production of IgA (p = 0.46) or IgM (p = 0.33), or on 5-year survival (RR [corrected] = 1.21, p = 0.10). Further, in patients possessing native NK cells, the absence of KIR ligands in donors for recipient-inhibitory KIR did not alter transplantation outcomes. This study suggests that inhibitory KIR/HLA interactions do not play a significant role in bone marrow transplantation for SCID.

Bone Marrow Transplantation↗

Anticoagulation monitoring during vascular surgery: accuracy of the Hemochron low range activated clotting time (ACT-LR).

BACKGROUND: Activated clotting time (ACT) is currently used to monitor high concentrations of heparin anticoagulation. A new instrument, the Hemochron Jr Signature device, has been specifically designed to measure ACT in low-range heparin plasma concentrations (ACT-LR). The purpose of this study was to compare ACT-LR with anti-Xa activity in patients receiving low-dose i.v. heparin during vascular surgery. METHODS: Thirty patients, undergoing arterial vascular surgery, were included in the study and received unfractionated heparin (initial dose 50 u kg(-1)). One hundred and thirty-two pairs of blood samples were simultaneously collected during surgery to determine ACT-LR and anti-Xa activity. Pearson correlation, Kappa test, ROC curve and a specific clinical interpretation of the correlation were performed. RESULTS: ACT-LR ranged from 68 to 380 s, anti-Xa activity from 0 to 1.45 u ml(-1). We observed a strong correlation between anti-Xa activity and ACT-LR (r(2)=0.87; P<0.0001). Accuracy of ACT-LR was good for anti-Xa activity up to 0.6 u ml(-1) (Kappa, 0.94; accuracy, 97%) and 0.8 u ml(-1) (Kappa, 0.79; accuracy, 90%), and poor for anti-Xa activity above 1 u ml(-1) (Kappa, 0.59). A clinical interpretation of the correlation graph found 98% of measured ACT-LR values to be accurate. CONCLUSION: Hemochron Jr Signature provides measurements of ACT-LR, which are accurate for monitoring heparin anticoagulation at anti-Xa activity below 0.8 u ml(-1).

Adult↗

Amplification of telomerase (hTERT) gene is a poor prognostic marker in non-small-cell lung cancer.

Telomerase reactivation is a hallmark of human carcinogenesis. Increased telomerase activity may result from gene amplification and/or overexpression. This study evaluates the prognostic value of hTERT gene amplification and mRNA overexpression in 144 resectable non-small-cell lung cancer (NSCLC) specimens. The hTERT gene copy number was assessed by quantitative polymerase chain reaction (qPCR) on laser-capture microdissected tumour cells of 81 tumours, and by fluorescence in situ hybridisation (FISH) on a subset of 59 tumours. hTERT mRNA level was determined by reverse transcription (RT)-qPCR in 130 tumours. In total, 57% of (46 out of 81) primary NSCLC specimens demonstrated hTERT amplification, which was significantly more common (P<0.001) in adenocarcinoma (30 out of 40) than in squamous cell carcinoma (13 out of 37). The hTERT mRNA overexpression was noted in 74% (94 out of 130) of tumours; it was more frequent in squamous cell than in adenocarcinoma (87 vs 68%, P=0.03). Overexpression was significantly associated with amplification (P=0.03), especially in adenocarcinoma. The hTERT gene amplification was prognostic for shorter recurrence-free survival (hazard ratio=2.16, P=0.03). These data indicate that gene amplification is an important mechanism for hTERT overexpression in lung adenocarcinoma and is an independent poor prognostic marker for disease-free survival in NSCLC.

Adult↗

On-line simultaneous monitoring of polarization mode dispersion and chromatic dispersion.

We have developed new expressions for power fading and average power fading owing to polarization mode dispersion (PMD) and chromatic dispersion in terms of the angle of precession of the output state of polarization about the PMD vector. Based on these expressions, a simple and novel pilot-tone-based technique for simultaneous monitoring of chromatic dispersion and PMD is proposed. Experimental results demonstrate the effectiveness of the proposed technique; these results agree well with the theoretical analysis.

Journal Article↗

Overexpression of PrPC and its antiapoptosis function in gastric cancer.

Cellular prion protein (PrP(C)), a glycosylphosphatidylinositol-anchored membrane protein, was found in our lab to be widely expressed in gastric cancer cell lines. In order to evaluate its biological significance in human gastric cancer, we investigated its expression in a large series of gastric tissue samples (n = 124) by immuno histochemical staining with the monoclonal antibody 3F4. Compared with normal tissues, gastric adenocarcinoma showed increased PrP(C) expression, correlated with the histopathological differentiation (according to the WHO and Lauren classifications) and tumor progression (as documented by pTNM staging). To better understand the underlying mechanism, we introduced the PrP(C) and two pairs of RNAi into the poorly differentiated gastric cancer cell line AGS and found that PrP(C) suppressed ROS and slowed down apoptosis in transfected cells. Further study proved that the apoptosis-related protein Bcl-2 was upregulated whereas p53 and Bax were downregulated in the PrP(C)-transfected cells. A reverse effect was observed in PrP(C) siRNA-transfected cells. These results strongly suggested that PrP(C) might play a role as an effective antiapoptotic protein through Bcl-2-dependent apoptotic pathways in gastric cancer cells. Further study into the mechanism of these relationships might enrich the knowledge of PrP, better our understanding of the nature of gastric carcinoma, and further develop possible strategies to block or reverse the development of gastric carcinoma.

Adult↗

Feasibility of closed-loop titration of propofol guided by the Bispectral Index for general anaesthesia induction: a prospective randomized study.

BACKGROUND: This study was designed to evaluate the feasibility of propofol infusion by a closed-loop system for the titration of anaesthetic induction guided by Bispectral Index. METHODS: Forty patients were prospectively and randomly allocated into two groups: the target control infusion (TCI) group, where propofol titration was performed manually guided by the Bispectral Index using a commercial pharmacokinetic model (Diprifusor device) and the closed-loop group where titration was performed using a proportional differential algorithm. For both groups, the objective was to achieve a Bispectral Index of 50. Remifentanil TCI was infused at a target of 2 ng mL-1 and was maintained constant throughout the study. Feasibility of automatic induction was evaluated with performance error and haemodynamic data. RESULTS: Bispectral Index overshoot (-9 +/- 13% vs. -16 +/- 20%, P = 0.035) and mean duration of induction (381 +/- 106 s vs. 490 +/- 131 s, P = 0.004) were lower in the closed-loop group than in the TCI group. Haemodynamic data were similar between groups with a similar use of ephedrine bolus. CONCLUSION: The system was able to allow induction clinically for all patients. Automated titration guided by Bispectral Index for propofol infusion was feasible without increase in haemodynamic adverse effects.

Algorithms↗

Abnormal expression and clinicopathologic significance of p120-catenin in lung cancer.

The aim of this study was to investigate the relationship between the expression of p120ctn in human lung squamous cell carcinoma, adenocarcinoma and its clinicopathologic significance. The expression of p120ctn in tumors and adjacent normal lung tissues from 143 patients was examined by immunohistochemistry and Western blot. Expression of p120ctn occurs mainly in the cell membrane of normal bronchial mucosa. Abnormal expression of p120ctn, including cytoplasmic and reduced membranous expression, was found in 114 of 143 specimens (79.7%) and was significantly associated with poor differentiation, high TNM stage, and lymph node metastasis (P<0.05 for each) but not with histologic subtype. The Kaplan-Meier survival test revealed that abnormal expression of p120ctn was related to poor survival (P<0.001). A Cox regression analysis revealed that abnormal p120ctn expression was an independent factor in predicting patient survival (P=0.024). Compared with that in normal lung tissues, membranous protein level was lower in tumors (P=0.003). Abnormal expression of p120ctn is associated with tumor progression and poor prognosis in lung squamous cell carcinoma and adenocarcinoma. Reduced expression or even the absence of p120ctn isoform 1 and 3 in tumor cell membranes may be responsible for the abnormal expression of p120ctn that has been found in lung cancer.

Adenocarcinoma↗

Atomic scale conductance induced by single impurity charging.

A scanning tunneling microscope was used to probe electron transport through an alkali doped C(60) monolayer crystal on Al(2)O(3) grown by the oxidation of NiAl(110). Each individual alkali atom forms a localized complex with the neighboring C(60) molecules. Charging of the complex induces a substantial rise in the current that persists outside the physical dimensions of the complex. This induction of the current rise is characterized by spatially resolved spectroscopy and mapping of the differential conductance (dI/dV) in the vicinity of the complex.

Journal Article↗

Chitosan/cellulose acetate microspheres preparation and ranitidine release in vitro.

New microspheres containing hydrophilic core and hydrophobic coating as a controlled-release system with no toxic reagents were proposed. Water in oil in water (W/O/W) emulsion and solvent evaporation methods were used to make chitosan/ cellulose acetate (CCA) microspheres sized 200 - 400 microm. Ranitidine hydrochloride, as a model drug, was investigated for its release properties in vitro. The loading efficiency and release rate of ranitidine were affected by chitosan concentration and molecular weight. Higher loadings were obtained at lower concentrations in the interval of 1% to 2%. With chitosan at a 2% concentration microspheres could be obtained with more spherical appearance, smaller size, and higher ranitidine loading efficiency microspheres than at other concentrations. Among the different molecular weight chitosan (47, 145, 308, 499, and 1130 KD) microspheres, the high molecular weight chitosan (1130 KD) microspheres had relatively high loading efficiency (10%). Molecular weight and concentration of chitosan as well as the size of microspheres affected the release of ranitidine. Microspheres smaller than 280 microm released the drug faster than did the bigger by about 10%. The optimal condition for the preparation of the microspheres was chitosan concentration 2%, molecular weight 1130 KD. The ranitidine release from the microspheres was 30% during 48 h in phosphate-buffer saline medium.

Administration, Oral↗

Overexpression of DARPP-32 in colorectal adenocarcinoma.

Dopamine and cAMP-regulated phosphoprotein (DARPP)-32 is a phosphoprotein that is centrally involved in dopamine signalling pathways. It may play an important role in gastric tumorigenesis. Our aim is to investigate the expression of DARPP-32 protein in colorectal adenocarcinoma. The expression of DARPP-32 was evaluated by immunohistochemical SABC staining and Western blotting. DARPP-32 was specifically localised in colorectal epithelium. The expression of DARPP-32 in colorectal adenocarcinoma tissues 33/42, 78.57% was higher than that in normal colon epithelial tissues (31/60, 51.67%, p <0.05). There was no significant relationship between the expression of DARPP-32 and the differentiation, metastasis and Dukes' stage of colorectal adenocarcinoma (p >0.05). Both DARPP-32 and its truncated isoform t-DARPP were overexpressed in colorectal adenocarcinoma (t=2.306, p=0.028), while t-DARPP was more frequently detected. These results showed that DARPP-32 may play an important role in the regulation of normal colorectal epithelial biology and carcinogenesis.

Adenocarcinoma↗

Tunable microwave filter that uses a high-birefringent fiber and a differential-group-delay element.

We propose and experimentally demonstrate a novel and simple photonic microwave notch filter that uses a high-birefringent fiber that gives a fixed differential group delay (DGD), together with a DGD element that gives a tunable DGD. This configuration overcomes the problems of optical coherence interference and chromatic dispersion, which may occur in schemes that use fiber delay lines or fiber gratings. Also presented is a theoretical analysis for the performance of the microwave filter that uses the present configuration. The present scheme provides a continuous tuning capability for changing the notch frequency. Measured notch rejection is greater than 40 dB. This scheme can operate over a wide wavelength range of the optical carrier. There is good agreement between experiment results and theoretical analysis.

Journal Article↗

Vibronic states in single molecules: C60 and C70 on ultrathin Al2O3 films.

Vibronic states are observed in single C(60) and C(70) molecules by scanning tunneling microscopy. When single fullerene molecules are adsorbed on a thin layer of Al(2)O(3) grown on a NiAl(110) substrate, equally spaced features are observed in the differential conductance (dI/dV), which are clearly resolved in d(2)I/dV(2) spectra. These features are attributed to the vibronic states of the molecule. The vibronic progressions are sensitive to the molecular orientations and can have different spacings in different electronic bands of the same molecule. For C(60,) these vibronic states are associated with the intramolecular A(g) and H(g) vibrational modes. Vibronic states are not resolved in molecules adsorbed on the metal surface. However, inelastic electron tunneling spectroscopy exhibits a vibrational mode at 64 meV for C(60) and 61 meV for C(70) adsorbed on NiAl(110).

Journal Article↗

[Analgesia after thoracotomy: French practice].

OBJECTIVE: To estimate qualitatively and quantitatively analgesic methods used after thoracotomy. METHODS: Postal questionnaire addressed to all French public (34 academic institutions, 37 public hospitals) and private hospitals (60), which routinely perform pulmonary surgery. RESULTS: Analysis of the questionnaires related only to those coming from academic institutions (rate of response of 85%) and from private hospitals (60%). Intravenous patient-controlled analgesia, thoracic epidural analgesia and intrathecal analgesia are the most frequently suggested techniques of analgesia. Thoracic epidural analgesia is more frequently suggested in private hospitals than in academic institutions (77% vs. 55%, NS). There is no significant difference between academic institutions and private hospitals regarding the practised analgesic technique. Analysis of the practices of thoracic epidural analgesia and of intrathecal analgesia in particular showed limited impact of guidelines concerning preoperative administration of anticoagulants in 15-20% of the centres. Only six (in the academic institutions) to 18% (in the private hospitals) of the patients receiving thoracic epidural analgesia were hospitalised in a surgical ward. Thoracic epidural analgesia is continued generally for more than 48 h; there is however a significant difference between centres since epidural analgesia is continued longer in academic institutions than in private hospitals. CONCLUSION: Intravenous patient-controlled analgesia and thoracic epidural analgesia are the most commonly analgesic techniques used after thoracotomy for pulmonary surgery. In the latter case, most centres choose to maintain these patients in high dependency units.

Academic Medical Centers↗

Identification of mariner elements from house flies (Musca domestica) and German cockroaches (Blattella germanica).

Full-length mariner elements were isolated and sequenced from house flies (Musca domestica) and German cockroaches (Blattella germanica). The amino acid sequence of the house fly mariner element (accession number: AF373028) showed 99.5% identity with Mos1 and peach elements, whereas the German cockroach mariner element (accession number: AF355143) showed 98.8% and 99.8% identity, respectively. Sequence analysis revealed that the mariner elements in house flies and German cockroaches differed from the active Mos1 mariner element by seven and 15 nucleotides, respectively. Four essential nucleotide substitutions at positions 64, 154, 305, and 1203, which have been proposed to contribute to the loss of activity of the inactive elements, were detected in the German cockroach mariner element. In contrast, although the mariner element in house flies contained substitutions at positions 64, 154, and 305, it retained T at position 1203, identical to active mariner elements. Mariner is present in approximately eight copies in the German cockroach genome.

Amino Acid Sequence↗

A heat inducible tyrosinase with distinct properties from Bacillus thuringiensis.

AIMS: The objective of this work was to purify the tyrosinase from Bacillusthuringiensis subsp. kurstaki (Bt) (CCTCC AB 90010) and study its enzymatic properties. METHODS AND RESULTS: A 'one-step' purification method was used in this work, which was an easy, high-yield purification method. Tyrosinase activity of this purity was measured under different conditions to study its kinetic characterizations. The optimum pH and thermal stability of this enzyme were also determined. The results revealed that the tyrosinase from Bt has distinct properties compared with those from other sources. CONCLUSIONS: A heat-inducible tyrosinase of a wild strain of Bt was identified and partially characterized. SIGNIFICANCE AND IMPACT OF THE STUDY: The distinct properties of Bt tyrosinase are important to the application of Bt as a biology pesticide.

Bacillus thuringiensis↗

Investigations of 99mTc morpholino pretargeting in mice.

This laboratory is exploring the use of morpholinos (MORFs), synthetic DNA analogues, for nuclear medicine applications, including pretargeting. The anti-CEA antibody MN14 was conjugated with an 18 mer MORF and with diethylenetriaminepentaacetic acid (DTPA) for 111In labelling. In a dual label pretargeting study, tumour-bearing nude mice received different doses of (MN14-DTPA-111In+MN14-MORF) followed, at various times after i.v. injection, by 0.15 microg complementary MORF (cMORF) radiolabelled with 99mTc via MAG(3). Animals were killed 3 h thereafter and tissues were counted for both radionuclides. The 99mTc-cMORF was also administered to tumour bearing mice that, 2 days previously, had received different doses of unlabelled MN14-MORF IgG or, as control, unlabelled Sandoglobulin IgG-MORF (Sandoz-MORF). Tumour uptake was higher at all time points for the labelled antibody itself versus labelled cMORF (8-10 vs 1.3-2.3%ID/g, respectively) in part due to the rapid clearance of cMORF through the kidneys. However, target to non-target ratios were superior for pretargeting at all time points and in all tissue except blood and kidneys. By pretargeting alone, these ratios were highest in all tissues for 15 microg compared to higher MN14-MORF dosages and in all cases were superior to that of the Sandoz-MORF control. The superior target to non-target ratios for pretargeting can be partially explained through calculations based on both radiolabels: after 24 h, only 0-6% of MORF on MN14 was bound by 99mTc-cMORF in liver and spleen suggesting that the antibody is sequestered in these organs and 'invisible' to labelled MORF. Fortunately, this was not the case in tumours in which 50-60% was bound. It is concluded that pretargeting using MORFs provided encouraging results in one mouse model/anti-tumour antibody system. The advantages of pretargeting in this model were evident in the superior target to non-target ratios obtained over conventional imaging.

Animals↗

Molecular cloning and functional characterization of Cynomolgus monkey (Macaca fascicularis) CC chemokine receptor, CCR3.

We have cloned and performed the first functional characterization of the chemokine receptor, CCR3, of Cynomolgus monkey (Macaca fascicularis). The deduced amino acid sequence of the cloned Cynomolgus CCR3 was found to be more similar to that of a previously-reported Rhesus (Macaca mulatta) CCR3 (99.4%) than that of a reported Cynomolgus CCR3 (98.0%). Stably-transfected Cynomolgus CCR3 bound human eotaxin (CCL11) with similar kinetics (Kd 240 pM) and was responsive to human CCR3 ligands (eotaxin [CCL11], eotaxin-2 [CCL24], and MCP4 [CCL13]) in Ca(2+) mobilization and chemotaxis assays, thus provides a useful alternative species model system for the analysis of modulators of eotaxin--CCR3 induced signaling and activation.

Amino Acid Sequence↗

Hyaluronan metabolism in rat tail skin following blockage of the lymphatic circulation.

This study was undertaken to explore the effects of lymphatic blockage on the metabolism of hyaluronan in the skin. In initial experiments, [3H] hyaluronan was injected subcutaneously into the tail skin of rats that either had no surgical intervention (control) or into those that had their lymphatic drainage blocked two hours earlier (acute lymphedema) or after the lymphatics had been blocked for three months (chronic lymphedema). The removal of tritiated hyaluronan from the injection sites was determined by the appearance of [3H] in the plasma. The results showed that the clearance of injected hyaluronan was delayed in rats with lymphatic blockage. The half- life of injected hyaluronan in the controls was approximately 70-75 hr, compared with approximately 105-110 hr in the lymph blocking rats. The levels of radioactivity in the plasma from rats with both acute and chronically blocked lymphatics were lower than that of control rats during the entire follow up period. In addition, biochemical analysis revealed that there was a significant increased amount of hyaluronan in the tail skin three months after lymphatic blocking. These results suggest that lymph absorption is an important factor in the transport of hyaluronan from the interstitium. Blockage of regional draining lymphatics likely impairs the catabolism of hyaluronan, which stagnates in skin tissue.

Animals↗