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Biomedical subjects

M Liu

Publications and source records attributed to M Liu.

At least 73 records · Page 4Linked to original sources

Ischemia-reperfusion decreases protein tyrosine phosphorylation and p38 mitogen-activated protein kinase phosphorylation in rat lung transplants.

BACKGROUND: Dramatic alterations of protein tyrosine phosphorylation have been found during the ischemia-reperfusion (IR) period of human lung transplantation. IR also induces activation of p38 mitogen-activated protein kinase (p38) in the heart and kidney. The objective of the present study was to determine whether these changes exist in a rat single-lung transplant model for further mechanistic investigations. METHODS: Isogeneic lung transplantation was performed from Lewis (LEW) to LEW rats, whereas allogeneic transplantation was from LEW to Brown Norway (BN) rats. Blood gases and peak airway pressure were monitored. Lung tissues were collected after 6 hours of cold ischemic preservation, after 30 minutes of warm ischemia for lung implantation, and after 2 hours of reperfusion. Protein tyrosine kinase (PTK) and phosphatase (PTP) activities were measured. Protein tyrosine phosphorylation, Src PTK and p38 expression and p38 phosphorylation were examined by western blotting. RESULTS: In both iso- and allografts, the lung function of transplants was very well preserved. Protein tyrosine phosphorylation, PTK and PTP activities were decreased significantly after 2 hours of reperfusion. Src protein level and phosphorylation of p38 were reduced after 2 hours of reperfusion. CONCLUSIONS: During the early IR period of lung transplantation, decreased protein tyrosine phosphorylation may be involved in apoptosis and other biologic changes. The lack of p38 activation suggests that activity of mitogen-activated protein kinase pathways in the lung transplantation setting may be different from other IR processes.

Animals↗

Inhibition of human leukemia in an animal model with human antibodies directed against vascular endothelial growth factor receptor 2. Correlation between antibody affinity and biological activity.

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) have been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis. We recently showed that certain 'liquid' tumors such as leukemia not only produce VEGF, but also express functional VEGFR, resulting in an autocrine loop for tumor growth and propagation. A chimeric anti-VEGFR2 (or kinase insert domain-containing receptor, KDR) antibody, IMC-1C11, was shown to be able to inhibit VEGF-induced proliferation of human leukemia cells in vitro, and to prolong survival of nonobese diabetic-severe combined immune deficient (NOD-SCID) mice inoculated with human leukemia cells. Here we produced two fully human anti-KDR antibodies (IgG1), IMC-2C6 and IMC-1121, from Fab fragments originally isolated from a large antibody phage display library. These antibodies bind specifically to KDR with high affinities: 50 and 200 pM for IMC-1121 and IMC-2C6, respectively, as compared to 270 pM for IMC-1C11. Like IMC-1C11, both human antibodies block VEGF/KDR interaction with an IC(50) of approximately 1 nM, but IMC-1121 is a more potent inhibitor to VEGF-stimulated proliferation of human endothelial cells. These anti-KDR antibodies strongly inhibited VEGF-induced migration of human leukemia cells in vitro, and when administered in vivo, significantly prolonged survival of NOD-SCID mice inoculated with human leukemia cells. It is noteworthy that the mice treated with antibody of the highest affinity, IMC-1121, survived the longest period of time, followed by mice treated with IMC-2C6 and IMC-1C11. Taken together, our data suggest that anti-KDR antibodies may have broad applications in the treatment of both solid tumors and leukemia. It further underscores the efforts to identify antibodies of high affinity for enhanced antiangiogenic and antitumor activities.

Animals↗

Shock absorption in lumbar disc prosthesis: a preliminary mechanical study.

Lumbar disc prostheses have been used in treating symptomatic degenerative disc diseases. A few prostheses of the ball-socket design are currently available for clinical use, the joint mechanism being materialized either with a hard polymer core or a metal-to-metal couple. Other prostheses of "shock absorber" design were not available at the time of the study. The objective of this work was to establish whether there was a difference in the shock absorption capacity between a device having an ultra-high-molecular-weight polyethylene center core and a device having a metal-on-metal bearing. Vibration and shock loading were applied to two lumbar total disc prostheses: PRODISC, manufactured by Spine Solutions, and MAVERICK Total Disc Replacement, manufactured by Medtronic Sofamor Danek. The shock absorption capacity of the device was evaluated by comparing the input and the output force measurements. The disc prosthesis was mounted onto a test apparatus. Each side of the device was equipped with a force sensor. The input shock load and the output resulting forces were simultaneously measured and recorded. The loading force pattern included 1). a static preload of 350 N plus an oscillating vibration of 100 N with frequency sweeping from 0 to 100 Hz and 2). a sudden shock load of 250 N applied over a 0.1-second interval. Both input and output signal data were processed and were transformed into their frequency spectrums. The vibration and shock transmissibility of the device, defined as the ratio of the output spectrum over the input spectrum, were calculated in sweeping the frequency from 0 to 100 Hz. The phase deviation was calculated to characterize the shock absorber effects. For both tested devices under vibration and shock loading, the phase angle displacement between the input and the output signals was 10 degrees. Under oscillating vibration loading, both tested devices had a transmission ratio higher than 99.8%. Over the frequency interval 1-100 Hz, the difference in transmission ratio between the two devices was <0.3%. Under sudden shock loading, both tested devices had a transmission ratio higher than 98%. The difference between the two devices was <0.8%. Both tested devices have identical vibration and shock transmissibility.

Arthroplasty, Replacement↗

CT slice index and thickness: impact on organ contouring in radiation treatment planning for prostate cancer.

OBJECTIVE: To assess the impact of CT slice index and thickness (3 mm versus 5 mm) on (i) prostate volume, dimensions, and isocenter coordinates, (ii) bladder and rectal volumes, and (iii) DRR quality, in the treatment of prostate cancer. METHODS: 16 patients with prostate cancer underwent two planning CT-scans using 3 and 5 mm slice index/thickness. Prostate, bladder, and rectum were outlined on all scans. Prostate isocenter coordinates, maximum dimensions, and volumes were compared along with bladder and rectal volumes. Bladder volumes and maximum diameters were further investigated using a second observer. A comparative analysis of DRR quality was conducted as well as a dosimetric analysis using DVH. RESULTS: The differences in measurements of prostate volume, isocenter coordinates and maximum dimensions between the 3 and 5 mm scans, were small and not statistically significant. Similar finding was seen for rectal volume. However, bladder volume was always larger on the 3 mm scan (mean difference=27.9 cc; SE=4.8 cc; 95% CI: 17.7-38.2 cc; p<0.001) and the findings were reproduced with the second observer (mean difference=31.9 cc; SE=4.7 cc; 95% CI: 21.9-41.9 cc; p<0.001). The differences in volume are caused by a slight increase in (1) the measurement of the longitudinal dimensions on the 3 mm scans, and (2) the slice by slice measured bladder area on the 3 mm scans. The latter is due to partial volume effect. The 3 mm DRR were slightly better than the 5 mm DRR. The bladder DVH differed significantly in some patients. CONCLUSION: Bladder volume is significantly larger on the 3 mm scans. Differences in contoured areas may be accounted for, in part, by the partial volume effect.

Adenocarcinoma↗

The quest of influenza A viruses for new hosts.

There is increasing evidence that stable lineages of influenza viruses are being established in chickens. H9N2 viruses are established in chickens in Eurasia, and there are increasing reports of H3N2, H6N1, and H6N2 influenza viruses in chickens both in Asia and North America. Surveillance in a live poultry market in Nanchang, South Central China, reveals that influenza viruses were isolated form 1% of fecal samples taken from healthy poultry over the course of 16 months. The highest isolation rates were from chickens (1.3%) and ducks (1.2%), followed by quail (0.8%), then pigeon (0.5%). H3N6, H9N2, H2N9, and H4N6 viruses were isolated from multiple samples, while single isolates of H1N1, H3N2, and H3N3 viruses were made. Representatives of each virus subtype were experimentally inoculated into both quail and chickens. All the viruses replicated in the trachea of quail, but efficient replication in chickens was confined to 25% of the tested isolates. In quail, these viruses were shed primarily by the aerosol route, raising the possibility that quail may be the "route modulator" that changes the route of transmission of influenza viruses from fecal-oral to aerosol transmission. Thus, quail may play an important role in the natural history of influenza viruses. The pros and cons of the use of inactivated and recombinant fowl pox-influenza vaccines to control the spread of avian influenza are also evaluated.

Animals↗

Frequencies of the major alleles of the Diego, Dombrock,Yt, and Ok blood group systems in the Chinese Han, Hui, and Tibetan nationalities.

The frequencies of the major alleles of the Diego,Dombrock,Yt,and Ok blood group systems in the Chinese Han, Hui, and Tibetan nationalities were determined using a DNA-based PCR-sequence-specific primers (SSP) genotyping technique. The frequencies of Dia, Dib, Doa, and Dob genes were 0.0295, 0.9705, 0.1159, and 0.8841 in 220 Chinese North Han, respectively. The Yta gene frequencies were 0.9928, 0.9917, and 0.9983 in 277 Han, 300 Hui, and 303 Tibetan blood donors, respectively. No Ok(a-) individuals were found in 304 Han, 300 Hui, and 303 Tibetan individuals.

Journal Article↗

Comparison of manual and computer-generated customized blocks for whole brain fields used in the treatment of medulloblastoma.

BACKGROUND: By using CT simulation and three-dimensional planning, we have developed a simple but accurate method of producing customized blocks for the cranial fields in the treatment of medulloblastoma. We compare here the margins and the volume of normal tissues included in the treatment volume with those obtained using blocks generated manually. PROCEDURE: Customized blocks for the whole brain field are generated using CT planning and autoblock function. The clinical target volume (CTV) is defined as the whole cerebrospinal fluid pathway, and the whole brain and spinal cord are contoured. A margin of 1.1 cm is generated using the autoblock function to account for set-up errors (3-5 mm) and penumbra (approximately 7 mm). A separate set of blocks was generated manually without the knowledge of the ones generated by the CT-simulator. These 2 sets of blocks were compared for a cohort of 7 consecutive patients. RESULTS: Overall, the manual blocks and the computer-generated blocks were quite similar. Those generated manually had more variations; they were always tighter (median of 6 mm tighter; range: 3-7 mm) at the level of the cribriform plate and in 5/7 patients were more generous (median of 6 mm more generous, range: 0-6 mm) at the temporal lobes. Dosimetric analysis showed that both methods provide adequate coverage of the CTV, with 100% of the CTV receiving > 95% of the prescribed dose for both. CONCLUSIONS: The customized block method for whole brain fields is simple to use and ensures adequate coverage of the target volume.

Cerebellar Neoplasms↗

Chitinolytic activities in Bacillus thuringiensis and their synergistic effects on larvicidal activity.

AIMS: To investigate the distribution of chitinase in Bacillus thuringiensis strains, and the enhancing effects of the chitinase-producing B. thuringiensis strains on insecticidal toxicity of active B. thuringiensis strain against Spodoptera exigua larvae. METHODS AND RESULTS: The chitinolytic activities of B.thuringiensis strains representing the 70 serotypes were investigated by the whitish opaque halo and the colorimetric method. Thirty-eight strains produced different levels of chitinase at pH 7.0, and so did 17 strains at pH 10.0. The strain T04A001 exhibited the highest production, reaching a specific activity of 355 U ml(-1) in liquid medium. SDS-PAGE and Western blotting showed that the chitinase produced by some B. thuringiensis strains had a molecular weight of about 61 kDa. The bioassay results indicated that the chitinase-producing B. thuringiensis strains could enhance the insecticidal activity of B. thuringiensis strain DL5789 against S. exigua larvae, with an enhancing ratio of 2.35-fold. CONCLUSION: This study demonstrated that chitinase was widely produced in B. thuringiensis strains and some of the strains could enhance the toxicity of active B. thuringiensis strain. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first investigation devoted exclusively to analyse the distribution of chitinase in B. thuringiensis. It infers that the chitinase produced by B. thuringiensis might play a role in the activity of the biopesticide.

Animals↗

Regulation of nociceptive neurons by nerve growth factor and glial cell line derived neurotrophic factor.

Nociceptive dorsal root ganglion (DRG) cells can be divided into three main populations, namely (1) small diameter non-peptide-expressing cells, (2) small-diameter peptide-expressing (calcitonin gene related peptide (CGRP), substance P) cells, and (3) medium-diameter peptide-expressing (CGRP) cells. The properties of these cell populations will be reviewed, with a special emphasis on the expression of the vanilloid (capsaicin) receptor VR1 and its regulation by growth factors. Cells in populations 1 and 2 express VR1, a nonselective channel that transduces certain nociceptive stimuli and that is crucial to the functioning of polymodal nociceptors. Cells in population 1 can be regulated by glial cell line derived neurotrophic factor (GDNF) and those in populations 2 and 3 by nerve growth factor (NGF). In vivo, DRG cells express a range of levels of VR1 expression and VR1 is downregulated after axotomy. However, treatment with NGF or GDNF can prevent this downregulation. In vitro, DRG cells also show a range of VR1 expression levels that is NGF and (or) GDNF dependent. Functional studies indicate that freshly dissociated cells also show differences in sensitivity to capsaicin. The significance of this is not known but may indicate a difference in the physiological role of cells in populations 1 and 2.

Afferent Pathways↗