Cloning and mapping MC1R to chromosome 16 in giant panda.
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Biomedical subjects
Publications and source records attributed to W Liu.
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Serial analysis of gene expression (SAGE) was used to examine the profile of expressed genes during embryonic development in the domesticated silkworm, Bombyx mori, after irradiation with Cobalt-60. A comparison of the SAGE sequence tags derived from irradiated embryos with those from normal embryos revealed 673 differentially expressed genes (P < 0.01 and at least three folds change). Of these, 292 genes were highly expressed in normal embryos and 381 genes were highly expressed in irradiated embryos. These results provide valuable information for understanding the mechanisms of radiation-induced changes in gene expression. In addition, it was noted that the generation of longer cDNA fragments from SAGE tags is an efficient way to identify genes, thereby facilitating the analysis of large numbers of unknown genes.
The protein components of the 2-nitrotoluene (2NT) and nitrobenzene dioxygenase enzyme systems from Acidovorax sp. strain JS42 and Comamonas sp. strain JS765, respectively, were purified and characterized. These enzymes catalyze the initial step in the degradation of 2-nitrotoluene and nitrobenzene. The identical shared reductase and ferredoxin components were monomers of 35 and 11.5 kDa, respectively. The reductase component contained 1.86 g-atoms iron, 2.01 g-atoms sulfur, and one molecule of flavin adenine dinucleotide per monomer. Spectral properties of the reductase indicated the presence of a plant-type [2Fe-2S] center and a flavin. The reductase catalyzed the reduction of cytochrome c, ferricyanide, and 2,6-dichlorophenol indophenol. The ferredoxin contained 2.20 g-atoms iron and 1.99 g-atoms sulfur per monomer and had spectral properties indicative of a Rieske [2Fe-2S] center. The ferredoxin component could be effectively replaced by the ferredoxin from the Pseudomonas sp. strain NCIB 9816-4 naphthalene dioxygenase system but not by that from the Burkholderia sp. strain LB400 biphenyl or Pseudomonas putida F1 toluene dioxygenase system. The oxygenases from the 2-nitrotoluene and nitrobenzene dioxygenase systems each had spectral properties indicating the presence of a Rieske [2Fe-2S] center, and the subunit composition of each oxygenase was an alpha(3)beta(3) hexamer. The apparent K(m) of 2-nitrotoluene dioxygenase for 2NT was 20 muM, and that for naphthalene was 121 muM. The specificity constants were 7.0 muM(-1) min(-1) for 2NT and 1.2 muM(-1) min(-1) for naphthalene, indicating that the enzyme is more efficient with 2NT as a substrate. Diffraction-quality crystals of the two oxygenases were obtained.
BACKGROUND: Darbepoetin alfa is an erythropoiesis-stimulating glycoprotein that functions by the same mechanism as recombinant human erythropoietin (rHuEPO), but has a three-fold longer serum half-life. Reduction in the frequency of darbepoetin alfa administration would be beneficial to patients with renal disease and their healthcare providers. This study evaluated the effect of extending the darbepoetin alfa dosing interval to once monthly in patients with chronic kidney disease (CKD) not receiving dialysis. METHODS: This study was a multicenter, open-label study of 97 patients with CKD not on dialysis. Patients receiving stable subcutaneous doses of darbepoetin alfa once every two weeks were converted to darbepoetin alfa once monthly for 29 weeks. The proportion of patients who successfully maintained hemoglobin concentrations between 10.0 and 12.0 g/dl and the mean darbepoetin alfa dose were evaluated. Safety measurements (e.g. adverse events, laboratory parameters, blood pressure) and seroreactivity were assessed. RESULTS: Hemoglobin concentration was maintained within the target range in 79% (95% confidence interval (CI) = 71% to 87%) of all patients receiving darbepoetin alfa and in 85% (95% Cl = 78% - 93%) of patients who completed the study period. The mean +/- standard deviation monthly darbepoetin alfa dose was similar between baseline (88.7 +/- 49.9 microg) and the evaluation period (86.6 +/- 78.8 microg). The safety profile for monthly darbepoetin alfa administration was comparable with that previously observed with more-frequent administration. CONCLUSION: Patients with CKD who are clinically stable on darbepoetin alfa administered once every two weeks can be safely and effectively converted to darbepoetin alfa administered once monthly.
INTRODUCTION: Etoricoxib is a second generation cyclooxygenase-2 inhibitor with a rapid-onset time and a long duration of action. It is ideal for providing pre-emptive analgesia for ambulatory surgeries. We hypothesised that pre-operative etoricoxib can decrease the use of fentanyl post-operatively, when compared with placebo in patients undergoing termination of pregnancy. We also compared their pain scores, time to discharge, side effects and satisfaction with analgesia post-operatively. METHODS: After approval by the hospital research ethics committee and receipt of informed written consent, we recruited 40 American Society of Anesthesiologists Physical Status Classification I and II patients scheduled for elective first trimester termination of pregnancy. Patients were randomly allocated to receive either oral etoricoxib 120 mg (Group E, n=20) or placebo tablet (Group P, n=20) pre-operatively. A blinded observer evaluated the post-operative pain scores, need for supplementary analgesia, side effects and satisfaction scores. Sample size was calculated (power of 0.8 and alpha=0.05) to detect a 20 percent difference in fentanyl usage. Amount of fentanyl used, pain scores and satisfaction scores were analysed using non-parametric tests. The incidence of side effects was analysed using chi-squared test. RESULTS: Etoricoxib 120 mg significantly decreased the amount of fentanyl required after termination of pregnancy compared to placebo (0 microg/patient, interquartile range [IQR] 0-25 versus 50 microg/patient, IQR 0-50, p-value is less than 0.05). Patients who received etoricoxib 120 mg also had significantly lower pain scores than the placebo group at time of discharge (8 +/- 11 versus 1 +/- 3, p-value is less than 0.05) and at six hours post operation (8 +/- 12 versus 0 +/- 0, p-value is less than 0.01). There was no difference in their side effects, and time to discharge and overall satisfaction were similar in both groups. CONCLUSION: Pre-operative administration of oral etoricoxib 120 mg decreased the use of fentanyl and pain scores after minor gynaecological surgery without significant side effects.
We report protocols and techniques to image and mechanically manipulate individual fibrin fibers, which are key structural components of blood clots. Using atomic force microscopy-based lateral force manipulations we determined the rupture force, FR, f fibrin fibers as a function of their diameter, D, in ambient conditions. As expected, the rupture force increases with increasing diameter; however, somewhat unexpectedly, it increases as FR approximately D1.30+/-0.06. Moreover, using a combined atomic force microscopy-fluorescence microscopy instrument, we determined the light intensity, I, of single fibers, that were formed with fluorescently labeled fibrinogen, as a function of their diameter, D. Similar to the force data, we found that the light intensity, and thus the number of molecules per cross section, increases as I approximately D1.25+/-0.11. Based on these findings we propose that fibrin fibers are fractals for which the number of molecules per cross section increases as about D1.3. This implies that the molecule density varies as rhoD approximately D -0.7, i.e., thinner fibers are denser than thicker fibers. Such a model would be consistent with the observation that fibrin fibers consist of 70-80% water and only 20-30% protein, which also suggests that fibrin fibers are very porous.
We report a new regime of single-surface multipactor that was observed during high-power testing of an 11.424-GHz alumina-based dielectric-loaded accelerating structure. Previous experimental observations of single-surface multipactor on a dielectric occurred in cases for which the rf electric field was tangential and the rf power flow was normal to the dielectric surface (such as on rf windows) and found that the fraction of power absorbed at saturation is approximately 1%, independent of the incident power. In this new regime, in which strong normal and tangential rf electric fields are present and the power flow is parallel to the surface, the fraction of power absorbed at saturation is an increasing function of the incident power, and more than half of the incident power can be absorbed. A simple model is presented to explain the experimental results.
Eph receptor tyrosine kinases (RTKs) and their membrane-bound ligands, the ephrins, are essential for embryonic vascular development. Recently, it has been demonstrated that overexpression of specific Ephs and ephrins is associated with a poor prognosis in human tumours. Our group has shown that EphB and the ephrin-B subfamilies are coexpressed in human colorectal cancer, and ephrin-B2 is expressed at higher levels in human colorectal cancer than in adjacent normal mucosa. As the Eph/ephrin system is involved in embryologic vasculogenesis and ephrin-B2 is expressed ubiquitously in all colon cancers studied in our laboratory, we hypothesised that overexpression of ephrin-B2 in colon cancer cells may induce tumour angiogenesis and increase tumour growth. To investigate this hypothesis, we stably transfected KM12L4 human colon cancer cells with ephrin-B2 to study its effect on tumour growth in vivo. We found that overexpression of ephrin-B2 markedly decreased tumour growth in a mouse xenograft model. Immunohistochemical staining showed that ephrin-B2 transfectants produced higher tumour microvessel density and lower tumour cell proliferation than did parental or vector-transfected control cells. Using (51)Cr-labelled red blood cells (RBCs) to determine the functional blood volume in tumours, we demonstrated that tumours from ephrin-B2-transfected cells had significantly decreased blood volume compared with tumours from parental or vector-transfected control cells. Evaluation of in vitro parameters of cell cycle mediators demonstrated no alteration in the cell cycle. Although ephrin-B2 transfection increased tumour vessel density, the decrease in blood perfusion suggests that these vessels may be 'dysfunctional'. We conclude that overexpression of ephrin-B2 suppresses tumour cell growth and vascular function in this in vivo colon cancer model.
OBJECTIVE: To compare the behavioral features and to investigate the neuroanatomic correlates of behavioral dysfunction in anatomically defined temporal and frontal variants of frontotemporal dementia (tvFTD and fvFTD). METHODS: Volumetric measurements of the frontal, anterior temporal, ventromedial frontal cortical (VMFC), and amygdala regions were made in 51 patients with FTD and 20 normal control subjects, as well as 22 patients with Alzheimer disease (AD) who were used as dementia controls. FTD patients were classified as fvFTD or tvFTD based on the relative degree of frontal and anterior temporal volume loss compared with controls. Behavioral symptoms, cerebral volumes, and the relationship between them were examined across groups. RESULTS: Both variants of FTD showed significant increases in rates of elation, disinhibition, and aberrant motor behavior compared with AD. The fvFTD group also showed more anxiety, apathy, and eating disorders, and tvFTD showed a higher prevalence of sleep disturbances than AD. The only behaviors that differed significantly between fvFTD and tvFTD were apathy, greater in fvFTD, and sleep disorders, more frequent in tvFTD. FvFTD was associated with greater frontal atrophy and tvFTD was associated with more temporal and amygdala atrophy compared with AD, but both groups showed significant atrophy in the VMFC compared with AD, which was not associated with VMFC atrophy. In FTD, the presence of many of the behavioral disorders was associated with decreased volume in right-hemispheric regions. CONCLUSION: FvFTD and tvFTD show many similarities in behavior, which appear to be associated with damage to right frontal and temporal structures.
The purpose of this study was to examine the effects of ZD6126, a novel vascular-targeting agent, on tumour growth and angiogenesis in an orthotopic model of gastric cancer. TMK-1 human gastric adenocarcinoma cells were injected into the gastric wall of nude mice. After the tumours were established (day 14), therapy was initiated. Mice (n=11-12/group) received (a). vehicle, (b). ZD6126 at 100 mg x kg day(-1) i.p. one time per week or (c) ZD6126 at 100 mg x kg day(-1) i.p. five times per week. Tumour mass, volume and the presence or absence of peritoneal carcinomatosis were determined at sacrifice on day 38. Tumours from each group were stained for markers of blood vessels, proliferation and apoptosis. To further define the time frame of the vascular-targeting effects of chronic therapy with ZD6126, TMK-1 cells were again injected into the gastric wall of mice in a second experiment. On day 14, a single i.p. injection of ZD6126 100 mg x kg(-1) mouse(-1) or vehicle was delivered. Groups of three mice each were killed and the tumours harvested at days 1, 3 and 5 post-ZD6126 injection. Tumours were processed and stained for endothelial and tumour cell apoptosis and proliferation. No overt toxicity was observed with ZD6126 therapy. ZD6126 led to a marked inhibition of tumour growth (82% decrease vs control (P<0.001)). ZD6126 also led to a significant decrease in the incidence of peritoneal carcinomatosis (10 out of 12 controls, vs one out of 12 ZD6126) (P<0.01). Histological analysis of tumours revealed large regions of central necrosis in the treated group, as well as a dramatic increase in tumour cell apoptosis (7.4-fold increase (P<0.001)), consistent with the vascular-targeting activity of ZD6126. Mice treated with ZD6126 demonstrated a 59% decrease in PCNA-positive cells (P< 0.02), indicating reduced tumour cell proliferation. In addition, tumours treated with ZD6126 exhibited a 40% decrease in microvessel density (P<0.05). Results from mice treated with a single injection of ZD6126 demonstrated the acute effects this agent has on the tumour vasculature. The ratio of endothelial cell apoptosis to endothelial cell proliferation was increased within 24 h of a single injection. In conclusion, ZD6126 significantly inhibited tumour growth and metastasis in an orthotopic model of human gastric adenocarcinoma, without detectable problematic adverse effects. These data suggest that ZD6126 may be worthy of investigation in the treatment of primary gastric adenocarcinoma.
Vascular endothelial growth factor (VEGF) is an intensively studied molecule that has significant potential, both in stimulating angiogenesis and as a target for antiangiogenic approaches. We utilised MCF-7 breast cancer cells transfected with either of two of the major VEGF isoforms, VEGF(121) or VEGF(165), or fibroblast growth factor-1 (FGF-1) to distinguish the effects of these factors on tumour growth, vascular function, and oxygen delivery. While each transfectant demonstrated substantially increased tumorigenicity and growth rate compared to vector controls, only VEGF(121) produced a combination of significantly reduced total and perfused vessel spacing, as well as a corresponding reduction in overall tumour hypoxia. Such pathophysiological effects are of potential importance, since antiangiogenic agents designed to block VEGF isoforms could in turn result in the development of therapeutically unfavourable environments. If antiangiogenic agents are also combined with conventional therapies such as irradiation or chemotherapy, microregional deficiencies in oxygenation could play a key role in ultimate therapeutic success.
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The cytotoxic and genotoxic effects of 1,2,4-trichlorobenzene (TCB), chlorobenzene (CB), and hexachlorobenzene (HCB) on root growth and DNA strand breakage damage of soybean nuclei in the test soil were studied using the comet assay. Results indicated that the root growth was significantly inhibited, and DNA strand breaks and the comet tail in the root tip nuclei were both induced after 48 h exposure with TCB concentrations of 50, 100, 200, 300 microg g(-1) in the soil. DNA strand breakage was more sensitive to the TCB than the root growth. There was a significant dose-response relationship between the TCB exposure and DNA strand breakage in the soybean nuclei. Thus it is possible for DNA strand breakage to be used as a biomarker of soybean exposed to TCB contamination. Significant cytotoxic threshold concentration of the TCB exposure on the root growth inhibition was determined as 61 microg g(-1) in the soil. The toxicity of 100-1,000 microg g(-1) CB and HCB to the soybean seedlings in the soil were not observed after 48 h or longer exposure.
A recently developed differential-aperture X-ray microscopy (DAXM) technique provides local structure and crystallographic orientation with submicron spatial resolution in three-dimensions; it further provides angular precision of approximately 0.01 degrees and local elastic strain with an accuracy of approximately 1.0 x 10(-4) using microbeams from high brilliance third generation synchrotron X-ray sources. DAXM is a powerful tool for inter- and intra-granular studies of lattice distortions and lattice rotations on mesoscopic length scales of tenths of microns to hundreds of microns that are largely above the range of traditional electron microscopy probes. Nondestructive, point-to-point, spatially resolved measurements of local lattice orientations in bulk materials provide direct information on geometrically necessary dislocation density distributions through measurements of the lattice curvature in plastically deformed materials. This paper reviews the DAXM measurement technique and discusses recent demonstrations of DAXM capabilities for measurements of microtexture, local elastic strain, and plastic deformation microstructure.
Several studies have demonstrated that lesion volumes computed from multiple planar slices through the region-of-interest (ROI) are more accurate than volumes estimated assuming simple shapes and incorporating single or orthogonal diameter estimates. However, manual delineation of boundaries on multiple planar 2-D images is tedious and labor-intensive. Automatic extraction of lesion boundaries is, therefore, attractive and imperative to remove subjectivity and reduce assessment time. This paper presents a semiautomated segmentation algorithm for thermal lesions on 3-D elastographic data to obtain both area and volume information. The semiautomated segmentation algorithm is based on thresholding and morphologic opening of both 2-D and 3-D elastographic data. Results obtained on 44 thermal lesions imaged in vitro using elastography were compared to manual delineation of both elastographic and pathology images. Results obtained using semiautomated segmentation demonstrate a close correspondence with manual delineation results. However, area and volume estimates obtained using both manual and semiautomated segmentation of lesions seen on elastograms slightly underestimate areas and volumes measured from pathology.
We evaluated the clinical response to low-dose etoposide in relapsed acute lymphoblastic leukemia (ALL). Of the 45 patients with ALL in first bone marrow relapse enrolled on the ALL R15 protocol, 44 had received epipodophyllotoxins during frontline therapy. In the first week of remission induction therapy, patients received etoposide (50 mg/m(2) per day) administered orally as a single agent once or twice daily. On Day 8, patients started to receive dexamethasone, vincristine, and L-asparaginase. Etoposide was administered until Day 22. Two courses of consolidation therapy were followed by continuation therapy or hematopoietic stem cell transplantation. After 7 days of single-agent etoposide treatment, peripheral blast cell counts (P=0.013) and percentages of bone marrow blasts (P=0.016) were significantly reduced. In all, 38 (84.4%) attained second remission. Only time to relapse was significantly associated with outcome (P=0.025): the 5-year event-free survival estimates (+/-se) were 52.0+/-9.6% for those with late relapse and 20.0+/-8.0% for those with early relapse. We conclude that low-dose etoposide administered orally has a cytoreductive effect in relapsed ALL.
Summary We report a case of protothecosis in an 18-year-old female student caused by Prototheca zopfii successfully treated with amikacin combined with tetracyclines. Zusammenfassung Es wird über eine Protothecose, verursacht durch Prototheca zopfii, bei einer 18-jährigen Studentin berichtet, die erfolgreich mit Amikacin in Kombination mit Tetracyclinen behandelt wurde.