Biomedical subjects
Publications and source records attributed to Feng Gao.
Lysozyme, a protein, has been found to be a new morphology-directing agent and a simple and mild bio-molecule assisted method has been proposed for the synthesis of single-crystal bismuth sulfide and oxide nanowires.
PURPOSE: To analyze the effects of preautografting treatment with rituximab (R) on stem-cell mobilization, post-transplantation complications, engraftment, disease-free survival, and overall survival in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Single-institution retrospective comparative outcome analysis in a cohort of 273 relapsed chemosensitive NHL patients of whom 127 (47%) received R pretransplantation. RESULTS: R was administered a median of 3 months before autologous transplantation. When compared to the nonrituximab group, R patients were older (56 v 50 years; P < .001), and had delays in post-transplantation platelets recovery (39 v 27 days; P = .001). Pretransplantation R did not affect stem-cell mobilization, post-transplantation early complications, duration of hospitalization, or mortality rates at days 30 and 100. In contrast to patients with low-grade NHL, both disease-free and overall survival rates were significantly better when R was included in the pretransplantation salvage therapy for patients with intermediate-grade NHL. CONCLUSION: In this large, single-center retrospective analysis, pretransplantation treatment with R was associated with improved survival in patients with intermediate-grade NHL, at the price, however, of a delay in platelet engraftment.
AIM: To characterize the histological types of esophageal and cardiac mucosa by endoscopic survey of a population in a high-risk area of esophageal cancer of China. METHODS: A selected cohort of residents in Cixian County during December 2001 and May 2002 was surveyed by using Lugol's staining, followed by computer-based statistical analysis of the data with SPSS 10.0 software. RESULTS: Histologically, the detection rates of squamous epithelial acanthosis, squamous epithelial atrophy, and basal cell hyperplasia in the esophagus were 1.9% (38/2,013), 0.1% (3/2,013) and 0.9% (18/2,013) respectively, and those of mild, moderate, and severe esophagitis were 34.9% (703/2,013), 1.6% (33/2,013) and 0.2% (2/2,013) respectively. Mild, moderate, and severe esophageal dysplasia were detected in 8.6% (172/2,013), 7.8% (157/2,013) and 2.6% (53/2,013) respectively in the selected population, whereas in situ carcinoma, intramucosal carcinoma, invasive squamous carcinoma of the esophagus in 2.5% (50/2,013), 0.2% (4/2,013) and 0.7% (14/2,013) respectively. The detection rates of non-atrophic gastritis and atrophic gastritis of the cardia were 36.3% (730/2,013) and 11.5% (232/2,013) respectively, with mild and severe dysplasia of the cardia detected in 2.5% (51/2,013) and 0.8% (17/2,013), respectively, in this population; the rates of intramucosal adenocarcinoma and invasive adenocarcinoma of the cardia were 0.1% (3/2,013) and 0.8% (17/2,013) respectively. The detection rate of esophageal cancer at early stage was 79.4% (54/68). The survey rate (ratio of examined population to expected population) was 73.8% (2,013/2,725). CONCLUSION: Histologic types of the esophageal and cardiac mucosa were characterized by endoscopic survey in a high-risk population of esophageal cancer, which may help the early detection and treatment of esophageal and cardiac cancers and dysplasia, and reduce the mortality of such malignancies.
Complex fluids comprising of surfactants with water and/or oil form a rich variety of dynamic self-assembled structures, ranging from spherical swollen micelles, viscous rod-like micelles, and bicontinuous microemulsions to ordered liquid crystalline phases. The wide range of practical and specialized applications of complex fluids has made them the subject of intense research for many decades. Here, we demonstrate for the first time how bicontinuous microemulsions containing equal masses of oil and sugar can be driven to the glassy state without phase separation at ambient temperatures by controlled desiccation of sugar-rich microemulsions. The robust nanostructure of these microemulsion glasses allows polymerization of hydrophobic liquid monomers within the interstices of the glassy microemulsion template without macroscopic phase separation. Yet after polymerization, the sugar and surfactant template can be easily removed by dissolution in water.
Loss of T cell homeostasis usually precedes the onset of AIDS. We hypothesized that rapid progressors may be transmitted with HIV-1 that is particularly able to perturb T cell homeostasis. To this end, we have tested two transmitted, syncytium-inducing (SI) viral isolates from a rapid progressor in two thymus models. One of the isolates (R3A) exhibited markedly rapid kinetics of replication and thymocyte depletion. These phenotypes mapped to the envelope, as a recombinant NL4-3 virus encoding the R3A envelope had similar phenotypes, even in the absence of nef. Notably, the viruses with high pathogenic activity in the thymus (R3A and NL4-R3A) did not show enhanced replication or cytopathicity in PHA-stimulated PBMCs. Furthermore, NL4-R3A did not enhance replication of the coinfected NL4-3 virus in the thymus, suggesting an intrinsic advantage of the R3A envelope. The R3A envelope showed higher entry activity in infecting human T cells and in depleting CD4+ thymocytes when expressed in trans. These data suggest that SI viruses with unique envelope functions which can overcome barriers to transmission may hasten disease progression by perturbing T cell homeostasis.
The surface chemistry of a model lubricant additive, tributyl phosphite (TBPi), is investigated on Fe3O4 in ultrahigh vacuum. A portion of the TBPi desorbs molecularly following adsorption at approximately 200 K, the remainder decomposing either by C-O bond scission to form 1-butyl species or by P-O bond cleavage to form butoxy species. Adsorbed butyl species either undergo beta-hydride elimination to desorb 1-butene or decompose to deposit carbon and hydrogen on the surface. The resulting adsorbed hydrogen reacts with the oxide to desorb water or with the butoxy species to form 1-butanol. Butoxy species are stable up to approximately 600 K at which temperature they also undergo beta-hydride elimination to form butanal and the released hydrogen reacts with other butoxy species to form 1-butanol. Only a small amount of carbon is deposited onto the surface following adsorption at approximately 200 K, which then desorbs as CO above approximately 750 K. Adsorbing TBPi at 300 K results in the deposition of more carbon and an Auger depth profile reveals that the carbon is located predominantly on the surface, while the phosphorus is rather uniformly distributed throughout the oxide film. This result is in accord with previous near-edge X-ray absorption fine structure measurements, which show the formation of phosphates and polyphosphate glasses. The resulting tribological film appears to be composed of a relatively hard polyphosphate glass formed by rapid diffusion of POx species into the oxide, covered by a low shear strength graphitic layer.
The effects on insulin secretion from INS-1 cells of varying concentrations of the sulfonylurea glyburide and the PDE3 inhibitor milrinone, separately and in combination were measured. Over a range of concentrations the effects of the two drugs in combination were more than additive. A response surface model was fit to the data and was found to describe the data well. From this model, it was apparent that a significant synergistic effect upon insulin secretion existed over a wide range of combinations of the two drugs.
The growth of ordered nanorods of mesoporous SBA-15 inside a porous alumina membrane has been achieved for the first time by a simple sol-gel method. The obtained SBA-15 nanorods themselves have ordered hexagonal mesochannels with a size of about 6 nm and have been arranged to form hexagonal arrays by the limitation of pores of the alumina membrane. The synthesized alumina membrane with mesoporous SBA-15 inside combines the advantages of porous alumina membranes and mesoporous SBA-15 and provides fine and vertical mesochannels, which may serve as a new and efficient mold and lead to extensive applications in nanodevice fabrication, biomacromolecule separations, etc.
Ten phosphatized specimens of a small (<180 micrometers) animal displaying clear bilaterian features have been recovered from the Doushantuo Formation, China, dating from 40 to 55 million years before the Cambrian. Seen in sections, this animal (Vernanimalcula guizhouena gen. et sp. nov.) had paired coeloms extending the length of the gut; paired external pits that could be sense organs; bilateral, anterior-posterior organization; a ventrally directed anterior mouth with thick walled pharynx; and a triploblastic structure. The structural complexity is that of an adult rather than a larval form. These fossils provide the first evidence confirming the phylogenetic inference that Bilateria arose well before the Cambrian.
1. Considerable evidence indicates that calcium plays a critical role in apoptosis. We have previously shown that benidipine, a vasodilatory calcium channel blocker, attenuates postischemia myocardial apoptosis. The present study was designed to determine the mechanisms by which benidipine exerts its antiapoptotic effect. 2. Adult male rats were subjected to 30 min of ischemia followed by 3 h of reperfusion. Rats were randomized to receive either vehicle or benidipine (10 microg x kg(-1), i.v.) 10 min before reperfusion. 3. Compared with rats receiving vehicle, those rats treated with benidipine had reduced postischemic myocardial apoptosis as evidenced by decreased TUNEL-positive staining (8.4+/-1.2 vs 15.3+/-1.3%, P<0.01) and caspase-3 activity (1.94+/-0.25 vs 3.43+/-0.29, P<0.01). 4. Benidipine treatment significantly reduced mitochondrial cytochrome c release and caspase-9 activation, but had no effect on caspase-8 activation, suggesting that benidipine exerts its antiapoptotic effect by inhibiting the mitochondrial-mediated, but not death receptor-mediated, apoptotic pathway. 4. 5. Benidipine treatment not only increased the maximal activity of ERK1/2 at 10 min after reperfusion, but also prolonged the duration of ERK1/2 activation. Benidipine treatment had no significant effect on other apoptotic regulating molecules, such as p38 MAPK. 6. Taken together, our present study demonstrated for the first time the differential regulation of a calcium channel blocker. Benidipine tilted the balance between ERK1/2 and p38 MAPK toward an antiapoptotic state, decreased mitochondrial cytochrome c release, reduced caspase-9 activation, and attenuated subsequent caspase-3 activation and postischemic myocardial apoptosis.
AIM: To investigate the significance of c-kit gene mutation in gastrointestinal stromal tumors (GIST). METHODS: Fifty two cases of GIST and 28 cases of other tumors were examined. DNA samples were extracted from paraffin sections and fresh blocks. Exons 11, 9 and 13 of the c-kit gene were amplified by PCR and sequenced. RESULTS: Mutations of exon 11 were found in 14 of 25 malignant GISTs (56%), mutations of exon 11 of the c-kit gene were revealed in 2 of 19 borderline GISTs (10.5%), and no mutation was found in benign tumors. The mutation rate showed significant difference (chi2=14.39, P<0.01) between malignant and benign GISTs. Most of mutations consisted of the in-frame deletion or replication from 3 to 48 bp in heterozygous and homozygous fashions, None of the mutations disrupted the downstream reading frame of the gene. Point mutations and frame deletions were most frequently observed at codons 550-560, but duplications were most concentrated at codons 570-585. No mutations of exons 9 and 13 were revealed in GISTs, Neither c-kit gene expression nor gene mutations were found in 3 leiomyomas, 8 leiomyosarcomas, 2 schwannomas, 2 malignant peripheral nerve sheath tumors, 2 intra-abdominal fibromatoses, 2 malignant fibrous histiocytomas and 9 adenocarcinomas. CONCLUSION: C-kit gene mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs and can help to differentiate GISTs from other mesenchymal tumors of gastrointestinal tract, such as smooth muscle tumors, schwannomas, etc.
One of the primary applications of diffuse optical imaging is to localize and quantify the changes in the cerebral oxygenation during functional brain activation. Up to now, data from an optical imager are simply presented as a two-dimensional (2D) topographic map using the modified Beer-Lambert law that assumes homogeneous optical properties beneath each optode. Due to the highly heterogeneous nature of the optical properties in the brain, the assumption is evidently invalid, leading to both low spatial resolution and inaccurate quantification in the assessment of haemodynamic changes. To cope with these difficulties, we propose a nonlinear tomographic image reconstruction algorithm for a two-layered slab geometry that uses time-resolved reflected light. The algorithm is based on the previously developed generalized pulse spectrum technique, and implemented within a semi-three-dimensional (3D) framework to conform to the topographic visualization and to reduce computational load. We demonstrate the advantages of the algorithm in quantifying simulated changes in haemoglobin concentrations and investigate its robustness to the uncertainties in the cortical structure and optical properties, as well as the effects of random noises on image quality. The methodology is also validated by experiments using a solid layered phantom.
BACKGROUND: Functional genomics studies are yielding information about regulatory processes in the cell at an unprecedented scale. In the yeast S. cerevisiae, DNA microarrays have not only been used to measure the mRNA abundance for all genes under a variety of conditions but also to determine the occupancy of all promoter regions by a large number of transcription factors. The challenge is to extract useful information about the global regulatory network from these data. RESULTS: We present MA-Networker, an algorithm that combines microarray data for mRNA expression and transcription factor occupancy to define the regulatory network of the cell. Multivariate regression analysis is used to infer the activity of each transcription factor, and the correlation across different conditions between this activity and the mRNA expression of a gene is interpreted as regulatory coupling strength. Applying our method to S. cerevisiae, we find that, on average, 58% of the genes whose promoter region is bound by a transcription factor are true regulatory targets. These results are validated by an analysis of enrichment for functional annotation, response for transcription factor deletion, and over-representation of cis-regulatory motifs. We are able to assign directionality to transcription factors that control divergently transcribed genes sharing the same promoter region. Finally, we identify an intrinsic limitation of transcription factor deletion experiments related to the combinatorial nature of transcriptional control, to which our approach provides an alternative. CONCLUSION: Our reliable classification of ChIP positives into functional and non-functional TF targets based on their expression pattern across a wide range of conditions provides a starting point for identifying the unknown sequence features in non-coding DNA that directly or indirectly determine the context dependence of transcription factor action. Complete analysis results are available for browsing or download at http://bussemaker.bio.columbia.edu/papers/MA-Networker/.
We present an extension and confirmation of our previously published method (J. Med. Chem. 2002, 45, 2867-2876) for the prediction of volume of distribution (VD) in humans for neutral and basic compounds. It is based on two experimentally determined physicochemical parameters, ElogD(7.4) and f(i(7.4)), the latter being the fraction of compound ionized at pH 7.4, and on the fraction of free drug in plasma (fu). By regressing the fraction unbound in tissues, fut, vs the above parameters, we demonstrate the ruggedness of the method in predicting VD through the Oie-Tozer equation, via the use of several testing approaches. A comparison is also presented between several methods based on animal pharmacokinetic data, using the same set of proprietary compounds, and it lends further support for the use of this method, as opposed to methods that require the gathering of pharmacokinetic data in laboratory animals. The reduction in the use of animals and the overall faster and cheaper accessibility of the parameters used make this method highly attractive for prospectively predicting the VD of new chemical entities in humans.
MOTIVATION: Since the early 1980s of the twentieth century, there has been great progress in the development of computational gene-finding algorithms. Some problems, however, have not yet been solved currently. Recognizing short genes in prokaryotes and short exons in eukaryotes is one of such problems. The paper is devoted to assessing various algorithms, including those currently available and the new ones proposed here, in order to find the best algorithm to solve the issue. RESULTS: The databases consisting of phase-specific coding and non-coding sequences of human genes with length of 192, 162, 129, 108, 87, 63 and 42 bp, respectively, have been established. Based on the databases and a standard benchmark, 19 algorithms were evaluated, which include the methods of Markov models with orders of 1 through 5, codon usage, hexamer usage, codon preference, amino acid usage, codon prototype, Fourier transform and 8 Z curve methods with various numbers of parameters. Consequently, the Z curve methods with 69 and 189 parameters are the best ones among them, based on the databases constructed here. In addition to the highest recognition accuracy confirmed by 10-fold cross-validation tests, the Z curve methods are much simpler computationally than the second best one, the fifth-order Markov chain model, in which 12 288 parameters are used. We hope that the Z curve methods presented in this paper would be beneficial to the further development of gene-finding algorithms. AVAILABILITY: The programs of various Z curve methods are available on request.
The PTB domain of mouse dok1 fusion protein has been overexpressed in Escherichia coli and crystallized in a form suitable for X-ray crystallographic study. Crystals have been obtained using the vapour-diffusion method and belong to space group P2(1)2(1)2(1). X-ray diffraction data were collected in-house to 2.5 A resolution. A selenomethionine (SeMet) dok1 PTB fusion-protein derivative was expressed using the same expression system, purified in a reductive environment and crystals were obtained under similar conditions. Subsequently, three different wavelength data sets from the derivative crystal were collected to 2.5 A resolution at SPring-8.
Whereas the major folate transporter, the reduced folate carrier (RFC), has a physiological pH optimum, transport activities for folates and antifolates have been detected with low pH optima. Because the interstitial pH in solid tumors is generally acidic, the mechanisms by which antifolates are transported at low pH could be an important determinant of drug activity under these conditions. The current study quantitated the low pH methotrexate (MTX) transport activity in human solid tumor cell lines from the National Cancer Institute tumor panel and other sources. MTX influx at pH 5.5 was equal to, or greater than, influx at pH 7.4 in 29 of 32 cell lines. To assess the role of RFC in transport at low pH in one of these cell lines, a HeLa clonal line (R5) was selected for MTX resistance due to a genomic deletion of the carrier gene. MTX influx was depressed by 70% in R5 versus wild-type HeLa cells at pH 7.4. At pH 6.5, influx in these two lines was similar; as the pH was decreased to 5.5 influx increased in both cell lines. Similarly, whereas net MTX uptake over 1 h was markedly decreased in R5 cells at pH 7.4, net uptake in HeLa and R5 cells was comparable at pH 6.5. Also, as compared with MCF7 breast cancer cells, MTX uptake was markedly decreased at pH 7.4, but only minimally at pH 6.5, in the MDA-MB-231 human breast cancer cell line that lacks RFC expression. When grown with folic acid (2 micro M) at pH 7.4, the IC(50) for MTX was 14-fold higher in R5 as compared with wild-type HeLa cells; the difference was only 4-fold when cells when grown at pH 6.9; the IC(50)s were identical at this pH when the medium folate was 25 nM 5-formyltetrahydrofolate. These data demonstrate that transport activity at low pH is prevalent in human solid tumors, is RFC-independent in R5 cells and MDA-MB-231 breast cancer cells, and can preserve MTX activity in the absence of RFC at an acidic pH relevant to solid tumors in vivo.
A biomolecule-assisted simple technique has been developed for the spontaneous ordering of the Bi2S3 nanorods into snowflakelike superstructures in high yield under microwave-hydrothermal conditions. In this method, glutathione (GSH) is used as both an assembling agent and a sulfur source. By controlling the molar ratio between bismuth nitrate and glutathione as well as the synthetic temperature, several kinds of Bi2S3 one-dimensional nanomaterials such as snowflakelike structures, nanowires constructed of particles, short nanorods, and fine and long nanowires have been controllably synthesized.