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Biomedical subjects

W Li

Publications and source records attributed to W Li.

At least 397 records · Page 22Linked to original sources
PubMed2000

MR angiography of the vascular tree from the aorta to the foot: combining two-dimensional time-of-flight and three-dimensional contrast-enhanced imaging.

A composite approach for magnetic resonance (MR) angiography of the lower extremities is described. Thirty patients were studied with this approach, which combined a two-dimensional (2D) time-of-flight (TOF) technique with a 3D contrast-enhanced technique. A head/neck coil was selected for imaging mid-foot to upper calf, and the body coil was used for the remainder of the peripheral vascular tree. Acquired data were transferred to a workstation for postprocessing. The final maximum intensity projection images, which display the entire vascular anatomy from aortic bifurcation to foot, were created using a 1024 x 1024 matrix. Very small arteries can be differentiated in critical regions like the calf and foot. Compared with TOF-2D alone, the scan time was reduced. This method offers another option for MR angiography of the lower extremities. J. Magn. Reson. Imaging 2000;12:884-889.

Adult↗
PubMed2000

Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice.

Interleukin-6 null (IL-6-/-) mice have impaired liver regeneration and increased liver necrosis following partial hepatectomy that is corrected with IL-6 treatment. Following acute carbon tetrachloride (CCl(4)) treatment, we found that IL-6-/- mice developed increased hepatocellular injury and defective regeneration with significant blunting of signal transducer-and-activator of transcription protein 3 (STAT3) and nuclear factor-kappaB (NF-kappaB) activation and reduced hepatocyte DNA synthetic and mitotic responses. After CCl(4) treatment, unlike partial hepatectomy, increased hepatocyte apoptosis was noted in IL-6-/- livers. Pretreatment with IL-6 before CCl(4) reduced acute CCl(4) injury and apoptosis and accelerated regeneration in both IL-6+/+ and -/- livers. Repetitive doses of CCl(4) in the presence or absence of phenobarbital resulted in increased injury and fibrosis in IL-6 -/- compared with +/+ livers. After acute and chronic injury, IL-6-/- livers showed the protracted presence of alpha-smooth muscle actin associated with activated stellate cells, indicating a disturbed response in wound healing that progressed to fibrosis. These data provide evidence for an important role for IL-6 in reducing CCl(4)-induced acute and chronic liver injury and fibrosis.

Actins↗
PubMed2000

Quaternary organization of the Staphylothermus marinus phosphoenolpyruvate synthase: angular reconstitution from cryoelectron micrographs with molecular modeling.

Digital electron images of frozen-hydrated preparations of the 2.25-MDa Staphylothermus marinus phosphoenolpyruvate synthase (EC 2.7.9.2) have been analyzed by single-particle classification and averaging and iterative quaternion-based angular reconstitution. Contrast transfer function correction of micrographs obtained at different defocus values was used to improve the informational quality of the projection averages. Three-dimensional reconstructions were obtained to roughly 3-nm spatial resolution, in which the 24 identical subunits were arranged to form an octahedral complex, although the amino-terminal nucleotide-binding domain was not resolved. An atomic model of the subunit was generated by homology modeling using as the reference the known X-ray crystallographic structure of the related enzyme pyruvate orthophosphate dikinase (EC 2.7.9.1) from Clostridium symbiosum (Protein Data Bank entry 1DIK). The S. marinus protein could be arranged into an assembly of 12 homodimers to match the three-dimensional reconstruction in terms of shape and size of the homodimers, as well as overall shape and size of the complex. The quaternary model indicated that active sites of three monomers were localized around cavities (or putative channels) centered at the threefold axes of rotational symmetry and that carboxyl-terminal alpha-helical segments of four monomers were localized at the fourfold axes of rotational symmetry where they could facilitate interdimer interaction. The quaternary arrangement also indicated numerous potential hydrophobic and electrostatic interactions at the interdimer interfaces that could contribute further to structural stability.

Bacterial Proteins↗
PubMed2000

5'-UTR structural organization, transcript expression, and mutational analysis of the human Rab geranylgeranyl transferase alpha-subunit (RABGGTA) gene.

Hermansky-Pudlak syndrome (HPS) is a recessively inherited disease with dysfunction of several related subcellular organelles including platelet-dense granules, melanosomes, and lysosomes. Our recent identification of the mutation in murine Rab geranylgeranyl transferase alpha-subunit gene (Rabggta) in one mouse model of HPS, the gunmetal mouse, suggested that human patients with similar phenotypes might have mutations in the human orthologous RABGGTA gene. This prompted reanalysis of the 5'-untranslated structure of the human RABGGTA gene in normal individuals and in patients with deficiencies of platelet-dense granules (alphadelta-SPD), alpha granules (alpha-SPD or gray platelet syndrome, GPS) or alpha plus dense granules (alphadelta-SPD). We report the complete sequence of intron alpha of RABGGTA and demonstrate that exon alpha is immediately upstream of intron alpha. The exon/intron structural organization of the 5'-untranslated region (UTR) of human RABGGTA was found to be similar to that of the mouse Rabggta gene. However, exons alpha and introns alpha are not homologous between mouse and human. Features of the 5'-UTR of RABGGTA suggest it is a housekeeping gene. While obvious disease-causing mutations of human RABGGTA were not found in our existing SPD patients by sequencing its entire coding region, several polymorphisms of RABGGTA including a putative cryptic splicing mutation in intron 4 were identified. Knowledge of the 5'-UTR structure of RABGGTA and its common polymorphisms will be useful for mutation screening or linkage analysis in patients with albinism, thrombocytopenia, or platelet SPD.

5' Untranslated Regions↗
PubMed2000

Prolongation of cardiac allograft survival using dendritic cells treated with NF-kB decoy oligodeoxyribonucleotides.

Dendritic cells (DC) classically promote immune responses but can be manipulated to induce antigen-specific hyporesponsiveness in vitro. The expression of costimulatory molecules (CD40, CD86, CD80) at the DC cell surface correlates with their capacity to induce or suppress immune responses. Expression of these molecules is associated with NF-kB-dependent transcription of their genes. DC tolerogenicity has been associated with impaired NF-kB-dependent transcription of costimulatory genes as well as NF-kB translocation to the nucleus. In this report, we demonstrate that double-stranded oligodeoxyribonucleotides containing binding sites for NF-kB (NF-kB ODN) are efficiently incorporated by bone marrow-derived DC and specifically inhibit NF-kB-dependent transcription of a reporter gene. Moreover, exposure of DC to the oligonucleotide decoys inhibited lipopolysaccharide (LPS)-induced nitric oxide production, a marker of DC maturation. Treatment of bone marrow-derived DC progenitors with NF-kB ODN selectively suppressed the cell-surface expression of costimulatory molecules without interfering with MHC class I or class II expression. Furthermore, NF-kB ODN DC induced allogeneic donor-specific hyporesponsiveness in mixed leukocyte cultures, and this was associated with inhibition of Th1-type cytokine production. Finally, infusion of NF-kB ODN-modified bone marrow-derived DC into allogeneic recipients prior to heart transplantation resulted in significant prolongation of allograft survival in the absence of immunosuppression. Specific interference with NF-kB and other transcriptional pathways involved in immune stimulation in DC using ODN decoy approaches could be one means to promote tolerance induction in organ transplantation.

Animals↗
PubMed2000

Pre-clinical experimental studies of indomethacin-releasing copper intrauterine device.

Effects of two types of intrauterine device (IUD) on the prostaglandins and endothelin (ET) in uterus and on the endometrial morphology in rats and rabbits, and Cu2+ releasing amounts of both IUDs in vitro were observed. The results showed that the inhibiting action of the indomethacin-releasing copper IUD (FICu-IUD) on the PGI2 was stronger than that on the TXA2, the ratio of 6-keto-PGF1 alpha/TXB2 was reduced with the increase of the doses. There were significant differences between the groups. The FICu-IUD could inhibit the rising of the ET level and lighten the endometrial impairment caused by the FCu-IUD, and promote copper ion release. It was suggested that indomethacin released by FICu-IUD could effectively reduce abnormal uterine bleeding.

Animals↗
PubMed2000

Cancer vaccines: single-epitope anti-idiotype vaccine versus multiple-epitope antigen vaccine.

In this study, we compared the immunogenicity and tumor-protective activity of anti-idiotypic antibodies mimicking a single tumor-associated epitope and tumor-associated antigen expressing multiple potentially immunogenic epitopes. We focused our study on the colorectal-carcinoma(CRC)-associated antigen GA733 (also known as CO17-1A/KS1-4/KSA/EpCAM). Monoclonal anti-idiotypic antibody (Ab2) BR3E4 was produced against murine anti-CRC mAb CO17-1A (Ab1) in rats. Full-length native GA733 protein was isolated from human tumor cells, and the extracellular domain protein (GA733-2E) was isolated from supernatants of recombinant baculovirus-infected insect cells by immunoaffinity chromatography. The immunomodulatory activity of the Ab2 was compared with that of the antigen, both in rabbits and in mice. Mice, like humans but not rabbits, express a GA733 antigen homologue on some of their normal tissues. Thus, these in vivo models allow the comparison of the immunogenicity of Ab2 and antigen in the presence (mice) and absence (rabbits) of normal tissue expression and immunological tolerance of the GA733 antigen homologue. In rabbits, aluminum-hydroxide(alum)-precipitated native GA733 antigen was superior to alum-precipitated Ab2 in inducing specific humoral immunity. In mice, alum-precipitated recombinant GA733-2E antigen, but not alum-precipitated Ab2, induced specific humoral immunity. However, when the Ab2 was administered to mice in Freund's complete adjuvant, specific humoral immune responses were elicited. Ab2 in complete Freund's adjuvant and GA733-2E in alum were compared for their capacity to induce antigen-specific cellular immunity in mice. Whereas lymphoproliferative responses were obtained with the recombinant antigen only, delayed-type hypersensitivity responses were obtained with both recombinant antigen and Ab2, although these responses were lower than after antigen immunization. The recombinant antigen in alum did not protect mice against challenge with antigen-positive syngeneic murine CRC cells. Similar studies with Ab2 BR3E4 mimicking the CO17-1A epitope were not possible because the tumor cells do not express this epitope after transfection with the human GA733-2 cDNA. However, similar studies with Ab2 mimicking the epitope defined by mAb GA733, which is expressed by the transfected tumor cells, indicated a lack of tumor-protective activity of this Ab2. In contrast, the full-length antigen expressed by recombinant adenovirus inhibited the growth of established tumors in mice. In conclusion, soluble antigen is a more potent modulator of humoral and cellular immune responses than Ab2, both administered in adjuvant. However, for induction of protective immunity, the immunogenicity of the antigen must be further enhanced, e.g., by expression of the antigen in a viral vector.

Adenocarcinoma↗
PubMed2000

Flavonoid constituents from Glycyrrhiza glabra hairy root cultures.

An unusual biflavonoid named licoagrodin was isolated from the hairy root cultures of Glycyrrhiza glabra (Leguminosae) along with three prenylated retrochalcones, licoagrochalcones B, C, D, a prenylated aurone, licoagroaurone and four known prenylated flavonoids, licochalcone C, kanzonol Y, glyinflanin B and glycyrdione A. From the glycosidic fraction, a isoflavone glycoside, licoagroside A, and a maltol glycoside, licoagroside B were isolated together with four known isoflavone glycosides, two flavone C-glycosides, and three other glycosides. Their structures were elucidated on the basis of spectroscopic evidence.

Chalcones↗
PubMed2000

Flow estimation using an intravascular imaging catheter.

Coronary flow assessment can be useful for determining the hemodynamic severity of a stenosis and to evaluate the outcome of interventional therapy. We developed a method for measuring the transverse flow through the imaging plane of an intravascular ultrasound (IVUS) catheter. This possibility has raised great clinical interest since it permits simultaneous assessment of vessel geometry and function with the same device. Furthermore, it should give more accurate information than combination devices because lumen diameter and velocity are determined at the same location. Flow velocity is estimated based on decorrelation estimation from sequences of radiofrequency (RF) traces acquired at nearly the same position. Signal gating yields a local estimate of the velocity. Integrating the local velocity over the lumen gives the quantitative flow. This principle has been calibrated and tested through computer modeling, in vitro experiments using a flow phantom and in vivo experiments in a porcine animal model, and validated against a Doppler element containing guide wire (Flowire) in humans. Originally the method was developed and tested for a rotating single element device. Currently the method is being developed for an array system. The great advantage of an array over the single element approach would be that the transducer has no intrinsic motion. This intrinsic motion sets a minimal threshold in the detectable velocity components. Although the principle is the same, the method needs some adaptation through the inherent different beamforming of the transducer. In this paper various aspects of the development of IVUS flow are reviewed.

Animals↗
PubMed2000

Independent mechanisms produce visually perceived eye level (VPEL) and perceived visual pitch (PVP).

Two aspects of the perception of extrapersonal space undergo systematic changes with variations in the pitch of the visual environment: (1) the physical elevation perceived to correspond to eye level (VPEL); and (2) the perception of the pitch of the visual environment (PVP). Thus, one might assume that both discriminations are controlled by a common mechanism utilizing visual information from the pitched surface. In fact this assumption has been made frequently, and - in different forms - underlies three substantial but very different historical streams in the literature. A quantitative theoretical development shows that two of these streams, although derived from very different viewpoints and appearing very different themselves (it is assumed that the basis for both PVP and VPEL is information about the pitch of the visual field in one, and information about the location of the subject's eye level within the visual field in the other), make identical predictions: each requires that the weighted sum of PVP and VPEL equal the magnitude of physical pitch and that the weighted sum of their first derivatives equal a constant. The third stream, which assumes that an internal representation of the visual field gives rise to both PVP and VPEL, requires that a weighted difference of PVP and VPEL be proportional to physical pitch and that the weighted difference of their derivatives equal a constant. In an experiment designed to examine the relation between VPEL and PVP, psychophysical measurements of VPEL and PVP were made on 20 subjects across a range of pitches from -30 degrees to +20 degrees. Contrary to the predictions from all three interpretations, we find no significant correlation between the two perceptual variables when the influence of pitch itself is removed, despite the fact that VPEL and PVP each increased systematically with increasing visual field pitch. The results not only rule out the specific predictions derived from all three historical streams, they also rule out any theoretical viewpoint that requires control of both perceptual responses by a single mechanism. The statistical independence between VPEL and PVP implies independence between the mechanisms that give rise to them. The correlation observed here and elsewhere between individual PVP and VPEL settings when the influence of the systematic variation of pitch is not eliminated is a consequence of the way in which variations in the two perceptions are generated experimentally, and not on an identity of the mechanisms mediating the generation of the two perceptual variables themselves.

Adolescent↗
PubMed2000

Linear combinations of signals from two lines of the same or different orientations.

Whereas the influence on the elevation of visually perceived eye level (VPEL) by two bilaterally symmetric, long (64 degrees-long), pitched-from-vertical lines in total darkness is only a little more than the average of the VPELs of the two lines measured separately [Matin & Li (1999). Vision Research, 39, 307-329], in the present experiments with 49 2-line combinations of seven orientations (-30 degrees to +30 degrees pitch), the VPEL for two short (12 degrees-long) lines equals the additive sum of the separate influences of the two lines. With one line at a fixed orientation, the slope of the VPEL-versus-pitch function with the second line variable equals the slope of the function when viewing one line alone, but is shifted from the 1-line-alone function by the magnitude of the VPEL of the fixed line. Both the near-averaging and the additivity are summarized by V(theta l, theta r) = k1 + k2 [V(theta l) + V(theta r)], where V(theta l) and V(theta r) are the 1-line VPELs for the pitches of the left and right lines, and V(theta l, theta r) is the 2-line VPEL; the slope constant k2 equals 0.5 for averaging, and 1.00 for simple additivity of the separate visual influences. Measured values are k2 = 0.99 and k2 = 0.61 for short and long lines, respectively. The shift of slope constant is determined by line length and not orientation: parallel and nonparallel lines follow the same rules of combination for short lines as they do for long lines. As for long lines, the short-line results are clear in showing that the visual influence on VPEL is controlled by an opponent-process mechanism. Although 'saturation-near-an-asymptote' along with opponency are required components of the interpretation for the basis of the combination of lines of different orientations and different lengths, they are not by themselves sufficient: All results conform to a neurophysiologically-based model [Matin and Li (1997b). Society for Neuroscience, 23, 175; Matin & Li, under review] that parallel processes feedforward signals from orientation-selective neural units in V1; the model accounts for the shift from additivity to near-averaging with increase in line length as a consequence of the increased contribution of shunting.

Humans↗
PubMed2000

QRS width in right bundle branch block. Accuracy and reproducibility of manual measurement.

BACKGROUND: The QRS prolongation and its relation to malignant ventricular arrhythmias are topics of interest. Controversies exist about the methodology of measuring the QRS. The aim of this study was to assess the accuracy and reproducibility of manual measurement of the QRS in standard electrocardiograms in patients with right bundle branch block and compare results with computer reading. METHODS AND RESULTS: Five experienced cardiologists at different levels of training were required to measure QRS duration in 30 electrocardiograms with different degrees of right bundle branch block collected from 24 randomly selected patients who had had radical repairs of tetralogy of Fallot. In each set of electrocardiograms there were six records which had been duplicated. The observers were neither told the purpose of the study nor how the electrocardiograms had been obtained, nor informed that some of the electrocardiograms were duplicates. Photocopies were identified by number, covering the patient's name and computerised measurement. Significant differences were found in the measurement of QRS in the same ECG calculated twice by the same observer (with an absolute variation up to 50 ms), within different observers (P=0.037) and measured manually or by computer (P=0.019). The width of the QRS did not influence the measurements as the biggest intra-observer variation (50 ms) was observed for relatively wide complex (median value between the two measurements 155 ms) and the biggest inter-observer (60 ms) for narrow complex (median value between the five measurements 110 ms). The QRS morphology appeared to influence the measurements, as the intra- and inter-observer variations were more consistent in the presence of obvious notching, slurrings and terminal slow vectors. CONCLUSIONS: Measurement of QRS is difficult, can be operator dependent and influenced by the presence of conduction abnormalities which reduce its accuracy and reproducibility.

Bundle-Branch Block↗
PubMed2000

Increased expression of apoptosis-linked gene 2 (ALG2) in the rat brain after temporary focal cerebral ischemia.

Calcium is an important mediator of programmed cell death induced by transient cerebral ischemia, and calcium-binding proteins have been implicated in calcium-regulated signal transduction. Apoptosis-linked gene 2 is a calcium-binding protein required for cell death induced by different apoptotic stimuli. By Western blot analysis, we found that apoptosis-linked gene 2 protein was expressed in normal brains, and that expression increased in ischemic brains after 20 or 90 min of transient focal cerebral ischemia. Immunocytochemistry showed increased apoptosis-linked gene 2 protein expression in frontal cortex, a region where neurons underwent ischemic stress but still survived, after 20 or 90 min of focal cerebral ischemia. Apoptosis-linked gene 2 protein was also up-regulated in the ischemic border-zone of parietal cortex 24h after 20 min of focal ischemia, and was remarkably over-expressed in the caudate-putamen and parietal cortex, (where cells are destined to die) 24h after 90 min of ischemia. The expression pattern of apoptosis-linked gene 2 protein was similar to that of deoxyribonucleic acid damage detected by Klenow labeling assay. Our results suggest that apoptosis-linked gene 2 may be involved in the regulation of cell death after transient focal cerebral ischemia.

Animals↗
PubMed2000

Semi-automated 96-well liquid-liquid extraction for quantitation of drugs in biological fluids.

A semi-automated liquid-liquid extraction (LLE) technique for biological fluid sample preparation was introduced for the quantitation of four drugs in rat plasma. All liquid transferring during the sample preparation was automated using a Tomtec Quadra 96 Model 320 liquid handling robot, which processed up to 96 samples in parallel. The samples were either in 96-deep-well plate or tube-rack format. One plate of samples can be prepared in approximately 1.5 h, and the 96-well plate is directly compatible with the autosampler of an LC/MS system. Selection of organic solvents and recoveries are discussed. Also, precision, relative error, linearity and quantitation of the semi automated LLE method are estimated for four example drugs using LC/MS/MS with a multiple reaction monitoring (MRM) approach. The applicability of this method and future directions are evaluated.

Algorithms↗
PubMed2000

Parallel electrosynthesis of alpha-alkoxycarbamates, alpha-alkoxyamides, and alpha-alkoxysulfonamides using the spatially addressable electrolysis platform (SAEP)

The spatially addressable electrolysis platform (SAEP) has been designed and constructed. It is demonstrated that the advantages of electrochemistry can be readily adapted to combinatorial chemistry and parallel synthesis formats. Parallel electrosynthesis of alpha-alkoxycarbamates, alpha-alkoxyamides, and alpha-alkoxysulfonamides via anodic oxidation of carbamates, amides, and sulfonamides, respectively, highlights the main features of the SAEP.

Journal Article↗