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Biomedical subjects

W Li

Publications and source records attributed to W Li.

At least 991 records · Page 55Linked to original sources
PubMed1996

Synthesis of chemoreversible prodrugs of ara-C with variable time-release profiles. Biological evaluation of their apoptotic activity.

N4-Dipeptidyl slow-release forms of the anticancer drug ara-C were prepared by acylation of the lithiated nucleotide with 4,4-dialkyloxazolinones. An azapeptide prodrug of ara-C was obtained by condensation of an amino acid hydrazide with an activated nucleotide urea. The use of unnatural amino acid residues at N4 prevented nonspecific proteolytic cleavage in biological medium. Ara-C prodrugs 10, 15, 17, and 19 released active drug with half-lives from a few minutes to several days, respectively. Activation via intramolecular N4-deacylation did not require enzymatic intervention but was strictly dependent on the structure of the peptide chain. The prodrugs 10, 15, and 17 produced similar growth inhibition as ara-C in cultured murine leukemia cells while the azapeptide prodrug 19 was less potent reflecting the slow release of active drug with this compound. All four prodrugs retained the ability to induce apoptosis in human HL-60 leukemia cells with kinetics dictated by the rate of intramolecular N4-deacylation. This the first demonstration for the control of apoptotic cell death by the modulation of drug release from prodrugs.

Animals↗
PubMed1996

Morphometric analysis in three-dimensional intracoronary ultrasound: an in vitro and in vivo study performed with a novel system for the contour detection of lumen and plaque.

Currently, automated systems for quantitative analysis by intracoronary ultrasound (ICUS) are restricted to the detection of the lumen. The aim of this study was to determine the accuracy and reproducibility of a new semiautomated contour detection method, providing off-line identification of the intimal leading edge and external contour of the vessel in three-dimensional ICUS. The system allows cross-sectional and volumetric quantification of lumen and of plaque. It applies a minimum-cost algorithm and the concept that edge points derived from previously detected longitudinal contours guide and facilitate the contour detection in the cross-sectional images. A tubular phantom with segments of various luminal dimensions was examined in vitro during five catheter pull-backs (1 mm/sec), and subsequently 20 diseased human coronary arteries were studied in vivo with 2.9F 30 MHz mechanical ultrasound catheters (200 images per 20 mm segment). The ICUS measurements of phantom lumen area and volume revealed a high correlation with the true phantom areas and volumes (r = 0.99); relative mean differences were -0.65% to 3.86% for the areas and 0.25% to 1.72% for the volumes of the various segments. Intraob-server and interobserver comparisons showed high correlations (r = 0.95 to 0.98 for area and r = 0.99 for volume) and small mean relative differences (-0.87% to 1.08%), with SD of lumen, plaque, and total vessel measurements not exceeding 7.28%, 10.81%, and 4.44% (area) and 2.66%, 2.81%, and 0.67% (volume), respectively. Thus the proposed analysis system provided accurate measurements of phantom dimensions and can be used to perform highly reproducible area and volume measurements in three-dimensional ICUS in vivo.

Algorithms↗
PubMed1996

Noninvasive assessment of regional ventilation in the human lung using oxygen-enhanced magnetic resonance imaging.

The imaging of regional ventilation in the lungs is essential for the evaluation of a variety of pathological conditions, such as emphysema, pneumonia and pulmonary embolism. We propose a novel approach for ventilation scanning, using magnetic resonance imaging (MRI) and inhaled molecular oxygen as a contrast agent, that directly depicts transfer of oxygen across the alveolus into the pulmonary vasculature. Molecular oxygen is only weakly paramagnetic but produces substantial signal changes in the lungs because of their large surface area. Ventilation defects were shown in a patient with bullous emphysema, and ventilation-perfusion mismatches were shown in two patients with pulmonary embolism.

Humans↗
PubMed1996

Visually perceived eye level is influenced identically by lines from erect and pitched planes.

The physical elevation that appears to correspond to eye level (VPEL), as measured with a small visual target, changes systematically with the orientation in depth ('visual pitch') of a visual field consisting of one or two pitched-from-vertical lines in darkness. The influence is large and, with a one-line stimulus, is only 15% smaller than the influence exerted by a complexly structured, well-illuminated, pitched visual field. A line from a frontoparallel plane can be presented to the same retinal locus as a pitched-from-vertical line; the three experiments in the present report were aimed at determining the influence on VPEL from such lines. In the first two experiments the subject viewed a visual field consisting of a one-line or two-line pitched-from-vertical stimulus from a pitched-only plane or an oblique one-line or two-line stimulus from an erect plane. Each of the pitched-from-vertical stimuli was presented at seven different orientations separated by 10 degrees over a +/-30 degrees range. Each of the oblique-line stimuli was presented at an orientation that resulted in stimulation to the same retinal locus as one of the conditions with pitched-from-vertical lines, and thus a range of 'equivalent pitches' was examined that corresponded to the range of pitches for the pitched-from-vertical lines. The variation in orientation of the oblique-line stimulus and the pitched-from-vertical stimulus each produced systematic changes in VPEL; the two were indistinguishable. A third experiment specifically designed to examine the possibility that either stimulus sequencing or lack of naivity of the subjects might have been involved turned up no such effects. It is concluded that the aspect of a line stimulus that controls the influence on VPEL is the orientation of the image of the line on a projection sphere centered on the nodal point of the eye or, as in the present experiments with viewing in primary position, the retinal locus stimulated; the orientation-in-depth of the stimulating line provides no additional influence on VPEL for the stationary, erect, monocularly viewing observer. The results are interpreted within the framework of the great-circle model.

Field Dependence-Independence↗
PubMed1996

Patterns that impair discrimination of line orientation in human vision.

The threshold for detecting a change in orientation away from the vertical of a briefly presented foveal line target is raised when there are immediately following visual presentations. This masking effect was examined by measuring the capacity of a variety of patterns to act as masks. When patterns were made of exactly the same number of light pixels, masking was least when they formed random dots and progressively became stronger as they formed lines of decreasing curvature from full circles to straight lines. The longer the lines, the stronger the masking. Threshold elevation was highest when the masking pattern was spatially superimposed on the line and was lessened when a large surround area was included, but there was still considerable masking when the interfering patterns were confined to the surround. By placing masks and test lines in different eyes, or by giving them opposite contrast polarity, almost complete interocular and interpolarity transfer was demonstrated. Relating these results to anatomical and electrophysiological findings about neurons in the primary visual cortex leads to the conclusion that the masking effects could have their substrates in interaction between cells in VI.

Humans↗
PubMed1996

Repair of dGMP hydroxyl radical adducts by verbascoside via electron transfer: a pulse radiolysis study.

The repair activity of verbascoside (VER), isolated from Pedicularis spicata, towards the oxidizing hydroxyl radical adduct of dGMP and its reaction mechanism were studied using pulse radiolysis. Upon pulse radiolysis of nitrous oxide saturated aqueous solution of 2'-deoxyguanosine-5'-monophosphate (dGMP) and VER, it was found that the transient absorption spectrum of the hydroxyl adduct of dGMP decays with the formation of that of the phenoxyl radical of VER, several tens of microseconds after the electron pulse. From the formation kinetics of the phenoxyl radical of VER, the rate constant of the repair reaction was determined to be 1.12 x 10(9) dm(3) mol(-1) s(-1).

Antioxidants↗
PubMed1996

Characterization of echinocandin-resistant mutants of Candida albicans: genetic, biochemical, and virulence studies.

The pneumocandins are potent antifungal agents of the echinocandin class which are under development for use as broad-spectrum antimycotic therapy. One important consideration for any new therapeutic class for treating serious fungal infections is the potential for drug resistance development. In this study we have isolated and characterized four independent spontaneous Candida albicans mutants resistant to the potent semisynthetic pneumocandin L-733,560. These mutants have many of the properties of FKS1/ETG1 echinocandin-resistant mutants of Saccharomyces cerevisiae, including (i) cross-resistance to other 1,3-beta-D-glucan synthase inhibitors, such as papulacandin and echinocandins, but no change in sensitivity to other antifungal agents; (ii) in vitro glucan synthase activity that is more resistant to pneumocandins than the wild-type parent enzyme; and (iii) semidominant drug resistance in spheroplast fusion strains. The mutants were compared with C. albicans echinocandin-resistant mutants isolated by mutagenesis by L. Beckford and D. Kerridge (mutant M-2) (abstr. PS3.11, in Proceedings of the XI Congress of the International Society for Human and Animal Mycology, Montreal, Canada, 1992) and by A. Cassone, R. E. Mason, and D. Kerridge (mutant CA-2) (Sabouraudia 19:97-110, 1981). All of the strains had resistant enzyme activity in vitro. M-2 grew poorly and had low levels of enzyme activity. In contrast, CA-2 and the spontaneous mutants grew as well as the parents and had normal levels of glucan synthase activity. These results suggest that these resistant mutants may have alterations in glucan synthase. CA-2 was unable to form germ tubes, an ability retained by the spontaneous mutants. The virulence of the spontaneous mutants was unimpaired in a mouse model of disseminated candidiasis, while M-2 and CA-2 were 2 orders of magnitude less virulent than their parent strains. Significantly, mice challenged with the spontaneous mutant CAI4R1 responded therapeutically to lower levels of L-733,560 than would he predicted by the increase in in vitro susceptibility.

Animals↗
PubMed1996

Cell proteins bind specifically to West Nile virus minus-strand 3' stem-loop RNA.

The first 96 nucleotides of the 5'noncoding region (NCR) of West Nile virus (WNV) genomic RNA were previously reported to form thermodynamically predicted stem-loop (SL) structures that are conserved among flaviviruses. The complementary minus-strand 3' NCR RNA, which is thought to function as a promoter for the synthesis of plus-strand RNA, forms a corresponding predicted SL structure. RNase probing of the WNV 3' minus-strand stem-loop RNA [WNV (-)3' SL RNA] confirmed the existence of a terminal secondary structure. RNA-protein binding studies were performed with BHK S100 cytoplasmic extracts and in vitro-synthesized WNV (-)3' SL RNA as the probe. Three RNA-protein complexes (complexes 1,2, and 3) were detected by a gel mobility shift assay, and the specificity of the RNA-protein interactions was confirmed by gel mobility shift and UV-induced cross-linking competition assays. Four BHK cell proteins with molecular masses of 108, 60, 50, and 42 kDa were detected by UV-induced cross-linking to the WNV (-)3' SL RNA. A preliminary mapping study indicated that all four proteins bound to the first 75 nucleotides of the WNV 3' minus-strand RNA, the region that contains the terminal SL. A flavivirus resistance phenotype was previously shown to be inherited in mice as a single, autosomal dominant allele. The efficiencies of infection of resistant cells and susceptible cells are similar, but resistant cells (C3H/RV) produce less genomic RNA than congenic, susceptible cells (C3H/He). Three RNA-protein complexes and four UV-induced cross-linked cell proteins with mobilities identical to those detected in BHK cell extracts with the WNV (-)3' SL RNA were found in both C3H/RV and C3H/He cell extracts. However, the half-life of the C3H/RV complex 1 was three times longer than that of the C3H/He complex 1. It is possible that the increased binding activity of one of the resistant cell proteins for the flavivirus minus-strand RNA could result in a reduced synthesis of plus-strand RNA as observed with the flavivirus resistance phenotype.

Animals↗
PubMed1996

Prostaglandin F2 alpha induces cardiac myocyte hypertrophy in vitro and cardiac growth in vivo.

Several prostaglandins [prostaglandin (PG) A2, -B2, -D2, -E2, -F2 alpha, and -I2 and carbaprostacyclin] and the thromboxane analogue U-46619 were analyzed for the ability to induce hypertrophy of rat neonatal cardiac ventricular myocytes. Myocyte hypertrophy was induced specifically by PGF2 alpha. Myocytes exposed to this prostanoid in culture increased in size and protein content. The contractile fibrils within the cells became organized into parallel arrays, and the cells tended to cluster and beat spontaneously. PGF2 alpha also induced the expression of c-fos, atrial natriuretic factor (ANF), and alpha-skeletal actin in these cells. The effects of PGF2 alpha were compared with several known cardiac myocyte hypertrophy factors (phenylephrine, endothelin-1, leukemia inhibitory factor, cardiotrophin-1, and angiotensin II). PGF2 alpha was found to be intermediate in potency among the factors but induced a level of ANF production that was approximately 10-fold higher than any of the other effectors. Responsiveness to PGF2 alpha was not limited to neonatal cardiocytes. Ventricular myocytes isolated from adult rats also responded specifically to PGF2 alpha with a morphological change similar to that observed with phenylephrine and by producing ANF. In rats, chronic administration of fluprostenol, a potent agonist analogue of PGF2 alpha, resulted in a dose-dependent increase in heart weight- and ventricular weight-to-body weight ratios. The amount of PGF2 alpha extractable from the hearts of rats with cardiac hypertrophy induced by myocardial infarction was also found to be greater than that in sham-operated control rats. These results indicate that PGF2 alpha may play an important role in inducing cardiac hypertrophy.

Aging↗
PubMed1996

Detection of two clusters of mechanical properties of smooth muscle along the airway tree.

Heterogeneity of function of airway smooth muscle along the airways may be of great importance in regulating regional ventilation and in the pathogenesis of asthma. To investigate the distribution of mechanical properties of airway smooth muscle along the airway, muscle strips free of cartilage and epithelium from the trachea down to bronchial generation 6 were studied by employing electrical field stimulation. Results showed that smooth muscle mechanical performance decreased progressively down the airway tree. Cluster analysis further indicated that smooth muscle from these airways could be divided into two groups: 1) an extrapulmonary group, which contains muscle from the trachea and bronchial generations 1 and 2 and is characterized by higher maximum shortening capacity and zero-load velocity of shortening (V0) in early shortening, the expected decrease of V0 values (the so-called latch phase) in the later phase of shortening, and lower sensitivity to stimulation; and 2) an intrapulmonary group, which contains bronchi from generations 3-6 and has a lower maximum shortening capacity and V0 in early shortening but higher sensitivity to stimulation. The relatively lower mechanical performance of intrapulmonary bronchial smooth muscle may represent a safety device that prevents excessive smooth muscle shortening in vivo.

Animals↗
PubMed1996

Classifying illusory contours by means of orientation discrimination.

1. Thresholds for discrimination of orientation were measured for solid and interrupted lines, and for illusory borders defined by offset abutting lines of a variety of configurations. 2. Illusory contours defined by orthogonal lines with a clear gap or overlap manifest excellent orientation discrimination even for very short exposure durations, and are robust to pattern motion and masking. The performance is almost as good as that for real lines. 3. When the contour is made up of abutting lines without gap or overlap, orientation discrimination is not nearly as good, and deteriorates further with short exposure duration, with target motion, and with masking. 4. The introduction of disparity in such illusory borders does not improve the discrimination of its orientation, so that concepts such as surface elaborations do not yet have to be invoked. 5. The results suggest that there is one class of illusory contour whose orientations can be discriminated by virtue of its delivering adequate stimuli to orientation-selective units in primary visual cortex. For contours with a uniform space-averaged luminance, the orientation discrimination is helped by the orthogonality of the generating lines, and this gives support to the concept that orthogonally oriented end-stopped neurons may participate in the orientation discrimination.

Discrimination, Psychological↗
PubMed1996

Genetic mapping of GLCLC, the human gene encoding the catalytic subunit of gamma-glutamyl-cysteine synthetase, to chromosome band 6p12 and characterization of a polymorphic trinucleotide repeat within its 5' untranslated region.

The first and rate-limiting step in the formation of glutathione is catalyzed by gamma-glutamylcysteine synthetase (glutamate-cysteine ligase, E.C. 6.3.2.2). Herein, we describe a trinucleotide repeat polymorphism located in the 5' untranslated region of the human gene, GLCLC, that encodes the catalytic subunit of this enzyme, and we genetically map GLCLC to band 6p12, 1.6 cM distal to D6S295.

Alleles↗
PubMed1996

Augmentation of trypsin resistance of retinal pigment epithelium adhesion in vitro by near ultraviolet.

In the process of subculturing near-ultraviolet (NUV)-irradiated retinal pigment epithelial (RPE) monolayers by trypsinization, we surprisingly found that the adhesion capacity of these cells was significantly enhanced. The nature of the enhanced cell adhesion induced by NUV was then studied. To quantitate this capacity, RPE monolayers were exposed to 0.05% trypsin in the presence of 0.53 mM EDTA for 10 min at 37 degrees C. The ratio of RPE cells remaining on the culture surface over total cells was measured and termed as trypsin resistance. (TR). TR of RPE cells without NUV irradiation was null (TR = 0). With NUV energy at 3.24 or 12.96 J/cm2, the RPE-TR was increased to 56.8 +/- 8.5 or 82.3 +/- 8.8%, respectively. With NUV irradiation above 12.96 J/cm2, TR reached a plateau, suggesting a maximal inducible adhesion capacity. When RPE cells were irradiated in an oxygen-free environment, TR was 33.5 +/- 1.6% lower than that in an oxygen-saturated condition, suggesting that it is an oxygen-related process. NUV-enhanced TR was inversely correlated with the concentration of trypsin or the trypsin digestion time. Moreover, NUV-induced TR was gradually diminished with elapsed time. The pre-exposed NUV energy inversely determined the degree of TR recovery. Cycloheximide, a protein synthesis inhibitor, prevented the recovery of TR. These results suggest that NUV-induced TR is a NUV-energy-dependent process. The new protein(s) which is required for TR recovery needs to be further identified.

Animals↗
PubMed1996

The influence of location of electrode on muscle fiber conduction velocity and EMG power spectrum during voluntary isometric contraction measured with surface array electrodes.

A surface array electrode was used to investigate muscle fiber conduction velocity (MFCV) and EMG power spectrum during voluntary isometric contraction of m. biceps brachii. The mean power frequency (MPF) and the total power (TP) at various locations of the muscle were obtained from the power spectrum. MFCVs at various locations of the muscle were measured directly using the averaging method. The values of MPF, TP and MFCV were identified with respect to the electrode locations on the m. biceps brachii. MPF was shown as high near the end-plate and low near the tendon of the muscle during contraction of 40% of isometric maximum voluntary contraction (MVC). TP showed low value near the end-plate and the tendon of the muscle fiber and different values at different location setting electrode during voluntary isometric contraction. TP at each location on the muscle surface increased when the contraction levels increased in the contractions range of 20 to 60% MVC. MFCVs showed a high value near the end-plate and the tendon of the muscle during the contraction of 40% MVC. These results indicated that MPF, TP and MFCV at different locations on the muscle were different along the length of the muscle fiber.

Adult↗
PubMed1996

Distribution of muscle fiber conduction velocity of M. biceps brachii during voluntary isometric contraction with use of surface array electrodes.

Surface electromyogram (EMG) was recorded in m. biceps brachii during the contractions of 20, 40 and 60% of maximum voluntary isometric contraction (MVC) in twelve healthy male subjects, using surface array electrodes. The distribution of muscle fiber conduction velocity (MFCV) was found directly using the averaging technique and the cross-correlation function technique. MFCVs in the region of 20-40 mm measured from end-plate denoted constant value of about 4 m/s in 20% MVC, while MFCVs in the region around end-plate and tendons showed about 10 m/s in 20% MVC. The values of MFCV depended on the contraction levels of muscle. The model for the generation of MFCV which considered the ensemble of muscle fibers with the shape of a cone was proposed. The theoretical values of MFCV by the muscle fiber ensemble model (MFE model) proposed in the paper showed in good agreement with the experimental results.

Action Potentials↗