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Biomedical subjects

Y Cheng

Publications and source records attributed to Y Cheng.

At least 145 records · Page 8Linked to original sources

p53 inactivating mutations in Chinese nasopharyngeal carcinomas.

Previously a low frequency of p53 mutations was detected in nasopharyngeal carcinoma (NPC) using molecular techniques to screen for mutations, yet immunohistochemical staining revealed a high frequency of p53 aberrant proteins. These findings might be attributed to the occurrence of p53 mutations outside the common hot spots and/or the inactivation of the protein through interactions with cellular or viral proteins. Using a previously established simple and sensitive p53 yeast functional assay, we blindly screened 25 nasopharyngeal biopsies for p53 mutations from exons 4 to 11. p53 was mutated in 27.3% of NPC specimens and in 0% of the nasopharyngeal biopsies from patients with non-malignant diseases. Two p53 mutations were detected in exon 7 and two were detected in exon 8. Interestingly, the exon 8 mutations observed in NPC lie in codons which appear to be hot spots for mutations in other head and neck cancers.

Adolescent↗

Electrocardiographic conduction disturbances in association with low-level lead exposure (the Normative Aging Study).

Recent research indicates that cumulative exposure to lead may be more toxic than previously thought. This study was undertaken to examine the relation of low-level lead exposure to electrocardiographic (ECG) conduction disturbances among 775 men who participated in the Normative Aging Study (average age 68 years; range 48 to 93). We used K-x-ray fluorescence to measure lead levels in the tibia and patella, and graphite furnace atomic absorption spectroscopy to measure blood lead levels. The mean (SD) values for blood lead, tibia lead, and patella lead were 5.8 (3.4) microg/dl, 22.2 (13.4) microg/g, and 30.8 (19.2) microg/g, respectively. Bone lead levels were found to be positively associated with heart rate-corrected QT and QRS intervals, especially in younger men. Specifically, in men <65 years of age, a 10 microg/g increase in tibia lead was associated with an increase in the QT interval of 5.03 ms (95% confidence interval [CI], 0.83 to 9.22) and with an increase in the QRS interval of 4.83 ms (95% CI, 1.83 to 7.83) in multivariate regression models. In addition, an elevated bone lead level was found to be positively associated with an increased risk of intraventricular block in men <65 years of age and with an increased risk of atrioventricular (AV) block in men > or = 65 years of age. After adjustment for age and for serum high-density lipoprotein (HDL) level, a 10 microg/g increase in tibia lead was associated with an odds ratio (OR) of 2.23 (95% CI, 1.28 to 3.90) for intraventricular block in men <65 years of age and with an OR of 1.22 (95% CI, 1.02 to 1.47) for AV block in men > or = 65 years of age. Blood lead level was not associated with any of the ECG outcomes examined. The results suggest that cumulative exposure to lead, even at low levels, may depress cardiac conduction.

Aged↗

Relation of nutrition to bone lead and blood lead levels in middle-aged to elderly men. The Normative Aging Study.

The relations of nutritional factors to lead accumulation in the body were examined cross-sectionally among 747 men aged 49-93 years (mean 67 years) in the Normative Aging Study in 1991-1995. Means (standard deviations) for blood lead, tibia lead, and patella lead were 6.2 (4.1) microg/dl, 21.9 (13.3) microg/g, and 32.0 (19.5) microg/g, respectively. In multiple regression models adjusting for age, education level, smoking, and alcohol consumption, men in the lowest quintile of total dietary intake levels of vitamin D (including vitamin supplements) (<179 i.u./day) had mean tibia and patella lead levels 5.6 microg/g and 6.0 microg/g higher than men with intake in the highest quintile (> or =589 i.u./day). Higher calcium intake was associated with lower bone lead levels, but this relation became insignificant when adjustment was made for vitamin D. The authors also observed inverse associations of blood lead levels with total dietary intake of vitamin C and iron. When analyses were controlled for patella lead, age, smoking, and alcohol consumption, men in the lowest vitamin C intake quintile (<109 mg/day) had a mean blood lead level 1.7 microg/dl higher than men in the highest quintile (> or =339 mg/day), while men in the lowest iron intake quintile (<10.9 mg/day) had a mean blood lead level 1.1 microg/dl higher than men in the highest quintile (> or =23.5 mg/day). This study suggests that low dietary intake of vitamin D may increase lead accumulation in bones, while lower dietary intake of vitamin C and iron may increase lead levels in the blood.

Aged↗

Virtual electrode-induced phase singularity: a basic mechanism of defibrillation failure.

Delivery of a strong electric shock to the heart remains the only effective therapy against ventricular fibrillation. Despite significant improvements in implantable cardioverter defibrillator (ICD) therapy, the fundamental mechanisms of defibrillation remain poorly understood. We have recently demonstrated that a monophasic defibrillation shock produces a highly nonuniform epicardial polarization pattern, referred to as a virtual electrode pattern (VEP). The VEP consists of large adjacent areas of strong positive and negative polarization. We sought to determine whether the VEP may be responsible for defibrillation failure by creating dispersion of postshock repolarization and reentry. Truncated exponential biphasic and monophasic shocks were delivered from a bipolar ICD lead in Langendorff-perfused rabbit hearts. Epicardial electrical activity was mapped during and after defibrillation shocks and shocks applied at the plateau phase of a normal action potential produced by ventricular pacing. A high-resolution fluorescence mapping system with 256 recording sites and a voltage-sensitive dye were used. Biphasic shocks with a weak second phase (<20% leading-edge voltage of the second phase with respect to the leading-edge voltage of the first phase) produced VEPs similar to monophasic shocks. Biphasic shocks with a strong second phase (>70%) produced VEPs of reversed polarity. Both of these waveforms resulted in extra beats and arrhythmias. However, biphasic waveforms with intermediate second-phase voltages (20% to 70% of first-phase voltage) produced no VEP, because of an asymmetric reversal of the first-phase polarization. Therefore, there was no substrate for postshock dispersion of repolarization. Shocks producing strong VEPs resulted in postshock reentrant arrhythmias via a mechanism of phase singularity. Points of phase singularity were created by the shock in the intersection of areas of positive, negative, and no polarization, which were set by the shock to excited, excitable, and refractory states, respectively. Shock-induced VEPs may reinduce arrhythmias via a phase-singularity mechanism. Strong shocks may overcome the preshock electrical activity and create phase singularities, regardless of the preshock phase distribution. Optimal defibrillation waveforms did not produce VEPs because of an asymmetric effect of phase reversal on membrane polarization.

Animals↗

Caspase inhibitor affords neuroprotection with delayed administration in a rat model of neonatal hypoxic-ischemic brain injury.

Programmed cell death (apoptosis) is a normal process in the developing nervous system. Recent data suggest that certain features seen in the process of programmed cell death may be favored in the developing versus the adult brain in response to different brain injuries. In a well characterized model of neonatal hypoxia-ischemia, we demonstrate marked but delayed cell death in which there is prominent DNA laddering, TUNEL-labeling, and nuclei with condensed chromatin. Caspase activation, which is required in many cases of apoptotic cell death, also followed a delayed time course after hypoxia-ischemia. Administration of boc-aspartyl(OMe)-fluoromethylketone, a pan-caspase inhibitor, was significantly neuroprotective when given by intracerebroventricular injection 3 h after cerebral hypoxia-ischemia. In addition, systemic injections of boc-aspartyl(OMe)-fluoromethylketone also given in a delayed fashion, resulted in significant neuroprotection. These findings suggest that caspase inhibitors may be able to provide benefit over a prolonged therapeutic window after hypoxic-ischemic events in the developing brain, a major contributor to static encephalopathy and cerebral palsy.

Amino Acid Chloromethyl Ketones↗

Functional evidence for a nasopharyngeal carcinoma tumor suppressor gene that maps at chromosome 3p21.3.

Nasopharyngeal carcinoma is a malignancy that is prevalent among populations from Southeast Asia. Epidemiological studies indicate that genetic predisposition, Epstein-Barr virus, and environmental conditions may play a role in determining incidence. Molecular studies have implicated a tumor suppressor gene(s) on the short arm of chromosome 3. In this study we provide functional evidence, via monochromosome transfer, for a tumor suppressor gene(s) activity in chromosome 3p21.3.

Animals↗

The reaction of lanthanide ions with n-doxyl stearic acids and its utilization for the ESR study on the permeability of lipid-bilayer of erythrocyte membrane to gadolinium ions.

The reaction of lanthanide ions with n-doxyl stearic acid (nDS) spin labels (n = 5,7,12,16) was investigated by the electron spin resonance technique in aqueous solution. Among the lanthanides, the Gd3+, Tb3+, Tm3+ and Ce3+ ions strongly quenched the ESR signal of spin labels, but the effects of La3+, Eu3+ and Lu3+ are very weak. The quenching effects are featured by: (1) the dependence on the concentration of lanthanide ions; (2) no obvious changes of the ESR line shape in the presence of lanthanide ions; (3) the quenching constant decreases in the order: Gd3+ > Tb3+ > Tm3+ > Ce3+; (4) the quenching effects of lanthanide ions are found to strikingly correlate with their magnetic properties. These findings indicate that the interaction of lanthanide ions with nitroxide oxygen leading to the reduction of ESR signal amplitude is dominated by their magnetic characteristics rather than the coordination effect. By labeling erythrocyte membrane with nDS, n = 5,7,12,16 at different depths, we studied the diffusion of Gd3+ into the lipid-bilayer of erythrocyte membrane by monitoring the reduction processes of the ESR signals of nitroxide spin labels located at different depths of membrane lipid-bilayer after addition of Gd3+. These results revealed that the Gd3+ ions can penetrate into the lipid-bilayer, though the entry rate is slow. It was shown that the Gd3+ ions bind to the membrane and enhance the permeability of extracellular ascorbate into erythrocyte membrane. The transport mechanism of Gd3+ ions through the lipid-bilayer might be involved in the Gd3+ cation-induced pore formation in the surface of membrane.

Ascorbic Acid↗

Bcl-xL is an antiapoptotic regulator for postnatal CNS neurons.

Bcl-xL is a death-inhibiting member of the Bcl-2/Ced9 family of proteins which either promote or inhibit apoptosis. Gene targeting has revealed that Bcl-xL is required for neuronal survival during brain development; however, Bcl-xL knock-out mice do not survive past embryonic day 13.5, precluding an analysis of Bcl-xL function at later stages of development. Bcl-xL expression is maintained at a high level postnatally in the CNS, suggesting that it may also regulate neuron survival in the postnatal period. To explore functions of Bcl-xL related to neuron survival in postnatal life, we generated transgenic mice overexpressing human Bcl-xL under the control of a pan-neuronal promoter. A line that showed strong overexpression in brainstem and a line that showed overexpression in hippocampus and cortex were chosen for analysis. We asked whether overexpression of Bcl-xL influences neuronal survival in the postnatal period by studying two injury paradigms that result in massive neuronal apoptosis. In the standard neonatal facial axotomy paradigm, Bcl-xL overexpression had substantial effects, with survival of 65% of the motor neurons 7 d after axotomy, as opposed to only 15% in nontransgenic littermates. To investigate whether Bcl-xL regulates survival of CNS neurons in the forebrain, we used a hypoxia-ischemia paradigm in neonatal mice. We show here that hypoxia-ischemia leads to substantial apoptosis in the hippocampus and cortex of wild-type neonatal mice. Furthermore, we show that overexpression of Bcl-xL is neuroprotective in this paradigm. We conclude that levels of Bcl-xL in postnatal neurons may be a critical determinant of their susceptibility to apoptosis.

Animals↗

Drosophila photoreceptors contain an autonomous circadian oscillator that can function without period mRNA cycling.

Circadian oscillations in period (per) mRNA and per protein (PER) constitute, in part, a feedback loop that is required for circadian pacemaker function in Drosophila melanogaster. Oscillations in PER are required for oscillations in per mRNA, but the converse has not been rigorously tested because of a lack of measurable quantities of per mRNA and protein in the same cells. This circadian feedback loop operates synchronously in many neuronal and non-neuronal tissues, including a set of lateral brain neurons (LNs) that mediate rhythms in locomotor activity, but whether a hierarchy among these tissues maintains this synchrony is not known. To determine whether per mRNA cycling is necessary for PER cycling and whether cyclic per gene expression is tissue autonomous, we have generated per01 flies carrying a transgene that constitutively expresses per mRNA specifically in photoreceptors, a cell type that supports feedback loop function. These transformants were tested for different aspects of feedback loop function including per mRNA cycling, PER cycling, and PER nuclear localization. Under both light/dark (LD) cycling and constant dark (DD) conditions, PER abundance cycles in the absence of circadian cycling of per mRNA. These results show that per mRNA cycling is not required for PER cycling and indicate that Drosophila photoreceptors R1-R6 contain a tissue autonomous circadian oscillator.

Animals↗

Characterization of the low magnification performance of a Philips CM300-FEG.

The low magnification performance of a Philips CM300-FEG transmission electron microscope was characterized in three different configurations: CM30-FEG Super Twin, CM30-FEG Twin and CM300-FEG Cryo Twin. Micrographs of gold single crystal, polycrystalline gold, graphitized carbon and copper chloropthalocyanine were recorded in the magnification range 2050x-100,000x using film as the recording medium and optical diffraction to assay image resolution. Lattice images of gold single crystals could be recorded on film with a resolution of 2.04 A at 10,500x; copper chloropthalocyanine lattice images could be recorded with a resolution of 6 A at 4500x and 12 A at 2050x. This indicates that the film has a line resolution as low as 2.1 microns or 470 lines/mm. The fact that lattice images from different specimens can be recorded at this line spacing regardless of magnification suggests that film rather than the microscope is the major limitation to image resolution at low magnification. The image resolution delivered by the microscope is also approximately 4x smaller than the capability of densitometers to digitize it. This suggests that there would be some benefit to digitization of micrographs at finer pixel sizes than currently possible. These observations indicate that tomography of radiation sensitive specimens, where the film is the recording medium, can be recorded at the lowest magnification consistent with digitizing capabilities and desired resolution with confidence in the microscope performance. The potential benefit lies in the possibility of obtaining more images for the same accumulated dose at low magnification and the possibility that more unit cells can be imaged both of which can contribute to the potential success of applying tomographic methods to radiation sensitive specimens.

Carbon↗

Effects of ursodeoxycholate and other bile salts on levels of rat intestinal alkaline sphingomyelinase: a potential implication in tumorigenesis.

Previous studies showed that bile salts had a promoting effect on colon cancer development and this effect was inhibited by ursodeoxycholate (UDC). We recently found that both human colorectal adenomas and carcinomas were associated with a specific decrease in alkaline sphingomyelinase activity. In this work, we compared the effects of ursodeoxycholate and other bile salts on the levels of rat intestinal alkaline sphingomyelinase both in the intestinal loops and after oral administration. Bile salts at different concentrations were injected into intestinal loops and the dissociation of alkaline sphingomyelinase from the mucosa was assayed. We found that bile salts, including taurocholate, taurodeoxycholate, glycocholate, glycochenodeoxycholate, and 3-(3-cholamidopropyl dimethylammonio)-1-propanesulonate (CHAPS), dose dependently dissociated alkaline sphingomyelinase from the intestinal mucosa. UDC alone did not dissociate the enzyme but significantly inhibited the dissociation caused by other bile salts and CHAPS. Feeding rats with 0.3% (w/w) taurocholate for four days decreased peak activity of intestinal alkaline sphingomyelinase by 39% and total activity in the intestine by 20% and increased the output of the enzyme in the feces. In contrast, feeding 0.3% (w/w) UDC for four days increased the peak activity of alkaline sphingomyelinase in the small intestine by 87% and the activity in the colon by 187%. The total activity of alkaline sphingomyelinase was increased by 80% and the output of the enzyme in the feces was only slightly increased by UDC administration. The changes in alkaline phosphatase after feeding taurocholate and UDC were much smaller. Our results indicate that UDC and other bile salts have different effects on the levels of alkaline sphingomyelinase, which may be implicated in their different influences on cancer development reported previously.

Administration, Oral↗

Occiput-cervical fusion for symptomatic atlantoaxial subluxation in a 32-month-old child with Down syndrome: a case report.

Atlantoaxial subluxation in Down syndrome rarely becomes neurologically symptomatic in very young children. The authors present a 32-month-old girl with Down syndrome, who had tetraporesis due to an atlantoaxial subluxation. She was treated with halo immobilization and partial reduction of the subluxation at first, followed by removal of posterior arch of the atlas and posterior fusion with wire fixation. Halo immobilization was continued for 3 months after operation. After 1-year follow-up, her motor functions were normal, and the dynamic roentgenogram of the cervical spines showed good stability. The authors recommend posterior fusion and postoperative halo immobilization for the treatment of the symptomatic atlantoaxial subluxation in young Down syndrome patients, even in a 32-month-old child.

Atlanto-Axial Joint↗

Virtual electrode effects in transvenous defibrillation-modulation by structure and interface: evidence from bidomain simulations and optical mapping.

INTRODUCTION: Our goal in this combined modeling and experimental study was to gain insight into the transmembrane potential changes in defibrillation conditions, namely, when shocks are delivered by an implantable cardioverter defibrillator (ICD). Two hypotheses concerning the presence and characteristics of virtual electrode effects (VEE) during an ICD shock were tested numerically and experimentally: (H1) anisotropy-dependent VEE are induced over a considerable portion of the "bulk" myocardium; and (H2) surface (epicardial and endocardial) VEE are generated under special tissue bath conditions and are not fully anisotropy determined. METHODS AND RESULTS: Optical mapping was performed on Langendorff-perfused rabbit hearts (n = 4) stained with di-4-ANEPPS. Monophasic shocks were applied during the plateau phase of an action potential through a 9-mm long distal electrode in the right or left ventricle and a 6-cm proximal electrode positioned 3 cm posteriorly to the heart. We modeled the experiment using an ellipsoidal bidomain heart with transmural fiber rotation, placed in a perfusing bath, and subjected to defibrillation shocks delivered by an electrode configuration as described. Our numerical simulations demonstrated VEE occupying a significant portion of the myocardium in the conditions of unequal anisotropy ratios for the intra- and extracellular domains. Statistically significant differences in epicardial polarization patterns were predicted numerically and confirmed experimentally when the interface conditions varied. CONCLUSION: The present study concludes that VEE are present in transvenous defibrillation. They are shaped by the combined effect of cardiac tissue characteristics and interface conditions. Because of their size, VEE might contribute significantly to defibrillation outcome.

Animals↗

Two alternatively spliced transcripts from the Drosophila period gene rescue rhythms having different molecular and behavioral characteristics.

The period (per) and timeless (tim) genes encode key components of the circadian oscillator in Drosophila melanogaster. The per gene is thought to encode three transcripts via differential splicing (types A, B, and C) that give rise to three proteins. Since the three per mRNA types were based on the analysis of cDNA clones, we tested whether these mRNA types were present in vivo by RNase protection assays and reverse transcriptase-mediated PCR. The results show that per generates two transcript types that differ only by the presence (type A) or absence (type B') of an alternative intron in the 3' untranslated region. Transgenic flies containing transgenes that produce only type B' transcripts (perB'), type A transcripts (perA), or both transcripts (perG) rescue locomotor activity rhythms with average periods of 24.7, 25.4, and 24.4 h, respectively. Although no appreciable differences in type A and type B' mRNA cycling were observed, a slower accumulation of PER in flies making only type A transcripts suggests that the intron affects the translation of per mRNA.

Alternative Splicing↗

Voltage-sensitive dye RH421 increases contractility of cardiac muscle.

Voltage-sensitive dyes and imaging techniques have proved to be indispensable tools for use in in vitro electrophysiological studies. To avoid motion artifacts in optical recordings, electromechanical uncouplers such as 2,3-butanedione monoxime (BDM) are required. In this study, we sought to determine whether the voltage-sensitive dye RH421 had an effect on the contractility of heart muscle, either alone or in the presence of BDM. Ventricular contractility was studied in (i) isolated rat myocytes and (ii) Langendorff-perfused rat hearts under control conditions, and during perfusion with RH421 or RH421 + BDM. The following results were obtained. (i) The amplitude of cell shortening increased progressively from 6.24 +/- 0.64 to 9.95 +/- 1.02 microm during 15 min of superfusion with 5 microM RH421 (n = 11), and further increased to 12.54 +/- 0.97 microm during washout. In seven cells first perfused with 15 mM BDM and then with 15 mM BDM + 5 microM RH421, the amplitude of the cell shortening first decreased from 5.17 +/- 0.51 to 0.41 +/- 0.19 microm, then the amplitude increased to 2.63 +/- 0.25 microm. (ii) Left ventricular pressure (LVP) of the heart (n = 7) was reduced by 15 mM BDM from 60.7 +/- 2.5 to 2.8 +/- 0.5 mmHg (1 mmHg = 133.3 Pa). LVP increased to 12.8 +/- 1.1 mmHg during subsequent perfusion with 10 microM RH421 in the presence of BDM and did not change (LVP = 12.4 +/- 2.4 mmHg) during washout of the dye. Therefore, RH421 increased the contractility of rat hearts and isolated myocytes with and without BDM.

Animals↗

[Histological evaluation of collagen-hydroxyapatite composite as osseous implants in the repair of mandibular defect].

To observe the collagen-hydroxylaptite composite in the repair of bone defect, ten minipigs were chosen to make a mandibular dafect measuring 2 cm in diameter and the composite was implanted, while the use of autogenous bone graft and the blank wese served as control. On the 4, 8, 12, 24 and 48 weeks after the operation, the animals were sacrificed and the samples were examined under light microscope. The result showed that: no infection or necrosis occurred. The composite coalesced with host bone and the outcome was similar to that of the autogenous bone graft. No foreign body giant cells or vacuum left from osteonecrosis was observed. It was suggested that the composite had the advantage of abundant supply, easy to handle and no harm. The biocompatibility was good and might be hopeful as a bone substitute.

Animals↗

Inhibitory effect of trapidil on proliferation of cultured rat aortic smooth muscle cells induced by endothelin-1.

AIM: To study the effect of trapidil (Tra) on endothelin-1-induced proliferation of cultured rat aortic vascular smooth muscle cells (VSMC). METHODS: The [3H]TdR incorporation into DNA assay, the number of VSMC, and cell cycle distribution were measured. RESULTS: Pretreated with endothelin-1 100 nmol.L-1, cell number, [3H]TdR uptake, and cell mitogenic activity increased 134% +/- 23%, 210% +/- 70%, and 86% +/- 18%, respectively. This proliferation was inhibited by Tra 5, 50, 500 mumol.L-1. The inhibitory rates were 12%-48%, 35%-54% and 15%-47%, respectively. Tra did not influence the proliferation of VSMC without endothelin-1 pretreatment. CONCLUSION: Tra antagonized the proliferation of VSMC induced by endothelin-1.

Animals↗