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Biomedical subjects

Y Cheng

Publications and source records attributed to Y Cheng.

At least 37 records · Page 2Linked to original sources
PubMed2004

Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients.

Treatment of severe acute respiratory syndrome (SARS) is experimental, and the effectiveness of ribavirin-steroid therapy is unclear. Forty SARS patients with progressive disease after ribavirin treatment and 1.5 g of pulsed methylprednisolone were given either convalescent plasma (n = 19) or further pulsed methylprednisolone (n = 21) in a retrospective non-randomised study. Good clinical outcome was defined as discharge by day 22 following the onset of symptoms. Convalescent plasma was obtained from recovered patients after informed consent. Patients in the plasma group had a shorter hospital stay (p 0.001) and lower mortality (p 0.049) than the comparator group. No immediate adverse effects were observed following plasma infusion.

Adult↗
PubMed2004

Clinical and radiological features of odontogenic ghost cell carcinoma: review of the literature and report of four new cases.

OBJECTIVES: To analyse systematically the clinical and radiological features of odontogenic ghost cell carcinoma (OGCC). METHODS: Clinical and radiological features of 22 OGCCs (4 new and 18 from the literature) were analysed. RESULTS: There were 17 (77%) males and 5 (23%) females (male-to-female ratio of 3.4:1). Ages ranged from 13 years to 72 years (mean 36.7) with a peak in the fourth (40.9%) and fifth (27.3%) decades. The maxilla was involved in 68% and the mandible in 32%. Our study confirmed that OGCC is more prevalent in Asians (12/18) than in other racial groups. The mixed radiolucent and radiopaque lesion pattern was the most frequent (14/19) compared with radiolucent lesions (5/19). 89% (17/19) showed poorly defined borders and 11% (2/19) showed well defined borders. Root resorption was reported in 31% (6/19) of patients and tooth displacements in 21%. CONCLUSIONS: OGCC demonstrates clinical and radiographic features of a malignant tumour with high recurrence.

Adult↗
PubMed2004

Osteoclast numbers in Lewis rats with adjuvant-induced arthritis: identification of preferred sites and parameters for rapid quantitative analysis.

This study defined the best site for quantifying osteoclasts in male Lewis rats with mycobacteria-induced adjuvant arthritis. Hind paw sections of normal and arthritic rats (n = 6 per group) taken 7 days after disease onset were stained for osteoclasts using an anti-human cathepsin K primary antibody. Erosions and osteoclasts were assessed using semiquantitative scores (entire section) and quantitative measures (in calcaneus, navicular tarsal, and tibia). Bone area in arthritic rats was significantly reduced (P </= 0.05) by 39-55%, with the greatest decrease in the tarsal. Osteoclasts in arthritic rats were significantly increased (P </= 0.05) relative to normal in calcaneus (sevenfold), tarsal (194-fold), and tibia (threefold). The most useful quantitative indices were bone area and total osteoclasts, both defined as a percentage of total area measured. Semiquantitative scores for bone erosion and osteoclasts paralleled the quantitative indices. These data show that the navicular tarsal is the most sensitive site at which to assess arthritis in rats with this variant of adjuvant-induced arthritis.

Animals↗
PubMed2003

Inhibition of nicotine-DNA adduct formation in mice by six dietary constituents.

Nicotine [3-(1-methyl-2-pyrrolidinyl)-pyridine] is a major alkaloid in tobacco products and has proven to be a potential genotoxic compound. Many natural dietary products can suppress the DNA adduction, and hence act as inhibitors of cancer. In this study, we investigated the inhibitory effects of curcumin, garlic squeeze, grapeseed extract, tea polyphenols, vitamin C, and vitamin E on nicotine-DNA adduction in vivo using an ultrasensitive method of accelerator mass spectrometry (AMS). The results demonstrated that all the dietary constituents induced marked dose-dependent decrease in nicotine-DNA adducts as compared with the control. The reduction rate reached about 50% for all agents, except garlic squeeze (40%), even at its highest dose level. Amongst the six agents, grapeseed extract exhibited the strongest inhibition to the DNA adduct formation. Therefore, we may arrive at a point that these dietary constituents are beneficial to prevent the harmful adduct formation, and thus to block the potential carcinogenesis induced by nicotine.

Animals↗
PubMed2002

Thalamic neuron apoptosis emerges rapidly after cortical damage in immature mice.

In adults and children, head trauma can have long-term neuropathological and functional consequences. The thalamus is a major site of remote neurodegeneration after cortical damage in adult humans and experimental animals, but less is known about thalamic responses to cortical injury in the immature brain. This study introduces an in vivo model of axotomy/target deprivation-induced neuronal apoptosis in the dorsal lateral geniculate nucleus of the thalamus produced by unilateral ablation of the occipital cortex in the immature mouse. We specifically examined whether occipital cortex ablation in the immature brain causes apoptotic death of projection neurons in the dorsal lateral geniculate nucleus. After unilateral occipital cortex aspiration, 10-day-old C57BL/6 mice were recovered for up to 28 days. Fluorogold-prelabeled thalamocortical projection neurons were apoptotic at 36-48 h after ablation. The structural progression of apoptosis in the immature lateral geniculate nucleus reveals typical chromatolytic morphology by 18-24 h, followed by cytoplasmic shrinkage and chromatin condensation characteristic of end-stage apoptosis after 36-48 h. Electron microscopy confirmed the presence of apoptosis. This study shows internucleosomal DNA fragmentation and expression of cleaved caspase-3 occurs rapidly, being noted first at 18 h, well before the peak of apoptotic cell death occurring at 36 h after cortical damage in the immature brain. From these data we suggest that axotomy/target deprivation-induced cell death in the immature brain may: (1) differ from that previously reported in adult mice with respect to the time required for progression to cell death; (2) be mediated by caspase-3 activation.

Animals↗
PubMed2002

Kinetics of defibrillation shock-induced response: design implications for the optimal defibrillation waveform.

INTRODUCTION: Implantable cardioverter defibrillator (ICD) therapy is a well-established therapy for treating patients at high risk for sudden cardiac death. Recently formulated virtual electrode polarization theory is a promising foundation for the theory of defibrillation. Yet, continuing optimization of defibrillation therapy is limited to primarily empirical methods due to difficulties in assessing kinetics of cellular response in whole heart models of defibrillation. The aim of this study was to evaluate the response of the myocardium in the context of virtual electrode polarization. METHODS AND RESULTS: We used a Langendorff-perfused rabbit heart model of ICD therapy and voltage-sensitive fluorescent dye imaging in order to map kinetics of trans membrane potential during both mono- and biphasic shocks applied at various phases of the QT-interval. Cellular response was fitted to a single exponential function using the Levenberg-Marquardt method. Time constants (tau) were measured in 45 288 optical records from 17 hearts. We found that cellular response depends upon both QT-phase of application, intensity, polarity, and phase of the biphasic waveform. Shocks of larger strengths produce a faster response. The tau of the first-phase negatively polarizing response was significantly larger compared with the positively polarizing response at intensities below 200 V, but smaller at 200 V and above. The tau of the second phase negatively polarizing response was always slower than the positively polarizing response, regardless of amplitude, and timing. Overall, tau ranged from 1.6 ms to 14.2 ms. CONCLUSIONS: The time constant of the membrane depends on the field, action potential phase and the shock polarity, but exceeds 1 msec. Therefore, we suggest using a slower shock leading edge, since the membrane cannot follow potentially damaging faster waveforms.

Animals↗
PubMed2001

Helicobacter pylori arginase inhibits nitric oxide production by eukaryotic cells: a strategy for bacterial survival.

The antimicrobial effect of nitric oxide (NO) is an essential part of innate immunity. The vigorous host response to the human gastric pathogen Helicobacter pylori fails to eradicate the organism, despite up-regulation of inducible NO synthase (iNOS) in the gastric mucosa. Here we report that wild-type strains of H. pylori inhibit NO production by activated macrophages at physiologic concentrations of l-arginine, the common substrate for iNOS and arginase. Inactivation of the gene rocF, encoding constitutively expressed arginase in H. pylori, restored high-output NO production by macrophages. By using HPLC analysis, we show that l-arginine is effectively consumed in the culture medium by wild-type but not arginase-deficient H. pylori. The substantially higher levels of NO generated by macrophages cocultured with rocF-deficient H. pylori resulted in efficient killing of the bacteria, whereas wild-type H. pylori exhibited no loss of survival under these conditions. Killing of the arginase-deficient H. pylori was NO-dependent, because peritoneal macrophages from iNOS(-/-) mice failed to affect the survival of the rocF mutant. Thus, bacterial arginase allows H. pylori to evade the immune response by down-regulating eukaryotic NO production.

Animals↗
PubMed2001

Differential localization of the neurofibromatosis 1 (NF1) gene product, neurofibromin, with the F-actin or microtubule cytoskeleton during differentiation of telencephalic neurons.

The protein product of the neurofibromatosis 1 gene, neurofibromin, is abundantly expressed in the cerebral cortex during development, but its physiological role remains unknown. To gain insights into the functions of neurofibromin in neurons, we examined patterns of expression and subcellular localization of neurofibromin during neuronal differentiation. Western blot analysis of telencephali homogenates throughout chick embryogenesis revealed that neurofibromin expression increased during embryonic development. Further analysis showed that telencephalic neurons were also enriched in neurofibromin in culture and that a biphasic gain in expression correlated well with both phases of differentiation in culture, first with a massive outgrowth of processes and gains in neurotransmitter phenotype differentiation, and then with synapse formation. Compared to proteins associated with distinct cytoskeleton systems, the pattern of neurofibromin expression correlated closely with that of the cortical cytoskeleton protein paxillin. Moreover, analysis of immunofluorescence staining of neurofibromin showed that in the presence of a protein crosslinker which preserves both soluble and filamentous cytoskeleton proteins after extraction with Triton X-100, neurofibromin colocalized with F-actin only during the first differentiation phase. This colocalization persisted when the actin cytoskeleton was collapsed with cytochalasin D treatment. In contrast, during the second phase of differentiation neurofibromin colocalized with microtubules, but not F-actin, and the staining pattern was disrupted with nocodazole, but not cytochalasin. A constant finding under all conditions was the presence of neurofibromin in the nucleus, which supports the idea that the bipartite nuclear targeting sequence between residues 2555 and 2572 of neurofibromin may be functional. In summary, we have shown that telencephalic neurons and astroblasts are enriched in neurofibromin and that the subcellular targeting of neurofibromin toward the actin or the microtubule cytoskeleton is developmentally regulated.

Actin Cytoskeleton↗
PubMed2001

Structure of the Sec23p/24p and Sec13p/31p complexes of COPII.

COPII-coated vesicles carry proteins from the endoplasmic reticulum to the Golgi complex. This vesicular transport can be reconstituted by using three cytosolic components containing five proteins: the small GTPase Sar1p, the Sec23p/24p complex, and the Sec13p/Sec31p complex. We have used a combination of biochemistry and electron microscopy to investigate the molecular organization and structure of Sec23p/24p and Sec13p/31p complexes. The three-dimensional reconstruction of Sec23p/24p reveals that it has a bone-shaped structure, (17 nm in length), composed of two similar globular domains, one corresponding to Sec23p and the other to Sec24p. Sec13p/31p is a heterotetramer composed of two copies of Sec13p and two copies of Sec31p. It has an elongated shape, is 28-30 nm in length, and contains five consecutive globular domains linked by relatively flexible joints. Putting together the architecture of these Sec complexes with the interactions between their subunits and the appearance of the coat in COPII-coated vesicles, we present a model for COPII coat organization.

COP-Coated Vesicles↗
PubMed2001

Drosophila fasciclinII is required for the formation of odor memories and for normal sensitivity to alcohol.

Drosophila fasciclinII (fasII) mutants perform poorly after olfactory conditioning due to a defect in encoding, stabilizing, or retrieving short-term memories. Performance was rescued by inducing the expression of a normal transgene just before training and immediate testing. Induction after training but before testing failed to rescue performance, showing that Fas II does not have an exclusive role in memory retrieval processes. The stability of odor memories in fasII mutants are indistinguishable from control animals when initial performance is normalized. Like several other mutants deficient in odor learning, fasII mutants exhibit a heightened sensitivity to ethanol vapors. A combination of behavioral and genetic strategies have therefore revealed a role for Fas II in the molecular operations of encoding short-term odor memories and conferring alcohol sensitivity. The preferential expression of Fas II in the axons of mushroom body neurons furthermore suggests that short-term odor memories are formed in these neurites.

Animals↗
PubMed2001

The Ras radiation resistance pathway.

The critical pathways determining the resistance of tumor cells to ionizing radiation are poorly defined. Because the ras oncogene, a gene activated in many human cancers treated with radiotherapy, can induce increased radioresistance, we have asked which Ras effector pathways are significant in conferring a survival advantage to tumor cells. The phosphoinositide-3-kinase (PI3K) inhibitor LY294002 radiosensitized cells bearing mutant ras oncogenes, but the survival of cells with wild-type ras was not affected. Inhibition of the PI3K downstream target p70S6K by rapamycin, the Raf-MEK-MAPK pathway with PD98059, or the Ras-MEK kinase-p38 pathway with SB203580 had no effect on radiation survival in cells with oncogenic ras. Expression of active PI3K in cells with wild-type ras resulted in increased radiation resistance that could be inhibited by LY294002. These experiments have indicated the importance of PI3K in mediating enhanced radioresistance and have implicated PI3K as a potential target for specific radiosensitization of tumors.

Animals↗
PubMed2001

Promoter methylation regulates Helicobacter pylori-stimulated cyclooxygenase-2 expression in gastric epithelial cells.

Cyclooxygenase (COX)-2, the inducible form of the rate-limiting enzyme for prostaglandin synthesis, is up-regulated in gastrointestinal cancers and is a key mediator of epithelial cell growth. Helicobacter pylori is causally linked to gastric cancer. In H. pylori gastritis, COX-2 expression localizes to the subepithelial region, with variable levels in the epithelium. In contrast, in gastric cancer, COX-2 strongly predominates in the epithelium, suggesting that the transition to consistent epithelial COX-2 overexpression may be a critical molecular event in gastric carcinogenesis. Because aberrant promoter methylation inhibits expression of a variety of genes in gastrointestinal cancers, we sought to determine whether methylation of the COX-2 promoter could regulate the response to H. pylori in gastric epithelial cells. We assessed COX-2 expression and promoter methylation status in six gastric epithelial cell lines. In all four of the cell lines that exhibited basal expression of COX-2 and a significant increase in expression in response to H. pylori, the COX-2 promoter was unmethylated, whereas in the two cell lines that did not express COX-2, the COX-2 promoter was methylated. Treatment of COX-2-methylated cells with the demethylating agent 5-azacytidine had a modest effect on COX-2 expression, but when 5-azacytidine-treated cells were subsequently stimulated with H. pylori, there was a significant, 5-10-fold enhancement of both COX-2 mRNA and protein expression and release of the COX-2 product, prostaglandin E2. In contrast, in COX-2-expressing cell lines that were unmethylated at the COX-2 promoter, 5-azacytidine had no effect on H. pylori-stimulated COX-2 expression. These findings suggest that loss of COX-2 methylation may facilitate COX-2 expression and promote gastric carcinogenesis associated with H. pylori infection.

Adenocarcinoma↗
PubMed2001

A single peripheral injection of basic fibroblast growth factor (bFGF) stimulates granule cell production and increases cerebellar growth in newborn rats.

The control of neuronal number is critical for coordinating innervation and target organ requirements. Although basic fibroblast growth factor (bFGF) is known to regulate neuron number in the developing embryonic cortex, its potential role during postnatal brain development remains undefined. To address this issue, the cerebellum, a site of postnatal neurogenesis, was used. Previously, we found that a single peripheral injection of bFGF in newborn rats elicited mitosis of neuronal precursors in the external germinal layer (EGL) 8 h after administration. We now define the sustained effects of bFGF treatment on postnatal granule cell production and cerebellar growth. Seventy-two h after a single injection of bFGF (20 ng/g) in newborn rats, the fraction of BrdU-labeled cells in the EGL increased by 46% without altering apoptotic cell number, consistent with enhanced precursor proliferation. Moreover, bFGF increased mitotically labeled cells by 100% and total cell density by 33% in the internal granular layer (IGL), the final destination of the EGL precursors. Because cerebellar volume also increased by 22%, bFGF-induced proliferation enhanced generation of total IGL neurons and increased cerebellar growth. These morphometric measures were corroborated independently by using DNA quantitation: cerebellar DNA content increased 16% after bFGF injection, consistent with increased neuron number. Furthermore, using DNA quantitation as an index, increased total cerebellar cell number elicited by bFGF injection persisted beyond the neurogenetic period, until P35. We conclude that a single postnatal injection of bFGF increases granule neuron number and enhances cerebellar growth following mitotic stimulation.

Age Factors↗
PubMed2001

Lanthanide ions induce hydrolysis of hemoglobin-bound 2,3-diphosphoglycerate (2,3-DPG), conformational changes of globin and bidirectional changes of 2,3-DPG-hemoglobin's oxygen affinity.

The changes in structure and function of 2,3-diphosphoglycerate-hemoglobin (2,3-DPG-Hb) induced by Ln(3+) binding were studied by spectroscopic methods. The binding of lanthanide cations to 2,3-DPG is prior to that to Hb. Ln(3+) binding causes the hydrolysis of either one from the two phosphomonoester bonds in 2,3-DPG non-specifically. The results using the ultrafiltration method indicate that Ln(3+) binding sites for Hb can be classified into three categories: i.e. positive cooperative sites (N(I)), non-cooperative strong sites (N(S)) and non-cooperative weak sites (N(W)) with binding constants in decreasing order: K(I)>K(S)>K(W). The total number of binding sites amounts to about 65 per Hb tetramer. Information on reaction kinetics was obtained from the change of intrinsic fluorescence in Hb monitored by stopped-flow fluorometry. Fluctuation of fluorescence dependent on Ln(3+) concentration and temperature was observed and can be attributed to the successive conformational changes induced by Ln(3+) binding. The results also reveal the bidirectional changes of the oxygen affinity of Hb in the dependence on Ln(3+) concentration. At the range of [Ln(3+)]/[Hb]<2, the marked increase of oxygen affinity (P(50) decrease) with the Ln(3+) concentration can be attributed to the hydrolysis of 2,3-DPG, while the slight rebound of oxygen affinity in higher Ln(3+) concentration can be interpreted by the transition to the T-state of the Hb tetramer induced by Ln(3+) binding. This was indicated by the changes in secondary structure characterized by the decrease of alpha-helix content.

2,3-Diphosphoglycerate↗
PubMed2001

Bone lead and blood lead levels in relation to baseline blood pressure and the prospective development of hypertension: the Normative Aging Study.

Between 1991 and 1997, the authors studied 833 participants of the Normative Aging Study in a substudy of bone lead levels (measured by K-shell x-ray fluorescence), blood lead levels, and hypertension. Among these subjects, 337 were classified as normotensive, and 182 and 314 were classified as having borderline and definite hypertension, respectively, at baseline. These bone and blood lead levels were typical of those of community-exposed men. Among the 519 subjects with no history of definite hypertension at baseline, cross-sectional analyses revealed positive associations between systolic blood pressure and bone lead levels. Of the 474 subjects who were free from definite hypertension at baseline and had follow-up data, 74 new cases of definite hypertension were reported. Baseline bone lead levels were positively associated with incidence of hypertension. In proportional hazards models that controlled for age, age squared, body mass index, and family history of hypertension, an increase in patella (trabecular) lead from the midpoint of the lowest quintile to that of the highest quintile was associated with a rate ratio of definite hypertension of 1.71 (95% confidence interval: 1.08, 2.70). No association was found with blood lead level. These results support the hypothesis that cumulative exposure to lead, even at low levels sustained by the general population, may increase the risk of hypertension.

Adult↗
PubMed2001

Ultrafast liquid chromatography/ultraviolet and liquid chromatography/tandem mass spectrometric analysis.

Optimal liquid chromatography/mass spectrometric [LC/MS(/MS)] analysis depends on both the LC selectivity and the electrospray efficiency. Here, we outline a simple and comprehensive LC/MS/MS strategy for the rapid analysis of a wide range of pharmaceutical compounds. To achieve ultrafast LC separation with little sacrifice in peak capacity, one needs to start with a column that provides a good peak capacity at short gradient run times; secondly, it is important to use high flow rates to achieve a good gradient peak capacity. Following this strategy, it was possible to baseline-resolve a mixture (containing acidic, neutral, and basic pharmaceutical analytes) in seconds. By coupling the selectivity provided by fast LC separation with the specificity of MS/MS detection, it is possible to separate and identify a wide range of analytes in 1-min gradient analyses. Also, the impact of mobile phase pH on both the chromatographic selectivity and the MS/MS sensitivity is demonstrated.

Chromatography, Liquid↗