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Biomedical subjects

H Ying

Publications and source records attributed to H Ying.

At least 19 recordsLinked to original sources

PPARgamma insufficiency promotes follicular thyroid carcinogenesis via activation of the nuclear factor-kappaB signaling pathway.

The molecular genetic events underlying thyroid carcinogenesis are poorly understood. Mice harboring a knock-in dominantly negative mutant thyroid hormone receptor beta (TRbetaPV/PV mouse) spontaneously develop follicular thyroid carcinoma similar to human thyroid cancer. Using this mutant mouse, we tested the hypothesis that the peroxisome proliferator-activated receptor gamma (PPARgamma) could function as a tumor suppressor in thyroid cancer in vivo. Using the offspring from the cross of TRbetaPV/+ and PPARgamma+/- mice, we found that thyroid carcinogenesis progressed significantly faster in TRbetaPV/PV mice with PPARgamma insufficiency from increased cell proliferation and reduced apoptosis. Reduced PPARgamma protein abundance led to the activation of the nuclear factor-kappaB signaling pathway, resulting in the activation of cyclin D1 and repression of critical genes involved in apoptosis. Treatment of TRbetaPV/PV mice with a PPARgamma agonist, rosiglitazone, delayed the progression of thyroid carcinogenesis by decreasing cell proliferation and activation of apoptosis. These results suggest that PPARgamma is a critical modifier in thyroid carcinogenesis and could be tested as a therapeutic target in thyroid follicular carcinoma.

Animals↗

Cloning and characterization of F-LANa, upregulated in human liver cancer.

Differentially expressed genes between normal liver and hepatocellular carcinomas were investigated using differential display. Consequently, we identified a fragment cDNA upregulated in tumor tissues. We screened the liver library and cloned the full-length cDNA, named F-LANa. Increased expression of F-LANa was confirmed by Northern blot analysis in 10 of 14 (71%) cases of hepatocellular carcinomas. Human F-LANa gene maps to chromosome 17p at D17S1828-D17S786, spans at least 11.8 kb, and contains 7 exons. This gene encodes a 239 aa protein exhibiting 97.9% similarity to the mouse ortholog gene, identified later by in silico cloning. Homology analysis was carried out in various species and showed that F-LANa was evolutionarily conserved from yeast to human. In addition, F-LANa antisense oligonucleotide suppressed F-LANa expression in human hepatocellular carcinoma BEL-7404 cells and significantly inhibited cell growth. Together, our data demonstrate that overexpression of evolutionarily conserved F-LANa occurs frequently and may play an important role in proliferation.

Amino Acid Sequence↗

Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration.

In this Phase I trial, patients' peripheral blood dendritic cells were pulsed with peptides eluted from the surface of autologous glioma cells. Three biweekly intradermal vaccinations of peptide-pulsed dendritic cells were administered to seven patients with glioblastoma multiforme and two patients with anaplastic astrocytoma. Dendritic cell vaccination elicited systemic cytotoxicity in four of seven tested patients. Robust intratumoral cytotoxic and memory T-cell infiltration was detected in two of four patients who underwent reoperation after vaccination. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous peptide-pulsed dendritic cell vaccine for patients with malignant glioma.

Adult↗

A noninvasive cross-correlation ultrasound technique for detecting spatial profile of laser-induced coagulation damage--an in vitro study.

A cross-correlation A-mode ultrasound technique is proposed for noninvasively detecting the spatial profile of coagulation damage in tissue being irradiated by laser. The basic assumption underlying this technique is that when coagulation is taking place in a tissue region, owing to thermally-induced structure changes in tissue, the waveform of echo signal scattered from that region should be changing accordingly. Our technique consists of four steps: 1) repeatedly sending the same acoustic signal to the tissue being heated; 2) tracking echo signals scattered from many small tissue regions using a cross-correlation echo-tracking technique; 3) quantifying waveform change of echo signal scattered from each region by means of cross-correlation coefficient between the currently acquired signal and a reference signal; 4) using the spatial profile of the degree of the waveform change to represent the tissue coagulation status at different depths. We carried out 23 heating experiments on fresh canine liver samples using a Nd:YAG laser (1,064 nm wavelength) at various light intensity (62 to 105 W/cm2) and exposure time (20 to 350 s). A 13-mm-diameter 10-MHz broadband single-element spherical focused ultrasound transducer was used. The spatial profiles of the degree of coagulation damage in the heated tissues, as determined by our technique, qualitatively agreed with the grossly inspected results. They also appeared to be consistent with the experimental and theoretical findings in the literature on laser-tissue interaction. Moreover, we developed an automatic procedure to compute the coagulation depth using the spatial profiles of the waveform change. We used the result as an indirect but quantitative means for evaluating the technique. Good overall agreement with a root mean square (rms) difference of only 0.81 mm was obtained between the computed and visually inspected final coagulation depths for the 23 experiments.

Animals↗

Innovative cancer vaccine strategies based on the identification of tumour-associated antigens.

The identification of tumour-associated antigens has opened up new approaches to cancer immunotherapy. While past research focused on CD8+ cytotoxic T-cell responses, accumulating evidence suggests that CD4+ T cells also play an important role in orchestrating the host immune response against cancer. In this article, we summarise new strategies for the identification of major histocompatibility complex (MHC) class II-associated tumour antigens and discuss the importance of engaging both CD4+ and CD8+ T cells in cancer immunotherapy. The cloning of MHC class I- or class II-associated antigens has made it possible to develop synthetic and recombinant cancer vaccines that express specific tumour antigens. There are three major types of synthetic and recombinant cancer vaccines: recombinant viral and bacterial vaccines; naked DNA or RNA vaccines; and recombinant protein and peptide vaccines. In this article, we also discuss a new generation of recombinant cancer vaccines, 'self-replicating' DNA and RNA vaccines. Studies on the mechanisms of 'self-replicating' nucleic acid vaccines revealed that the enhanced immunogenicity was not due to an enhanced antigen expression, suggesting that the quantitative difference may not be as important as the qualitative difference in antigen presentation. The presence of the RNA replicase in the 'self-replicating' nucleic acid vaccines mimics alphavirus infection, which triggers the innate antiviral pathways of the host cells. Studies on how viral and cellular modulators of the innate antiviral pathways affect vaccine function should provide molecular insights crucial to future vaccine design.

Animals↗

Antisense of ATP synthase subunit e inhibits the growth of human hepatocellular carcinoma cells.

Differentially expressed genes between normal and hepatocellular carcinoma tissues were investigated using differential display. We identified a cDNA fragment that was overexpressed in cancer tissue. Homology analysis showed that the sequence was identical to human ATP synthase subunit e (hAS-e). Moreover, Northern blot analysis demonstrated that hAS-e was overexpressed in 10 of 11 (91%) specimens of hepatocellular carcinoma compared with corresponding normal tissues. We introduced antisense hAS-e into a human hepatocellular carcinoma BEL-7404 cell and found that downregulation of the hAS-e led to cell growth inhibition. It was also found that the antisense transfection could decrease the serum-stimulated activation of mitogen-activated protein kinase (MAP kinase). Together, the results suggest that antisense of hAS-e can inhibit cell proliferation through the MAP kinase pathway. Our data indicate that hAS-e may become a new target in gene therapy.

Base Sequence↗

[Spectral interferences of rare earth elements observed with a high resolution inductively coupled plasma atomic emission spectrometer. VI. Spectral interferences of lanthanum, terbium, holmium and erbium as matrices].

The spectral interferences of La, Tb, Ho and Er (1,000 micrograms.mL-1, separately) as matrices on the other rare earth elements (REEs, 1 or 5 micrograms.mL-1) were studied with a high resolution ICP atomic emission spectrometer with a grating of 3,600 grooves/mm. Totally 66 analytical lines of 15 REEs were selected as the prominent lines in the spectral interference studies. The overlapping profiles of analytical lines and interference line were obtained by scanning different solutions (blank, analyte, and four REE matrices, individually) within the selected wavelength windows (0.2 nm for each analytical line). Some new spectral lines of La, Tb, Ho and Er were observed. The "best" analytical lines of 14 REEs were recommended based on the Q-values and the true detection limits.

Erbium↗

Enhancement of tumor-specific immune response with plasmid DNA replicon vectors.

To enhance the immunogenicity of nucleic acid vaccines, we used plasmid DNA vectors that contained replicons derived from the prototype alphavirus, Sindbis, and another alphavirus, Semliki Forest virus. When transfected into cells or injected directly into animal muscle, these plasmids launch a self-replicating RNA vector (replicon) which in turn directs the expression of a model tumor antigen. Immunization with plasmid DNA replicons elicited immune responses at doses 100 to 1000-fold lower than conventional DNA plasmids and effectively treated mice bearing an experimental tumor expressing the model antigen. Significantly, replicon-based DNA plasmids did not produce a greater quantity of antigen; instead, antigen production differed qualitatively. Plasmid DNA replicons mediated antigen production that was homogeneous in all transfected cells and associated with the apoptotic death of the host cells. Because of their safety and efficacy, plasmid DNA replicons may be useful in the development of recombinant vaccines for infectious diseases and cancer.

Animals↗

The promise of nucleic acid vaccines.

Establishing the effective use of 'naked' nucleic acids as vaccines would undoubtedly be one of the most important advances in the history of vaccinology. While nucleic acids show much promise for use as vaccine vectors in experimental animals, not a single naked nucleic acid vector has been approved for use in humans. Indeed, data from human clinical trials is scant: nucleic acid vaccines have not been clearly demonstrated to have any convincing efficacy in the prevention or treatment of infectious disease or cancer. Here we illustrate possible mechanisms underlying effective nucleic acid vaccination. We focus on progress that has been made in the improvement of their function. Additionally, we identify promising new strategies and try to forecast future developments that could lead to the real success of nucleic acid vaccines in the prevention and treatment of human disease.

DNA Replication↗

Zinc-induced neuronal death in cortical neurons.

Although Zn2+ is normally stored and released in the brain, excessive exposure to extracellular Zn2+ can be neurotoxic. The purpose of the present study was to determine the type of neuronal cell death, necrosis versus apoptosis, induced by Zn2+ exposure. Addition of 10-50 microM ZnCl2 to the bathing medium of murine neuronal and glial cell cultures induced, over the next 24 hrs., Zn2+-concentration-dependent neuronal death; some glial death also occurred with Zn2+ concentrations above 30 microM. The neuronal death induced by 20 microM Zn2+ was characterized by coarse chromatin condensation, the formation of apoptotic bodies, and internucleosomal DNA fragmentation. It was attenuated in cortical cell cultures prepared from mice null for the bax gene, and by the caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-CH2F (ZVAD, 100 microM), but not by the NMDA receptor antagonist, D-2-amino-5-phosphonovalerate (D-APV, 200 microM ). In contrast, the neuronal death induced by 50 microM Zn2+ was characterized by plasma membrane disruption and random DNA fragmentation; this death was attenuated by D-APV, but exhibited little sensitivity to ZVAD or deletion of bax. These results suggest that Zn2+ can induce cell death with characteristics of either apoptosis or necrosis, depending on the intensity of the Zn2+ exposure.

2-Amino-5-phosphonovalerate↗

[Study on human leukemia cell apoptosis inducing effect of fraction C of Naja naja Actra Venom].

OBJECTIVE: To study the effect and mechanism of fraction C isolated from Naja naja Actra Venom (FCNNAV) in inducing apoptosis of human leukemia cells. METHODS: Light microscope, transmission electron microscope, DNA electrophoresis, flow cytometry and RT-PCR assay were used to observe the changes of human leukemia cells in morphology and biochemistry, and Bcl-2/Bax expression after exposing to FCNNAV. RESULTS: FCNNAV could induce HL60 cells apoptosis demonstrated by the typical morphological and biochemical changes. Flow cytometry showed that J6-1, K562, HL60 and fresh leukemia cells apoptosis could be induced by FCNNAV, and the apoptosis rate was dose-dependent. RT-PCR detection showed the Bcl-2 gene expression of HL60 cells was down-regulated by FCNNAV, whereas the Bax expression was unaffected. CONCLUSION: FCNNAV could induce apoptosis of human leukemia cells and this effect is related to down-regulation of Bcl-2 gene expression level.

Adolescent↗

[Spectral interferences of rare earth elements with a high resolution sequential ICP-AES. IV. Spectral interferences of europium and gadolinium].

The spectral interferences of Eu and Gd(100 micrograms.mL-1, separately) as matrices on the other REEs(1 or 5 micrograms.mL-1) were studied with a high resolution sequential ICP-AES with a grating of 3,600 grooves/mm. Totally 66 prominent lines of 14 REEs were selected as the analytical lines for the spectral interference studies. The overlapping profiles of analytical lines and interference lines were obtained by scanning four solutions(blank, analyte, Eu matrix, and Gd matrix, individually) within the selected wavelength windows (0.2 nm for each analytical line). Some new emission lines of Eu and Gd were observed. The obtained information of spectral interferences would be very useful for the selection of the best analytical lines for the determination of REEs in the other REEs matrices.

Europium↗

DNA and RNA-based vaccines: principles, progress and prospects.

DNA vaccines were introduced less than a decade ago but have already been applied to a wide range of infectious and malignant diseases. Here we review the current understanding of the mechanisms underlying the activities of these new vaccines. We focus on recent strategies designed to enhance their function including the use of immunostimulatory (CpG) sequences, dendritic cells (DC), co-stimulatory molecules and cytokine- and chemokine-adjuvants. Although genetic vaccines have been significantly improved, they may not be sufficiently immunogenic for the therapeutic vaccination of patients with infectious diseases or cancer in clinical trials. One promising approach aimed at dramatically increasing the immunogenicity of genetic vaccines involves making them 'self-replicating'. This can be accomplished by using a gene encoding RNA replicase, a polyprotein derived from alphaviruses, such as Sindbis virus. Replicase-containing RNA vectors are significantly more immunogenic than conventional plasmids, immunizing mice at doses as low as 0.1 microg of nucleic acid injected once intramuscularly. Cells transfected with 'self-replicating' vectors briefly produce large amounts of antigen before undergoing apoptotic death. This death is a likely result of requisite double-stranded (ds) RNA intermediates, which also have been shown to super-activate DC. Thus, the enhanced immunogenicity of 'self-replicating' genetic vaccines may be a result of the production of pro-inflammatory dsRNA, which mimics an RNA-virus infection of host cells.

Animals↗

The antiviral enzymes PKR and RNase L suppress gene expression from viral and non-viral based vectors.

Expression of transfected genes is shown to be suppressed by two intracellular enzymes, RNase L and protein kinase PKR, which function in interferon-treated cells to restrict viral replication. RNase L(-/-) or PKR(-/-) murine embryonic fibroblasts produced enhanced levels of protein from transfected genes compared with wild-type cells. Increased expression of exogenous genes in RNase L(-/-) cells correlated with elevated levels of mRNA and thus appeared to be due to enhanced mRNA stability. Plasmid encoding adenovirus VA RNAs was able to further enhance accumulation of the exogenous gene transcript and protein, even in cells lacking PKR. In contrast to the increased expression of transfected genes in cells lacking RNase L or PKR, expression of endogenous host genes was unaffected by the absence of these enzymes. In addition, a dominant-negative PKR mutant improved expression from a conventional plasmid vector and from a Semliki Forest virus derived, self-replicating vector. These results indicate that viral infections and transfections produce similar stress responses in mammalian cells and suggest strategies for selectively increasing expression of exogenous genes.

Adenoviridae↗

A fuzzy logic approach to identifying brain structures in MRI using expert anatomic knowledge.

We report a novel computer method for automatic labeling of structures in 3D MRI data sets using expert anatomical knowledge that is coded in fuzzy sets and fuzzy rules. The method first identifies major structures and then uses spatial relationships to these landmarks to recognize other structures. This labeling process simulates the iterative process that we ourselves use to locate structures in images. We demonstrate its application in three data sets, labeling brain MRI by locating the longitudinal and lateral fissures and the central sulci and then determining boundaries for the frontal lobes. Our method is adaptable to the identification of other anatomical structures.

Brain↗

A multi-gate time-of-flight technique for estimation of temperature distribution in heated tissue: theory and computer simulation.

Non-invasive determination of temperature distribution in biological media is important in many heating-related studies, such as thermal treatment. In this paper, we present an in vitro ultrasound technique for estimation of temperature distribution in heated tissue. Our technique consists of two major steps: (1) using multiple time gates to track echo signals scattered from tissue regions at different depths; (2) estimating temperature distribution based on heating-induced changes of arrival times of echo signals scattered from the targeted tissue regions. We use the conventional cross-correlation approach to track echoes. For temperature estimation, we have developed an iterative method that takes into account the influences of thermal expansion and heating-induced change in the speed of sound on the time of flight. We have introduced a concept of thermal sensitivity of the time of flight and used it to derive a theoretical formula that relates the achievable accuracy on the estimation of tissue temperature to seven parameters. The seven parameters are tissue thermal sensitivity of the time of flight, signal-to-noise ratio, bandwidth and center frequency of the signal, degree of signal decorrelation induced by changes in tissue physical properties during tissue heating, and widths and spacing of the time gates. We tested our technique by computer simulation, using a random discrete scatterer model and temperature distribution data acquired in our laser heating experiments on prostate tissue of live dog. Simulation results showed that our technique could accurately estimate the temperature distribution in the heated tissue. Our technique is fast in terms of computation and could be used as a research tool for in vitro real-time monitoring of temperature distribution in tissue under hyperthermal heating.

Acoustics↗

Treatment of carotid-cavernous sinus fistulas retrograde via the superior ophthalmic vein (SOV).

BACKGROUND: Carotid-cavernous sinus fistula is an old difficulty in neurosurgery. At present, the main way to deal with it is by embolizing the fistula via an arterial route. But if the fistula is small or supplied by several branches, it is difficult to embolize via an arterial approach. METHODS: In this report, 21 patients with carotid-cavernous sinus fistulae were successfully cured by embolizing the fistula via the SOV approach. RESULTS: All patients were cured, and there were no serious postoperative complications. Follow-up has been carried out in 19 cases for 8 months to more than 4 years; no recurrence manifested. CONCLUSION: For carotid-cavernous sinus fistulae that cannot be embolized arterially, the superior ophthalmic vein route is an easy, safe, effective and promising approach.

Adolescent↗