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Biomedical subjects

H Ying

Publications and source records attributed to H Ying.

At least 37 records · Page 2Linked to original sources

Cancer therapy using a self-replicating RNA vaccine.

'Naked' nucleic acid vaccines are potentially useful candidates for the treatment of patients with cancer, but their clinical efficacy has yet to be demonstrated. We sought to enhance the immunogenicity of a nucleic acid vaccine by making it 'self-replicating'. We accomplished this by using a gene encoding an RNA replicase polyprotein derived from the Semliki forest virus, in combination with a model antigen. A single intramuscular injection of a self-replicating RNA immunogen elicited antigen-specific antibody and CD8+ T-cell responses at doses as low as 0.1 microg. Pre-immunization with a self-replicating RNA vector protected mice from tumor challenge, and therapeutic immunization prolonged the survival of mice with established tumors. The self-replicating RNA vectors did not mediate the production of substantially more model antigen than a conventional DNA vaccine did in vitro. However, the enhanced efficacy in vivo correlated with a caspase-dependent apoptotic death in transfected cells. This death facilitated the uptake of apoptotic cells by dendritic cells, providing a potential mechanism for enhanced immunogenicity. Naked, non-infectious, self-replicating RNA may be an excellent candidate for the development of new cancer vaccines.

Animals↗

[S-phase arrest associated apoptosis leads to diversities of drug resistance and mutation rate in human breast cancer cells].

To find out different abilities of drug resistance and mutation rate and its fundamental mechanism among the human breast cancer cells, two variants, L-2 and Br-1, derived from a common parent cell line of MDA-MB-435, were assayed for sensitivity to PALA and determined for their mutation rate to drug resistance by clone formation and fluctuation analysis respectively. Further, by means of cell growth rate test, flow cytometry, measurement of DNA fragmentation and western blot, the relationship between drug resistance and mutation rate and cell cycle control and apoptosis was explored. The results showed that the mechanism of S-phase arrest associated apoptosis created such a different ability of drug resistance and stability of genome in two cell lines with identical p53 mutation.

Antineoplastic Agents↗

Regulation of mouse CD72 gene expression during B lymphocyte development.

CD72 is a 45-kDa transmembrane glycoprotein that is predominantly expressed on cells of the B lineage except plasma cells. Previously, we identified the 255-bp minimal mouse CD72 promoter capable of tissue-specific and developmental stage-specific expression. DNase I footprinting analysis of the 255-bp CD72 promoter revealed three protected elements, footprint (FP) I, FP II, and FP III. FP II, which extends from nucleotide -189 to -169 of the mouse CD72 promoter, exhibited both tissue-specific and developmental stage-specific activity that was reflective of the activity of the CD72 gene in vivo. In this report, we show that FP II is specifically recognized by the transcription factor B cell-specific activator protein (BSAP). Mutations eliminating the binding of BSAP in reporter constructs also eliminated the increase of reporter activity in B cells. In addition, cotransfections with reporter constructs plus different amounts of expression plasmids for BSAP showed that CD72 promoter activity was up-regulated by BSAP in plasmacytoma cells and T cells in a dose-dependent manner. Moreover, the expression level of CD72 decreased 10-fold on normal plasma cells. Compared with the presence of BSAP binding in mature B cells, the binding of BSAP was undetectable in those plasma cells. This study strongly suggests that BSAP-FP II interaction plays a critical role in determining the cell-type specificity of the CD72 promoter. The absence of positive factors such as BSAP accounts for at least part of the loss of mouse CD72 expression in plasma cells and thus might be common for the down-regulation of many molecules at the plasma cell stage.

Animals↗

PU.1/Spi-1 is essential for the B cell-specific activity of the mouse CD72 promoter.

CD72 is a 45-kDa glycoprotein that is predominantly expressed on cells of the B lineage, except for plasma cells. Its expression pattern is representative of many B cell-specific proteins, which are essential for B cell development and activation but are down-regulated after B cells become terminally differentiated plasma cells. We have examined the promoter region of the mouse CD72 gene to identify sequences responsible for this regulatory pattern. The CD72 gene does not have an obvious TATAA box. Primer extension assays identified multiple transcription initiation sites. Deletion analyses have identified the 255-bp minimal promoter required for tissue-specific and developmental stage-specific expression. DNase I footprinting analysis of the CD72 minimal promoter revealed three protected elements: FP I, FP II, and FP III. Sequences corresponding to FP I or III gave increased reporter gene activity specifically in B cells, but not in T cells or NIH-3T3 cells. Sequences corresponding to FP II gave increased reporter gene activity in mature B cells, but not in plasma cells or non-B cells. Electrophoretic mobility shift assays and DNase I protection analyses revealed that FP I was bound by the transcription factor PU.1/Spi-1. Transient reporter analyses with plasmid bearing the mutated PU.1 binding site showed that binding of PU.1 is necessary for the increase in CD72 promoter activity in B cells. These results suggest that the 255-bp CD72 promoter confers both tissue specificity and developmental stage specificity, and that the B cell and macrophage-specific transcription factor PU.1 is essential for regulating the tissue specificity of the mouse CD72 promoter.

Animals↗

[Relationship between the expression level of alpha-MHC gene and cardiac contractility during heart failure].

To investigate the molecular basis of the decrease in myocardial contractility during heart failure, an animan model of heart failure was set up by means of deoxycorticosterone-acetate impregnated silicone rubber implants in wistar rats. Cardiac contractility in normal and heart failure rats was examined, and gene expression of its myocardial contractile protein, alpha-MHC, was quantitatively analyzed at gene transcription level by using RNA slot blot hybridization. The results showed that the cardiac contractility and the alpha-MHC mRNA levels in heart failure rats were all lower than those in the normal. Statistical analysis showed a positive correlation between the cardiac contractility and the gene expression of alpha-MHC (r = 0.4143, n = 43, P < 0.05). The above results indicate that gene expression level of alpha-MHC is one of the key factors determining cardiac contractility.

Animals↗

[Augmented effect of Composite Radix Salviae Miltiorrhizae Injection on radiosensitivity of leukemia cells].

OBJECTIVE: To explore the effect of Composite Radix Salviae Miltiorrhizae Injection (CSMI) on radiosensitivity of leukemia cells. METHODS: Semisolid agar culture and flow cytometry assay were performed for studying the change in radiosensitivity of HL60 cell line and fresh human leukemia cells after exposing to CSMI. RESULTS: The D0(the inverse of the slope of the survival curve) and SF2(survival fraction at 2 Gy) of HL60 cell line were decreased from 1.53, 0.34 to 0.93, 0.12, respectively and apoptosis rates after radiation were raised significantly by CSMI. Furthermore, the concentration of CSMI and the time of mixed culture with CSMI before irradiation had positive relation to the effects mentioned above. Compared with control group, CSMI could increase the radiation-induced apoptosis of fresh leukemia cells (5.89 +/- 2.91% vs 12.05 +/- 3.06%). CONCLUSION: CSMI could obviously enhance the radiosensitivity of leukemia cells.

Drugs, Chinese Herbal↗

[Influences of Freon-12 (CF2CCl2) on the electron number densities in an inductively coupled plasma (ICP) measured with Halpha line--the applications of ICP in the disposal of hazardous waste].

The inductively coupled plasma was applied to decompose Freon 12 (CF2CCl2). The efficiency of the decomposition was indirectly evaluated by comparing the electron number densities in the central channel of the ICP with the addition of different amounts of Freon-12. Halpha line (656.3nm) was used to measure the electron number density due to Hbeta line (486.1nm) is seriously interfered with the addition of Freon-12 under the selected operating conditions. The "thermal pinch" effect was found with the addition of Freon-12, which is beneficial to the complete decomposition of the compound.

English Abstract↗

[Correction of spectral interferences by ICP-AES primary expert system].

A subpackage for spectral interference correction has been set up in ICP-AES primary expert system. Some numerical recipes have been applied in this subpackage, such as curve smoothing, derivative spectrum, FFT technique, spectral resolving etc. A comprehensive method for spectral interference correction is presented. All these numeric recipes have been tested with simulated data and also utilized in several typical examples of real spectra. Results are satisfactory.

English Abstract↗

[Study of spectral interferences of REEs with the matrix of dy for a high resolution ICP-AES].

The spectral interferences of the matrix of Dy on other REEs have been studied for a high resolution ICP-AES with a grating of 3600 grooves/mm. 66 analytical lines of 14 REEs have been selected as the prominent lines in the spectral interference studies. Three kinds of databases for Dy lines have been established for the spectra search and recognition. Thus, these databases can provide information of Dy lines accurately and conveniently.

English Abstract↗

High density lipoprotein decreases beta-amyloid toxicity in cortical cell culture.

A hallmark of Alzheimer's disease (AD) is the extracellular deposition and accumulation of a 39-43 amino peptide, known as the amyloid beta (A beta) protein, within the brain. It has been postulated that A beta may in some way contribute directly to AD pathogenesis. The epsilon 4 allele of apolipoprotein E (apoE) is a major AD risk factor. Since both apoE and A beta are components of lipoproteins in plasma and cerebrospinal fluid, we asked whether lipoproteins and apoE isoforms would modify the toxicity of A beta (1-42) in cortical cell cultures. We show that high density lipoprotein with or without apoE reduces A beta toxicity and that apoE in the absence of lipoproteins does not affect A beta toxicity. These results suggest that interactions between A beta and lipoproteins in the brain could influence AD pathogenesis.

Alleles↗

Enzymes in intestinal juice from patients with liver diseases and colon polyps: measurement of bilirubin, alkaline phosphatase, aspartate aminotransferase and lactate dehydrogenase.

Since the amounts of hepatogenous enzymes discharged into the intestinal tract remain unknown, this study was initiated to evaluate the amounts of the enzymes in the intestinal tract. Whole gut lavage fluid (polyethyleneglycol electrolyte solution) was administered orally to 42 subjects, consisting of 5 patients with hepatoma, 10 with chronic hepatitis, 10 with colon polyps, and 17 control subjects without liver disease. Two hr after the large intestinal lavage, the digestive tract juice was aspirated by colonoscopy, and the bilirubin (Bil), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in the aspirates were measured. A positive correlation between the AST and LDH values was found, and a significant difference in these values between the hepatic disorders and the normal controls was noticed. A significant positive correlation between the ALP and Bil values was found, and a statistical difference in these values between the group of colon polyps and the controls and other groups was observed. This lavage fluid technique enables to estimate the amounts of hepatic enzymes discharged into the intestinal tract, thereby opening a new avenue for future enzyme research.

Adult↗

Structure of the mouse CD72 (Lyb-2) gene and its alternatively spliced transcripts.

The complete sequence of the CD72 gene from the C57L mouse, including the 5' and 3' flanking sequences, is reported. The gene spans 6830 base pairs and includes nine exons surrounding eight introns. It does not have an obvious TATAA box, so it belongs to a group of genes with TATA-less promoters that are regulated during mammalian immunodifferentiation. cDNA sequence comparisons among CD72a, CD72b, and CD72c alleles have demonstrated two distinct seven amino acid insertion/deletions among these allelic variants. Based on our genomic sequence studies as well as PCR analyses, we found that different strains of mice can alternatively or exclusively use either of two AG sites surrounding the 21-bp insertion/deletions as 3' splice sites in an allele-specific manner. Other alternative splicing events, such as exon skipping, also contribute to CD72 polymorphism. In mouse splenic B cells there are allele-specific distributions of CD72 mRNAs that contain sequences from both exon 3 and exon 4, from either exon 3 or exon 4, or from neither exon 3 nor 4. It is unclear what the in vivo function might be of the proteins encoded by the mRNA forms lacking these exon sequences.

Alternative Splicing↗

Socio-economic status and micro-environmental factors in relation to the risk of Japanese encephalitis: a case-control study.

In a population-based case-control study in Southern Henan Province, central China, children suffering from Japanese encephalitis (JE) were compared with neighborhood controls matched by age and sex in terms of several social and environmental variables. Factors found by crude analysis to be associated with an increased risk of JE included lower family income, lower parental education, living in houses near the periphery of villages and poor quality of houses. When adjustment was made for confounding variables, only the association of house location within village remained of borderline significance (OR = 0.51, 95% CI = 0.15 approximately 1.03). It is suggested that the beneficial effect of higher family income and parental education was partly due to the fact that those parents might be more conscious about having their children vaccinated in the situation where there was a shortage of JE vaccine in the study area.

Animals↗

Prognostic factors of early sequelae and fatal outcome of Japanese encephalitis.

A clinical case control study to identify prognostic factors present at hospital admission associated with early sequelae and fatal outcome of acute Japanese encephalitis (JE) was carried out in Gusi county, Henan Province, central China from June to September 1991. A total of 70 patients with laboratory-confirmed acute JE were studied, of whom 3 cases died and 33 cases had neurological or psychiatric sequelae at the end of three months follow-up. The results showed that acute JE at younger age, with higher body temperature, high white cell count in CSF, and deep coma present at hospital admission were markers for unfavorable outcomes (sequelae or fatal). A history of the vaccination was not correlated with the early sequelae and fatal outcome of the disease. The paper suggests that early diagnosis and treatment and universal JE vaccination for all susceptible populations are keys for decreasing incidence of sequelae and fatal outcome of acute JE.

Acute Disease↗

Ultrasonic Doppler detection of laser-tissue interaction.

Laser therapy for the safe and effective coagulation and ablation of tissues requires precise control of the amount of energy delivered to and absorbed by the volume of tissue of interest. We propose that an ultrasonic transducer pointing in the same direction as the laser fiber could be used to monitor the changes in ultrasonic properties caused by the absorption of light by the tissue. A modified 20 MHz pulsed Doppler was used to evaluate the ultrasonic effects of 35 exposures of beef liver and muscle to a high power diode laser in vitro in real time. We found two distinct levels of acoustic activity in the tissue. Type 1 activity consisted of slow variations in the phase and small changes in the amplitude of the echoes, while type 2 activity consisted of large and rapid fluctuations in amplitude and phase. We found that the residual increase in echogenicity of the tissue and the delay to the onset of type 2 activity were functions of laser power and tissue type and were correlated to lesion severity. We hypothesize that type 1 activity corresponds to motion (thermal expansion and contraction) of the tissue, and that type 2 activity corresponds to the creation of gas bubbles (vaporization) in the tissue. We conclude that the absorption of energy changes the acoustic properties of tissue during and after exposure and that Doppler signal processing can be used to differentiate various levels of laser-tissue interaction in real time.

Animals↗

Propofol prevents or elevates the threshold for lidocaine-induced seizures in rats.

Hypothesizing that propofol's pro and anticonvulsant effects might be dose dependent, we determined the effect of 25, 50, and 100% of a previously determined anesthetic dose of propofol for rats on the amount of lidocaine required to induce seizures. Lidocaine was infused at 2.5 mg kg-1 min-1 into animals that were receiving either (a) 70% N2O balance O2 (n = 10), control group, (b) 2 mg kg-1 bolus followed by 12 mg kg-1 h-1 propofol infusion with 70% N2O (n = 10), group 2, (c) 4 mg kg-1 followed by 24 mg kg-1 h-1 propofol with 70% N2O (n = 20), group 3, (d) 8 mg kg-1 followed by 48 mg kg-1 h-1 propofol with 70% N2O (n = 10), group 4, or (e) 8 mg kg-1 followed by 48 mg kg-1 h-1 propofol without N2O (n = 10), group 5. Temperature PaCO2, and pH were maintained within normal limits until disturbed by seizure activity or lidocaine toxicity. The plasma concentration of lidocaine required to induce electroencephalographically (EEG) detected seizures was 8.7 +/- 0.7 micrograms ml-1 in control animals, 16 +/- 1.7 micrograms ml-1 in group 2, and 32 +/- 4 micrograms ml-1 in 13 animals from group 3 that experienced a seizure (p < 0.01). Seizures did not occur in seven of 20 group 3 rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗