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Biomedical subjects

L Cheng

Publications and source records attributed to L Cheng.

At least 271 records · Page 15Linked to original sources

[The effects of high dietary zinc on alloxan induced diabetic mice].

The effects of high dietary zinc on alloxan induced diabetic mice were studied. The results showed that high zinc could sharply decrease the body weight and increase food intake, water intake and urine of diabetic mice, and increase blood sugar levels in diabetic mice. After alloxan injection in diabetic model group, urine sugar levels reached [symbol: see text] at the 2nd day and [symbol: see text] at the 6th day. After alloxan injection in high-zinc-diabetic mice group, urine sugar levels reached [symbol: see text] and [symbol: see text] at the 2nd and the 4th day, respectively. These results suggested that the high level of dietary zinc may be damage to diabetic patients.

Animals↗

[Processing technology of rhizoma Arisaematis (Pinellia pedatisecta Schott)].

Using the qualitative standard of Rhizoma Arisaematis stipulated in Pharmacopoeia and combining with the toxic reaction in experimental mice, the optimum amount of KAl(SO4)2.12H2O for eliminating the toxic reaction of Rhizoma Arisaematis was selected. Based on the comparison of experiments, two new technologies for processing Rhizoma Arisaematis have been established. Pilot production shows that these technologies are feasible for mass production.

Animals↗

[Effect of processing on toxcicity and analgesia of radix Aconiti coreani].

The experimental results showed that the Radix Aconiti Coreani and its processed products did not have remarkable toxic effect in p.o. But there was significant toxicity before processing and weakened toxicity after processing in i.p. In the skin test, the Radix Aconiti Coreani and its processed products showed no stimulating effect. The analgesic experiment showed that the Radix Aconiti Coreani and its steamed products could inhibit the pain. The products processed with bean curd and ginger-KAl(SO4)2.12H2O also could alleviate the pain induced by acetic acid, but no remarkable effect was observed in mice on the pain induced by hot plate.

Analgesics↗

[Optimization of technical parameters for processing radix Aconiti coreani].

Based on the determination of guanfu A, hypaconitine, and total alkaloids, along with the experiment of acute toxicity of sliced Radix Aconiti Coreani and in compliance with the quality standard stipulated in pharmacopeia-surface features cross section colour and odor of sliced Radix Aconiti Co-reani the technology of processing Radix Aconiti Coreani has been optimized to be steaming the drug for four hours.

Aconitine↗

[The development of an computerized analysis system for the women pelvic cavity impedance rheogram].

This article introduces the components and functions of an computered analysis system for the women pelvic cavity impedance rheogram. It can sample the pelvic cavity impedance rheogram signal of the body double-side and the reference ECG signal. With help of manual intervence, it also can automatically recognize characteristic points of the pelvic cavity impedance rheogram and measure the parameters. It can correct the recognized characteristic points simultaneously and print the pelvic cavity impedance rheogram of the body double-side and 15 characteristic data parameters. After clinical applying, the analysis results of mors 100 patients make clear that: this system has remarkably clinical significance for diagnosis of the women pelvic cavity extravasated blood and evaluation of treating effect, so it has much better clinical applied expectation.

Equipment Design↗

Seizure: a rare and transient cause of portal venous gas.

Gas in the hepatic portal venous system has been noted to be a complication of a wide range of intra-abdominal catastrophes that involve damage to bowel mucosa. We describe a patient who, after a seizure, was found to have portal venous gas on sonography and CT. The search for other possible causes revealed negative results. This case demonstrates a rare cause of hepatic portal venous gas that is self-resolving and clinically benign.

Adult↗

Out of hours cross-cover between oral and maxillofacial surgery and ear, nose and throat surgery.

Emergency cross-cover between two specialties, oral and maxillofacial surgery and ear, nose and throat surgery, has been introduced and run successfully in York District Hospital for the last 18 months in order to reduce the working hours of junior doctors, as recommended by the New Deal. During this trial period of out of normal hours cross-cover in a two-tier system, we have found that the new arrangement has increased our shared knowledge, understanding and practical experience of both specialties as well as satisfying the service needs with no significant clinical problems arising.

Education, Medical, Graduate↗

Optimized codon usage and chromophore mutations provide enhanced sensitivity with the green fluorescent protein.

The green fluorescent protein (GFP) from Aequorea victoria is a versatile reporter protein for monitoring gene expression and protein localization in a variety of cells and organisms. Despite many early successes using this reporter, wild type GFP is suboptimal for most applications due to low fluorescence intensity when excited by blue light (488 nm), a significant lag in the development of fluorescence after protein synthesis, complex photoisomerization of the GFP chromophore and poor expression in many higher eukaryotes. To improve upon these qualities, we have combined a mutant of GFP with a significantly larger extinction coefficient for excitation at 488 nm with a re-engineered GFP gene sequence containing codons preferentially found in highly expressed human proteins. The combination of improved fluorescence intensity and higher expression levels yield an enhanced GFP which provides greater sensitivity in most systems.

Animals↗

Reduced DNA repair capacity in lung cancer patients.

Although lung cancer is the paradigm of a tobacco-induced malignancy, host-specific factors modulate susceptibility to tobacco carcinogenesis. Variations in DNA repair may influence the rate of removal of DNA damage and of fixation of mutations. To test the hypothesis that genetically determined DNA repair capacity (DRC) modulates lung cancer susceptibility, we conducted a pilot case-control study of 51 patients with newly diagnosed, previously untreated lung cancer and 56 controls identified from local community centers and frequency matched to the cases on age, sex, and ethnicity. The subjects were ascertained and interviewed for an ongoing molecular epidemiological investigation of lung cancer susceptibility. We measured DRC in the subjects' peripheral blood lymphocytes by using the host-cell reactivation assay, which measures cellular reactivation of a reporter gene damaged by exposure to 75 microM benzo(a)pyrene diol epoxide. The mean level of DRC in cases (3.3%) was significantly lower than that in controls (5.1%) (P < 0.01). Only nine cases (18%) had DNA repair levels greater than the median value of repair in the controls. This median level of DRC in controls was used as the cutoff value for calculating the odds ratios. After adjustment for age, sex, ethnicity, and smoking status, the cases were five times more likely than the controls to have reduced DRC (odds ratio, 5.7; 95% confidence interval, 2.1-15.7). Younger cases (< 65 years) and smokers were more likely than controls to have reduced DRC. These findings suggest that individuals with reduced DRC are at an increased risk of developing lung cancer.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Benzo(a)pyrene diol epoxide-induced chromosomal aberrations and risk of lung cancer.

Benzo(a)pyrene is considered a classic DNA-damaging carcinogen and is one of a multitude of polycyclic aromatic hydrocarbons commonly found in tobacco smoke and in the ambient environment. In this report, we describe the characteristics of chromosomal aberrations induced in vitro by activated benzo(a)pyrene diol epoxide (BPDE) in lymphocyte cultures of 172 normal individuals ages 19-95 years and present the analysis of a pilot case-control study of 33 lung cancer patients and 96 selected controls without history of cancer and frequency matched on age (50-85 years) to the cases. The BPDE-induced chromosomal aberrations were predominantly single chromatid breaks, with few isochromatid breaks or exchange figures. In the 172 normal subjects, the frequencies of both spontaneous and BPDE-induced chromatid breaks were not correlated with age, sex, ethnicity, or tobacco use. However, the frequency of BPDE-induced chromatid breaks was significantly correlated with the frequency of spontaneous chromatid breaks (r = 0.19, P < 0.05). In addition, Hispanics had significantly higher mean BPDE-induced chromatid breaks than did non-Hispanic whites (P < 0.01). From the case-control analyses, the frequency of BPDE-induced chromosomal aberrations was significantly higher in cases (mean, 0.67 breaks/cell) than in controls (mean, 0.41 breaks/cell; P < 0.0001). An adjusted odds ratio of 6.53 (95% confidence interval, 3.74-11.4) for lung cancer was associated with increased frequency of these chromosomal aberrations. The higher rate of BPDE-induced chromosomal aberrations may be due to inefficient DNA repair. These findings warrant additional molecular epidemiological studies. The BPDE mutagen sensitivity assay will facilitate epidemiological studies of genetic susceptibility to smoking-related cancers.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

In vitro induction of benzo(a)pyrene diol epoxide-DNA adducts in peripheral lymphocytes as a susceptibility marker for human lung cancer.

Given the same exposure, DNA adduct profiles can be considered as a phenotypic marker for carcinogen metabolism and DNA repair, which may reflect individual susceptibility to chemical carcinogenesis. Based on this notion, we have established a straightforward assay that measures induced DNA adducts in peripheral lymphocytes exposed in vitro to a model carcinogen, benzo(a)pyrene diol epoxide (BPDE) by 32P-postlabeling. To test the hypothesis that the levels of induced DNA adducts are a predictor for cancer risk, we conducted a pilot study of 21 lung cancer patients and 41 healthy frequency-matched controls. We found that the peripheral lymphocytes of cancer patients tended to accumulate higher levels of BPDE-DNA adducts than controls did (mean +/- SE of relative adduct labeling x 10(7) value; 59.6 +/- 12.0 versus 39.4 +/- 6.1 for cases and controls, respectively; P = 0.09). Using the tertile relative adduct labeling value of controls (10 adducts/10(7) nucleotides) as the cutoff point, 18 of 21 cases and 23 of 41 controls distributed above this level (odds ratio, 4.7; 95% confidence interval, 1.2-18.5). In logistic regression analysis, the level of induced adduct was an independent risk factor (odds ratio, 6.4; 95% confidence interval, 1.3-29.4) after adjustment for the potential confounding factors, i.e., age, sex, ethnicity, and smoking. Stratified analyses showed that greater differences in DNA adduct levels induced by BPDE between cases and controls were observed in individuals younger than 65 years and in nonsmokers. Despite the small sample size, the significant association between the level of BPDE-induced DNA adducts and risk for lung cancer suggests that this assay is a promising method for further investigations.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Different patterns of TCR transgene expression in single-positive and double-negative T cells. Evidence for separate pathways of T cell maturation.

Two lines of transgenic mice were established using the TCR alpha (V alpha 4.4-J alpha 24)- and beta (V beta 9-D beta 1.1-J beta 2.1)-chain genes from a cloned CD4-CD8-alpha beta + (double-negative; DN) T cell line from BALB/c mice. The TCR genes were expressed in CD4+CD8- and CD4-CD8+ (single-positive; SP) and double-positive (DP) T cells in the thymus, and in SP T cells in the peripheral lymphoid tissues, and marrow in one transgenic mouse line, and predominantly in DN T cells in the other. Bone marrow precursor cells from only the DN mouse line generated T cells expressing the V beta 9 transgene during tissue culture. V beta 9+ T cells were found in DN but not SP transgenic mice backcrossed to BALB/c nu/nu mice. The results suggest two separate pathways of T cell maturation, one which generates SP T cells in the thymus, and another which generates DN T cells in both the thymus and bone marrow.

Amino Acid Sequence↗

CWR22 xenograft as an ex vivo human tumor model for prostate cancer gene therapy.

BACKGROUND: Lack of well-defined relevant in vivo or in vitro tumor models is one of the major limitations in assessing candidate therapeutic regimens, especially gene therapy, for prostate cancer. Since gene therapy is emerging as a potentially powerful therapeutic modality, it is desirable to evaluate this approach for the treatment of human prostate cancer. PURPOSE: We sought to establish a relevant ex vivo tumor model for gene therapy studies of human prostate cancer. METHODS: We constructed and established a transgenic human tumor model consisting of three major components: 1) human primary prostate cancer cells, CWR22, reactivated for growth after storage in liquid nitrogen; 2) a collagen gel ex vivo tissue culture system useful for short-term maintenance and manipulation of CWR22 cells under in vitro experimental conditions; and 3) a high-velocity, particle-mediated gene transfer system that is highly efficient in the ex vivo transfection of target cells. Prostate-specific antigen (PSA) levels in the cell culture media were monitored after transfecting CWR22 cells with candidate therapeutic genes, including the cytokines human interleukin 2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF), both as complementary DNAs [cDNAs]). CWR22 cells, transfected with firefly luciferase cDNA as a reporter gene, served as control cells for cytokine gene expression. CWR22 cells, transfected with the bacterial beta-galactosidase cDNA as a reporter gene, were used to assess the efficiency of gene transfer. Transcription of each of the cDNAs was driven by the cytomegalovirus (CMV) early gene promoter. RESULTS: The three-dimensional organization of tumor cells and functional characteristics of human prostate cancers were maintained in this ex vivo model of prostate cancer. Candidate therapeutic genes, CMV-IL-2 and CMV-GM-CSF, were expressed at peak levels of up to 38 ng of protein per 10(6) cells every 24 hours. IL-2 and GM-CSF secretion was sustained at approximately 40%-50% of peak levels during the entire experimental period (9-10 days in culture). At 7 days after gene delivery, a more than twofold reduction in the secretion of PSA was detected in the IL-2 (3.8 +/- 1.3 ng/10(4) cells every 24 hours [mean +/- standard deviation]) or GM-CSF (4.0 +/- 1.7 ng/10(4) cells every 24 hours) cDNA transfected cells as compared with the control cells transfected with luciferase cDNA (9.3 +/- 1.0 ng/10(4) cells every 24 hours). Up to 10% of the cells transfected with beta-galactosidase cDNA expressed measurable beta-galactosidase activity. CONCLUSION: This study demonstrated an efficient, rapid, and reliable system for gene transfer and expression in primary human prostatic carcinoma cells maintained in a collagen gel culture system. IMPLICATIONS: Our findings suggest a broad application of this CWR22 xenograft primary culture system as an ex vivo tumor model for the evaluation and characterization of various candidate therapeutic genes for human prostate cancer gene therapy, including a cytokine gene-modified tumor vaccine strategy.

Animals↗

Biochemical characterization of ezrin-actin interaction.

The highly related actin isoforms are thought to have different functions. We recently demonstrated a polarized distribution of actin isoforms in gastric parietal cells and association of gastric ezrin with the cytoplasmic beta-actin isoform (Yao, X., Chaponnier, C., Gabbiani, G., and Forte, J. G. (1995) Mol. Biol. Cell. 6, 541-557). Here we used ultrastructural immunocytochemistry to verify that beta-actin is located within canalicular microvilli and the apical cortex of parietal cells, similar to the localization reported for ezrin. Furthermore, we tested whether ezrin binds preferentially to cytoplasmic beta-actin compared with the skeletal muscle alpha-actin isoform. Purified cytoplasmic beta-actin (from erythrocytes) and skeletal alpha-actin were assembled with gastric ezrin. Co-sedimentation experiments showed that gastric ezrin selectively co-pelleted with the beta-actin isoform and only very poorly with alpha-actin. Binding of erythrocytic beta-actin to ezrin is saturable with a molar ratio of approximately 1:10 (ezrin:actin) and a dissociation constant approximately 4.6 x 10(-8) M. In addition, ezrin promoted pyrene-labeled actin assembly, with predominant effects on filament elongation and a distinct preference for beta-actin compared with alpha-actin. Given these isoform-selective associations, we speculate that actin isoforms might segregate into different functional domains and exert specificity by interacting with isoform-orientated binding proteins.

Actins↗

PDGF receptor-to-nucleus signaling of p91 (STAT1 alpha) transcription factor in rat smooth muscle cells.

Vascular smooth muscle cells (VSMC) are the predominant cell type in the media of a normal artery. Injury to the vessel wall leads to platelet deposition and the release of numerous factors, including PDGF, which exerts its biological effects by binding to specific surface receptors on the smooth muscle cell membrane. We demonstrate that PDGF-stimulated smooth muscle cells activate the STAT (signal transducers and activators of transcription) family of proteins in addition to other signaling pathways (e.g., RAS-RAF-MAP Kinase). We show that the transcription factor p91 (STAT1 alpha) is rapidly activated by PDGF in VSMC and specifically binds to the regulatory elements SIE or GAS. We hypothesize that signal transduction by p91 plays an important role in VSMC, especially after injury with the release of growth factors such as PDGF.

Animals↗