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Biomedical subjects

Z Dong

Publications and source records attributed to Z Dong.

At least 235 records · Page 13Linked to original sources
PubMed1997

Neutralization of endogenous interferon-beta increases the efficiency of adenoviral vector-mediated gene transduction.

One reason for low transduction efficiency and, hence, the inefficiency of gene therapy using adenoviral vectors may be the natural antiviral defense mechanisms of hosts. In this study, we investigated the effects of endogenous interferon-beta (IFN-beta) on gene transduction by adenoviral vectors. Infection of murine macrophages with Ad5CMV-LacZ produced increased expression of endogenous IFN-beta. Neutralization with anti-IFN-beta antibody (but not control immunoglobulin) during infection with the vector enhanced expression of LacZ. In contrast, IFN-beta gene expression was not detected in readily transduced NIH 3T3 cells, and the transduction efficiency of NIH 3T3 cells was unaffected by the antibody. LacZ gene expression in NIH 3T3 cells was decreased when cocultured with macrophages or in the presence of exogenous IFN-beta. The addition of the anti-IFN-beta antibody reversed this inhibition. These results demonstrate that IFN-beta-mediated cellular antiviral mechanisms are a barrier to gene transduction by adenoviral vectors.

3T3 Cells↗
PubMed1997

Grafting assay distinguishes promotion sensitive from promotion resistant JB6 cells.

The JB6 mouse epidermal cell system has been used extensively as an in vitro transformation model for the study of tumor promotion. The standard JB6 cell assay for promotion of transformation is carried out in soft agar or other anchorage independent conditions. The present study was directed to the development of an in vivo model to distinguish the promotion resistant (P-) and promotion sensitive (P+) progression phenotypes. Results indicate that the grafting assay distinguishes P- and P+ cells in vivo with P+ but not P- cells forming tumors within 7-9 weeks. Expression of dominant negative mutant jun TAM67 blocks both anchorage independent transformation response and graft bed tumor formation by P+ cells, suggesting that the requirement for AP-1 activation in transformation now applies in vivo. Expression of mutated p53 produced a gain of P+ phenotype in P- cells in vitro, but not in vivo. Histochemical and Northern blot analysis for expression of various keratinocyte markers revealed no evidence for expression, suggesting a loss of keratinocyte markers following establishment in culture. In summary, the skin-grafting assay described in this study appears to be a valid in vivo assay for distinguishing the preneoplastic progression phenotypes represented by JB6 P- and P+ cells.

Animals↗
PubMed1997

Direct correlation between DNA repair capacity and metastatic potential of K-1735 murine melanoma cells.

The purpose of this study was to determine whether the ability of K-1735 murine melanoma cells to repair DNA damage correlates with their metastatic potential. Three nonmetastatic clones, four metastatic clones, and three somatic-cell hybrids between metastatic and nonmetastatic clones were exposed to incident ultraviolet (UV) light (254 nm). Cell survival was determined by the microculture tetrazolium assay, which measures cell metabolic activity. DNA repair capacity was determined with a host-cell reactivation assay, which measures the activities of chloramphenicol acetyltransferase encoded by the reporter gene in both UV-damaged and undamaged plasmid (control) pCMV cat 40 h after transfection. No discernible differences in transfection efficiencies were found between K-1735 clones with low and high metastatic potential or between cells transfected with UV-damaged and control plasmids. DNA repair capacity directly correlated with cell survival (p < 0.05) and with metastatic potential in the K-1735 clones and somatic cell hybrids (p < 0.05). These data suggest that the intrinsic resistance of melanoma metastases to systemic chemotherapy may be due, in part, to the cells' enhanced DNA repair capacity.

Animals↗
PubMed1997

CD8+ T cells are activated during the early Th1 and Th2 immune responses in a murine Lyme disease model.

T-helper responses following Borrelia burgdorferi infection in mice determine susceptibility to Lyme arthritis. The ratio of interleukin 4-positive, CD4+ to gamma interferon (IFN-gamma)-positive, CD4+ T cells was significantly greater in infected BALB/cJ mice than in infected C3H/HeJ mice. Increased numbers of IFN-gamma-producing cells predicted greater arthritis severity, and CD8+ T cells were the main source of IFN-gamma in both strains.

Animals↗
PubMed1997

[Effect of dietary VE on the contents of salivary acid and MDA in RBC membrane].

Vitamin E can protect membrane from the damage of lipid peroxidation, Salivary acid is the residual of carbohydrate on the membrane. To evaluate the effect of dietary VE on salivary acid, the contents of MDA and salivary acid of erythrocyte (RBC) membrane of rats were measured. The rats were fed with different amounts of dietary VE and stayed at different temperatures. The results revealed that the content of salivary acid of RBC membrane reduced markly (P < 0.01) and the content of MDA of RBC membrane was stable (P > 0.05) after the rats were exposed to cold for 10 days. High dietary VE intake increased the content of salivary acid of RBC membrane (P < 0.01). There was no correlation between the content of salivary acid and MDA of RBC membrane. It suggested that dietary VE could raise the content of salivary acid in RBC membrane, but it can not be explained by the reduction of LPO.

Animals↗
PubMed1997

[Management of acute arterial occlusion of limbs: an analysis of 105 cases].

105 cases of acute arterial occlusion of limbs were admitted to our hospital from march 1982 to September 1996. We compared the treatment results of the patients with acute embolism and acute thrombosis. The limb-salvage rate of 86.8% in patients with embolic occlusion was higher than that of 57.9% in patients with thrombotic occlusion (P < 0.01), while the mortality rate of 8% patients associated with thrombosis was lower than that of 15.7% with embolism (P < 0.01). The results of limb salvage and mortality were related to different etiology of acute arterial occlusion, embolism and thrombosis.

Acute Disease↗
PubMed1997

[Clinical significance of multidrug resistance gene(mdr1) expression in patients with acute leukemia].

OBJECTIVE: To evaluate relationship between drug resistance of leukemia cells and prognosis. METHODS: The expression of multidrug resistance gene(mdr1) mRNA was measured in 85 patients with acute leukemia and in 20 normal controls by using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The mdr1 positive rate in untreated group was 44.7%. The CR rate differed significantly between mdr1+ (23.9%) and mdr1-(88.5%)(P < 0.005). The mdr1 positive rate of refractory-relapsed group was higher than that in CR group (P < 0.001). The mdr1 mRNA expression level of refractory-relapsed group was higher than that in CR group. A gradually increasing level of mdr1 mRNA expression in CR patients indicated early relapse. The mdr1 positive rate in normal contral and long-term surviver patients was very low. The mdr1 expression was correlated with French-American-Birtish Cooperative Group (FAB) classification. CONCLUSION: The mdr1 expression correlated with chemotherapeutic effect and prognosis. It is an unfavorable prognostic factor for patients with acute leukemia.

Adolescent↗
PubMed1997

[Measurement of minimal cross-sectional area of the nasal cavity and distance of minimal cross-section area from the nostril in healthy Chinese by acoustic rhinometry].

1,355 healthy Chinese, 3-86 years old, were measured with acoustic rhinometry. The range of normal value of minimal cross-sectional area (MCA) of the nasal cavity and distance of minimal cross-section area from the nostril (DCA) were obtained and the association of MCA and DCA with age in children and juvenile were discussed. The results showed that the range of MCA of unilateral nasal cavity was 0.192-0.915 cm2, DCA was 0.300-2.554 cm. The changes of MCA and DCA were highly associated with age in children and juvenile (P < 0.01). In adults, there was significant difference of MCA and DCA between different sexes in the different groups. It was demonstrated that these data could provide available information for the study of nasal physiology and pathophysiology, as well as for the diagnosis and judgement of therapeutic effectiveness of nasal diseases.

Acoustics↗
PubMed1997

[A preliminary study on the effect of estrogen on nasal mucosal hyperreactivity].

To understand the mechanism of the effect of estrogen on nasal mucosal hyperreactivity, animal models (guinea pigs) with different levels of estradiol (E2) were observed as follows: 1. effect of the change of E2 levels on E2 receptors (E2R) content in nasal mucosa; 2. effect of E2 level changes on histamine content in nasal mucosa and on nasal mucosal eosinophil and mast cell counts; 3. effect of E2 on release of cytokine IL-6 from macrophages. The results showed that high level of E2 might reduce the E2R content and eoinophil count but no significant effect on mast cells count and histamine content. The secretion of IL-6 from the macrophages was suppressed by E2 within concentration range of 3.13-50 micrograms/L. It was suggested that estradiol may play a complicated role in nasal mucosal hyperreactivity.

Animals↗
PubMed1997

[The effects of menthol, borneolum and moschus on nasal airflow sensation and nasal resistance].

Menthol and borneolum have been used widely in traditional Chinese medicine for the treatment of nasal obstruction, but the mechanism has been still unknown. The effects of inhalation of menthol, borneolum, moschus on nasal resistance and airflow sensation were investigated in 52 subjects. All of these medicines could cause a highly significant enhancement of nasal airflow sensation but had no effect on nasal resistance. Therefore this sort of medicine is regarded as pseudo nasal decongestant.

Adult↗
PubMed1997

[Peri-operative death in patients undergone lung cancer resection].

OBJECTIVE: To ascertain the causes of peri-operative death in patients with lung cancer. METHODS: Five cases died in the peri-operative period in 174 lung cancer patients undergone resection were analyzed. RESULTS: Two cases died from pulmonary edema and/or atelectasis; one died from acute myocardial infarction and ventricular fibrillation; one had sudden death immediately after withdrawal of endotracheal tube; the other one died of brain matastasis and multiple organ failure. CONCLUSION: Cardio-pulmonary complications are the major causes of peri-operative death in lung cancer patients. Appropriate preventive meassures should be taken to reduce operative mortality.

Adenocarcinoma↗
PubMed1997

Response of Schwann cells to mitogens in vitro is determined by pre-exposure to serum, time in vitro, and developmental age.

We compared the mitogenic response of Schwann cells freshly isolated from adult, neonatal, and embryonic nerves, and compared these cells with cells that had been cultured in serum for 5 days. DNA synthesis in response to growth factors was measured using bromodeoxyuridine and immunocytochemistry. Freshly isolated adult Schwann cells were unresponsive to growth factors with or without forskolin to elevate intracellular cAMP levels. After 5 days of culture in serum, or alternatively in defined medium containing fibroblast growth factor 2 plus forskolin, or neu-differentiation factor beta2, adult cells were responsive to mitogens, whereas cells cultured in defined medium alone remained unresponsive. Serum also increased expression of type 1 fibroblast growth factor receptor. Freshly isolated embryonic and neonatal Schwann cells in contrast responded to growth factors even in the absence of forskolin. This responsiveness changed with time in culture. Neonatal cells cultured for 5 days in defined medium in the presence or absence of serum no longer responded to FGF alone, but required forskolin for a mitogenic response. Thus, the response of freshly isolated cells to mitogens is developmentally regulated; extrinsic signals are required to render adult cells responsive to mitogens; and with time in culture, neonatal cells develop a requirement for cAMP elevation for mitogenic response.

Animals↗
PubMed1997

Internucleosomal DNA cleavage triggered by plasma membrane damage during necrotic cell death. Involvement of serine but not cysteine proteases.

Autolytic DNA breakdown, detected as smears in electrophoretic gels, is a late event in necrosis. On the other hand, internucleosomal DNA cleavage, visualized as ladders, is thought to be a hallmark of apoptosis. We now report that this specific form of DNA fragmentation also occurs during necrosis and is an early event but appears to be triggered by proteolytic mechanisms significantly different from those documented in apoptosis. Treatment of MDCK cells with a mitochondrial uncoupler and a Ca2+ ionophore led to ATP depletion, necrotic morphology, and progressive fragmentation of DNA in an internucleosomal or ladder pattern. DNA breakdown was immediately preceded by increased permeability of the plasma membrane to macromolecules. Provision of glycine along with the noxious agents did not modify the extent of ATP depletion, but prevented plasma membrane damage. This was accompanied by complete inhibition of DNA fragmentation. Internucleosomal DNA cleavage was observed also during necrosis after rapid permeabilization of plasma membranes by detergents or streptolysin-O in hepatocytes, thymocytes, and P19, Jurkat, and MDCK cells. DNA fragmentation associated with necrosis was Ca2+/Mg2+ dependent, was suppressed by endonuclease inhibitors, and was abolished by serine protease inhibitors but not by inhibitors of interleukin-1 beta converting enzyme (ICE)-related proteases or caspases. Moreover, unlike apoptosis, it was not accompanied by caspase-mediated proteolysis. On the other hand, the cleavage-site-directed chymotryptic inhibitor N-tosyl-L-phenylalanyl-chloromethyl ketone (TPCK) suppressed DNA fragmentation not only in necrotic cells but also during Fas-mediated apoptosis, without inhibiting caspase-related proteolysis. The results suggest a novel pathway of endonuclease activation during necrosis not involving the participation of caspases. In addition, they indicate that techniques based on double-strand DNA breaks may not reliably differentiate between apoptosis and necrosis.

Adenosine Triphosphate↗
PubMed1997

Abrogation of tumorigenicity and metastasis of murine and human tumor cells by transfection with the murine IFN-beta gene: possible role of nitric oxide.

The purpose of this study was to determine whether sustained local production of murine IFN-beta (mIFN-beta) could inhibit the tumorigenicity and metastasis of human and murine tumor cells implanted into nude mice. Human melanoma cells (A375SM), renal carcinoma cells (SN12PM6), and colon carcinoma cells (KM12SM) were transfected with mIFN-beta or a control neomycin resistance vector. All cell lines grew well in culture. Tumor cells were injected into the subcutis, kidney, spleen, or lateral tail vein of nude mice. Parental or control transfected cells produced local tumors and experimental or spontaneous lung metastases, whereas mIFN-beta-transfected cells did not. In vivo survival experiments using [125I]IdUdR-labeled cells showed that by day 7 after s.c. implantation, all IFN-beta-transfected cells died. IFN-beta transfection prevented the outgrowth of parental or control-transfected cells only when they were injected together with transfected cells into one site, suggesting that IFN-beta promoted a local lysis of the bystander cells. Similar indirect antitumor activity was demonstrated in various human (KM12SM and SN12PM6) and murine (CT-26 colon carcinoma, RENCA renal cell carcinoma, and 3LL Lewis lung carcinoma) tumors. The IFN-beta-transfected tumor cells stimulated a high level of nitric oxide production by murine macrophages under in vitro and in vivo conditions, which correlated with the vigorous nonspecific antitumor activity. Collectively, these results demonstrate that local production of IFN-beta can eradicate tumor cells of different histology by inducing inducible nitric oxide synthase expression in infiltrating cells.

Animals↗
PubMed1997

Therapy of human transitional cell carcinoma of the bladder by oral administration of the epidermal growth factor receptor protein tyrosine kinase inhibitor 4,5-dianilinophthalimide.

Epidermal growth factor receptor (EGF-R), a transmembrane glycoprotein that mediates the mitogenic response of cells to epidermal growth factor, is highly expressed on malignant human bladder cancer cells. The 4,5-dianilinophthalimides represent a novel class of inhibitors of the EGF-R family of tyrosine kinase with selectivity at the enzymatic and cellular levels. Two compounds of this class, CGP 54211 and CGP 53353, inhibited tyrosine kinase activity of the EGF-R in five different human transitional cell carcinoma lines. The compounds also produced cytostasis in vitro. Highly metastatic human 253J B-V cells were implanted in the bladder wall of nude mice. The daily oral administration of CGP 54211 inhibited the level of EGF-R phosphorylation in this tumor; necrosis and inhibition of tumor growth paralleled this inhibition.

Adenosine Triphosphate↗
PubMed1996

Ultraviolet B-induced activated protein-1 activation does not require epidermal growth factor receptor but is blocked by a dominant negative PKClambda/iota.

The exposure of mammalian cells to UV irradiation leads to the activation of transcription factors such as activated protein-1 (AP-1) and NFkappaB. It is postulated that epidermal growth factor (EGF) receptor, but not protein kinase C (PKC), is the major membrane mediator in UV-induced signal transduction. Since UVB is responsible for most of the carcinogenic effects of sun exposure, we investigated the role of EGF receptors and PKC in UVB-induced AP-1 activation. Our results indicated that while the down-regulation of novel PKC (nPKC) and conventional PKC (cPKC) by pretreatment of cells with 12-O-tetradecanoyl phorbol-13-acetate cannot block UVB-induced AP-1 activity, it can block 12-O-tetradecanoyl phorbol-13-acetate-induced AP-1 activity. Further, the dominant negative mutant PKClambda/iota blocked UVB-induced AP-1 activity in all doses and time courses studied. In contrast, UVB-induced AP-1 activity from cells devoid of EGF receptor (B82) was not significantly different from that of the stable transfectants with a kinase-deficient EGF receptor (B82M721) or those with a wild-type EGF receptor (B82L) at all UVB irradiation doses and time courses studied. All of this evidence indicated that aPKC, but not EGF receptor, is involved in UVB-induced AP-1 activation.

Animals↗
PubMed1996

Differential regulation of metalloelastase activity in murine peritoneal macrophages by granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor.

We investigated the regulation of elastase activity in murine peritoneal macrophages by different cytokines and bacterial LPS. Thioglycolate-elicited mouse peritoneal exudate macrophages secrete a metalloproteinase that degrades elastin. Incubation of peritoneal exudate macrophages with LPS and IFN-gamma significantly inhibited the production of elastase by a mechanism independent of nitric oxide, superoxide, and hydrogen peroxide. The cytokines IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, TNF, TGF-alpha and -beta, basic fibroblast growth factor, monocyte chemotactic factor-1, and granulocyte CSF (G-CSF) had no significant effect on the production of elastase by macrophages. In contrast, granulocyte-macrophage CSF (GM-CSF) increased the production of elastase in a dose-dependent manner, and with macrophage CSF (M-CSF) inhibited it. Elastin zymography demonstrated that the modulation of elastolytic activity in macrophages was associated with changes in the level of metalloelastase protein. The stimulation of elastase activity by GM-CSF and the inhibition of elastase activity by LPS, IFN-gamma, and M-CSF occurred at the level of transcription. LPS and M-CSF also augmented the expression level of tissue inhibitors of metalloproteinase mRNA. The increased mRNA steady state level of murine macrophage elastase induced by GM-CSF resulted from both increased transcription and enhanced stability. The modulation of metalloelastase activity in macrophages by IFN-gamma, M-CSF, and GM-CSF suggests that these molecules may control the degradation of elastin fibers in lungs or blood vessels.

Animals↗