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Biomedical subjects

C Bao

Publications and source records attributed to C Bao.

At least 19 recordsLinked to original sources
PubMed2006

A mutated human tumor necrosis factor-alpha improves the therapeutic index in vitro and in vivo.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that has cytotoxic, cytostatic and immunomodulatory effects on malignant tumors. However, clinical trials have revealed high systemic toxicity and this has hampered its utilization as an anti-cancer agent. In this study, a human TNF-alpha mutant was created and tested for its anti-tumor effects. METHODS: The TNF mutant (recombinant mutated human TNF; rmhTNF) was prepared by protein engineering in which amino acids Pro, Ser and Asp at positions 8, 9 and 10 of TNF-alpha were substituted by Arg, Lys and Arg, and C terminal Leu157 was substituted by Phe, along with deletion of the first seven N-terminal amino acids. Prokaryotic expression recombinant vector pBV-mhTNF containing the PLPR promotor was constructed and transformed into E. coli DH5alpha. The rmhTNF was expressed in a partially soluble form in DH5alpha, purified from the supernatant of cell lysate by ammonia sulfate precipitation and two sequential chromatographic steps. RESULTS: The purified rmhTNF was >95% pure by SDS-PAGE stained with silver and high-pressure size exclusion chromatography (SEC-HPLC). Its yield was about 1.22 mg/g wet cell paste. The mutant rmhTNF exhibited an approximately 50-fold increase in cytotoxicity relative to the wild-type rhTNF on the mouse fibroblast cell line L929 in a standard cytotoxicity test, and at least and at least 50 times higher LD50 as wild type rhTNF in mice. In vivo biological activity studies carried out on tumor cell transplanted mice and nude mice also showed a more effective cytotoxicity of rmhTNF than rhTNF. DISCUSSION: These results suggest that rmhTNF has potential for developing an effective anti-tumor reagent for some tumors.

Animals↗
PubMed2001

Intersection of interferon and hypoxia signal transduction pathways in nitric oxide-induced tumor apoptosis.

Activated macrophages play a central role in antitumor immunity. However, the stimuli that activate macrophages to kill tumor cells are not completely understood. Because the center of solid tumors can be hypoxic, we hypothesized that hypoxia may be an important signal in activating macrophages to kill tumor cells. Hypoxia stimulates IFN-primed macrophages to express the inducible nitric oxide synthase (NOS2) and to synthesize nitric oxide (NO). We show that this synergy between IFN and hypoxia is mediated by the direct interaction of the hypoxia inducible factor-1 (HIF-1) and IFN regulatory factor-1 (IRF-1), which are both required for the hypoxic transcription of NOS2. This interaction between HIF-1 and IRF-1 may explain the mechanism by which macrophages infiltrating into tumors are activated to express NOS2 and to produce NO, a mediator of tumor apoptosis.

Animals↗
PubMed2001

Talbot effect interpreted by number theory.

An interpretation of the Talbot effect in a tapered gradient-index medium by number theory as the output/input relationship between the integer and the noninteger difference of position and the slope of rays is presented. Unit cell and transverse magnification for Talbot images are evaluated, and two criteria for angular magnification are defined. The study is particularized to a finite set of diffracted rays.

Journal Article↗
PubMed2000

Regulation of plasminogen activator inhibitor-1 and urokinase by hyaluronan fragments in mouse macrophages.

Pulmonary inflammation and fibrosis are characterized by increased turnover and production of the extracellular matrix as well as an impairment of lung fibrinolytic activity. Although fragments of the extracellular matrix component hyaluronan induce macrophage production of inflammatory mediators, the effect of hyaluronan on the fibrinolytic mediators plasminogen activator inhibitor (PAI)-1 and urokinase-type plasminogen activator (uPA) is unknown. This study demonstrates that hyaluronan fragments augment steady-state mRNA, protein, and inhibitory activity of PAI-1 as well as diminish the baseline levels of uPA mRNA and inhibit uPA activity in an alveolar macrophage cell line. Hyaluronan fragments alter macrophage expression of PAI-1 and uPA at the level of gene transcription. Similarly, hyaluronan fragments augment PAI-1 and diminish uPA mRNA levels in freshly isolated inflammatory alveolar macrophages from bleomycin-treated rats. These data suggest that hyaluronan fragments influence alveolar macrophage expression of PAI-1 and uPA and may be a mechanism for regulating fibrinolytic activity during lung inflammation.

Amiloride↗
PubMed2000

The relationship between Th1/Th2-type cells and disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the imbalance of Th1/Th2-type cytokines in patients with systemic lupus erythematosus (SLE) and its relation to disease activity. METHODS: Intracellular cytokines were determined by flow-cytometry following whole-blood culture. RESULTS: Patients with systemic lupus erythematosus disease activity index (SLEDAI) > 10 had statistically significantly fewer CD4+ or CD8+ T cells producing IFN-gamma than patients with SLEDAI = 0, SLEDAI 1-10 or healthy controls (P < 0.01, P < 0.01 or P < 0.05, respectively). Patients with SLEDAI > 10 also had decreased ratio of IFN-gamma/IL-4 positive CD4+ or CD8+ T cells, compared with patients with SLEDAI = 0, SLEDAI 1-10 or healthy controls (P < 0.05). The decreased Th1 or Tc1 cells and the ratios of IFN-gamma: IL-4 positive CD4+ T-cells were significantly correlated with disease activity (P < 0.05). CONCLUSION: SLE is characterized by an imbalance of Th1/Th2 and Tc1/Tc2 cytokines. The decreased Th1 or Tc1 cells and the Th1/Th2 ratio are related to disease activity.

Adult↗
PubMed2000

[Histological study on the polyhydroxybutyric ester(PHB) membrane used for guided bone regeneration around titanium dental implants].

OBJECTIVE: To evaluate the effects of PHB membrane around dental titanium implants used in guided bone regeneration technique. METHODS: Endosseous cylindrical implants were placed in dogs' mandibles after extraction of all the mandibular premolars and the first molars immediately. Ideal implant placement sites were modified by creating standardized 3 mm x 5 mm facial dehiscent defects. The defects were covered with PHB membrane and titanium membrane respectively, then the membranes were fixed on the periosteum by sutures, and the remainder served as controls. Tissue closure was achieved with mattress and interrupted single sutures, and antibiotic injection was given to the dogs in the following 3 days. The dogs were divided into three groups according to the healing time of 1, 2 and 3 months, then the three groups of dogs were sacrificed. After that, tissue blocks containing the implants and the control ones were removed and studied by gross observation, X-ray radiograph and fluorescence microscope, and the surfaces of the membranes were observed by scanning electron microscope. The specimen used for light microscope study were fixed with 10% formaldehyde for 24 hours, and decalcified with 0.5 mol/L EDTA for 2 weeks. After the titanium implants were carefully removed, the tissue blocks were embedded into the paraffin wax, and the sections were obtained. RESULTS: The PHB membrane degraded slowly and partly 3 months after placement, and the biodegradable property of the PHB membrane deserved a longer period of study; The bone defects covered with PHB and titanium membrane were filled with much more new bone than that of the control group. CONCLUSION: PHB membrane can enhance bone formation and can be used for guided bone regeneration.

Animals↗
PubMed2000

[Relationships between ankylosing spondylitis and ear disease].

OBJECTIVE: To explore whether patients with ankylosing spondylitis (AS) have hearing loss and the pattern of hearing loss. METHODS: Questionnaire, physical examination of the ear, nose and throat, hearing test and sero-immunity examinations were conducted in 34 patients (68 ears) with AS. RESULTS: Among 34 patients, 11 cases reported decrease in the sound perception, and 24 cases (41 ears, 60.3%) had hearing loss as evidenced by the pure tone audiometry. In those patients with hearing loss, 2 ears with perforation of tympanic membrane showed conductive hearing loss and the remainder 39 ears showed sensorineural hearing loss in which 26 ears (66.7%) experienced high frequency hearing loss. Auditory brainstem responses were normally presented in 26 case, whereas abolished in 1 case (2 ears) with severe hearing loss. Examinations of sero-immunity showed a positive response in HLA-B27, but negative responses in the antinuclear antibody and rheumatoid factor. The percentage of the C-reactive protein increase was 81.8%. Autoantibodies anaginst the inner ear were positive in 9 cases (28.1%). In addition, all other immunological examinations revealed certain changes. CONCLUSION: More than half of the patients with AS had sensorineural hearing loss, particularly in the high frequency range. This hearing loss is paralleled by abnormal immunology and is a local expression of systemic autoimmune disease. Therefore, periodical hearing tests are necessary for these patients.

Adolescent↗
PubMed1999

Inducible nitric oxide synthase protection against coxsackievirus pancreatitis.

Coxsackievirus infection causes myocarditis and pancreatitis in humans. In certain strains of mice, Coxsackievirus causes a severe pancreatitis. We explored the role of NO in the host immune response to viral pancreatitis. Coxsackievirus replicates to higher titers in mice lacking NO synthase 2 (NOS2) than in wild-type mice, with particularly high viral titers and viral RNA levels in the pancreas. Mice lacking NOS have a severe, necrotizing pancreatitis, with elevated pancreatic enzymes in the blood and necrotic acinar cells. Lack of NOS2 leads to a rapid increase in the mortality of infected mice. Thus, NOS2 is a critical component in the immune response to Coxsackievirus infection.

Acute Disease↗
PubMed1999

An inducible nitric-oxide synthase (NOS)-associated protein inhibits NOS dimerization and activity.

A variety of transcriptional and post-transcriptional mechanisms regulate the expression of the inducible nitric-oxide synthase (iNOS, or NOS2). Although neurons and endothelial cells express proteins that interact with and inhibit neuronal NOS and endothelial NOS, macrophage proteins that inhibit NOS2 have not been identified. We show that murine macrophages express a 110-kDa protein that interacts with NOS2, which we call NOS-associated protein-110 kDa (NAP110). NAP110 directly interacts with the amino terminus of NOS2, and inhibits NOS catalytic activity by preventing formation of NOS2 homodimers. Expression of NAP110 may be a mechanism by which macrophages expressing NOS2 protect themselves from cytotoxic levels of nitric oxide.

Amino Acid Sequence↗
PubMed1999

Interaction of interferon regulatory factor-1 and nuclear factor kappaB during activation of inducible nitric oxide synthase transcription.

We investigated the molecular mechanism for the synergistic induction of inducible nitric oxide synthase transcription by TNF-alpha and IFN-gamma. Since TNF-alpha and IFN-gamma stimulate cells in part by activating NF-kappaB and IRF-1, we hypothesized that these two transcription factors interact with each other. IRF-1 and NF-kappaB co-localize in the nucleus of stimulated macrophages. Co-immunoprecipitation experiments show that IRF-1 and NF-kappaB interact in stimulated but not resting cells. Super-shift experiments show that IRF-1 and NF-kappaB interact while binding to their respective DNA binding sites. These results demonstrate the existence of a physical interaction between IRF-1 and NF-kappaB proteins in vivo. We next suggested that this interaction between IRF-1 and NF-kappaB bends the DNA of the iNOS promoter region. Using a cyclization assay, we demonstrate that nuclear extracts from stimulated cells accelerate the rate of conversion of a linear to circular DNA, compared to extracts from resting cells. However, stimulated nuclear extracts cannot affect the rate of cyclization of a promoter with a mutant IRE or kappaB site. Furthermore, stimulated nuclear extracts depleted of IRF-1 and NF-kappaB cannot induce cyclization. We conclude that IRF-1 and NF-kappaB interact in vivo, and that this interaction physically bends the indicible nitric oxide synthase promoter DNA. This interaction may explain the mechanism by which IFN-gamma synergistically augments inducible nitric oxide synthase transcription.

Animals↗
PubMed1999

Induction and regulation of macrophage metalloelastase by hyaluronan fragments in mouse macrophages.

Although the metalloproteinase murine metalloelastase (MME) has been implicated in lung disorders such as emphysema and pulmonary fibrosis, the mechanisms regulating MME expression are unclear. Low m.w. fragments of the extracellular matrix component hyaluronan (HA) that accumulate at sites of lung inflammation are capable of inducing inflammatory gene expression in macrophages (Mphi). The purpose of this study was to examine the effect of HA fragments on the expression of MME in alveolar Mphi. The mouse alveolar Mphi cell line MH-S was stimulated with HA fragments over time, total RNA was isolated, and Northern blot analysis was performed. HA fragments induced MME mRNA in a time-dependent fashion, with maximal levels at 6 h. HA fragments also induced MME protein expression as well as enzyme activity. The induction of MME gene expression was specific for low m.w. HA fragments and dependent upon new protein synthesis; it occurred at the level of gene transcription. We also examined the effect of HA fragments on MME expression in inflammatory alveolar Mphi from bleomycin-injured rat lungs. Although normal rat alveolar Mphi did not express MME mRNA in response to HA fragments, alveolar Mphi from the bleomycin-treated rats responded to HA fragment stimulation by increasing MME mRNA levels. Furthermore, baseline and HA fragment-induced MME gene expression in alveolar Mphi from bleomycin-treated rats was inhibited by IFN-gamma. These data suggest that HA fragments may be an important mechanism for the expression of MME by Mphi in inflammatory lung disorders.

Animals↗
PubMed1999

Kalirin inhibition of inducible nitric-oxide synthase.

Nitric oxide (NO) acts as a neurotransmitter. However, excess NO produced from neuronal NO synthase (nNOS) or inducible NOS (iNOS) during inflammation of the central nervous system can be neurotoxic, disrupting neurotransmitter and hormone production and killing neurons. A screen of a hippocampal cDNA library showed that a unique region of the iNOS protein interacts with Kalirin, previously identified as an interactor with a secretory granule peptide biosynthetic enzyme. Kalirin associates with iNOS in vitro and in vivo and inhibits iNOS activity by preventing the formation of iNOS homodimers. Expression of exogenous Kalirin in pituitary cells dramatically reduces iNOS inhibition of ACTH secretion. Thus Kalirin may play a neuroprotective role during inflammation of the central nervous system by inhibiting iNOS activity.

Adrenocorticotropic Hormone↗
PubMed1999

[Surveillance and diagnosis of laryngeal burn].

OBJECTIVE: To explore early diagnosis and treatment of laryngeal burn, in order to prevent laryngeal obstruction, define the prevention of laryngemphraxis, and elect optimal time of treatment and appropriate treatment. METHODS: A total of 18 patients suffering from laryngeal burn were repeatedly examined with a fiberlaryngoscope. Each part of the larynx was assessed for the degree of congestion, swelling, blister formation and impairment of laryngeal function, and the effects of these pathologies on breathing. RESULTS: Our observations showed that classification of inhalation injury according to anatomical division could not reflect the severity of the injury. For this reason, every changes in each part of the larynx was analyzed. A classification consisting of 3 types of laryngeal injury was proposed in respect to 3 predisposing factors of laryngeal obstruction. This classification could serve as a guide for treatment. CONCLUSION: A clearcut diagnosis of laryngeal inhalation injury is a pre-requisite for the choice of the correct treatment and the decision on the time for surgical intervention, thus laryngeal obstruction could be avoided, and death rate of early stage of inhalation injury could also be lowered.

Adult↗
PubMed1998

Hyaluronan fragments synergize with interferon-gamma to induce the C-X-C chemokines mig and interferon-inducible protein-10 in mouse macrophages.

Hallmarks of chronic inflammation and tissue fibrosis are increased influx of activated inflammatory cells, mediator release, and increased turnover and production of the extracellular matrix (ECM). Recent evidence has suggested that fragments of the ECM component hyaluronan play a role in chronic inflammation by inducing macrophage expression of chemokines. Interferon-gamma (IFN-gamma), an important regulator of macrophage functions, has been shown to induce the C-X-C chemokines Mig and IP-10. These chemokines affect T-cell recruitment and inhibit angiogenesis. The purpose of this investigation was to determine the effect of hyaluronan (HA) on IFN-gamma-induced Mig and IP-10 expression in mouse macrophages. We found a marked synergy between HA and IFN-gamma on Mig and IP-10 mRNA and protein expression in mouse macrophages. This was most significant with Mig, which was not induced by HA alone. The synergy was specific for HA, was not dependent on new protein synthesis, was not mediated by tumor necrosis factor-alpha, was selective for Mig and IP-10, and occurred at the level of gene transcription. These data suggest that the ECM component HA may influence chronic inflammatory states by working in concert with IFN-gamma to alter macrophage chemokine expression.

Animals↗
PubMed1998

Regulation of hyaluronan-induced chemokine gene expression by IL-10 and IFN-gamma in mouse macrophages.

Turnover of the extracellular matrix (ECM), activation of macrophages, and accumulation of chemokines/cytokines are all hallmarks of chronic inflammation. Extracellular matrix components, such as hyaluronan (HA), have recently been shown to influence macrophage effector functions, such as the release of inflammatory chemokines and cytokines. Although low m.w. fragments of the glycosaminoglycan HA induce macrophages to secrete numerous inflammatory mediators, the mechanisms regulating ECM-induced macrophage activation are poorly understood. We have examined the effects of IL-10 and IFN-gamma on HA-induced chemokine gene expression in primary mouse macrophages. We found that IL-10 and IFN-gamma independently inhibit HA-induced expression of macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and KC at both the mRNA and protein levels. Whereas IL-10 inhibited most of the HA-induced chemokines tested, IFN-gamma selectively inhibited only MIP-1alpha, MIP-1beta, and KC. This inhibition did not require prestimulation and occurred even when the cytokines were added up to 3 h after stimulation with HA. For MIP-1alpha, the inhibition by IFN-gamma occurred at the level of transcription, whereas IL-10 predominantly decreased the stability of MIP-1alpha mRNA. IFN-gamma and IL-10 equally inhibited macrophage expression of MIP-1beta mRNA at the level of transcription, but MIP-1beta mRNA stability was decreased to a greater extent by IL-10. These data identify a previously unrecognized role for IL-10 and IFN-gamma as regulators of ECM-induced macrophage expression of inflammatory chemokines.

Animals↗
PubMed1998

[Relationship between body surface zinc loss and dietary zinc intake in children].

OBJECTIVE: To study the effects of body surface loss of zinc on the determination of dietary supply of zinc. METHODS: Body surface loss of zinc was determined in 24 preschool children with normal zinc nutrition (Group A) and zinc malnutrition (Group B). RESULTS: Body surface loss of zinc was 0.25 and 0.23 mg daily in Groups A and B with dietary zinc intake of 5.45 and 5.03 mg, respectively, and 0.29 and 0.25 mg daily with dietary zinc intake of 7.20 and 6.73 mg, respectively. The body surface loss of zinc accounted for five percent of the total. CONCLUSION: Considering the loss of zinc from body surface, it is suggested that dietary zinc supply be increased by 21 percent. When children is in good status of zinc nutrition, body surface loss of zinc correlates proportionally with their dietary zinc intake.

Child↗