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Biomedical subjects

Z Cao

Publications and source records attributed to Z Cao.

At least 91 records · Page 5Linked to original sources

Prevention of murine influenza A virus pneumonitis by surfactant nano-emulsions.

Non-ionic surfactant nano-emulsions have extensive anti-microbial activity and are biocompatible with skin and mucous membranes at effective concentrations. Two nano-emulsion formulations (8N8 and 20N10) made from soybean oil, tributyl phosphate and Triton X-100, were tested for their ability to prevent murine influenza virus pneumonia in vivo. In the initial study, CD-1 mice were administered various dilutions of the nano-emulsions intranasally, and safe dosages and concentrations were determined. Non-toxic concentrations of the nano-emulsions were then mixed with influenza virus and applied to the nares of mice. Animals receiving mixtures of two different emulsions (8N8 or 20N10) and a LD50 of virus survived the challenge without evidence of viral infection. To determine if the nano-emulsions could prevent influenza virus infection in vivo when used as a prophylactic treatment, the nano-emulsions (8N8 at 1.0% and 20N10 at 1.0% or 0.2%) were applied to mouse nares 90 min before exposure to 5x10(5) p.f.u./ml virus by nebulized aerosol. Animals pretreated with the nano-emulsions had significantly decreased clinical signs of infection. Only 26.0% (8N8 at 1.0%), 31.25% (20N10 at 1.0%) and 37.0% (20N10 at 0.2%) of animals pretreated with nano-emulsion died from pneumonitis, whereas >80.0% of mock pretreated animals succumbed to infection (P<0.005). These findings suggest that non-ionic surfactant nano-emulsions have therapeutic potential for the prevention of influenza virus infection in vivo.

Animals↗

Immune response to plasmid DNA encoding HPV16-L1 protein.

OBJECTIVE: To test the immunogenicity of recombinant plasmid DNA containing human papillomavirus type 16-L1 (HPV16-L1) coding sequence of mice. METHODS: The HPV16-L1 encoding sequence was generated by polymerase chain reaction (PCR), and inserted into TA cloning vector PCR II, then cloned in the eukaryotic expression vector pcDNA3.1 with CMV promoter. The recombinant plasmid DNA pcDNA-L1 was transferred into Cos-7 cells and used to immunize BALB/c mice via muscular injection. The expression of HPV16-L1 in transferred cells was identified by immunospot and immunocytochemistry, which tested specific anti-HPV16-L1 antibody in the serum of immunized mice. RESULTS: Using the immunospot technique, we found L1 protein expression in pcDNA-L1 transferred cells. The immunocytochemistry studies demonstrated that the L1 protein was located in nuclei. In immunized mice, specific anti-HPV16-L1 antibodies could be detected by immunospot and immunocytochemistry 28 days after the first immunization and last at least 41 days. CONCLUSIONS: We constructed HPV16-L1 eukaryotic expressing plasmid whose DNA could induce immunohumoral response in mice. This observation will be helpful in designing HPV16 prophylactic vaccine.

Animals↗

[CO2 laser-microscopy technique in treating tumors near the sella turcica].

OBJECTIVE: To assess the laser-microscopy technique in dealing with tumors near the sella turcica. METHODS: Sixteen patients with tumors near the sella turcica who had been treated surgically by laser-microscopy technique from October 1996 to June 1998 in Haikou municipal hospital were analyzed retrospectively. RESULTS: In these patients, 11 patients had tumors bodies excised totally, and 5 had tumors bodies excised partially. All of then were followed up for 4 to 30 months. The curative effects were satisfactory. In 9 patients with defect in vision before operation, 6 showed obvious improvement, 2 moderate improvement, and 1 unmarked improvement. In 6 patients with endocrinopathy before operation, 4 returned to normal, and 2 showed improvement. In 4 patients with intracranial hypertension before operation, symptoms were retrieved. Only one patient who had diabetes insipidus after operation, and recovered after medication. CONCLUSIONS: CO(2) laser-microscopy technique the treatment of tumors near the sella turcica is advantageous: few accidental injuries because of its high-accuracy; less harassment to the hypophysis and subthalamus; less complication; small exposure of operative field; less bleeding and clear operative field; no stimulation of metastasis of carcinoma;and no interference of bioelectric current.

Adult↗

[Relationship between vulvar dystrophy, malignant tumor and the estrogen progestin receptor].

In order to investigate the relationship between vulvar dystrophy, malignant tumor, and estrogen, progestin receptor, we made an analysis on estrogen and progestin receptor (ER, PR) contents in 31 cases of vulvar dystrophy and 19 cases of malignant tumor, using the dextran-coated charcoal method. The Results showed that ER content of the mixed type was higher than that of the atrophic type. PR content of the mixed type was higher than that of the hyperplastic type; and the PR content of the hyperplastic type was higher than that of the atrophic type. The relationship between ER and PR contents of the vulvar dystrophy and adjacent normal tissue was in positive correlation. The PR content of vulvar squamous cell carcinoma went down along with the drop of its dedifferentiation degree. The PR content of carcinoma was much lower than that of the adjacent normal tissue. The results of suggest that the study provided theoretic basis for endocrinotherapy of the vulvar dystrophy, PR in malignant tumor is regarded as one of the indexes to predict prognosis.

Biomarkers, Tumor↗

[Effects of electromagnetic radiation from cellular telephone handsets on symptoms of neurasthenia].

In order to study the effects of electromagnetic radiation from cellular telephone handsets on symptoms of neurasthenia, 115 and 101 persons with or without handsets were selected. The subjects were investigated by questionnaire on their general health, lifestyle, habit, mental stress, the frequency of using the handsets, living and working environment, the cases of suffered from diseases and symptoms of neurasthenia. The data were analyzed by Chi-square test and Logistic regression statistics. The results showed that the time of using handset was positively associated with depression (P < 0.05), nausea (P < 0.01) and loss of appetite(P < 0.05). The results showed that long time use of cellular telephone handset could induce the symptoms of neurasthenia.

Female↗

[Long-term follow-up result of partial laryngectomy].

OBJECTIVE: To study the long-term follow-up result of partial laryngectomy and reservation of laryngeal function. METHODS: Three hundred and seventy-nine patients who underwent partial laryngectomy from 1986 to 1995 were summarized (male 290 cases, female 89 cases). Among them, 184 cases were supraglottic carcinomas (T1 8 cases, T2 115, T3 48, T4 13, according to UICC in 1992), 192 cases were glottic carcinomas (T1 115, T2 63, T3 13, T4 1), 3 cases were transglottic carcinomas (T2 1, T3 2). In common 8 kinds of operations were performed: 26 cases underwent cordectomy, 138 vertical laryngectomy, 7 frontolateral laryngectomy, 12 horizontal glottic laryngectomy (middle part of the larynx), 58 supraglottic laryngectomy, 95 horizontovertical (3/4) laryngectomy, 24 subtotal laryngectomy with cricoglossoepiglottic anastomosis, 19 near-total laryngectomy with cricoglossal anastomosis (with reservation of unilateral arytenoid cartilage). 193 cases underwent concurrent neck dissection(121 unilateral, 72 bilateral). RESULTS: All cases restored their phonation and overcame aspiration with removing nasal feeding from 7 to 23 days after operations. 362 cases were decannulated from 9 days to 3 months after operations. Another 8 cases were decannulated after a secondary plastic operation. Decannulation rate was 97.6%. The three, five and ten year survival rates were 86.8% (329/379), 81.3% (266/327) and 69.4% (120/173) respectively. CONCLUSION: Partial laryngectomy is a kind of radical operation with reservation of laryngeal function. Mastering indications strictly, correct operation choices, excellent surgical skills and perfect repairing technique are bases of improving life qualities and curative effect.

Adult↗

[Basement membrane in squamous cell carcinomas of the larynx: an immunohistochemical study].

OBJECTIVE: The study was to assess the distribution of basement membrane(BM) in laryngeal squamous cell carcinomas(LSCC). Correlation of BM and clinical parameters (TNM stage, histological grading, invasion mode, lymph node metastasis) was also examined. METHODS: The expression of BM around tumor cell was determined in 40 cases of LSCC by using monoclonal antibody against human type IV collagen. An intact continuous BM was found in 17 cases (42.5%), while partial or widespread loss of the BM was detected in the other 23 cases (57.5%). RESULTS: In cases with poor histological differentiation, the defect of BM was more severe than that in cases with high or middle histological differentiation (P < 0.05). Moreover, diffuse invasion carcinomas revealed lower type IV collagen expression comparing with cases with better tumor-host border (P < 0.05). There was a higher risk of regional lymph node metastasis among cases with poor BM expression (P < 0.01), but there was no association of clinical stage with BM defect (P > 0.05). CONCLUSION: These observations indicated that testing the distribution of BM seems to be useful to evaluate the histological grading of malignancy of laryngeal carcinoma and be helpful to prognosticate the frequency of regional lymph node metastasis.

Aged↗

[A quantum chemical study of pi-back-donation bond and Raman intensity of 1 sigma + electronic state of Pt-CO molecule].

The Raman spectroscopic properties of Pt-CO molecule have been investigated based on the electronic state 1 sigma + determined by the HF and B3LYP methods. The result shows that the calculated stretching vibrational frequencies of the Pt-C and C-O bonds depend on the method and the basis sets used. It indicates that it is important to adopt an appropriate method to describe pi-donation and pi-back-donation bond. The result of the differential Raman scattering cross section for the stretching vibrations of the Pt-C and C-O bond shows that the latter is significantly larger value compared to the former.

Adsorption↗

Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase.

Stimulation of the type 1 IL-1R (IL-1R1) and the IL-18R by their cognate ligands induces recruitment of the IL-1R-associated kinase (IRAK). Activation of IRAK leads in turn to nuclear translocation of NF-kappaB, which directs expression of innate and adaptive immune response genes. To study IRAK function in cytokine signaling, we generated cells and mice lacking the IRAK protein. IRAK-deficient fibroblasts show diminished activation of NF-kappaB when stimulated with IL-1. Immune effector cells without IRAK exhibit a defective IFN-gamma response to costimulation with IL-18. Furthermore, mice lacking the Irak gene demonstrate an attenuated response to injected IL-1. Deletion of Irak, however, does not affect the ability of mice to develop delayed-type hypersensitivity or clear infection with the intracellular parasite, Listeria monocytogenes. These results demonstrate that although IRAK participates in IL-1 and IL-18 signal transduction, residual cytokine responsiveness operates through an IRAK-independent pathway.

Animals↗

IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family.

The interleukin-1 receptor-associated kinase (IRAK) was first described as a signal transducer for interleukin-1 (IL-1) and has later been implicated in signal transduction of other members of the Toll/IL-1 receptor family. We now report the identification and characterization of a novel IRAK-like molecule. In contrast to the ubiquitously expressed IRAK and IRAK-2, this new IRAK-like molecule is found mainly in cells of monomyeloic origin and is, therefore, designated IRAK-M. Although IRAK-M and IRAK-2 exhibit only a negligible autophosphorylation activity, they can reconstitute the IL-1 response in a 293 mutant cell line lacking IRAK. In addition, we show for the first time that members of the IRAK family are indispensable elements of lipopolysaccharide signal transduction. The discovery of IRAK-M adds another level of complexity to our understanding of signaling by members of the Toll/IL-1 receptor family.

Adaptor Proteins, Signal Transducing↗

TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling.

Bone resorption and remodeling is an intricately controlled, physiological process that requires the function of osteoclasts. The processes governing both the differentiation and activation of osteoclasts involve signals induced by osteoprotegerin ligand (OPGL), a member of tumor necrosis factor (TNF) superfamily, and its cognate receptor RANK. The molecular mechanisms of the intracellular signal transduction remain to be elucidated. Here we report that mice deficient in TNF receptor-associated factor 6 (TRAF6) are osteopetrotic with defects in bone remodeling and tooth eruption due to impaired osteoclast function. Using in vitro assays, we demonstrate that TRAF6 is crucial not only in IL-1 and CD40 signaling but also, surprisingly, in LPS signaling. Furthermore, like TRAF2 and TRAF3, TRAF6 is essential for perinatal and postnatal survival. These findings establish unexpectedly diverse and critical roles for TRAF6 in perinatal and postnatal survival, bone metabolism, LPS, and cytokine signaling.

Animals↗

The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway.

Interleukin-1 (IL-1) is a proinflammatory cytokine that has several effects in the inflammation process. When it binds to its cell-surface receptor, IL-1 initiates a signalling cascade that leads to activation of the transcription factor NF-kappaB and is relayed through the protein TRAF6 and a succession of kinase enzymes, including NF-kappaB-inducing kinase (NIK) and I kappaB kinases (IKKs). However, the molecular mechanism by which NIK is activated is not understood. Here we show that the MAPKK kinase TAK1 acts upstream of NIK in the IL-1-activated signalling pathway and that TAK1 associates with TRAF6 during IL-1 signalling. Stimulation of TAK1 causes activation of NF-kappaB, which is blocked by dominant-negative mutants of NIK, and an inactive TAK1 mutant prevents activation of NF-kappaB that is mediated by IL-1 but not by NIK. Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity. Our results indicate that TAK1 links TRAF6 to the NIK-IKK cascade in the IL-1 signalling pathway.

Calcium-Calmodulin-Dependent Protein Kinases↗

Stimulation of tumors to synthesize tumor necrosis factor-alpha in situ using 5,6-dimethylxanthenone-4-acetic acid: a novel approach to cancer therapy.

The selective induction of tumor vascular collapse represents an exciting approach to cancer treatment. However, clinical evaluation of tumor necrosis factor-alpha (TNF), an agent that accomplishes this goal, has been limited by systemic toxicity, and clinical approaches using bacterial components to induce TNF production have also been disappointing. Our laboratory has developed synthetic low molecular weight inducers of TNF, including 5,6-dimethylxanthenone-4-acetic acid (DMXAA), as an alternative strategy. DMXAA induces rapid vascular collapse in transplantable murine tumors and induces TNF synthesis in vitro in both murine and human systems. We show here that the extent of DMXAA-induced TNF synthesis is greater in tumors than that in the spleen, liver, or serum. As shown by in situ hybridization studies of the murine Colon 38 tumor, DMXAA induced tumor as well as host cells to express TNF mRNA. The distribution of cells containing TNF mRNA in tumor tissues after DMXAA administration contrasted significantly with that obtained after lipopolysaccharide (LPS) treatment, although splenic and hepatic tissues showed a similar distribution of TNF mRNA-positive cells. In the Colon 38 tumor, the action of LPS was limited to host cells in the periphery of the vessels. DMXAA treatment induced 7-fold higher peak TNF levels in tumor than in serum. In contrast, LPS treatment induced 9-fold higher TNF levels in serum than in tumor. DMXAA induced 35-fold higher TNF activity in the Colon 38 tissue than did LPS. One ovarian, one squamous, and three melanoma human tumor xenografts implanted in athymic nude mice expressed TNF mRNA of human and murine origin in response to DMXAA, confirming that DMXAA can activate both host and tumor cells. The use of low molecular weight agents to induce TNF synthesis in situ in the tumor represents a novel approach to TNF-mediated therapy of cancers.

Animals↗

Acute hypermagnesemia and respiratory arrest following infusion of MgSO4 for tocolysis.

Hypermagnesemia (6.95 mmol/l) and respiratory arrest occurred to a 20-year-old female (G3P2002) at 26 weeks of gestation during tocolytic treatment with MgSO4.7H2O (density greater than plasmalyte) injected into an i.v. infusion bag containing 1 l of plasmalyte without mixing. The patient was rescued with calcium gluconate and normal pregnancy continued. It is important to adequately mix an i.v. solution after adding a drug particularly when the drug-containing solution has greater density than the parent i.v. solution.

Adult↗

Thalidomide increases both intra-tumoural tumour necrosis factor-alpha production and anti-tumour activity in response to 5,6-dimethylxanthenone-4-acetic acid.

5,6-Dimethylxanthenone-4-acetic acid (DMXAA), synthesized in this laboratory and currently in phase I clinical trial, is a low molecular weight inducer of tumour necrosis factor-alpha (TNF-alpha). Administration of DMXAA to mice with established transplantable tumours elicits rapid vascular collapse selectively in the tumour, followed by extensive haemorrhagic necrosis mediated primarily through the production of TNF-alpha. In this report we have investigated the synthesis of TNF-alpha mRNA in hepatic, splenic and tumour tissue. Co-administration of thalidomide with DMXAA increased anti-tumour activity and increased intra-tumoural TNF-alpha production approximately tenfold over that obtained with DMXAA alone. Thalidomide increased splenic TNF-alpha production slightly but significantly decreased serum and hepatic levels of TNF-alpha induced with DMXAA. Lipopolysaccharide (LPS) induced 300-fold higher serum TNF-alpha than did DMXAA at the maximum tolerated dose, but induced similar amounts of TNF-alpha in spleen, liver and tumour. Splenic TNF-alpha activity induced with LPS was slightly increased with thalidomide, but serum and liver TNF-alpha levels were suppressed. Thalidomide did not increase intra-tumoural TNF-alpha production induced with LPS, in sharp contrast to that obtained with DMXAA. While thalidomide improved the anti-tumour response to DMXAA, it had no effect on the anti-tumour action of LPS that did not induce a significant growth delay or cures against the Colon 38 tumour. The increase in the anti-tumour action by thalidomide in combination with DMXAA corresponded to an increase in intra-tumoural TNF-alpha production. Co-administration of thalidomide may represent a novel approach to improving selective intra-tumoural TNF-alpha production and anti-tumour efficacy of DMXAA.

Animals↗

Role of hyperlipidemia in progressive renal disease: focus on diabetic nephropathy.

BACKGROUND: It has been suggested that lipids promote renal injury and that 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors confer renoprotection in certain renal diseases, including diabetic nephropathy. METHODS: Sprague-Dawley rats were randomized to sham, subtotal nephrectomy (STNx) or STNx + atorvastatin groups. After 12 weeks, proteinuria, renal function, glomerular injury, renal transforming growth factor-beta (TGF-beta) gene expression and macrophage (ED1-positive cells) accumulation were assessed. In addition, the effects of HMG CoA reductase in human diabetic nephropathy were reviewed. RESULTS: Atorvastatin therapy was associated with a modest reduction in proteinuria and glomerulosclerosis without influencing lipid levels or renal function in STNx rats. These effects were associated with decreased renal TGF-beta 1 gene expression and less glomerular and tubulointerstitial macrophage accumulation. The renoprotective effects of HMG CoA reductase inhibitors in both insulin- and non-insulin-dependent diabetic subjects with either incipient or overt nephropathy appear to be highly variable. CONCLUSIONS: HMG CoA reductase inhibition appears to confer renoprotection via effects on prosclerotic cytokines such as TGF-beta and macrophage accumulation, independent of their lipid-lowering properties. The role of lipid-lowering agents in early or overt diabetic nephropathy remains to be fully ascertained.

Animals↗

A novel surfactant nanoemulsion with broad-spectrum sporicidal activity against Bacillus species.

Two nontoxic, antimicrobial nanoemulsions, BCTP and BCTP 401, have been developed. These emulsions are composed of detergents and oils in 80% water. BCTP diluted up to 1:1000 inactivated>90% of Bacillus anthracis spores in 4 h and was also sporicidal against three other Bacillus species. This sporicidal activity is due to disruption of the spore coat after initiation of germination without complete outgrowth. BCTP 401 diluted 1:1000 had greater activity than BCTP against Bacillus spores and had an onset of action of <30 min. Mixing BCTP or BCTP 401 with Bacillus cereus prior to subcutaneous injection in mice reduced the resulting skin lesion by 99%. Wound irrigation with BCTP 1 h after spore inoculation yielded a 98% reduction in skin lesion size, and mortality was reduced 3-fold. These nanoemulsion formulas are stable, easily dispersed, nonirritant, and nontoxic compared with other available sporicidal agents.

Animals↗

Induction of ribosome methylation in MLS-resistant Streptococcus pneumoniae by macrolides and ketolides.

One major mechanism for resistance to macrolide antibiotics in Streptococcus pneumoniae is MLS (macrolide, lincosamide, and streptogramin B) resistance, manifested when the 23S rRNA is methylated by the product of an erm gene. This modification results in the decreased binding of all known macrolide, lincosamide, and streptogramin B antibiotics to the ribosome. More than 30 ermAM-containing clinical isolates of S. pneumoniae were examined in our lab and showed high-level resistance (MIC > or =128 microg/ml) to erythromycin, azithromycin, tylosin, clindamycin, and ketolide (macrolides that lack the cladinose sugar) TE-802. We found that the new generation of ketolides A965 and A088 displayed variable activity against the same group of resistant S. pneumoniae strains. To understand the basis of variability of the minimal inhibitory concentration (MIC) values of A965 and A088, we examined the effects of a series of macrolides and ketolides on the level of 23S rRNA methylation in five ermAM-containing resistant S. pneumoniae isolates. We show here that the basal levels of ribosomal methylation vary from strain to strain. The level of rRNA methylation can be strongly induced by erythromycin, azithromycin, and TE-802, resulting in high-level of resistance to these compounds. Ketolide A965 and A088, however, are weak inducers at sub-MIC drug concentrations, therefore showing variable activities in strains with differential methylation levels.

Anti-Bacterial Agents↗