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Biomedical subjects

L Qiao

Publications and source records attributed to L Qiao.

At least 37 records · Page 2Linked to original sources
PubMed2000

Induction of an HPV 6bL1-specific mucosal IgA response by DNA immunization.

Human papillomavirus (HPV) plays a crucial role in the development of human anogenital dysplasia. To prevent infection, it is important to induce an HPV-specific mucosal immune response. We investigated whether DNA vaccination would induce an intravaginal mucosal antibody response against HPV 6bL1. New Zealand White rabbits were immunized with an HPV 6bL1 DNA vaccine by one of the three routes: muscular, vaginal, or rectal. We found that vaginal immunization of rabbits with HPV 6bL1 DNA induced 6bL1 virus-like particle-specific lgA antibodies in vaginal secretions. They were detectable until at least 14 weeks after the first immunization. The antibodies also showed neutralizing activity in a hemagglutination inhibition assay. No mucosal immune response was detected in vaginal secretions of rabbits immunized intramuscularly or intrarectally. Our data suggest that vaginal immunization with HPV 6bL1 DNA induces long-lasting IgA responses with neutralizing activity in vaginal secretions of rabbits.

Administration, Intravaginal↗
PubMed2000

3-(Hydroxymethyl)-bearing phosphatidylinositol ether lipid analogues and carbonate surrogates block PI3-K, Akt, and cancer cell growth.

Phosphatidylinositol 3-kinase (PI3-K) phosphorylates the 3-position of phosphatidylinositol to give rise to three signaling phospholipids. Binding of the pleckstrin homology (PH) domain of Akt to membrane PI(3)P's causes the translocation of Akt to the plasma membrane bringing it into contact with membrane-bound Akt kinase (PDK1 and 2), which phosphorylates and activates Akt. Akt inhibits apoptosis by phosphorylating Bad, thus promoting its binding to and blockade of the activity of the cell survival factor Bcl-x. Herein we present the synthesis and biological activity of several novel phosphatidylinositol analogues and demonstrate the ability of the carbonate group to function as a surrogate for the phosphate moiety. Due to a combination of their PI3-K and Akt inhibitory activities, the PI analogues 2, 3, and 5 proved to be good inhibitors of the growth of various cancer cell lines with IC(50) values in the 1-10 microM range. The enhanced Akt inhibitory activity of the axial hydroxymethyl-bearing analogue 5 compared to its equatorial counterpart 6 is rationalized based upon postulated differences in the H-bonding patterns of these compounds in complex with a homology modeling generated structure of the PH domain of Akt. This work represents the first attempt to examine the effects of 3-modified PI analogues on these two crucial cell signaling proteins, PI3-K and Akt, in an effort to better understand their cell growth inhibitory properties.

Antineoplastic Agents↗
PubMed2000

Linear PADRE T helper epitope and carbohydrate B cell epitope conjugates induce specific high titer IgG antibody responses.

Linear carbohydrate-peptide constructs based on the 13 amino acid nonnatural pan DR epitope (PADRE) and carbohydrate B cell epitopes are demonstrated to be potent immunogens. These data support our belief that PADRE should be considered as an alternative to more complex carriers for use in prophylaxis and therapeutic vaccines. Two model carbohydrate-PADRE glycoconjugates were used to demonstrate that PADRE could effectively provide T cell help for carbohydrate-specific Ab responses. Conjugates of PADRE covalently linked to the human milk oligosaccharide, lacto-N-fucopentose II or a dodecasaccharide derived from Salmonella typhimurium O-Ag induced high titer IgG Ab responses in mice, which were comparable to glycoconjugates employing human serum albumin (HSA) as the carrier protein. Different adjuvants, in combination with PADRE conjugates, allowed for the modulation of the isotype profile with alum supporting an IgG1 profile; QS-21 an IgG2a, 2b profile, while an alum/QS-21 mixture generated a balanced IgG1/IgG2b isotype profile. As defined by binding to synthetic glycoconjugates, dodecasaccharide-specific Abs exhibited fine specificity similar to protective polyclonal Ab responses previously reported for dodecasaccharide-protein conjugates. The same Abs bound to intact S. typhimurium cells, suggesting that biologically relevant specificities were produced. The affinity of the dodecasaccharide-specific Abs was further shown to be comparable to that of a well-characterized, high affinity monoclonal anti-carbohydrate Ab recognizing the same epitope.

Adjuvants, Immunologic↗
PubMed2000

Infrared spectroscopic study of cervical smears in patients with HIV: implications for cervical carcinogenesis.

Patients with HIV have an increased incidence of cervical cancer, necessitating increased surveillance. Infrared spectroscopy (IRS) has the potential of aiding the diagnosis of cervical neoplasia and also of providing clues into its pathogenesis. We studied by IRS cervical scrapings from 22 HIV-infected and 23 control women; 8 of the former and none of the latter had dysplasia. The infrared spectra followed three patterns, designated pattern I (similar to that previously associated with normal cervical samples), pattern II (intermediate between patterns I and III), and pattern III (associated with cervical neoplasia). Compared with HIV-negative controls, HIV-infected women had a higher prevalence of pattern III and a lower prevalence of pattern II; these differences were statistically significant (P = .015 by chi2 analysis). Similar spectroscopic changes were present even when only the cytologically normal samples from HIV-positive and HIV-negative women were analyzed. We speculate that these changes may reflect early structural changes associated with cervical neoplasia that are not detectable cytologically. The infrared spectra in the region 950 to 1,300 cm(-1) could not differentiate cervical samples from HIV-infected and uninfected patients. The potential practical applications of IRS in HIV cervical disease are discussed.

Adenocarcinoma↗
PubMed2000

Comparison of cytokines and CD80 for enhancement of immunogenicity of cervical cancer cells.

Tumor cells fail to activate specific cytotoxic T lymphocytes due to lack of costimulatory molecules e.g. CD80 (B7.1). We were able to render cervical carcinoma cells immunogenic by introduction of the CD80 gene into the tumor cells. In order to enhance the efficiency of T cell activation we investigated whether addition of interleukins would augment immunostimulation by CD80. To this end, allogeneic T cells were stimulated with CD80-expressing HeLa cells or CaSki cells in the absence or presence of IL-2, IL-7, IL-12, or combinations thereof. The proliferative response of the T cells was determined. CD80-transduced HeLa or CaSki cells induced a stronger proliferative response in allogeneic T cells than parental or mock transfected control cells. All three interleukins enhanced the proliferative response of allogeneic T cells to CD80-expressing tumor cells. IL-2 or IL-7 had stronger effects in expanding the T cells than IL-12. Combination of IL-2 and IL-7 resulted in best T cell expansion. The proliferating T cells were mainly CD8+ cells with MHC class I restricted and unrestricted cytotoxic activity. Stimulation with CD80 alone or in combination with IL-7 induced mainly cytotoxic T lymphocytes. IL-2, IL-12 or the combination of IL-2 and IL-7 induced natural killer cell-like activity and specific cytolytic activity against parental and CD80-positive tumor cells. Our data suggest that the expression of both CD80 and IL-2 plus IL-7 can enhance the efficacy of tumor vaccines.

B7-1 Antigen↗
PubMed2000

A role for both Ets and C/EBP transcription factors and mRNA stabilization in the MAPK-dependent increase in p21 (Cip-1/WAF1/mda6) protein levels in primary hepatocytes.

In primary hepatocytes and HepG2 hepatoma cells, prolonged activation of the p42/44 mitogen-activated protein kinase (MAPK) pathway is associated with a reduction in DNA synthesis, mediated by increased expression of the cyclin-dependent kinase inhibitor protein p21 (Cip-1/WAF1/mda6) (p21). This study was performed to evaluate the contribution of transcriptional and post-transcriptional regulation in this response. Prolonged activation of the MAPK pathway in wild-type or p21 null hepatocytes caused a large decrease and increase, respectively, in DNA synthesis. Prolonged activation of the MAPK pathway in either wild-type or p21 antisense HepG2 cells also caused large decreases and increases, respectively, in DNA synthesis. MAPK signaling increased the phosphorylation of the transcription factors Ets2, C/EBPalpha, and C/EBPbeta, and rapidly increased transcription from the p21 promoter via multiple Ets- and C/EBP-elements within the enhancer region. Eight hours after MAPK activation, loss of C/EBPbeta or Ets2 function significantly reduced MAPK-stimulated transcription from the p21 promoter and abolished increased p21 protein expression. At this time, MAPK signaling increased both p21 mRNA and p21 protein stabilities that were also demonstrated to be essential for a profound increase in p21 protein levels. Thirty-six hours after MAPK activation, transcription from the p21 promoter was still significantly reduced in cells without either C/EBPbeta or Ets2 function; however, these cells were now capable of exhibiting a partial increase in p21 protein expression. In contrast, loss of C/EBPalpha function modestly reduced MAPK-stimulated transcription from the p21 promoter but strongly inhibited the ability of prolonged MAPK activation to increase protein levels of p21. This data suggested that prolonged enhancement of p21 protein levels may be under posttranscriptional control. In agreement with this hypothesis, prolonged MAPK signaling further increased p21 mRNA stability at 36 h, compared with the 8-h time point. Our data argue that MAPK signaling increased p21 promoter activity via multiple transcription factors, which alone were insufficient for a robust prolonged increase in p21 protein levels in primary hepatocytes, and that to increase p21 protein levels also required enhanced stabilization of p21 mRNA and p21 protein. Collectively, these data suggest that loss of transcription factor and mRNA/protein stabilization functions correlates with an inability of MAPK signaling to cause growth arrest versus proliferation in primary hepatocytes.

Animals↗
PubMed2000

Cervical cancer cells induce apoptosis of cytotoxic T lymphocytes.

The goal of immunotherapy is to eliminate tumors by generating tumor-specific cytotoxic T lymphocytes (CTLs) in patients or by adoptively transferring ex vivo-activated CTLs into patients. Clinical trials have shown that tumor-specific CTLs often disappear before tumors are completely eliminated. In this study, the authors show that CTLs specific for cervical tumor cells undergo apoptosis after they are co-cultured with cervical tumor cells. The established cervical tumor cell lines and cervical cancer tissues express CD95 (Fas/Apo-1) ligand. The tumor cell-induced T-cell apoptosis can be blocked by an inhibitory anti-CD95 (APO-1/Fas) antibody, indicating that tumor cells induce apoptosis of CTLs through CD95-CD95 ligand interaction. Addition of interleukin-2 (IL-2) and IL-7 into the culture rescues the CTL from tumor cell-induced apoptosis. The rescued T cells retain their full antitumor cytotoxicity. These data suggest that human cervical tumor cells might actively down-regulate a cellular immune response by inducing apoptosis of specific T cells during immunotherapy. Local use of IL-2 and IL-7 as adjuvants may promote survival of the CTL and, thus, enhance the efficacy of immunotherapy.

Apoptosis↗
PubMed2000

Long-term results of functional hemispherectomy for intractable seizures.

OBJECTIVE: From May 1989 to April 1997, functional hemispherectomy was performed in 8 cases of intractable seizures. We retrospectively analyzed our experience to evaluate the seizure control and complications of this surgical technique. METHODS: Following Dr. Rasmussen's model of functional hemispherectomy or performing a modification of this operation, we removed the sensorimotor cortex and temporal lobe associated with disconnection of the remaining portions of the frontal lobe and parieto-occipital lobe. RESULTS: All the patients were followed up for 3-11 years (mean 6.7 years). Satisfactory seizure control was obtained in all the cases. Life quality improved and patients worked or studied well after the operations. No cases of superficial cerebral hemosiderosis were found. CONCLUSION: Modified functional hemispherectomy may allow the patients to lead more independent lives by leading to a cessation or reduced frequency of seizures.

Adolescent↗
PubMed2000

Decreased Akt kinase activity and insulin resistance in C57BL/KsJ-Leprdb/db mice.

Recent studies suggest that the serine/threonine kinase protein kinase B (PKB or Akt) is involved in the pathway for insulin-stimulated glucose transporter 4 (GLUT4) translocation and glucose uptake. In this study we examined the components of the Akt signaling pathway in skeletal muscle and adipose tissue in vivo from C57BL/KsJ-Lepr(db/db) mice (db/db), a model of obesity, insulin resistance, and type II diabetes. There were no changes in the protein levels of GLUT4, p85alpha, or Akt in tissues from db/db mice compared with non-diabetic littermate controls (+/+). In response to acute insulin administration, GLUT4 recruitment to the plasma membrane increased twofold in muscle and adipose tissue from +/+ mice, but was significantly reduced by 42-43% (P<0.05) in both tissues from db/db mice. Insulin increased Akt-Ser(473) phosphorylation by two- to fivefold in muscle and adipose tissue from all mice. However, in db/db mice, maximal Akt-Ser(473) phosphorylation was decreased by 32% (P<0.05) and 69% (P<0.05) in muscle and adipose tissue respectively. This decreased phosphorylation in db/db mice corresponded with a significant decrease in maximal Akt kinase activity using a glycogen synthase kinase-3 fusion protein as a substrate (P<0.05). The level of insulin-stimulated tyrosine phosphorylation of p85alpha from phosphatidylinositol 3 (PI 3)-kinase, which is upstream of Akt, was also reduced in muscle and adipose tissue from db/db mice (P<0.05); however, there was no change in extracellular signal-regulated kinase-1 or -2 phosphorylation. These data implicate decreased insulin-stimulated Akt kinase activity as an important component underlying impaired GLUT4 translocation and insulin resistance in tissues from db/db mice. However, impaired insulin signal transduction appears to be specific for the PI 3-kinase pathway of insulin signaling, while the MAP kinase pathway remained intact.

Animals↗
PubMed2000

[Study on the hepatitis virus infection among medical professionals].

OBJECTIVE: In order to find out the present situation of hepatitis virus infection among medical professionals. METHODS: 140 medical professionals were studied on their serum HBsAg, anti - HBs, anti - HCV using EIA, and HEV - IgG, HGV - IgG with ELISA. RESULTS: The infection rates of HBsAg, HCV, HEV and HGV of medical professionals were 7.8%, 1.4%, 7.1% and 7.1% respectively with an overall infection rate of 23.5%. The infection rates for the clinical group and the non - clinical group were 33.3% and 12.3% respectively [with significant differences (P < 0.01)]. The infection rates of HEV and HGV for the clinical group were 8.0% and 12.0% respectively. It was found no superimposing infection in non - clinical group but was in clinical group. CONCLUSION: The result suggested that the infection rate of hepatitis virus in the medical professionals in the clinical group was higher than in the non - clinical group.

Adult↗
PubMed2000

[Effect of rhubarb on oxygen radicals leakage from mitochondria of intestinal mucosa in burned rats].

OBJECTIVE: To investigate the effects of rhubarb on oxygen radicals leakage from the mitochondria of intestinal mucosa in burned rats. METHODS: The activity of cytochrome oxidase and superoxide dismutase (SOD) in mitochondria isolated from intestinal mucosa of burn model of rats was used to evaluate the oxygen radicals leakage from the mitochondria. And the SOD and malondialdehyde (MDA) levels in plasma, liver, intestinal mucosa and its mitochondria were also determined. RESULTS: After burn injury, the activity of cytochrome oxidase in intestinal mucosa decreased as the time elapses, rhubarb could improve it obviously. Furthermore, rhubarb could reduce the massive consumption of SOD and production of MDA obviously increased in plasma, liver, intestinal mucosa and its mitochondria after burning. CONCLUSION: Rhubarb could enhance the activity of cytochrome oxidase and SOD in small intestine mucosal epithelia in burned rats, thus the oxygen radicals leakage from the mitochondria to be reduced.

Animals↗
PubMed2000

[Vasomotor rhinitis following endoscopic sinus surgery: 5 cases report].

OBJECTIVE: To investigate the possibility of endoscopic sinus surgery causing vasomotor rhinitis. METHOD: A retrospective study of 300 patients who received endoscopic sinus surgery. 5 cases out of 300 suffered from vasomotor rhinitis 1-3 weeks following endoscopic sinus surgery. Radio frequency cautery of agger nasi mucous was applied to all 5 patients. RESULT: After 4-6 months of follow-up, 4 cases out of 5 with vasomotor rhinitis were effective and 1 improved. CONCLUSION: Endoscopic sinus surgery may be causative factor for vasomotor rhinitis.

Adolescent↗
PubMed2000

[The expression of transforming growth factor alpha and its receptor in nasal polyps].

OBJECTIVE: To assess the possible role of expression of TGF alpha and EGFR in nasal polyps and its relationship with PCNA labeling index. METHOD: Specimens from 20 patients of nasal polyps were studied with immunohistochemical technique. RESULT: The expression of TGF alpha, EGFR and PCNA were increased in the epithelium, gland cells and inflammatory cells of nasal polyps. There was a close correlation between the intensities of TGF alpha, EGFR and PCNA. CONCLUSION: TGF alpha may play a key role in epithelial cell proliferation in nasal polyps.

Adult↗
PubMed1999

Probing the binding of indolactam-V to protein kinase C through site-directed mutagenesis and computational docking simulations.

Protein kinase C (PKC) comprises a family of ubiquitous enzymes transducing signals by the lipophilic second messenger sn-1, 2-diacylglycerol (DAG). Teleocidin and its structurally simpler congener indolactam-V (ILV) bind to PKC with high affinity. In this paper, we report our computational docking studies on ILV binding to PKC using an automatic docking computer program, MCDOCK. In addition, we used site-directed mutagenesis to assess the quantitative contribution of crucial residues around the binding site of PKC to the binding affinity of ILV to PKC. On the basis of the docking studies, ILV binds to PKC in its cis-twist conformation and forms a number of optimal hydrogen bond interactions. In addition, the hydrophobic groups in ILV form "specific" hydrophobic interactions with side chains of a number of conserved hydrophobic residues in PKC. The predicted binding mode for ILV is entirely consistent with known structure-activity relationships and with our mutational analysis. Our mutational analysis establishes the quantitative contributions of a number of conserved residues to the binding of PKC to ILV. Taken together, our computational docking simulations and analysis by site-directed mutagenesis provide a clear understanding of the interaction between ILV and PKC and the structural basis for design of novel, high-affinity, and isozyme-selective PKC ligands.

Animals↗
PubMed1999

Benzolactam (BL) enhances sAPP secretion in fibroblasts and in PC12 cells.

Activation of protein kinase C is known to favor the alpha-secretase processing of the Alzheimer's disease (AD) amyloid precursor protein (APP), resulting in the generation of non-amyloidogenic soluble APP (sAPP). Consequently, the relative secretion of amyloidogenic Abeta1-40 and Abeta1-42(3) is reduced. This is particularly relevant since fibroblasts and other cells expressing APP and presenilin AD mutations secrete increased amounts of total Abeta and/or increased ratios of Abeta1-42(3)/Abeta1-40. Interestingly, PKC defects have been found in AD brain alpha and beta isoforms) and in fibroblasts (alpha isoform) from AD patients. Here, we use a novel PKC activator (benzolactam, BL) with improved selectivity for the alpha, beta and gamma isoforms to enhance sAPP secretion in fibroblasts from AD patients and in PC12 cells. Incubation (2 h) of AD fibroblasts with BL (1 and 10 microM) resulted in significant increases of sAPP secretion over basal levels. sAPP secretion in BL-treated AD cells was also slightly higher compared to control BL-treated fibroblasts, which only showed significant increases of sAPP secretion after treatment with 10 microM BL. Staurosporine (a PKC inhibitor) eliminated the effects of BL in both control and AD fibroblasts. BL and a related compound (LQ12) also caused an approximately 3-fold sAPP secretion in PC12 cells. The use of a novel and possibly non-tumorigenic PKC activator may prove useful to favor non-amyloidogenic APP processing and is, therefore, of potential therapeutic value.

Alzheimer Disease↗