Biomedical subjects

Z Li

Publications and source records attributed to Z Li.

At least 19 recordsLinked to original sources

PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗

PubMed2007

Development of indirect enzyme-linked immunosorbent assay with nucleoprotein as antigen for detection and quantification of antibodies against avian influenza virus.

Avian influenza (AI) is a serious infectious disease caused by avian influenza virus (AIV) belonging to type A Orthomyxovirus. In the present study, we developed an indirect enzyme-linked immunosorbent assay (ELISA) employing E. coli-expressed full-length nucleoprotein (NP) of H9N2 avian influenza virus for the detection and quantification of antibodies against AIV nucleoprotein. The NP-ELISA was compared with the AI agar gel propagation (AGP) test, haemagglutination inhibition (HI) test, and IDEXX-FlockChek ELISA using 263 sera. The NP-ELISA was significantly more sensitive than the AGP and HI tests, and showed 96.2% agreement ratio with IDEXX-FlockChek ELISA. With results obtained using the NP-ELISA, an ELISA titre (ET) prediction equation, with which the ELISA titres of a flock or individual chickens can be determined, was derived from a positive/negative (P/N) ratio standard curve. The NP-ELISA enables an alternative rapid serological diagnosis and is suitable for influenza A antibody screening, especially in species that harbour several influenza subtypes.

Animals↗

PubMed2007

Immunohistochemical analyses on serum proteins in nephrons of protein-overload mice by "in vivo cryotechnique".

Immunohistochemical analyses on local distributions of serum proteins in living mouse kidneys are usually difficult to examine with conventional preparation methods. By using our "in vivo cryotechnique" combined with freeze-substitution, we have checked immunolocalizations of the serum proteins in nephrons of bovine serum albumin (BSA)-overload mice, and compared them with those obtained by the conventional preparation methods. In two days of daily BSA-injected mice, the immunolocalization of BSA could be observed in Bowman's space and urinary tubules with their overt proteinuria, where another endogenous mouse albumin was similarly immunolocalized. The leakage of BSA and mouse albumin in Bowman's space and their reabsorption into proximal tubules were detected in 55% of nephrons, where no leakage of immunoglobulin G1 (IgG1) was detected. However, the leakage of IgG1, in addition to BSA and mouse albumin, was detected in the other nephrons. By carefully examining immunolocalizations of BSA and IgG1, they were obviously different from those obtained by the conventional preparation methods without normal blood circulation into the kidneys. The immunolocalizations of both BSA and mouse serum proteins could be directly analyzed with the "in vivo cryotechnique", suggesting that functional damage to glomerular filtration barriers are different at early stages of the BSA-overload mouse model, depending on each nephron of living mice.

Albuminuria↗

PubMed2006

Brain ethanol levels in rats after voluntary ethanol consumption using a sweetened gelatin vehicle.

A novel procedure for initiation of voluntary ethanol consumption in the rat was evaluated in terms of ease of initiation, consistency, and resulting brain ethanol levels. The "jello shot" consists of 10% ethanol in gelatin along with a caloric source (Polycose). Initiation of "jello shot" consumption in Sprague-Dawley rats required no food or water restriction and resulted in initial daily (8.4+/-0.6 g/kg body weight) and eventual hourly (1.1+/-0.1 g/kg body weight) intake of ethanol comparable to other procedures using either alcohol-preferring or non-genetically selected rats. Rat intake of ethanol via "jello shots" recovered quickly from environmental alterations and surgical implantation of a guide cannula. During 1-h free access sessions, consumption of the "jello shot" occurred during the initial 10 min and resulted in a dose-related increase in ethanol levels in nucleus accumbens measured using microdialysis. These brain ethanol levels were comparable to those achieved using other self-administration methods. However, when 0.5 g/kg ethanol was gavaged either in "jello shot" or saline, there was about a 20% decrease in brain ethanol concentrations after gavage of the "jello shot" compared to saline. Even so, lack of a need for initial food or water deprivation and the rapidity with which stable self-administration can be achieved both suggest utility of the "jello shot" as a completely voluntary ethanol procedure.

Alcohol Drinking↗

PubMed2006

Glucagon receptor knockout mice are resistant to diet-induced obesity and streptozotocin-mediated beta cell loss and hyperglycaemia.

AIMS/HYPOTHESIS: Under normal physiological conditions, glucagon signalling is important in glucose homeostasis. Hyperglucagonaemia or altered insulin:glucagon ratio plays a role in maintaining hyperglycaemia in subjects with type 2 diabetes. It has been reported that glucagon receptor knockout (Gcgr (-/-)) mice develop normally and have lower plasma glucose on a normal diet. The goal of the current research was to further investigate the role of glucagon signalling in metabolic control and glucose homeostasis. METHODS: Gcgr (-/-) mice were challenged with a high-fat diet (HFD) and with streptozotocin, which induces beta cell damage. They were then analysed for whole-body and serum metabolic phenotypes as well as pancreatic islet morphology. RESULTS: In comparison with wild-type mice, Gcgr (-/-) mice exhibited decreased body weight and food intake, reduced plasma glucose levels, and improved oral and intraperitoneal glucose tolerance. Elevated glucagon-like peptide-1 levels and reduced gastric emptying were also observed in Gcgr (-/-) mice, which also had reduced HFD-induced hyperinsulinaemia and hyperleptinaemia, and were resistant to the development of hepatic steatosis. In addition, Gcgr (-/-) mice were resistant to STZ-induced hyperglycaemia and pancreatic beta cell destruction. CONCLUSIONS/INTERPRETATION: This study demonstrates that blocking glucagon signalling by targeted Gcgr gene deletion leads to an improvement in metabolic control in this mouse model.

Animals↗

PubMed2006

Exploration of the emergence of the Victoria lineage of influenza B virus.

The Victoria lineage represented by B/Victoria/2/87 is one of the two major distinctive haemagglutinin (HA) lineages of influenza B virus, and its recent re-emergence has aroused great concerns. However, it remains unknown when, where, and how this HA lineage emerged in the world. In this study, the HA1 domain of the HA gene of fourteen influenza B viruses isolated in China in 1972-1984 was sequenced. The sequences were phylogenetically analyzed with the HA1 sequences of 41 other important influenza B isolates. The results unveiled some earlier footprints of the Victoria lineage in China, and the epidemic history of the Victoria lineage could be traced back from the year 1985 to 1975. Moreover, phylogenetic analysis, the history of China, and the epidemiology of influenza B virus indicated that the Victoria lineage possibly emerged in China in the 1970s through gradual evolution from a minor lineage.

Amino Acid Sequence↗

PubMed2006

Juvenile ossifying fibroma of the maxilla.

Juvenile ossifying fibroma is a rare fibro-osseous neoplasm in young children. This lesion is locally aggressive and spreads quickly, and because it has a very high recurrence rate complete excision is essential. Reported here is a case of a massive juvenile ossifying fibroma of the maxilla in an 11-year-old male child. A titanium mesh was used to reconstruct the facial contour after a left total maxillectomy, achieving a satisfactory facial appearance.

Child↗

PubMed2006

Sensitive and selective liquid chromatography-mass spectrometry method for the quantification of rosiglitazone in human plasma.

A sensitive and selective high-performance liquid chromatography-electrospray ionisation-tandem mass spectrometry (HPLC-ESI-MS-MS) method for determination of rosiglitazone in human plasma has been developed. After the addition of the internal standard, plasma samples were precipitated by acetonitrile. The compounds were separated on a proC18 column using a mixture of ammonium acetate buffer (0.02 M, pH 6.5) and acetonitrile (in the ratio of 47:53, v/v) as mobile phase. A Finnigan LCQdeca plus ion trap mass spectrometer connected to a Finnigan Surveyor HPLC was used to develop and validate the method. Linearity was established for the range of concentrations 1-1000 ng/ml with a coefficient of determination (r(2)) of 0.999. The intra-day accuracy for rosiglitazone ranged from 110.0 to 99.2% at low, medium and high levels. The inter-day accuracy was less than 15%. The lower limit of quantitation (LLOQ) was identified reproducible at 1.0 ng/ml with a precision of 5.7%. After validation, the method was used to study the pharmacokinetic profile of rosiglitazone in five healthy volunteers after administration of a single oral dose (4.0mg). The proposed method enabled the unambiguous evaluation and quantitation of rosiglitazone for pharmacokinetic, bioavailability or drug-drug interaction studies. A possible chromatography peak (m/z 121, its parent ion m/z 344) of N-demethyl rosiglitazone was observed at 3.49 min during determining rosiglitazone. This may be also a potential method for simultaneous determination of rosiglitazone and its metabolite N-demethyl rosiglitazone concentrations in plasma.

Administration, Oral↗

PubMed2006

Different expression of synemin isoforms in glia and neurons during nervous system development.

The synemin gene encodes proteins belonging to the intermediate filament family. These proteins confer resistance to mechanical stress and modulate cell shape. Three synemin isoforms, of 180 (H), 150 (M) and 41 (L) kDa, are produced by alternative splicing of the pre-mRNA and are regulated differently during development. The three isoforms differ in their C-terminal tail domains, while their IF rod domains are identical. Synemins H/M occurred together with nestin and vimentin in glial progenitors during the early differentiation of the developing mouse central nervous system. They are later found in GFAP-labeled cells. In contrast, the L isoform appeared only in neurons, together with neurofilaments and betaIII-tubulin in the brain after birth. However, synemin L appeared from E13 in the peripheral nervous system, where it was confined to the neurons of spinal ganglia. In the meantime, the synemin H/M isoforms were found in both the neurons and Schwann cells of the sensorial ganglia from E11. Tissue fractionation and purification of IFs from adult mouse spinal cord revealed that the synemin L isoform binds to neurofilaments associated with the membrane compartment. This report describes the synthesis of the three synemin isoforms by selective cell types, and their temporal and spatial distributions. Mechanisms specific to neurons and glia probably control the splicing of the common synemin mRNA and the synthesis of each synemin isoform.

Alternative Splicing↗

PubMed2006

Gene therapy by membrane-expressed superantigen for alpha-fetoprotein-producing hepatocellular carcinoma.

Staphylococcus enterotoxin A (SEA) is a powerful immunostimulant, which can stimulate T cells bearing certain T-cell receptor beta-chain variable regions, when bound to major histocompatibility complex II molecules. In vivo administration of intact superantigen in sufficient therapeutic amounts risks unwanted cytotoxicity against normal cells. In this study, we used SEA fused with CD80 transmembrane region (named as SEAtm) driven by alpha-fetoprotein (AFP) enhancer/promoter to reduce toxicity and to improve safety and efficiency in the application of SEA. We demonstrated that SEAtm by adenovirus from the AFP enhancer/promoter (AdAFPSEA) could be expressed on the surface of AFP-producing cell line Hepa1-6 instead of non-AFP-producing cell lines. Hepa1-6 infected by recombinant adenovirus stimulated proliferation of splenocytes and activated CD4(+) and CD8(+) T cells in vitro. After AdAFPSEA was injected into the subcutaneously established hepatoma in vivo, the expression of SEA was detected in tumor tissues, which subsequently induced tumor-specific cytotoxic T cells in spleen. Moreover, hepatocellular carcinoma (HCC) xenografts were suppressed by treatment with AdAFPSEA and the survival time of treated mice was prolonged. These findings suggest that membrane-expressed SEA by adenovirus from AdAFPSEA can generate stronger local and systemic antitumor responses against HCC.

Adenoviridae↗

PubMed2006

Antisense Smo under the control of the PTCH1 promoter delivered by an adenoviral vector inhibits the growth of human pancreatic cancer.

Hedgehog (Hh) signaling pathway is crucial in growth and patterning during embryonic development. Recent data have shown an association of its activation with cancer formation and maintenance. A ligand-dependent activation, where Hh components (SHH, PTCH1, Smo and GLi1) are aberrantly expressed with PTCH1 being a negative feedback regulator, is a newly identified mechanism for pancreatic carcinogenesis. In this study, we developed a cell-specific cytotoxic model for the treatment of human pancreatic cancer (HPC) in which expression of antisense Smo (SAS) was under the control of the PTCH1 promoter (ptch/p) delivered by an adenoviral vector (Ad-ptch/p-SAS). We observed that the cell-specific cytotoxicity in HPC cells depended on the expressions of inherent PTCH1, Smo and GLi1 in the target cells in which the Hh pathway was presumed to be activated. Fluorescence-activated cell sorting analysis indicated that the cell death was apoptosis. Western blot showed that Smo protein in the infected cells significantly decreased. Furthermore, an in vivo experiment demonstrated that such Hh activity-cell-specific cytotoxicity was achieved by daily intratumoral injection of Ad-ptch/p-SAS (10(9) plaque-forming unit) for 5 days. Our study suggests that targeting at the Hh signaling pathway may be an effective novel gene therapeutic strategy alone or in combination with other agents for the treatment of pancreatic cancer.

Adenoviridae↗

PubMed2006

Downregulation of Bim by brain-derived neurotrophic factor activation of TrkB protects neuroblastoma cells from paclitaxel but not etoposide or cisplatin-induced cell death.

Chemoresistance and increased expression of TrkB and brain-derived neurotrophic factor (BDNF) are biomarkers of poor prognosis in tumors from patients with neuroblastoma (NB). Previously, we found BDNF activation of TrkB through PI3K/Akt protects NB from etoposide/cisplatin-induced cell death. In this study, the role of Bim, a proapoptotic protein, was investigated. Bim was involved in paclitaxel but not etoposide or cisplatin-induced cell death in NB cells. Pharmacological and genetic studies showed that BDNF-induced decreases in Bim were regulated by MAPK and not PI3K/Akt pathway. Both MAPK and PI3K pathways were involved in BDNF protection of NB cells from paclitaxel-induced cell death, while PI3K predominantly mediated BDNF protection of NB cells from etoposide or cisplatin-induced cell death. These data indicate that different chemotherapeutic drugs induce distinct death pathways and growth factors utilize different signal transduction pathways to modulate the effects of chemotherapy on cells.

Antineoplastic Agents↗

PubMed2006

Evaluating a new method to judge dialysis treatment using online measurements of ionic clearance.

New technology now supports direct online measurements of total dialysis dose per treatment, Kt. An outcome-based, nonlinear method for estimating target Kt in terms of ionic clearance measurements and body surface area (BSA) has been described recently. This is a validation study of the new method that evaluates the relationship between the (actual Kt-target Kt) difference and death risk. Patients with Kt measurements during March 2004 were identified (N=59,644). Target Kt was determined for each patient using the new method. Patients were then grouped by (actual Kt-target Kt) decile. They were also grouped by (actual URR-target URR) decile. Cox analysis-based risk profiles were constructed using those groupings. The (actual Kt-target Kt) difference profiles suggested improving death risk as Kt increased from below target to equal target. Risk ratios then flattened and remained so until (actual Kt-target Kt) reached the highest decile at which it appeared to improve, suggesting a possible biphasic profile. The (URR-target URR) risk profile was U-shaped. Death risk was related to the difference between the actual Kt and a target Kt value selected using the new nonlinear method. The method is therefore valid for prescribing and monitoring hemodialysis treatment.

Body Surface Area↗

PubMed2006

Low doses of dietary lead are associated with a profound reduction in the time to the onset of puberty in female mice.

We report results from a replication in second and third generation female mice of accelerated time to puberty associated with low Pb exposure levels . Mice in the 2nd generation study are offspring of mice from the initial study; the 3rd generation mice are offspring from mice in the 2nd generation study. For each generation the time to puberty onset was markedly influenced by exposure to dietary lead. Modest increases in blood lead concentration from a normal background of 2-3 to 8-13 micro g/dl delayed the onset of puberty by 10-20% from a normal of 33-35 days to about 40-43 days; reducing blood lead from 2-3 to 0.7 micro g/dl was associated with profound acceleration of puberty to 21 days, an enhancement by over 30%. This dose-response relationship, which replicates previous novel findings, has possible ecological as well as public health significance and indicates that lead is able to induce biologically significant changes at blood lead levels previously thought to be without effect.

Administration, Oral↗

PubMed2006

Association of preconceptional health care utilization and early initiation of prenatal care.

OBJECTIVE: To assess whether women having preconceptional health care utilization were more likely to have early initiation of prenatal care than were women not having preconceptional health care utilization. STUDY DESIGN: In this cohort study, data were collected prospectively from a population-based Perinatal Health Care Surveillance System in China. The analysis included 195 796 women who delivered single live births in 13 cities/counties during 1997 to 2000. Mantel-Haenszel test was employed to calculate risk ratios and 95% confidence intervals (CI). Multivariate logistic regression was conducted to assess the association between preconceptional health care utilization and early initiation of prenatal care after controlling for maternal residence, age at delivery, educational attainment, occupation, parity, preconceptional medical disorders, and high-risk medical experiences during the first trimester. SPSS 11.5 (SPSS Inc.) was employed for data analysis. RESULTS: Women having preconceptional health care utilization were 2.6 times (95%CI: 2.5 to 2.6) more likely to have early initiation of prenatal care compared with women not having preconceptional health care utilization. When stratified by maternal residence, age at delivery, educational attainment, occupation, parity, preconceptional medical disorder, high-risk medical experiences during the first trimester, and preconceptional medical disorders, this association still existed. After controlling for stratification factors mentioned above and the interaction of maternal age, educational attainment, and parity, women having preconceptional health care utilization were 2.7 times (95%CI: 2.6 to 2.8) more likely to have early initiation of prenatal care than were women not having preconceptional health care utilization. CONCLUSION: Women who had preconceptional health care utilization were more likely to have early prenatal care than were women not having preconceptional health care utilization.

Adult↗

PubMed2006

Measurements of the exclusive decays of the upsilon(5S) to meson final states and improved B(s)* mass measurement.

Using 420 pb(-1) of data collected on the upsilon(5S) resonance with the CLEO III detector, we reconstruct B mesons in 25 exclusive decay channels to measure or set upper limits on the decay rate of upsilon(5S) into B meson final states. We measure the inclusive B cross section to be sigma(upsilon(5S) --> BB(X)) = (0.177 +/- 0.030 +/- 0.016) nb and make the first measurements of the production rates of sigma(upsilon(5S) --> B*B*) = (0.131 +/- 0.025 +/- 0.014) nb and sigma(upsilon(5S) --> BB*) = (0.043 +/- 0.016 +/- 0.006) nb, respectively. We set 90% confidence level limits of sigma(upsilon(5S) -->BB) < 0.038 nb, sigma(upsilon(5S) --> B(*)B(*)pi) < 0.055 nb and sigma(upsilon(5S) --> BBpipi) < 0.024 nb. We also extract the most precise value of the B(s)* mass to date, M(B(s)*) = (5411.7 +/- 1.6 +/- 0.6) MeV/c2.

Journal Article↗

PubMed2006

Experimental limits on weak annihilation contributions to decays.

We present the first experimental limits on high-q2 contributions to charmless semileptonic decays of the form expected from the weak annihilation (WA) decay mechanism. Such contributions could bias determinations of /Vub/ from inclusive measurements of B-->Xulupsilon. Using a wide range of models based on available theoretical input we set a limit of GammaWA/Gammab-->u<7.4% (90% confidence level) on the WA fraction, and assess the impact on previous inclusive determinations of /Vub/.

Journal Article↗

PubMed2006

Action mechanisms and structure-activity relationships of PI3Kgamma inhibitors on the enzyme: a molecular modeling study.

Action mechanisms of four types of PI3Kgamma inhibitors were investigated on the ligand-binding pocket (LBP) of PI3Kgamma with molecular modeling method. At first five compounds whose complex structures with PI3Kgamma were available experimentally were used to validate the reliability of docking program Autodock3.0. The results demonstrated that the program could reproduce the bound conformations of those compounds in crystal structures. Then the program was used to dock all the four types of PI3Kgamma inhibitors into the LBP of the enzyme. The predicted activities of these compounds were in agreement with their experimental activities, and a pharmacophore model was hence derived for these compounds, which consisted of one hydrophobic portion flanked by two symmetric hydrophilic portions. Furthermore, the structure-activity relationships of PI3Kgamma inhibitors were elucidated and the activity differences between them were discussed.

Adenosine Triphosphate↗