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H Zhao

Publications and source records attributed to H Zhao.

At least 19 recordsLinked to original sources
PubMed2006

Assessment of the relative skin sensitization potency of siloranes and bis-GMA using the local lymph node assay and QSAR predicted potency.

Siloranes are silicon and oxirane (epoxy) containing monomers used for new dental composite development. The siloranes 3,4-epoxycyclohexylethyl-cyclopolymethylsiloxane (Tet-Sil) and bis-3,4-epoxycyclohexylethyl-phenyl-methylsilane (Ph-Sil) have in common cycloaliphatic epoxy moieties. The epoxy group is of concern in their biocompatibility since most epoxy compounds are known skin sensitizers. The objective of this study was to determine the in vivo skin sensitization potency of the siloranes in the local lymph node assay. A comparison was made with well-known chemical allergens, bis-GMA and DNCB. Female mice (CBA/CaJ) were exposed topically (dorsum of both ears) to several doses of acetone:olive oil in the ratio of 4:1 v/v. Doses were defined by a predictive structure-activity model (QSAR) for contact sensitization. Lymph node cell (LNC) proliferation was measured on the sixth day by incorporation of radioactive thymidine into DNA of lymph node cells. The effective concentration (EC3) that produced a 3-fold stimulation in LNC proliferation relative to controls was extrapolated from dose-response curves. DNCB was a strong sensitizer (EC3 = 0.06%). The EC3 values of Ph-Sil and bis-GMA were 19% and 45%, respectively, making these weak contact sensitizers. Tet-Sil did not increase lymph node proliferation when compared with controls. In contrast to Tet-Sil, the unpolymerized monomers Ph-Sil and bis-GMA have the capacity to induce LNC proliferation, characteristic of a T-cell mediated skin contact sensitization.

Animals↗
PubMed2006

The role of Ret receptor tyrosine kinase in dopaminergic neuron development.

Glial cell line-derived neurotrophic factor (GDNF) is one of the most potent trophic factors identified for promoting survival and function of dopaminergic (DA) neurons in the midbrain. Ret, a member of the receptor tyrosine kinase (RTK) superfamily transduces GDNF signaling. The role of Ret in the development of DA neurons is not clear however. Here we demonstrate the involvement of Ret in the DA neuron development both in vitro and in vivo. The dopamine transporter (DAT) gene was clearly induced in rat embryonic neural precursors that had been transfected with Ret. Temporary blockade of Ret expression in embryos using Ret antisense oligonucleotides (Ret-AS-ODN) in vivo led to reduced striatal DA content and a decrease of tyrosine hydroxylase (TH) positive fibers in the striatum. Additionally, some DA neurons in the substantia nigra (SN) underwent apoptotic cell death following the Ret-AS-ODN treatment. Taken together, the data suggest that normal function of Ret is required in vivo for the maturation of DA neurons, in particular for cell survival and fiber innervation. We further demonstrated Ret-induced expression of DAT in vitro.

Animals↗
PubMed2006

Role of enteral nutrition supplemented with ebselen and EHEC in pancreatitis-associated multiple organ dysfunction in rats.

OBJECTIVES: To investigate potential effects of ebselen and ethylhydroxyethyl cellulose (EHEC) on the acute phase responses and the severity of multiple organ dysfunction associated with acute pancreatitis. METHODS: Acute pancreatitis was induced by intraductal infusion of 5% sodium taurodeoxycholate. The increase of total protein content in the BALF was used as an indication for acute lung injury, plasma amylase for pancreatic damage, plasma bilirubin for acute liver dysfunction, and plasma creatinine for acute kidney dysfunction. Levels of interleukin (IL)-6, macrophage inflammatory protein (MIP)-2 in the BALF were determined by ELISA. RESULTS: There was a dose-related tendency for ebselen or EHEC alone to prevent organ dysfunction and reduce elevated plasma levels of IL-6 and ICAM-1 expression on circulating leukocytes 12 h after AP induction. The combination of ebselen and EHEC significantly prevented pancreatitis-induced multiple organ injury, IL-6 production and ICAM-1 expression in rats and exhibited better effects than either monocompound alone. CONCLUSION: The combination of ebselen and EHEC may be a new potential for treatment of acute severe pancreatitis.

Amylases↗
PubMed2006

Gingival epithelial cells heterozygous for Toll-like receptor 4 polymorphisms Asp299Gly and Thr399ile are hypo-responsive to Porphyromonas gingivalis.

The Toll-like receptor (TLR)4 is the major sensor for bacterial lipopolysaccharide and its two common co-segregating polymorphisms, Asp299Gly and Thr399Ile, which occur at a frequency of between 6 and 10%, have been associated with infectious diseases, LPS hypo-responsiveness and cardiovascular disease. Porphyromonas gingivalis is a Gram-negative bacterium implicated in chronic periodontitis and is a known TLR4 and TLR2 agonist. We obtained two gingival epithelial cell primary cultures from subjects heterozygous for the TLR4 polymorphism Asp299Gly and compared response characteristics with similar cells from patients (four) with the wild-type TLR4 genes. Cytokine responses and transcriptome profiles of gingival epithelial cell primary culture cells to TNFalpha challenge were similar for all primary epithelial cell cultures. P. gingivalis challenge, however, gave markedly different responses for Asp299Gly heterozygous and wild-type epithelial cell cultures. The epithelial cells heterozygous for the TLR4 polymorphism Asp299Gly were functionally hypo-responsive, evidenced by differences in BD-2 mRNA expression, mRNA response profile by microarray analysis and by pro-inflammatory and chemokine cytokines at the protein and mRNA level. These findings emphasize variance in human epithelial cell TLRs, linked with Asp299Gly carriage, which results in a hypo-responsive epithelial cell phenotype less susceptible to Gram-negative diseases and associated systemic conditions.

Amino Acid Substitution↗
PubMed2005

Extent and consistency across generations of linkage disequilibrium in commercial layer chicken breeding populations.

Recent studies report a surprisingly high degree of marker-to-marker linkage disequilibrium (LD) in ruminant livestock populations. This has important implications for QTL mapping and marker-assisted selection. This study evaluated LD between microsatellite markers in a number of breeding populations of layer chickens using the standardized chi-square (chi(2')) measure. The results show appreciable LD among markers separated by up to 5 cM, decreasing rapidly with increased separation between markers. The LD within 5 cM was strongly conserved across generations and differed among chromosomal regions. Using marker-to-marker LD as an indication for marker-QTL LD, a genome scan of markers spaced 2 cM apart at moderate power would have good chances of uncovering most QTL segregating in these populations. However, of markers showing significant trait associations, only 57% are expected to be within 5 cM of the responsible QTL, and the remainder will be up to 20 cM away. Thus, high-resolution LD mapping of QTL will require dense marker genotyping across the region of interest to allow for interval mapping of the QTL.

Animals↗
PubMed2005

Calcitonin gene-related peptide and substance P contribute to reduced blood pressure in sympathectomized rats.

CGRP and substance P (SP) are produced in dorsal root ganglia (DRG) sensory neurons and modulate vascular tone. Sympathetic and sensory nerves compete for NGF, a potent stimulator of CGRP and SP, and it has been suggested that sympathetic hyperinnervation in spontaneously hypertensive rats may reduce the availability of NGF to sensory nerves, thus reducing CGRP and SP. The purpose of this study was to determine whether destruction of peripheral sympathetic nerves in normal rats would increase the availability of NGF for sensory neurons and enhance expression of CGRP and SP. Sympathectomy was produced in rats by guanethidine sulfate administration. Control rats received saline. Sympathectomized rats displayed reductions in blood pressure (BP) and atria norepinephrine levels, whereas NGF levels in the DRG, spleen, and ventricles were increased. Sympathectomy also enhanced CGRP and SP mRNA and peptide content in DRG. Administration of CGRP and SP receptor antagonists increased the BP in sympathectomized rats but not in the controls. Thus sympathectomy enhances sensory neuron CGRP and SP expression that contributes to the BP reduction.

Animals↗
PubMed2005

Use of CD34+ autologous stem cell transplantation in the treatment of children with refractory systemic lupus erythematosus.

We report on the unique effects and benefits of autologous stem cell transplantation in childhood systemic lupus erythematosus (SLE) and describe this procedure in two young girls with severe and refractory disease. The patients' stem cells were mobilized with granulocyte colony-stimulating factor (G-CSF) and collected by CS-3000 Blood Cell Separator (Baxter Healthcare, Round Lake, Ill., USA), and the CliniMACS CD34+ cell selection device (Miltenyi Biotech, Bergisch Gladbach, Germany) was used to obtain CD34+ cells. A total of 1.7x10(6) and 1.0x10(6)/kg CD34+ cells were obtained, with 2.0x10(5) and 1.0x10(4)/kg of CD3+ cells remaining, respectively. The conditioning regimen consisted of cyclophosphamide (50 mg/kg per day for 4 days) plus antithymocyte globulin (ATG-Fresenius, 5 mg/kg per day for 3 days). Neutrophil counts recovered within 9 days in both cases. Within 15 days, the platelet counts recovered and were sustained over 100x10(9)/l. Cushingoid features disappeared completely 3 months after transplantation because of the removal of corticosteroid medication. One 13-year-old child increased her height by 5 cm in 6 months after stopping steroids. She had not increased her height in her previous 7 years of disease. As of the time of this report, the first patient remains in clinical and laboratory remission for nearly 4 years, while the second suffered a relapse of thrombocytopenia 9 months post-transplantation. One residual effect of their treatment is that their CD4+ cell counts remained in the lower range after one year of transplant. The effect of this conditioning regimen plus CD34+ autologous stem cell transplantation on these two children with refractory SLE was beneficial, but long-term follow-up data and additional experience with this procedure are required. Autologous stem cell transplantation may limit the long-term toxicity of therapy in childhood SLE.

Adolescent↗
PubMed2005

Physicochemical characterisation of residual hemicelluloses isolated with cyanamide-activated hydrogen peroxide from organosolv pre-treated wheat straw.

Seven residual hemicellulosic preparations (19.6-45.0% of the original hemicelluloses) were extracted from wheat straw pre-treated with various organic solvents using 1.8% H2O2-0.18% cyanamide at 50 degrees C and pH 10.0 for 4 h. Their chemical compositions and physicochemical properties were determined using GC, HPLC, GPC, FT-IR and 13NMR spectroscopy. The results indicated that all the residual hemicellulosic preparations were heteropolysaccharides containing xylose, glucose, arabinose, galactose, mannose, rhamnose and 4-O-methyl-alpha-D-glucopyranosyluronic acid. The predominant monosaccharide was xylose, ranging between 67.7% and 81.9% of the total neutral sugars, composed mainly of L-arabino-(4-O-methyl-D-glucurono)-D-xylan. The content of contaminant lignin in the isolated residual hemicelluloses was 2.89-5.31%. The Mw values of the two residual hemicellulosic preparations H6 and H7 (42,710 and 44,080 g mol-1, respectively) obtained from the aqueous-alcohol pre-treated straw were much higher than those of H1-H5 (12,980-15,950 g mol-1) extracted from the organic acid pre-treated straw.

Carbohydrates↗
PubMed2005

Effect of dimethyl sulfoxide on post-thaw viability assessment of CD45+ and CD34+ cells of umbilical cord blood and mobilized peripheral blood.

BACKGROUND: The effect of dimethyl sulfoxide (Me2SO) on enumeration of post-thaw CD45+ and CD34+ cells of umbilical cord blood (HPC-C) and mobilized peripheral blood (HPC-A) has not been systematically studied. METHODS: Cells from leukapheresis products from multiple myeloma patients and umbilical cord blood cells were suspended in 1, 2, 5, or 10% Me2SO for 20 min at 22 degrees C. Cells suspended in Me2SO were then immediately assessed or assessed following removal of Me2SO. In other samples, cells were suspended in 10% Me2SO, cooled slowly to -60 degrees C, stored at -150 degrees C for 48 h, then thawed. The thawed cells in 10% Me2SO were diluted to 1, 2, 5, or 10% Me2SO, held for 20 min at 22 degrees C and then immediately assessed or assessed after the removal of Me2SO. CD34+ cell viability was determined using a single platform flow cytometric absolute CD34+ cell count technique incorporating 7-AAD. RESULTS: The results indicate that after cryopreservation neither recovery of CD34+ cells nor viability of CD45+ and CD34+ cells from both post-thaw HPC-A and HPC-C were a function of the concentration of Me2SO. Without cryopreservation, when Me2SO is present recovery and viability of HPC-C CD34+ cells exposed to 10% Me2SO but not CD45+ cells were significantly decreased. Removing Me2SO by centrifugation significantly decreased the viability and recovery of CD34+ cells in both HPC-A and HPC-C before and after cryopreservation. DISCUSSION: To reflect the actual number of CD45+ cells and CD34+ cells infused into a patient, these results indicate that removal of Me2SO for assessment of CD34+ cell viability should only be performed if the HPC are infused after washing to remove Me2SO.

Antigens, CD34↗
PubMed2005

Circadian firing-rate rhythms and light responses of rat habenular nucleus neurons in vivo and in vitro.

The suprachiasmatic nuclei of the anterior hypothalamus serve as the principal pacemaker of the mammalian circadian system. Among its efferent targets are the habenular nucleus (Hb), especially the lateral Hb (LHb), which plays an important role in conveying input from the limbic forebrain to midbrain structures. We recorded extracellularly from single neurons in the LHb and medial Hb (MHb), both in vivo and using an in vitro slice preparation, to assess their responses to retinal illumination and the rhythmicity of their firing rates. Of cells recorded in the LHb, 42% were tonically activated or suppressed by retinal illumination, while significantly fewer cells recorded in the MHb responded to retinal illumination (19%). Of photically responsive cells, 68% in the LHb were activated and the remainder suppressed, while only 25% of those recorded in the MHb were activated. Cells in both the LHb and MHb showed higher baseline firing rates during the day than during the night in vivo, while photic responses were of significantly larger amplitude among LHb cells during the projected night than during the projected day. LHb cells recorded in vitro maintained their rhythmicity for two circadian cycles, but MHb cells did not show a rhythm in vitro. The habenula may play a role in linking circadian and motivational systems and may contribute to photic regulation of these systems, as well as to the rhythmicity of their function.

Action Potentials↗
PubMed2005

Lycium barbarum glycoconjugates: effect on human skin and cultured dermal fibroblasts.

Lycium barbarum L. (Solanaceae) glycoconjugates (LbGp) display an interesting array of anti-apoptotic and antioxidant properties, which may be beneficial for human skin. We therefore set out to determine the effects of LbGp in full-thickness human skin, and in dermal fibroblasts. It was found that LbGp decreased the level of MMP (matrix metalloproteinase)-1 significantly, but not that of MMP-3 or -13, in the whole human skin system, without compromising the viability of the skin. Consistently, LbGp inhibited skin expansion under mechanical stress, which in this model depends on the activity of MMP-1. We found that one of L. barbarum glycoconjugates, the LbGp5, promoted the survival of human fibroblasts cultured in suboptimal conditions. Furthermore, in the presence of LbGp5, these cultures also contained higher levels of the MMP-1 substrate--collagen type I. Together these results suggest that L. barbarum glycoconjugates in general, and LbGp5 in particular, may have important skin-protective properties.

Antioxidants↗
PubMed2005

Evaluation of linkage disequilibrium measures between multi-allelic markers as predictors of linkage disequilibrium between markers and QTL.

Effectiveness of marker-assisted selection (MAS) and quantitative trait loci (QTL) mapping using population-wide linkage disequilibrium (LD) between markers and QTL depends on the extent of LD and how it declines with distance in a population. Because marker-QTL LD cannot be observed directly, the objective of this study was to evaluate alternative measures of observable LD between multi-allelic markers as predictors of usable LD of multi-allelic markers with presumed biallelic QTL. Observable LD between marker pairs was evaluated using eight existing measures and one new measure. These consisted of two pooled and standardized measures of LD between pairs of alleles at two markers based on Lewontin's LD measure, two pooled measures of squared correlations between alleles, one standardized measure using Hardy-Weinberg heterozygosities, and four measures based on the chi-square statistic for testing for association between alleles at two loci. In simulated populations with a range of LD generated by drift and a range of marker polymorphism, marker-marker LD measured by a standardized chi-square statistic (denoted chi(2')) was found to be the best predictor of useable marker-QTL LD for a group of multi-allelic markers. Estimates of the level and decline of marker-marker LD with distance obtained from chi(2') were linearly and highly correlated with usable LD of those markers with QTL across population structures and marker polymorphism. Corresponding relationships were poorer for the other marker-marker LD measures. Therefore, when LD is generated by drift, chi(2') is recommended to quantify the amount and extent of usable LD in a population for QTL mapping and MAS based on multi-allelic markers.

Alleles↗
PubMed2005

Survival and complications in thalassemia.

The life expectancy of patients with thalassemia major has significantly increased in recent years, as reported by several groups in different countries. However, complications are still frequent and affect the patients' quality of life. In a recent study from the United Kingdom, it was found that 50% of the patients had died before age 35. At that age, 65% of the patients from an Italian long-term study were still alive. Heart disease is responsible for more than half of the deaths. The prevalence of complications in Italian patients born after 1970 includes heart failure in 7%, hypogonadism in 55%, hypothyroidism in 11%, and diabetes in 6%. Similar data were reported in patients from the United States. In the Italian study, lower ferritin levels were associated with a lower probability of experiencing heart failure and with prolonged survival. Osteoporosis and osteopenia are common and affect virtually all patients. Hepatitis C virus antibodies are present in 85% of multitransfused Italian patients, 23% of patients in the United Kingdom, 35% in the United States, 34% in France, and 21% in India. Hepatocellular carcinoma can complicate the course of hepatitis. A survey of Italian centers has identified 23 such cases in patients with a thalassemia syndrome. In conclusion, rates of survival and complication-free survival continue to improve, due to better treatment strategies. New complications are appearing in long-term survivors. Iron overload of the heart remains the main cause of morbidity and mortality.

Adolescent↗
PubMed2005

Studies involving the GH-IGF axis: Lessons from IGF-I and IGF-I receptor gene targeting mouse models.

The IGFs are ubiquitous and have pleoitropic effects. They are critical for normal growth and development, and for normal functioning of adult tissues. A liver-specific gene-deletion knockout of the IGF-I gene resulted in a mouse model with reduced circulating IGF-I levels, that led to insulin resistance due to the secondary elevation of circulating GH levels. The reduction in circulating IGF-I levels was also associated with a reduction in cancer growth and metastases in three cancer models, one for colon cancer and two for breast cancer. A second mouse model, using the transgenic approach, inhibited the IGF-I and insulin receptor function in skeletal muscle, and resulted in severe insulin resistance in muscle followed by insulin resistance in fat and liver and, eventually, beta-cell dysfunction and development of Type 2 diabetes. This progression from insulin resistance to Type 2 diabetes was most likely due to lipotoxicity with elevated serum and tissue triglyceride levels. Evidence supporting the hypothesis came from the use of fibrates and leptin injections, each of which enhanced fatty acid (FA) oxidation in liver and muscle and was associated with a reversal of the insulin resistance and diabetes.

Animals↗
PubMed2004

Therapeutic effects of dengue 2 virus capsid protein and staphylococcal nuclease fusion protein on dengue-infected cell cultures.

Dengue infection poses a serious public health problem in most tropical and subtropical areas. No effective antiviral drugs or vaccines are currently available against dengue infection. To explore the feasibility of using capsid-targeted viral inactivation (CTVI) as an antiviral strategy against dengue infection, we constructed a plasmid expressing a fusion protein consisting of staphylococcal nuclease (SN) fused to dengue 2 virus capsid protein (D2C), and investigated its effects on the production of infectious virions when introduced into BHK cells infected with dengue virus. The results indicated that D2C-SN can be expressed and tolerated in this mammalian cell culture. The enzymatically active SN moiety was incorporated into nascent virions during the process of viral assembly. By comparing the effects of incorporated SN and SN*, an enzymatically inactive missense mutant form of wild-type SN, on the infectivity of progeny virions, we clearly demonstrated that nucleolytic activity was the major antiviral mechanism. Expression of D2C-SN fusion protein as a therapeutic agent resulted in a reduction in infectious titers of 12- to 60-fold. Therefore, dengue virus may be particularly vulnerable to a CTVI therapeutic approach.

Animals↗
PubMed2004

Effects of aversive stimuli on learning and memory in Arctic ground squirrels.

The present study was designed to assess effects of aversive stimuli on learning and memory in wild-caught Arctic ground squirrels (AGS, Spermophilus parryii) using an active avoidance learning paradigm. Results indicate that animals trained with low-value aversive stimuli (air puffs and lights) retained the task better than animals trained with high-value aversive stimuli (air puffs, lights, and foot shock). Poor retention could not be explained by learning impairment, fear-induced freezing behavior or the effects of massed versus spaced training trials. Wild-caught AGS readily hibernate under laboratory conditions and provide a model of pronounced adult synaptic plasticity associated with emergence from hibernation. Characterization of learning and retention using active avoidance as well as other learning paradigms is a first step towards developing behavioral paradigms to assess cognitive function in this wild-trapped species. The present study shows that captive AGS are sensitive to aversive stimuli, argues for a direct effect on retention and suggests that high baseline levels of stress in a captive population may influence behavioral measures. The results further suggest that future studies of the effects of hibernation on learning and retention of active avoidance tasks employ low-level aversive stimuli.

Animals↗
PubMed2004

Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility.

PURPOSE: Our research program uses genetic linkage and association analysis to identify human seizure sensitivity and resistance alleles. Quantitative trait loci mapping in mice led to identification of genetic variation in the potassium ion channel gene Kcnj10, implicating it as a putative seizure susceptibility gene. The purpose of this work was to translate these animal model data to a human genetic association study. METHODS: We used single stranded conformation polymorphism (SSCP) electrophoresis, DNA sequencing and database searching (NCBI) to identify variation in the human KCNJ10 gene. Restriction fragment length polymorphism (RFLP) analysis, SSCP and Pyrosequencing were used to genotype a single nucleotide polymorphism (SNP, dbSNP rs#1130183) in KCNJ10 in epilepsy patients (n = 407) and unrelated controls (n = 284). The epilepsy group was comprised of patients with refractory mesial temporal lobe epilepsy (n = 153), childhood absence (n = 84), juvenile myoclonic (n = 111) and idiopathic generalized epilepsy not otherwise specified (IGE-NOS, n = 59) and all were of European ancestry. RESULTS: SNP rs#1130183 (C > T) alters amino acid 271 (of 379) from an arginine to a cysteine (R271C). The C allele (Arg) is common with conversion to the T allele (Cys) occurring twice as often in controls compared to epilepsy patients. Contingency analysis documented a statistically significant association between seizure resistance and allele frequency, Mantel-Haenszel chi square = 5.65, d.f. = 1, P = 0.017, odds ratio 0.52, 95% CI 0.33-0.82. CONCLUSION: The T allele of SNP rs#1130183 is associated with seizure resistance when common forms of focal and generalized epilepsy are analyzed as a group. These data suggest that this missense variation in KCNJ10 (or a nearby variation) is related to general seizure susceptibility in humans.

Chi-Square Distribution↗