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Biomedical subjects

X Liu

Publications and source records attributed to X Liu.

At least 73 records · Page 4Linked to original sources

Comparison of ozone uptake and sensitivity between a phytotron study with young beech and a field experiment with adult beech (Fagus sylvatica).

Chamber experiments on juvenile trees have resulted in severe injury and accelerated loss of leaves along with reduced biomass production under chronically enhanced O3 levels. In contrast, the few studies conducted on adult forest trees in the field have reported low O3 sensitivity. In the present study, young beech in phytotrons was more sensitive to O3 than adult beech in the field, although employed O3 regimes were similar. The hypotheses tested were that: (1) differences in O3 uptake were caused by the ontogenetically higher stomatal conductance of young compared to adult trees, (2) the experimental settings in the phytotrons enhanced O3 uptake compared to field conditions, and (3) a low detoxification capacity contributes to the higher O3 sensitivity of the young trees. The higher O3 sensitivity of juvenile beech in the phytotrons is demonstrated to relate to both the experimental conditions and the physiological responsiveness inherent to tree age.

Air Pollutants↗

Induction of suppressors of cytokine signaling (SOCS) in the retina during experimental autoimmune uveitis (EAU): potential neuroprotective role of SOCS proteins.

Suppressors of cytokine signaling (SOCS) are implicated in immunopathogenic mechanisms of autoimmune diseases. We show here that SOCS expression in retina is temporarily correlated with progression of experimental autoimmune uveitis (EAU), an organ-specific autoimmune disease that serves as model of human uveitis. Peak of EAU correlates with highest SOCS genes expression while disease resolution coincides with their down-regulation. Surprisingly, SOCS5 is constitutively expressed in retina. SOCS5 expression increases significantly during EAU and remains elevated even after disease resolution. Our data suggest that cytokine-inducible SOCS members may be involved in negative regulation of inflammatory cytokines activities during EAU, while constitutively expressed SOCS5 may have neuroprotective functions.

Animals↗

Vascular endothelial growth factor and its receptor Flk-1 are expressed in the hippocampus following entorhinal deafferentation.

Vascular endothelial growth factor (VEGF) has been thought of as a mitogen that promotes proliferation of endothelial cells and as a neurotrophic factor that stimulates neurogenesis and axonal growth in both peripheral and central nervous systems. To investigate the potential involvement of VEGF in the lesion-induced reorganization in the brain, the expression changes of VEGF and its receptor Flk-1 were analyzed in the mouse hippocampus after transections of the entorhinal afferents. In situ hybridization and immunohistochemistry showed the time-dependent expression upregulation of VEGF mRNA and protein in the entorhinally denervated hippocampal stratum lacunosum-moleculare and dentate outer molecular layer, which initiated by 3 days postlesion, reached its maximum at 7-15 days postlesion, still persisted by 30 days postlesion for protein, and recovered to the normal levels at 30 days postlesion for mRNA and at 60 days postlesion for protein. Double labeling of VEGF and glial fibrillary acidic protein revealed that VEGF-expressing cells in the denervated areas were reactive astrocytes. Semi-quantitative RT-PCR analysis showed that VEGF receptor Flk-1 mRNA was also time-dependently upregulated in the deafferented hippocampus with its maximal elevation at 7-15 days postlesion while the Flt-1 mRNA levels remained unchanged at any time point we examined. Immunohistochemistry analysis also displayed the upregulation of Flk-1 protein in the denervated stratum lacunosum-moleculare and outer molecular layer with a time course similar to that of VEGF mRNA upregulation. Flk-1 receptors were found to be expressed not only by reactive astrocytes but also by neurites, which most likely belong to sprouting axons by 7 days postlesion and regrowing dendrites by 15-30 days postlesion. From these data we suggest that the spatiotemporal upregulation of VEGF and Flk-1 in the hippocampus is induced by entorhinal deafferentation and that VEGF may be involved in the structural reorganization in the deafferented hippocampus via directly or indirectly promoting neurite growth.

Animals↗

Glucagon expression shift in a syngeneic single-donor intrahepatic rat islet transplantation model.

In the native rat pancreas glucagon is expressed by alpha cells in the outer layer of the spheroid islet, producing a circular immunohistochemical staining pattern. We asked whether this pattern would remain unchanged after short-term and long-term intrahepatic islet transplantation. Islets of inbred Lewis rats were isolated with liberase, purified by discontinuous density gradients, handpicked, and cultured for 24 hours. After rats were rendered diabetic with streptozotocin, islets were implanted intraportally. Transplanted animals were sacrificed at 1 to 2 days (n = 5) or 100 days (n = 6). Islet clusters were detected by hematoxylen-and-eosin staining. Serial slides were stained for glucagon and insulin with the alkaline phosphatase and alkaline phosphate method at 1 to 2 days after transplantation islets with strong insulin expression were found within the portal vein branches. However, glucagon staining showed an incomplete circular staining pattern. After 100 days insulin expression remained strong, whereas only few glucagon-expressing cells were detected. Intrapancreatic islets showed inversion of the ratio of insulin- to glucagon-positive cells in favor of the glucagon-expressing cells that now composed the major part of the islet. Streptozotocin had selectively damaged beta cells in the recipient. In transplanted islets glucagon expression faded over time, possibly due to a functional involution process or to stress/inflammatory mechanisms during the isolation, transplantation, and the posttransplantation periods.

Animals↗

Increased fluid secretion after adenoviral-mediated transfer of the human aquaporin-1 cDNA to irradiated miniature pig parotid glands.

The treatment of most head and neck cancer patients includes ionizing radiation (IR). Salivary glands in the IR field suffer irreversible damage. Previously, we reported that adenoviral (Ad)-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to rat submandibular glands following IR restored salivary flow to near normal levels. It is unclear if this strategy is useful in larger animals. Herein, we evaluated AdhAQP1-mediated gene transfer after parotid gland IR (20 Gy) in the miniature pig. Sixteen weeks following IR, salivation from the targeted gland was decreased by >80%. AdhAQP1 administration resulted in a dose-dependent increase in parotid salivary flow to approximately 80% of pre-IR levels on day 3. A control Ad vector was without significant effect. The effective AdhAQP1 dose was 2.5 x 10(5) pfu/microl infusate, a dose that leads to comparable transgene expression in murine and minipig salivary glands. Three days after Ad vector administration little change was observed in clinical chemistry and hematology values. These findings demonstrate that localized delivery of AdhAQP1 to IR-damaged salivary glands increases salivary secretion, without significant general adverse events, in a large animal model.

Adenoviridae↗

Dendritic cells transduced with an adenovirus vector encoding interleukin-12 are a potent vaccine for invasive pulmonary aspergillosis.

Invasive pulmonary aspergillosis (IPA) is a common and devastating pneumonia. We developed a novel antiinfective vaccine that couples the potent Ag-presenting capacity of dendritic cells (DCs) with paracrine delivery of interleukin-12 (IL-12) to local immune response sites. Our results showed that DCs engulfed Aspergillus conidia through coiling phagocytosis. Transfection of DCs with adenovirus encoding the cDNA of IL-12 did not affect their morphology and capacity to engulf conidia. The transduced DCs secreted IL-12, which was biologically active, to induce the production of gamma interferon (IFN-gamma) from spleen cells. Adoptive transfer of DCs pulsed with heat-inactivated Aspergillus fumigatus (HAF) to naive mice induced the Ag-specific production of IFN-gamma; the transduced HAF-pulsed DCs augmented this immune response further. Animals receiving HAF-pulsed DCs had lower fungal burdens, a more than three-fold higher survival rate at day 3. This protection was associated with a pronounced enhancement in the Aspergillus-specific IFN-gamma response. IL-12-engineered DCs augmented this protection strikingly as judged by a higher survival, and almost no Aspergillus could be detected in the lung of mice that had received IL-12-transduced HAF-pulsed DCs. These results suggest that antigen-pulsed DCs and IL-12 gene therapy could be used as adjunct therapy for aspergillosis.

Adenoviridae↗

Lentiviral siRNAs targeting multiple highly conserved RNA sequences of human immunodeficiency virus type 1.

The high mutation rate of the human immunodeficiency virus (HIV) makes it difficult for any therapy employing a single anti-HIV targeting mechanism to sustain prolonged effect. In an attempt to explore novel therapy for AIDS, we developed and tested lentiviral small interfering RNA (siRNA) vectors targeting multiple highly conserved regions in the HIV type 1 (HIV-1) genome. The siRNA expression cassette was cloned into an extensively deleted HIV-1-derived lentiviral self-inactivating insulator (SIN) insulator [corrected] vector. Although some of the siRNAs targeting sites were also present in the helper construct of the vector system, the production of these lentiviral siRNA vectors were not significantly affected. When tested against different HIV-1 strains including pNL4-3 (subtype B), p89.6 (subtype B) and p90CF402.1.8 (subtype A/E recombinant), the siRNAs targeting conserved gag, pol, int and vpu, but not U3, nef or U5 regions, efficiently inhibited replication of all three viral strains. These lentiviral siRNA vectors also protected host cells from syncytium-forming macrophage- and T-cell-tropic HIV-1-induced cytotoxicity. Transduction of a long-term chronically infected human lymphoma cell line with lentiviral siRNAs resulted in stable inhibition of HIV-1 replication. Northern analysis showed that both genomic and subgenomic viral RNA species were downregulated. In addition, the viral RNA was inhibited in both the nuclear and cytoplasmic compartments of [corrected] chronically infected cells after prolonged passage, suggesting that [corrected] lentiviral siRNAs have a nuclear effect [corrected] Using these lentiviral siRNA [corrected] vectors, we further demonstrated reduced replication kinetics of HIV-1 in primary human peripheral blood lymphocytes. These results suggest that lentiviral siRNAs targeting multiple conserved HIV-1 sequences holds significant promise for the treatment of HIV-1 infections.

Base Sequence↗

Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions.

Organophosphates (OPs) are routinely used as pesticides in agriculture and as insecticides within the household. Our prior work on Reelin and APOE delineated a gene-environment interactive model of autism pathogenesis, whereby genetically vulnerable individuals prenatally exposed to OPs during critical periods in neurodevelopment could undergo altered neuronal migration, resulting in an autistic syndrome. Since household use of OPs is far greater in the USA than in Italy, this model was predicted to hold validity in North America, but not in Europe. Here, we indirectly test this hypothesis by assessing linkage/association between autism and variants of the paraoxonase gene (PON1) encoding paraoxonase, the enzyme responsible for OP detoxification. Three functional single nucleotide polymorphisms, PON1 C-108T, L55M, and Q192R, were assessed in 177 Italian and 107 Caucasian-American complete trios with primary autistic probands. As predicted, Caucasian-American and not Italian families display a significant association between autism and PON1 variants less active in vitro on the OP diazinon (R192), according to case-control contrasts (Q192R: chi2=6.33, 1 df, P<0.025), transmission/disequilibrium tests (Q192R: TDT chi2=5.26, 1 df, P<0.025), family-based association tests (Q192R and L55M: FBAT Z=2.291 and 2.435 respectively, P<0.025), and haplotype-based association tests (L55/R192: HBAT Z=2.430, P<0.025). These results are consistent with our model and provide further support for the hypothesis that concurrent genetic vulnerability and environmental OP exposure may possibly contribute to autism pathogenesis in a sizable subgroup of North American individuals.

Aryldialkylphosphatase↗

Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations.

The dystrobrevin-binding protein 1 (DTNBP1) gene on chromosome 6p has emerged as a potential susceptibility gene for schizophrenia. Although a number of attempts to replicate the original association finding have been successful, they have not identified any obvious pathogenic variants or a single at risk haplotype common to all populations studied. In the present study we attempted further replication in an independent sample of 638 nuclear families from the Han Chinese population of Sichuan Province, SW China. We also examined 580 Scottish schizophrenic cases and 620 controls. We genotyped 10 single-nucleotide polymorphisms (SNPs) in DTNBP1 that were used in the original report of association, plus rs2619538 (SNP 'A') in the putative promoter region, which has also been associated with schizophrenia. In the Chinese trios we found that two SNPs (P1635 and P1765) were significantly overtransmitted, but with alleles opposite to those reported in the original studies. SNPs P1757 and P1765 formed a common haplotype, which also showed significant overtransmission. In the Scottish cases and controls, no individual markers were significantly associated with schizophrenia. A single haplotype, which included rs2619538 and P1583, and one rare haplotype, composed of P1320 and P1757, were significantly associated with schizophrenia, but no previously reported haplotypes were associated. Based on the data from the Chinese population, our results provide statistical support for DTNBP1 as a susceptibility gene for schizophrenia, albeit with haplotypes different from those of the original study. However, our lack of replication in the Scottish samples also indicates that caution is warranted when evaluating the robustness of the evidence for DTNBP1 as genetic risk factor for schizophrenia.

Alleles↗

Electrocatalytic proton reduction by dithiolate-bridged diiron carbonyl complexes: a connection to the H-cluster?

Spectroscopic and electrochemical investigation of electrocatalytic proton reduction by Fe(2)(mu-pdt)(CO)(6), 1, have been interpreted in terms of a reaction scheme involving sequential electron-proton reactions to give a two-electron, two-proton product that undergoes rate-limiting dihydrogen elimination. Further reduction, at slightly higher negative potentials, gives a more reactive product and this process dominates reactions conducted at higher acid concentrations. Inhibition of the electrocatalytic reaction by CO is due to the more efficient loss of catalyst and this is best modelled by a reaction that is second order in terms of 1(-). During electrocatalytic proton reduction a new species is observed, which features a bridging CO group and the wavenumbers of the nu(CO) modes of the terminally bound carbonyl groups are similar to those of the carbonyl groups bound to the oxidized form of the H-cluster.

Catalysis↗

A dominant form of congenital stationary night blindness (adCSNB) in a large Chinese family.

Summary A pedigree of congenital stationary night blindness (CSNB) is described in a large Chinese family. The clinical description, pedigree, dark adaptation and elctroretinogram (ERG) studies indicate that the patients have an autosomal dominant form (ad) of CSNB. The disorder has been transmitted through at least 12 generations with over 40 affected individuals identified. The ERG data reveal that affected persons have severely diminished b-wave responses to dim light, but normal a-wave and subnormal b-wave responses to maximum light stimuli. The dark adaptation curves of three patients show a monophase curve, typical for night blindness. We have excluded the five previously known mutations in the three genes (RHO, PDE6B and GNAT1) associated with adCSNB, and linkage studies have excluded tight linkage between the disease locus and markers associated with these three genes. Thus, this family has adCSNB caused by a different gene from the previously identified RHO, PDE6B, and GNAT1.

Adult↗

Effects of 17beta-estradiol on blood-brain barrier disruption in focal ischemia during GABA(A) receptor inhibition.

We performed this study to determine whether gamma-aminobutyric acid (GABA(A)) receptor inhibition could reverse the effect of 17beta-estradiol on blood-brain barrier (BBB) disruption in focal cerebral ischemia. Young ovariectomized rats were implanted with a 500 microg 17beta-estradiol 21-day release pellet or with a vehicle pellet 21 days before the experiments. Forty-five minutes after middle cerebral artery (MCA) occlusion, half of each group was infused with bicuculline (a GABA(A) receptor antagonist) 1 mg/kg/min for 2 min followed by 0.1 mg/kg/min up to the end of experiments. The other half was infused with the same volume of normal saline. The transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid and the volume of 3H-dextran distribution (70,000 Daltons) were determined to measure the degree of BBB disruption one hour after MCA occlusion. In the control vehicle-treated animals, the Ki in the ischemic cortex (7.2 +/- 2.6 microl/g/min) was higher than in the contralateral cortex (2.5 +/- 1.4 microl/g/min). After bicuculline infusion, the Ki in the ischemic cortex increased (10.6 +/- 5.4 microl/g/min) although the increase was not statistically significant. In the 17beta-estradiol treated animals, the Ki in the ischemic cortex (3.8 +/- 1.6 microl/g/min) was lower than control vehicle-treated rats. With bicuculline infusion, the Ki in the ischemic cortex (14.5 +/- 6.8 microl/g/min) was markedly increased. In the non-ischemic cortex, there was no significant difference in Ki among the experimental groups. The volume of dextran distribution was not significantly different between the experimental groups in the ischemic or non-ischemic cortex. Our data suggests that part of the reason for the decreased BBB disruption in the focal ischemic area after 17beta-estradiol treatment could be due to the interaction between GABA(A) receptors and 17beta-estradiol.

Algorithms↗

Transient overexpression of gamma interferon promotes Aspergillus clearance in invasive pulmonary aspergillosis.

Cytokines are critical molecules necessary for normal lung pathogen host defences. Gamma interferon (IFN-gamma) and T1-phenotype immune responses are important components of host defence against Aspergillus. Therefore, we hypothesized that transient overexpression of IFN-gamma within the lung could augment host immunity against Aspergillus. Here it was showed that intranasal administration of 5 x 10(7) colony-forming units (CFU) of Aspergillus fumigatus (Af ) induced the expression of IFN-gamma. Mice were intranasally (i.n) administrated with 5 x 10(8) PFU of a recombinant adenovirus vector containing the murine IFN-gamma cDNA (AdmIFN-gamma), and challenged 24 h later with Af. We observed that i.n. administration of AdmIFN-gamma resulted in about a fourfold increase in levels of IFN-gamma and IL-12 within the lung, about a 75% reduction in lung fungal contents at day 2 and a more than threefold higher survival rate in the AdmIFN-gamma-treated group compared to the controls (P < 0.01). This protection effect was not found when AdmIFN-gamma was i.p. administrated. Alveolar macrophages and lung leucocytes isolated from i.n. AdmIFN-gamma-treated animals displayed enhanced killing of intracellular Aspergillus organisms ex vivo. These results demonstrate that transient overexpression of IFN-gamma could augment host defence against Aspergillus.

Adenoviridae↗

HLA-DPA1 promoter haplotypes are differently distributed in southern Chinese ethnic groups.

DPA1 gene is one of the human leukocyte antigen (HLA) class II genes and its promoter is highly polymorphic. From comparative studies among five southern Chinese populations, Jing, Li, Bai, Lahu, and Meizhou Han, we describe their single-nucleotide polymorphism (SNP)/haplotype frequency data of HLA-DPA1 gene promoter in this study. Within the 760-bp promoter region, we have identified 21 SNPs and nine possible haplotypes. Pair-wise comparisons show similar frequencies distribution of the HLA-DPA1 promoter haplotypes among Jing, Li, and Bai, whereas all pair-wise comparisons involved with Lahu or Meizhou Han and other ethnic groups show remarkable difference. The differences in frequencies of HLA-DPA1 promoter alleles may reveal different ethnic origins and demographic histories of the five populations. Our study may help distinguishing each of these populations by sequence variations of HLA-DPA1 promoter, which may be served as functional molecular markers for clinical and immunological studies involving the DPA1 locus.

Alleles↗

Identification of a novel HLA-DRB1 allele (HLA-DRB1*111902*).

In this paper, we report a new HLA-DRB1 allele identified in a male acute myeloid leukaemia Chinese patient. This sample was initially typed as DRB1*11XX using commercial polymerase chain reaction-sequence-specific primers kit. When it was typed using a chip-based sequence-specific oligonucleotide technique, a novel hybridization pattern that does not match any known alleles was observed. Through sequencing, we have identified this allele as a new HLA-DRB1 allele, which was later named HLA-DRB1*111902 by the WHO Nomenclature Committee. The sequence of this new allele differs from DRB1*111901 by one nucleotide (from G to C) at 203nt of exon 2 but does not cause any amino acid substitution.

Alleles↗

Identification of a novel HLA-A allele HLA-A*2451 in a Chinese donor.

A novel human leucocyte antigen-A (HLA-A) allele, A*2451, has been identified during routine sequence-specific oligonucleotide typing and sequence-based typing of a sample from a registered donor of the Chinese Marrow Donor Program. The A*2451 allele differs from the closest matching allele A*2415 by one nucleotide substitution in exon 3, nt 363 G-->A, resulting in an amino acid change from M ATG to I ATA at codon 121.

Alleles↗

Association analysis of the RGS4 gene in Han Chinese and Scottish populations with schizophrenia.

We investigated the RGS4 as a susceptibility gene for schizophrenia in Chinese Han (184 trios and 138 sibling pairs, a total of 322 families) and Scottish (580 cases and 620 controls) populations using both a family trio and case-control design. Both the samples had statistical power greater than 70% to detect a heterozygote genotype relative risk of >1.2 for frequent RGS4-risk alleles. We genotyped four single nucleotide polymorphisms (SNPs) which have previously been associated with schizophrenia as either individually or part of haplotypes. Allele frequencies and linkage disequilibrium between the SNPs was similar in the two populations. In the Chinese sample, no individual SNPs or any of their haplotypes were associated with schizophrenia. In the Scottish population, one SNP (SNP7) was significantly over-represented in the cases compared with the controls (0.44 vs. 0.38; A allele; chi(2) 7.08, P = 0.011 after correction for correlation between markers by permutation testing). One two-marker haplotype, composed of alleles T and A of SNP4 and SNP7, respectively, showed individual significance after correction by permutation testing (chi(2) 6.8; P = 0.04). None of the full four-marker haplotypes showed association, including the G-G-G-G haplotype previously associated with schizophrenia in more than one sample and the A-T-A-A haplotype. Thus, our data do not directly replicate previous associations of RGS4, but association with SNP 7 in the Scottish population provides some support for a role in schizophrenia susceptibility. We cannot conclusively exclude RGS4, as associated haplotypes are likely to be surrogates for unknown causative alleles, whose relationship with overlying haplotypes may differ between the population groups. Differences in the association seen across the two populations could result from methodological factors such as diagnostic differences but most likely result from ethnic differences in haplotype structures within RGS4.

Case-Control Studies↗