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Biomedical subjects

M Xue

Publications and source records attributed to M Xue.

At least 19 recordsLinked to original sources

Characterization of a novel DRB1*14 allele (DRB1*1449) in the Han-Chinese population.

We report here a novel human leukocyte antigen (HLA) allele, DRB1*1449, in the Han-Chinese population. The nature of the new allele was confirmed by the sequencing-based typing (SBT) method. Genomic DNA and six subclones containing DNA fragment of DRB1 exon 2 were sequenced in both forward and reverse directions. The exon 2 nucleotide sequence of DRB1*1449 is closely related to DRB1*1432 allele based on sequence homology. It has four nucleotide (nt) substitutions at positions 71, 196, 244 and 245 in exon 2, which lead to changes of amino acid sequences. The serological assignment of DRB1*1449 is DR14 based on the serological HLA typing result. This novel allele might be a result of recombination between DRB1*1402 and DRB1*140101 like alleles, which are very common among Chinese population.

Alleles↗

Identification of an HLA-B*07 allele variant (B*0740) in the Chinese Han population.

A novel HLA-B*07 allele, B*0740, has been identified by sequence-based typing (SBT) in the Chinese Han population. This new allele is identical to B*0705 and B*0706 for exons 2, 3, and 4, except for a single nucleotide at position 605 of codon 202 in exon 3 (AAG-->ATG) leading to an amino acid change from lysine to methionine. SBT was performed following allele separation using the Haploprep method. The serological equivalence of B*0740 to the B7 antigen did not change.

Alleles↗

A novel HLA allele, DRB1*1609, identified in the Chinese Han population*.

A novel human leucocyte antigen-DRB1*16 (HLA-DRB1*16) allele (DRB1*1609) has been identified by sequencing-based typing (SBT) in Chinese Han population. This new allele has identical nucleotide sequence to DRB1*160101 in exon 2, except for a single-nucleotide substitution from A to T at position 127. This change leads to an amino acid change from tyrosine to phenylalanin at residue 47 (Y47F). SBT was performed for cloned DRB1*16-specific polymerase chain reaction fragment. The serological phenotype of DRB1*1609 is equivalent to DR16 antigen.

Alleles↗

A novel nanoporous graphitic composite.

A novel nanoporous composite containing micrographitic carbon layers is synthesized by preliminarily expanding the interlayer of an oxidized product of graphite using surfactant, followed by Si bridging/pillaring, and carbonization.

Journal Article↗

G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion: an excellent alternative for high-risk leukemia.

Based on our encouraging results of G-CSF-primed HLA-matched related marrow transplants for high-risk leukemia, we extended the study from matched related to haploidentical transplants using G-CSF primed marrow and sequential immunosuppressants to prevent both graft-versus-host disease (GVHD) and host-versus-graft rejection (HVGR). Fifteen high-risk leukemia patients, who needed urgent transplantation but lacked an HLA-matched donor, underwent G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion. Donors were given G-CSF (Lenograstim) at 3-4 microg/kg/day for 7 days prior to marrow harvest. GVHD and HVGR prophylaxis were combined in the sequential usage of cyclosporin A, methotrexate, anti-thymocyte globulin and mycophenolate mofetil. All patients established sustained trilineage engraftment at a median of 19 days and 21 days for neutrophil and platelets respectively. G-CSF priming significantly increased CD34(+) and CFU-GM cells, reduced total lymphocytes and reversed the CD4(+)/CD8(+) ratio in the donor marrow. The incidence of grade II-IV acute GVHD was 33.3%. Nine patients survived more than a year with a Karnofsky performance status of 100%. Estimated overall disease-free survival at 2 years was 60 +/- 7%. In conclusion, using G-CSF priming marrow grafts along with sequential immunosuppressants provided an excellent alternative for the treatment of high-risk hematological malignancy in patients who lack matched donors.

Adolescent↗

Balance of pro- and anti-inflammatory cytokines correlates with outcome of acute experimental Pseudomonas aeruginosa keratitis.

The purpose of this study was to elucidate the expression of pro- and anti-inflammatory cytokines in mouse corneas infected with Pseudomonas aeruginosa. Three bacterial strains (invasive, cytotoxic, or CLARE [contact lens-induced acute red eye]) which have recently been shown to produce distinct patterns of corneal disease in the mouse were used. The left mouse (BALB/c) corneas were scarified and infected with 2 x 10(6) CFU of one of the three P. aeruginosa strains, while right eyes served as controls. Animals were examined at 1, 4, 8, 16, and 24 h with a slit lamp biomicroscope to grade the severity of infection. Following examination, eyes were collected and processed for histopathology, multiprobe RNase protection assay for cytokine mRNA, enzyme-linked immunosorbent assay to quantitate cytokine proteins, and myeloperoxidase activity to quantitate polymorphonuclear leukocytes. The kinetics of appearance and magnitude of expression of key cytokines varied significantly in the three different phenotypes of P. aeruginosa infection. The predominant cytokines expressed in response to all three phenotypes were interleukin-1 beta (IL-1 beta), IL-1Ra, and IL-6. In response to the invasive strain, which induced severe corneal inflammation, significantly lower ratios of IL-1Ra to IL-1 beta were present at all time points, whereas corneas challenged with the CLARE strain, which induced very mild inflammation, showed a high ratio of IL-1Ra to IL-1 beta. The outcome of infection in bacterial keratitis correlated with the relative induction of these pro- and anti-inflammatory cytokines, and exogenous administration of recombinant rIL-1Ra (rIL-1Ra) was able to reduce the disease severity significantly. These findings point to the therapeutic potential of rIL-1Ra protein in possible treatment strategies for bacterial keratitis.

Acute Disease↗

Intracerebral infusion of a second-generation ciliary neurotrophic factor reduces neuronal loss in rat striatum following experimental intracerebral hemorrhage.

Neuronal and glial cell death in the striatum of a rat model of collagenase-induced intracerebral hemorrhage begins at 1 day and continues for at least 3 weeks. We hypothesized that administration of a neurotrophic agent would reduce neuronal loss in this experimental model. Because it has been shown to protect striatal neurons against excitotoxic injury, a second-generation ciliary neurotrophic factor (CNTF) (AXOKINE) was administered by continuous intracerebral infusion (2 microg/day) beginning 28 h after hemorrhage and continuing for 2 weeks. Magnetic resonance imaging showed that the hematoma size was comparable in control and treated rats prior to treatment. Counts of medium-sized striatal neurons within 320 microm of the hematoma 8 weeks after the hemorrhage revealed a slight but statistically significant benefit with a 42.5% loss in treated rats compared to 51.7% loss in controls. The results suggest that AXOKINE might be protective of striatal neurons in the vicinity of a hemorrhagic lesion.

Animals↗

Effect of FK-506 on inflammation and behavioral outcome following intracerebral hemorrhage in rat.

Beginning 15 min after induction of intracerebral hemorrhage (ICH) by intrastriatal administration of collagenase, rats were treated intramuscularly with FK-506 (3 mg/kg) or with vehicle. Treatment was repeated daily for 7 days. MR imaging 1, 7, and 28 days post-ICH showed that treatment did not affect hematoma size or its subsequent resolution. Two days post-ICH, neutrophil infiltration around the hematoma was decreased in the FK-506-treated rats, as was the number of TUNEL-positive cells at the edge of the hematoma and in the peripheral region. The decreased inflammatory response was accompanied by functional improvement in the treated rats. The neurological deficit induced by the ICH (beam walking ability, postural reflex, spontaneous circling) was significantly decreased from 3 to 21 days post-ICH by treatment with FK-506. Skilled use of the forelimb ipsilateral to the ICH was improved and sensory neglect of the same limb was decreased 8-9 weeks post-ICH in rats treated with FK-506. However, neuronal loss assessed 9 weeks post-ICH was not different in the treated and untreated rats.

Animals↗

Clathrin-dependent and clathrin-independent endocytosis are differentially sensitive to insertion of poly (ethylene glycol)-derivatized cholesterol in the plasma membrane.

We examined the effect of a cholesterol derivative, poly (ethylene glycol) cholesteryl ether on the structure/function of clathrin-coated pits and caveolae. Addition of the compound to cultured cells induced progressive smoothening of the surface. Markedly, when the incorporated amount exceeded 10% equivalent of the surface area, fluid pinocytosis, but not endocytosis of transferrin, became inhibited in K562 cells. In A431 cells, both clathrin-independent fluid phase uptake and the internalization of fluorescent cholera-toxin B through caveolae were inhibited with concomitant flattening of caveolae. In contrast, clathrin-mediated internalization of transferrin was not affected until the incorporated poly (ethylene glycol) cholesteryl ether exceeded 20% equivalent of the plasma membrane surface area, at which point opened clathrin-coated pits accumulated. The cells were ruptured upon further addition of poly (ethylene glycol) cholesteryl ether. We propose that the primary reason for the differential effect of poly (ethylene glycol) cholesteryl ether is that the bulk membrane phase and caveolae are both more elastic than the rigid clathrin-coated pits. We analyzed the results with the current mechanical model (Rauch and Farge, Biophys J 2000;78:3036-3047) and suggest here that the functional clathrin-lattice is much stiffer than typical phospholipid bilayers.

Biological Transport↗

Effector mechanisms of protection against Pseudomonas aeruginosa keratitis in immunized rats.

Pseudomonas aeruginosa is an opportunistic pathogen which causes sight-threatening corneal infections in humans. The purpose of this study was to evaluate various immunization routes that may provide protection against Pseudomonas keratitis and to define the molecular mechanisms involved in the protection. Sprague-Dawley rats (10 to 12 weeks old) were immunized using paraformaldehyde-killed P. aeruginosa (strain 6206) via oral, nasal, and intra-Peyer's patch (IPP) routes followed by an ocular topical booster dose. Scratched corneas were challenged with an infective dose of P. aeruginosa. Following clinical examination, eyes were enucleated for histology, polymorphonuclear leukocyte (PMN) quantitation, bacterial count, enzyme-linked immunosorbent assay, and RNase protection assay. PMN infiltration was higher early (4 h) during the infection in immunized rats than in nonimmunized rats. Later during the infection, the number of PMNs diminished in immunized rats while in nonimmunized animals the number of PMNs continued to increase. Bacteria were cleared much faster from immunized groups than from the nonimmunized group, and the nasally immunized group had the most efficacious response among the immunized groups. Nasal and IPP immunization groups had increased cytokine expression of interleukin-2 (IL-2) and IL-5 and differed from each other for IL-6. All three immunized groups had significantly reduced IL-1 beta levels when compared with the nonimmunized rats and a significantly altered profile for CINC-1 expression. This study has shown that the route of immunization modulates the inflammatory response to ocular P. aeruginosa infection, thus affecting the severity of keratitis and adverse pathology, with nasal immunization being the most effective.

Administration, Intranasal↗

Antisense oligodeoxynucleotide inhibition of tumor necrosis factor-alpha expression is neuroprotective after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) expression is increased in brain after cerebral ischemia, although little is known about its abundance and role in intracerebral hemorrhage (ICH). A TNF-alpha-specific antisense oligodeoxynucleotide (ORF4-PE) was used to study the extent to which TNF-alpha expression influenced neurobehavioral outcomes and brain damage in a collagenase-induced ICH model in rat. METHODS: Male Sprague-Dawley rats were anesthetized, and ICH was induced by intrastriatal administration of heparin and collagenase. Immediately before or 3 hours after ICH induction, ORF4-PE was administered directly into the site of ICH. TNF-alpha mRNA and protein levels were measured by reverse transcriptase-polymerase chain reaction and immunoblot analyses. Cell death was measured by terminal deoxynucleotidyl transferase-mediated uridine 5'triphosphate-biotin nick end labeling (TUNEL). Neurobehavioral deficits were measured for 4 weeks after ICH. RESULTS: ICH induction (n=6) elevated TNF-alpha mRNA and protein levels (P:<0.01) at 24 hours after the onset of injury compared with sham controls (n=6). Immunohistochemical labeling indicated that ICH was accompanied by elevated expression of TNF-alpha in neutrophils, macrophages, and microglia. Administration of ORF4-PE (2.0 nmol) directly into striatal parenchyma, 15 minutes before (n=4) or 3 hours after (n=6) ICH, decreased levels of TNF-alpha mRNA (P:<0.001) and protein (P:<0. 01) in the brain tissue surrounding the hematoma compared with animals treated with saline alone (n=6). Mean+/-SEM striatal cell death (cells per high-powered field) was also reduced in animals receiving ORF4-PE (34.1+/-5.0) compared with the saline-treated ICH group (80.3+/-7.50) (P:<0.001). ORF4-PE treatment improved neurobehavioral deficits observed at 24 hours (P:<0.001) after induction of ICH (n=6) compared with the untreated ICH group (n=6). This improvement was maintained at 28 days after hemorrhage induction (P:<0.001). CONCLUSIONS: These results indicate a pathogenic role for TNF-alpha during ICH and demonstrate that reducing TNF-alpha expression using antisense oligodeoxynucleotides is neuroprotective.

Animals↗

Acute tissue damage after injections of thrombin and plasmin into rat striatum.

BACKGROUND AND PURPOSE: Extravasation of blood is associated with intracerebral hemorrhage and head trauma. The mechanism of brain cell injury associated with hemorrhage differs from that due to pure ischemia. The purpose of this study was to investigate the acute changes after intracerebral injections of proteins that are involved in blood clotting and clot lysis. METHODS: Sixty-eight adult rats were subjected to stereotaxic intrastriatal injections of normal saline (5 microL), low- (2.5 U/5 microL) and high-dose (25 U/5 microL) thrombin, low- (0.1 microgram/5 microL) and high-dose (1 microgram/5 microL) tissue plasminogen activator, low- (0.05 U/5 microL) and high-dose (0.5 U/5 microL) plasminogen, and low- (0.335 U/5 microL) and high-dose (3.35 U/5 microL) plasmin. Forty-eight hours later rats were perfusion fixed. Brain damage area, eosinophilic neurons, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)-positive cells, infiltrating neutrophils, CD8a immunoreactive leukocytes, and reactive microglia were quantified. RESULTS: Damage area in striatum, dying cells, inflammatory cells, and microglial reaction were significantly greater after the high-dose plasminogen, plasmin, and thrombin injections. Tissue plasminogen activator injections were associated with mild inflammation. CONCLUSIONS: These results suggested that thrombin and plasmin are harmful to brain cells in vivo. Although the doses required to cause damage are relatively great in consideration of the plasma content of these proteins, their pathological effect might be enhanced through synergism with other mechanisms.

Acute Disease↗

Morphological study of erythrocyte shapes in red pulp of mouse spleens revealed by an in vivo cryotechnique.

The purpose of this study was to clarify erythrocyte shapes in splenic cords of living mouse spleens, using our in vivo cryotechnique followed by scanning (SEM) or transmission (TEM) electron microscopy. Some spleens of mice were quickly frozen by the in vivo cryotechnique while their hearts were beating under anesthesia. In contrast, other spleens were prepared by an in vitro freezing method after they were taken out from the abdominal cavity. They were routinely freeze-substituted, and prepared for SEM and TEM. A few mouse spleens were also routinely fixed and embedded in Quetol-812 to obtain conventional morphology. Erythrocytes in living mouse spleens showed a variety of shapes with narrow spaces between them, trapped among reticular fiber tissues. Similar various shapes of erythrocytes were kept in the red pulp even after blocking normal blood circulation, as prepared by the in vitro freezing method. In comparison to the above-mentioned findings, some erythrocytes were changed to biconcave discoid shapes by the conventional immersion fixation with chemical fixatives. They also showed wide spaces between each other among reticular fiber tissues. Such conventional morphological studies could hardly reveal the in vivo shapes of erythrocytes in functioning spleens with normal blood circulation. In contrast, the various shapes of erythrocytes in the functioning spleens were demonstrated by our in vivo cryotechnique. It is suggested that most erythrocytes congesting in spleens keep their original configuration in spite of microenviromental alteration in splenic blood circulation.

Animals↗

[Investigation of water sorption and solubility of three denture soft lining materials].

This assay was made to investigate the water sorption and solubility of autopolymerizing hydrogel, acrylic resin and silicone denture soft lining materials. The test discs with 50 mm in diameter and 1 mm in thickness were prepared according to powder and liquid ratio. The weight of sample was measured after 24 h drying (m1). The sample was put into artificial saliva and distilled water for 7 d and 28 d, the moisture weight was measured after soaking (m2). After drying again, the last data of weight (m3) was acquired till the constant mass was recorded. Finally the values of water sorption and water solubility were calculated respectively with statistical analysis. The results showed the means of percentage about absorption at 7 d and 28 d were 28.62% and 24.96% for hydrogel, 1.89% and 1.65% for acrylic resin, 0.25% and 0.29% for silicone in artificial saliva. The percentage solubility at two stages were 0.56% and 0.51% for hydrogel, 0.74% and 0.83% for acrylic resin, 0.10% and 0.12% for silicone. In distilled water, the means of percentage about absorption at 7 d and 28 d were 30.15% and 27.85% for hydrogel, 3.64% and 6.17% for acrylic resin, 0.83% and 0.98% for silicone. The percentage solubility at two stages were 0.79% and 1.16% for hydrogel, 0.86% and 1.01% for acrylic resin, 0.10% and 0.14% for silicone respectively. The conclusion is that the order of percentage about absorption for these three denture soft lining materials were hydrogel > acrylic resin > silicone. The percentage solubility of acrylic resin was higher than that of the other two materials because of the plasticizer existing in acrylic resin material. In some degree, the ionic component increased may affect water sorption and solubility. Further clinical demonstration is needed for this hydrogel with higher percentage absorption.

Absorption↗

Low incidence of severe aGVHD and accelerating hemopoietic reconstitution in allo-BMT using lenograstim stimulated BM cells.

OBJECTIVES: To investigate the efficacy of accelerating hemopoietic reconstraction and reducing a graft versus host disease (GVHD) in Allo-BMT receiving lenograstim stimulated donor marrow and to assess the preliminary biological mechanism. METHODS: The donors for thirty patients (study group) with leukemia were given lenograstim 3-4 micrograms.kg-1.d-1 for seven days prior to marrow harvest. The results of subsequent engraftment in the recipients was compared with fifteen donors without G-CSF (control group). Five donors themselves were studied to assess the effects of lenograstion on hematopoietic progenitor cells and lymphocyte subsets in BM. RESULTS: The stimulated bone marrow contained a higher number of nucleated cells, CFU-GM and CD34+ cells (P < 0.01). The hematopoetic reconstitution was accelerated. Until granulocyte counts exceeded 0.5 x 10(9)/L and plalete counts exceeded 20 x 10(9)/L, the days were 16.7 +/- 3.2 and 18.4 +/- 3.0 days as compared with those of the control group (22.5 +/- 5.1 and 26.3 +/- 5.9 days respectively, P < 0.01). The incidence of grade II-IV aGVHD was very low, only one case with grade II aGVHD on the skin in the study group. Four out of fifteen patients (26.7%) in the control group had grade II-IV aGVHD (P < 0.05). The number of T lymphocyte subsets in the harvested BM stimulated by G-CSF changed. In comparison with the control group, CD4+ decreased and CD8+ increased significantly (P < 0.01). The changes of progenitor cells and T lymphocyte subsets in BM from pre- to post-G-CSF stimulation indicated that the percentage of CD4+ cells reduced (P < 0.05), that of CD8+ cells, and that of CD34+ increased (P < 0.01). The incidence of chronic GVHD and relapse of leukemia were not different significantly between both groups. CONCLUSIONS: Allogenic bone marrow transplant (Allo-BMT) donors given G-CSF can accelerate engraftment and minimize the incidence of severe aGVHD. There is a trend in favour of improved transplant-related complications.

Acute Disease↗

Structure-activity relationships study at the 3'-N position of paclitaxel. Part 2: synthesis and biological evaluation of 3'-N-thiourea- and 3'-N-thiocarbamate-bearing paclitaxel analogues.

The syntheses and preliminary biological evaluation of 3'-N-thiocarbamate- and 3'-N-thiourea-bearing paclitaxel analogues, 4a-f and 5a-e, are described. 3'-N-thiocarbamates 4a-e were found to be more potent than paclitaxel in both the tubulin polymerization assay and the in vitro cytotoxicity assay. Several derivatives of this class such as 4c, 4d, and 4e also exhibited some in vivo activity.

Antineoplastic Agents, Phytogenic↗

Intracerebral injection of autologous whole blood in rats: time course of inflammation and cell death.

Intracerebral hemorrhage is associated with stroke and head trauma. The purpose of this study was to study brain inflammation and cell death in adult rats 1 h to 4 weeks after injection of blood into the striatum. Terminal dUTP nick-end-labeling positive dying cells were evident 4 h to 4 weeks post-hemorrhage. Neutrophil infiltration was brief and peaked at 48 h. CD8a immunoreactive lymphocytes, possibly natural killer cells, became apparent at 48 h and persisted for 1 week. Microglial reaction was evident at 4 h and persisted for 4 weeks. We conclude that extravascular blood causes a mixed inflammatory cell reaction in brains that is maximal from 48-72 h following hemorrhage. This is associated with death of brain cells over a prolonged period of at least 4 weeks.

Animals↗

Intracortical hemorrhage injury in rats : relationship between blood fractions and brain cell death.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage is associated with stroke and head trauma. The purposes of this study were to investigate the effect of intracortical injections of autologous whole blood and blood components on inflammatory cell infiltration and brain cell death and to determine if nonhemorrhagic lesions differ in these respects. METHODS: Eighty-seven adult rats were subjected to intracortical injections of autologous whole blood or allogeneic plasma, erythrocytes, leukocytes, "activated" leukocytes, and serum. Injections of saline or mineral oil were controls. Blood injections were compared with cortical freeze injury and pial devascularization. Rats were perfusion-fixed 48 hours after injection or lesioning. Eosinophilic neurons, TUNEL-positive cells, brain damage area, infiltrating neutrophils, and CD8a-immunoreactive lymphocytes were quantified. RESULTS: Damage area, dying cells, and inflammatory infiltrate were significantly greater after autologous whole blood, leukocyte, and "activated" leukocyte injections than injection of other fractions. CONCLUSIONS: These results suggest that extravasated whole blood causes a greater degree of cortical cell death and inflammation than ischemic lesions of similar size. Leukocytes "activated" by systemic illness might exacerbate the injury. Secondary hemorrhagic phenomena suggest that the harmful effect is directed toward both brain cells and the vasculature. Further studies are required to delineate the mechanism(s).

Animals↗