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Biomedical subjects

Zhi Liu

Publications and source records attributed to Zhi Liu.

90 records · Page 5Linked to original sources
PubMed2003

Immunodominance among herpes simplex virus-specific CD8 T cells expressing a tissue-specific homing receptor.

The study of immunodominance within microbe-specific CD8 T cell responses has been challenging. We used a previously undescribed approach to create unbiased panels of CD8 cytotoxic T lymphocyte clones specific for herpes simplex virus type 2, a pathogen with a complex genome encoding at least 85 polypeptides. Circulating herpes simplex virus type 2-specific cells were enriched and cloned after sorting for expression of the skin homing-associated receptor, cutaneous lymphocyte-associated antigen, bypassing restimulation with antigen. The specificity of the resultant cytotoxic clones was determined. Clonal frequencies were compared with each other and with the total number of cytotoxic clones. For each subject within the homing receptor-positive compartment, the CD8 cytotoxic response was dominated by T cells specific for only a few peptides. Previously undescribed antigens and epitopes in viral tegument, capsid, or scaffold proteins were immunodominant in some subjects. Clone enumeration analyses were confirmed in some subjects with dominance studies by using herpes simplex mutants, vaccinia recombinants, and/or enzyme-linked immune spots. We conclude that among circulating cells expressing a homing-associated receptor, during chronic herpes type 2 infection, the CD8 T cell response becomes quite focused despite the presence of many potential antigenic peptides.

Antigens, CD↗
PubMed2003

Decoding of synaptic voltage waveforms by specific classes of recombinant high-threshold Ca(2+) channels.

Studies suggest that the preferential role of L-type voltage-sensitive Ca(2+) channels (VSCCs) in coupling strong synaptic stimulation to transcription is due to their selective activation of local chemical events. However, it is possible that selective activation of the L-type channel by specific voltage waveforms also makes a contribution. To address this issue we have examined the response of specific Ca(2+) channel types to simulated complex voltage waveforms resembling those encountered during synaptic plasticity (gamma and theta firing frequency). L-, P/Q- and N-type VSCCs (alpha1C, alpha1A, alpha1B/beta1B/alpha2delta, respectively) were all similarly activated by brief action potential (AP) waveforms or sustained step depolarization. When complex waveforms containing large excitatory postsynaptic potentials (EPSPs), APs and spike accommodation were applied under voltage clamp we found that the integrated L-type VSCC current was approximately three times larger than that produced by the P/Q- or N-type Ca(2+) channels (gamma frequency 1 s stimulation). For P/Q- or N-type channels the complex waveforms led to a smaller current than that expected from the response to a simple 1 s step depolarization to 0 or +20 mV. EPSPs present in the waveforms favoured the inactivation of P/Q- and N-type channels. In contrast, activation of the L-type channel was dependent on both EPSP- and AP-mediated depolarization. Expression of P/Q-type channels with reduced voltage-dependent inactivation (alpha1A/beta2A/alpha2delta) or the use of hyperpolarized intervals between AP stimuli greatly increased their response to complex voltage stimuli. We propose that in response to complex synaptic voltage waveforms P/Q- and N-type channels can undergo selective voltage-dependent inactivation leading to a Ca(2+) current mediated predominantly by L-type channels.

Action Potentials↗
PubMed2003

Mild oxidation of alcohols with O-iodoxybenzoic acid (IBX) in ionic liquid 1-butyl-3-methyl-imidazolium chloride and water.

[reaction: see text] A mild, efficient, and eco-friendly procedure for the oxidation of alcohols with IBX in ionic liquid [bmim]Cl and water has been developed. Simply stirring of a solution of the alcohol and IBX in [bmim]Cl/water at room temperature followed by extraction with ether or ethyl acetate and removal of the solvent gives excellent yields of the corresponding carbonyl compounds. Recycling and reuse of the oxidant and ionic liquid have also been reported.

Journal Article↗
PubMed2003

Enhancing the oral bioavailability of the poorly soluble drug dicumarol with a bioadhesive polymer.

This article investigates the effect of particle size and the incorporation of a bioadhesive polymer, poly(fumaric-co-sebacic) anhydride p(FA:SA), on the relative bioavailability of dicumarol. A novel method was used to reduce particle size of the drug, and encapsulated formulations were fabricated using a phase inversion technique to produce nanospheres and microspheres with varying size. Groups of Yorkshire swine were catheterized and gavaged after fasting for 12 h with each formulation in a 50 mg/mL suspension. Blood was collected at different time points, from 0 to 96 h, and pharmacokinetic analysis revealed that formulations incorporating the smaller drug particles showed the highest bioavailability: micronized drug with 7% p(FA:SA) 17:83 polymer had 190% relative bioavailability, and phase inverted p(FA:SA) 17:83 microspheres with 31% (w/w) loading had 198% relative bioavailability to spray dried formulation. Formulations with larger drug particles achieved 71% relative bioavailability. A nonadhesive formulation, fabricated with poly(lactic acid) (PLA), showed 91% relative bioavailability. Both particle size and polymer composition play a role in oral absorption of dicumarol.

Adhesives↗
PubMed2003

Delivery of an anticancer drug and a chemosensitizer to murine breast sarcoma by intratumoral injection of sulfopropyl dextran microspheres.

Intratumoral injection of controlled-release microsphere formulations of anticancer compounds has the potential to selectively increase tumour exposure to drugs. This work aimed to evaluate the therapeutic effect and toxicity of microsphere formulations containing the anticancer drug, doxorubicin, in a murine tumour model. The effect of co-administration of verapamil, a P-glycoprotein modulator or chemosensitizer, was investigated. Initial in-vitro studies confirmed the ability of verapamil to enhance the accumulation of both doxorubicin and [(99mTc)]sestamibi, also a P-glycoprotein substrate, in EMT6 murine breast sarcoma cells and a doxorubicin-selected multidrug-resistant variant, EMT6/AR1.0. Ex-vivo studies using confocal microscopy demonstrated release of doxorubicin from microspheres and diffusion of the drug through tissue. For in-vivo studies, EMT6 and EMT6/AR1.0 cells were grown in BALB/c mice. Following intratumoral injection of doxorubicin-loaded microspheres, alone or in combination with verapamil-loaded microspheres, the tumour diameter was measured serially as an indication of therapeutic effect, while the weight, appearance, and behaviour of the mice were monitored as an indication of general toxicity. Intratumoral injections of doxorubicin-loaded microspheres were tolerated much better than systemic administration of equivalent drug concentrations. There was a modest (up to 34%) delay of tumour growth compared with groups receiving no treatment or blank microspheres. Co-injection of verapamil microspheres with doxorubicin microspheres produced a moderate increase in toxicity but no further delay in tumour growth. Controlled-release microsphere formulations of anticancer agents administered intratumorally were an efficient way to deliver high drug doses to the tumour with little systemic toxicity.

Animals↗
PubMed2003

Immunopathology of bullous pemphigoid, an autoimmune and inflammatory skin blistering disease.

Bullous pemphigoid (BP) was first described by Lever in 1953 as a subepidermal blistering disease. Key immunohistological features of BP include dermo-epidermal junction (DEJ) separation, an inflammatory cell infiltrate in the upper dermis, and autoantibodies directed against two emidesmosomal antigens, BP230 and BP180. In 1993, an IgG passive transfer mouse model of BP was developed by administering rabbit anti-murine BP180 antibodies to neonatal mice. This model recapitulates the key features of human BP. Systematic dissection of this BP model has revealed that subepidermal blistering is initiated by anti-BP180 antibodies and mediated by complement activation, mast cell degranulation, and neutrophil infiltration. Proteinases and reactive oxygen species released by infiltrating neutrophils work together to damage the basement membrane zone (BMZ), causing a subepidermal blister. Recently, another novel mouse model for BP has been developed by active immunization. C57BL/6J mice actively immunized with murine BP180 develop BP-like skin lesions. The IgG passive transfer and active models of BP provide us with invaluable in vivo systems not only for dissecting cellular and humoral responses in BP but also for developing effective therapies for this disease.

Amino Acid Sequence↗
PubMed2003

[Relation of resting energy expenditure to respiratory mechanics and arterial blood gases in chronic obstructive pulmonary disease patients].

OBJECTIVE: To investigate the relationships of the rest energy expenditure to the respiratory mechanics and arterial blood gases in chronic obstructive pulmonary disease (COPD) patients. METHODS: Twenty six patients with COPD and 21 healthy subjects were involved in the study. The rest energy expenditure (REE), oxygen consumption (VO(2)), carbon dioxide production (VCO(2)) and respiratory quotient (RQ) were measured with indirect energy measurements of canopy test; the arterial blood gases were measured soon after energy measurements; then routine pulmonary function, P(0.1) and P(IMAX) were measured at rest. RESULTS: (1) The REE/day, P(0.1)/P(IMAX) and heart rate (HR) in the COPD group [(1,577.69 +/- 311.31) kcal, 0.068 +/- 0.026 and (83.46 +/- 11.36) BPM, respectively] were significantly higher than those in the healthy control group [(1,388.29 +/- 194.89) kcal, 0.039 +/- 0.014 and (69.71 +/- 5.73) BPM, respectively, P < 0.05 for all]; the forced expiratory volume in one second (FEV(1))% of predicted, partial pressure of oxygen in artery (PaO(2)) and arterial oxygen saturation (SaO(2)) in the COPD group [(50.46 +/- 21.35)%, (77.72 +/- 8.84) mm Hg and (92.54 +/- 2.55)%, respectively] were significantly lower than those in the control group [(92.29 +/- 11.91)%, (92.50 +/- 3.82) mm Hg and (96.29 +/- 1.87)%, respectively, P < 0.01 for all]. (2) In COPD group, the REE/day was positively correlated with body height, body weight, body mass index, P(0.1)/P(IMAX) and HR (r = 0.57, 0.65, 0.62, 0.41 and 0.51, respectively, P < 0.05 for all), negatively correlated with FEV(1)%, PaO(2) and SaO(2) (r = -0.43, -0.47 and -0.32, respectively, P < 0.05 for all); the P(0.1) was negatively correlated with PaO(2) and SaO(2) (r = -0.62 and -0.53, respectively, P < 0.01). CONCLUSION: The rest energy expenditure of COPD patients was significantly higher than that of healthy subjects. This increase in REE was not only attributed to the airway obstruction and the damaged gas exchange, but may be related to the elevated respiratory drive and dysfunction of respiratory muscles as well.

Aged↗
PubMed2003

[Use of methyl parathion (MP)-degrading strain DLL-E4 (Pseudomonas sp.) to remove MP residue on the surface of agricultural products].

In this paper, derivations from DLL-E4, including fermented liquid, its centrifuged (3000 x g, 10 min) supernatant, pellet extract with supersonic, crude enzyme(supernatant and pellet extract), detergent, and mixture of detergent and pellet extract, were used to degrade the MP residue on the surface of Chinese cabbage, tea and cucumber. The results showed that all of them were effective, with the best effect of 100%. Some constituents in the supernatant of fermented liquid could stimulate the enzymatic activity. For tea, the mixture of detergent and enzyme was more effective, but the opposite was found for the other two crops. In all treatments, crude enzyme and pellet extract had the best effect, and the rational added amount of enzyme was 2%, 5% and 10% for cucumber, Chinese cabbage and tea, respectively. Crude enzyme also could degrade methamidophos phoxim and chlorpyrifos.

Biodegradation, Environmental↗
PubMed2003

[Construction of genetic engineering microogranism of salt tolerant degrading strain].

H1 ( Halomonas sp.) was a strain of salt tolerance (18% NaCl, W/V) and degrading phenylacetic acid, plasmid pDT3 was a derivation of pUC19 inserted mpd gene (methyl parathion degrading gene), which is obtained from methyl parathion (MP) degrading strain DLL-E4 (Pseudomonas putida). Recombinant plasmids pKT-MP and pBBR-MP were constructed by inserting Hind III fragment (which include whole mpd gene) of pDT3 into broad host vector pKT230 and pBBR1-MCS2. With the aid of help-plasmid pRK2013, pKT-MP and pBBR-MP were transferred into H1 (called tri-parent conjugation) and multi-functioned GEMs H-pKT-MP and H-pBBR-MP were constructed, which were salt tolerant, phenylacetic acid-degrading and MP-degrading. The activity of MP hydrolase of H-pBBR-MP and H-pKT-MP was 1 x and 2 x the one of DLL-E4. The MP hydrolase activity of two GEMs were constant.

Conjugation, Genetic↗
PubMed2002

Macrophages, but not T and B lymphocytes, are critical for subepidermal blister formation in experimental bullous pemphigoid: macrophage-mediated neutrophil infiltration depends on mast cell activation.

Bullous pemphigoid (BP) is a subepidermal blistering disease associated with autoantibodies against two hemidesmosomal proteins, BP180 and BP230. Numerous inflammatory cells infiltrate the upper dermis in BP. We have previously shown by passive transfer studies that Abs to the ectodomain of murine BP180 are capable of triggering blisters in mice that closely mimic human BP. Experimental BP depends on complement activation and neutrophil infiltration. In the present study, we investigated the relative contribution of neutrophils, mast cells (MCs), macrophages (Mphi), and lymphocytes and their functional relationship in the immunopathogenesis of this disease model by using mice deficient in these cells. Wild-type, T cell-deficient, and T and B cell-deficient mice injected intradermally with pathogenic anti-murine BP180 IgG exhibited extensive subepidermal blisters. In contrast, mice deficient in neutrophils, MCs, and Mphi were resistant to experimental BP. MCs play a major role in neutrophil recruitment into the dermis. Furthermore, Mphi-mediated neutrophil infiltration depends on MC activation/degranulation.

Animals↗
PubMed2002

A subset of pemphigus foliaceus patients exhibits pathogenic autoantibodies against both desmoglein-1 and desmoglein-3.

In pemphigus vulgaris the major pathogenic antibody binds desmoglein-3, and mediates mucosal disease. Development of cutaneous disease is associated with acquisition of antibodies to desmoglein-1. In pemphigus foliaceus, and its endemic form, fogo selvagem by contrast, the major pathogenic antibody recognizes desmoglein-1 and mediates cutaneous disease only. In this study, we sought to determine the prevalence of antibodies to desmoglein-3 in patients with pemphigus foliaceus and fogo selvagem. We produced recombinant desmoglein-1 and desmoglein-3, and used them in highly sensitive and specific enzyme-linked immunosorbent assays, as well as immunoprecipitation assays. We detected antibodies to desmoglein-3 in 19 of 276 patients with pemphigus foliaceus and fogo selvagem, who had cutaneous disease only. We showed that these antibodies to desmoglein-3 could be absorbed in a concentration-dependent manner by desmoglein-3 but not by desmoglein-1. Also antibodies to desmoglein-1 could be absorbed in a concentration-dependent manner by desmoglein-1 but not desmoglein-3. This suggests that two separate species of antibody are present rather than one antibody capable of cross-reacting with both desmoglein-1 and desmoglein-3. Finally, it was shown that affinity-purified antibodies to desmoglein-3 from patients with pemphigus foliaceus and fogo selvagem induced a pemphigus vulgaris-like skin disease in mice by passive transfer. These results suggest that a subset of patients with pemphigus foliaceus and fogo selvagem have antibodies to desmoglein-3 that may be involved in the pathogenesis of their cutaneous disease.

Animals↗
PubMed2002

Effective dosing regimen of 1-aminobenzotriazole for inhibition of antipyrine clearance in rats, dogs, and monkeys.

1-Aminobenzotriazole (ABT) has been extensively used as a nonspecific inhibitor of cytochromes p450 (p450s) in animals for mechanistic studies, and antipyrine (AP) has been used as a probe for hepatic oxidative metabolic capacity determination in vivo. The method of use of ABT has been variable from lab to lab due largely to unknown pharmacokinetics of ABT itself and incomplete information on various p450s inhibited. The oral pharmacokinetic profiles of ABT were generated in rats, dogs, and monkeys in the dose range of 5 to 200 mg/kg. The results showed that after single oral doses of 50 mg/kg in rats, and 20 mg/kg in dogs and monkeys, the plasma concentrations were high and were sustained for over 24 h. In vitro, inhibition of various expressed p450s upon 30-min preincubation with ABT (0-500 micro M) showed that CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A4 were inhibited in a dose-dependent manner. The intravenous pharmacokinetics of AP also was affected in a dose-dependent manner in all species, treated 2 h earlier with ABT. Thus, the plasma clearance of AP was inhibited by 88% in rats pretreated with 50 mg/kg ABT and 96% in dogs and 83% in monkeys pretreated with 20 mg/kg ABT. Based on these data in rats, dogs, and monkeys, and the established safety profile of ABT in rats dosed up to 100 mg/kg, a pretreatment at 2 h with a single oral dose of ABT at 100 mg/kg in rats (providing 93% inhibition) and 20 mg/kg in dogs and monkeys effectively inhibited the clearance of the probe compound.

Animals↗
PubMed2002

Expression of cutaneous lymphocyte-associated antigen by CD8(+) T cells specific for a skin-tropic virus.

Virus-specific CD8(+) T cells traffic to infected tissues to promote clearance of infection. We used herpes simplex virus type 2 (HSV-2) as a model system to investigate CD8(+) T cell trafficking to the skin in humans. Using human leukocyte antigen (HLA) class I tetramers, we observed that HSV-specific CD8(+) T cells in the peripheral blood expressed high levels of cutaneous lymphocyte-associated antigen (CLA). In contrast, CD8(+) T cells specific for non-skin-tropic herpesviruses lacked CLA expression. CLA-positive HSV-2-specific CD8(+) T cells had the characteristics of central memory cells, expressing CCR7, CD62L, and CD28, and they proliferated briskly in response to antigen. CLA is related to a functional E-selectin ligand, and both E-selectin and CLA-positive cells were detected in HSV-2-infected skin. HSV-2-specific T cells adhered to cells transfected with E-selectin. A higher proportion of HSV-specific CD8(+) T cells recovered from herpes lesions express CLA compared with blood, consistent with a role for CLA in skin homing. To our knowledge, this is the first report of expression of tissue-specific adhesion-associated molecules by virus-specific CD8(+) T cells. The evaluation of vaccines for skin and mucosal pathogens should include study of the induction of appropriate tissue-specific homing molecules.

Animals↗
PubMed2002

Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice.

Antineutrophil cytoplasmic autoantibodies (ANCAs) are identified in the circulation of approximately 80% of patients with pauci-immune necrotizing and crescentic glomerulonephritis and systemic small vessel vasculitis, such as microscopic polyangiitis and Wegener granulomatosis. The most common antigen target for ANCAs is myeloperoxidase (MPO), which is found in neutrophils and monocytes. We report definitive experimental animal evidence that ANCAs are pathogenic. MPO knockout (Mpo(-/-)) mice were immunized with mouse MPO. Splenocytes from these mice or from control mice were injected intravenously into recombinase-activating gene-2-deficient (Rag2(-/-)) mice, which lack functioning B lymphocytes and T lymphocytes. All mice that received splenocytes developed mild to moderate glomerular immune deposits, but only mice that received 1 x 10(8) or 5 x 10(7) anti-MPO splenocytes developed severe necrotizing and crescentic glomerulonephritis, granulomatous inflammation, and systemic necrotizing vasculitis, including necrotizing arteritis and hemorrhagic pulmonary capillaritis. To test the pathogenic potential of antibodies alone, purified anti-MPO IgG or control IgG was injected intravenously into Rag2(-/-) mice and wild-type mice. Mice that received anti-MPO IgG but not mice that received control IgG developed focal necrotizing and crescentic glomerulonephritis with a paucity of glomerular Ig deposition. Thus, anti-MPO IgG alone was able to cause pauci-immune glomerular necrosis and crescent formation in the absence of functional T or B lymphocytes in Rag2(-/-) mice and in the presence of an intact immune system in wild-type C57BL/6J mice. This animal model offers strong support for a direct pathogenic role for ANCA IgG in human glomerulonephritis and vasculitis.

Adoptive Transfer↗
PubMed2002

Need for GLUT4 activation to reach maximum effect of insulin-mediated glucose uptake in brown adipocytes isolated from GLUT4myc-expressing mice.

There is a need to understand whether the amount of GLUT4 at the cell surface determines the extent of glucose uptake in response to insulin. Thus, we created a heterozygous mouse expressing modest levels of myc-tagged GLUT4 (GLUT4myc) in insulin-sensitive tissues under the control of the human GLUT4 promoter. Insulin stimulated 2-deoxyglucose uptake 6.5-fold in isolated brown adipocytes. GLUT1 did not contribute to the insulin response. The stimulation by insulin was completely blocked by wortmannin and partly (55 +/- 2%) by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. Insulin increased surface exposure of GLUT4myc twofold (determined by fluorescent or enzyme-linked myc immunodetection in intact adipocytes). Such increase was completely blocked by wortmannin but insensitive to SB203580. Insulin increased the kinase activity of the p38 MAPK beta-isoform 1.9-fold without affecting p38-alpha. In summary, the GLUT4myc mouse is a promising model for measuring GLUT4 translocation in intact primary cells. It affords direct comparison between GLUT4 translocation and glucose uptake in similar cell preparations, allowing one to study the regulation of GLUT4 activity. Using this animal model, we found that stimulation of glucose uptake into brown adipocytes involves both GLUT4 translocation and activation.

Adipocytes↗
PubMed2002

[Clinical analysis of 7 patients with Gerstmann syndrome secondary to cerebral vascular disease].

OBJECTIVE: To analyze clinical features of patients with Gerstmann syndrome (GS). METHODS: We retrospectively analysed the clinical manifestations of 7 patients (6 men and 1 woman) with GS secondary to cerebral vascular diseases and reviewed the literatures. RESULTS: The age ranged from 51 to 70 years with a mean of 70 years. They all had sudden onset and the tetrad of GS-finger agnosia, left-right disorientation, agraphia and acalculia, 3 patients accompanied by incomplete aphasia, 3 by anomic aphasia, 2 by alexia and 1 by constructional apraxia. Cranial computed tomographic scan showed low-density focus of the left parietal lobe in 6 cases and high-density focus of the left parietal lobe in 1 case. CONCLUSION: GS has the high value in localization and the lesion is mainly localized to angular gyrus of the dominant hemisphere.

Aged↗
PubMed1996

5-(Trimethylstannyl)-2H-pyran-2-one and 3-(Trimethylstannyl)-2H-pyran-2-one: New 2H-Pyran-2-one Synthons.

5-(Trimethylstannyl)-2H-pyran-2-one (11) and 3-(trimethylstannyl)-2H-pyran-2-one (30), readily prepared from the corresponding bromo-2H-pyran-2-ones, undergo Pd(0)-catalyzed coupling reactions with a variety of enol triflates to give 5- and 3- substituted 2H-pyran-2-ones, respectively. This reaction is applicable to the enol triflates of 14beta-hydroxy-17-ketosteroids, and therefore may prove useful in convergent syntheses of lucibufagins and bufadienolides.

Journal Article↗