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Biomedical subjects

H Yang

Publications and source records attributed to H Yang.

At least 55 records · Page 3Linked to original sources
PubMed2005

Lyophilized paclitaxel magnetoliposomes as a potential drug delivery system for breast carcinoma via parenteral administration: in vitro and in vivo studies.

PURPOSE: The study reports in vitro and biological evaluation of lyophilized negatively charged paclitaxel magnetic liposomes as a potential carrier for breast carcinoma via parenteral administration. METHODS: Paclitaxel in magnetoliposomes were extracted by centrifugation and quantified by high-performance liquid chromatography (HPLC). Biological properties were studied using pharmacokinetics, in vivo distribution and cytotoxicity assays, as well as a mouse model of EMT-6 breast cancer. METHODS: Pharmacokinetic studies showed that encapsulation of paclitaxel in magnetoliposomes produced marked difference over the drug in Cremophor EL/ethanol pharmacokinetics, with an increased t(1/2beta) 19.37 h against 4.11 h. For in vivo distribution, paclitaxel concentration of lyophilized magnetoliposomes in the tumor was much higher than that of lyophilized conventional liposomes or Cremophor EL/ethanol, whereas in heart it was much lower than the latter two formulations via s.c. and i.v. administration. Lyophilized paclitaxel magnetic liposomes showed more potency on the therapy of breast cancer than other formulations via s.c. and i.p. administration. CONCLUSIONS: The current study demonstrates that paclitaxel magnetoliposomes can effectively be delivered to tumor and exert a significant anticancer activity with fewer side effects in the xenograft model.

Animals↗
PubMed2005

Vitronectin stabilizes thrombi and vessel occlusion but plays a dual role in platelet aggregation.

The role of vitronectin (Vn) in thrombosis is currently controversial; both inhibitory and supportive roles have been reported. To monitor directly the function of Vn in thrombotic events at the site of vascular injury, we studied Vn-deficient (Vn-/-) and wild-type (WT) control mice with two real-time intravital microscopy thrombosis models. In the mesenteric arteriole model, vessel injury was induced by ferric chloride. We observed unstable thrombi and a significantly greater number of emboli in Vn-/- mice. Vessel occlusion was also delayed and frequent vessel re-opening occurred. In the cremaster muscle arteriole model, vessel injury was induced by a nitrogen dye laser. We observed significantly fewer platelets, lower fibrin content, and unstable fibrin within the thrombi of Vn-/- mice. To define further the role of Vn in thrombus growth, we studied platelet aggregation in vitro. Consistent with our in vivo data, the second wave of thrombin-induced aggregation of gel-filtered platelets was abolished at a low concentration of thrombin in Vn-/- platelets. Interestingly, adenosine diphosphate (ADP)-induced platelet aggregation was significantly increased in Vn-/- platelet-rich plasma (PRP) and this effect was attenuated by adding purified plasma Vn. We also observed increased platelet aggregation induced by shear stress in Vn-/- whole blood. These data demonstrate that Vn is a thrombus stabilizer. However, in contrast to released platelet granule Vn which enhances platelet aggregation, plasma Vn inhibits platelet aggregation.

Adenosine Diphosphate↗
PubMed2005

Intestinal intraepithelial lymphocyte derived angiotensin converting enzyme modulates epithelial cell apoptosis.

BACKGROUND & AIMS: Intestinal adaptation in short bowel syndrome (SBS) consists of increased epithelial cell (EC) proliferation as well as apoptosis. Previous microarray analyses of intraepithelial lymphocytes (IEL) gene expression after SBS showed an increased expression of angiotensin converting enzyme (ACE). Because ACE has been shown to promote alveolar EC apoptosis, we examined if IEL-derived ACE plays a role in intestinal EC apoptosis. METHODS: Mice underwent either a 70% mid-intestinal resection (SBS group) or a transection (Sham group) and were studied at 7 days. ACE expression was measured, and ACE inhibition (ACE-I, enalaprilat) was used to assess ACE function. RESULTS: IEL-derived ACE was significantly elevated in SBS mice. The addition of an ACE-I to SBS mice resulted in a significant decline in EC apoptosis. To address a possible mechanism, tumor necrosis factor alpha (TNF-alpha) mRNA expression was measured. TNF-alpha was significantly increased in SBS mice, and decreased with ACE-I. Interestingly, ACE-I was not able to decrease EC apoptosis in TNF-alpha knockout mice. CONCLUSIONS: This study shows a previously undescribed expression of ACE by IEL. SBS was associated with an increase in IEL-derived ACE. ACE appears to be associated with an up-regulation of intestinal EC apoptosis. ACE-I significantly decreased EC apoptosis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Arg9-peptide facilitates the internalization of an anti-CEA immunotoxin and potentiates its specific cytotoxicity to target cells.

Arginines-containing membrane translocational signals (MTS), such as Tat(47-57) and VP22(267-300), and synthetic arginine-rich peptides have been reported to be efficient carriers for transporting various types of biomolecules into cytoplasmic and nuclear compartments of living cells. Among those arginines-containing MTS, a 9-mer arginine peptide (Arg9) was proved the most economical and efficient. We fused Arg9-peptide to an anti-CEA (Carcinoembryonic antigen) immunotoxin, PE35/CEA(Fv)/KDEL, at the position between the toxin moiety and the binding moiety. Strong binding and internalization of this fusion protein was observed in all detected cell lines, but little cytotoxicity to the cells that lack the CEA molecules on the cell surface was detected. However, the cytotoxicity besides the binding activity of the fusion protein to specific tumor cells expressing large amount of CEA molecules on the cell surface was improved markedly, indicating that the Arg9-peptide is capable of facilitating the receptor-mediated endocytosis of this immunotoxin, which leads to the increase of the specific cytotoxicity of this immunotoxin.

Arginine↗
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

High mobility group box 1 (HMGB1) protein: possible amplification signal in the pathogenesis of falciparum malaria.

High mobility group box 1 (HMGB1) protein, a DNA-binding protein that can also act as a pro-inflammatory cytokine if released from cells, is an important amplification signal in various forms of inflammation. The concentration of HMGB1 in serum taken at admission was increased in falciparum malaria in sixteen African children, more so in fatal cases than in those who subsequently recovered (P<0.001). Serum from both non-fatal (P=0.0048) and fatal (P<0.001) cases contained significantly more circulating HMGB1 than did serum from healthy Caucasian adults. These data provide an additional argument that malaria is fundamentally a systemic inflammatory state. In keeping with its developing role in sepsis, HMGB1 may enhance and prolong the inflammatory processes, and thus illness, in malaria.

Child↗
PubMed2005

Association of post-thaw viable CD34+ cells and CFU-GM with time to hematopoietic engraftment.

In all, 78 peripheral hematopoietic progenitor cell collections from 52 patients were evaluated using our previously published validated post-thaw assays at the time of collection and following transplantation by assessment of viable CD34(+) cells, and granulocyte-macrophage colony-forming units (CFU-GM) cryopreserved in quality control vials. The median (range) post-thaw recovery of viable CD34(+) cells and CFU-GM was 66.4% (36.1-93.6%) and 63.0% (28.6-85.7%), respectively, which did not show significant correlation with the engraftment of either neutrophils (P=0.136 and 0.417, respectively) or platelets (P=0.88 and 0.126, respectively). However, the reinfused viable CD34(+) cells/kg of patient weight pre- or post-cryopreservation showed significant correlation to engraftment of neutrophils (P=0.0001 and 0.001, respectively) and platelets (P=0.023 and 0.010, respectively), whereas CFU-GM pre- or post-cryopreservation was significantly correlated to neutrophils (P=0.011 and 0.007, respectively) but not to platelets (P=0.112 and 0.100, respectively). The results show that post-cryopreservation assessment of viable CD34(+) cells or CFU-GM is as reliable a predictor of rapid engraftment as that of pre-cryopreservation measures. Therefore, the post-cryopreservation number of viable CD34(+) cells or CFU-GM should be used to eliminate the risks of unforeseen cell loss that could occur during cryopreservation or long-term storage.

Adult↗
PubMed2005

Workplace and HIV-related sexual behaviours and perceptions among female migrant workers.

Data from 1,543 female migrants working in eight occupational clusters in Beijing and Nanjing, China were analysed to examine the association of workplace with HIV-related behaviours and perceptions. For sexually experienced women (n = 666, 43.2%), those working in entertainment establishments or personal service (e.g., nightclubs, dancing halls, barbershops, beauty salons, massage parlours, etc.) engaged in risky sexual practices twice as frequently as those working in non-entertainment establishments (e.g. restaurants, stalls, domestic service, factories, etc.). About 10% of women in the entertainment establishments reported having sold sex, 30% having multiple sexual partners and 40% having sex with men with multiple sexual partners. The rate of consistent condom use was less than 15%. They also tended to have a higher level of perceptions of both peer risk involvement and positive expectancy of risk behaviours, and lower perceptions of severity of STDs and HIV. For women who were not sexually experienced, those working in 'stalls' or 'domestic service' tended to perceive higher peer risk involvement, less severity of HIV infection, and less effectiveness of protective behaviour. The occupational pattern of sexual risk behaviours and perceptions observed in the current study indicates employment conditions are associated with HIV risk. Intervention strategies should be tailored to address occupational-related factors.

Adolescent↗
PubMed2005

Ex vivo expansion of umbilical cord blood.

The efficacy of cord blood (CB) transplantation is limited by the low cell dose available. Low cell doses at transplant are correlated with delayed engraftment, prolonged neutropenia and thrombocytopenia and elevated risk of graft failure. To potentially improve the efficacy of CB transplantation, approaches have been taken to increase the cell dose available. One approach is the transplantation of multiple cord units, another the use of ex vivo expansion. Evidence for a functional and phenotypic heterogeneity exists within the HSC population and one concern associated with ex vivo expansion is that the expansion of lower 'quality' hematopoietic progenitor cells (HPC) occurs at the expense of higher 'quality' HPC, thereby impacting the reserve of the graft. There is evidence that this is a valid concern while other evidence suggests that higher quality HPC are preserved and not exhausted. Currently, ex vivo expansion processes include: (1) liquid expansion: CD34+ or CD133+ cells are selected and cultured in medium containing factors targeting the proliferation and self-renewal of primitive hematopoietic progenitors; (2) co-culture expansion: unmanipulated CB cells are cultured with stromal components of the hematopoietic microenvironment, specifically mesenchymal stem cells (MSC), in medium containing growth factors; and (3) continuous perfusion: CB HPC are cultured with growth factors in 'bioreactors' rather than in static cultures. These approaches are discussed. Ultimately, the goal of ex vivo expansion is to increase the available dose of the CB cells responsible for successful engraftment, thereby reducing the time to engraftment and reducing the risk of graft failure.

Cell Culture Techniques↗
PubMed2005

High overall in vitro efficiency of porcine handmade cloning (HMC) combining partial zona digestion and oocyte trisection with sequential culture.

We investigated the in vitro developmental competence of porcine embryos produced from in vitro matured (IVM) oocytes by improved HMC and parthenogenetic activation (PA). Embryos were cultured in a modified North Carolina State University (NCSU37) medium. Firstly, we compared the developmental competence between oocytes from sows and gilts by zona-intact (ZI) and zona-free (ZF) PA. Significantly higher (p < 0.05) blastocyst rates were obtained from sow oocytes (42 +/- 4% for ZF and 55 +/- 6% for ZI) than gilt oocytes (20 +/- 2% for ZF and 26 +/- 5% for ZI). Secondly, sow oocytes were used to establish the modified HMC that was based on a modified enucleation with partial zona digestion and trisection of porcine oocytes and the use of three cytoplasts and one somatic cell for embryo reconstruction. In vitro fertilization (IVF) and in parallel ZF PA were used as the control systems. After oocyte trisection, >90% of oocyte fragments were recovered, resulting in an average of 37 reconstructed embryos from 100 oocytes. Blastocyst rates of HMC, IVF, and ZF PA embryos were 17 +/- 4%, 30 +/- 6%, and 47 +/- 4%, respectively. Our results prove that HMC in pigs may result in high in vitro efficiency up until the blastocyst stage. In vivo developmental competence will be confirmed in embryo transfer experiments.

Animals↗
PubMed2005

Serum immunoglobulins in psoriatic erythroderma.

The cause of psoriatic erythroderma (PE) is still unknown. Elevation of serum IgE has been reported in erythroderma, and as serum hyper-IgE is Th2 cell dominated it is of interest to investigate the serum IgE level in PE. In this study, the level of immunoglobulins in the sera of PE patients was analysed by a retrospective case-control study using psoriasis vulgaris (PV) patients as controls. The PE and PV patients were matched in a 1:3 pattern: the first three age and sex matched PV inpatients were selected. All of the subjects were nonatopic and without allergic history. The serum IgE level was found to be elevated in 81.3% of the PE group, which is much higher than that (6.3%) of the controls (odds ratio, 65.0; 95% CI, 11.7-361.2; P < 0.001; chi2 test). The mean level of serum IgE was much higher in the PE group (272.38 +/- 207.63 IU/mL vs. 53.20 +/- 86.05 IU/mL, P < 0.001, Student's t-test). No differences were found for other immunoglobulins. These results suggest that in PE the Th1/Th2 cell imbalance may be switched from Th1 dominant to Th2 dominant. The exact role of serum IgE in PE should be investigated further.

Adolescent↗
PubMed2005

Activity of adefovir dipivoxil against all patterns of lamivudine-resistant hepatitis B viruses in patients.

One hundred and thirty-one post-liver transplantation patients with chronic hepatitis B and failing lamivudine therapy with detectable serum hepatitis B virus (HBV) deoxyribonucleic acid by hybridization assays or > or =1 x 10(6) copies/mL by polymerase chain reaction, and elevated alanine transaminase levels despite continuous lamivudine, were enrolled in an open-label study of adefovir dipivoxil. The B and C domains of HBV polymerase were sequenced for baseline samples to determine the presence of lamivudine resistance mutations. The results showed that 98% of the samples had tyrosine-methionine-aspartate-aspartate (YMDD) mutations, indicating a strong correlation between the above clinical definition of lamivudine treatment failure and the presence of YMDD mutations. In addition to the rtM204V/I and the rtL180M mutations, the mutation rtV173L was identified in 19% of patients. Four major patterns of lamivudine-resistant HBV were identified: rtL180M + rtM204V (60%), rtV173L + rtL180M + rtM204V (19%), rtM204I (9%) and rtL180M + rtM204I (9%). Treatment with adefovir dipivoxil showed similar antiviral efficacy in patients with lamivudine-resistant virus from all four patterns.

Adenine↗
PubMed2005

Recurrence of symptomatic atrial fibrillation after successful catheter ablation of atrioventricular accessory pathways: a multivariate regression analysis.

The primary aim of this study is to investigate the factors related to the recurrence of atrial fibrillation (AF) after a successful ablation of atrioventricular accessory pathway. Thirty-seven patients with spontaneous AF (study group) were selected from 401 consecutive patients who underwent radiofrequency catheter ablation of atrioventricular accessory pathway. A multivariate regression analysis was used in order to evaluate the relationships between AF recurrence and patients' age, sex, atrial size, left ventricular function, location of accessory pathways, heart rate during atrioventricular re-entrant tachycardia and atrial vulnerability (induction of sustained AF) after a successful ablation. Atrioventricular accessory pathway was abolished in 36 of the study group patients and 351 of the control group patients. During the follow-up of 36 +/- 11 months, four patients (11.1%) from the study group experienced sustained AF. Multivariate regression analysis showed that, in patients with pre-ablation AF, older age and post-ablation atrial vulnerability were the only independent predictive factors for AF recurrence. We concluded that radiofrequency catheter ablation of atrioventricular accessory pathway greatly reduces the risk of AF in patients who had a history of symptomatic AF. Older patients and patients with inducible AF after accessory pathway ablation are at an increased risk of AF recurrence. These patients should be closely monitored after successful ablation of atrioventricular accessory pathways.

Adult↗
PubMed2005

First experience with direct, selective factor Xa inhibition in patients with non-ST-elevation acute coronary syndromes: results of the XaNADU-ACS Trial.

BACKGROUND: Unfractionated heparin is widely used in patients with non-ST-elevation acute coronary syndromes but has important limitations. Anticoagulants with predictable kinetics and anticoagulant effects, better efficacy, and greater safety are needed. OBJECTIVE: To investigate the efficacy and safety of a direct, selective factor Xa inhibitor, DX-9065a (Daiichi Pharmaceuticals LTD, Inc.) compared with heparin, in patients with non-ST-elevation acute coronary syndromes. PATIENTS AND METHODS: Patients (n = 402) from the USA, Canada, and Japan were randomized to blinded, weight-adjusted heparin, low-dose DX-9065a, or high-dose DX-9065a. RESULTS: The primary efficacy endpoint of death, myocardial infarction, urgent revascularization, or ischemia on continuous ST-segment monitoring occurred in 33.6%, 34.3%, and 31.3% of patients assigned to heparin, low-dose DX-9065a, and high-dose DX-9065a (P = 0.91 for heparin vs. combined DX-9065a). The composite of death, myocardial infarction, or urgent revascularization occurred in 19.5%, 19.3%, and 11.9% (P = 0.125 for heparin vs. high-dose DX-9065a) of patients; major or minor bleeding occurred in 7.7%, 4.2%, and 7.0% of patients; and major bleeding in 3.3%, 0.8%, and 0.9% of patients. Higher concentrations of DX-9065a were associated with a lower likelihood of ischemic events (P = 0.03) and a non-significant tendency toward a higher likelihood of major bleeding (P = 0.32). CONCLUSIONS: In this small phase II trial, there was a non-significant tendency toward a reduction in ischemic events and bleeding with DX-9065a compared with heparin in patients with acute coronary syndromes. The absence of an effect on ST-monitor ischemia warrants further investigation. These data provide the rationale for adequately powered studies of DX-9065a in acute coronary syndromes or percutaneous intervention.

Acute Disease↗
PubMed2005

Variations in the behaviors to novel objects among five inbred strains of mice.

Novelty stimuli cause various behavioral responses, such as exploration and avoidance, and contextual variables may contribute to the behavioral outputs. Here, we tried to compare the behavioral responses to novel objects of five inbred strains of mice (C57BL/6J, 129/svJae, C3H/HeJ, BALB/cJ and DBA/2J) by using a modified novel object test where a small light-weight cube wrapped with paper was presented to mice in a home cage without beddings. In response to these objects, the C57BL/6J, 129/svJae and C3H/HeJ mice showed mild exploratory behaviors, such as approaching, sniffing or brief contact. In striking contrast, the BALB/cJ and DBA/2J mice, which have been known to show high avoidance/low exploration in other behavioral paradigms, exhibited play-like secondary reactions toward the objects after initial primary exploratory behaviors. Specifically, DBA/2J mice would move the object around in the cage, holding it with their mouths, and BALB/cJ mice would gnaw the object, eventually stripping off the wrapping paper. Such behaviors decreased when similar objects were presented repeatedly. The present results suggest that active manipulations of novel objects may be a relevant parameter for measuring novelty-induced behaviors in mice and appear to be strongly influenced by genetic factors.

Animals↗
PubMed2005

Atazanavir signature I50L resistance substitution accounts for unique phenotype of increased susceptibility to other protease inhibitors in a variety of human immunodeficiency virus type 1 genetic backbones.

Substitution of leucine for isoleucine at residue 50 (I50L) of human immunodeficiency virus (HIV) protease is the signature substitution for atazanavir (ATV) resistance. A unique phenotypic profile has been associated with viruses containing the I50L substitution, which produces ATV-specific resistance and increased susceptibility to most other approved HIV protease inhibitors (PIs). The basis for this unique phenotype has not been clearly elucidated. In this report, a direct effect of I50L on the susceptibility to the PI class is described. Cell-based protease assays using wild-type and PI-resistant proteases from laboratory and clinical isolates and in vitro antiviral assays were used to demonstrate a strong concordance between changes in PI susceptibility at the level of protease inhibition and changes in susceptibility observed at the level of virus infection. The results show that the induction of ATV resistance and increased susceptibility to other PIs by the I50L substitution is likely determined at the level of protease inhibition. Moreover, the I50L substitution functions to increase PI susceptibility even in the presence of other primary and secondary PI resistance substitutions. These findings may have implications regarding the optimal sequencing of PI therapies necessary to preserve PI treatment options of patients with ATV-resistant HIV infections.

Amino Acid Substitution↗
PubMed2005

Relation of sexual risks and prevention practices with individuals' stigmatising beliefs towards HIV infected individuals: an exploratory study.

OBJECTIVE: To investigate how an individual's stigmatising beliefs towards people living with HIV are related to his or her own sexual risk and protective behaviours. METHODS: A cross sectional survey was conducted to assess HIV related stigmatising beliefs, risk sexual behaviours, and preventive practices among sexually experienced rural to urban migrants aged 18-30 years in 2002 in Beijing and Nanjing, two large Chinese cities. RESULTS: Among 2153 migrants, 7.2% reported having had more than one sexual partner in the previous month, 9.9% had commercial sex partners, and 12.5% had an episode of a sexually transmitted disease (STD). Only 18% reported frequently or always using condoms, with 20% sometimes or occasionally using them. 57% of the Chinese migrants were willing to take a voluntary HIV test, and 65% had HIV related stigmatising beliefs towards people living with HIV. Multiple logistic regression analysis depicts that individual's stigmatising beliefs towards people with HIV were positively associated with having had an episode of an STD, having multiple sex partners, or having had commercial sex partners, and were negatively associated with condom use and the willingness to accept an HIV test. CONCLUSION: The finding that one's own stigmatising belief is a potential barrier to HIV related preventive practices highlights the difficulties and challenges in implementing behavioural interventions.

Adolescent↗