Biomedical subjects

H Qian

Publications and source records attributed to H Qian.

At least 19 recordsLinked to original sources

PubMed2007

Anti-CD45RB monoclonal antibody prolongs renal allograft survival in cynomolgus monkeys.

Previously, an anti-CD45RB monoclonal antibody (mAb) has been shown to induce murine allograft tolerance. The present study was performed to assess the ability of an anti-human CD45RB mAb to prevent rejection in a monkey MHC-mismatched kidney transplant model. The recipients were allocated into the following treatment groups: (1) isotype control IgG; (2) mouse anti-human CD45RB IgG1 (6G3); (3) human-mouse chimeric anti-CD45RB-IgG1 (C6G3-IgG1); (4) human-mouse chimeric anti-CD45RB-IgG2 (C6G3-IgG2); (5) tacrolimus at a subtherapeutic dose and (6) tacrolimus and C6G3-IgG1 in combination. Monotherapy with anti-CD45RB mAb significantly prolonged renal allograft survival to a median survival of 21 days. Adding a subtherapeutic dose of tacrolimus improved the efficacy of the anti-CD45RB mAb, achieving a median survival of 85 days, whereas a subtherapeutic dose of tacrolimus alone only moderately prolonged survival to 27 days. Treatment with anti-CD45RB mAb resulted in an alteration of the CD45RB(hi) : CD45RB(lo) cell ratio in the peripheral blood. We have, for the first time, demonstrated that an anti-human CD45RB mAb (6G3) can prolong graft survival. Induction with an anti-CD45RB mAb improves the efficacy of tacrolimus in the prevention of rejection. These encouraging results indicate that an anti-CD45RB mAb may be valuable in future clinical transplantation.

Animals↗

PubMed2006

High pH accelerates GABA deactivation on perch-rho1B receptors.

The ionotropic GABA(C) receptor, formed by GABA rho subunits, is known to be modulated by a variety of endogenous compounds, as well as by changes in pH. In this study, we explore the proton sensitivity of the GABA rho subunits cloned from the perch retina, and report a novel action of high pH on the homomeric receptor formed by one of the GABA rho subunits, the perch-rho(1B) subunit. Raising extracellular pH to 9.5 significantly accelerated GABA deactivation responses elicited from oocytes expressing the perch-rho(1B) subunit, and reduced its sensitivity to GABA. The change in the kinetics of the GABA-offset response occurred without altering the maximum response amplitude, and the reduced GABA sensitivity was independent of membrane potential. Although acidification of the extracellular solution also accelerated GABA deactivation for all other GABA rho receptors examined in this study, the effects of high pH were unique to the homomeric receptor formed by the perch-rho(1B) subunit. In addition, we found that, unlike the effects on the response to the naturally occurring full agonist GABA, the responses elicited by partial agonists (imidazole-4-acetic acid (I4AA) and beta-alanine) in the presence of the high pH solution showed a significant reduction in the maximum response amplitude. When considered in terms of a model describing the activation of GABA(C) receptors, in which pH can potentially affect either the binding affinity or the rate of channel closure, the results were consistent with the view that external alkalization reduces the gating efficiency of the receptor. To identify the proton sensitive domain(s) of the perch-rho(1B) receptor, chimeras were constructed by domain swapping with other perch-rho subunits. Analysis of the pH sensitivities of the various chimeric receptors revealed that the alkaline-sensitive residues are located in the N-terminal region of the perch-rho(1B) subunit.

Animals↗

PubMed2006

Associations between socioeconomic status and cancer survival: choice of SES indicator may affect results.

PURPOSE: Two previous studies, by Gorey et al. and Boyd et al., compared associations between socioeconomic status (SES) and cancer survival in Canada and the United States. Both studies used SES information from population censuses linked to cancer registries. This study investigates why two similar studies led to apparently conflicting results. METHODS: We conducted analyses following analytic details provided by the previously published studies to describe cancer survival in Toronto, Canada, and Detroit, MI. We examined the effects of choice of census indicators and census levels on the observed SES-related gradients in cancer survival. RESULTS: Significant associations between SES and cancer survival were observed in Toronto for several major disease sites when median household income was used as an SES indicator. Associations were weaker when a poverty indicator was used. In Detroit, similar SES gradients were observed by using both income and poverty as SES indicators. When SES quintiles were represented by income ranks, SES-associated survival gradients were much steeper in Detroit than Toronto. When SES was described by the median income in each quintile, gradients were similar in the two cities. CONCLUSIONS: The apparent contradiction in results of two previous studies is related to the choice of SES indicators. Poverty may not be an indicator of choice for such an intercountry comparison.

Data Interpretation, Statistical↗

PubMed2006

Renoprotective effects of combination of angiotensin converting enzyme inhibitor with mycophenolate mofetil in diabetic rats.

OBJECTIVE AND DESIGN: Previously it was shown that blocking of the renin-angiotensin system (RAS) by angiotensin converting enzyme (ACE) inhibitors, or suppression of inflammatory responses by immunosuppressive drugs such as mycophenolate mofetil (MMF) could attenuate renal injury in diabetic rats. Whether RAS blockade combined with an immunosuppressive drug provides superior renoprotection against diabetic nephropathy has not been clearly delineated. MATERIALS: Diabetes was induced by injection of streptozotocin after uninephrectomy. TREATMENT: Rats were randomly separated into five groups: control, diabetes, diabetes treated with enalapril (an ACE inhibitor, 10 mg/kg/d by gastric gavage), diabetes treated with MMF (10 mg/kg/d by gastric gavage), or diabetes treated with a combination of both agents and were followed for 8 weeks. METHODS: 24 h urinary albumin excretion rate (AER) was determined, renal injury was evaluated, immunohistochemistry for ED-1 macrophage marker, intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were performed, and expression of transforming growth factor (TGF)-beta1 protein was determined by Western blotting analysis. RESULTS: Diabetes was associated with a considerable increase in AER. Both enalapril and MMF retarded the increase in albuminuria, which was nearly completely abrogated by combination therapy. Increased glomerular volume and tubulointerstitial injury index in diabetic rats was attenuated by treatment with either enalapril or MMF and further reduced by the combination of the two. Elevated malondialdehyde levels in renal tissue were reduced by enalapril or MMF and, more effectively, by combined enalapril with MMF. Renal overexpression of ICAM-1 was not retarded by enalapril and attenuated by MMF or combined enalapril with MMF. Combination therapy was associated with a superior suppression of diabetes-induced macrophage recruitment and overexpression of MCP-1 and TGFbeta1 compared to either monotherapy in renal tissue. CONCLUSION: The combination of enalapril and MMF confers superiority over monotherapy in renoprotection, a mechanism which may be at least partly correlated with synergistic suppression of increased macrophage recruitment and overexpression of MCP-1 and TGF-beta1 in renal tissue in diabetic rats.

Albuminuria↗

PubMed2006

Metabolic futile cycles and their functions: a systems analysis of energy and control.

It has long been hypothesised that futile cycles in cellular metabolism are involved in the regulation of biochemical pathways. Following the work of Newsholme and Crabtree, a quantitative theory was developed for this idea based on open-system thermodynamics and metabolic control analysis. It is shown that the stoichiometric sensitivity of an intermediary metabolite concentration with respect to changes in steady-state flux is governed by the effective equilibrium constant of the intermediate formation, and the equilibrium can be regulated by a futile cycle. The direction of the shift in the effective equilibrium constant depends on the direction of operation of the futile cycle. High stoichiometric sensitivity corresponds to ultrasensitivity of an intermediate concentration to net flow through a pathway; low stoichiometric sensitivity corresponds to super-robustness of concentration with respect to changes in flux. Both cases potentially play important roles in metabolic regulation. Futile cycles actively shift the effective equilibrium by expending energy; the magnitude of changes in effective equilibria and sensitivities is a function of the amount of energy used by a futile cycle. This proposed mechanism for control by futile cycles works remarkably similar to kinetic proofreading in biosynthesis. The sensitivity of the system is also intimately related to the rate of concentration fluctuations of intermediate metabolites. The possibility of different roles for the two major mechanisms within cellular biochemical regulation, namely reversible chemical modifications via futile cycles and shifting equilibrium by macromolecular binding, are discussed.

Biological Clocks↗

PubMed2006

Dispersion of exhaled droplet nuclei in a two-bed hospital ward with three different ventilation systems.

UNLABELLED: Effective ventilation in general hospital wards is important for controlling the airborne transmission of infectious respiratory diseases. Experiments have been carried out to increase our understanding of the interaction of the breathing flows of two individuals in a full-scale experimental hospital ward with three ventilation systems, i.e. mixing, downward and displacement ventilation. Two life-size breathing thermal manikins were used to simulate a source patient and a receiving patient. The exhalation jet from a bed-lying manikin was visualized using smoke. N2O was used as tracer gas to simulate the droplet nuclei exhaled by patients; and the spatial distribution of its concentrations was measured. Our experimental results show that for both mixing and downward ventilation, the exhaled jet penetrates a short distance and is diluted quickly by ventilation air. The exhaled droplet nuclei are well mixed in the ward. Bed distance does not affect the personal exposure of the receiving patient. For displacement ventilation, the exhaled jet can penetrate a long distance. A high concentration layer of exhaled droplet nuclei because of thermal stratification locking has also been observed with displacement ventilation. This work is useful for identifying an appropriate ventilation method that can remove droplet nuclei more effectively and minimize the risk of cross-infections in a hospital ward environment. PRACTICAL IMPLICATIONS: As one of the major potential sources for infectious droplet nuclei in a hospital environment, exhalation flows of an infected patient can interact with the respiratory activities of other close individuals and with the room ventilation systems. Our latest results provide information on the penetration of exhalation jets into the ambient environment in different ventilation systems. This work is useful in identifying an appropriate and effective ventilation method for removing droplet nuclei more effectively, and thus minimizing the risk of cross-infections in hospital wards with multiple beds.

Air Movements↗

PubMed2005

Improving the energy resolution of X-ray and electron energy-loss spectra.

We discuss some practical problems of improving the resolution of X-ray and electron spectra. Iterative Bayesian methods promise greater resolution enhancement than Fourier techniques but they also give rise to spectral artifacts. Satellite peaks are generated adjacent to strong peaks in the original spectrum and oscillatory artifacts become prominent after a large number of iterations, particularly when the original data contain high noise content. In the case of valence-electron energy-loss spectra, satellite peaks are reduced by removing the zero-loss peak prior to spectral sharpening. Even so, care should be exercised in interpreting low intensity at low energy loss (after sharpening) as evidence for a bandgap in the electronic density of states.

Journal Article↗

PubMed2005

An asymptotic comparative analysis of the thermodynamics of non-covalent association.

There is an ambiguity in the theoretical models for computing association constants, the key observable in a laboratory, of non-covalent associations. We show that three different models give unique result asymptotically in the limit of strong associate. For weak associations, the disagreement reflects the nature of ill-defined "associated complex'' which can be defined, among various ways, either geometrically or thermodynamically depending on measurement techniques. Furthermore, even when the free energy of association is unique, the corresponding entropy and enthalpy can still be different from different types of measurements--a surprising source of entropy-enthalpy compensation. This work provides a mathematical basis for modeling non-covalent association processes in biology.

Algorithms↗

PubMed2005

The GABA rho1 subunit interacts with a cellular retinoic acid binding protein in mammalian retina.

Interactions between the intracellular domain of ligand-gated membrane receptors and cytoplasmic proteins play important roles in their assembly, clustering, and function. In addition, protein-protein interactions may provide an alternative mechanism by which neurotransmitters activate intracellular pathways. In this study, we report a novel interaction between the GABA rho1 subunit and cellular retinoic acid binding protein in mammalian retina that could serve as a link between the GABA signaling pathway and the control of gene expression in neurons. The interaction between the intracellular loop of the human GABA rho subunit and cellular retinoic acid binding protein was identified using a CytoTrap XR yeast two-hybrid system, and was further confirmed by co-precipitation of the human GABA rho subunit and cellular retinoic acid binding protein from baboon retinal samples. The cellular retinoic acid binding protein binding domain on the human rho1 subunit was located to the C-terminal region of human GABA rho subunit, and the interaction of the human GABA rho subunit with cellular retinoic acid binding protein could be antagonized by a peptide derived from within the binding domain of the rho1 subunit. Since cellular retinoic acid binding protein is a carrier protein for retinoic acid, we investigated the effect of GABA on retinoic acid activity in neuroblastoma cells containing endogenously expressed cellular retinoic acid binding protein. In the absence of the rho1 receptor, these cells showed enhanced neurite outgrowth when exposed to retinoic acid and GABA had no effect on their response to retinoic acid. In contrast, cells stably transfected with the human rho1 subunit showed a significantly reduced sensitivity to retinoic acid when exposed to GABA. These results suggest that the GABA receptor subunit effectively altered gene expression through its interaction with the cellular retinoic acid binding protein pathway.

Animals↗

PubMed2005

Drug resistance and neurotransmitter receptors of nematodes: recent studies on the mode of action of levamisole.

Here we review recent studies on the mode of action of the cholinergic anthelmintics (levamisole, pyrantel etc.). We also include material from studies on the free living nematode Caenorhabditis elegans. The initial notion that these drugs act on a single receptor population, while attractive, has proven to be an oversimplification. In both free living and parasitic nematodes there are multiple types of nicotinic acetylcholine receptor (nAChR) on the somatic musculature. Each type has different (sometimes subtly so) pharmacological properties. The implications of these findings are: (1) combinations of anthelmintic that preferentially activate a broad range of nAChR types would be predicted to be more effective; (2) in resistant isolates of parasite where a subtype has been lost, other cholinergic anthelmintics may remain effective. Not only are there multiple types of nAChR, but relatively recent research has shown these receptors can be modulated; it is possible to increase the response of a parasite to a fixed concentration of drug by altering the receptor properties (e.g. phosphorylation state). These findings offer a potential means of increasing efficacy of existing compounds as an alternative to the costly and time consuming development of new anthelmintic agents.

Adenosine Triphosphate↗

PubMed2005

Role of air distribution in SARS transmission during the largest nosocomial outbreak in Hong Kong.

UNLABELLED: Severe acute respiratory syndrome (SARS) is primarily transmitted by bio-aerosol droplets or direct personal contacts. This paper presents a detailed study of environmental evidence of possible airborne transmission in a hospital ward during the largest nosocomial SARS outbreak in Hong Kong in March 2003. Retrospective on-site inspections and measurements of the ventilation design and air distribution system were carried out on July 17, 2003. Limited on-site measurements of bio-aerosol dispersion were also carried out on July 22. Computational fluid dynamics simulations were performed to analyze the bio-aerosol dispersion in the hospital ward. We attempted to predict the air distribution during the time of measurement in July 2003 and the time of exposure in March 2003. The predicted bio-aerosol concentration distribution in the ward seemed to agree fairly well with the spatial infection pattern of SARS cases. Possible improvement to air distribution in the hospital ward was also considered. PRACTICAL IMPLICATIONS: Our study revealed the need for the development of improved ventilation and air-conditioning systems in an isolation ward or a general hospital ward for infectious respiratory diseases. The outbreak in Ward 8A, which was in a general hospital and could house nearly 40 patients, demonstrated the cross-infection risks of respiratory infectious diseases in hospitals if a potential highly infectious patient was not identified and isolated. Our example simulation, which extended the SARS Busters' design for an isolation room to Ward 8A, demonstrated that there was room for improvement to minimize cross-infection in large general hospital wards.

Aerosols↗

PubMed2004

When 6 is 9: 'uncoupled' AT1 receptors turn signalling on its head.

The type 1 angiotensin receptor (AT(1)) activates an array of intracellular signalling pathways that control cell and tissue responses to the peptide hormone angiotensin II (AngII). The capacity of AT(1) receptors to initiate and maintain such signals has typically been explained on the basis of conventional heterotrimeric guanine nucleotide binding protein (G protein) activation, specifically G(q/11). Accumulating evidence from studies utilising a variety of AT(1) receptor mutants and AngII analogues indicates that some important downstream effects of AT(1) receptors are independent of classical G protein coupling. Importantly, AT(1) receptor-mediated endocytosis, tyrosine phosphorylation signalling and mitogen-activated protein kinase activation as well as transactivation of the epidermal growth factor receptor can occur in G(q/11)-uncoupled receptor mutants. These observations point to a functional partitioning of AT(1) receptor signals that permits separation of short-term AngII actions (e.g., vasoconstriction) from more extended events, such as pathological cell growth in heart and blood vessels, and may open up new avenues for selective antagonism.

Animals↗

PubMed2004

Chemosensitization of breast carcinoma cells with the use of bcl-2 antisense oligodeoxynucleotide.

This study was designed to observe whether the rates of apoptosis induced in the breast cancer cell line MCF-7 by 5-fluorouracil (5-FU) could be enhanced by transfecting bcl-2 antisense oligonucleotide (ASODN). In our experiment, bcl-2 ASODNs and control ODNs including untreated control, sense ODN and scrambled ODN, were transfected into MCF-7 cells. Changes in expression of the bcl-2 gene were examined by Western blot; cell growths were detected by MTT assay, and apoptosis rates were detected by flow cytometry (FCM). Expression of bcl-2 protein after transfection of bcl-2 ASODN was significantly lower than control ODNs. Moreover, incubation of MCF-7 with bcl-2 ASODN prior to 5-FU treatment caused remarkable loss of viable cells compared with all other control ODNs (P < 0.01). FCM showed the apoptosis rates for ASODN, untreated control, sense ODN and scrambled ODN (29.8 +/- 7.4)%, (8.0 +/- 2.3)%, (15.0 +/- 5.1)% and (16.5 +/- 7.1)%, respectively. Compared with control ODNs, ASODN achieved the strongest effect in terms of enhancing apoptosis (P < 0.01). These results suggest that combining bcl-2 ASODN with 5-FU led to synergistic cytotoxicity.

Antimetabolites, Antineoplastic↗

PubMed2004

Immunohistochemical localization and expression of fibromodulin in adult rat periodontium and inflamed human gingiva.

OBJECTIVE: The aim of this study was to determine the distribution and expression of fibromodulin in adult rat periodontal tissues and inflamed human gingiva. MATERIALS AND METHODS: The distribution of fibromodulin in rat molar periodontium and human gingival tissue was studied by immunohistochemistry. The expression of fibromodulin mRNA from human gingival fibroblasts, periodontal ligament fibroblasts and osteoblasts was studied by reverse transcription-polymerase chain reaction (RT-PCR). For comparative purposes, the distribution and mRNA expression of collagen types I and III, as well as the two small leucine-rich proteoglycans decorin and biglycan were also studied. RESULTS: In the adult rat periodontium, fibromodulin was distributed in the suprabasal gingival epithelium, gingival and periodontal fibroblasts as well as their surrounding extracellular matrices. Strong expression was noted in the palatal gingival tissues and the interfaces of the periodontal ligament with alveolar bone and cementum. In human gingival tissues, staining of fibromodulin was detected in the connective tissue of inflamed gingiva associated with both gingivitis and periodontitis; whereas, weak staining for this molecule was noted in healthy gingival tissues. The expression of mRNA for fibromodulin was strongest in the cultured osteoblasts. Periodontal ligament fibroblasts showed only a weak level of expression for fibromodulin mRNA. CONCLUSIONS: Fibromodulin is differentially expressed throughout the periodontium being primarily associated with collagen type I in non-mineralized sites. In addition fibromodulin showed an upregulation in inflamed gingival tissue.

Animals↗

PubMed2003

Tissue engineering for bone regeneration using differentiated alveolar bone cells in collagen scaffolds.

Regeneration of osseous defects by a tissue-engineering approach provides a novel means of treatment utilizing cell biology, materials science, and molecular biology. In this study the concept of tissue engineering was tested with collagen type I matrices seeded with cells with osteogenic potential and implanted into sites where osseous damage had occurred. Explant cultures of cells from human alveolar bone and gingiva were established. When seeded into a three-dimensional type I collagen-based scaffold, the bone-derived cells maintained their osteoblastic phenotype as monitored by mRNA and protein levels of the bone-related proteins including bone sialoprotein, osteocalcin, osteopontin, bone morphogenetic proteins 2 and 4, and alkaline phosphatase. These in vitro-developed matrices were implanted into critical-size bone defects in skulls of immunodeficient (SCID) mice. Wound healing was monitored for up to 4 weeks. When measured by microdensitometry the bone density within defects filled with osteoblast-derived matrix was significantly higher compared with defects filled with either collagen scaffold alone or collagen scaffold impregnated with gingival fibroblasts. New bone formation was found at all the sites treated with the osteoblast-derived matrix at 28 days, whereas no obvious new bone formation was identified at the same time point in the control groups. In situ hybridization for the human-specific Alu gene sequence indicated that the newly formed bone tissue resulted from both transplanted human osteoblasts and endogenous mesenchymal stem cells. The results indicate that cells derived from human alveolar bone can be incorporated into bioengineered scaffolds and synthesize a matrix, which on implantation can induce new bone formation.

Alveolar Process↗

PubMed2003

Modification of polymer surfaces: optimization of approaches.

Modification of polymer surfaces to achieve a surface with enhanced compatibility is an important means of obtaining improved biomaterials. Techniques are available for altering the hydrophilicity or charge of a surface, attaching macromolecules or attempting to resemble cell membranes. Relevant to the clinical success of a modified surface is the modification procedure and a procedure based on incorporation as opposed to surface treatment has potential advantages. The modification of plasticized vinyl chloride (PVC) by the incorporation of cyclodextrins is described. In comparison to unmodified PVC controls, cyclodextrin incorporation reduced fibrinogen adsorption, with the extent of reduction dependent on the type and quantity of cyclodextrin incorporated.

Adsorption↗

PubMed2001

Nitric oxide synthase (nNOS) gene transfer modifies venous bypass graft remodeling: effects on vascular smooth muscle cell differentiation and superoxide production.

BACKGROUND: Pathological vascular remodeling in venous bypass grafts (VGs) results in smooth muscle cell (SMC) intimal hyperplasia and provides the substrate for progressive atherosclerosis, the principal cause of late VG failure. Nitric oxide (NO) bioactivity is reduced in VGs, in association with increased vascular superoxide production, but how these features relate to pathological VG remodeling remains unclear. We used gene transfer of the neuronal isoform of nitric oxide synthase (nNOS) to investigate how increased NO production modulates vascular remodeling in VGs and determined the effects on late VG phenotype. METHODS AND RESULTS: New Zealand White rabbits (n=60) underwent jugular-carotid interposition bypass graft surgery with intraoperative adenoviral gene transfer of nNOS or beta-galactosidase. Vessels were analyzed after 3 days (early, to investigate acute injury/inflammation) or 28 days (late, to investigate SMC intimal hyperplasia). In early VGs, nNOS gene transfer significantly increased NOS activity and substantially reduced adhesion molecule expression and inflammatory cell infiltration. In late VGs, recombinant nNOS protein was no longer evident, but there were sustained effects on VG remodeling, resulting in a striking reduction in SMC intimal hyperplasia, a more differentiated intimal SMC phenotype, and reduced vascular superoxide production. CONCLUSIONS: Intraoperative nNOS gene transfer has sustained favorable effects on VG remodeling and on the vascular phenotype of mature VGs. These findings suggest that early, transient modification of the response to vascular injury is a powerful approach to modulate VG biology and highlight the potential utility of NOS gene transfer as a therapeutic strategy in VGs.

Adenoviridae↗

PubMed2001

Nonequilibrium steady-state circulation and heat dissipation functional.

A nonequilibrium steady-state (NESS), different from an equilibrium, is sustained by circular balance rather than detailed balance. The circular fluxes are driven by energy input and heat dissipation, accompanied by a positive entropy production. Based on a Master equation formalism for NESS, we show the circulation is intimately related to the recently studied Gallavotti-Cohen symmetry of heat dissipation functional, which in turn suggests a Boltzmann's formulalike relation between rate constants and energy in NESS. Expanding this unifying view on NESS to diffusion is discussed.

Journal Article↗