Biomedical subjects

Ming Zhang

Publications and source records attributed to Ming Zhang.

At least 163 records · Page 9Linked to original sources

PubMed2004

Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury.

Reperfusion injury of ischemic tissue represents an acute inflammatory response that can cause significant morbidity and mortality. The mechanism of injury is not fully elucidated, but recent studies indicate an important role for natural antibody and the classical pathway of complement. To test the hypothesis that injury is initiated by specific IgM, we have screened a panel of IgM-producing hybridomas prepared from peritoneal cells enriched in B-1 cells. One clone, CM22, was identified that could restore pathogenic injury in RAG-1(-/-) mice in an intestinal model of ischemia/reperfusion (I/R). In situ activation of the classical pathway of complement was evident by deposition of IgM, complement C4, and C3 in damaged tissue after passive transfer of CM22 IgM. Sequence analysis of CM22 Ig heavy and light chains showed germ-line configurations with high homology to a V(H) sequence from the B-1 repertoire and a V(K) of a known polyreactive natural IgM. These data provide definitive evidence that I/R injury can be initiated by clonally specific natural IgM that activates the classical pathway of complement. This finding opens an avenue for identification of I/R-specific self-antigen(s) and early prevention of injury.

Animals↗

PubMed2004

Maspin plays an essential role in early embryonic development.

Maspin (Mp) is a member of the serpin family with inhibitory functions against cell migration, metastasis and angiogenesis. To identify its role in embryonic development in vivo, we generated maspin knockout mice by gene targeting. In this study, we showed that homozygous loss of maspin expression was lethal at the peri-implantation stage. Maspin was specifically expressed in the visceral endoderm after implantation; deletion of maspin interfered with the formation of the endodermal cell layer, thereby disrupting the morphogenesis of the epiblast. In vitro, the ICM of the Mp(-/-) blastocysts failed to grow out appropriately. Data from embryoid body formation studies indicated that the Mp(-/-) EBs had a disorganized, endodermal cell mass and lacked a basement membrane layer. We showed that the embryonic ectoderm lineage was lost in the Mp(-/-) EBs, compared with that of the Mp(+/+) EBs. Re-expression of maspin partially rescued the defects observed in the Mp(-/-) EBs, as evidenced by the appearance of ectoderm cells and a layer of endoderm cells surrounding the ectoderm. In addition, a maspin antibody specifically blocked normal EB formation, indicating that maspin controls the process through a cell surface event. Furthermore, we showed that maspin directly increased endodermal cell adhesion to laminin matrix but not to fibronectin. Mp(+/-) endodermal cells grew significantly slower than Mp(+/+) endodermal cells on laminin substrate. We conclude that deletion of maspin affects VE function by reducing cell proliferation and adhesion, thereby controlling early embryonic development.

Animals↗

PubMed2004

Titania-coated polystyrene hybrid microballs prepared with miniemulsion polymerization.

Hybrid microballs with polystyrene cores coated by titania nanoparticles were prepared in miniemulsion polymerization. Acrylic acid was used as a comonomer to promote locating titania nanoparticles on the polymer's surface. The addition of a hydrophobic agent effectively prevents monomer diffusing into the aqueous phase. The morphology of hybrid particles was examined with the transmission electron microscope, and its change pattern with reactive conditions was observed. The infrared spectra of hybrid nanoparticles showed that there existed a certain interaction between titania nanoparticles and polymers. The crystallization morphology of hybrid particles before and after calcination was characterized with X-ray diffraction.

Journal Article↗

PubMed2004

Expression and regulation of tumor suppressor gene maspin in human bladder cancer.

Maspin is a member of serine protease inhibitor family with tumor suppressing activity for breast and prostate cancers, acting at the level of tumor invasion and metastasis. However, there have been no published data regarding the role of maspin in human bladder cancer. We evaluated maspin expression in 65 series of bladder cancer samples (22 transurethral resection (TUR) and 43 radical cystectomy) and studied the regulatory mechanism of maspin gene activation in bladder cancer cells. Maspin expression was immunohistochemically detected in four (18.2%) patients with TUR and 22 (51.2%) patients with radical cystectomy whereas no expression was observed in normal transitional cells located at tumor-free area in bladder. The maspin expression was significantly correlated with the development of muscle invasive bladder cancer (P=0.00008). Using a luciferase reporter system, maspin promoter activity was induced in the maspin-positive bladder cancer cell lines as well as maspin-negative RT4 cells. Furthermore, treatment with the DNA methyltransferase inhibitor, 5-aza-2' deoxycytidine, and histone deacetylase inhibitor, trichostatin A, led to re-expression of maspin in RT4 cells. Our results indicate that maspin may contribute to bladder cancer development and that DNA methylation and histone deacetylation may be important for regulating maspin gene activation in bladder cancer cells.

Adult↗

PubMed2004

Glutamate receptor antagonists protect from virus-induced neural degeneration.

Neuronal damage during acute viral encephalomyelitis can result directly from virus infection or indirectly from the host immune response to infection. In neurodegenerative diseases and stroke, neuronal death also can result from excess release of excitatory amino acid neurotransmitters, such as glutamate. To determine the role of glutamate excitotoxicity in fatal alphavirus-induced paralytic encephalomyelitis, we treated mice infected with neuroadapted Sindbis virus (NSV) with antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtypes of glutamate receptors. Both apoptotic and necrotic neurons in the hippocampus were decreased in animals treated with MK-801, an NMDA receptor antagonist, or GYKI-52466, an AMPA receptor antagonist. However, only AMPA receptor blockade prevented damage to spinal cord motor neurons and protected mice from paralysis and death due to NSV infection. Protection was not caused by altered virus replication because treatment did not affect virus distribution and actually delayed virus clearance. These results provide evidence that NSV infection activates neurotoxic pathways that result in aberrant glutamate receptor stimulation and neuronal damage. Furthermore, AMPA receptor-mediated motor neuron death is an important contributor to paralysis and mortality in acute alphavirus-induced encephalomyelitis.

Alphavirus Infections↗

PubMed2004

Skin ligaments: regional distribution and variation in morphology.

Skin ligaments (SL) (L. retinacula cutis) are present extensively in the face, hands, feet, and in breast tissue, but have seldom been reported elsewhere in the body. The traditional histological view of the subcutaneous region is that it comprises a matrix of loose connective tissue devoid of fibrous specializations. The purpose of this study was to determine the structure and distribution of skin ligaments. Eight embalmed cadavers (3 males, 5 females, 69-90 years of age) were used in this study. Tissue was prepared using the E12 plastination technique. Macroscopic and microscopic examination demonstrated the widespread presence in the limbs and most of the rest of the body of fibrous strands linking the base of the dermis and the superficial fibers of the underlying deep fascia. The morphology and distribution of these skin ligaments were similar in the individuals examined. Variations in the structure of the skin ligaments depended on the presence of underlying muscle, neurovascular bundles, intermuscular septa and adipose tissue. We conclude that skin ligaments are complex fibrous structures that are present over most of the body. They form an extensive peripheral network in the subcutaneous fat. These 'ligaments' seem to provide an anchorage of skin to deep fascia that is flexible and yet resistant to mechanical loading from multi-directional forces. The use of the E12 plastination technique coupled with fluorescent confocal microscopy has been of benefit in visualizing and delineating SLs from other soft tissue structures in three planes.

Aged↗

PubMed2004

Effective induction of immune tolerance by portal venous infusion with IL-10 gene-modified immature dendritic cells leading to prolongation of allograft survival.

Dendritic cells (DC) not only initiate T cell responses, but are also involved in the induction of tolerance. The functional properties of DC are strictly dependent on their state of maturation. It has been shown that immature DC can induce immune tolerance and prolong allograft survival. Interleukin-10 (IL-10) is an important immunosuppressive cytokine which inhibits maturation and function of DC. In order to improve the tolerogenicity of DC, we and others showed that adenovirus vectors can effectively mediate IL-10 genetic modification of DC, and IL-10 genetic modification can inhibit MHC II, B7.2, and CD40 expression, IL-12 secretion and the T cell stimulatory capacity of DC. The primary aim of this study is to examine the in vivo effects of this approach on allograft survival in a murine cardiac allograft transplantation model. To our surprise,we observed that infusion of immature DC genetically modified to express IL-10 (DC-IL-10) via the tail vein could not prolong allograft survival in the recipients, but shortened their survival. More interestingly, portal venous infusion of DC-IL-10 markedly prolonged allograft survival. The diverse effects of DC-IL-10 infusion through different routes may be due to the different immune responses to alloantigens in recipients that received DC-IL-10 via either the portal or the tail vein. Decreased cytotoxicity, polarization of Th2 response, poor T cell stimulating activity of liver DC and enhanced incidence of donor DC in the recipients may contribute to the more efficient prolongation of allograft survival observed after portal venous infusion of DC-IL-10. These results suggest that portal venous infusion may be an effective approach for immature DC to induce immune tolerance or hyporesponsiveness against donor antigens, and prolong allograft survival.

Animals↗

PubMed2004

Comparing the ESA HPLC total homocysteine assay with electrochemical detection to the CDC in-house HPLC assay with fluorescence detection.

BACKGROUND: Environmental science has developed a simple high performance liquid chromatography (HPLC) assay with electrochemical detection for total homocysteine (tHcy) measurement that does not require derivatization of free thiols. We evaluated this method and compared it with the CDC HPLC assay with fluorescence detection (FD). METHODS: tHcy is measured after reduction of disulfides/protein-bound thiols and protein precipitation using four channels of an ESA CoulArray detector. L-homocystine is used as calibrator, penicillamine as internal standard. RESULTS: Aqueous calibration of the ESA assay resulted in overestimation of tHcy by approximately 30% compared to the HPLC-FD method. Calibration in plasma alleviated the matrix effect. The within- (n=3) and between-run (n=20) imprecision was <6%, the linearity up to 100 micromol/l was excellent, and the recovery of tHcy added to plasma was nearly complete (98.7%+/-2.3%). Good correlation was observed between both methods for 266 plasma samples. The ESA assay showed a minimal negative bias of 0.28 micromol/l (3.3%). CONCLUSION: The ESA tHcy assay performed well in terms of accuracy and precision, and showed good agreement with the CDC HPLC-FD assay when calibrated in plasma. The major advantage of this assay is that it does not require sample derivatization. Disadvantages include instability of the prepared samples for prolonged storage and matrix effects.

Calibration↗

PubMed2004

Effects of plantar fascia stiffness on the biomechanical responses of the ankle-foot complex.

BACKGROUND: The plantar fascia is one of the major stabilizing structures of the longitudinal arch of human foot, especially during midstance of the gait cycle. Knowledge of its functional biomechanics is important for establishing the biomechanical rationale behind different rehabilitation, orthotic and surgical treatment of plantar fasciitis. This study aims at quantifying the biomechanical responses of the ankle-foot complex with different plantar fascia stiffness. METHODS: A geometrical detailed three-dimensional finite element model of the human foot and ankle, incorporating geometric and contact nonlinearities was constructed by 3D reconstruction of MR images. A sensitivity study was conducted to evaluate the effects of varying elastic modulus (0-700 MPa) of the plantar fascia on the stress/strain distribution of the bony, ligamentous and encapsulated soft tissue structures. FINDINGS: The results showed that decreasing the Young's modulus of plantar fascia would increase the strains of the long and short plantar and spring ligaments significantly. With zero fascia Young's modulus to simulate the plantar fascia release, there was a shift in peak von Mises stresses from the third to the second metatarsal bones and increased stresses at the plantar ligament attachment area of the cuboid bone. Decrease in arch height and midfoot pronation were predicted but did not lead to the total collapse of foot arch. INTERPRETATION: Surgical dissection of the plantar fascia may induce excessive strains or stresses in the ligamentous and bony structures. Surgical release of plantar fascia should be well-planned to minimise the effect on its structural integrity to reduce the risk of developing arch instability and subsequent painful foot syndrome.

Adult↗

PubMed2004

Load transfer mechanics between trans-tibial prosthetic socket and residual limb--dynamic effects.

The effects of inertial loads on the interface stresses between trans-tibial residual limb and prosthetic socket were investigated. The motion of the limb and prosthesis was monitored using a Vicon motion analysis system and the ground reaction force was measured by a force platform. Equivalent loads at the knee joint during walking were calculated in two cases with and without consideration of the material inertia. A 3D nonlinear finite element (FE) model based on the actual geometry of residual limb, internal bones and socket liner was developed to study the mechanical interaction between socket and residual limb during walking. To simulate the friction/slip boundary conditions between the skin and liner, automated surface-to-surface contact was used. The prediction results indicated that interface pressure and shear stress had the similar double-peaked waveform shape in stance phase. The average difference in interface stresses between the two cases with and without consideration of inertial forces was 8.4% in stance phase and 20.1% in swing phase. The maximum difference during stance phase is up to 19%. This suggests that it is preferable to consider the material inertia effect in a fully dynamic FE model.

Amputation Stumps↗

PubMed2004

Finite element modeling of the contact interface between trans-tibial residual limb and prosthetic socket.

Finite element method has been identified as a useful tool to understand the load transfer mechanics between a residual limb and its prosthetic socket. This paper proposed a new practical approach in modeling the contact interface with consideration of the friction/slip conditions and pre-stresses applied on the limb within a rectified socket. The residual limb and socket were modeled as two separate structures and their interactions were simulated using automated contact methods. Some regions of the limb penetrated into the socket because of socket modification. In the first step of the simulation, the penetrated limb surface was moved onto the inner surface of the socket and the pre-stresses were predicted. In the subsequent loading step, pre-stresses were kept and loadings were applied at the knee joint to simulate the loading during the stance phase of gait. Comparisons were made between the model using the proposed approach and the model having an assumption that the shape of the limb and the socket were the same which ignored pre-stress. It was found that peak normal and shear stresses over the regions where socket undercuts were made reduced and the stress values over other regions raised in the model having the simplifying assumption.

Algorithms↗

PubMed2004

Murine hindlimb reperfusion injury can be initiated by a self-reactive monoclonal IgM.

BACKGROUND: Murine hindlimb reperfusion injury (I/R), is initiated by activation of the classical pathway of complement. Complement receptor-2 knockout mice (Cr2-/-) are protected from I/R injury due to defective B-1 cells with a resulting deficient natural immunoglobulin M (IgM) repertoire. Cr2-/- and wild type (WT) mice were studied to isolate the antibody or antibodies responsible for initiation of I/R. METHODS: IgM-secreting B-1 cell clones were produced with hybridoma technology from WT cells. Of 21 clones tested in murine I/R models, only 1 clone, CM22, was found to restore injury in protected mice. Cr2-/- mice reconstituted with IgM from individual clones, WT serum, or saline were subjected to 2 hours hindlimb ischemia and 3 hours reperfusion and compared with WT. RESULTS: Muscle injury in Cr2-/- mice reconstituted with CM22 was similar to injury in WT mice reconstituted with saline and Cr2-/- mice reconstituted with WT serum. This injury was 137% greater (P < .05) than in both Cr2-/- mice reconstituted with saline and those reconstituted with a different IgM clone, CM31. IgM and C3 deposition was found only on injured muscle of WT mice or Cr2-/- mice reconstituted with CM22 or WT serum. CONCLUSION: A single clone of self-reactive IgM, CM22, can initiate complement-dependent I/R injury.

Animals↗

PubMed2004

Extracorporeal high intensity focused ultrasound ablation in the treatment of 1038 patients with solid carcinomas in China: an overview.

The ideal treatment of localized cancer should directly cause an irreversible and complete death of tumor cells without damage to surrounding normal tissue. High intensity focused ultrasound (HIFU) is such a potential treatment, which induces a complete coagulative necrosis of a tumor at depth through the intact skin. The idea that using an extracorporeal source of therapeutic ultrasound was introduced more than 50 years ago [J. Gen. Physiol. 26 (1942) 179]. However, up to now, most of the studies on HIFU have been dealing with animal experiments because this extracorporeal technique is very complicated in clinical applications. The purpose of this study is to introduce Chinese clinical experience of using extracorporeal HIFU for the treatment of patients with various kinds of solid tumor. From December 1997 to October 2001, a total of 1038 patients with solid tumors underwent HIFU ablation in China. Among them, 313 patients were treated at the Chongqing University of Medical Sciences, China. Pathological examination showed that the target region presented clear evidence of cellular destruction. Small blood vessels less than 2 mm in diameter were severely damaged. Follow-up diagnostic imaging revealed that there was no, or reduced, blood supply, and no uptake of radioisotope in the treated tumor after HIFU, both indicating a positive therapeutic response and an absence of viable tumor. Imaging at 6-12 months showed obvious regression of the lesion. Four-year follow-up data were significantly observed in patients with hepatocellular carcinoma, osteosarcoma, and breast cancer. An extremely low major complication rate was noted. It is concluded that HIFU ablation is a safe, effective, and feasible modality for the ablation of carcinomas.

China↗

PubMed2004

Role of stem cell homing in myocardial regeneration.

Recent studies have demonstrated the potential for myocardial regeneration at the time of myocardial infarction. Our lab focuses on understanding how stem cells home to injured tissue. We believe that a detailed analysis of the biological responses to tissue injury not only gives us insight into how damage occurs, but can also yield insight into how the body attempts to repair itself. In the case of the heart, we have shown that these "healing pathways" are only expressed for a short time following injury, and this may be why myocardial damage is usually irreversible. Furthermore, work suggests that deciphering these "healing pathways" and re-establishing their expression at time remote from injury offers an avenue for developing novel therapeutics that ultimately may allow us to orchestrate and exaggerate the healing process at time remote from tissue injury.

Animals↗

PubMed2004

Gene expression in intrahepatic tumors through DNA recombination by a replication-activated adenovirus vector.

One strategy for improving selectivity of gene therapy is the use of a replication-activated adenovirus vector that mediates transgene expression specifically in tumor cells through homologous recombination of viral genomes. In this study, we compared replication-activated adenovirus containing inverted repeats (Ad.IR-BG) with IR-deficient virus (Ad.BG) for selective gene expression in hepatocellular carcinoma and colon carcinoma metastases in the liver. We found that Ad.IR-BG conferred specific gene expression in both carcinoma cells, with minimal expression in hepatocytes and colon epithelial cells. This occurred through viral DNA recombination in Ad.IR-BG-infected tumor cells but not in normal cells. Hydroxyurea, which blocks DNA replication, inhibited DNA recombination and beta-gal expression in Ad.IR-BG-infected but not Ad.BG-infected tumor cells. Finally, systemic injection of Ad.IR-BG into tumor xenografts in nude mice significantly improved selectivity of gene expression in tumors with minimal expression in normal tissues. Viral DNA recombination, which was absent in normal liver, was detected in Ad.IR-BG-infected tumors but not in Ad.BG-infected tissue. These findings demonstrated that replication-activated adenovirus can mediate tumor-specific gene expression through viral DNA recombination, which is otherwise deficient in normal cells.

Adenoviridae↗

PubMed2004

DBMap: a space-conscious data visualization and knowledge discovery framework for biomedical data warehouse.

Advances in digital imaging modalities as well as other diagnosis and therapeutic techniques have generated a massive amount of diverse data for clinical research. The purpose of this study is to investigate and implement a new intuitive and space-conscious visualization framework, called DBMap, to facilitate efficient multidimensional data visualization and knowledge discovery against the large-scale data warehouses of integrated image and nonimage data. The DBMap framework is built upon the TreeMap concept. TreeMap is a space constrained graphical representation of large hierarchical data sets, mapped to a matrix of rectangles, whose size and color represent interested database fields. It allows the display of a large amount of numerical and categorical information in limited real estate of the computer screen with an intuitive user interface. DBMap has been implemented and integrated into a large brain research data warehouse to support neurologic and neuroradiologic research at the University of California, San Francisco Medical Center. For imaging specialists and clinical researchers, this novel DBMap framework facilitates another way to better explore and classify the hidden knowledge embedded in medical image data warehouses.

Algorithms↗

PubMed2004

Signaling through 3',5'-cyclic adenosine monophosphate and phosphoinositide-3 kinase induces sodium/iodide symporter expression in breast cancer.

The sodium/iodide symporter (NIS) is a membrane transport glycoprotein normally expressed in the thyroid gland and lactating mammary gland. NIS is a target for radioiodide imaging and therapeutic ablation of thyroid carcinomas and has the potential for similar use in breast cancer treatment. To facilitate NIS-mediated radionuclide therapy, it is necessary to identify signaling pathways that lead to increased NIS expression and function in breast cancer. We examined NIS expression in mammary tumors of 14 genetically engineered mouse models to identify genetic manipulations associated with NIS induction. The cAMP and phosphoinositide-3 kinase (PI3K) signaling pathways are associated with NIS up-regulation. We showed that activation of PI3K alone is sufficient to increase NIS expression and radioiodide uptake in MCF-7 human breast cancer cells, whereas cAMP stimulation increases NIS promoter activity and NIS mRNA levels but is not sufficient to increase radioiodide uptake. This study is the first to demonstrate that NIS expression is induced by cAMP and/or PI3K in breast cancer both in vivo and in vitro.

Animals↗

PubMed2004

Changes in the proportion and number of Pax(7+ve) and MF20(+ve) myoblasts during chick myogenesis in the head and limb.

Previous studies suggested that all myoblasts are present in the head and limb prior to the commencement of primary myotube formation. As a consequence, these myoblasts must be in various developmental states during myogenesis, i.e. proliferating, differentiating or terminally differentiated. There are few in vivo studies investigating dynamic quantitative changes of subgroups of these myoblasts during myogenesis. In this report, using anti-Pax7 and anti-myosin heavy chain antibodies, we examined the quantitative change of proliferating (Pax7(+ve)) and terminally differentiated (MF20(+ve)) myoblasts during primary and secondary myogenesis in the chick head and limb. Our results show that during primary myogenesis, less than 30% of myoblasts are in the proliferating phase, but as soon as secondary myogenesis begins, over 95% of myoblasts start to proliferate. Moreover, we have found that the proportion of terminally differentiated myoblasts is maintained at a low level (less than 3%) during primary and secondary myogenesis.

Animals↗