Search PubMed⌕ Search

Biomedical subjects

Ming Zhang

Publications and source records attributed to Ming Zhang.

At least 73 records · Page 4Linked to original sources

Attenuation of skeletal muscle reperfusion injury with intravenous 12 amino acid peptides that bind to pathogenic IgM.

BACKGROUND: The injury sustained by reperfused skeletal muscle is inflammatory and is initiated by binding of pre-formed IgM to involved tissue, followed by local complement activation and further inflammation. A clone of natural IgM has been described that initiates this injury, suggesting that specific antigens are exposed on ischemic tissues that act as ligands for this pathogenic antibody. In these experiments, we examine the properties of short peptide sequences, and their homologues, that bind to the antigen-combining site of this pathogenic IgM clone. METHODS: A 12-mer phage display library was biopanned with the pathogenic IgM clone and then negatively selected against an inactive natural IgM clone. All 8 clones that bound specifically to the pathogenic IgM had closely related amino acid sequences. P8 is the clone that bound most avidly. Tissue lysates from ischemic tissue were reacted with pathogenic IgM, and immune complexes isolated and analyzed on SDS-PAGE. Bands were excised and sequenced, identifying non-muscle myosin as the protein reacting with pathogenic antibody in ischemic gut and glycogen phosphorylase as the counterpart in ischemic skeletal muscle. Both proteins contain sequence homologous to P8; N2 and GP1 are the natural 12-mers homologues that are contained within non-muscle myosin and glycogen phosphorylase, respectively. Wild-type C57/Bl6 mice, divided into groups receiving saline, P8, N2, GP1, or a random peptide at the start of the experiment, were subjected to 2 hours of tourniquet induced hind limb ischemia and 3 hours of reperfusion. Muscle was assessed for injury with histology and for immune activation with histochemistry. RESULTS: Intravenous administration of P8, N2, and GP1 led to significant attenuation of muscle injury (13 +/- 1.8 injured fibers/50 counted, 12 +/- 0.81, 8.0 +/- 0.73 respectively) after reperfusion injury compared to animals receiving saline (26 +/- 2.3) or the same mass of a random peptide (22 +/- 2.3), P less than .05. This level of protection from injury is comparable to that seen in the absence of antibody altogether. As well, P8-treated animals exhibited a marked decrease in deposition of IgM (as well as C3) in comparison to saline treated controls. CONCLUSIONS: Specific peptide blockade of an injury-inducing IgM clone decreased the local consequences of skeletal muscle ischemia/reperfusion injury in wild-type animals that have the full repertoire of IgM specificities. This indicates that the antibodies that initiate reperfusion injury have specificity only for P8-related antigens. This could also indicate that the variety of relevant ischemic antigens is quite restricted.

Animals↗

Quantifying the regional load-bearing ability of trans-tibial stumps.

This paper reports findings of experiments aiming to (1) compare the load tolerant ability over different regions of stumps of lower limb amputees, (2) study the effect of walking on the load tolerant ability, and (3) examine the distal-end weight-bearing ability supported by different interface materials. The method was to apply increasing load to the stump up to the pain level through a force transducer or a digital scale, considering the effect of regional difference, walking, and interface materials. The results show that the patellar tendon and the distal end of the fibula were the best and worst load-tolerant region, respectively. Walking with prostheses tended to increase the load-tolerant ability, which is thought to be due to the massage-like effect of the socket. Different interface materials did not significantly alter the distal-end weight-bearing ability. However, there was a great difference in the distal-end weight-bearing ability among different subjects.

Adult↗

Fatigue test of low-cost flexible-shank monolimb trans-tibial prosthesis.

Monolimb refers to a kind of trans-tibial prostheses with the socket and shank moulded into one piece of thermoplastic material. If properly designed, the shank of a monolimb can deflect which may compensate for the lost ankle plantarflexion and dorsiflexion to some extent. However, provision of shank flexibility is usually accompanied by reduced structural strength of the entire prosthesis. In the recent work using finite element analysis and the Taguchi method, the dimensions of the shank for the monolimb were derived which aimed at giving high shank flexibility and reasonable strength to resist static load. Yet, fatigue testing has not been performed. Fatigue failure may happen when a relatively low level of load is applied repeatedly. This study aimed to document the fatigue life of two flexible-shank monolimbs, by applying cyclic force of 800 N at the forefoot region for 500,000 cycles. Results showed that the design of the foot bolt adaptor played an important role in the structural integrity of the monolimb. One monolimb completed the fatigue test of 500,000 cycles without visual material yield, but with 3.8 degrees change in dorsiflexion angle when the load was removed.

Artificial Limbs↗

Tumor necrosis factor alpha and macrophages in the brain of herpes simplex virus type 1-infected BALB/c mice.

After uniocular anterior chamber (AC) inoculation of herpes simplex virus type 1 (HSV-1), virus and TNF alpha (TNF-alpha) are detected in the suprachiasmatic nuclei (SCN). The goal of this study was to investigate the role of TNF-alpha and macrophages in the brain of HSV-1-infected BALB/c mice. Mice were treated with thalidomide for TNF-alpha inhibition or injected with clodronate liposomes to deplete macrophages, and the AC of one eye (ipsilateral) was injected with HSV-1 (KOS). The location of HSV-1, macrophages, and TNF-alpha was determined by fluorescence immunohistochemistry and the titer of virus was determined by plaque assay. Inhibition of TNF-alpha was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and depletion of macrophages was assessed by flow cytometry. In thalidomide-treated mice, TNF-alpha RNA levels were reduced in the SCN. Both SCN were infected by day 5 post inoculation (p.i.) and the titer of virus in the SCN contralateral to the side of injection was increased. The number of splenic macrophages was significantly reduced in clodronate-treated mice compared with controls. In macrophage-depleted mice, both SCN were infected at day 6 p.i. and the titer of virus in the SCN of these mice was increased at days 6 and 7 p.i. compared with controls. The titer of virus in the contralateral (uninoculated) eye of macrophage-depleted mice was increased at day 7 p.i. Fewer F4/80+ cells were observed in the SCN of macrophage-depleted mice. The results of these studies suggest that TNF-alpha plays a role in limiting virus replication in the SCN of euthymic BALB/c mice and that one source of TNF-alpha is macrophages.

Animals↗

On the adaptive detection of blood vessels in retinal images.

This paper proposes an automated blood vessel detection scheme based on adaptive contrast enhancement, feature extraction, and tracing. Feature extraction of small blood vessels is performed by using the standard deviation of Gabor filter responses. Tracing of vessels is done via forward detection, bifurcation identification, and backward verification. Tests over twenty images show that for normal images, the true positive rate (TPR) ranges from 80% to 91%, and their corresponding false positive rates (FPR) range from 2.8% to 5.5%. For abnormal images, the TPR ranges from 73.8% to 86.5% and the FPR ranges from 2.1% to 5.3%, respectively. In comparison with two published solution schemes that were also based on the STARE database, our scheme has lower FPR for the reported TPR measure.

Algorithms↗

Gait analysis of low-cost flexible-shank transtibial prostheses.

The latest lower-limb prosthetic designs have been incorporated with dynamic elastic response (DER) components to enhance prosthesis flexibility, which are suggested to be beneficial to gait. Although DER prosthetic. feet are preferred by most transtibial amputees and their benefits to gait are supported by some biomechanical studies, many are still utilizing the simple conventional solid ankle cushioned heel (SACH) designs because of the lower cost. The monolimb, a transtibial prosthesis with the socket and the shank molded from a single piece of thermoplastic material, perhaps is an alternative to DER feet for providing flexibility at the shank. In addition to shank flexibility, low cost and light weight are other characteristics of monolimbs. In spite of the potential benefits, little analysis has been done to examine the simple-structured monolimb prosthesis. The main aim of this study is to evaluate the gait and perception of unilateral transtibial amputees using a flexible elliptical-shank monolimb as compared to a thicker circular-shank monolimb and a conventional rigid-shank prosthesis. Results suggested that a properly designed monolimb may potentially offer similar functional advantages to the relatively expensive DER feet.

Adolescent↗

Extracellular ATP stimulates exocytosis via localized Ca(2+) release from acidic stores in rat pancreatic beta cells.

Three different methods, membrane capacitance (C(m)) measurement, amperometry and FM dye labeling were used to investigate the role of extracellular ATP in insulin secretion from rat pancreatic beta cells. We found that extracellular application of ATP mobilized intracellular Ca(2+) stores and synchronously triggered vigorous exocytosis. No influence of ATP on the readily releasable pool of vesicles was observed, which argues against a direct modulation of the secretory machinery at a level downstream of Ca(2+) elevation. The stimulatory effects of ATP were greatly reduced by intracellular perfusion of BAPTA but not EGTA, suggesting a close spatial association of fusion sites with intracellular Ca(2+) releasing sites. ATP-induced Ca(2+) transients and exocytosis were not blocked by thapsigargin (TG), by a ryanodine receptor antagonist or by dissipation of pH in acidic stores by monensin alone, but they were greatly attenuated by IP(3) receptor inhibition as well as ionomycin plus monensin, suggesting involvement of IP(3)-sensitive acidic Ca(2+) stores. Taken together, our data suggest that extracellular ATP triggers exocytosis by mobilizing spatially limited acidic Ca(2+) stores through IP(3) receptors. This mechanism may explain how insulin secretion from the pancreas is coordinated through diffusible ATP that is co-released with insulin.

Adenosine Triphosphate↗

Curcumin regulated shift from Th1 to Th2 in trinitrobenzene sulphonic acid-induced chronic colitis.

AIM: To investigate the therapeutic effects of curcumin (Cur) on trinitrobenzene sulphonic acid (TNBS)-induced colitis and the effects of Cur on the balance of Th1/Th2 cytokines. METHODS: Colitis was induced by TNBS and treated with Cur (30 mg/kg/d, ip), dexamethasone (Dex, 2 mg/kg/d), or Cur plus dexamethasone (Cur+Dex, 30 mg/kg/d Cur ip+2 mg/kg/d Dex,ip). mRNA in colon mucosa were detected by real-time quantitative polymerase chain reaction. Intracellular cytokines were detected by flow cytometry and concentrations of cytokines in sera were detected by enzyme-linked immunosorbent analysis. RESULTS: Both Cur and Dex improved body weight loss, ameliorated histological images and decreased macroscopic score and myeloperoxidase activity. Cur decreased the expression of Th1 cytokines (IL-12, IFN-gamma, TNF-alpha, IL-1) and increased the expression of Th2 cytokines (IL-4 and IL-10) in colon mucosa. Cur also increased the proportion of IFN-gamma/IL-4 in splenocytes and circulation. Dex and Cur+Dex decreased the expression of Th1 cytokines but could not increase the expression of Th2 cytokines and the proportion of IFN-gamma/IL-4. CONCLUSION: Cur exerted therapeutic effects on colitis by regulating the shift from Th1 to Th2.

Animals↗

Consequences of partial and total plantar fascia release: a finite element study.

BACKGROUND: Plantar fasciotomy, a common operative procedure to relieve chronic heel pain, has been suggested to decrease foot arch stability. A systematic evaluation of the biomechanical consequences of partial or total plantar fascia release is essential to the understanding of the biomechanical rationale behind these operative procedures. METHODS: A geometrical detailed three-dimensional (3-D) finite element (FE) model of the human foot and ankle, incorporating geometrical and contact nonlinearities, was constructed by 3-D reconstruction of MR images. Partial and complete plantar fascia releases were simulated to evaluate the corresponding biomechanical effects on load distribution of the bony, ligamentous, and encapsulated soft-tissue structures. RESULTS: Partial and total plantar fascia release may decrease arch height but did not necessarily cause total collapse of the foot arch even with additional dissection of the long plantar ligament. Operative release of the plantar fascia was compromised by increased strains of the plantar ligaments and intensified stress in the midfoot and metatarsal bones. Load redistribution among the centralized metatarsal bones and focal stress relief at the calcaneal insertion were predicted with different types of fasciotomy. CONCLUSIONS: The FE model suggested that plantar fascia release may provide relief of focal stress and therefore could relieve associated heel pain. However, these operative procedures may pose a risk to arch stability and clinically may produce dorsolateral midfoot pain. The initial strategy for treating plantar fasciitis should be nonoperative. If surgery is necessary, partial release of less than 40% of the fascia is recommended to minimize the effect on arch instability and maintain normal foot biomechanics.

Adult↗

Targeting maspin in endothelial cells to induce cell apoptosis.

The diseases of cancer remain as some of the leading causes of death in the industrialised world, although there are a multitude of technologies being used in the field of medical oncology to combat these diseases and scientific research continues to make discoveries to improve patient outcomes. Some of this research has focused on the maspin gene and protein. Maspin is predicted to be a unique serpin with tumour suppressor activity. Recent studies have explored the use of maspin as a therapeutic agent against cancer. In one study, maspin was found to inhibit cancer growth and metastasis in a breast cancer mouse model through a maspin DNA-liposome therapy. A separate study showed the ability of maspin to induce apoptosis in tumour-specific endothelial cells. Taken together, these studies demonstrate the potential use of maspin as a viable anticancer therapeutic agent.

Animals↗

[Construction of tumor cell-specific expression vector modulated by human telomerase reserse transcription gene core promoter].

AIM: To construct the tumor cell-specific expression vector modulated by human telomerase reserse transcription gene (hTERT) core promoter. METHODS: The hTERT gene core promoter fragment was amplified by PCR using the total genomic DNA from SKOV3 cells as template. The amplified gene fragment was subsequently cloned into pIRES2-EGFP vector. Then the expression vector modulated by hTERT core gene promoter was transfected into tumor cell lines, HO-8910, Hela and normal ECV304 cells through lipofectamine, respectively. The activity of reporter gene GFP was detected 48 h after transfection. RESULTS: There was significant transcriptional activity in 3 kinds of transfected tumor cells, while no transcriptional activity was detected in transfected normal cells. CONCLUSION: The hTERT core gene promoter has the tumor specificity, suggesting that the specific expression vector modulated by hTERT core gene promoter may be a novel and promising approach to the tumor treatment.

Cell Line, Tumor↗

[Construction of TRAIL gene eukaryotic expression vector modulated by hTERT gene core promoter and its effect on apoptosis of ovarian cancer cells].

AIM: To construct the TNF-related apoptosis inducing ligand(TRAIL) gene eukaryotic expression vector modulated by human telomerase reserse transcriptase (hTERT) gene core promoter and to study its effect on apoptosis of ovarian cancer cells. METHODS: Genomic RNA was extracted from human placenta tissues and the fragment of TRAIL was obtained by RT-PCR. The amplified gene fragment was subsequently cloned into hTERTpromoter-pIRES2-EGFP vector and CMV promoter-pIRES2-EGFP vector after sequencing. The hTERTpromoter-pIRES2-EGFP-TRAIL and CMV promoter-pIRES2-EGFP-TRAIL eukaryotic expression vectors were constructed respectively. The recombinant plasmids were transfected into ovarian carcinoma cell line, SKOV3, and the levels of mRNA were determined by RT-PCR. The cell cycle and apoptosis rate of SKOV3 cells were determined by FCM. RESULTS: The constructed two recombinant vectors were verified by restriction enzyme digestion analysis and DNA sequencing. After being transfected with two recombinant vectors, the growth of SKOV3 cells was strongly inhibited and apoptotic features appeared. CONCLUSION: The recombinant eukaryotic expression vector has been constructed successfully. TRAIL gene driven by hTERTpromoter can be obviously expressed in ovarian carcinoma SKOV3 cells, suggesting that the specific expression vector modulated by hTERT core gene promoter may be a novel and promising approach to the tumor treatment.

Apoptosis↗

[Farnesyl transferase inhibitors--a novel agent for breast cancer].

The ras family of proto-oncogenes are upstream mediators of several essential cellular signal transduction pathways involved in cell proliferation and survival. Point mutations of ras oncogenes result in constitutive activation of oncogenic Ras. The key step in post-translational processing of Ras protein is farnesylation by farnesyl transferase. Inhibitors of this enzyme were developed initially as a therapeutic strategy for Ras-mutated tumors. Moreover, it is now clear that farnesyl transferase inhibitors (FTIs) have activity independent of Ras, and show some effects on tumors without oncogenic ras mutations. Preclinical data show that FTIs can inhibit proliferation of breast cancer cells in vitro and in vivo, and phase II studies of FTI-R115777 in advanced breast cancer show encouraging results. Therefore, FTIs, used alone or with other agents, may be a novel therapeutic approach for breast cancer.

Antineoplastic Agents↗

[Safety and efficacy of intracoronary transplantation of G-CSF mobilized autologous peripheral blood stem cells in patients with acute myocardial infarction].

OBJECTIVE: To investigate the safety and efficacy of intracoronary transplantation of G-CSF mobilized autologous peripheral blood stem cells in patients with acute myocardial infarction (AMI). METHODS: Patients with AMI were randomly assigned to receive intracoronary PBSCs transplantation following bone marrow cells mobilization by granulocyte colony-stimulating factor (300-600 microg/day subcutaneously for 5 days) in addition to standard therapy (standard drug therapy and PCI, PBSCs transplantation group, n = 35) or standard therapy (standard drug therapy and PCI, n = 35). One day after G-CSF treatment was finished the patient's mononuclear cells were harvested by Baxter CS 3000 blood cell separator in a volume of 57 ml and then transferred into the infarct related artery by occluding the over the wire balloon and infusing artery through balloon center lumen. Complications during intervention and left ventricular function at baseline and 6 months thereafter were monitored. RESULTS: No severe side effects of G-CSF treatment could be observed. Malignant arrhythmias were not observed either. Left ventricular function was significantly improved 6 months after G-CSF mobilized autologous peripheral blood stem cell transplantation compared to baseline (global left ventricular function ejection fraction: 57.1 +/- 7.8 vs. 50.0 +/- 8.2%, P < 0.0001; WMSI: 1.101 +/- 0.118 vs. 1.219 +/- 0.190, P < 0.0001; left end-systolic volume: 52.6 +/- 20.3 vs. 63.8 +/- 23.9 ml, P = 0.01 and left end-diastolic volume: 119.2 +/- 30.3 vs. 134.2 +/- 36.7 ml, P = 0.07) while these parameters remained unchanged in the control group. CONCLUSION: The present study demonstrates that G-CSF mobilized autologous intracoronary PBSCs transplantation is a safe and feasible treatment for patients with AMI and global left ventricular function is improved and left ventricular remodeling attenuated at six-month follow-up.

Aged↗

[Alteration of expression of survivin in HL-60 cells treated with chemotherapeutic drugs].

Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, expressed in the most human cancers but not in terminally differentiated adult tissues, so survivin may be a target for tumor therapy. In addition, some scholars found that survivin expression is associated with the resistance in chemotherapy. To explore the relationship between survivin and drug-resistance, the alteration of survivin mRNA and protein of HL-60 cells treated with daunomycin (DNR), mitoxantrone (MIT) and arsenic trioxide (As2O3) was investigated, the expressions of survivin mRNA and survivin protein were detected on the first and third day by RT-PCR and Western blot, respectively. The results showed that survivin mRNA levels all decreased after the first day of treatment with drugs. It was decreased by 10% in DNR group, 40% (P < 0.01) in MIT group, and 25% (P < 0.01) in As2O3 group in comparison with control cells. In the third day, the survivin mRNA treated with DNR was up-regulated by 20% (P < 0.05), compared with the first day, and MIT was up-regulated by 65% (P < 0.01), but As2O3 was still down-regulated by 32% (P < 0.01). In Western blot, survivin protein level increased 14% after treated with DNR for three days, compared with the control cells, and 11% in MIT, but decreased by 82% in As2O3. It is concluded that after treatment with chemotherapeutic drugs, the survivin level descended at first day and then ascended obviously. This phenomenon may be associated with the resistance in chemotherapy for leukemia. On the other hand, As2O3 shows a different mechanism that may play a significant role to reverse resistance.

Antineoplastic Agents↗

[Dimensional differences in craniofacial morphologies of prepubescence Class II patients with deep and shallow mandibular antegonial notching].

OBJECTIVE: To identify certain craniofacial characteristics of untreated prepubescence Class II patients with deep and shallow mandibular notching. METHODS: 18 untreated preadolescent Class II patients with deep mandibular notching and 17 untreated preadolescent Class II patients with shallow mandibular notching were selected. Each subject's pretreatment lateral cephalogram was traced. Seventeen angular and eleven linear measurements were made. The means and standard deviations were calculated for each parameter. The significance of difference between mean values was evaluated by the Independent-Samples T test. Differences were considered statistically significant when the P value was 0.05 or less. RESULTS: There was no difference in ANB between two groups, but deep notch cases had more retrusive maxillary and mandibles with shorter maxillary and corpus. In vertical direction, subjects with a deep mandibular notch had a longer lower facial height and more vertically directed mandibular plane angle than did shallow notch cases, these may be caused by the increasing of alveolar height of maxillary, smaller ramus height and greater gonial angle. CONCLUSION: There were some differences in the craniofacial morphologies between deep and shallow notching groups of preadolescent Class II patients. Compared with shallow notching group, the mandibles with the deep notching rotated downward and backward and have more vertical directed tendency, but there have no obviously difference in horizontal relationship of maxillary and mandible between two groups.

Cephalometry↗

A robust design procedure for improvement of quality of lower-limb prosthesis.

Lower-limb prostheses are used to restore amputee's walking. Monolimb is one of the designs referring to socket and the shank being molded into one piece of thermoplastic material. Appropriate shank flexibility of a monolimb can improve gait of an amputee. However, during the fabrication, the variations of design variables are inevitably produced which may lead the unexpected shank deflection and directly influence on gait efficiency of an amputee. This paper presents a robust design procedure for improvement of quality of the monolimb by simultaneously minimizing performance variations caused by variations in design variables and bringing the mean value of performance on target. The robust design procedure embodies the integration of response surface methodology with genetic algorithms. Response surface models are developed for the responses of monolimb as functions of design variables over the region of interest and genetic algorithms are employed to find the robust solution. A robust design of monolimb is performed for an amputee subject and the results show that the robust design can design a "robust" monolimb which provides specified performance targets that are minimally sensitive to the variations of design variables. This indicates that robust design may have the potential application in improving the quality of the prescribed prosthesis.

Algorithms↗