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Biomedical subjects

M Zhang

Publications and source records attributed to M Zhang.

At least 1,063 records · Page 59Linked to original sources
PubMedDate not supplied

Protein engineering and NMR studies of calmodulin.

The calcium regulatory protein calmodulin (CaM) plays a role as an on-off switch in the activation of many enzymes and proteins. CaM has a dumbbell shaped structure with two folded domains, which are connected by a flexible linker in solution. The calmodulin-binding domains of the target proteins are contained in 20 residue long amino acid sequences, that share no obvious amino acid sequence homology. In this contribution, we discuss the features of CaM, which allow it to be rather promiscuous, and bind effectively to all these distinct domains. In particular, we describe the role of the methionine-rich hydrophobic surfaces of the protein in providing a malleable and sticky surface for binding many hydrophobic peptides. The enzyme activation properties of various Met --> Leu mutants of CaM are discussed. In addition, the role of the flexible linker region that connects the two domains is also analyzed. Finally, we describe various NMR and spectroscopic experiments that aid in determining the CaM-bound structures of synthetic peptides containing various CaM-binding domains. All structures analyzed to date are alpha-helical when bound to CaM, and they interact with CaM only through amino acid sidechains. This form of protein-protein interaction is rather unique, and may contribute to CaM's capacity to bind effectively to such a wide range of distinct partners.

Amino Acid Sequence↗
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Identification of a potential HIV-induced source of bystander-mediated apoptosis in T cells: upregulation of trail in primary human macrophages by HIV-1 tat.

The induction of apoptosis in T cells by bystander cells has been repeatedly implicated as a mechanism contributing to the T cell depletion seen in HIV infection. It has been shown that apoptosis could be induced in T cells from asymptomatic HIV-infected individuals in a Fas-independent, TNF-related apoptosis-inducing ligand (TRAIL)-dependent manner if the cells were pretreated with anti-CD3. It has also been shown that T cells from HIV-infected patients were even more sensitive to TRAIL induction of apoptosis than they were to Fas induction. Recently, it has been reported that in an HIV-1 SCID-Hu model, the vast majority of the T cell apoptosis is not associated with p24 and is therefore produced by bystander effects. Furthermore, few apoptotic cells were associated with neighboring cells which were positive for either Fas ligand or TNF. However, most of the apoptotic cells were associated with TRAIL-positive cells. The nature of these TRAIL-positive cells was undetermined. Here, we report that HIV infection of primary human macrophages switches on abundant TRAIL production both at the RNA and protein levels. Furthermore, more macrophages produce TRAIL than are infected by HIV, indicating that a bystander mechanism may, at least in part, upregulate TRAIL. Exogenously supplied HIV-1 Tat protein upregulates TRAIL production by primary human macrophages to an extent indistinguishable from infection. The results suggest a model in which HIV-1-infected cells produce extracellular Tat protein, which in turn upregulates TRAIL in macrophages which then can induce apoptosis in bystander T cells.

Apoptosis↗
PubMedDate not supplied

Differences in horizontal, neoclassical facial canons in Chinese (Han) and North American Caucasian populations.

To better our ability to analyze the facial disproportions of patients of Chinese ancestry, we compared the validity of four neoclassical canons of facial proportion in Chinese and North American Caucasians populations. We tested the frequency of four horizontal facial canons and their eight variations in 206 healthy adults (105 males and 101 females, 18-25 years old) belonging to the predominant ethnic group (Han: 400 million) of the Chinese population, and compared them to those of 103 healthy young North American Caucasian adults. The nose width corresponded to one-quarter of the face width (the nasofacial canon) significantly more frequently in Chinese participants (51.5%) than in Caucasian adults (36.9%). The nose was narrower than one-quarter of the face width in 38.8% of North American Caucasians and in 21.8% of Chinese; this difference was also statistically significant. In defiance of the naso-oral canon, the mouths of Chinese people were significantly more often narrower than 1.5 times the nose width (71.8%), while in North American Caucasian ethnics the mouth was significantly more frequently wider (60.2%).

Adult↗
PubMedDate not supplied

Neuronal switching of sensorimotor transformations for antisaccades.

The influence of cognitive context on orienting behaviour can be explored using the mixed memory-prosaccade, memory-antisaccade task. A symbolic cue, such as the colour of a visual stimulus, instructs the subject to make a brief, rapid eye movement (a saccade) either towards the stimulus (prosaccade) or in the opposite direction (antisaccade). Thus, the appropriate sensorimotor transformation must be switched on to execute the instructed task. Despite advances in our understanding of the neuronal processing of antisaccades, it remains unclear how the brain selects and computes the sensorimotor transformation leading to an antisaccade. Here we show that area LIP of the posterior parietal cortex is involved in these processes. LIP's population activity turns from the visual direction to the motor direction during memory-antisaccade trials. About one-third of the visual neurons in LIP produce a brisk, transient discharge in certain memory-antisaccade trials. We call this discharge 'paradoxical' because its timing is visual-like but its direction is motor. The paradoxical discharge shows, first, that switching occurs already at the level of visual cells, as previously proposed by Schlag-Rey and colleagues; and second, that this switching is accomplished very rapidly, within 50 ms from the arrival of the visual signals in LIP.

Animals↗
PubMedDate not supplied

Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption.

Vascular endothelial growth factor (VEGF) is an important mediator of the intense angiogenesis which is characteristic of glioblastoma. While genetic manipulation of VEGF/VEGF receptor expression has previously been shown to inhibit glioblastoma growth, to date, no study has examined the efficacy of pharmacologic blockade of VEGF activity as a means to inhibit intracranial growth of human glioblastoma. Using intraperitoneal administration of a neutralizing anti-VEGF antibody, we demonstrate that inhibition of VEGF significantly prolongs survival in athymic rats inoculated in the basal ganglia with G55 human glioblastoma cells. Systemic anti-VEGF inhibition causes decreased tumor vascularity as well as a marked increase in tumor cell apoptosis in intracranial tumors. Although intracranial glioblastoma tumors grow more slowly as a consequence of anti-VEGF treatment, the histologic pattern of growth suggests that these tumors adapt to inhibition of angiogenesis by increased infiltration and cooption of the host vasculature.

Animals↗
PubMedDate not supplied

Nuclear magnetic resonance studies of the structure of B50/neuromodulin and its interaction with calmodulin.

B50/neuromodulin is a neuronal phosphoprotein that is found in association with the inner membrane of nerve cells. In this work, we have studied the structure of bovine B50 in aqueous solution (pH 7.5) by 1H nuclear magnetic resonance (NMR) spectroscopy and our results indicate that B50 is an unstructured protein under these conditions. One-dimensional 1H-NMR titration studies of the interaction between B50 and calmodulin (CaM) have shown that B50 does not interact with (or) interacts very weakly with apo-CaM in solution; neither does B50 interact with Ca(2+)-CaM. These NMR data are consistent with an earlier observation that B50 is not capable of binding apo-CaM in vitro unless some nonionic detergent is present. We have also detected aromatic NMR peaks for a new posttranslational modification that might involve the His residues of the protein. The interaction of a 14-residue peptide (I38-L51) encompassing the CaM-binding domain of B50 with CaM was also studied by NMR. We have found from two-dimensional transferred nuclear Overhauser enhancement experiments that the B50 peptide binds weakly to apo-CaM in an alpha-helical conformation; the alpha-helix appears to be induced by the binding of the peptide to apo-CaM.

Amino Acid Sequence↗
PubMedDate not supplied

Ozone-induced augmentation of eicosanoid metabolism in human nasal mucosa in vitro.

The increase in airway responsiveness induced by ozone exposure is associated with airway inflammation as evidenced by an increase in inflammatory mediators such as cyclooxygenase and lipoxygenase product formation found in bronchoalveolar lavage fluid, nasal lavage fluid and epithelial cell cultures. To examine eicosanoid metabolism after exposure to ozone, human nasal mucosa derived from 21 patients undergoing surgical therapy for chronic nasal obstruction was cultured with a specially designed in vitro organ culture device and exposed to 0.1 ppm ozone for 24 h. Eicosanoid formation was analyzed by the release of cyclooxygenase and lipoxygenase products into the culture supernatant (measured by enzyme immunoassay). Experiments revealed ozone-induced increases in cyclooxygenase and lipoxygenase product formation with significant increases in prostaglandin F2alpha (PGF2alpha), thromboxane B2 (TXB2) and leukotriene B4 (LTB4) (p<0.05). Moreover, we found an increase in the concentration of LTC4/D4/E4 in the supernatant of ozone-exposed mucosal samples, which however does not reach statistical significance. There was a significant correlation between PGF2alpha and TXB2 (r = 0.71, p<0.001). These results extend previous results from in vivo chamber studies suggesting that the mode of action of ozone is an oxidative reaction resulting in an increased activity of arachidonic acid metabolism in the airways with a subsequent increase in the concentration of cyclooxygenase and lipoxygenase products.

Eicosanoids↗
PubMedDate not supplied

Mathematical modeling of phosphorus losses from land application of hog and cattle manure.

Mathematical models may provide a means to estimate phosphorus (P) losses from land application of manure. Phosphorus losses typically occur during brief episodes of runoff and erosion. Models must be able to simulate P losses during these episodes by representing the basic chemical, physical, and biological processes by which these losses occur. The mathematical model ecosys combines dynamic distributed flow of solutes and nonsolutes through runoff and erosion with convective-dispersive transport of solutes, and both biologically and thermodynamically driven transformations between solutes and nonsolutes. This model was tested against P lost in runoff, erosion, and leachate measured during 90 min of controlled rainfall at 65 mm h(-1) on soils from six sites at which different rates of manure had been applied over the previous 3 to 6 yr. Transport and transformation kinetics in the model enabled it to simulate changes of dissolved inorganic phosphorus (DIP) in runoff from >1.0 to <0.05 mg L(-1) and changes of total phosphorus (TP) in sediment from 15 to 3 mg L(-1) measured during controlled rainfall on soils with diverse P contents. Results from 60-yr model runs using these kinetics with different application rates of cattle manure indicated that (i) a positive interaction exists between annual rainfall and application rate on P losses and (ii) rates greater than 30 Mg ha(-1) yr(-1) would cause TP concentrations in water leaving the site to rise above acceptable limits. The interaction between rainfall and rate suggests that P losses from manure application at any site should be assessed under the upper range of likely rainfall intensities.

Agriculture↗
PubMedDate not supplied

Preparation and properties of polyurea microcapsules with non-ionic surfactant as emulsifier.

Polyurea microcapsules containing oily substances were prepared by using cyanate and polyamine as the monomers with non-ionic surfactant as the emulsifiers. Results showed that TDI-DETA microcapsules had the best stability. The mean diameter decreased and the size distribution curves became narrower and sharper as the stirring speed and the emulsifier concentration during emulsification increased. Addition of Tween 80 to aqueous solution containing OP led to an increase in microcapsule diameter and wider distribution of microcapsules due to the changes in interfacial tension. The isoelectric point of the polyurea microcapsules was found to be pH 5.8.

Capsules↗
PubMedDate not supplied

Study on polyamide microcapsules containing oily liquids.

Oily liquids were microencapsulated within polyphthalamide membranes with dodecyl sulphonate sodium (DSS) as an emulsifier. The mean diameter and the distribution, as well as the zeta-potential, of the microcapsules were analysed. It was found that the mean diameter decreases with an increase in stirring speed and emulsifier concentration during the emulsification step. The addition of DSS to aqueous phase resulted in a decrease in zeta-potential of the microcapsules.

Capsules↗
PubMedDate not supplied

Effect of operation variables and monomers on the properties of polyamide microcapsules.

Oil containing microcapsules were prepared by using phthaloyl dichloride as an oil-soluble monomer and diethylene triamine (DETA) as a water-soluble monomer. The diameter of the microcapsules decreased and their distribution became narrower and sharper as the emulsifying time was increased within the initial period of 45 s, beyond which no appreciable changes in the diameter and its distribution were observed. Once DETA was introduced into the aqueous solution to initiate the interfacial polycondensation reaction, reducing the stirring speed diminished the formation of the membrane fragments, but resulted in an increase in the microcapsule diameter. This indicates that the strength of the initial membrane is not strong enough to prevent the microcapsules from coalescing. Raising the volume fraction of the dispersed phase led to a larger diameter and a wider distribution of the microcapsules. When ortho-, meta- or para-phthaloyl dichloride was used as the oil-soluble monomer, both the diameter and the zeta-potential of the microcapsules decreased in the order: ortho-->meta-->para-, indicating that the steric effect of the monomers plays an important role in the microencapsulation process.

Capsules↗
PubMedDate not supplied

Apoptosis induction in fludarabine resistant malignant B-1 cells by G2-M cell cycle arrest.

A malignant B-1 cell line from a mouse model of CLL was resistant to fludarabine, but could be induced to undergo apoptosis by mitotic spindle inhibitors, colcemid or nocodazole, which blocked these cells in the G2-M phases of cell cycle prior to apoptosis induction. Bax mRNA levels increased with relative constitutive expression of bcl-2 mRNA levels. The mRNA levels of B-cell-specific-activator-protein (BSAP) decreased with colcemid treatment. This study shows that mitotic spindle inhibitors can induce apoptosis in fludarabine-resistant malignant B-1 cells by altering levels of bax/ bcl-2 ratio and BSAP which play different roles in cell cycle regulation and apoptosis induction.

Animals↗
PubMedDate not supplied

Expression of variant CD44 containing variant exon v8-10 in gallbladder cancer.

We studied the Cd44v8-10 expression in gallbladder cancer immunohistochemically. Eighteen of 37 gallbladder cancer tissues expressed CD44v8-10. There were significant correlations between CD44v8-10 immunoreactivity and perineural invasion, venous invasion, and lymph node metastasis. Patients with CD44v8-10-positive tumors showed poor prognoses, whereas those with CD44v8-10-negative tumors had favorable prognoses. A multivariate analysis using the Cox regression model showed the immunoreactivity of CD44v8-10 to be an independent prognostic indicator of gallbladder cancer. The results suggest that CD44v8-10 expression may be a biologic marker of prognostic significance in gallbladder cancer.

Antigens, CD↗
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State-of-the-art research in lower-limb prosthetic biomechanics-socket interface: a review.

Scientific studies have been conducted to quantify attributes that may be important in the creation of more functional and comfortable lower-limb prostheses. The prosthesis socket, a human-machine interface, has to be designed properly to achieve satisfactory load transmission, stability, and efficient control for mobility. The biomechanical understanding of the interaction between prosthetic socket and the residual limb is fundamental to such goals. The purpose of this paper is to review the recent research literature on socket biomechanics, including socket pressure measurement, friction-related phenomena and associated properties, computational modeling, and limb tissue responses to external mechanical loads and other physical conditions at the interface. There is no doubt that improved biomechanical understanding has advanced the science of socket fitting. However, the most recent advances in the understanding of stresses experienced at the residual limb have not yet led to enough clinical consensus that could fundamentally alter clinical practice. Efforts should be made to systematically identify the major discrepancies. Further research should be directed to address the critical controversies and the associated technical challenges. Developments should be guided to offer clinicians the quantification and visualization of the interaction between the residual limb and the prosthetic socket. An understanding of comfort and optimal load transfer as patterns of socket interface stress could culminate in socket design expert systems.

Amputation Stumps↗
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A study of the stability of W/O/W multiple emulsions.

The stability of W/O/W emulsions has been studied in batch agitators. The surfactants suitable for W/O/W emulsions were screened and the factors affecting the emulsion stability were also studied. Results showed that polyamine E644 was an excellent emulsifier for W/O emulsions since the emulsion stabilized by it has not only good stability but also shows smaller swelling. The stability of the emulsion increases with increase in membrane viscosity and concentration of surfactant, but decreases with increase in concentration of the internal reagent in the internal phase and the carriers in the membrane. Raising the agitation speed and the time for preparing the W/O emulsion is beneficial to membrane stability due to formation of smaller internal droplets, but raising the speed for dispersing the W/O emulsion in the external phase results in an increase in membrane breakage.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

Beta-amyloid precursor protein accumulates in axons around hematogenous metastases of the human brain: immunohistochemical observations.

Axonal changes which develop around hematogenous metastases of the human brain were studied by immunohistochemistry using a monoclonal antibody to beta-amyloid precursor protein (beta APP) and the ABC method combined with glucose-glucose oxidase technique and nickel enhancement. The metastases were obtained from 18 autopsy cases with pulmonary carcinomas and 6 control cases without clinical history or gross pathology of brain diseases. beta APP immunoreactive material was present in distended axons around all the investigated metastases. Such immunoreactive axons were located close to the invading tumor cells. No immunoreactivity was seen in 5 of the 6 controls. Our investigation indicates that axonal transport is disturbed around metastases, made visible by the accumulation of beta APP immunoreactive material. The axonal dysfunction may well influence the clinical symptoms in cases with brain metastases.

Adult↗