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Biomedical subjects

J Zhang

Publications and source records attributed to J Zhang.

At least 289 records · Page 16Linked to original sources
PubMed2002

Expression of hypoxia-inducible factors in human endometrium and suppression of matrix metalloproteinases under hypoxic conditions do not support a major role for hypoxia in regulating tissue breakdown at menstruation.

BACKGROUND: Classical studies in monkeys suggested that menstruation results from vasoconstriction, hypoxia and necrosis. The heterodimeric hypoxia-inducible factor (HIF) complex is critical in oxygen homeostasis via increased stability of HIF-1alpha/2alpha monomers, and these act as markers of hypoxia. We hypothesized that focal hypoxia in perimenstrual endometrium results in locally increased matrix metalloproteinases (MMP), leading to tissue destruction. METHODS: HIF-1alpha, HIF-2alpha and HIF-1beta were immunolocalized in cycling endometrium. Endometrial stromal cells were cultured under hypoxic and normoxic conditions and MMP measured by zymography and Western blots. RESULTS: HIF-1alpha and HIF-2alpha were detected in only some endometrial samples, and not confined to the perimenstrual tissue. Where present, they were primarily cytoplasmic, not nuclear. HIF-1beta was localized in epithelium, leukocytes and some decidual cells. Cultured endometrial stromal cells responded to hypoxia with increased cellular HIF-1alpha and secreted vascular endothelial growth factor. ProMMP-1 and proMMP-3 production was reduced in response to hypoxia regardless of the steroidal milieu (no added steroids, estrogen or estrogen plus progesterone). Active MMP-2 and membrane type 1 MMP but not proMMP-2 or proMMP-9 production were also inhibited by hypoxia. CONCLUSIONS: These results do not support a role for hypoxia in the focally increased production and activation of MMP observed prior to and during menstruation.

Aryl Hydrocarbon Receptor Nuclear Translocator↗
PubMed2002

Decreased tissue inhibitor of metalloproteinase in the endometrium of women using depot medroxyprogesterone acetate: a role for altered endometrial matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in the pathogenesis of abnormal uterine bleeding?

BACKGROUND: Abnormal uterine bleeding is commonly associated with progestin-only contraceptives, including depot medroxyprogesterone acetate (DMPA), and remains the main reason why these agents are discontinued. Matrix metalloproteinases (MMP), enzymes which degrade specific extracellular matrix components, and leukocytes are implicated in menstruation. Alteration in endometrial MMP-9 and leukocytes has been described in users of other progestin-only contraceptives, suggesting a potential role in the pathogenesis of abnormal uterine bleeding. METHODS: This study describes the immunohistochemical localization of MMP-9, the tissue inhibitors of metalloproteinases (TIMP)-1, TIMP-2 and TIMP-3, and leukocytes [CD3+ T lymphocytes, CD68+ macrophages and CD56+ uterine natural killer cells (uNK cells)] in the endometrium of women using DMPA. Comparison is made with perimenstrual endometria from normal cycling women. RESULTS: Similar to the perimenstrual period, an influx of MMP-9 positive cells (identified as neutrophils and CD3+ T cells on the basis of dual immunofluorescence), macrophages and uNK cells was observed in the endometrium of DMPA users. However, significantly more endometrial T lymphocytes were observed in DMPA users. Immunoreactive TIMP, present in all endometrial compartments, demonstrated a significantly decreased immunostaining intensity score in endometrial epithelium (TIMP-1 and TIMP-2), stroma (TIMP-1, TIMP-2 and TIMP-3), endothelium (TIMP-1 and TIMP-2) and vascular smooth muscle (TIMP-1) of DMPA users compared with controls. No correlation was observed between the parameters studied and bleeding patterns reported by subjects. CONCLUSIONS: These findings provide additional evidence for the importance of the MMP/TIMP balance in the loss/maintenance of endometrial integrity and in the complex pathological mechanisms involved in the troubling side-effect of menstrual bleeding disturbance.

Contraceptive Agents, Female↗
PubMed2002

Penetration of linezolid into bone, fat, muscle and haematoma of patients undergoing routine hip replacement.

Twelve patients undergoing total hip replacement were given 600 mg of linezolid as a 20 min iv infusion along with conventional prophylaxis of 1 g of cefamandole immediately before surgery. Routine total hip arthroplasty was carried out, and at timed intervals during surgery samples of bone, fat, muscle and blood were collected for assay by high-performance liquid chromatography analysis. Samples of the haematoma fluid that formed around the operation site and further blood samples for assay were also collected at timed intervals following the operation. The penetration of linezolid into bone was rapid, with mean concentrations of 9.1 mg/L (95% CI 7.7-10.6 mg/L) achieved at 10 min after the infusion, decreasing to 6.3 mg/L (95% CI 3.9-8.6 mg/L) at 30 min. Correction for the simultaneous blood concentrations gave mean values for bone penetration of 51% at 10 min, 60% at 20 min and 47% at 30 min. Although the penetration of linezolid into fat was also rapid, mean concentrations and degree of penetration were c. 60% of those in bone; at 10 min they were 4.5 mg/L (95% CI 3.0-6.1 mg/L; penetration 27%); at 20 min they were 5.2 mg/L (95% CI 4.0-6.4 mg/L; penetration 37%); and at 30 min, 4.1 mg/L (95% CI 3.3-4.8 mg/L; penetration 31%). For muscle the corresponding values were 10.4 mg/L (95% CI 8.1-12.7 mg/L; penetration 58%) at 10 min, 13.4 mg/L (95% CI 10.2-16.5 mg/L; penetration 94%) at 20 min and 12.0 mg/L (95% CI 9.2-14.8 mg/L; penetration 93%) at 30 min. Mean concentrations of linezolid in the haematoma fluid drained from around the operation site were 8.2 mg/L at 6-8 h and 5.6 mg/L at 10-12 h after the infusion, and 7.0 mg/L at 2-4 h following a second 600 mg infusion given 12 h post-operatively. We conclude that linezolid exhibits rapid penetration into bone, fat and muscle of patients undergoing hip arthroplasty, to achieve levels in excess of its MIC for susceptible organisms (< or=4 mg/L); therapeutic concentrations were maintained in the haematoma fluid that surrounds the operation site for >16 h.

Acetamides↗
PubMed2002

An assessment of the potential for reducing future combat deaths through medical technologies and training.

BACKGROUND: We examined clinical records of combat casualties that died subsequent to reaching a medical treatment facility in an effort to determine whether new medical technologies or enhanced training might contribute to a reduction in combat deaths. METHODS: Hospital records of 210 fatal combat casualties were independently reviewed by four surgeons. The surgeons assessed each fatality to determine whether it would be preventable if the trauma were sustained today and treated with currently available technology and training. RESULTS: In 8% of the cases, the four surgeons independently agreed that the deaths would be possibly preventable if the same traumas were incurred today. In an additional 17% of the cases, three of the four surgeons judged the deaths to be possibly preventable today. Causes of death viewed as most likely to be salvageable today included hemorrhage, severe burns, pulmonary edema, and sepsis. The medical technologies most often mentioned to have a potentially lifesaving effect were ventilators/respirators, computed tomographic scanners, ultrasound, and antibiotics. Areas of training most often mentioned to have a potential impact on the salvageability of the trauma cases reviewed were damage control, ventilator management, liver packing, respiratory distress management, and burn management. CONCLUSION: Surgeons reviewing records of past combat deaths indicated that reductions in the incidence of combat deaths through deployment of improved medical technologies and training is possible. Deployment of the noted technologies and proficiency in the cited training has the potential for reducing deaths by 8% to 25% when compared with the died-in-hospital incidence among casualties in the last sustained conflict.

Adult↗
PubMed2002

Robust relational parsing over biomedical literature: extracting inhibit relations.

We describe the design of a robust parser for identifying and extracting biomolecular relations from the biomedical literature. Separate automata over distinct syntactic domains were developed for extraction of nominal-based relational information versus verbal-based relations. This allowed us to optimize the grammars separately for each module, regardless of any specific relation resulting in significantly better performance. A unique feature of this system is the use of text-based anaphora resolution to enhance the results of argument binding in relational extraction. We demonstrate the performance of our system on inhibition-relations, and present our initial results measured against an annotated text used as a gold standard for evaluation purposes. The results represent a significant improvement over previously published results on extracting such relations from Medline: Precision was 90%, Recall 57%, and Partial Recall 22%. These results demonstrate the effectiveness of a corpus-based linguistic approach to information extraction over Medline.

Abstracting and Indexing↗
PubMed2002

Grafting sulfobetaine monomer onto the segmented poly(ether-urethane) surface to improve hemocompatibility.

Polyurethanes are widely used as blood-contacting biomaterials, due to their good biocompatibility and mechanical properties. Nevertheless, their blood compatibility is still not adequate for more demanding applications. Surface modification is an effective way to improve the hemocompatibility for biomaterials. The purpose of the present study was to synthesize a novel nonthrombogenic biomaterial by modifying the surface of polyurethane. Ozonization was used to introduce active peroxide groups onto the segmented poly(ether-urethane) (SPEU) film surface and graft polymerization of N,N'-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate (DMAPS), a sulfobetaine structure, onto the ozone-activated SPEU surface was conducted. The SPEU-g-PDMAPS film was characterized by ATR-FTIR, XPS, and contact angle measurements. ATR-FTIR and XPS confirmed the graft polymerization. The grafted film possessed a relatively hydrophilic surface, as revealed by contact angle measurement. The blood compatibility of the grafted films was evaluated by a platelet-rich plasma (PRP) adhesion study and scanning electron microscopy, using SPEU film as the reference. No platelet adhesion was observed for the grafted films incubated with PRP at 37 degrees C for 60 and 180 min. This new sulfobetaine structure grafted biomaterial might have potential for biomedical applications.

Betaine↗
PubMed2002

Morphology of poly(methacrylic acid)/poly(N-isopropyl acrylamide) interpenetrating polymeric networks.

The morphology of interpenetrating polymeric networks (IPNs) composed of the temperature-sensitive poly(N-isopropyl acrylamide) (PNIPAAm) and the pH-sensitive poly(methacrylic acid) (PMAA) were investigated by scanning electron microscopy (SEM). The IPN hydrogels were prepared by a sequential UV polymerization method. SEM studies were conducted on IPN hydrogel samples dried by different methods, and the influence on the IPN structure was discussed. The environmental conditions induced morphological changes for these dual sensitive IPN hydrogels which were studied by cryogenic SEM, when the gels were analyzed in their wet state. The results showed that the porous size in the IPN was strongly influenced by the environmental pH and temperature. Decrease in pH and increase in temperature resulted in significant pore size decrease for the swollen IPNs hydrogels.

Acrylic Resins↗
PubMed2002

Identification of cis-DNA regions controlling Bmp4 expression during tooth morphogenesis in vivo.

Epithelial-mesenchymal interactions are required for tooth formation. Bone morphogenetic protein 4 (Bmp4) is a crucial signaling molecule during this process. For better understanding of the role of the Bmp4 gene during tooth development, we studied the mechanisms that control its temporal and spatial expression during development. Using a transgenic approach, we determined that the domains which controlled Bmp4 expression in epithelium-derived ameloblasts were located in the region between 0.26 kb and 1.1 kb of the murine Bmp4 promoter. In contrast, the domains controlling Bmp4 expression in mesenchyme-derived odontoblasts and pulp cells existed in other regions of the Bmp4 gene. We have also demonstrated that the domains controlling Bmp4 expression in primordial tooth cells differ from those controlling Bmp4 expression in mature tooth tissues. The determination of unique domains by controlling the expression of the Bmp4 gene suggests that different transcriptional factors regulate the Bmp4 level at different stages during tooth morphogenesis.

Ameloblasts↗
PubMed2002

Variability and lack of predictive ability of asthma end-points in clinical trials.

While a consensus definition of the clinical parameters important in asthma control exists, an adequate objective definition of a response to asthma treatment and parameters for prediction of that response remain undefined. Given that asthma is a complex biological disease and that different parameters may measure dissimilar aspects of the disease status, this study assessed the relationship among several end-points of asthma control, and attempted to select a combination of variables measured before (baseline characteristics) or early in asthma therapy which would be predictive of a long-term clinical response. Data from two previously reported clinical studies which included montelukast, inhaled beclomethasone, and placebo in mild-to-moderate asthmatics (n=1,576) were analysed. The forced expiratory volume in one second (FEV1), daily symptoms score (DSS), beta-agonist use, and morning peak expiratory flow (PEFAM) were recorded during the baseline period and throughout the 12-week treatment period. For the long-term response, as measured during the last 9 weeks of treatment, there was a large within-patient variability and no more than a moderate correlation between the changes in FEV1 and PEFAM; DSS and FEV1; and DSS and beta-agonist use. The overall predictive values for FEV1 and DSS were 70-80%. The results showed that multiple measurements over a length of time are needed to establish a more complete profile of response, and that demographic and early treatment responses had a small but inadequate ability to predict future response. This study demonstrates the complex relationship among asthma end-points and the difficulty of reliably estimating long-term response using common, surrogate clinical markers of asthma control.

Adolescent↗
PubMed2001

A synthetic pentasaccharide with GTPase activity.

The design, synthesis, and preliminary evaluation of the first example of synthetic pentasaccharide (1) that shows marked rate enhancement and specificity for the hydrolysis of GTP to GDP and orthophosphate (OP) are reported. At the concentration ratios of GTP/1 = 3.6 and GTP/Mg(2+) = 1 (pH 7.1, 50 degrees C), a rate enhancement of about 500-fold was obtained.[reaction: see text]

Carbohydrate Conformation↗
PubMed2001

Effects of noise on the off rate of Ca(2+) binding proteins in a coupled biochemical cell system.

We investigated numerically the kinetic properties of calcium binding proteins by using a three-calcium store model and discussed the response of a two-way coupled biochemical cell system, whose subsystems were coupled via diffusion-like cytosolic calcium transfer through gap junctions, to the external stimulation. When we used noise to modulate the off rate of the Ca(2+) binding proteins in simulation, an SR-like phenomenon of synchronous oscillations is observed. In addition, the interaction involving noise, coupling and the dynamics of Ca(2+) binding proteins is discussed.

Animals↗
PubMed2001

Activation of the NPTA element of the CYP2A3 gene by NFI-A2, a nasal mucosa-selective nuclear factor 1 isoform.

The aim of this study was to determine whether the NPTA element of the olfactory mucosa-predominant CYP2A3 gene can be activated by NFI-A2, a recently identified member of the nuclear factor 1 family of transcription factors. Isoform-specific RNA-PCR confirmed that NFI-A2 is mainly expressed in rat olfactory mucosa. A full-length NFI-A2 cDNA was isolated from a cDNA library of rat olfactory mucosa and was used for preparation of a construct encoding a fusion protein of NFI-A2 with the yeast GAL4 activation domain. Expression of the fusion protein in yeast was detected with an antibody to NFI-A. The fusion protein activated the expression of a LacZ reporter gene in yeast one-hybrid assays with a reporter construct containing the NPTA element, but not with other constructs lacking the NPTA element. These findings suggest that NFI-A2 may be involved in the tissue-selective transcriptional activation of the CYP2A3 gene in the olfactory mucosa.

Amino Acid Sequence↗
PubMed2001

Genetically encoded reporters of protein kinase A activity reveal impact of substrate tethering.

The complexity and specificity of many forms of signal transduction are widely suspected to require spatial microcompartmentation of protein kinase and phosphatase activities, yet current relevant imaging methods such as phosphorylation-specific antibodies or fluorescent peptide substrates require fixation or microinjection and lack temporal or spatial resolution. We present a genetically encoded fluorescent reporter for protein kinase A (PKA) consisting of fusions of cyan fluorescent protein, a phosphoamino acid binding domain (14-3-3tau), a consensus substrate for PKA, and yellow fluorescent protein. cAMP elevations cause 25-50% changes in the ratios of yellow to cyan emissions in live cells caused by phosphorylation-induced changes in fluorescence resonance energy transfer. The reporter response was accelerated by tethering to PKA holoenzyme and slowed by localization to the nucleus. We demonstrate that deliberate redistribution of a substrate or colocalizing a substrate and PKA can modulate its susceptibility to phosphorylation by the kinase. The successful design of a fluorescent reporter of PKA activity and its application for studying compartmentalized and dynamic modulation of kinases lays a foundation for studying targeting and compartmentation of PKA and other kinases and phosphatases.

Amino Acid Sequence↗
PubMed2001

The intersectin 2 adaptor links Wiskott Aldrich Syndrome protein (WASp)-mediated actin polymerization to T cell antigen receptor endocytosis.

Induction of T cell antigen receptor (TCR) endocytosis has a significant impact on TCR signaling and T cell behavior, but the molecular interactions coordinating internalization of the activated TCR are poorly understood. Previously we have shown that TCR endocytosis is regulated by the Wiskott Aldrich Syndrome protein (WASp), a cytosolic effector which, upon interaction with the cdc42 Rho GTPase, couples TCR engagement to Arp 2/3 complex-mediated actin polymerization. Here we report that WASp associates in T cells with intersectin 2, an endocytic adaptor containing multiple domains including a Dbl homology (DH) domain with the potential to activate Rho GTPases. Intersectin 2 association with WASp increases after TCR engagement, and its overexpression in Cos-7 cells induces WASp translocation to endocytic vesicles within which intersectin 2 colocalizes with both WASp and cdc42. Intersectin 2, but not a DH domain-deleted (DeltaDH) form of intersectin 2, and stimulation via the TCR also trigger the activation of cdc42. Induction of TCR internalization is also augmented by intersectin 2 and severely impaired by latrunculin B treatment. Thus, intersection 2 appears to function cooperatively with WASp and cdc42 to link the clathrin endocytic machinery to WASp-mediated actin polymerization and ultimately to occupancy-induced TCR endocytosis.

Actins↗
PubMed2001

Long plasma channels generated by femtosecond laser pulses.

Generation of a long plasma channel by femtosecond laser pulses is investigated. The results show that the balance between the nonlinear self-focusing of the laser beam and plasma defocusing forms a long plasma channel, which guides the laser beam to propagate a long distance in air. This phenomenon can be used to trigger lightning.

Journal Article↗
PubMed2001

Assays of methylenetetrahydrofolate reductase and methionine synthase activities by monitoring 5-methyltetrahydrofolate and tetrahydrofolate using high-performance liquid chromatography with fluorescence detection.

We developed a method for assays of methylenetetrahydrofolate reductase and methionine synthase activities by monitoring their products of 5-methyltetrahydrofolate (5-CH(3)-H(4)folate) and tetrahydrofolate (H(4)folate) directly, using high-performance liquid chromatography with fluorescence detection. Folate derivatives and enzymes were stable in the assay process. No reagents in the assay mixture were found to disturb the separation and detection of both H(4)folate and 5-CH(3)-H(4)folate in our assay system. The detection limit of this method was less than 20 nM H(4)folate or 5-CH(3)-H(4)folate in the enzyme assay system. This analytical method, therefore, has a sensitivity high enough to obtain accurate parameters of Michaelis-Menten kinetics and for assays of crude extracts from various biological samples. In addition, the analytical procedure is very simple and economical; it may be a useful tool for studying methylenetetrahydrofolate reductase and methionine synthase activities.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2001

A dual role for the zebrafish unplugged gene in motor axon pathfinding and pharyngeal development.

On their way toward their synaptic targets, motor growth cones encounter multiple choice points, where they are confronted with trajectory choices. We have previously shown that the zebrafish unplugged gene acts as a somite-derived cue controlling pathway choice of primary motor axons. Here, we demonstrate that this trajectory choice is not exclusively controlled by a single unplugged-dependent process, but depends on the coordinated function of additional cues. We also show that secondary motor neurons, most similar to those in birds and mammals, depend on the unplugged gene to navigate a choice point, suggesting that primary and secondary motor neurons share common mechanisms controlling axonal path selection. Moreover, we show that the unplugged gene plays an additional role guiding secondary motor axons through a single segmental nerve. Finally, we report that unplugged larvae display a striking pharyngeal arch defect, consistent with a dual function of the unplugged gene in axonal guidance and cell motility.

Alleles↗