Resolution 'scaling law' in MRI of articular cartilage.
Explore the source record for details and available documents.
Cartilage, Articular↗
Biomedical subjects
Y Xia
Publications and source records attributed to Y Xia.
Functional duality of merlin: a conundrum of proteome complexity.
Merlin and ezrin proteins belong to the same gene family, i.e., MERM containing merlin, ezrin radixin and moesin. Members of this family possess an extensive homology in their amino acid sequences. It has been shown that merlin is a tumor suppressor, while ezrin is a promoter in tumor progression. The expression of these two proteins is commonly found inversely proportional to each other in cancer cells, i.e. down-regulation of merlin concomitant with over-expression of ezrin and vice versa. However, when determining merlin and ezrin in ovarian carcinoma cells, we have observed that both merlin and ezrin could be over-expressed simultaneously in some ovarian cancer (OVCA) cell lines and OVCA ascites cells, suggesting that merlin could be an oncoprotein rather than a tumor suppressor protein in certain OVCA cells. The functional duality of merlin might represent a paradigm in proteome complexity and is especially important in investigating multifactorial diseases such as cancer.
Cell Line, Tumor↗
Circulation DNA: biological implications for cancer metastasis and immunology.
Circulation cell free DNA (cf-DNA) is of considerable interest to oncology researchers seeking to isolate specific cancer markers. Here, we focus on the origin and biological implications of cf-DNA, exploring its potential roles in cancer biology and medicine. We hypothesize that cf-DNA is primarily released by living cancer cells in addition to apoptotic or necrotic cancer cells for three reasons: (1) following radiotherapy, cf-DNA quantities are significantly reduced in a high percentage of patients although radiation-induced massive apoptosis is expected; (2) cancer cell DNA concentration in cultured supernatants increases with cell proliferation when few apoptotic or necrotic cells are present; and (3) DNA concentration increases in normal lymphocyte cultures following stimulation with phytohemagglutinin, lipopolysaccharide or antigen. Our hypotheses have major biological implications in cancer biology. First, cancer cf-DNA may transform normal cells and form adjacent or remote metastases or second primary cancer. In this context, we also have raised an alarming advice that the cancer may be potentially infectious. Secondly, if a normal cf-DNA contains cytokine sequence, it may behave like an intrinsic DNA vaccine, producing therapeutic cytokine. If normal cf-DNA contains a sequence of a non-mutated oncogene or tumor suppressor gene, homologous recombination with the cancer genome may occur leading to knock out mutated oncogene or tumor suppressor gene that could thus elicit a spontaneous remission of cancer.
Animals↗
Trophoblast signalling: knowns and unknowns--a workshop report.
Explore the source record for details and available documents.
Calcineurin↗
mTOR: a placental growth signaling sensor.
The proliferation and differentiation of trophoblast cells is under the control of a variety of hormones and growth factors and is influenced by nutrient availability. The intracellular signaling pathways acting downstream of these mitogenic factors and nutrients to regulate trophoblast proliferation and placental development are poorly understood. Immortalized human trophoblast cells were used (HTR-8/SVneo) to investigate trophoblast proliferation in response to angiopoietin-2 (Ang-2), a major angiogenic factor and glucose (a major nutrient). Trophoblast cell proliferation was induced through activation of the phosphatidylinositol-3 (PI-3) kinase and the mammalian target of rapamycin (mTOR) signaling pathways, following Tie-2 receptor activation. Glucose also stimulated trophoblast cell proliferation through mTOR signaling. Ang-2 activated mTOR via PI-3 kinase-dependent signaling; whereas glucose-mediated mTOR activation was PI-3 kinase-independent and involved a novel nutrient sensor, glutamine fructose-6-phosphate amidotransferase (GFAT). Metabolites of the GFAT reaction acted upstream of mTOR and functioned as a nutrient sensor to regulate trophoblast cell proliferation in response to glucose. Overall, the results show that growth factor and nutrient signaling converge at tuberin, an upstream regulator of mTOR and that mTOR functions as an important placental growth signaling sensor. These results are the first to link mTOR with GFAT metabolites as nutrient sensors for trophoblast cell proliferation.
Angiopoietin-2↗
Adjusting lung cancer risks for temporal and spatial variations in radon concentration in dwellings in Gansu Province, China.
Our recent study in Gansu Province, China reported an increasing risk of lung cancer with increasing residential radon concentration that was consistent with previous pooled analyses and with meta-analyses of other residential studies (Wang et al., Am. J. Epidemiol. 155, 554-564, 2002). Dosimetry used current radon measurements (1-year track-etch detectors) in homes to characterize concentrations for the previous 30 years, resulting in uncertainties in exposure and possibly reduced estimates of disease risk. We conducted a 3-year substudy in 55 houses to model the temporal and spatial variability in radon levels and to adjust estimates of radon risk. Temporal variation represented the single largest source of uncertainty, suggesting the usefulness of multi-year measurements to assess this variation; however, substantial residual variation remained unexplained. The uncertainty adjustment increased estimates of the excess odds ratio by 50-100%, suggesting that residential radon studies using similar dosimetry may also underestimate radon effects. These results have important implications for risk assessment.
Adult↗
Mechanism of RNA 2'-O-methylation: evidence that the catalytic lysine acts to steer rather than deprotonate the target nucleophile.
The weight of current evidence suggests that RNA 2'-O-MTases employ an S(N)2 mechanism with an in-line attack of the target nucleophile upon the methyl group of the AdoMet cofactor. It has been suggested that, like the phosphohydrolytic enzymes, ribozymes, and nucleic acid polymerases, the RNA 2'-O-MTases initially activate the substrate's attacking hydroxyl oxygen by deprotonation. Here, evidence is presented that the vaccinia virus mRNA cap specific 2'-O-MTase VP39 does not promote RNA 2'-oxyanion formation but that instead it acts by steering a hydroxyl oxygen orbital toward the cofactor methyl center.
Carbon Isotopes↗
Detecting structural changes in early experimental osteoarthritis of tibial cartilage by microscopic magnetic resonance imaging and polarised light microscopy.
OBJECTIVES: To detect changes in the collagen fibril network in articular cartilage in a canine experimental model of early osteoarthritis (OA) using microscopic magnetic resonance imaging (microMRI) and polarised light microscopy (PLM). METHODS: Eighteen specimens from three pairs of the medial tibia of an anterior cruciate ligament transection canine model were subjected to microMRI and PLM study 12 weeks after surgery. For each specimen, the following experiments were carried out: (a) two dimensional microMRI images of T(2) relaxation at four orientations; (b) the tangent Young's modulus; and (c) two dimensional PLM images of optical retardance and fibril angle. Disease induced changes in tissue were examined across the depth of the cartilage at a microMRI resolution of 13.7-23.1 microm. RESULTS: Several distinct changes from T(2) weighted images of cartilage in OA tibia were seen. For the specimens that were covered at least in part by the meniscus, the significant changes in microMRI included a clear shift in the depth of maximum T(2) (21-36%), a decrease in the superficial zone thickness (37-38%), and an increase in cartilage total thickness (15-27%). These microMRI changes varied topographically in the tibia surface because they were not significant in completely exposed locations in medial tibia. The microMRI results were confirmed by the PLM measurements and correlated well with the mechanical measurements. CONCLUSION: Both microMRI and PLM can detect quantitatively changes in collagen fibre architecture in early OA and resolve topographical variations in cartilage microstructure of canine tibia.
Animals↗
Implication of therapeutic cloning for organ transplantation.
Replacement of damaged myocardium with electrically functional, contracting syncytium with a balanced blood supply remains a key goal for the treatment of hearts damaged by coronary heart disease or other disorders. Stem cell therapy offers a potential solution. This paper describes the value of in vitro stem cell research to unravel the roles of key regulatory molecules in embryogenesis of myocardium and blood vessels. Studies have shown that functioning myocytes can be derived from stem cells in vitro and engrafted into infarcted areas of heart where they develop into functional adult like cardiomyocytes with action potentials and capacity for beta adrenergic and muscarinic regulation. Further studies have identified specific roles for platelet endothelial cell adhesion molecule (PECAM), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) in the sequential differentiation of blood vessels and capillaries.
Animals↗
Interpreting time-series analyses for continuous-time biological models--measles as a case study.
An increasing number of recent studies involve the fitting of mechanistic models to ecological time-series. In some cases, it is necessary for these models to be discrete-time approximations of continuous-time processes. We test the validity of discretization in the case of measles, where time-series models have recently been developed to estimate ecological parameters directly from data. We find that a non-homogeneous contact function is necessary to capture the host-parasite interaction in a discrete-time model, even in the absence of heterogeneities due to spatial or age structure. We derive a mathematical relationship describing the expected departure from mass-action transmission in terms of the epidemiological parameters in the model, and identify conditions under which the discretization process may fail.
Birth Rate↗
Slow excitatory synaptic transmission mediated by P2Y1 receptors in the guinea-pig enteric nervous system.
Electrophysiological recording was used to study a type of slow excitatory postsynaptic potential (slow EPSP) that was mediated by release of ATP and its action at P2Y1 receptors on morphologically identified neurones in the submucosal plexus of guinea-pig small intestine. MRS2179, a selective P2Y1 purinergic receptor antagonist, blocked both the slow EPSP and mimicry of the EPSP by exogenously applied ATP. Increased conductance accounted for the depolarization phase of the EPSP, which occurred exclusively in neurones with S-type electrophysiological behaviour and uniaxonal morphology. The purinergic excitatory input to the submucosal neurones came from neighbouring neurones in the same plexus, from neurones in the myenteric plexus and from sympathetic postganglionic neurones. ATP-mediated EPSPs occurred coincident with fast nicotinic synaptic potentials evoked by the myenteric projections and with noradrenergic IPSPs evoked by sympathetic fibres that innervated the same neurones. The P2Y1 receptor on the neurones was identified as a metabotropic receptor linked to activation of phospholipase C, synthesis of inositol 1,4,5-trisphosphate and mobilization of Ca2+ from intracellular stores.
Adenosine Diphosphate↗
Concentrations of progesterone, follistatin, and follicle-stimulating hormone in peripheral plasma across the estrous cycle and pregnancy in merino ewes that are homozygous or noncarriers of the Booroola gene.
The circulating concentrations of progesterone, FSH, and follistatin across the estrous cycle and gestation were compared in Australian merino sheep that were homozygous for the Booroola gene, FecB, or were noncarriers. The Booroola phenotype is due to a point mutation in the bone morphogenetic protein receptor 1B. Progesterone concentrations began to rise earlier and were higher in the Booroola ewes than in the noncarriers on most days of the luteal phase but not during the follicular phase of the cycle. Follistatin concentrations remained unchanged across the estrous cycle in both groups of ewes, with no differences between genotypes. FSH concentrations were higher in Booroola ewes than in noncarrier ewes on most days of the estrous cycle, with a significantly higher and broader peak of FSH around the time of estrus. Progesterone concentrations were significantly higher in early and midgestation in Booroola ewes but were lower toward the end of gestation than those in noncarriers. FSH declined in both groups across gestation, with lower concentrations of FSH in Booroola ewes during midgestation. Follistatin remained unchanged across gestation in Booroola ewes and noncarrier ewes with a twin pregnancy but declined across gestation in noncarrier ewes with a singleton pregnancy. These results suggest that follistatin concentration is not regulated by the FecB gene during the estrous cycle and pregnancy but is influenced by the number of fetuses. However, the FecB gene appears to positively affect both progesterone and FSH during the estrous cycle and across pregnancy, which suggests that bone morphogenetic proteins play an important role in the regulation of both hormones.
Animals↗
Differential neuronal activation in the hypothalamic paraventricular nucleus and autonomic/neuroendocrine responses to I.C.V. endotoxin.
The paraventricular nucleus (PVN) of the hypothalamus is a key site for regulating neuroendocrine and autonomic activities. To study the role of the PVN activation in brain inflammation-induced autonomic/endocrine responses, lipopolysaccharide (LPS; 0.5 or 5 microg) was administered i.c.v. and rats were killed 1, 3 or 6 h after the injection. I.c.v. LPS-0.5 microg did not cause changes in mean arterial pressure (MAP) over 6 h, whereas LPS-5 micro induced a temporary decrease in MAP approximately 30 min after the injection. LPS at either dose increased heart rate. Whereas induction of Fos-like immunoreactivity was confined to the dorsal medial parvocellular division (mpd) of the PVN with the lower dose, labeling was found throughout the PVN with the higher dose. At 3 h, LPS-5 microg also stimulated increases in arginine vasopressin (AVP) heteronuclear RNA levels in the posterior magnocellular and dorsal parvocellular divisions of the PVN at 3 h, and activation of catecholaminergic neurons in the hypothalamus and brainstem. Increases in tyrosine hydroxylase (TH) mRNA levels were found in the locus coeruleus at 6 h. LPS at both doses elevated plasma ACTH levels and corticotropin-releasing factor gene expression in the mpd of the PVN. I.c.v. LPS induced IL-1beta mRNA in the meninges and ventricular ependymal lining at 1 h, and in the periventricular PVN at 3 h. Induction of IL-1beta mRNA was found in the lung at 1 h, and a significant increase in plasma LPS binding protein occurred at 3 h. These findings suggest that PVN activation induced by the lower dose of LPS is related primarily to increases in activity of the HPA axis, whereas the higher dose of LPS more widely activates autonomic regulatory centers including the PVN and also stimulates changes in sympathetic output and hypothalamic AVP synthesis. Activation of the PVN by i.c.v. LPS likely occurs through both central and systemic routes. Differential neuronal activation in the PVN is functionally related to autonomic/endocrine responses elicited by brain inflammation.
Animals↗
The total volume and the complete thickness of articular cartilage determined by MRI.
Explore the source record for details and available documents.
Cartilage Diseases↗
Imaging the velocity profiles in tubeless siphon flow by NMR microscopy.
We report on the use of NMR micro-imaging to observe flow within a tubeless siphon. The flow is maintained in a visco-elastic liquid of high extensional viscosity, namely 0.5% w/v 8 million Dalton polyethylene oxide in water. The velocity profiles reveal a significant velocity gradient in the vertical direction as well as a transition from near-Poiseuille flow at the pipe entrance to plug flow far from the pipe entrance towards the base of the tubeless siphon.
Feasibility Studies↗
Apoptotic markers are increased in platelets stored at 37 degrees C.
BACKGROUND: PLTs for transfusion lose viability during storage in blood banking. This loss of viability is accelerated at 37 degrees C, as is the risk of bacterial contamination, and has led to the selection of 22 degrees C as the routine storage temperature. Because PLTs contain an intact apoptotic mechanism, we sought to determine whether PLTs undergo apoptosis during storage and whether storage at 37 degrees C accelerated this process. STUDY DESIGN AND METHODS: PLT-rich plasma from PLT concentrates was stored at 37 or 22 degrees C in small aliquots or whole bags, with and without cell-permeable caspase inhibitors. Number of PLTs, pH, LDH level, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium activity were analyzed over time. PLT lysates were prepared and tested for the presence and activation of apoptotic proteins by enzyme assay and Western blotting. RESULTS: PLT viability was greatly reduced after 1 to 2 days of storage at 37 degrees C; however, signs of apoptosis were evident by 3 hours after temperature shift. In temperature-stressed PLTs only, a gradual rise in caspase-3 activity was detected that correlated with the appearance of the 17- to 20-kDa cleavage products of caspase-3. Gelsolin, a caspase-3 substrate, underwent cleavage within the same time frame. Bcl-xL and caspase-2 also declined significantly; caspase-9 activity rose. Specific caspase inhibitors could prevent caspase activation but did not improve PLT cellular viability at 37 degrees C. CONCLUSIONS: PLTs contain apoptotic proteins that are activated during PLT storage at 37 degrees C and may account for the rapid decline in PLT cellular viability. Although ineffective here, inhibition of PLT apoptosis may improve PLT cellular viability.
Apoptosis↗
Confinement of molecular liquids: consequences on thermodynamic, static and dynamical properties of benzene and toluene.
We relate the dynamical behavior of molecular liquids confined in mesoscopic cylindrical pores to the thermodynamic properties, heat capacity and density and to the static structure by combining different experimental methods (H-NMR, calorimetry, elastic and inelastic neutron scattering, numerical simulations). The crystallization process is greatly reduced or avoided by confinement under standard cooling conditions, instead a glass transition temperature T(g) at the 1000s time scale can be observed. The pore averaged local structure of the confined liquid is not noticeably affected when "excluded-volume" corrections are carefully applied, but follows the density changes reflected by the Bragg peak intensities of the porous matrices. The pore size dependence of T(g) is dominated by two factors, surface interaction and finite-size effect. For the smallest pores ([Formula: see text], [Formula: see text] being the van der Waals radius of a molecule), one observes an increase of T(g) and a broadening of the transition region, related to the interaction with the surface that induces a slowing-down of the molecules close to the wall. This is confirmed by neutron scattering experiments and molecular-dynamics simulations at shorter time scales and higher temperatures, which indicate a remaining fraction of frozen molecules. For larger pore sizes, taking the decrease of density under confinement conditions into account, a decrease of T(g) is observed. This could be related to finite-size effects onto the putative cooperativity length that is often invoked to explain glass formation. However, no quantitative determination of this length (not to mention its T-dependence) can be extracted, since the interaction with the wall itself introduces an additional length that adds to the complexity of the problem.
Journal Article↗
Study of severe hepatitis treated with a hybrid artificial liver support system.
Artificial liver support system (ALSS) has been used to treat hepatic failure and has significantly decreased the mortality. TECA hybrid artificial liver support system (TECA-HALSS), which combines the hollow fiber bioreactor with a plasma exchange circuit, was used to assess the efficacy, safety and feasibility in treating severe hepatitis patients. The hybrid artificial liver support system (HALSS) consists of a bioreactor containing more than 5 x10(9) porcine hepatocytes and plasma exchange device. Fifteen patients with severe hepatitis were treated with this hybrid system. All patients experienced a reduction in symptoms such as fatigue, abdominal distention or ascites. After each treatment serum total bilirubin decreased markedly while prothrombin activity increased. There were ten patients whose progress of hepatocyte necrosis was stopped after HALSS treatment, and finally they recovered completely. One patient received liver transplantation after HALSS therapy and survived. No serious adverse events were noted in the fifteen patients.
Adult↗