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Biomedical subjects

H Li

Publications and source records attributed to H Li.

At least 145 records · Page 8Linked to original sources

PET-based molecular imaging in neuroscience.

Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and "phenotyping" of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed.

Alzheimer Disease↗

Field evaluation of a test for praziquantel resistance in Schistosoma sp.

A simple rapid test for detecting praziquantel resistance in Schistosoma sp., involving change in shape of miracidia on exposure to praziquantel, was evaluated in China. Tests on miracidia hatched from eggs collected from naturally infected goats were run in a field laboratory in Jiangxi Province and a research laboratory in Shanghai. The mean values in the two laboratories were not significantly different, but the variation between individual samples in the two laboratories suggests that a delineating dose will be required for routine diagnosis of resistance. Confirmation that resistance would have been detected in Schistosoma japonicum must await the isolation of a resistant isolate. The tests suggested that the infection in the goats was susceptible to praziquantel as did chemotherapy of water buffaloes with 25mg/kg. This gave a 95% cure rate on the first treatment and 100% with a second treatment, similar to that found previously in human patients.

Animals↗

Uterine artery blood flow velocity waveforms during uterine contractions.

OBJECTIVE: No quantitative or qualitative Doppler velocimetry classification of vascular flow resistance covering all stages of forward and reversed flows exists. The objective of this study was to characterize uterine artery (UtA) flow velocity waveforms (FVWs) obtained during an oxytocin challenge test (OCT) and compare them to FVWs in spontaneous normal labor. METHODS: Uterine artery Doppler velocimetry was performed during and between uterine contractions in 61 high-risk pregnancies subjected to an OCT and in 20 normal pregnancies undergoing spontaneous labor. FVWs were classified relative to the presence of forward/absent/reversed flow during systole and diastole, and the time-averaged flow velocity over the heart cycle. RESULTS: Eleven different FVW classes were identified. No relationship between FVWs recorded during uterine inertia and contractions was found (P >/= 0.2). In both groups, only forward FVWs were recorded between contractions, whereas during contractions flow reversal was more common in the OCT group (P </= 0.002). In cases of predominantly reversed flow, a reciprocal relationship to FVW classes recorded in the contralateral artery was found. CONCLUSIONS: UtA FVW patterns recorded during uterine contractions were not predicted by flow patterns recorded during uterine inertia. Reversal of flow direction was more common during oxytocin-induced uterine contractions than during spontaneous contractions. In cases of predominantly reversed flow, domains of the uterus may be supplied by blood from the contralateral UtA. These observations give new insights into the circulatory dynamics of the uterus during labor, and also point to a possible vasoconstrictory effect in the UtAs of oxytocin at high concentrations.

Arteries↗

Fenofibrate inhibits angiogenesis in vitro and in vivo.

Fenofibrate, a peroxisome proliferator-activated receptor (PPAR)-alpha activator, used as a normolipidemic agent, is thought to offer additional beneficial effects in atherosclerosis. Since angiogenesis is involved in plaque progression, hemorrhage, and instability, the main causes of ischemic events, this study was designed to evaluate the action of fenofibrate on angiogenesis. Our results show that fenofibrate (i) inhibits endothelial cell proliferation induced by angiogenic factors, followed at high concentrations by an increase in apoptosis, (ii) inhibits endothelial cell migration in a healing wound model, (iii) inhibits capillary tube formation in vitro, and (iv) inhibits angiogenesis in vivo. Concerning the mechanism of action, the inhibition of endothelial cell migration by fenofibrate can be explained by a disorganization of the actin cytoskeleton. At the molecular level, fenofibrate markedly decreased basic fibroblast growth factor-induced Akt activation and cyclooxygenase 2 gene expression. This inhibition of angiogenesis could participate in the beneficial effect of fenofibrate in atherosclerosis.

Actins↗

Association analysis of bone mineral density and single nucleotide polymorphisms in two candidate genes on chromosome 1p36.

Two candidate genes for bone mineral density (BMD), tumor necrosis factor alpha receptor 2 (TNFRSF1B) and lysyl hydroxylase (PLOD1), have been scanned for single nucleotide polymorphisms (SNPs) within their coding and promoter regions. These two genes, separated by about 200 kb, are located within the chromosomal interval 1p36.2-1p36.3 that has been linked to femoral neck BMD. In a patient population (n = 104) of European descent, there were four SNPs within TNFRSF1B and six SNPs within PLOD1 that occurred with greater than 5% frequency. There was significant linkage disequilibrium within both genes. Single marker analysis revealed significant association for one SNP located in intron 6 of PLOD1 and lumbar spine BMD (P = 0.01). Allelic haplotypes that encompassed the four SNPs in TNFRSF1B or the six SNPs in PLOD1 were assigned using a Bayesian algorithm as implemented in the program Haplotyper. Association of TNFRSF1B haplotypes with femoral neck BMD was statistically significant (P = 0.01). Similarly, PLOD1 haplotypes demonstrated a statistically significant association with spinal BMD (P = 0.04). These findings strengthen the potential importance of chromosome 1p36.2-1p36.3 in contributing to BMD variation, and are consistent with genetic variation in either PLOD1, TNFRSF1B or nearby genes playing a role in the phenotype.

Antigens, CD↗

Molecular characterization of a distinct potyvirus from whitegrass in China.

Apotyvirus isolated from perennial whitegrass ( Pennisetum centrasiaticum Tzvel.) in North China was characterized at the molecular level. The 3' terminal nucleotide (nt) sequence of 1669 nt of the viral RNA genome has been determined, which covered the coding region of the C-terminal part of the large nuclear inclusion protein (NIb, RNA polymerase), capsid protein (CP) gene and the 3' nontranslated region (NTR). The CP gene consisted of 909 nt (including the stop codon) encoding 302 amino acid residues, and the 3' NTR was 241 nt in length excluding the polyadenylated tract. Sequence comparison of the amino acids of CPs showed that this virus was most closely related to Sorghum mosaic virus and Maize dwarf mosaic virus with percent identities of 77% to 78% while that of the 3' NTRs suggested that it was most closely related to Zea mosaic virus with identity of 72%. This virus isolate was to some extent closely related to other members of the Sugarcane mosaic virus subgroup of potyviruses for the CP amino acid sequences. Phylogenetic analyses of the sequences indicated that this virus isolate represented a distinct potyvirus, and the name Pennisetum mosaic virus (PenMV) is proposed.

Capsid Proteins↗

Immunohistochemical localisation of extracellular matrix proteins in the periodontium during cementogenesis in the rat molar.

OBJECTIVE: The development of the periodontium involves the coordinated expression of numerous extracellular matrix (ECM) macromolecules and their receptors (integrins). The aim of this study was to determine the expression of selected hard and soft tissue matrix molecules and the integrin alpha5beta1 in the periodontal tissues, during cementogenesis in the rat molar. METHODS: Using immunohistochemical methods, the distribution of the extracellular matrix proteins, fibronectin, tenascin, and bone sialoprotein (BSP), as well as the integrin subunits alpha5 and beta1 were studied in rats aged 3, 5 and 8 weeks. RESULTS: Fibronectin was widely distributed in the gingival epithelium, gingival connective tissue and in the periodontal ligament. Tenascin expression was less marked compared with fibronectin, but was more distinctly associated with cells and peri-cellular areas of the epithelial-connective tissue interface, the gingiva and within the periodontal ligament. The fibronectin-receptor alpha5beta1 integrins were expressed by epithelial cells, periodontal ligament cells and gingival fibroblasts. A notable finding was the increased staining intensity of fibronectin, tenascin and alpha5beta1 integrin in all 5-week old molar sections in the periodontal ligament matrix and cells, apical to the cemento-enamel junction (CEJ) along the alveolar crest (AC) ridge height. Bone sialoprotein was distinctly associated with the hard tissues of the periodontium as acellular cementum and alveolar bone matrix expressed bone sialoprotein throughout all sections, in all age groups. CONCLUSIONS: In conclusion, this study has demonstrated the selective distribution of several hard and soft tissue matrix molecules during periodontogenesis. The results highlight the complex nature of interactions of various proteins and molecules during development. The interactions between these molecules and their specific roles in development and regeneration await further investigation.

Animals↗

In vitro behavior of HVOF sprayed calcium phosphate splats and coatings.

Hydroxyapatite (HA) coatings and splats deposited by high velocity oxy-fuel (HVOF) spray technique was investigated in vitro. HA coatings prepared from two different HA powder size range (30+/-5 and 50 +/-5 microm) were immersed in a simulated body fluid with various incubation periods of maximum 6 weeks. The dissolution/precipitation behavior was studied and the degradation of HA coatings caused by in vitro ageing was demonstrated by measuring the changes in flexural modulus through a 3-point bend test. It was found that the dissolution and precipitation behavior of the coatings was significantly dependent upon the incipient coating phase composition and the precipitation of bone-like hydroxyapatite on the coating's surface was found to be directly related to the dissolution process. Higher dissolution rates of tricalcium phosphate, tetracalcium phosphate and amorphous calcium phosphate relative to HA, resulted in accelerated precipitation. Furthermore, analysis of coatings' surface morphology demonstrated that advanced precipitation invariably occurred at regions where dissolution took place. Results showed that the changes in flexural modulus of investigated HA coatings accompanying different incubation duration was not systematic but was found to be dependent upon changes of coating structure and other factors brought about by in vitro ageing. In vitro investigation of individual HA splats collected from different HA particle sizes revealed, after 3 days ageing, that the rate ratio of precipitation to dissolution was directly determined by the local phase composition, and this phenomenon could be effectively used to explain the behavior of thermally sprayed HA coatings in vitro. It implied that the precipitation was strongly dependent on the first molecule attachment. To achieve rapid precipitation in vitro, partial molten state of HA particles during HVOF coating deposition was recommended.

Anions↗

Characterization of the bone-like apatite precipitated on high velocity oxy-fuel (HVOF) sprayed calcium phosphate deposits.

Bone-like apatite was precipitated on the surface of thermal sprayed calcium phosphate coatings following in vitro incubation in a simulated body fluid. The coatings were initially deposited on titanium alloy substrates by the high velocity oxy-fuel (HVOF) spray technique. Structural characterization and mechanical evaluation of the precipitated apatite layer were conducted. Results showed that the precipitation rate was directly influenced by the local Ca(2+) concentration in the vicinity of the coating's surface and that preferential dissolution of certain phases was found to accelerate the precipitation of the bone-like apatite. The dense precipitates exhibited a competitive Young's modulus value of approximately 120GPa, which was obtained through nanoindentation. This compared favorably to the calcium phosphate matrix. Differences in microstructure at various locations within the layer resulted in altered Young's modulus and microhardness values. Precipitation mechanism investigation was carried out through a comparative experiment. Chemical analysis showed that the precipitation of bone-like apatite on the calcium phosphate coating was quite conceivably a partial diffusion-controlled process.

Apatites↗

Impact formation and microstructure characterization of thermal sprayed hydroxyapatite/titania composite coatings.

Formation mechanism of hydroxyapatite (HA)/titania (TiO(2)) composite coating deposited by high velocity oxy-fuel (HVOF) thermal spray process was studied, and its structural characterization was conducted and elaborated in this paper. The impact theory was employed to analyze the formation procedure of the HA/titania composite coatings. Results revealed that the crater caused by the impact of entirely unmelted TiO(2) particles on the HA matrix during coating formation was of smaller dimensions than the original size of the reinforcements. It was found that chemical reaction between the mechanically blended HA and TiO(2) powder took place exclusively during the impingement stage, and calcium titanate, CaTiO(3), was one notable by-product. The bonding between the HA matrix and TiO(2) reinforcement might have been achieved predominantly through a chemical bond that resulted from the mutual chemical reactions among the components. Differential scanning calorimetry analyses showed that the chemical reaction between HA and TiO(2) was at approximately 1410 degrees C. The TiO(2) addition was found to exert particular effects on the thermal behavior of HA at elevated temperatures, during both heating and cooling cycles. Transmission electron microscopy observation identified the chemical reaction zone between HA and TiO(2), which revealed an improved splats' interface. The reaction zone demonstrated some influence on the grain size of HA nearby during resolidification of the melted portion. A structural model was proposed to illustrate the location of the different phases in the HA/titania composite coating.

Calorimetry, Differential Scanning↗

Processing-microstructure-property relations in HVOF sprayed calcium phosphate based bioceramic coatings.

Hydroxyapatite (HA) based bioceramic coatings were deposited onto titanium alloy substrates using the high velocity oxy-fuel (HVOF) spray technique. This study aimed to reveal the relations among processing parameters, microstructure, and properties of the bioceramic coatings. The processing conditions were altered through changing the starting HA powder size, content of bioinert ceramic additives or composite powder preparation techniques. Coating structure was characterized through scanning electron microscopy (SEM) and transmission electron microscopy (TEM); and the mechanical properties, Young's modulus and fracture toughness, of the coatings were evaluated through indentation techniques. Results demonstrated dominant influence of the melt state of HA powders on the phase composition of resultant coatings, and it was found that the HVOF HA coatings possess competitive mechanical properties. Furthermore, addition of titania or zirconia, as secondary phase in HA, showed promising effect on improving the mechanical properties of the HVOF HA-based coatings. Chemical reactions between HA and titania; and, HA and zirconia during coating deposition were revealed and characterized. Incorporation modes of the additives into HA and their reinforcing mechanisms were elucidated. The relationship among the processing, microstructure, and mechanical properties of the HVOF sprayed bioceramic coatings was summarily examined.

Bone Substitutes↗

Effect of spark plasma sintering on the microstructure and in vitro behavior of plasma sprayed HA coatings.

The crystalline phases and degree of crystallinity in plasma sprayed calcium phosphate coatings on Ti substrates are crucial factors that influence the biological interactions of the materials in vivo. In this study, plasma sprayed hydroxyapatite (HA) coatings underwent post-spray treatment by the spark plasma sintering (SPS) technique at 500 degrees C, 600 degrees C, and 700 degrees C for duration of 5 and 30 min. The activity of the HA coatings before and after SPS are evaluated in vitro in a simulated body fluid. The surface microstructure, crystallinity, and phase composition of each coating is characterized by scanning electron microscopy and X-ray diffractometry before, and after in vitro incubation. Results show that the plasma sprayed coatings treated for 5 min in SPS demonstrated increased proportion of beta-TCP phase with a preferred-orientation in the (214) plane, and the content of beta-TCP phase corresponded to SPS temperature, up to 700 degrees C. SPS treatment at 700 degrees C for 30 min enhanced the HA content in the plasma spray coating as well. The HA coatings treated in SPS for 5 min revealed rapid surface morphological changes during in vitro incubation (up to 12 days), indicating that the surface activity is enhanced by the SPS treatment. The thickest apatite layer was found in the coating treated by SPS at 700 degrees C for 5 min.

Biomimetic Materials↗

Adenosine suppresses the response of neurons to gaba in the superficial laminae of the rat spinal dorsal horn.

With the nystatin-perforated whole-cell patch-clamp recording technique, the modulatory effects of adenosine on GABA-activated whole-cell currents were investigated in neurons acutely dissociated from the superficial laminae (laminae I and II) of the rat spinal dorsal horn. The results showed that: (1) GABA acted on GABA(A) receptor and elicited inward Cl(-) currents (I(GABA)) at a holding potential (V(H)) of -40 mV; (2) adenosine suppressed GABA-induced Cl(-) current with affecting neither the reversal potential of I(GABA) nor the apparent affinity of GABA to its receptor; (3) N6-cyclo-hexyladenosine, a selective A(1) adenosine receptor agonist, mimicked the suppressing effect of adenosine on I(GABA), whereas 8-cyclopentyl-1,3-dipropylxanthine, a selective A(1) adenosine receptor antagonist, blocked the suppressing effect of adenosine; (4) chelerythrine, an inhibitor of protein kinase C, reduced the suppressing effect of adenosine on I(GABA); (5) pretreatment with 1,2-bis-(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxy-methyl) ester, a Ca(2+) chelator, did not affect adenosine-induced suppression of I(GABA). The results indicate that: (1) the suppression of adenosine on I(GABA) is mediated by adenosine A(1) receptor and through a Ca(2+)-independent protein kinase C transduction pathway; (2) the interactions between adenosine and GABA might be involved in the modulation of nociceptive information transmission at spinal cord level.

Adenosine↗

Serotonin type II receptor activation facilitates synaptic plasticity via N-methyl-D-aspartate-mediated mechanism in the rat basolateral amygdala.

The modulation of synaptic plasticity by serotonin type II (5-hydroxytryptamine type II (5-HT(2)))-receptor stimulation was explored using intracellular, field potential and Fura-2 fluorescence image recordings in a rat amygdala slice preparation. Bath application of 5HT(2) receptor agonist 1-(2,5)-dimethoxy-4-iodophen-2-aminopropane (DOI) transformed theta-burst-stimulated (TBS) synaptic plasticity from short-term potentiation to long-term potentiation. DOI enhanced N-methyl-D-aspartate (NMDA) receptor-mediated potentials and calcium influx without affecting the resting membrane potential or input resistance of the neurons. In contrast, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate receptor-mediated excitatory synaptic responses were unaffected by DOI. The facilitating effects of DOI were blocked by the 5-HT(2) receptor antagonist, ketanserin, and by the 5-HT(2C)-receptor selective antagonist, RS102221. These results indicate that 5-HT(2)-receptor activation enhances NMDA receptor-mediated synaptic function in the basolateral amygdala (BLA).

Amygdala↗

Intrinsic collaterals of layer 6 Meynert cells and functional columns in primate V1.

Meynert cells are a distinct type of large neuron which project to area MT/V5 and to subcortical targets, including the superior colliculus. They have recently been shown to have extensive intrinsic collaterals spreading up to 8.0 mm within layer 6 of area V1 [J Comp Neurol 441 (2001) 134]. Using intrinsic signal imaging combined with tracer injections, this study investigates how Meynert cell collaterals are mapped in relation to the functional architecture of area V1 in macaque monkeys. In particular, we examined whether terminations of individual axon segments are selective for same-eye or opposite-eye domains. Analysis of 39 anterogradely labeled axon segments (from six injection sites in four hemispheres) showed that terminal segments cross over several pairs of ocular dominance columns (ODCs) and contact both left- and right-eye ODCs, with a slight bias for the contralateral eye. This contrasts with the same-eye bias previously reported for intrinsic collaterals of pyramidal neurons in layer 3. The suggestion is that the system of Meynert intrinsic collaterals is involved with binocular interactions over wide sectors of the visual field. This might be related to processes such as optic flow or, especially given the wide-field spread, even contour completion or interpolation.

Animals↗

Interferon-gamma upregulates MUC1 expression in haematopoietic and epithelial cancer cell lines, an effect associated with MUC1 mRNA induction.

Epithelial mucin-1 (MUC1) is an important target antigen that it is overexpressed in both epithelial and haematological cancers including multiple myeloma (MM) and some lymphomas and leukaemias. MUC1 has adhesive and immunosuppressive properties, which may promote cancer progression. These studies evaluated the effect of IFNs on MUC1 expression, since these agents are widely used in clinical cancer therapy. MUC1 and interferon (IFN) receptor expression were measured by radioligand binding. Changes in MUC1 mRNA levels in response to IFN-gamma were assessed by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). IFN-gamma was found to be a more potent inducer of MUC1 expression than IFN-alpha. 125I-IFN binding studies indicated that both IFN receptors were expressed in most of the cell lines. With IFN-gamma treatment, there was upregulation of MUC1 mRNA. IFN-gamma has a more consistent and more potent effect upon MUC1 induction than IFN-alpha. The ability to upregulate MUC1 across a broad range of cancer types by a clinically available cytokine, IFN-gamma, has important implications for enhancing immunotherapeutic approaches targeting MUC1.

Antineoplastic Agents↗

[Porcine malignant catarrhal fever: diagnostic findings and first detection of the pathogenic agent in diseased swine in Switzerland].

For the first time Ovine Herpesvirus 2 (OvHV-2) was identified in Swiss pigs as the causative agent of Porcine Malignant Catarrhal Fever (MCF). Diseased animals from two farms were observed to show weakness, anorexia, fever up to 41 degrees C, and neurological symptoms, i.e. ataxia, convulsions and hyperesthesia, erosion on the snout and in the oral and nasal mucosa, as well as multiple skin lesions. Histopathological findings included severe non-purulent inflammation with mononuclear cell infiltration in several organs. Most dominant were meningo-encephalitis, disseminated nephritis as well as purulent catarrhalic bronchopneumonia. The findings were quite reminiscent of the lesions due to MCF in cattle and give therefore substantial proof to use Porcine Malignant Catarrhal Fever as the term for the disease. Identification of the causative agent was done with a quantitative PCR specific for OvHV-2. Different tissues from diseased animals were positive. Furthermore, one animal which had been ill for more than five days tested positive for antibodies against an epitope conserved among MCF viruses. Serum samples from diseased animals reacted negative towards Classical Swine Fever- and Pseudorabies virus antigen. A weakly positive reaction against porcine enterovirus type I argued against the involvement of enteroviruses in the observed disease. Moreover, by means of different conventional PCRs, we detected the newly discovered porcine lymphotropic herpesviruses for the first time in Switzerland and could at the same time exclude their involvement in Porcine Malignant Catarrhal Fever.

Animals↗