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Biomedical subjects

L He

Publications and source records attributed to L He.

At least 37 records · Page 2Linked to original sources
PubMed2004

Positive association of the DIO2 (deiodinase type 2) gene with mental retardation in the iodine-deficient areas of China.

BACKGROUND: Iodine deficiency is the commonest cause of preventable mental retardation (MR) worldwide. However, in iodine-deficient areas not everyone is affected and familial aggregation is common. This suggests that genetic factors may also contribute. Thyroid hormone (TH) plays an important role in fetal and early postnatal brain development. The pro-hormone T4 (3,3',5,5'-triiodothyronine) is converted in the brain to its active form, T3, or its inactive metabolite, reverse T3, mainly by the action of deiodinase type 2 (DIO2). METHODS: To investigate the potential genetic contribution of the DIO2 gene, we performed a case-control association study using three common SNPs in the gene (rs225014, rs225012, and rs225010) that were in strong linkage disequilibrium with each other. RESULTS: Single marker analysis showed a positive association of MR with rs225012 and rs225010. Particularly with rs255012 [corrected], CC [corrected] genotype frequency was significantly higher in MR cases than in controls (chi squared [corrected] = 9.18, p = 0.00246). When we compared the distributions of common haplotypes, we also found significant differences between mental retardation and controls in the haplotype combination of rs225012 and rs225010 (chi2 = 15.04, df 2, global p = 0.000549). This association remained significant after Bonferroni correction (p = 0.0016470). CONCLUSION: We conclude that allelic variation in the DIO2 gene may affect the amount of T3 available and in an iodine-deficient environment may partly determine overall risk of MR.

Adolescent↗
PubMed2003

Novel germanium-based magnetic semiconductors.

Epitaxial synthesis and properties of novel Co and Mn-doped Ge magnetic semiconductors were studied. Epitaxial growth of high quality films with high doping concentrations has been stabilized by the use of two dopants. The magnetic and transport properties of the system exhibit high T(C) and large magnetoresistance effects that can be controlled systematically by the doping concentration. The maximum T(C) achieved in the semiconducting materials is approximately 270 K at a composition of Co0.12Mn0.03Ge0.85.

Journal Article↗
PubMed2003

Apolipoprotein E -491 promoter polymorphism is an independent risk factor for Alzheimer's disease in the Chinese population.

Polymorphisms at positions -491, -427 and -219 in the promoter region of the Apolipoprotein E APOE gene have been variously reported to confer an increased risk of developing Alzheimer's disease (AD) independent of the effect of epsilon 2, 3 or 4 alleles in exon 4. In order to assess APOE promoter polymorphisms as independent risk factors in AD we have compared results in 183 definite or probable AD cases with 133 controls. We assayed markers at sites -491, -427, -219, and +113 in APOE gene and a polymorphic Hha1 site in the nearby APOC1 gene. We found that APOE promoter polymorphisms and APOC1 insertion alleles were significantly associated with AD. However, after stratification for epsilon 4 allele, only the A allele at -491 in APOE remained significantly associated with AD. The effects of the other markers depended almost entirely upon linkage disequilibrium with epsilon 4 allele, and only trends remained when cases and controls were stratified for the presence or absence of epsilon 4 allele. This occurred irrespective of whether markers were examined separately or together as haplotypes. So in the Chinese population only APOE -491 promoter alleles confer significant risk of AD independent of epsilon 4 status.

Aged↗
PubMed2003

Proteomic analysis of the cerebrospinal fluid of patients with schizophrenia.

We applied proteomics technologies to analyze the cerebrospinal fluid of patients with schizophrenia. Such an analysis can result in the identification of proteins, which may play a role in the disease progress and thus lead to the discovery of clues of the etiology of schizophrenia. Cerebrospinal fluid from patients and controls was analyzed by two-dimensional gels and the proteins were identified by matrix-assisted laser desorption ionization mass spectrometry (MS) in the MS and MS/MS mode. 54 different gene products were identified, which were mainly plasma proteins. The level of apolipoprotein A-IV was significantly decreased in the schizophrenic patients compared to that in the controls. Little is known about the function of this apolipoprotein in the central nervous system. The levels of certain other proteins, like haptoglobin, fibrinogen, complement component 3, and Gc-globulin, were altered in the disease group as well, however, the changes did not reach a statistical significance.

Apolipoproteins A↗
PubMed2003

CD8+ T cells, NK cells and IFN-gamma are important for control of tumor with downregulated MHC class I expression by DNA vaccination.

One of the major hurdles facing cancer immunotherapy is that cancers may downregulate expression of MHC class I molecules. The development of a suitable tumor model with downregulated MHC class I expression is critical for designing vaccines and immunotherapeutic strategies to control such tumors. We developed an E7-expressing murine tumor model with downregulated MHC class I expression, TC-1 P3 (A15). Using this model, we tested DNA and vaccinia vaccines for their ability to control tumors with downregulated MHC class I expression. We found that vaccination with DNA encoding E7 linked to Mycobacterial heat shock protein 70 (HSP70) generated a significant antitumor effect against TC-1 P3 (A15), while vaccination with E7/HSP70 vaccinia did not generate an appreciable antitumor effect. Lymphocyte depletion experiments revealed that both CD8+ T cells and NK cells were essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15). Furthermore, tumor protection experiments using IFN-gamma knockout mice revealed that IFN-gamma was essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15). Our results demonstrate that vaccination with E7/HSP70 DNA results in a significant antitumor effect against a neoplasm with downregulated MHC class I expression and the importance of CD8+ T cells, NK cells, and IFN-gamma in generating this antitumor effect.

Animals↗
PubMed2003

Somatic mitochondrial DNA mutations in adult-onset leukaemia.

Mitochondrial genome instability has recently been demonstrated in a wide variety of human tumours and is implicated in the development of the myelodysplastic syndromes, a heterogeneous group of haematological disorders with an increased risk of malignant transformation. We therefore investigated the incidence of somatic mitochondrial DNA (mtDNA) mutations in patients with adult-onset leukaemia. We sequenced the entire mitochondrial genome from both normal tissue (buccal epithelial cells) and the leukaemia from 24 patients with adult-onset leukaemia. Somatic mtDNA mutation was present in nine individuals ( approximately 40%) and in each case the tumour genome differed from the normal genome sequence by a single sequence change. Using PCR-RFLP analysis and real-time PCR, we have studied in detail the mutation present in one patient with acute lymphatic leukaemia, demonstrating that the mutation is associated specifically with the leukaemia.

Adolescent↗
PubMed2003

Fluorescence resonance energy transfer from cyan to yellow fluorescent protein detected by acceptor photobleaching using confocal microscopy and a single laser.

One manifestation of fluorescence resonance energy transfer (FRET) is an increase in donor fluorescence after photobleaching the acceptor. Published acceptor-photobleaching methods for FRET have mainly used wide-field microscopy. A laser scanning confocal microscope enables faster and targeted bleaching within the field of view, thereby improving speed and accuracy. Here we demonstrate the approach with CFP and YFP, the most versatile fluorescent markers now available for FRET. CFP/YFP FRET imaging has been accomplished with a single laser (argon) available on virtually all laser-scanning confocal microscopes. Accordingly, we also describe the conditions that we developed for dual imaging of CFP and YFP with the 458 and 514 argon lines. We detect FRET in a CFP/YFP fusion and also between signalling molecules (TNF-Receptor-Associated-Factors or TRAFs) that are known to homo- and heterotrimerize. Importantly, we demonstrate that appropriate controls are essential to avoid false positives in FRET by acceptor photobleaching. We use two types of negative control: (a) an internal negative control (non-bleached areas of the cell) and (b) cells with donor in the absence of the acceptor (CFP only). We find that both types of negative control can yield false FRET. Given this false FRET background, we describe a method for distinguishing true positive signals. In summary, we extensively characterize a simple approach to FRET that should be adaptable to most laser-scanning confocal microscopes, and demonstrate its feasibility for detecting FRET between several CFP/YFP partners.

Bacterial Proteins↗
PubMed2003

Glucose inhibition of the induction of CYP2E1 mRNA expression by ethanol in FGC-4 cells.

1. Rats fed intragastrically with ethanol-containing diets made with low levels of carbohydrates have greater CYP2E1 induction than rats fed similar diets made with high carbohydrate levels. 2. FGC-4 rat hepatoma cells were used to test the hypothesis that carbohydrates could down-regulate ethanol-induced CYP2E1 induction. 3. FGC-4 cells grown in a glucose-free media and treated with 1-100 mM ethanol for 24 h exhibited a dose-dependent increase (p < 0.05) in CYP2E1, with maximum mRNA steady-state (3.8-fold) or protein (3.1-fold) levels measured at 30 or 100 mM ethanol, respectively. 4. In cells treated with 30 mM ethanol, a glucose concentration-dependent inhibition (p < 0.05) of CYP2E1 mRNA was observed between 2.5 and 10 mM glucose. 5. Induction by 30 mM ethanol of CYP2E1 protein was reduced in cells co-treated with 1 mM or greater glucose concentration and complete inhibition was measured with 5 mM glucose co-treatment. 6. These data demonstrate that under culture conditions of extremely low carbohydrate concentrations: (1) ethanol treatment of FGC-4 cells results in elevated steady-state levels of CYP2E1 mRNA and protein; and (2) glucose inhibits this increase. 7. It is concluded that glucose can negatively regulate CYP2E1 expression and could at least partially explain the greater induction of hepatic CYP2E1 in rats fed low carbohydrate ethanol-containing diets compared with high carbohydrate diets at the same ethanol level.

Animals↗
PubMed2003

Endotoxin tlerance inhibits lipopolysaccharide-initiated acute pulmonary inflammation and lung injury in rats by the mechanism of nuclear factor-kappaB.

In this study, the effect of endotoxin tolerance on lipopolysaccharide (LPS)-initiated pulmonary inflammation, the local production of tumour necrosis factor-alpha (TNF-alpha) and the cytokine-induced neutrophil attractant (CINC), as well as the activation of nuclear factor-kappaB (NF-kappaB) and its subunit composition, were examined in vivo. Endotoxin tolerance was reproduced by four consecutive daily intraperitoneal injections of 0.6 mg/kg of Escherichia coli 055:B5 LPS. Compared with control rats, endotoxin-tolerant rats failed to increase the permeability of pulmonary microvascular or recruit neutrophil to lung tissue upon restimulation with 6 mg/kg of LPSs. Pretreatment with LPSs inhibited the protein level of TNF-alpha in bronchoalveolar lavage fluid (BALF) and mRNA expression of CINC in lung tissue in response to subsequent LPS stimulation. These changes were accompanied by the suppression of activation of NF-kappaB, including the low level of total amount of DNA-binding activity and high percentage of non-transactive p50 homodimers. These data demonstrate that endotoxin tolerance can alleviate the LPS-induced acute neutrophilic pulmonary inflammation in rats and can inhibit the proinflammatory cytokines in lung and suggest that endotoxin tolerance might result from the unresponsiveness of NF-kappaB and persistent high percentage of p50 homodimers. Therefore, the phenomenon of endotoxin tolerance might be used as a strategy for the prevention or treatment of LPS-associated acute respiratory distress syndrome in which excessive or dysregulated inflammation leads to acute lung injury.

Acute Disease↗
PubMed2003

Pharmacological strategies to block rod photoreceptor apoptosis caused by calcium overload: a mechanistic target-site approach to neuroprotection.

PURPOSE: Photoreceptor apoptosis and resultant visual deficits occur in humans and animals with inherited, and disease-, injury- and chemical-induced retinal degeneration. Our aims were three-fold: 1) to determine the kinetics of rod apoptosis and Ca2+ overload in Pde6b9rd1) mice and developmentally lead-exposed rats, 2) to establish a pathophysiologically-relevant model of Ca2+ overload/rod-selective apoptosis in isolated rat retina and 3) to examine different mechanistic based neuroprotective strategies that would abrogate or mollify rod Ca2+ overload/apoptosis. METHODS: Retinal morphometry and elemental calcium content ([Ca]) determined the kinetics of rod apoptosis and Ca2+ overload. A multiparametric analysis of apoptosis including rod [Ca], a live/dead assay, rod oxygen consumption, cytochrome c immunoblots and caspase assays was combined with pharmacological studies of an isolated rat retinal model of rod-selective Ca2+ overload/apoptosis. RESULTS: Ca2+ overload preceded rod apoptosis in mice and rats, although the extent and kinetics in each differed significantly. The isolated rat model of rod Ca2+ overload/apoptosis showed that blockade of Ca2+ entry through rod cGMP-activated channels with L-cis diltiazem was partially neuroprotective, whereas blockade of Ca2+ entry into rods through L-type Ca2+ channels with D-cis diltiazem or verapamil provided no protection. Inhibition of the mitochondrial Na+/Ca2+ exchanger with D-cis diltiazem provided no protection. CsA and NIM811, mitochondrial permeability transition pore (mPTP) inhibitors, blocked all Ca(2+)-induced apoptosis, whereas the caspase-3 inhibitor DEVD-fmk only blocked the downstream cytochrome c-induced apoptosis. CONCLUSIONS: The successful pharmacological neuroprotective strategies for rod Ca2+ overload/apoptosis targeted the rod cGMP-activated channels or mPTP, but not the rod L-type Ca2+ channels.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Effects of chronic ethanol on hepatic and renal CYP2C11 in the male rat: interactions with the Janus-kinase 2-signal transducer and activators of transcription proteins 5b pathway.

Chronic alcohol intake in male rats results in: 1) demasculinization of the GH pulse pattern; 2) reduced serum testosterone concentrations; and 3) decreased expression hepatic CYP2C11. Hepatic CYP2C11 expression is regulated by the male pattern of GH through the Janus-kinase/signal transducer and activators of transcription proteins (JAK/STAT) signal transduction pathway in the male rat. Renal CYP2C11 is regulated by testosterone, not GH. The involvement of the JAK/STAT5b signal transduction pathway in renal CYP2C11 signaling has not been studied. We tested the hypothesis that ethanol reduces CYP2C11 levels by interfering with the JAK/STAT5b pathway. Using a total enteral nutrition (TEN) model to feed rats a well-balanced diet, we have studied the effects of chronic ethanol intake (21 d) on hepatic and renal JAK/STAT pathway of adult male rats (8-10/group). We found decreased hepatic and renal expression of CYP2C11 in ethanol-fed rats with concomitant decreases in STAT5b and phospho-STAT5b, decreased in vitro hepatic STAT5b binding to a CYP2C11 promoter element and no effects on hepatic GHR levels. Ethanol caused tissue specific effects in phospho-JAK2 and JAK2, with increased levels in the liver, but decreased JAK2 expression in the kidney. We conclude that ethanol suppression of CYP2C11 expression is clearly associated with reductions in STAT5b levels, but not necessarily in reductions of JAK2 levels. The mechanisms underlying ethanol-induced suppression of STAT5b is yet to be determined, as is the question of whether this is secondary to hormonal effects or a direct ethanol effect.

Alcoholism↗
PubMed2003

Role of the mitochondrial permeability transition in apoptotic and necrotic death after ischemia/reperfusion injury to hepatocytes.

Reperfusion of ATP-depleted tissues after warm or cold ischemia causes pH-dependent necrotic and apoptotic cell death. In hepatocytes and other cell types as well, the mechanism underlying this reperfusion-induced cell death involves onset of the mitochondrial permeability transition (MPT). Opening of permeability transition (PT) pores in the mitochondrial inner membrane initiates the MPT, an event blocked by cyclosporin A (CsA) and pH less than 7.4. Thus, both acidotic pH and CsA prevent MPT-dependent reperfusion injury. Glycine also blocks reperfusion-induced necrosis but acts downstream of PT pore opening by stabilizing the plasma membrane. After the MPT, ATP availability from glycolysis or other source determines whether cell injury after reperfusion progresses to ATP depletion-dependent necrosis or ATP-requiring apoptosis. Thus, apoptosis and necrosis after reperfusion share a common pathway, the MPT. Cell injury progressing to either necrosis or apoptosis by shared pathways can be more aptly termed necrapoptosis.

Animals↗
PubMed2002

Optimizing and quantifying fusion of liposomes to mammalian sperm using resonance energy transfer and flow cytometric methods.

BACKGROUND: Liposomes are used to carry pharmaceutical agents and to alter the lipid composition of cell membranes. This study compared resonance energy transfer (RET), fluorescence dequenching, and flow cytometry as monitors and quantifiers of fusion between liposomes and mammalian spermatozoa. METHODS: Preliminary experiments used RET to determine the optimum sperm concentration for fusion of DL-alpha-phosphatidylcholine dipalmitoyl (PC)/DL-alpha-phosphatidylethanolamine dipalmitoyl (PE) liposomes at 35 degrees C +/- 5 mM Ca2+. Microscopy confirmed the fusion of liposomes, not just adhesion (n = 3). Dequenching tested the time-dependent fusion of liposomes of two different lipid compositions to sperm, both, (n = 3) +/- 1 mM Ca2+ and (n = 3) without Ca2+ at two sperm concentrations. Finally, flow cytometry absolutely quantified the percentage of sperm fusing to liposomes at different liposome-to-sperm ratios (n = 4) and with sperm from different donors (n = 3). RESULTS: RET detected fusion of liposomes with sperm and microscopy confirmed the interaction to be true fusion. Dequenching detected more fusion of liposomes with sperm at 100 x 10(6) sperm per milliliter than at lower concentrations (P < 0.05). Fusion dynamics differed with lipid composition but Ca2+ had no effect. Flow cytometry reliably quantified the percentage of sperm fusing with liposomes, which varied from bull to bull (P < 0.05). CONCLUSION: Liposome fusion with mammalian sperm membranes can be quantified cytometrically and varies with lipid composition, sperm-to-liposome ratio, and individual animals.

Animals↗
PubMed2002

Carbonate apatite coating on titanium induced rapidly by precalcification.

Chemical treatments have been thought to be promised methods for improving bioactivity of titanium. In this work, the effect of precalcification with boiling saturated Ca(OH)2 solution on bioactivation of titanium was investigated. After precalcification and soaking in supersaturated Ca-P solution (SCP), calcium phosphate rapidly precipitated onto the surfaces of titanium, and after only three days an uniform apatite layer was found up to thickness of a few micrometers. The observation using scanning electron microscopy (SEM) showed that the coating was composed of a number of small crystal grains. The investigation by X-ray energy dispersion spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) indicated that the coating was Ca-deficient carbonate apatite. Based on the analyses for the surfaces and SCP, a mechanism of precipitation of apatite was proposed in thermal dynamics and kinetics.

Apatites↗
PubMed2002

Characterization of surface oxide films on titanium and bioactivity.

Biological properties of titanium implant depend on its surface oxide film. In the present study, the surface oxide films on titanium were characterized and the relationship between the characterization and bioactivity of titanium was studied. The surface oxide films on titanium were obtained by heat-treatment in different oxidation atmospheres, such as air, oxygen and water vapor. The bioactivity of heat-treated titanium plates was investigated by immersion test in a supersaturated calcium phosphate solution. The surface roughness, energy morphology, chemical composition and crystal structure were used to characterize the titanium surfaces. The characterization was performed using profilometer, scanning electronic microscopy, ssesile drop method, X-ray photoelectron spectroscopy, common Bragg X-ray diffraction and sample tilting X-ray diffraction. Percentage of surface hydroxyl groups was determined by X-ray photoelectron spectroscopy analysis for titanium plates and density of surface hydroxyl groups was measured by chemical method for titanium powders. The results indicated that heat-treatment uniformly roughened the titanium surface and increased surface energy. After heat-treatment the surface titanium oxide was predominantly rutile TiO(2), and crystal planes in the rutile films preferentially orientated in (1 1 0) plane with the highest density of titanium ions. Heat-treatment increased the amount of surface hydroxyl groups on titanium. The different oxidation atmospheres resulted in different percentages of oxygen species in TiO(2), in physisorbed water and acidic hydroxyl groups, and in basic hydroxyl groups on the titanium surfaces. The immersion test in the supersaturated calcium phosphate solution showed that apatite spontaneously formed on to the rutile films. This revealed that rutile could be bioactivated. The analyses for the apatite coatings confirmed that the surface characterization of titanium has strong effect on bioactivity of titanium. The bioactivity of the rutile films on titanium was related not only to their surface basic hydroxyl groups, but also to acidic hydroxyl groups, and surface energy. Heat-treatment endowed titanium with bioactivity by increasing the amount of surface hydroxyl groups on titanium and its surface energy.

Journal Article↗
PubMed2002

A family-based and case-control association study of the NOTCH4 gene and schizophrenia.

Recently a strong positive association between schizophrenia and Notch4 has been reported. Both individual markers and haplotypes showed association with the disease, with five markers (three microsatellites and two SNPs) being tested. In order to test this finding we genotyped these markers in the Han Chinese population using a sample of 544 cases and 621 controls as well as >300 trios. Analysis of allele, genotype and haplotype frequencies in both samples showed no association between the markers and the disease. Our results would indicate that a significant role for the Notch4 gene in schizophrenia can be ruled out in the Han Chinese. However, similar studies are necessary in the Caucasian population as linkage disequilibrium arrangements and founder effects may differ between these two populations.

Adolescent↗